Neuronal plasticity of the "brain-skin connection": stress-triggered up-regulation of neuropeptides in dorsal root ganglia and skin via nerve growth factor-dependent pathways.
Emerging research indicates that central-nervous stress perception is translated to peripheral tissues such as the skin not only via classical stress hormones but also via neurotrophins and neuropeptides. This can result in neurogenic inflammation, which is likely to contribute to the triggering and/aggravation of immunodermatoses. Although the existence of such a "brain-skin connection" is supported by steadily increasing experimental evidence, it remains unclear to which extent perceived stress affects the sensory "hardwiring" between skin and its afferent neurons in the corresponding dorsal root ganglia (DRG). In this paper, we provide experimental evidence in a murine model of stress (exposure of C57BL/6 mice to sound stress) that stress exposure, or intracutaneous injection of recombinant nerve growth factor (NGF) to mimic the skin's response to stress, up-regulate the percentage of substance P (SP)+ or calcitonin gene-related peptide (CGRP)+ sensory neurons in skin-innervating DRG. Further, we show that the number of SP+ or CGRP+ sensory nerve fibers in the dermis of stressed C57BL/6 mice is significantly increased. Finally, we document that neutralization of NGF activity abrogates stress-induced effects on the percentage of SP+ and CGRP+ sensory neurons in skin-innervating DRG as well as on dermal sensory nerve fibers. These data suggest that high stress perception results in an intense cross talk between the skin and skin-innervating DRG, which increases the likelihood of NGF-dependent neurogenic skin inflammation by enhancing sensory skin innervation.


3D-printed membrane for guided tissue regeneration.
Three-dimensional (3D) printing is currently being intensely studied for a diverse set of applications, including the development of bioengineered tissues, as well as the production of functional biomedical materials and devices for dental and orthopedic applications. The aim of this study was to develop and characterize a 3D-printed hybrid construct that can be potentially suitable for guided tissue regeneration (GTR). For this purpose, the rheology analyses have been performed on different bioinks and a specific solution comprising 8% gelatin, 2% elastin and 0.5% sodium hyaluronate has been selected as the most suitable composition for printing a structured membrane for GTR application. Each membrane is composed of 6 layers with strand angles from the first layer to the last layer of 45, 135, 0, 90, 0 and 90°. Confirmed by 3D Laser Measuring imaging, the membrane has small pores on one side and large pores on the other to be able to accommodate different cells like osteoblasts, fibroblasts and keratinocytes on different sides. The ultimate cross-linked product is a 150μm thick flexible and bendable membrane with easy surgical handling. Static and dynamic mechanical testing revealed static tensile modules of 1.95±0.55MPa and a dynamic tensile storage modulus of 314±50kPa. Through seeding the membranes with fibroblast and keratinocyte cells, the results of in vitro tests, including histological analysis, tissue viability examinations and DAPI staining, indicated that the membrane has desirable in vitro biocompatibility. The membrane has demonstrated the barrier function of a GTR membrane by thorough separation of the oral epithelial layer from the underlying tissues. In conclusion, we have characterized a biocompatible and bio-resorbable 3D-printed structured gelatin/elastin/sodium hyaluronate membrane with optimal biostability, mechanical strength and surgical handling characteristics in terms of suturability for potential application in GTR procedures.


[Radiation levels in working sites where X-ray is used for medical diagnosis].
The radiation levels were measured in 109 working sites in 12 counties or municipalities of our district where X-ray was used for medical diagnosis. At the same time the effectiveness of some radioprotective facilities was assessed. The results showed that in the working sites with the ordinary protection, the average exposure rate of the surface of the worker's chest was 3.43 x 10(-8) mC/kg.s; in the sites with poor protection the average rate of exposure was the highest (about 273 x 10(-8) mC/kg.s); in the sites with other types of protection the rate was less than 10.80 x 10(-8) mC/kg.s; the exposure rate using lead chairs and aprons was 18.6 times and 5.8 times respectively lower than those without.


Does gender moderate the relationship between polydrug use and sexual risk-taking among Australian secondary school students under 16 years of age?
This study examines the association of alcohol and polydrug use with risky sexual behaviour in adolescents under 16 years of age and if this association differs by gender. The sample consisted of 5412 secondary school students under 16 years of age from Victoria, Australia. Participants completed an anonymous and confidential survey during class time. The key measures were having had sex before legal age of consent (16 years), unprotected sex before 16 (no condom) and latent-class derived alcohol and polydrug use variables based on alcohol, tobacco, cannabis, inhalants and other illegal drug use in the past month. There were 7.52% and 2.55% of adolescents who reported having sex and having unprotected sex before 16 years of age, respectively. After adjusting for antisocial behaviours, peers' drug use and family and school risk factors, girls were less likely to have unprotected sex (odds ratio = 0.31, P = 0.003). However, the interaction of being female and polydrug use (odds ratio = 4.52, P = 0.004) was significant, indicating that girls who engaged in polydrug use were at higher risk of having unprotected sex. For boys, the effect of polydrug use was non-significant (odds ratio = 1.44, P = 0.310). Discussion and Conclusions For girls, polydrug use was significantly associated with unprotected sex after adjusting for a range of risk factors, and this relationship was non-significant for boys. Future prevention programs for adolescent risky sexual behaviour and polydrug use might benefit from a tailored approach to gender differences. [Chan GCK, Kelly AB, Hides L, Quinn C, Williams JW. Does gender moderate the relationship between polydrug use and sexual risk-taking among Australian secondary school students under 16 years of age? Drug Alcohol Rev 2016;35:750-754].


Properties of SEPT9 isoforms and the requirement for GTP binding.
Members of the evolutionarily conserved septin family of genes are emerging as key components of several cellular processes including membrane trafficking, cytokinesis, and cell-cycle control events. SEPT9 has been shown to have a complex genomic architecture, such that up to 15 different isoforms are possible by the shuffling of five alternate amino termini and three alternate carboxy termini. Genomic and transcriptional alterations of SEPT9 have been associated with neoplasia. The present study has used a Sept9-specific antibody to determine the pattern of isoform expression in a range of tumour cell lines. Western blot analysis indicated considerable variation in the relative amounts and isoform content of Sept9. Immunofluorescence studies showed a range of patterns of cytoplasmic localization ranging from mainly particulate to mainly filamentous. Expression constructs were also generated for each amino terminal isoform to investigate the patterns of localization of individual isoforms and the effects on cells of ectopic expression. The present study shows that the epsilon isoform appears filamentous in this overexpression system while the remaining isoforms are particulate and cytoplasmic. Transient transfection of individual constructs into tumour cell lines results in cell-cycle perturbation with a G2/M arrest and dramatic growth suppression, which was greatest in cell lines with the lowest amounts of endogenous Sept9. Similar phenotypic observations were made with GTP-binding mutants of all five N-terminal variants of Sept9. However, dramatic differences were observed in the kinetics of accumulation of wild-type versus mutant septin protein in transfected cells. In conclusion, the present study shows that the expression patterns of Sept9 protein are very varied in a panel of tumour cell lines and the functional studies are consistent with a model of septin function as a component of a molecular scaffold that contributes to diverse cellular functions. Alterations in the levels of Sept9 protein by overexpression of individual isoforms can clearly perturb cellular behaviour and may thus provide a mechanistic explanation for observations of deranged septin expression in neoplasia.


Influenza virus immunosensor with an electro-active optical waveguide under potential modulation.
Here we report the development of a novel immunosensor-based strategy for label-free detection of viral pathogens by incorporating a sandwich bioassay onto a single-mode, electro-active, integrated optical waveguide (EA-IOW). Our strategy begins with the functionalization of the electro-active waveguide surface with a capture antibody aimed at a specific virus antigen. Once the target antigen is bound to the photonic interface, it promotes the binding of a secondary antibody that has been labeled with a methylene blue (MB) dye. The MB is a redox-active probe whose optical absorption can be electrically modulated and interrogated with high sensitivity by a propagating waveguide mode. In this effort, we have targeted the hemagglutinin (HA) protein from the H5N1 avian influenza A virus to demonstrate the capabilities of the EA-IOW device for detection and quantification of an important antigen. Our initial results for the HA H5N1 influenza virus show a remarkable limit of detection in the pico-molar range.


[Breast cancer metastasis in distal phalanx of the big toe. Case report].
Breast cancer represents the most prevalent malignancies in women and bone is the first site of metastasis in 26-50% of cases. Usually metastasis involve limbs in 16%. We present a rare case of 47-year-old woman, who underwent to monolateral mastectomy for lobular cancer. After 8 years from surgery, she presented pain, swelling and functional limitations, gradually increasing, to the left big toe. X-rays and MRI showed a lucent area of bone destruction on the shaft of the distal phalanx of the left big toe. Surgical biopsy on the excised bone assessed for breast cancer metastasis.


Specificities of Human Hepatocellular Carcinoma Developed on Non-Alcoholic Fatty Liver Disease in Absence of Cirrhosis Revealed by Tissue Extracts ¹H-NMR Spectroscopy.
There is a rising incidence of non-alcoholic fatty liver disease (NAFLD) as well as of the frequency of Hepato-Cellular Carcinoma (HCC) associated with NAFLD. To seek for putative metabolic pathways specific of the NAFLD etiology, we performed comparative metabolomics between HCC associated with NAFLD and HCC associated with cirrhosis. The study included 28 pairs of HCC tissue versus distant Non-Tumoral Tissue (NTT) collected from patients undergoing hepatectomy. HCC was associated with cirrhosis (n = 9), normal liver (n = 6) and NAFLD (n = 13). Metabolomics was performed using 1H-NMR Spectroscopy on tissue extracts and combined to multivariate statistical analysis. In HCC compared to NTT, statistical models showed high levels of lactate and phosphocholine, and low level of glucose. Shared and Unique Structures (SUS) plots were performed to remove the impact of underlying disease on the metabolic profile of HCC. HCC-cirrhosis was characterized by high levels of β-hydroxybutyrate, tyrosine, phenylalanine and histidine whereas HCC-NAFLD was characterized by high levels of glutamine/glutamate. In addition, the overexpression glutamine/glutamate on HCC-NAFLD was confirmed by both Glutamine Synthetase (GS) immuno-staining and NMR-spectroscopy glutamine quantification. This study provides evidence of metabolic specificities of HCC associated with non-cirrhotic NAFLD versus HCC associated with cirrhosis. These alterations could suggest activation of glutamine synthetase pathway in HCC-NAFLD and mitochondrial dysfunction in HCC-cirrhosis, that may be part of specific carcinogenic processes.


Measuring hospital inefficiency: the effects of controlling for quality and patient burden of illness.
To assess the impact of employing a variety of controls for hospital quality and patient burden of illness on the mean estimated inefficiency and relative ranking of hospitals generated by stochastic frontier analysis (SFA). This study included urban U.S. hospitals in 20 states operating in 2001. DATA DESIGN/DATA COLLECTION: We took hospital data for 1,290 hospitals from the American Hospital Association Annual Survey and the Medicare Cost Reports. We employed a variety of controls for hospital quality and patient burden of illness. Among the variables we used were a subset of the quality indicators generated from the application of the Patient Safety Indicator and Inpatient Quality Indicator modules of the Agency for Healthcare Research and Quality, Quality Indicator software to the Healthcare Cost and Utilization Project (HCUP), State Inpatient Databases. Measures of a component of patient burden of illness came from the application of the Comorbidity Software to HCUP data. We used SFA to estimate hospital cost-inefficiency. We tested key assumptions of the SFA model with likelihood ratio tests. The measures produced by the Comorbidity Software appear to account for variations in patient burden of illness that had previously been masquerading as inefficiency. Outcome measures of quality can provide useful insight into a hospital's operations but may have little impact on estimated inefficiency once controls for structural quality and patient burden of illness have been employed. Choices about controlling for quality and patient burden of illness can have a nontrivial impact on mean estimated hospital inefficiency and the relative ranking of hospitals generated by SFA.


Use of wound dressings to enhance prevention of pressure ulcers caused by medical devices.
Medical device related pressure ulcers (MDR PUs) are defined as pressure injuries associated with the use of devices applied for diagnostic or therapeutic purposes wherein the PU that develops has the same configuration as the device. Many institutions have reduced the incidence of traditional PUs (sacral, buttock and heel) and therefore the significance of MDR PU has become more apparent. The highest risk of MDR PU has been reported to be patients with impaired sensory perception, such as neuropathy, and an impaired ability for the patient to communicate discomfort, for example, oral intubation, language barriers, unconsciousness or non-verbal state. Patients in critical care units typify the high-risk patient and they often require more devices for monitoring and therapeutic purposes. An expert panel met to review the evidence on the prevention of MDR PUs and arrived at these conclusions: (i) consider applying dressings that demonstrate pressure redistribution and absorb moisture from body areas in contact with medical devices, tubing and fixators, (ii) in addition to dressings applied beneath medical devices, continue to lift and/or move the medical device to examine the skin beneath it and reposition for pressure relief and (iii) when simple repositioning does not relieve pressure, it is important not to create more pressure by placing dressings beneath tight devices.


Connecting core percolation and controllability of complex networks.
Core percolation is a fundamental structural transition in complex networks related to a wide range of important problems. Recent advances have provided us an analytical framework of core percolation in uncorrelated random networks with arbitrary degree distributions. Here we apply the tools in analysis of network controllability. We confirm analytically that the emergence of the bifurcation in control coincides with the formation of the core and the structure of the core determines the control mode of the network. We also derive the analytical expression related to the controllability robustness by extending the deduction in core percolation. These findings help us better understand the interesting interplay between the structural and dynamical properties of complex networks.


Integrin alphaVbeta5 is not involved in adeno-associated virus type 2 (AAV2) infection.
alphaVbeta5 integrin was recently proposed as a coreceptor for adeno-associated virus type 2 (AAV2) infection (Summerford et al., 1999, Nat. Med. 5, 78-82), based mainly on the direct binding of AAV2 to denatured beta5 by virus overlay assay. In studies using purified natural or recombinant human integrin alphaVbeta5 we were unable to demonstrate AAV2 binding, either by virus overlay or by liquid binding assay. Furthermore, neither purified integrin alphaVbeta5, nor RGD peptides, nor functional blocking monoclonal antibody blocked rAAV2 transduction. These data strongly suggest that integrin alphaVbeta5 is not involved in AAV2 infection.


[Skin disorders in diabetes mellitus].
Diabetes mellitus is one of the most common diseases in the Western industrialized countries with about 300 million affected patients worldwide. The hyperglycemic state of diabetes mellitus leads to changes in practically every cell type and organ of the human body. Skin changes are considered the most common manifestations of diabetes mellitus. As skin changes can manifest before onset of diabetes mellitus they may have a diagnostic relevance. Other changes and diseases of the skin develop during the course of diabetes mellitus and may be associated with complications in internal organs or may occur as an adverse effect of antidiabetic therapy. In particular the presence of the diabetic foot syndrome is associated with significantly increased morbidity and mortality of diabetes patients as well as with markedly elevated direct and indirect costs for the health care system. In this article the most common skin diseases of patients with diabetes mellitus as well as their pathophysiology and current treatment are reviewed.


Skeletal muscle mass: evaluation of neutron activation and dual-energy X-ray absorptiometry methods.
Although skeletal muscle (SM) is a major body component, whole body measurement methods remain limited and inadequately investigated. The aim of the present study was to evaluate the Burkinshaw in vivo neutron activation analysis (IVNA)-whole body 40K-counting and dual-energy X-ray absorptiometry (DXA) methods of estimating SM by comparison to adipose tissue-free SM measured using multiscan computerized axial tomography (CT). In the Burkinshaw method the potassium-to-nitrogen ratios of SM and non-SM lean tissue are assumed constant; in the DXA method the ratio of appendicular SM to total SM is assumed constant at 0.75. Seventeen healthy men [77.5 +/- 13.8 (SD) kg body wt] and eight men with acquired immunodeficiency syndrome (AIDS; 65.5 +/- 7.6 kg) completed CT, IVNA, and DXA studies. SM measured by CT was 34.4 +/- 6.2 kg for the healthy subjects and 27.2 +/- 4.0 kg for the AIDS patients. Compared with CT, the Burkinshaw method underestimated SM by an average of 6.9 kg (20.1%, P = 0.0001) and 6.3 kg (23.2%, P = 0.01) in the healthy men and the men with AIDS, respectively. The DXA method minimally overestimated SM in both groups (2.0 kg and 5.8% in healthy men, P = 0.001; 1.4 kg and 5.1% in men with AIDS, P = 0.16). This overestimate could be explained by a higher actual than assumed ratio of DXA-measured appendicular SM to total body SM (actual = 0.79 +/- 0.05, assumed = 0.75). The current study results reveal that large errors are present in the Burkinshaw SM method and that substantial refinements in the models that form the basis of this IVNA approach are needed. The model on which the DXA-SM method is based also needs further minor refinements, but this is a promising in vivo approach because of less radiation exposure and lower cost than the IVNA and CT methods.


Increased nerve growth factor and its receptors in atopic dermatitis: an immunohistochemical study.
Evidence suggests that neurotrophins may regulate certain immune functions and inflammation. In the present study, the localization and distribution of nerve growth factor (NGF) and its receptors were explored using immunohistochemical methods, with the aim of detecting the cause of the neurohyperplasia in early lesions of atopic dermatitis (AD). In AD involved skin, strong NGF-immunoreactive (IR) cells were observed in the epidermis. In some cases, a huge number of infiltrating cells with stronger NGF immunoreactivity was seen mainly in the dermal papillae. Some trkA immunoreactivity was observed in the outer membrane of cells in the basal and spinal layers of the epidermis. In the papillary dermis, a larger number of cells demonstrated strong trkA immunoreactivity. The p75 NGFr-IR nerve fibre profiles were increased (900 per mm(2); p<0.001) compared to normal [the involved skin also differed from the uninvolved skin (p<0.05)] in the dermal papillae. These nerve fibres were larger, coarser and branched, some of them terminated at p75 NGFr-IR basal cells, and also revealed a stronger fluorescence staining than the controls or the uninvolved skin. In normal healthy volunteers and AD uninvolved skin, the NGF immunoreactivity was weak in the basal layer of epidermis. Only a few trkA positive cells were seen in the basal layer of the epidermis and upper dermis. The IR epidermal basal cells revealed a striking patchy arrangement with strong p75 NGFr immunostaining in the peripheral part of the cells, and short and thick NGFr-IR nerve fibre profiles appeared as smooth endings scattered in the dermis including the cutaneous accessory organs. Using NGF and p75 NGFr double staining, both immunoreactivities showed a weak staining in the epidermis and dermis in normal and uninvolved skin. In the involved dermis of AD, the intensity of p75 NGFr-IR nerves was stronger in areas where there were also increased numbers of NGF-IR cells. These findings indicate that NGF and its receptors may contribute to the neurohyperplasia of AD.


Boryl-substituted low-valent heavy group 14 compounds.
Low valent group 14 compounds exhibit diverse structures and reactivities. The employment of diazaborolyl anions (NHB anions), isoelectronic analogues to N-heterocyclic carbenes (NHCs), in group 14 chemistry leads to the exceptional structures and reactivity. The unique combination of σ-electron donation and pronounced steric hindrance impart distinct structural characteristics to the NHB-substituted low valent group 14 compounds. Notably, the modulation of the HOMO-LUMO gap in these compounds with the diazaborolyl substituents results in novel reaction patterns in the activation of small molecules and inert chemical bonds. This review mainly summarizes the recent advances in NHB-substituted low-valent heavy Group 14 compounds, emphasizing their synthesis, structural characteristics and application to small molecule activation.


[An electrophysiological study of the brain of rats with different resistances to oxygen deficiency in acute hypoxia].
The Fourier spectre of power (SP) and bioelectrical activity of the cortex, hippocampus and hypothalamus were studied in unrestrained rats with high (HR) and low (LR) resistance to oxygen deficiency before and after their stay at the "altitude" of about 11,000 m. After acute hypobaric hypoxia there were the EEG changes in LR rats: displacement of the SP peak in low-frequency activity and decreasing of absolute power of all the ranges of SP. In one hour after the "altitude", these EEG parameters were restored. The EEG of the HR rats was not altered. The cortex of the brain seems to be the most susceptible to hypoxia.


Infectivity enhanced, hTERT promoter-based conditionally replicative adenoviruses are useful for SCLC treatment.
Treatment of advanced small-cell lung cancer (SCLC) remains one of the major challenges in current medicine because of the high morbidity and mortality of the disease. Advanced stage lung cancer is refractory to conventional therapies and it also has an extremely poor prognosis. As a result, new therapeutic approaches are needed. Telomere maintenance to the regulation of replicative lifespan strongly implies that alterations in telomere biology play an important role during malignant transformation. Cancers that exhibit high levels of telomerase activity, such as all of the SCLC, were examined in a previous study. In this study, we turned the expression of human telomerase reverse transcriptase (hTERT) by tumors to a therapeutic advantage using a conditionally replication-competent adenovirus (CRAd) in which the expression of E1 (early region 1) is controlled by the hTERT promoter. This virus achieved good levels of viral replication in SCLC cells and induced a substantial anticancer effect in vitro and in vivo. As a further enhancement, the cancer cell killing effect was improved with a tropism modification of the virus to express the knob domain of Ad3 (serotype 3 adenovirus), and this improved infectivity for cancer cells. Conversely, the hTERT promoter has low activity in normal tissues, and the CRAd caused no damage to normal lung fibroblast cells. Since the telomerase activity is common in many types of cancers, these CRAds may be applicable to a wide range of tumors. We concluded that the use of hTERT promoter-based CRAds may be a potentially effective strategy for cancer treatment.


Shape and size of non-spherical silver nanoparticles: implications for calculating nanoparticle number concentrations.
The international drive to measure accurate number concentrations of nanoparticles is impeded by the typically heterogeneous populations of non-spherical nanoparticles. The irregular shape and size of "50 nm" silver nanoparticles is studied using Electron Tomography. It is evidenced that even for highly symmetrical particles the volume can be over 20% less than that of the circumscribed sphere; more irregularly shaped particles can have volumes of over 45% less. On this basis, criteria are provided to determine the particle sphericity from 2D projections obtained from Electron Microscopy, including an empirical method for particle volume estimation. The results allow the visualisation of irregularly shaped particles, revealing the presence of previously unseen voids in the nanoparticle structure. Comparison of tomographic data with other commonly used particle-sizing methods exposes the limitations of these methods in studying nanoparticle populations that exhibit heterogeneity.


Melting of two-dimensional solids.
Recent theoretical predictions indicate that melting of a two-dimensional solid may be caused by spontaneous creation of dislocations. The theory predicts that melting occurs by a two-step process involving an intermediate phase, called the hexatic phase, in which there is order in the local crystalline axes but not in the positions of atoms. These ideas are being tested by numerical simulations and by experiments on electrons on liquid helium, liquid crystal films, and rare gas layers adsorbed on graphite. Experiments on liquid crystal films indicate that the three-dimensional analog of the hexatic phase exists, and xenon on graphite exhibits a melting transition close to the form predicted.


μ opioid receptor carboxyl terminal-derived peptide alleviates morphine tolerance by inhibiting β-arrestin2.
The interaction between the μ opioid receptor (MOR) and β-arrestin2 serves as a model for addressing morphine tolerance. A peptide was designed to alleviate morphine tolerance through interfering with the interaction of MOR and β-arrestin2. We developed a peptide derived from MOR. The MOR-TAT-pep peptide was expressed in E. coli Bl21(DE3) and purified. The effects of MOR-TAT-pep in alleviating morphine tolerance was examined through behavior tests. The potential mechanism was detected by Western blotting, Mammalian Two-Hybrid and other techniques. The pretreatment with MOR-TAT-pep prior to morphine usage led to an enhanced analgesic effectiveness of morphine and a significant reduction in the development of morphine tolerance. The peptide directly interacted with β-arrestin2 during morphine treatment and deceased the membrane recruitment of β-arrestin2. MOR-TAT-pep effectively suppressed the increase of β-arrestin2 induced by morphine. The MOR-TAT-pep could alleviate morphine tolerance through inhibition of β-arrestin2.


Double-blind Randomized Study to Evaluate the Safety and Efficacy of Over-the-counter Tooth-whitening Agents Containing 2.9% Hydrogen Peroxide.
In this double-blind randomized study, we evaluated the safety and efficacy of over-the-counter (OTC) bleaching products that included 2.9% hydrogen peroxide (H2O2) with two methods of application: strip and paint-on. A commonly used product was selected for each type (strip and paint-on) of OTC bleaching agent. In total, 75 volunteers were assigned randomly into five groups: two test groups (strip and paint-on), two negative control groups (products without H2O2), and one positive control group (dentist-supervised home bleaching). The tooth shade was evaluated with a spectrophotometer and Vita shade guide at baseline and 2 weeks and 4 weeks after use. To document any adverse reactions, such as hypersensitivity or tissue irritation, all patients were examined and the Gingival Index (GI), Plaque Index (PI), and a visual analog scale (VAS) measuring the cold response were obtained. There were significant differences among the five groups ( p<0.001). The positive control showed the greatest color changes; then, in decreasing order, the strip-type test group, paint-on-type test group, and negative controls. The strip-type bleaching agent was significantly more effective than the paint-on-type agent and the negative control, while it was significantly less effective than the dentist-supervised home bleaching. Regardless of the treatment group, the canines showed greater color changes than did the central or lateral incisors. Some cases of gingival irritation and hypersensitivity were observed, but they were mild and reversible. GI, PI, and VAS scores were not significantly changed. Within the limitations of this study, the results indicated that the strip-type and paint-on-type OTC bleaching agents were significantly less efficacious than was dentist-supervised home bleaching; however, they showed acceptable safety and efficacy. The strip-type was more effective than was the paint-on-type in this study.


Discovering shared cardiovascular dynamics within a patient cohort.
Cardiovascular variables such as heart rate (HR) and blood pressure (BP) are robustly regulated by an underlying control system. Time series of HR and BP exhibit distinct dynamical patterns of interaction in response to perturbations (e.g., drugs or exercise) as well as in pathological states (e.g., excessive sympathetic activation). A question of interest is whether "similar" dynamical patterns can be identified across a heterogeneous patient cohort. In this work, we present a technique based on switching linear dynamical systems for identification of shared dynamical patterns in the time series of HR and BP recorded from a patient cohort. The technique uses a mixture of linear dynamical systems, the components of which are shared across all patients, to capture both nonlinear dynamics and non-Gaussian perturbations. We present exploratory results based on a simulation study of the cardiovascular system, and real recordings from 10 healthy subjects undergoing a tilt-table test. These results demonstrate the ability of the proposed technique to identify similar dynamical patterns present across multiple time series.


[Immunosuppressive treatment of patients with a nephrotic syndrome due to minimal change glomerulopathy].
Prednisone monotherapy is the treatment of choice for patients with a nephrotic syndrome due to minimal change glomerulopathy. In adult patients treatment should be continued for at least 24 weeks. Within this period a remission of proteinuria will occur in 75 to 90% of the patients. Patients who do not respond satisfactorily to prednisone treatment can be treated with alkylating agents. Cyclophosphamide is the drug used most commonly. Prolonged treatment (> 12 weeks) is associated with a high risk of infertility. If alkylating agents cannot be used, prolonged treatment with ciclosporine is an option.


An Empirical Understanding of the Glycosylation Reaction.
Reliable glycosylation reactions that allow for the stereo- and regioselective installation of glycosidic linkages are paramount to the chemical synthesis of glycan chains. The stereoselectivity of glycosylations is exceedingly difficult to control due to the reaction's high degree of sensitivity and its shifting, simultaneous mechanistic pathways that are controlled by variables of unknown degree of influence, dominance, or interdependency. An automated platform was devised to quickly, reproducibly, and systematically screen glycosylations and thereby address this fundamental problem. Thirteen variables were investigated in as isolated a manner as possible, to identify and quantify inherent preferences of electrophilic glycosylating agents (glycosyl donors) and nucleophiles (glycosyl acceptors). Ways to enhance, suppress, or even override these preferences using judicious environmental conditions were discovered. Glycosylations involving two specific partners can be tuned to produce either 11:1 selectivity of one stereoisomer or 9:1 of the other by merely changing the reaction conditions.


Hypertension Canada's 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults.
Hypertension Canada provides annually updated, evidence-based guidelines for the diagnosis, assessment, prevention, and treatment of hypertension. This year, we introduce 10 new guidelines. Three previous guidelines have been revised and 5 have been removed. Previous age and frailty distinctions have been removed as considerations for when to initiate antihypertensive therapy. In the presence of macrovascular target organ damage, or in those with independent cardiovascular risk factors, antihypertensive therapy should be considered for all individuals with elevated average systolic nonautomated office blood pressure (non-AOBP) readings ≥ 140 mm Hg. For individuals with diastolic hypertension (with or without systolic hypertension), fixed-dose single-pill combinations are now recommended as an initial treatment option. Preference is given to pills containing an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in combination with either a calcium channel blocker or diuretic. Whenever a diuretic is selected as monotherapy, longer-acting agents are preferred. In patients with established ischemic heart disease, caution should be exercised in lowering diastolic non-AOBP to ≤ 60 mm Hg, especially in the presence of left ventricular hypertrophy. After a hemorrhagic stroke, in the first 24 hours, systolic non-AOBP lowering to < 140 mm Hg is not recommended. Finally, guidance is now provided for screening, initial diagnosis, assessment, and treatment of renovascular hypertension arising from fibromuscular dysplasia. The specific evidence and rationale underlying each of these guidelines are discussed.


Leukocyte telomere length in patients with transfusion-dependent thalassemia.
Thalassemia is a hereditary hemolytic anemia with a severity ranging from mild, non-transfusion dependent to severe chronic anemia requiring lifelong transfusion. Transfusional iron overload is a major complication in patients with transfusion-dependent thalassemia (TDT). Telomeres are sequences of nucleotides forming the end caps of chromosomes that act as a DNA repair system. Iron overload in thalassemia can cause increased oxidative stress which leads to cellular damage and senescence. This may result in telomere length shortening. The degree of telomere length shortening may reflect the severity of thalassemia. This research aimed to study the leukocyte telomere length in patients with TDT in comparison to non-thalassemic individuals and to identify the clinical and laboratory parameters that are associated with telomere length. We conducted a cross-sectional study in patients with TDT aged ≥18 years. Leukocyte telomere length was measured by real-time quantitative PCR. Sixty-five patients with TDT were enrolled onto the study. There were 37 female patients (54.4%). The median age was 27 (18-57) years, and mean pre-transfusion hemoglobin level was 7.1 (± 1.07) g/dL. The mean telomere to single copy gene (T/S) ratios of patients with TDT and the controls were 0.72 ± 0.18 and 0.99 ± 0.25, respectively (p < 0.0001). There was a significant correlation between the T/S ratio and age (p = 0.0002), and hemoglobin level (p = 0.044). There was no correlation between telomere length and other factors. Our study showed that TDT patients had shorter leukocyte telomere length compared with controls. Leukocyte telomere shortening in TDT was an aging-dependent process and associated with lower hemoglobin level.


Nest etiquette--where ants go when nature calls.
Sanitary behaviour is an important, but seldom studied, aspect of social living. Social insects have developed several strategies for dealing with waste and faecal matter, including dumping waste outside the nest and forming specialised waste-storage chambers. In some cases waste material and faeces are put to use, either as a construction material or as a long-lasting signal, suggesting that faeces and waste may not always be dangerous. Here we examine a previously undescribed behaviour in ants - the formation of well-defined faecal patches. Lasius niger ants were housed in plaster nests and provided with coloured sucrose solution. After two months, 1-4 well defined dark patches, the colour of the sucrose solution, formed within each of the plaster nests. These patches never contained other waste material such as uneaten food items, or nestmate corpses. Such waste was collected in waste piles outside the nest. The coloured patches were thus distinct from previously described 'kitchen middens' in ants, and are best described as 'toilets'. Why faeces is not removed with other waste materials is unclear. The presence of the toilets inside the nest suggests that they may not be an important source of pathogens, and may have a beneficial role.


False-positive Gen-Probe direct Mycobacterium tuberculosis amplification test results for patients with pulmonary M. kansasii and M. avium infections.
The Gen-Probe Amplified Mycobacterium Tuberculosis Direct (MTD) test has been approved for use in the United States for the rapid diagnosis of pulmonary tuberculosis in patients with acid-fast smear-positive sputum samples since 1996. Four patients infected with human immunodeficiency virus and one chronic pulmonary-disease patient seen in our institutions with abnormal chest radiographs and fluorochrome stain-positive sputa were evaluated for tuberculosis, including performance of the MTD test on expectorated sputum samples. Three of these five patients' sputa were highly smear-positive (i.e. , more than 100 bacilli per high-power field), while two patient's sputa contained 1 to 10 bacilli per field. MTD results on sputum specimens from these patients ranged from 43,498 to 193,858 relative light units (RLU). Gen-Probe has defined values of at least 30,000 RLU as indicative of a positive test, i.e., the presence of Mycobacterium tuberculosis RNA. Four of the patients' sputum cultures yielded growth of M. kansasii within 6 to 12 days, and the fifth produced growth of M. avium only. One patient's culture contained both M. kansasii and M. avium, but none of the initial or follow-up cultures from these five patients revealed M. tuberculosis. However, subsequent cultures from three of the patients again revealed M. kansasii. During the period of this study, in which MTD tests were performed on smear-positive sputum specimens from 82 patients, four of seven patients with culture-proven M. kansasii pulmonary infections yielded one or more false-positive MTD tests. The MTD sensitivity observed in this study was 93.8%, and the specificity was 85.3%. Five cultures of M. kansasii (including three of these patients' isolates and M. kansasii ATCC 12478), and cultures of several other species were examined at densities of 10(5) to 10(7) viable CFU/ml by the MTD test. All five isolates of M. kansasii and three of three isolates of M. simiae yielded false-positive test results, with readings of 75,191 to 335,591 RLU. These findings indicate that low-level false-positive MTD results can occur due to the presence of M. kansasii, M. avium, and possibly other Mycobacterium species other than M. tuberculosis in sputum. Low-level positive MTD results of 30,000 to 500,000 RLU should be interpreted in light of these findings. It remains to be determined if the enhanced MTD test (MTD 2) recently released by Gen-Probe will provide greater specificity than that observed in this report with its first-generation test.


Low yield for routine laboratory checks in follow-up of coeliac disease.
To evaluate the yield of routine laboratory tests and Dual Energy X-ray Absorptiometry (DEXA) scans in coeliac disease. A retrospective analysis of medical files of all followed-up patients with coeliac disease attending Rijnstate Hospital in 2016 was conducted with respect to blood tests of hemoglobin, vitamin B12, folate acid, iron status, calcium, vitamin D, glucose, thyroid function, DEXA-scans and related symptoms or signs of abnormalities. All patients had positive coeliac serology and/or biopsy-proven coeliac disease and attended regular visits after diagnosis. The chi-square test for trend was used for statistical analysis: a two-tailed probability of p < 0.05 was considered significant. We analyzed 250 patients with a median follow-up of 7.8 (1-22) years. At diagnosis, we found anemia in 24.4%, iron deficiency in 38%, folic acid deficiency in 22.6% and vitamin B12 deficiency in 15.9%. All deficiencies recovered within 1-2 years with or without supplements. Deficiencies or autoimmune diseases occurred in 50 patients (37 possibly coeliac-related) during follow-up. Twelve cases of coeliac-related deficiencies or autoimmune diseases occurred in patients with normal values at diagnosis of whom 10 were asymptomatic (incidence 10/1000 patient years). Osteoporosis and osteopenia were present in 23.3% and 35% at diagnosis. In most patients bone mineral density (BMD) improved or stabilized during follow up (p < 0.05), 8% deteriorated. The incidence of asymptomatic coeliac-related deficiencies or autoimmune diseases is low in patients with normal values at diagnosis. Therefore, routine laboratory screening is not necessary in this group: attending regular follow-up visits should be sufficient. DEXA scans are recommended.


E7386, a Selective Inhibitor of the Interaction between β-Catenin and CBP, Exerts Antitumor Activity in Tumor Models with Activated Canonical Wnt Signaling.
The Wnt/β-catenin signaling pathway plays crucial roles in embryonic development and the development of multiple types of cancer, and its aberrant activation provides cancer cells with escape mechanisms from immune checkpoint inhibitors. E7386, an orally active selective inhibitor of the interaction between β-catenin and CREB binding protein, which is part of the Wnt/β-catenin signaling pathway, disrupts the Wnt/β-catenin signaling pathway in HEK293 and adenomatous polyposis coli (APC)-mutated human gastric cancer ECC10 cells. It also inhibited tumor growth in an ECC10 xenograft model and suppressed polyp formation in the intestinal tract of ApcMin /+ mice, in which mutation of Apc activates the Wnt/β-catenin signaling pathway. E7386 demonstrated antitumor activity against mouse mammary tumors developed in mouse mammary tumor virus (MMTV)-Wnt1 transgenic mice. Gene expression profiling using RNA sequencing data of MMTV-Wnt1 tumor tissue from mice treated with E7386 showed that E7386 downregulated genes in the hypoxia signaling pathway and immune responses related to the CCL2, and IHC analysis showed that E7386 induced infiltration of CD8+ cells into tumor tissues. Furthermore, E7386 showed synergistic antitumor activity against MMTV-Wnt1 tumor in combination with anti-PD-1 antibody. In conclusion, E7386 demonstrates clear antitumor activity via modulation of the Wnt/β-catenin signaling pathway and alteration of the tumor and immune microenvironments, and its antitumor activity can be enhanced in combination with anti-PD-1 antibody. SIGNIFICANCE: These findings demonstrate that the novel anticancer agent, E7386, modulates Wnt/β-catenin signaling, altering the tumor immune microenvironment and exhibiting synergistic antitumor activity in combination with anti-PD-1 antibody.


Informed consent for medical research by the elderly.
Much has been written about the possible lack of capacity of the elderly, especially certain vulnerable populations of older individuals, to give informed consent for medical research. Several small studies have shown a deficit for comprehension of consent material, by the elderly, especially those with less education, but this appears small in comparison to an overall deficit in the general population. A number of investigations have suggested that deficits in executive control functions (ECFs) may be related to lack of capacity to make clinical judgments, but these have yet to be applied to research. Many methods have been piloted to measure capacity and to improve comprehension, some of which may help, although none has been proved conclusively to do either. As the elderly experience significant morbidity and mortality from a vast array of illnesses, the use of the elderly as subjects of medical research is especially important. To prevent older individuals from being coerced into participating or potentially being harmed by scientific investigation, they must give informed consent to their involvement. However, there are many studies to suggest that they are not well informed. A discussion ensued in the 1970s and 1980s about whether or not the elderly deserved special protection as a class of individuals, based on their possible increased risk during medical experimentation, but it was ultimately decided that, because the majority of elderly are perceived to be cognitively intact, they need not receive additional safeguards (High & Doole, 1995, Behavioral Science and Law, 13, 319-335). The U.S. Department of Health and Human Services in 2000 (Federal Registrar Rules and Regulations, 46, 8366-8392) reviewed existing protections for subjects of human research and deemed they were inadequate, issuing new guidelines. This article reviews evidence that differences exist between the ability of young and old in their capacity to give consent. Alterations in methods of obtaining consent may help individuals to give a more informed consent, and even enable subjects who lack the capacity to consent, such as cognitively impaired individuals, to participate in research. However an ideal means of screening or altering the consent process has yet to be devised. Many of these methods are briefly considered.


[Recurrence of inguinal hernia (problems and ways of treatment)].
Results of treatment of 1643 patients with inguinal hernia were analyzed, recurrence of hernia was in 8% of them. Recurrence of inguinal hernia after plastic reconstruction of anterior wall of inguinal space was in 8.2%, posterior--in 6.2% patients. Methods of reinforcement of anterior wall are preferable as the most physiological and the least traumatical. In creation of external inguinal ring the authors make suture through inguinal ligaments out of pubic tubercle. Recurrence after this operation was 1.5%.


Merkel cell carcinoma.
Merkel cell carcinoma (MCC) is a rare but aggressive neuroendocrine tumour of the skin with high rate of local recurrence and distant metastatic potential leading to poor outcomes. Merkel cells are normally found as innervated clusters of cells around hair follicles in the basal layer of the epidermis and are thought to function as touch receptors. Here, we describe a case of MCC in a 71-year-old female and provide an up-to-date review of the literature pertinent to the management of MCC.


In-hospital care pathways for stroke.
Care within a stroke unit reduces death or dependency after stroke. However, studies have found significant variations in clinical practice, access to stroke unit care, organisation of patient care, and clinical outcome. Stroke care pathways have been introduced as a method to promote organised and efficient patient care that is based on best evidence and guidelines. We aimed to assess the effects of care pathways, as compared to standard medical care, among patients with acute stroke who had been admitted to hospital. We searched the Cochrane Stroke Group Specialised Trials Register (last searched in May 2001), the Cochrane Controlled Trials Register (Issue 4, 2000), MEDLINE (1975-2000), EMBASE (1980-2000), CINAHL (1982-2000), the Index to Scientific and Technical Proceedings (ISTP, May 2001), and HealthSTAR (May 2001). We also handsearched the Journal of Managed Care (1997 to 1998), which was later renamed the Journal of Integrated Care (1998 to 2001). Reference lists of articles were searched. We considered randomised controlled trials and non-randomised studies (quasi-randomised trials, comparative studies, controlled and uncontrolled before and after studies, and interrupted time series) that compared care pathway care with standard medical care. One reviewer selected studies for inclusion and the other independently checked the decisions. Two reviewers independently assessed the methodological quality of the studies. One reviewer extracted the data and the other checked the extracted data. Data from randomised and non-randomised studies were analysed separately. We found significant statistical heterogeneity in the analysis of two outcomes (computed tomography brain scanning and duration of stay). There were three randomised controlled trials (total of 340 patients) and seven non-randomised studies (total of 1673 patients) that compared care pathway care with standard medical care. We found no difference between care pathway and control groups in terms of death, dependency, or discharge destination. Evidence from mainly non-randomised studies suggests that patients managed using a care pathway may be: a) less likely to suffer a urinary tract infection (OR 0.38, CI 0.18 to 0.79), b) less likely to be readmitted (OR 0.11, CI 0.03 to 0.39), and c) more likely to have a computed tomography brain scan (OR 3.66, CI 1.45 to 9.27) or carotid duplex study (OR 2.45, CI 1.3 to 4.61). Evidence from randomised trials suggests that patient satisfaction and quality of life may be significantly lower in the care pathway group (P=0.02 and P<0.005 respectively). The use of care pathways to manage stroke patients in hospital may be associated with both positive and negative effects on the process of care and clinical outcomes. Since most of the results have been derived from non-randomised studies, they are likely to be influenced by potential biases and confounding factors. There is currently insufficient supporting evidence to justify routine implementation of care pathways for acute stroke management or stroke rehabilitation.


Diagnosis and management of diabetes and the relationship of dglucose to kidney function.
This article reviews different glycemic parameters and is aimed to clarify the most dependable glycemic parameter that predicts renal preservation. Glycosylated hemoglobin (HbA1c) and fasting blood glucose (FBG) are the most commonly ordered tests for the diagnosis of diabetes and are also used to indicate prevention of microvascular complications associated with diabetes. Some experts have concluded that HbA1c remains the only test that can predict microvascular complications but HbA1c is misleading with anemia. Other experts have reported that elevation of 2 hour postprandial glucose (2hPPG) or postprandial hyperglycemia is critical for the development of diabetic complications Measurement of parameters under fasting conditions is convenient in both clinical and research settings and are used to establish clinical guidelines for diabetes management and for rating efficacy of management. Despite the use of these diagnostic markers and a plethora of oral antidiabetic agents to treat diabetes, diabetic complications namely; cardiovascular disorders (CVD), end stage renal disease (ESRD) and amputation are on the rise. Although affirmative data on many of the complications are not available, the United States Renal Data System on ESRD is a testimonial to poor diabetes care. We have innovated dglucose (2hPPG-FBG) and found that dglucose relates significantly to renal function change measured by serum creatinine levels or estimated glomerular filtration rate. Our current study on dglucose confirms our previous finding and validates the importance of dglucose to aid in the management of diabetes and prevents diabetic complications. In conclusion, the new finding in this study is dglucose (2h-postprandial glucose-Fasting glucose) which convincingly relates to renal function changes. Since dglucose is a product of 2hPP glucose, keeping 2hPPG under tight control with intensive insulin therapy is fundamentally important. Further blood pressure control avoiding the use of renin-angiotensin inhibitor therapy is additive to renal protection in diabetes.


Structure and DNA binding of alkylation response protein AidB.
Exposure of Escherichia coli to alkylating agents activates expression of AidB in addition to DNA repair proteins Ada, AlkA, and AlkB. AidB was recently shown to possess a flavin adenine dinucleotide (FAD) cofactor and to bind to dsDNA, implicating it as a flavin-dependent DNA repair enzyme. However, the molecular mechanism by which AidB acts to reduce the mutagenic effects of specific DNA alkylators is unknown. We present a 1.7-A crystal structure of AidB, which bears superficial resemblance to the acyl-CoA dehydrogenase superfamily of flavoproteins. The structure reveals a unique quaternary organization and a distinctive FAD active site that provides a rationale for AidB's limited dehydrogenase activity. A highly electropositive C-terminal domain not present in structural homologs was identified by mutational analysis as the DNA binding site. Structural analysis of the DNA and FAD binding sites provides evidence against AidB-catalyzed DNA repair and supports a model in which AidB acts to prevent alkylation damage by protecting DNA and destroying alkylating agents that have yet to reach their DNA target.


[Miliary tuberculosis and adult respiratory distress syndrome in an infant].
We report on a 7 months old infant, who was admitted to our hospital with the tentative diagnosis of interstitial pneumonia. The infant was treated with erythromycin because of a positive mycoplasma antigen test in the nasopharyngeal mucus and the radiological findings. A tension pneumothorax led to rapid respiratory deterioration and a severe ARDS developed. A sustained respiratory stabilization could not be achieved. The diagnosis miliary tuberculosis was detected on autopsy. A parenchymal focus was found subpleurally in the left lung with a massive hematogenous spread and a tuberculous meningitis. The source of infection could not be identified in the family or in persons known to have had contact to the infant. The tuberculin skin test (PPD) was negative. Clinical, radiological and pathological findings are demonstrated.


Acute iatrogenic polycythemia induced by massive red blood cell transfusion during subtotal abdominal colectomy.
A 46 year old man was transfused ten units of packed red blood cells during subtotal colectomy after intraoperative point-of-care testing values demonstrated hemoglobin values less than seven grams per deciliter (g/dL). A postoperative hemoglobin analyzed in a standard hematologic laboratory revealed a hemoglobin value of 27.8 g/dL. He underwent emergent red blood cell depletion therapy which decreased his hemoglobin to 7.5 g/dL. The physiologic consequences of iatrogenic polycythemia caused by massive transfusion during major abdominal surgery must take into account the fluid shifts that interplay between the osmotic load, viscosity of blood, and postoperative third spacing of fluid. Treatment of acute iatrogenic polycythemia can be effectively accomplished by red blood cell depletion therapy. However, fluid shifts caused by massive transfusion followed by rapid red cell depletion produce a unique physiologic state that is without a well-described algorithm for management.


Effects of particle size and formaldehyde treatment of soybean meal on milk production and composition for dairy cows.
Twenty-four lactating dairy cattle were used to study the effects of formaldehyde treatment and reduction of particle size of soybean meal on milk production and composition. Cows were fed diets containing one of the following soybean meals: 1) untreated, coarse; 2) untreated, fine; 3) formaldehyde-treated, fine. Formaldehyde reduced the solubility of soybean meal protein from 22.7 to 2.9%. Grinding soybean meal reduced particle size from 842 to 249 micron. Formaldehyde treatment did not affect intake or milk production but resulted in higher efficiency of milk production (1.43 versus 1.46 kg fat-corrected milk/kg dry matter intake). Milk protein (3.08 versus 2.85%) and solids-not-fat (8.51 versus 8.35%) contents were reduced by formaldehyde. Cows fed fine soybean meal had higher dry matter intakes (22.0 versus 20.8 kg dry matter/day) and gained more body weight; however, milk production was not affected by particle size. Grinding soybean meal reduced production efficiency (1.47 versus 1.42 kg milk/kg dry matter intake) and milk fat (3.70 versus 3.33%). Lack of production response and reduced milk protein from formaldehyde treatment suggests possible overprotection of protein. Fine grinding of soybean meal appeared to favor body weight gain rather than milk production.


Surgical planing of the skin; dichlorotetrafluoro-ethane as a freezing agent.
Surgical skin planing is, in the hands of an experienced operator, a safe and highly effective procedure for treating a number of cutaneous defects, most notably pitted acne scars. The operation is facilitated by the use of a new instrument (jet-spray handpiece) which allows the operator to freeze the skin and plane it almost simultaneously, and by a new freezing agent, dichlorotetrafluoro-ethane, which adds to the safety by eliminating the old hazards of inflammability, explosion, and the toxic inhalation of ethyl chloride. The ability to sharply differentiate between keloid and hypertrophic scar is fundamental to surgical skin planing. A hypertrophic scar results from the removal or destruction of the cutaneous appendages (hair follicles, oil and sweat glands and ducts); whereas a keloid is an idiosyncratic response without regard to damage of the appendages.Properly performed surgical planing does not entirely remove these appendages and therefore healing occurs without scarring.


Functional Outcomes Following Posterior Cruciate Ligament and Posterolateral Corner Reconstructions. A Three-year Experience in Seremban, Malaysia.
This study was conducted to evaluate the demographics, causes and outcomes of patients who underwent Posterior Cruciate Ligament (PCL) reconstruction and/or Posterolateral Corner (PLC) reconstruction performed at our institution over the last three years. Sub-analysis was performed to assess the impact of delay from injury to surgery and how this affected outcomes. From an initial number of 10 patients, seven were contactable and available for analysis. All patients underwent PCL and/or PLC reconstruction (modified Larson's procedure) between 2017 and 2019. The mean age of our cohort was 31.4±9.6 years (range, 21 to 46). Assessment of functional outcomes pre- and post-operatively were done using the Lysholm knee scoring scale, the Knee injury and Osteoarthritis Outcome Score (KOOS) and visual analogue scale (VAS). The mean follow-up from operation at time of reporting was seven months (range, 2 to 12 months). There were four combined PCL and PLCs, two isolated PLCs and one patient who underwent an isolated PCL reconstruction. There were significant improvements between pre-operative and post-operative in all functional outcome scores utilised following PCL reconstruction and/or modified Larson's reconstruction. Lysholm knee scoring scale improved from pre-operative to post-operative at 41.14±12.32 to 74.86±13.52 (p=0.0001), KOOS from 49.71±11.19 to 71.43±13.84 (p=0.001), and VAS from 5.71±2.06 to 2.86±2.48 (p=0.001). Our sub-analysis showed that higher functional outcomes were present when surgery was done less than six months from the time of index injury. There were no complications (eg. Infections, revisions) in this cohort at the time of reporting. Reconstructive surgery for PCL and/or PLC injury is successful in increasing the functional outcomes of patients post-operatively. Delays from injury to surgery remains a problem in the public setting as patients may need to await appropriate imaging and approval of funding. Increased awareness for early surgical intervention may improve overall outcomes of PCL and/or PLC reconstruction in Malaysia.


Body mass index and breast cancer risk in Japan: a pooled analysis of eight population-based cohort studies.
A positive association between body mass index (BMI) and breast cancer risk among postmenopausal women has been reported, and a weak inverse association has been suggested among premenopausal women from studies in the Western population. The effects of BMI on breast cancer have remained unclear among the Asian population, especially in premenopausal women. We assessed the associations between BMI and breast cancer incidence by a pooled analysis from eight representative large-scale cohort studies in Japan. Cancer incidence was mainly confirmed through regional population-based cancer registries and/or through active patient notification from major local hospitals. Breast cancer was defined as code C50 according to ICD10. Pooled estimates of the hazard ratios (HRs) and 95% confidence interval (CIs) for breast cancer were calculated using random-effects models. Analytic subjects were 183 940 women, 1783 of whom had breast cancer during 2 194 211 person-years of follow-up. A positive association between BMI and the risk of postmenopausal breast cancer was observed (trend P<0.001). The HRs for premenopausal breast cancer were 1.05 (95% CI 0.56-1.99), 1.07 (95% CI 0.76-1.52), 0.91 (95% CI 0.64-1.30), 1.15 (95% CI 0.76-1.73), 1.45 (95% CI 0.71-2.94), and 2.25 (95% CI 1.10-4.60), respectively, in BMIs of <19, 19 to <21, 21 to <23, 25 to <27, 27 to <30, and ≥30 kg/m2. These results were not substantially altered after excluding the patients who were diagnosed with breast cancer in the first 2 years of follow-up. The increased risk of postmenopausal breast cancer among women with higher BMIs was confirmed in Japanese. A borderline-significant positive association between BMI and premenopausal breast cancer was observed, suggesting that body mass in Asian women might have opposite effects on breast cancer compared with Western women.


Tissue plasminogen activator induced fibrinolysis: standardization of method using thromboelastography.
Fibrinolysis is a complex physiological process that involves the interaction of several anticoagulant proteins. Defects of the fibrinolytic system are extremely difficult to diagnose and study because there are no standardized tests available. Thromboelastography is a novel method that allows the study of both coagulation and fibrinolysis using one sample of whole blood, thereby allowing a more physiologic assessment of the coagulation process. Several in-vitro studies have been attempted to determine whether thromboelastography would be a useful assay for the study of fibrinolysis but have reported problems with reproducibility and reliability. Here we report the process involved in developing a thromboelastographic assay in which tissue plasminogen activator (t-PA) is used to induce fibrinolysis. The assay was standardized to ensure that the concentration of the coagulation inducer (tissue factor) and fibrinolytic agent (t-PA) was adequate to induce a clot with lysis parameters that were reproducible and reliable. This method can be used to rapidly assess the intrinsic fibrinolytic potential of whole blood. Our assay showed that it could rapidly predict high levels of plasminogen activator inhibitor, and this information would be beneficial in patients with acute stroke or myocardial infarction.


Clinical-pathological correlations of BAV and the attendant thoracic aortopathies. Part 2: Pluridisciplinary perspective on their genetic and molecular origins.
Bicuspid aortic valve (BAV) arises during valvulogenesis when 2 leaflets/cusps of the aortic valve (AOV) are fused together. Its clinical manifestations pertain to faulty AOV function, the associated aortopathy, and other complications surveyed in Part 1 of the present bipartite-series. Part 2 examines mainly genetic and epigenetic causes of BAV and BAV-associated aortopathies (BAVAs) and disease syndromes (BAVD). Part 1 explored the heterogeneity among subsets of patients with BAV and BAVA/BAVD, and investigated abnormal fluid dynamic stress and strain patterns sustained by the cusps. Specific BAV morphologies engender systolic outflow asymmetries, associated with abnormal aortic regional wall-shear-stress distributions and the expression/localization of BAVAs. Understanding fluid dynamic factors besides the developmental mechanisms and underlying genetics governing these congenital anomalies is necessary to explain patient predisposition to aortopathy and phenotypic heterogeneity. BAV aortopathy entails complex/multifactorial pathophysiology, involving alterations in genetics, epigenetics, hemodynamics, and in cellular and molecular pathways. There is always an interdependence between organismic developmental signals and genes-no systemic signals, no gene-expression; no active gene, no next step. An apposite signal induces the expression of the next developmental gene, which needs be expressed to trigger the next signal, and so on. Hence, embryonic, then post-partum, AOV and thoracic aortic development comprise cascades of developmental genes and their regulation. Interdependencies between them arise, entailing reciprocal/cyclical mutual interactions and adaptive feedback loops, by which developmental morphogenetic processes self-correct responding to environmental inputs/reactions. This Survey can serve as a reference point and driver for further pluridisciplinary BAV/BAVD studies and their clinical translation.


Disparities in early exposure to book sharing within immigrant families.
This study examined the early developmental context of children in immigrant families (CIF), measured by the frequency with which parents share books with their children. Trends in the frequency with which parents report book sharing, defined in this analysis as reading or sharing picture books with their young children, were analyzed across immigrant and nonimmigrant households by using data from the 2005, 2007, and 2009 California Health Interview Survey. Stepwise multivariate logistic regression assessed the likelihood that CIF shared books with parents daily. In this study, 57.5% of parents in immigrant families reported daily book sharing (DBS), compared with 75.8% of native-born parents. The lowest percentage of DBS was seen in Hispanic families with 2 foreign-born parents (47.1%). When controlling for independent variables, CIF with 2 foreign-born parents had the lowest odds of sharing books daily (odds ratio [OR]: 0.61; 95% confidence interval [CI]: 0.54-0.68). When stratified by race/ethnicity, separate multivariate logistic regressions revealed CIF status to be associated with lower odds of DBS for Asian (OR: 0.56; 95% CI: 0.38-0.81) and Hispanic CIF (OR: 0.49; 95% CI: 0.42-0.58). There is an association between the lower odds of DBS and parental immigrant status, especially for Hispanic and Asian children. This relationship holds after controlling for variables thought to explain differences in literacy-related practices, such as parental education and income. Because book sharing is central to children's development of early literacy and language skills, this disparity merits further exploration with the aim of informing future interventions.


Predictive Value of 18F-Florbetapir and 18F-FDG PET for Conversion from Mild Cognitive Impairment to Alzheimer Dementia.
The present study examined the predictive values of amyloid PET, 18F-FDG PET, and nonimaging predictors (alone and in combination) for development of Alzheimer dementia (AD) in a large population of patients with mild cognitive impairment (MCI). Methods: The study included 319 patients with MCI from the Alzheimer Disease Neuroimaging Initiative database. In a derivation dataset (n = 159), the following Cox proportional-hazards models were constructed, each adjusted for age and sex: amyloid PET using 18F-florbetapir (pattern expression score of an amyloid-β AD conversion-related pattern, constructed by principle-components analysis); 18F-FDG PET (pattern expression score of a previously defined 18F-FDG-based AD conversion-related pattern, constructed by principle-components analysis); nonimaging (functional activities questionnaire, apolipoprotein E, and mini-mental state examination score); 18F-FDG PET + amyloid PET; amyloid PET + nonimaging; 18F-FDG PET + nonimaging; and amyloid PET + 18F-FDG PET + nonimaging. In a second step, the results of Cox regressions were applied to a validation dataset (n = 160) to stratify subjects according to the predicted conversion risk. Results: On the basis of the independent validation dataset, the 18F-FDG PET model yielded a significantly higher predictive value than the amyloid PET model. However, both were inferior to the nonimaging model and were significantly improved by the addition of nonimaging variables. The best prediction accuracy was reached by combining 18F-FDG PET, amyloid PET, and nonimaging variables. The combined model yielded 5-y free-of-conversion rates of 100%, 64%, and 24% for the low-, medium- and high-risk groups, respectively. Conclusion:18F-FDG PET, amyloid PET, and nonimaging variables represent complementary predictors of conversion from MCI to AD. Especially in combination, they enable an accurate stratification of patients according to their conversion risks, which is of great interest for patient care and clinical trials.


Comparison of eating attitudes and behaviors among adolescent and young women with type 1 diabetes mellitus and phenylketonuria.
The purpose of this study was to assess the eating attitudes and behaviors associated with two chronic diseases that have strong dietary treatment components: type 1 diabetes mellitus and phenylketonuria (PKU). Participants consisted of female campers and staff members who were attending one of two summer camps that specialize in the care of females with type 1 diabetes mellitus (N = 54) and PKU (N = 30). Eating attitudes and behaviors, psychological adjustment, and disease-specific knowledge were assessed using standardized and nonstandardized self-report questionnaires. There was no overall difference in the presence of disordered eating symptomatology between those with diabetes and those with PKU. However, differences in patterns of eating attitudes and behaviors were observed. The data suggest that living with chronic diseases which are treated with dietary management may adversely affect eating attitudes and behaviors and may increase susceptibility to the development of eating disturbances.


Quality improvement of melt extruded laminar systems using mixture design.
This study investigates the application of melt extrusion for the development of an oral retard formulation with a precise drug release over time. Since adjusting the formulation appears to be of the utmost importance in achieving the desired drug release patterns, different formulations of laminar extrudates were prepared according to the principles of Experimental Design, using a design for mixtures to assess the influence of formulation composition on the in vitro drug release from the extrudates after 1h and after 8h. The effect of each component on the two response variables was also studied. Ternary mixtures of theophylline (model drug), monohydrate lactose and microcrystalline wax (as thermoplastic binder) were extruded in a lab scale vertical ram extruder in absence of solvents at a temperature below the melting point of the binder (so that the crystalline state of the drug could be maintained), through a rectangular die to obtain suitable laminar systems. Thanks to the desirability approach and a reliability study for ensuring the quality of the formulation, a very restricted optimal zone was defined within the experimental domain. Among the mixture components, the variation of microcrystalline wax content played the most significant role in overall influence on the in vitro drug release. The formulation theophylline:lactose:wax, 57:14:29 (by weight), selected based on the desirability zone, was subsequently used for in vivo studies. The plasma profile, obtained after oral administration of the laminar extruded system in hard gelatine capsules, revealed the typical trend of an oral retard formulation. The application of the mixture experimental design associated to a desirability function permitted to optimize the extruded system and to determine the composition space that ensures final product quality.


Relationship of destructive periodontal disease to the acute-phase response.
Destructive periodontal diseases have been associated with an increased risk of atherosclerotic complications; however, the potential mechanisms are yet to be defined. Inflammation plays a central role in atherosclerosis since C-reactive protein (CRP), an acute-phase protein monitored as a marker of inflammatory status, has been identified as a major risk factor for atherosclerotic complications. Recent reports that destructive periodontal diseases can increase CRP values present the possibility that the acute-phase response may link these 2 disease processes. The objective of the present investigation was to determine the effect of destructive periodontal disease status, severity, and progression on components of the acute-phase response in an urban minority population. Clinical measurements recorded included probing depth, attachment level, gingival erythema, bleeding upon probing, suppuration, and plaque. Disease progression was defined as a >2 mm loss of attachment 2 months post-baseline. Serum antibody was measured by enzyme-linked immunosorbent assay. CRP was measured using a high-sensitivity CRP (hsCRP) assay. A commercial laboratory measured serum glucose (non-fasting), albumin, cholesterol, high-density lipoprotein (HDL), triglycerides, low-density lipoprotein (LDL), and iron. Increased serum IgG antibody to Porphyromonas gingivalis, but not to 5 other species, was associated with periodontal disease status, increased severity, and progression as were age, male gender, and smoking. Cholesterol and LDL were increased in disease, and HDL and iron were increased in health. hsCRP, glucose, and cholesterol increased with disease progression. By regression analysis, IgG antibody to P. gingivalis correlated with age, probing depth, and hsCRP, and negatively correlated with albumin and iron. By logistic regression, subjects who experienced multiple sites of disease progression and elevated antibody to P. gingivalis increased the odds ratio of hsCRP>2.08 mg/l by 14.1 and 5.6, respectively. These results suggest that destructive periodontal disease and disease progression are associated with changes in serum components consistent with an acute-phase response.


In vitro blood-brain barrier models--latest advances and therapeutic applications in a chronological perspective.
The first generation of in vitro models providing successful isolation of viable brain endothelial cells from different species, which could be maintained in cell culture, have emerged around thirty years ago. However, the time consuming and the difficulty of working with primary culture cells led to the development of simpler models employing cell lines with blood-brain barrier properties. The creation, in late nineties, of a transgenic mouse harboring the temperature sensitive simian virus 40 large T-antigen as a source of conditionally immortalized brain endothelial cell lines circumvented the problems of in vitro transfection of tumour inducing gene in primary cells. These different ways to obtain cultures of brain endothelial cells have profited from the discovery of different cellular factors that allow the growth of differentiated cells on plastic filters. Although cell preparations and culture conditions of brain endothelial cells are based on the same principle, there are two main models for studying the blood-brain barrier: the static and the more recently described dynamic model. Dynamic models were created in order to replicate the physiological in vivo environment of the blood-brain barrier. The large pool of in vitro models is being enlarged since each laboratory improves its model adding small differences adapted to the research interests. The great impact of blood-brain barrier studies in the development of therapies related to the central nervous system supports the interests of this review about in vitro models.


Zinc and zinc transporters in normal prostate and the pathogenesis of prostate cancer.
Zinc is an essential metal for all cells. It plays a role in a wide variety of physiological and biochemical processes. In the prostate epithelial cell the accumulation of high cellular zinc is a specialized function that is necessary for these cells to carry out the major physiological functions of production and secretion of citrate. The production of citrate and its secretion into prostatic fluid is a differentiated function of the prostate epithelial cells that is apparently important for reproduction. The loss of citrate and zinc accumulation is the most consistent and persistent characteristic of prostate malignancy. This characteristic of prostate cancer indicates that the lost ability of the malignant cells to accumulate zinc and citrate is an important factor in the development and progression of malignancy. The lost ability of the epithelial cells to accumulate zinc and thus to also accumulate citrate is the result of decreased expression of specific zinc uptake transporters. The purpose of this presentation is to review the current understanding of zinc and zinc homeostasis in the prostate and the role of zinc and zinc transporters in the normal function of the prostate and the pathogenesis of prostate cancer.


The Effect of the Postural Control Strategy on the Recognition Error of Center-of-Pressure Sway.
The purpose of this study was to examine the effect of postural control strategies on the recognition error (RE) of center-of-pressure (COP) sway forward based on perceived exertion. Participants were 43 middle-aged or elderly people. We measured the maximum COP sway forward (100% center-of-pressure distance(COP-D)), 60% and 30% COP-D of 100% COP-D based on perceived exertion, and participants were classified into the good balance group and bad balance group by RE. The RE and trunk and leg angles were evaluated during COP sway forward. Results showed that RE being significantly higher for 30% COP-D and the group with a larger RE had a significantly larger trunk angle. Therefore, they may have used hip strategy predominantly to perform postural control ability, not only maximum values, but also on perceived exertion.


Parenchymal and vascular magnetic resonance imaging of the brain after extracorporeal membrane oxygenation.
Three-dimensional (volume) magnetic resonance angiography is a new and noninvasive method for imaging the intracranial vasculature. The combination of magnetic resonance angiography and conventional magnetic resonance imaging was used to evaluate brain parenchyma and vessels in 30 survivors of extracorporeal membrane oxygenation. Magnetic resonance imaging findings were abnormal in 33% of the patients, with no increased frequency of right hemispheric lesions. Magnetic resonance angiography demonstrated good intracranial flow in all infants and demonstrable right internal carotid arterial flow in 35% of those patients with permanent carotid ligation. An abnormal magnetic resonance imaging study was found more often in infants with abnormal predischarge neurologic examination results. These techniques have several advantages over other neuroimaging modalities, including better definition of deep structures, myelin formation, and intracranial vasculature, the absence of bone artifact, and the elimination of catheter or contrast use.


[Urologic manifestations of primary hyperparathyroidism].
We report on 79 patients with primary hyperparathyroidism (PHPT) and analyze the urological manifestations, analytical and histopathological changes commonly encountered in this disease. The importance of repeating calcium studies in patients with recurrent calcium stone formation is underscored. The appropriate metabolic work up should be performed when elevated values are detected.


Detecting subtle signs of depression with automated speech analysis in a non-clinical sample.
Automated speech analysis has gained increasing attention to help diagnosing depression. Most previous studies, however, focused on comparing speech in patients with major depressive disorder to that in healthy volunteers. An alternative may be to associate speech with depressive symptoms in a non-clinical sample as this may help to find early and sensitive markers in those at risk of depression. We included n = 118 healthy young adults (mean age: 23.5 ± 3.7 years; 77% women) and asked them to talk about a positive and a negative event in their life. Then, we assessed the level of depressive symptoms with a self-report questionnaire, with scores ranging from 0-60. We transcribed speech data and extracted acoustic as well as linguistic features. Then, we tested whether individuals below or above the cut-off of clinically relevant depressive symptoms differed in speech features. Next, we predicted whether someone would be below or above that cut-off as well as the individual scores on the depression questionnaire. Since depression is associated with cognitive slowing or attentional deficits, we finally correlated depression scores with performance in the Trail Making Test. In our sample, n = 93 individuals scored below and n = 25 scored above cut-off for clinically relevant depressive symptoms. Most speech features did not differ significantly between both groups, but individuals above cut-off spoke more than those below that cut-off in the positive and the negative story. In addition, higher depression scores in that group were associated with slower completion time of the Trail Making Test. We were able to predict with 93% accuracy who would be below or above cut-off. In addition, we were able to predict the individual depression scores with low mean absolute error (3.90), with best performance achieved by a support vector machine. Our results indicate that even in a sample without a clinical diagnosis of depression, changes in speech relate to higher depression scores. This should be investigated in more detail in the future. In a longitudinal study, it may be tested whether speech features found in our study represent early and sensitive markers for subsequent depression in individuals at risk.


New Developments in Microbiome in Alcohol-Associated and Nonalcoholic Fatty Liver Disease.
Alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are important causes of morbidity and mortality worldwide. The intestinal microbiota is involved in the development and progression of both ALD and NAFLD. Here we describe associated changes in the intestinal microbiota, and we detail randomized clinical trials in ALD and NAFLD which evaluate treatments modulating the intestinal microbiome including fecal microbiota transplantation, probiotics, prebiotics, synbiotics, and antibiotics. Finally, we discuss precision medicine approaches targeting the intestinal microbiome to ameliorate ALD and NAFLD.


Direct Measures of Medication Effects: Exploring the Scientific Utility of Behavior-Analytic Assessments.
The purpose of the current study was to explore the scientific utility of two behavior analytic assessments (i.e., progressive ratio and demand assessments) for psychotropic medication evaluation. For a sample of 23 children with disabilities who were prescribed medication, we conducted a series of generalizability and optimization studies to identify sources of score variance and conditions in which stable estimates of behavior can be obtained. To inform construct validity, we calculated correlations between scores from each assessment and those from a standardized behavior rating scale (Aberrant Behavior Checklist-Second Edition; ABC-2). Results offer initial support for the scientific utility of progressive ratio scores. More research is needed to evaluate sensitivity to change and construct validity of scores from these and other behavior analytic assessments.


Flexible Two-Phase studies for rare exposures: Feasibility, planning and efficiency issues of a new variant.
The two-phase design consists of an initial (Phase One) study with known disease status and inexpensive covariate information. Within this initial study one selects a subsample on which to collect detailed covariate data. Two-phase studies have been shown to be efficient compared to standard case-control designs. However, potential problems arise if one cannot assure minimum sample sizes in the rarest categories or if recontact of subjects is difficult. In the case of a rare exposure with an inexpensive proxy, the authors propose the flexible two-phase design for which there is a single time of contact, at which a decision about full covariate ascertainment is made based on the proxy. Subjects are screened until the desired numbers of cases and controls have been selected for full data collection. Strategies for optimizing the cost/efficiency of this design and corresponding software are presented. The design is applied to two examples from occupational and genetic epidemiology. By ensuring minimum numbers for the rarest disease-covariate combination(s), we obtain considerable efficiency gains over standard two-phase studies with an improved practical feasibility. The flexible two-phase design may be the design of choice in the case of well targeted studies of the effect of rare exposures with an inexpensive proxy.


Structural monitoring and modeling of the mechanical deformation of three-dimensional printed poly(ε-caprolactone) scaffolds.
Three-dimensional (3D) printed poly(ε-caprolactone) (PCL) based scaffolds have being proposed for different tissue engineering applications. This study addresses the design and fabrication of 3D PCL constructs with different struts alignments at 90°, 45° and 90° with offset. The morphology and the mechanical behavior under uniaxial compressive load were assessed at different strain percentages. The combination of a new compressionCT device and micro computed tomography (micro-CT) allowed understanding the influence of pore geometry under controlled compressive strain in the mechanical and structural behavior of PCL constructs. Finite element analysis (FEA) was applied using the micro-CT data to modulate the mechanical response and compare with the conventional uniaxial compression tests. Scanning electron microscopic analysis showed a very high level of reproducibility and a low error comparing with the theoretical values, confirming that the alignment and the dimensional features of the printed struts are reliable. The mechanical tests showed that the 90° architecture presented the highest stiffness. With the compressionCT device was observed that the 90° and 90° with offset architectures presented similar values of porosity at same strain and similar pore size, contrary to the 45° architecture. Thus, pore geometric configurations affected significantly the deformability of the all PCL scaffolds under compression. The prediction of the FEA showed a good agreement to the conventional mechanical tests revealing the areas more affected under compression load. The methodology proposed in this study using 3D printed scaffolds with compressionCT device and FEA is a framework that offers great potential in understanding the mechanical and structural behavior of soft systems for different applications, including for the biomedical engineering field.


Roux-en-Y gastric bypass after previous unsuccessful gastric restrictive surgery.
In the treatment of morbid obesity, simple gastric restrictive methods such as silicone adjustable gastric banding, vertical banded gastroplasty, and nonadjustable gastric banding often fail to control weight in the long run or give rise to intolerable side effects. Here we review our results from conversion of such failures to Roux-en-Y gastric bypass. The study comprised 44 patients (median age 42 years, range 24 to 60 years) who underwent revision surgery in 1996 and 1997. Body mass index at revision was 35 kg/m(2) (range 21 to 49 kg/m(2)). Previous bariatric procedures included silicone adjustable gastric banding (n = 26), vertical banded gastroplasty (n = 13), and gastric banding (n = 5). The most common reasons for conversion after silicone adjustable gastric banding and nonadjustable gastric banding were band erosion (n = 12) and esophagitis (n = 11). Staple line disruption (n = 12) with subsequent weight loss failure was the primary cause after vertical banded gastroplasty. There were no postoperative deaths or anastomotic leaks. One patient underwent reexploration because of an infected hematoma. Reflux symptoms and vomiting resolved promptly. At global assessment 2 years later, 70% of the patients were very satisfied. Median body mass index had decreased to 28 kg/m(2) (range 18 to 42 kg/m(2)). No patient was lost to follow-up. As reported previously, failure after vertical gastric banding can be treated by conversion to Roux-en-Y gastric bypass with good results. In this study we found that failure after silicone adjustable gastric banding can be treated successfully with Roux-en-Y gastric bypass as well.


Therapeutic Instruments Targeting Meibomian Gland Dysfunction.
The most prevalent type of meibomian gland dysfunction (MGD), which is obstructive, is the main cause of evaporative dry eye and is characterized by changes in the meibum composition and duct obstruction. Eyelid hygiene has usually been the most common clinical approach. However, alternative therapies for MGD are emerging on the market. Some warming and humidity devices have led to an improvement in the signs and symptoms in MGD patients. Likewise, eyelid massaging and cleaning devices are also beneficial for ocular signs and symptoms; however, patients usually need more than one session to maintain the therapeutic effect. Thermal pulsation has been reported to be more efficient than other strategies, and the effects can last up to 12 months. Moreover, intense pulsed light therapy has been demonstrated to improve ocular signs and symptoms alone and in combination with other therapies. Proper counseling of clinicians considering MGD status and patient compliance will help patients to undergo the adequate technique that best suits their condition.


[Assessment on Minnesota Living with Heart Failure Questionnaire in the Principle of Chinese Civilization and Traditional Medicine Characteristics].
Objective To assess Minnesota living with heart failure questionnaire in the principle of Chinese civilization and Traditional Medicine characteristics (C-MLHF). Methods A survey was con- ducted in 124 heart failure ( HF) patients using C-MLHF and Minnesota living with heart failure question- naire (MLHF). Reliability, validity, feasibility, and the correlation of New York Heart Association (NYHA) classification was compared between the two questionnaires. Results The recovery of C-MLHF was 95. 2% (118/124) ,the effective rate was 97. 5% (115/118), Cronbach's α was 0. 896, and the validity ranged 0. 505 -0. 875. The correlation with MLHF was 0. 946 (P <0. 01) , the correlation with NYHA classi- fication was 0. 524 (P <0. 05). The recovery of MLHF was 95. 2% (118/124) , the effective rate was 88. 1%(104/118) , Cronbach's a was 0. 889, and the validity ranged 0. 487 -0. 787. The correlation with NYHA classification was 0. 468 (P <0. 05). Conclusions The C-MLHF had better feasibility, reliability, validity, and relativity between feasibility/reliability and NYHA classification, as compared with MLHF. In conclusion C-MLHF was more suitable for assessing quality of life for Chinese HF patients.


MR spectroscopy of the fetal brain: is it possible without sedation?
The quality of spectroscopic studies may be limited because of unrestricted fetal movement. Sedation is recommended to avoid motion artefacts. However, sedation involves side effects. The aim of this study was to assess the feasibility and quality of brain (1)H-MR spectroscopy in unsedated fetuses and to evaluate whether quality is dependent on the type of spectra, fetal presentation, GA, and/or fetal pathology. Seventy-five single-voxel spectroscopic studies of the fetal brain, performed at gestational weeks 19-38 at 1.5T, were evaluated retrospectively. A PRESS (TE = 144 or 35 ms) was used. Fetal presentation, GA, and kind of pathology were recorded. The quality of the spectra was assessed by reviewing the spectral appearance (line width, signal-to-noise) of the creatine resonance obtained relative to concentrations (ratios-to-creatine) of choline, myo-inositol, and NAA. Of 75 studies, 50 (66.6%) were rated as readable: short TE = 17/50 (34%), long TE = 33/50 (66%), cephalic presentation in 36/50 (72%) studies, breech in 10/50 (20%) studies, and "other" presentation in 4/50 (8%) studies (mean GA, 31.0 weeks). Twenty-eight of 50 fetuses (56%) showed normal development (short TE = 12/28, long TE = 16/28), and 22/50 (44%) showed pathology. Of the 75 studies, 25 (33.3%) were not readable: short TE = 14/25 (56%), long TE = 11/25 (44%), cephalic presentation in 20/25 (80%) studies, breech in 4/25 (16%) studies, and other presentation in 1 study (4%) (mean GA, 30.1 week). Thirteen of 25 fetuses (52%) showed normal development; 12/25 (48%) showed pathology. Statistical analysis revealed no impact of the different parameters on the quality of spectra. Single-voxel spectroscopy can be performed in approximately two-thirds of unsedated fetuses, regardless of the type of spectra, fetal presentation, GA, and pathology.


Salt adaptability in a halophytic soybean (Glycine soja) involves photosystems coordination.
Glycine soja is a halophytic soybean native to saline soil in Yellow River Delta, China. Photosystem I (PSI) performance and the interaction between photosystem II (PSII) and PSI remain unclear in Glycine soja under salt stress. This study aimed to explore salt adaptability in Glycine soja in terms of photosystems coordination. Potted Glycine soja was exposed to 300 mM NaCl for 9 days with a cultivated soybean, Glycine max, as control. Under salt stress, the maximal photochemical efficiency of PSII (Fv/Fm) and PSI (△MR/MR0) were significantly decreased with the loss of PSI and PSII reaction center proteins in Glycine max, and greater PSI vulnerability was suggested by earlier decrease in △MR/MR0 than Fv/Fm and depressed PSI oxidation in modulated 820 nm reflection transients. Inversely, PSI stability was defined in Glycine soja, as △MR/MR0 and PSI reaction center protein abundance were not affected by salt stress. Consistently, chloroplast ultrastructure and leaf lipid peroxidation were not affected in Glycine soja under salt stress. Inhibition on electron flow at PSII acceptor side helped protect PSI by restricting electron flow to PSI and seemed as a positive response in Glycine soja due to its rapid recovery after salt stress. Reciprocally, PSI stability aided in preventing PSII photoinhibition, as the simulated feedback inhibition by PSI inactivation induced great decrease in Fv/Fm under salt stress. In contrast, PSI inactivation elevated PSII excitation pressure through inhibition on PSII acceptor side and accelerated PSII photoinhibition in Glycine max, according to the positive and negative correlation of △MR/MR0 with efficiency that an electron moves beyond primary quinone and PSII excitation pressure respectively. Therefore, photosystems coordination depending on PSI stability and rapid response of PSII acceptor side contributed to defending salt-induced oxidative stress on photosynthetic apparatus in Glycine soja. Photosystems interaction should be considered as one of the salt adaptable mechanisms in this halophytic soybean.


Analyzing Dirac Cone and Phonon Dispersion in Highly Oriented Nanocrystalline Graphene.
Chemical vapor deposition (CVD) is one of the most promising growth techniques to scale up the production of monolayer graphene. At present, there are intense efforts to control the orientation of graphene grains during CVD, motivated by the fact that there is a higher probability for oriented grains to achieve seamless merging, forming a large single crystal. However, it is still challenging to produce single-crystal graphene with no grain boundaries over macroscopic length scales, especially when the nucleation density of graphene nuclei is high. Nonetheless, nanocrystalline graphene with highly oriented grains may exhibit single-crystal-like properties. Herein, we investigate the spectroscopic signatures of graphene film containing highly oriented, nanosized grains (20-150 nm) using angle-resolved photoemission spectroscopy (ARPES) and high-resolution electron energy loss spectroscopy (HREELS). The robustness of the Dirac cone, as well as dispersion of its phonons, as a function of graphene's grain size and before and after film coalescence, was investigated. In view of the sensitivity of atomically thin graphene to atmospheric adsorbates and intercalants, ARPES and HREELS were also used to monitor the changes in spectroscopic signatures of the graphene film following exposure to the ambient atmosphere.