Informal online opinions: Medico-legal considerations in new and social media.
Doctors are increasingly discovering that using social media, both via public platforms and closed forums, is a powerful tool to develop a professional presence, share information and network with colleagues. While new technology can open up opportunities to engage, educate and inform, it is important also to recognise that doctors' legal and professional obligations apply equally online. The aim of this article is to raise awareness of and share information about legal and professional obligations when using social media, particularly in the context of seeking peer professional advice or informal input from colleagues. While doctors' legal and professional obligations continue to apply online, the technology can create additional complexities. Being aware of these complexities will assist doctors to optimise their use of social media while still complying with those obligations.


Discrimination of Breast Cancer Based on Ultrasound Images and Convolutional Neural Network.
The aim of our study was to establish an artificial intelligence tool for the diagnosis of breast disease base on ultrasound (US) images. A deep learning algorithm Efficient-Det assisted US diagnosis method was developed to determine breast suspicious lesions as benign, malignant, or normal. Totally 1181 US images from 487 patients of our hospital and 694 publicly accessible images were employed for modeling, including 558 benign images, 370 malignant images, and 253 normal tissue images. The actual diagnosis results for the patients were determined by the biopsy or surgery. Efficient-Det was first retrained using an exclusive public breast cancer US dataset with transfer learning techniques. A blind test set consisting of 50 benign, 50 malignant, and 50 normal tissue images was randomly picked from the patients' images as the independent test set to test its searching ability on suspicious tumor regions. Furthermore, the confusion matrix and classification accuracy were employed as evaluation metrics to select the optimal classification models. Efficient-Det has demonstrated remarkable progress in general image recognition tasks with specific advantages of locating and identifying tumor areas simultaneously. Compared to the manual method (mean accuracy: 95.3% and 60 s per image) and traditional feature engineering method (mean accuracy: 90% and 15 s per image), our Efficient-Det has the capability of providing a competitive (mean accuracy: 92.6%) and fast (0.06 s per image) classification result. The deployment of Efficient-Det in our local breast cancer discrimination task exhibits specific applicability within real clinical workflows.


A new polymorph of benzene-1,2-diamine: isomorphism with 2-aminophenol and two-dimensional isostructurality of polymorphs.
A new crystalline form of benzene-1,2-diamine, C(6)H(8)N(2), crystallizing in the space group Pbca, has been identified during screening for cocrystals. The crystals are constructed from molecular bilayers parallel to (001) that have the polar amino groups directed to the inside and the aromatic groups, showing a herringbone arrangement, directed to the outside. The known monoclinic form and the new orthorhombic polymorph exhibit two-dimensional isostructurality as the crystals consist of nearly identical bilayers. In the monoclinic form, neighbouring bilayers are generated by a unit translation along the a axis, whereas in the orthorhombic form they are generated by a c-glide. Moreover, the new form of benzene-1,2-diamine is essentially isomorphous with the only known form of 2-aminophenol.


Engineering stop gaps of inorganic-organic polymeric 3D woodpile photonic crystals with post-thermal treatment.
A method is reported for improving the spatial resolution and engineering the stop gaps of the inorganic-organic 3D woodpile photonic crystals (PhCs). The approach is based on the two-photon polymerization (2PP) of an inorganic-organic hybrid material and a post-thermal treatment (PTT) process. The effects of PTT on polymerized 1D, 2D and 3D structures have been characterized. Ultimately, the feature size of the suspended rods has been reduced to approximately 33 nm and the spatial resolution of inorganic-organic 3D woodpile PhCs has been improved from approximately 150 nm to approximately 86 nm. The approach is also demonstrated as a powerful tool to engineer the stop gaps of 3D PhCs. In particular, a combination of PTT and the threshold fabrication technique leads to the stop gap of a 3D woodpile PhC that can be tuned over a large wavelength range of approximately 318 nm from the near-infrared to visible region.


Animal-assisted interventions research: issues and answers.
Animal visitation programs have been used in a wide variety of clinical settings with predominantly positive outcomes reported anecdotally. However, there is also a growing body of research investigating the effects of these interventions. Developing and conducting rigorous studies of animal interventions can be a complex and challenging process, The purpose of this article is to identify and discuss several issues arising with this type of research and to posit suggestions for avoiding pitfalls.


Miliary tuberculosis involving the central nervous system.
A woman with chronic systemic lupus erythematosus (SLE) was treated with prednisone, and developed an acute febrile neuroinfection. The magnetic resonance images (MRI) showed miliary micronodular lesions distributed diffusely within the central nervous system and lungs. Lumbar puncture showed pleocytosis with predominance of polymorphonuclear leukocytes, hypoglycorrhachia, elevated proteins and smears positive for acid-fast bacilli. The diagnosis was confirmed by culture of Mycobacterium tuberculosis in the cerebrospinal fluid and bronchial biopsy tissue. She was treated with ethambutol, rifampin, isoniazid and pyrazinamide. MRI taken one month later showed significant improvement, but leg weakness persisted. Epidemiologic research showed her uncle with cavitary tuberculosis as the source of infection. He was also treated with combined antituberculous chemotherapy.


An oral vaccine against candidiasis generated by a yeast molecular display system.
Enolase 1 (Eno1p) of Candida albicans is an immunodominant antigen. However, conventional technologies for preparing an injectable vaccine require purification of the antigenic protein and preparation of an adjuvant. To develop a novel type of oral vaccine against candidiasis, we generated Saccharomyces cerevisiae cells that display the Eno1p antigen on their surfaces. Oral delivery of the engineered S. cerevisiae cells prolonged survival rate of mice that were subsequently challenged with C. albicans. Given that a vaccine produced using molecular display technology avoids the need for protein purification, this oral vaccine offers a promising alternative to the use of conventional and injectable vaccines for preventing a range of infectious diseases.


Nupr1 regulates palmitate-induced apoptosis in human articular chondrocytes.
Obesity, a major risk factor for the development of osteoarthritis (OA), is associated with increased circulating levels of free fatty acids (FFA). However, the role of these FFAs in OA pathophysiology is not clearly understood. In the present study, we found that palmitate treatment of human primary articular chondrocytes increased the expression of ER stress markers [activating transcription factor 4 (ATF4), C/EBP homologous protein (CHOP)] and apoptosis markers [cytochrome c and cleaved caspase-3 (CC3)]. Palmitate treatment also increased the expression of Nuclear protein 1 (Nupr1) and tribbles related protein 3 (TRB3), which are known negative regulators of cell survival pathways. Knockdown of Nupr1 or CHOP expression inhibited palmitate mediated increased expression of TRB3 and CC3, indicating that Nupr1 and CHOP cooperate to regulate cell survival and apoptotic pathways in human chondrocytes. Nupr1 knockdown had no effect on CHOP expression whereas CHOP knockdown abolished the palmitate-mediated Nupr1 expression, indicating that CHOP is functional upstream to Nupr1 in this pathway. Moreover, overexpression of Nupr1 markedly increased the basal expression of pro-apoptotic molecules, including cytochrome c and CC3. Taken together, our study demonstrates that Nupr1 plays a crucial role in palmitate-induced apoptosis in human chondrocytes and Nupr1 as a potential novel drug target for the treatment of OA.


Setting up a journal club for healthcare professionals in an older people's residential care setting.
With the rise in the number of older people in the population and new developments in older people's services such as integrated care hubs, there is a need for healthcare professionals working with older people to keep up to date with the latest research. This article describes the process of establishing a multidisciplinary journal club in a residential care setting and recognising the potential of such clubs to develop staff members' critical thinking, presentation and communication skills. The authors emphasise the importance of fostering a culture of learning in older people's services and describe how a journal club can support healthcare professionals to maintain their knowledge and improve care.


Nodulation of Cyclopia spp. (Leguminosae, Papilionoideae) by Burkholderia tuberum.
Species of the genus Burkholderia, from the Betaproteobacteria, have been isolated from legume nodules, but so far they have only been shown to form symbioses with species of Mimosa, sub-family Mimosoideae. This work investigates whether Burkholderia tuberum strains STM678 (isolated from Aspalathus carnosa) and DUS833 (from Aspalathus callosa) can nodulate species of the South African endemic papilionoid genera Cyclopia (tribe Podalyrieae) and Aspalathus (Crotalarieae) as well as the promiscuous legume Macroptilium atropurpureum (Phaseoleae). Bacterial strains and the phylogeny of their symbiosis-related (nod) genes were examined via 16S rRNA gene sequencing. Seedlings were grown in liquid culture and inoculated with one of the two strains of B. tuberum or with Sinorhizobium strain NGR 234 (from Lablab purpureus), Mesorhizobium strain DUS835 (from Aspalathus linearis) or Methylobacterium nodulans (from Crotalaria podocarpa). Some nodules, inoculated with green fluorescence protein (GFP)-tagged strains, were examined by light and electron microscopy coupled with immunogold labelling with a Burkholderia-specific antibody. The presence of active nitrogenase was checked by immunolabelling of nitrogenase and by the acetylene reduction assay. B. tuberum STM678 was also tested on a wide range of legumes from all three sub-families. Nodules were not formed on any of the Aspalathus spp. Only B. tuberum nodulated Cyclopia falcata, C. galioides, C. genistoides, C. intermedia and C. pubescens. It also effectively nodulated M. atropurpureum but no other species tested. GFP-expressing inoculant strains were located inside infected cells of C. genistoides, and bacteroids in both Cyclopia spp. and M. atropurpureum were immunogold-labelled with antibodies against Burkholderia and nitrogenase. Nitrogenase activity was also shown using the acetylene reduction assay. This is the first demonstration that a beta-rhizobial strain can effectively nodulate papilioinoid legumes. Papilionoid legumes from widely different tribes can be nodulated by beta-rhizobia, forming both indeterminate (Cyclopia) and determinate (Macroptilium) nodules.


Transfected MDCK cell line with enhanced expression of CYP3A4 and P-glycoprotein as a model to study their role in drug transport and metabolism.
The aim of this study was to characterize and utilize MDCK cell line expressing CYP3A4 and P-glycoprotein as an in vitro model for evaluating drug-herb and drug-drug of abuse interactions. MDCK cell line simultaneously expressing P-gp and CYP3A4 (MMC) was developed and characterized by using expression and activity studies. Cellular transport study of 200 μM cortisol was performed to determine their combined activity. The study was carried across MDCK-WT, MDCK-MDR1 and MMC cell lines. Similar studies were also carried out in the presence of 50 μM naringin and 3 μM morphine. Samples were analyzed by HPLC for drug and its CYP3A4 metabolite. PCR, qPCR and Western blot studies confirmed the enhanced expression of the proteins in the transfected cells. The Vivid CYP3A4 assay and ketoconazole inhibition studies further confirmed the presence of active protein. Apical to basal transport of cortisol was found to be 10- and 3-fold lower in MMC as compared to MDCK-WT and MDCK-MDR1 respectively. Higher amount of metabolite was formed in MMC than in MDCK-WT, indicating enhanced expression of CYP3A4. Highest cortisol metabolite formation was observed in MMC cell line due to the combined activities of CYP3A4 and P-gp. Transport of cortisol increased 5-fold in the presence of naringin in MMC and doubled in MDCK-MDR1. Cortisol transport in MMC was significantly lower than that in MDCK-WT in the presence of naringin. The permeability increased 3-fold in the presence of morphine, which is a weaker inhibitor of CYP3A4. Formation of 6β-hydroxy cortisol was found to decrease in the presence of morphine and naringin. This new model cell line with its enhanced CYP3A4 and P-gp levels in addition to short culture time can serve as an invaluable model to study drug-drug interactions. This cell line can also be used to study the combined contribution of efflux transporter and metabolizing enzymes toward drug-drug interactions.


Proportion of syphilis and hepatitis B and C virus infections among the Integrated Counselling and Testing Centre attendees of a tertiary care hospital.
Human Immunodeficiency Virus (HIV) affects the immune system of the body, causing a breakdown in its normal defenses and leaving it vulnerable to a host of life-threatening diseases. High-risk behaviors and routes of transmission for sexually transmitted infections such as syphilis, hepatitis B and hepatitis C are identical with HIV. This study was conducted to assess the proportion of syphilis and hepatitis B and C virus infections in HIV-positive and HIV-negative individuals, and their association with socioeconomic and other factors in Integrated Counselling and Testing Centre (ICTC) attendees, and to determine the association of absolute CD4+ T-lymphocyte count with these co-infections in HIV-positive individuals. The study was conducted in the Department of Microbiology of a tertiary care hospital. It included 100 HIV-positive individuals and 100 matched HIV-negative controls attending the ICTC. HIV-positive patients on antiretroviral therapy and patients with history of current/past treatment for chronic hepatitis infection were excluded from the study. Blood samples were tested for HIV, syphilis, and hepatitis B and C infections. The prevalence of syphilis, hepatitis B, and hepatitis C was observed in 3.5%, 2%, and 10% of patients, respectively. The frequency of hepatitis B virus (HBV) infection in HIV-positive and HIV-negative individuals was 1% and 3%, respectively. Hepatitis C virus (HCV) infection among HIV-positive and HIV-negative patients was 16% and 4%, respectively. Syphilis was seen in 7% of the HIV-infected patients. The mean CD4+ count for the HIV-positive patients with either syphilis, HBV, or HCV infections was 252 ± 137.5 cells/μl. Significant associations between HIV infection and education below high school, IV drug abuse, and multiple sexual partners were observed. The HIV-infected patients were observed to be at an increased risk of acquiring syphilis and HCV co-infections through the shared routes of transmission. Routine screening of these patients for concurrent syphilis and viral hepatitis may aid in prompt diagnosis and treatment with improved outcomes, which in turn may decrease the further spread of these infections.


Control of aromatase in hippocampal neurons.
Our knowledge on estradiol-induced modulation of synaptic function in the hippocampus is widely based on results following the application of the steroid hormone to either cell cultures, or after the treatment of gonadectomized animals, thus ignoring local neuronal estrogen synthesis. We and others, however, have shown that hippocampus-derived estradiol also controls synaptic plasticity in the hippocampus. Estradiol synthesis in the hippocampus is regulated by several mechanisms, which are reviewed in this report. The regulation of the activity of aromatase, the final enzyme of estrogen biosynthesis, by Ca(2+) transients, is of particular interest. Aromatase becomes inactivated as soon as it is phosphorylated by Ca(2+)-dependent kinases upon calcium release from internal stores. Accordingly, thapsigargin dephosphorylates aromatase and stimulates estradiol synthesis by depletion of internal Ca(2+) stores. Vice versa, letrozole, an aromatase inhibitor, phosphorylates aromatase and reduces estradiol synthesis. Treatment of the cultures with 17β-estradiol results in phosphorylation of the enzyme and increased aromatase protein expression, which suggests that estradiol synthesis in hippocampal neurons is regulated in an autocrine manner.


Spontaneous occurrence of early region 1A reiteration mutants of type 5 adenovirus in persistently infected human T-lymphocytes.
Mutants of type 5 adenovirus (Ad5) with reiterated DNA sequences in the E1a region appeared in a human T-lymphocyte cell line, Molt-4, persistently infected with H5sub304, a deletion/substitution mutant that has a wild-type phenotype in viral replication. Endonuclease analyses and DNA sequencing revealed DNA reiteration in each mutant. In the four representative mutants investigated, the DNA reiterations all started within a six-base-pair consensus sequence, G(or C)CTGTG, located in the second exon of the E1a region (at nt 1333, 1367, or 1419). There was not any DNA homology between the breakpoints in the second exon and the inserting sequences (starting at nt 532, 710, or 792). Northern analyses suggested that the reiterated splicing sites of the representative mutants were all used in RNA splicing, and the closest donor and recipient joints were used most frequently. These observations imply that during persistent infection Ad5 underwent spontaneous mutations by sequence-specific breakage and nonhomologous end-end joining recombination events. These E1a reiteration mutants could be propagated in HeLa, A549, and KB cells; they were genetically stable; and they killed CREF cells at a strikingly high frequency. Preliminary observations tend to correlate this CREF cell killing with the accumulation of the early viral proteins and/or viral DNA in the infected cells. This degree of cell damage was not observed in Ad5wt or H5sub304 infection of CREF cells. The observed E1a reiterations provide a model to gain insight into understanding the evolutionary events of some, if not all, adenovirus types during many years of symbiotic, persistent relationship in human tonsils and adenoids and possibly other lymphoid organs.


Peptide-Appended Nanosonosensitizers Targeting Tumor Glycolysis for Synergistic Sonodynamic-Immunometabolic Therapy of Spinal-Metastasized Tumors.
Despite recent advancements in cancer immunotherapy, challenges have yet to be surmounted to achieve two major goals of magnifying antitumor immunity and remodeling the immunosuppressive tumor microenvironment. Here, a nanosystem (ODM-R) that integrates oxygen-deficient molybdenum oxide (ODM) nanosonosensitizers and R7 peptides with tumor metabolism regulation effects is designed and fabricated for synergistic sonodynamic-immunometabolic therapy of spinal-metastasized tumors. The ODM generates reactive oxygen species upon ultrasound irradiation to implement sonodynamic therapy (SDT), inducing cancer cell apoptosis and immunogenic cell death. The R7 attached on ODM markedly inhibits the uptake of glucose and excretion of lactic acid in cancer cells by perturbing the glycolysis process. The combination of SDT and tumor glycolysis obstruction by ODM-R guarantees satisfactory efficacy in synergizing with PD-L1 antibody to eradicate spinal-metastasized tumors, achieving concurrent sonodynamic-triggered immune activation and immunosuppressive tumor microenvironment remodeling. This work provides a proof-of-concept of nanosonosensitizers for boosting cancer immunotherapy by SDT and tumor metabolic regulation.


Citrullinated fibrinogen impairs immunomodulatory function of bone marrow mesenchymal stem cells by triggering toll-like receptor.
Bone marrow mesenchymal stem cells (BMSC) have been shown to possess immunomodulatory activities, while its role in rheumatoid arthritis (RA) remains unknown. Citrullinated fibrinogen (cfb) has been considered as a specific autoantigen in RA pathogenesis. Our study aims to determine the role of cfb on immunomodulatory function of BMSC. We demonstrated the specific role of toll-like receptor 4 (TLR4)-NFκB pathway in the pro-inflammatory response of BMSC to cfb with increased production of interleukin (IL)-6, IL-8 and chemokine CC motif ligand 2 (CCL2). Moreover, cfb impaired BMSC-mediated suppression of peripheral blood mononuclear cells (PBMC) proliferation and reduced the production of the key immunomodulatory molecule indoleamine 2,3-dioxygenase (IDO) in BMSC. We have uncovered a previously unrecognized role of cfb in interfering BMSC-mediated immunoregulation in RA. Cfb could act as a damage-associated molecule pattern (DAMP) for BMSC and thereby contribute to the propagation of inflammation in RA.


Neurosyphilis manifesting as a focal mass lesion: computed tomographic and magnetic resonance imaging features--case report.
The computed tomographic (CT) and magnetic resonance (MR) imaging findings in a middle-aged male with cerebral syphilis are described. He presented with convulsive seizures and focal neurological deficits. A CT scan revealed a slightly enhanced, low-density mass in the left parieto-occipital region. MR imaging showed low intensity on T1-weighted images and high intensity on T2-weighted images. He was initially diagnosed as having a low-grade glioma. However, intraoperative histological examination of a small surgical specimen revealed no tumor cells but heavy infiltration of inflammatory cells in the meninges and cerebral parenchyma. Immunostaining for Treponema organisms by the peroxidase-antiperoxidase method was positive. Although the clinical and radiological findings are nonspecific, neurosyphilis should be considered in any patient in whom a nonspecific mass lesion is demonstrated by CT and MR imaging.


Biosynthesis of panaxynol and panaxydol in Panax ginseng.
The natural formation of the bioactive C17-polyacetylenes (-)-(R)-panaxynol and panaxydol was analyzed by 13C-labeling experiments. For this purpose, plants of Panax ginseng were supplied with 13CO2 under field conditions or, alternatively, sterile root cultures of P. ginseng were supplemented with [U-13C6]glucose. The polyynes were isolated from the labeled roots or hairy root cultures, respectively, and analyzed by quantitative NMR spectroscopy. The same mixtures of eight doubly 13C-labeled isotopologues and one single labeled isotopologue were observed in the C17-polyacetylenes obtained from the two experiments. The polyketide-type labeling pattern is in line with the biosynthetic origin of the compounds via decarboxylation of fatty acids, probably of crepenynic acid. The 13C-study now provides experimental evidence for the biosynthesis of panaxynol and related polyacetylenes in P. ginseng under in planta conditions as well as in root cultures. The data also show that 13CO2 experiments under field conditions are useful to elucidate the biosynthetic pathways of metabolites, including those from roots.


The role of gamma-synuclein in cocaine-induced behaviour in rats.
The aim of this study was to investigate the role of gamma-synuclein in the rewarding effects of chronic cocaine administration and its putative interaction with the dopamine transporter (DAT). For this purpose, regulatable lentiviruses driving overexpression of the rat gamma-synuclein or DAT have been prepared, as well as lentiviruses expressing siRNAs, aimed at silencing either DAT or gamma-synuclein mRNA expression. Overexpression of DAT in the nucleus accumbens (NAc) induced a 35% decrease in locomotor activity, which could be abolished when the same animal was fed doxycycline. Furthermore, local inhibition of DAT in the NAc, using lentiviruses expressing siRNAs targeted against DAT, resulted in significant hyperlocomotion activity (72% increase over controls). By contrast, overexpression of gamma-synuclein in the NAc alone had no effect, while local silencing lead to a significant decrease in cocaine-induced locomotor activity (47% decrease compared with controls). Surprisingly, coinjection lentiviruses expressing DAT and gamma-synuclein - leading to overexpression of both proteins in the NAc - resulted in a strong increase in cocaine-induced rat locomotor activity (52% increase compared with controls), which was abolished upon locally silencing these genes, suggesting a synergetic role of both proteins, possibly mediated through a direct interaction.


HIF-1α is essential for effective PMN bacterial killing, antimicrobial peptide production and apoptosis in Pseudomonas aeruginosa keratitis.
Hypoxia-inducible factor (HIF)-1α, is a transcription factor that controls energy metabolism and angiogenesis under hypoxic conditions, and a potent regulator of innate immunity. The studies described herein examined the role of HIF-1α in disease resolution in BALB/c (resistant, cornea heals) mice after ocular infection with Pseudomonas (P.) aeruginosa. Furthermore, the current studies focused on the neutrophil (PMN), the predominant cell infiltrate in keratitis. Using both siRNA and an antagonist (17-DMAG), the role of HIF-1α was assessed in P. aeruginosa-infected BALB/c mice. Clinical score and slit lamp photography indicated HIF-1α inhibition exacerbated disease and corneal destruction. Real time RT-PCR, immunohistochemistry, ELISA, Greiss and MPO assays, bacterial load, intracellular killing, phagocytosis and apoptosis assays further tested the regulatory role of HIF-1α. Despite increased pro-inflammatory cytokine expression and increased MPO levels after knocking down HIF-1α expression, in vivo studies revealed a decrease in NO production and higher bacterial load. In vitro studies using PMN provided evidence that although inhibition of HIF-1α did not affect phagocytosis, both bacterial killing and apoptosis were significantly affected, as was production of antimicrobial peptides. Overall, data provide evidence that inhibition of HIF-1α converts a normally resistant disease response to susceptible (corneal thinning and perforation) after induction of bacterial keratitis. Although this inhibition does not appear to affect PMN transmigration or phagocytosis, both in vivo and in vitro approaches indicate that the transcriptional factor is essential for effective bacterial killing, apoptosis and antimicrobial peptide production.


MIPS: Functional dynamics in evolutionary pathways of plant kingdom.
The myo-inositol biosynthesis pathway triggering protein MIPS is best known for its necessity, ubiquitous nature and occurrence throughout all living kingdom. However, the functional disparity of MIPS genes in green plant is still viable. The present work considered a comprehensive genome-wide analysis from sequenced plants to identify MIPS homologs in respective organisms and their genomic architecture. Variation of MIPS gene expression in twelve different species in diverse conditions has also been analysed. All MIPS genes share a conserved sequence property in most of its coding region, but its regulatory elements, gene structure and expression network vary significantly. Phylogenetic inference confirms the evolution of MIPS from a single common algal ancestor to seed plants and acquiring functional variation through genomic control. This paper represents MIPS as a model for studying gene duplication, functional divergence and diversification events in plant lineages.


[Arthrodesis of the ankle joint: effect of the position of the arthrodesis on the foot. Apropos of a series of 50 cases reviewed with an average follow-up of 9 years].
A functional assessment of fifty patients after ankle arthrodesis for post traumatic arthritis was carried out by means of an extensive clinical evaluation after an average follow-up of nine years. The data on position of ankle arthrodesis and gait analysis were examined to determine the effect of arthrodesis of the ankle on the subtalar and small joints of the foot. The Duquennoy point system was used to grade the ankle clinically and a new radiological method to determine the sagittal position of the ankle arthrodesis was developed. Equinus position was related with clinical damage on sub talar joint, and anterior cavus foot (92.8 per cent). This position was related with metatarsalgia in 26.9 per cent. Calcaneus position was related with posterior cavus foot (verticalization of the calcaneus). This position was related with the best functional results on walking, jumping and running. this study has showed that the ideal position of fusion of the ankle was neutral or slight flexion, slight valgus angulation of the hind part of the foot and 10 degrees of external rotation.


Surface-enhanced Raman scattering for the detection of polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) is a multi-factorial heterogeneous syndrome that affects many women of reproductive age. This work demonstrates how the surface-enhanced Raman scattering (SERS) technique can be used to differentiate between PCOS and non-PCOS patients. We determine that the use of SERS, in conjunction with partial least squares (PLS) and principal component analysis (PCA), allows us to detect PCOS in patient samples. Although the role of chemerin in the pathogenesis of PCOS patients is not clear, this work enables us to measure their chemerin levels using the PLS regression method.


Research Progress of Bile Acids in Cancer.
Bile acids (BAs) were originally known as detergents to facilitate the digestion and absorption of lipids. And our current knowledge of BAs has been extended to potential carcinogenic or cancer suppressor factors due to constant research. In fact, BAs were regarded as a tumor promoters as early as the 1940s. Differential bile acid signals emitted by various bile acid profiles can produce distinct pathophysiological traits, thereby participating in the occurrence and development of tumors. Nevertheless, in recent years, more and more studies have noticed the value of BAs as therapeutic targets. And several studies have applied BAs as a therapeutic agent for various diseases including cancer. Based on the above evidence, we acknowledge that the role of BAs in cancer has yet to be exploited, although considerable efforts have been made to probe the functions of BAs. In this review, we describe the characteristics of BAs as a double-edged sword in cancer, hoping to provide references for future cancer treatments.


Warfarin Related Kidney Damage: A Confusing Case of Thrombophlebitis Masquerading as Infection.
Anticoagulant-related nephropathy (ARN) is a rare, newly recognized cause of acute kidney injury and significant but underdiagnosed complication of anticoagulation therapy. ARN occurs in patients taking oral anticoagulant therapy most often warfarin or a novel oral anticoagulant (NOAC). It is a potentially devastating disorder with serious renal consequences and increased all-cause mortality. Anticoagulant-related nephropathy presents as an acute kidney injury (AKI) in the setting of a supratherapeutic INR with profuse glomerular hemorrhage seen as renal tubules filled with red cells and red cell casts on renal biopsy. Being that millions of Americans are on warfarin, a thorough understanding and awareness of the clinical presentation, diagnosis, and therapeutic interventions are crucial to protecting the renal function, lowering all-cause mortality and optimizing treatment. Our goal is to provide education on a newly recognized form of AKI and significant but underdiagnosed complication of anticoagulation therapy.


"Being Persistent without Being Pushy": Student Reflections on Vaccine Hesitancy.
Our goal as pediatric educators is to graduate physicians who have witnessed effective approaches and have grasped the nuances of communication strategies between vaccine-hesitant families and health care providers. We identified vaccine hesitancy as a recurring topic in 19 of 304 medical student reflective narratives addressing an issue in professionalism or systems-based practice. We conducted content analysis on the narratives in order to gain a better understanding of student perceptions of visits in which they observed a provider discussing vaccine hesitancy with a parent. We identified four major themes: perceived effectiveness of provider-family communication, student reaction to the encounter, physician approach to vaccine hesitancy, and gaps in students' own knowledge. Most students described communication positively, despite only 4 of 19 observing eventual vaccine acceptance. Information regarding vaccines, vaccine delivery, and approaches to vaccine hesitancy needs to be introduced and enhanced in the educational curriculum of providers at all levels, including medical students, resident physicians, and attending physicians, in order to ensure that providers possess the comprehension and communication skills to ethically optimize vaccine uptake among patients.


GTP-activated communication between distinct inositol 1,4,5-trisphosphate-sensitive and -insensitive calcium pools.
Inositol 1,4,5-trisphosphate (InsP3) is an established mediator of intracellular Ca2+ signals but little is known of the nature and organization of Ca2+ regulatory organelles responsive to InsP3. Here we derive new information from the study of Ca2+ movements induced both by InsP3 and a specific GTP-activated Ca2+ translocation process. The latter mechanism is clearly distinct from that activated by InsP3 and may involve the translocation of Ca2+ between compartments without its release into the cytosol. This idea is supported by the fact that GTP activates Ca2+ movement into the InsP3-releasable pool. In the light of this evidence we postulated that there are two intracellular Ca2+ pools distinguishable by InsP3-sensitivity and oxalate-permeability, and that movement between them is activated by GTP. We report here direct evidence for the existence and separation of two distinct Ca2+-pumping compartments with properties coinciding with those predicted. Of these, the InsP3-sensitive Ca2+ pool is identified within a purified rough endoplasmic reticulum fraction, an observation consistent with recent InsP3 receptor-localization studies. Ca2+ translocation between pools may reflect function of a class of small GTP-binding proteins known to mediate interorganelle transfer in eukaryotic cells.


Half a century of changing mercury levels in Swedish freshwater fish.
The variability of mercury (Hg) levels in Swedish freshwater fish during almost 50 years was assessed based on a compilation of 44 927 observations from 2881 waters. To obtain comparable values, individual Hg concentrations of fish from any species and of any size were normalized to correspond to a standard 1-kg pike [median: 0.69 mg kg⁻¹ wet weight (ww), mean ± SD: 0.84 ± 0.67 mg kg⁻¹ ww]. The EU Environmental Quality Standard of 0.02 mg kg⁻¹ was exceeded in all waters, while the guideline set by FAO/WHO for Hg levels in fish used for human consumption (0.5-1.0 mg kg⁻¹) was exceeded in 52.5 % of Swedish waters after 2000. Different trend analysis approaches indicated an overall long-term decline of at least 20 % during 1965-2012 but trends did not follow any consistent regional pattern. During the latest decade (2003-2012), however, a spatial gradient has emerged with decreasing trends predominating in southwestern Sweden.


Relactation.
Relactation means reestablishment of a milk supply and nursing after the cessation of nursing for a variable period. Induced nonpuerperal lactation means establishing a milk supply in a woman who has never been pregnant. When motivation and the breasts have both been carefully examined, preparation includes breast stimulation (by hand or pump), nipple toughening and sometimes hormonal preparation. Careful management of supplemental feedings is important.


What do primary care patients think about generic drugs?
To examine the attitude of patients towards generic drugs and prescriptions containing generic drugs as an alternative to brand-name products, with a special focus on information on patients attitude to generic drugs provided by their general practitioners (GPs). A total of 804 patients in 31 general practices were surveyed using a self-questionnaire. The influence of age, sex, education, disease, knowledge of generic drugs, experience with generic substitution and information provided by the GP on patient attitudes towards generic drugs and substitutions were examined. Nearly two thirds of the patients (509/804) stated that they knew of the difference between brand-name drugs and generics; of these, one third were not satisfied with the information given by their GPs and 37% of patients expressed general skepticism towards generic drugs because of their lower price. This attitude was more frequent among those who felt that generic prescribing was "invented" to solve the financial crisis in the German health insurance system at their expense (odds ratio (OR): 6.2; 95% confidence interval: 4.0 - 9.8) and those who had not been confronted personally with a generic substitution (OR: 1.8; 1.3 3.0). Patients who had been skeptical when first confronted with a generic substitution were more frequently among those who considered inexpensive drugs to be inferior (OR: 4.5; 2.0 10.4) and they were frequently not satisfied with the information on substitution provided by their GP (OR: 2.7; 1.2 - 5.9). GPs are in an ideal position to inform their patients adequately about the equivalence of brand-name and generic drugs. However, the patient view that inexpensive drugs must be inferior may be difficult to rectify in the short term.


Expermental salmonellosis. XI. Induction of cellular immunity and formation of antibody by transfer agent of mouse mononuclear phagocytes.
When mice were injected intraperitoneally with a ribonucleic acid (RNA) preparation extracted from the peritoneal mononuclear phagocytes (termed monocytes) of immunized mice, these macrophages developed cellular immunity and cellular antibodies. The peritoneal monocytes were obtained from normal mice and maintained in tissue culture bottles in a homogeneous cell population. When they were treated in vitro with an immune RNA preparation, they acquired cellular immunity, and cellular antibodies were detectable in such monocytes. These results suggest that the mononuclear phagocytic cell line constitutes a cell line responsible for antibody formation.


1 kW, 200 mJ picosecond thin-disk laser system.
We report on a laser system based on thin-disk technology and chirped pulse amplification, providing output pulse energies of 200 mJ at a 5 kHz repetition rate. The amplifier contains a ring-type cavity and two thin Yb:YAG disks, each pumped by diode laser systems providing up to 3.5 kW power at a 969 nm wavelength. The average output power of more than 1 kW is delivered in an excellent output beam characterized by M2=1.1. The output pulses are compressed to 1.1 ps at full power with a pair of dielectric gratings.


Adipose tissue distribution and quantification of PPARbeta/delta and PPARgamma1-3 mRNAs: discordant gene expression in subcutaneous, retroperitoneal and visceral adipose tissue of morbidly obese patients.
Adipose tissue (AT) metabolism is altered in obese subjects, and the reestablishment of energy homeostasis requires the identification and regulation of genes with altered patterns. The aim of this study was to compare mRNA expression of PPARbeta/delta and PPARgamma1-3 in morbidly obese and nonobese patients. The expression pattern of these receptors in various abdominal adipose tissues, subcutaneous (SAT), retroperitoneal (RAT) and visceral (VAT), was also evaluated. The AT depots were obtained by surgery. Total RNAs were extracted using TRIzol. PPARs reverse transcripts were determined by quantitative polymerase chain reaction (qRT-PCR). The amounts of PPARP/8 mRNA in different depots of morbidly obese AT showed a significant decrease in VAT (P < 0.05). In the non-obese group, the level of PPARbeta/delta was higher in SAT (P < 0.05), but PPARgamma1-3 was not differentially expressed in obese and non-obese depots. When comparing obese and non-obese, the results revealed a decrease in PPARPbeta/delta expression in SAT (P = 0.058) and VAT (P = 0.094) of the morbidly obese. PPARgamma1-3 mRNA expression was increased significantly in SAT (P = 0.022) and decreased in RAT (P = 0.034) in morbidly obese subjects. PPARbeta/delta expression in SAT and VAT correlated negatively with hip size and insulin serum respectively. PPARgamma1-3 expression in RAT correlated negatively with waist and hip circumference and in VAT correlated positively with waist size. The present study demonstrates that PPARbeta/delta and PPARgamma1-3 mRNAs are quantitatively different in AT of morbidly obese individuals compared to non-obese, and that PPARbeta/delta mRNA levels are characteristic for each AT depot.


[Pregnancy and periodontal health. Study of 133 pregnant women].
The pregnancy is a modified physiological state having consequences on the buccal sphere generally and on the periodontal tissues in particular. We proceeded to the periodontal exam of 133 pregnant women; in spite of a relatively acceptable hygiene, 73.7% of them present periodontal changes. These changes concern especially the superficial periodontal. We did not observe the presence of deep pockets periodontal. It emerges of our study that neither the period of pregnancy, nor the parity have influence in the importance of the periodontal hurts.


Interfacial Superassembly of Mesoporous Titania Nanopillar-Arrays/Alumina Oxide Heterochannels for Light- and pH-Responsive Smart Ion Transport.
Stimuli-responsive nanochannels have attracted extensive attention in various fields owing to their precise regulation ability of ionic transportation. However, the poor controllability and functionality as well as responding to only one type of external stimulus still impede the development of the smart nanochannels. Here, we demonstrate a novel heterogeneous membrane composed of ordered mesoporous titania nanopillar-arrays/anodic aluminum oxide (MTI/AAO) using an interfacial superassembly strategy, which can achieve intelligent light and pH multimodulation ion transport. The MTI/AAO membranes are generated through the self-assembly of templates, followed by interfacial superassembly of micelles on AAO, and then the nanostructure and phase transformation of titania. The presence of the MTI layer with anatase crystal endows the heterogeneous membrane with an excellent light-responsive current density of 219.2 μA·cm-2, which is much higher than that of a reported traditional light-responsive nanofluidic device. Furthermore, the MTI/AAO heterogeneous membranes with an asymmetric structure exhibit excellent rectification performance. Moreover, pH-regulated surface charge polarity leads to a reversal of current rectification polarity. This light and pH multiresponsive membrane realizes efficient, sensitive, and stable ion regulation, extending the traditional nanochannel from single modulation to smart multimodulation.


[Emotional facial recognition difficulties as primary deficit in children with attention deficit hyperactivity disorder: a systematic review].
It has recently been warned that children with attention deficit hyperactivity disorder (ADHD) show a deficit in emotional competence and emotional intelligence, specifically in their ability to emotional recognition. A systematic review of the scientific literature in reference to the emotional recognition of facial expressions in children with ADHD is presented in order to establish or rule the existence of emotional deficits as primary dysfunction in this disorder and, where appropriate, the effect size of the differences against normal development or neurotypical children. The results reveal the recent interest in the issue and the lack of information. Although there is no complete agreement, most of the studies show that emotional recognition of facial expressions is affected in children with ADHD, showing them significantly less accurate than children from control groups in recognizing emotions communicated through facial expressions. A part of these studies make comparisons on the recognition of different discrete emotions; having observed that children with ADHD tend to a greater difficulty recognizing negative emotions, especially anger, fear, and disgust. These results have direct implications for the educational and clinical diagnosis of ADHD; and for the educational intervention for children with ADHD, emotional education might entail an advantageous aid.


Device-measured sedentary time in Norwegian children and adolescents in the era of ubiquitous internet access: secular changes between 2005, 2011 and 2018.
Access to screen-based media has been revolutionized during the past two decades. How this has affected sedentary time (ST) accumulation in children is poorly understood. This study, based on the Physical Activity among Norwegian Children Study (PANCS), uses accelerometer data from population-based samples of 9- and 15-year-olds, collected in 2005 (n = 1722), 2011 (n = 1587) and 2018 (n = 1859). Secular changes between surveys were analysed using random-effects linear regression models adjusted for survey-specific factors. Data on ST were collected using hip-worn ActiGraphs and ST was defined using a threshold equivalent to <100 counts/min. Sedentary bouts were grouped by duration: <1, 1-5, 5-15, 15-30 and ≥30 min. Between 2005 and 2018, ST increased by 29 min/day in 9-year-old boys (95% CI: 19, 39; P <0.001), by 21 min/day in 15-year-old boys (95% CI: 8, 34; P = 0.002) and by 22 min/day in 15-year-old girls (95% CI: 10, 35; P <0.001), but not in 9-year-old girls at 6 min/day (95% CI: -3, 16; P = 0.191). All age-sex groups accumulated less ST in bouts lasting <5 min and more ST in longer bouts, particularly in 5-15-min bouts. Adolescent girls also increased ST accumulation in 15-30-min and ≥30-min bouts. Changes were largely mirrored before, during and after school on weekdays and during weekend days. Coinciding with the introduction of smartphones, tablets and near-universal internet access, total daily ST and ST accumulated in prolonged sedentary bouts increased between 2005 and 2018 in children and adolescents.


Aberrant expression of interleukin-10 in rheumatoid arthritis: Relationship with IL10 haplotypes and autoantibodies.
Interleukin 10 (IL-10) is an immunomodulatory cytokinethat plays a central rolein the pathogenesis of autoimmune diseases. Different studies consistently show increased IL-10 serum levels in rheumatoid arthritis (RA) and it appears to be caused by genetic variants. Three polymorphisms situated at positions -1082, -819 and -592 of IL10 gene and its major haplotypes have been associated with regulating IL10 promoter activity. In this study, we evaluated whether IL10 haplotypes are associated with mRNA expression and IL-10 serum levels as well as susceptibility to RA in a Western Mexican population. A total of 240 RA patients and 240 control subjects (CS) were included. Genotyping of IL10 polymorphisms was performed by PCR and PCR-RFLP, respectively. IL10 mRNA expression was determined by real-time PCR and IL-10 serum levels were measured using an ELISA kit. IL10 mRNA expression was 50-fold higher in RA patients than CS (p<0.001), while IL-10 serum levels did not show differences between groups. However, high IL-10 serum levels were positively related to a higherseropositivityfor rheumatoid factor (FR) and anti-CCP antibodies (p<0.05). No significant differences between the distribution of haplotype frequencies were observed between both study groups, but GCC haplotype was associated with higher IL-10 serum levels compared with the ACC and ATA haplotypes in RA patients (p<0.05). In addition, patients carrying ATA and GCC haplotypes showed higher mRNA expression than ACC (5.4-fold and 8.8-fold, respectively) and surprisingly, this trend was reversed in the controls, although it was not significant. In conclusion, our findings suggest that IL10 (GCC, ACC, and ATA) haplotypes may not be a susceptibility marker for RA in a population from Western Mexico. Nevertheless, independently of the presence of these variants, there is an aberrant overexpression of IL10 gene in RA, and it may play an important role in the pathogenesis of RA.


Obesity induced rapid melanoma progression is reversed by orlistat treatment and dietary intervention: role of adipokines.
Obesity, owing to adiposity, is associated with increased risk and development of various cancers, and linked to their rapid growth as well as progression. Although a few studies have attempted to understand the relationship between obesity and melanoma, the consequences of controlling body weight by reducing adiposity on cancer progression is not well understood. By employing animal models of obesity, we report that controlling obesity either by orlistat treatment or by restricting caloric intake significantly slows down melanoma progression. The diminished tumor progression was correlated with decreased fat mass (adiposity) in obese mice. Obesity associated factors contributing to tumor progression were decreased in the experimental groups compared to respective controls. In tumors, protein levels of fatty acid synthase (FASN), caveolin (Cav)-1 and pAkt, which are tumor promoting molecules implicated in melanoma growth under obese state, were decreased. In addition, increased necrosis and reduction in angiogenesis as well as proliferative markers PCNA and cyclin D1 were observed in tumors of the orlistat treated and/or calorically restricted obese mice. We observed that growth of melanoma cells cultured in conditioned medium (CM) from orlistat-treated adipocytes was reduced. Adipokines (leptin and resistin), via activating Akt and modulation of FASN as well as Cav-1 respectively, enhanced melanoma cell growth and proliferation. Together, we demonstrate that controlling body weight reduces adipose mass thereby diminishing melanoma progression. Therefore, strategic means of controlling obesity by reduced caloric diet or with antiobesity drugs treatment may render obesity-promoted tumor progression in check and prolong survival of patients.


Elucidation of the Streptomyces coelicolor pathway to 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde, an intermediate in prodiginine biosynthesis.
The biosynthetic pathway to 4-methoxy-2,2'-bipyrrole-5-carboxaldehyde (MBC), a key intermediate in the biosynthesis of prodiginine antibiotics in Streptomyces coelicolor, has been elucidated using a combination of gene replacements and feeding experiments with chemically synthesised MBC and a synthetic analogue of a pathway intermediate.


Effect of ethanol on pancreatic lysosomes in rats: a possible mechanism for alcoholic pancreatitis.
Four-hour infusion of ethanol (0.5 g/kg.hr) and additional 2-hour infusion of caerulein (0.2 microgram/kg.hr) and secretin (0.2 CU/kg.hr) caused hyperamylasemia, pancreatic edema and pancreatic histological changes such as interstitial edema and acinar cell vacuolization in the rat. Such a combined treatment also induced a redistribution of lysosomal enzyme cathepsin B, from the lysosomal fraction to the zymogen fraction in subcellular fractionation. Only ethanol infusion caused marginal changes in all these parameters. Moreover, 4-hour pre-infusion of ethanol caused a significant increase in pancreatic cathepsin B output stimulated by caerulein (0.2 microgram/kg.hr) and secretin (0.2 CU/kg.hr) compared with the control rats. This pretreatment of ethanol also caused a significant increase in cathepsin B/amylase output ratio. These results indicate that ethanol administration, if combined with exocrine stimulation, causes a colocalization of lysosomal hydrolases with digestive enzymes in the same subcellular compartment as well as in the pancreatic ductal space, and also suggest one possible mechanism for alcoholic pancreatitis both within and outside the acinar cells, since cathepsin B can activate trypsinogen.


Hyperechogenic renal tumours.
58 hyperechogenic renal tumours from the years 1978-1983 were studied to elucidate whether it would be possible to discriminate between malignant and benign tumours with the aid of echo strength and homogeneity. 42 tumours were malignant (renal carcinomas) and 16 benign (15 angiomyolipomas and one hemangioma). 5% of the malignant tumours were highly echogenic (the echo strength equal to or higher than that of sinusal area) and 95% moderately echogenic ( echostrength higher than that of parenchyma and lower than that of sinusal area), and 12% had homogeneous and 88% nonhomogeneous echo pattern. 75% of the benign tumours were highly and 25% moderately echogenic, while 94% were homogeneous and 6% nonhomogeneous. It is not possible to differentiate with absolute reliability between malignant and benign hyperechogenic renal tumours on the basis of the ultrasonographic finding.


[Prognostic factors for in-hospital mortality in patients with acute kidney injury requiring continuous renal replacement therapy undergoing surgery for acute Stanford type A aortic dissection].
Objective: To evaluate prognostic factors for in-hospital mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) undergoing surgery for acute Stanford type A aortic dissection. Methods: Retrospective analysis were conducted for 60 patients diagnosed with AKI requiring CRRT undergoing surgery for acute Stanford type A aortic dissection at Beijing Anzhen Hospital, Capital Medical University from March 2015 to September 2016. There were 43 male and 17 female patients with an mean age of (50±14) years. Demographic characteristics, diagnosis, perioperative periodrelated data, clinical parameters during CRRT were collected to set up a database. The patients were divided into survival group and non-survival group according to in-hospital mortality. The prognostic factors of mortality in-hospital after AKI requiring CRRT were analyzed by multivariate Logistic regression analysis regression. Results: In the 60 adult patients who had received CRRT, 21 patients (35.0%) died. There were significant differences between died and survival patients on proportion of age>60 years (χ(2)=6.851, P=0.003), lactic acid levels at 12-hour after CRRT (t=-3.631, P=0.004), lactic acid levels at 24 hours after CRRT (t=-2.986, P=0.032), proportion of body mass index >25 kg/m(2) (χ(2)=5.660, P=0.041), cardiopulmonary bypass time (t=-2.720, P=0.001). Multivariate Logistic regression analysis revealed that age≥60 years (OR=16.450, 95% CI: 2.172 to 84.589); high lactic acid levels at 12-hour after CRRT (OR=1.719, 95% CI: 1.998 to 2.960) and long cardiopulmonary bypass time (OR=1.028, 95% CI: 1.004 to 1.052) (all P<0.05) were independent prognostic factors of in-hospital mortality. Conclusions: Age ≥60 years, high lactic acid levels at 12-hour after CRRT and long cardiopulmonary bypass time were independent prognostic factors of patients with AKI requiring CRRT after aortic surgery. Proper identification and management shall improve the prognosis of patients.


Single exposure three-dimensional imaging of dusty plasma clusters.
We have worked out the details of a single camera, single exposure method to perform three-dimensional imaging of a finite particle cluster. The procedure is based on the plenoptic imaging principle and utilizes a commercial Lytro light field still camera. We demonstrate the capabilities of our technique on a single layer particle cluster in a dusty plasma, where the camera is aligned and inclined at a small angle to the particle layer. The reconstruction of the third coordinate (depth) is found to be accurate and even shadowing particles can be identified.


Tips on Raising Reliable Local Perforator Flaps.
From early on in the development of plastic surgery, it was quickly realized that utilizing locally adjacent tissue, or "matching like with like," yielded superior aesthetic reconstructions to those in which the tissue was derived from a distant location. In many cases, the use of a local perforator flap is a simpler procedure with less patient morbidity and a quicker recovery from surgery. The difficulty with local perforator flaps has been locating the supplying perforators, ensuring that the flap has a robust and reliable blood supply, and that sufficient tissue is able to be transferred. The recent reappraisal of our understanding of the blood supply of the integument has allowed, for the first time, the capacity to accurately and inexpensively, without the need for "high tech equipment," locate perforators, as they emerge from the deep fascia into the overlying integument, and through a better understanding of the interconnecting anastomotic vessels between perforators reliably predict how much tissue can be safely raised on a single perforator, before surgery. Further, through the use of strategic "delay," it is possible to manipulate the interconnecting vessels between the selected perforator and its surrounding neighbors to design a flap of tissue of any dimension, composed of whatever tissue we require, and safely transfer that tissue locally, or if required, distantly, as a free flap. This article will highlight these advances, explain their relevance in raising reliable local perforator flaps, and will, where possible, call attention to any pearls and pitfalls, and how to avoid complications.


Comparison of the air-Q intubating laryngeal airway and the cobra perilaryngeal airway as conduits for fiber optic-guided intubation in pediatric patients.
One of the methods proposed in cases of difficult airway management in children is using a supraglottic airway device as a conduit for tracheal intubation. The aim of this study was to compare the efficacy of the Air-Q Intubating Laryngeal Airway (Air-Q) and the Cobra Perilaryngeal Airway (CobraPLA) to function as a conduit for fiber optic-guided tracheal intubation in pediatric patients. A total of 60 children with ages ranging from 1 to 6 years, undergoing elective surgery, were randomized to have their airway managed with either an Air-Q or CobraPLA. Outcomes recorded were the success rate, time and number of attempts required for fiber optic-guided intubation and the time required for device removal after intubation. We also recorded airway leak pressure (ALP), fiber optic grade of glottic view and occurrence of complications. Both devices were successfully inserted in all patients. The intubation success rate was comparable with the Air-Q and the CobraPLA (96.7% vs. 90%), as was the first attempt success rate (90% vs. 80%). The intubation time was significantly longer with the CobraPLA (29.5 ± 10.9 s vs. 23.2 ± 9.8 s; P < 0.05), but the device removal time was comparable in the two groups. The CobraPLA showed a significantly higher ALP (20.8 ± 5.2 cmH2O vs. 16.3 ± 4.5 cmH2O; P < 0.001), but the fiber optic grade of glottic view was comparable with the two devices. The CobraPLA was associated with a significantly higher incidence of blood staining of the device on removal and post-operative sore throat. Both the Air-Q and CobraPLA can be used effectively as a conduit for fiber optic-guided tracheal intubation in children. However, the Air-Q proved to be superior due to a shorter intubation time and less airway morbidity compared with the CobraPLA.


The implications for everyday life of incident self-reported visual decline among people over age 65 living in the community.
We examined the consequences of incident self-reported vision loss among a cohort of community-living people aged 66 years and older. Those with visual decline were older than those reporting constant excellent or good vision, but not different in any other demographic characteristic, the use of formal support services, the use of health services, or ADL (activities of daily living) functioning. Controlling for age and sex, vision loss was associated with unmet instrumental ADL needs such as housekeeping, grocery shopping, and food preparation, and with physical and emotional disabilities. We discuss the implications of these disabilities in terms of the challenges to the aging and blindness service delivery systems.


Heparin rescues factor V Leiden-associated placental failure independent of anticoagulation in a murine high-risk pregnancy model.
Low molecular weight heparin (LMWH) is being tested as an experimental drug for improving pregnancy outcome in women with inherited thrombophilia and placenta-mediated pregnancy complications, such as recurrent pregnancy loss. The role of thrombotic processes in these disorders remains unproven, and the issue of antithrombotic prophylaxis is intensely debated. Using a murine model of factor V Leiden-associated placental failure, we show that treatment of the mother with LMWH allows placental development to proceed and affords significant protection from fetal loss. Nonetheless, the therapeutic effect of LMWH is not replicated by anticoagulation; fondaparinux and a direct Xa inhibitor, C921-78, achieve anticoagulation similar to LMWH but produce little or no improvement in pregnancy outcome. Genetic attenuation of maternal platelet aggregation is similarly ineffective. In contrast, even a partial loss of thrombin sensitivity of maternal platelets protects pregnancies. Neonates born from these pregnancies are growth retarded, suggesting that placental function is only partially restored. The placentae are smaller but do not reveal any evidence of thrombosis. Our data demonstrate an anticoagulation-independent role of LMWH in protecting pregnancies and provide evidence against the involvement of thrombotic processes in thrombophilia-associated placental failure. Importantly, thrombin-mediated maternal platelet activation remains central in the mechanism of placental failure.


[Molecular aspects of aminoglycoside nephrotoxicity].
Aminoglycosides are potent bactericidal antibiotics particularly active against aerobic Gram-negative bacteria. This review focuses on the recent concept of a molecular understanding of aminoglycoside-induced nephrotoxicity. As receptor-mediated endocytosis plays an important role in the accumulation of aminoglycosides in renal proximal tubules, the biochemical properties of the two main receptors, megalin and cubilin, involved in this process are described. Literature data on megalin and acidic phospholipids as potential targets for preventing aminoglycoside-induced nephrotoxicity are also presented.


Caregiving appraisal and disease activity in early inflammatory arthritis.
The caregiving process accompanying inflammatory arthritis can be stressful to both caregivers and care recipients. In this study, we examined how caregiving involvement and caregiving appraisal as perceived by both patients and their caregiving spouses relate to disease activity and mental health of patients in early inflammatory arthritis. Patients in the early phase (> 6 weeks, <18 months duration) of inflammatory arthritis were recruited from a larger early inflammatory arthritis registry, which recorded sociodemographic data and disease characteristics. Disease activity was measured with the Disease Activity Score in 28 joints (DAS28). Current depressive symptoms were measured using the Center for Epidemiologic Studies - Depression Mood Scale. Patient and spouse perceived caregiving involvement and caregiving appraisal were assessed using the Caregiving Involvement Questionnaire and Caregiving Appraisal Scale, respectively. The study sample consisted of 73 patients living with spouse. Mean age was 54 years, 64.4% were women and mean illness duration was 7.48 months. Patients' positive caregiving appraisal was associated with less disease activity (DAS28) (p = 0.003) and less total depressive mood (p < 0.001). In multivariate analysis, patients' appraisal of the caregiving context was negatively associated with disease activity (DAS28) after controlling for caregiving involvement and depression (p = 0.035). This study indicates that, in early inflammatory arthritis, patients' caregiving appraisal might be important to consider when assessing disease activity. Clinicians are encouraged to include both patients and their spouse caregivers in interventions.


The inhibition of mucopeptide synthesis by benzylpenicillin in relation to irreversible fixation of the antibiotic by staphylococci.
1. Benzylpenicillin is irreversibly fixed to staphyloccoci by a reaction that obeys second-order kinetics, whereas the progress of inhibition of mucopeptide synthesis obeys first-order kinetics after a short lag during which the antibiotic has no effect. 2. When the micro-organisms are saturated with benzylpenicillin they can still make mucopeptide in solutions containing chloramphenicol at a normal rate after a lag period. 3. About 90% of the benzylpenicillin stays fixed to the cells after mucopeptide synthesis has reached its maximum and constant rate. 4. During the phase when mucopeptide synthesis by cells saturated with benzylpenicillin is accelerating, a small number of additional sites that fix benzylpenicillin is revealed. The number of these sites reaches a maximum and constant value at about the same time as mucopeptide biosynthesis reaches a maximum and constant rate. 5. Staphylococci saturated with benzylpenicillin are exceedingly sensitive to fresh additions of the antibiotic. 6. The degree of inhibition of mucopeptide synthesis caused by these small amounts of antibiotic agrees with the degree of substitution by benzylpenicillin of the newly revealed or ;sensitive' sites. 7. Since these sensitive sites are revealed during incubation of the bacteria with chloramphenicol it is unlikely that they are due to newly formed protein. 8. On the basis of these results, a hypothesis for the inhibition by penicillin of the cross-linking reaction in the terminal stages of mucopeptide synthesis is suggested.


Interleukin 4 induces rapid mucin transport, increases mucus thickness and quality and decreases colitis and Citrobacter rodentium in contact with epithelial cells.
Citrobacter rodentium infection is a murine model for pathogenic intestinal Escherichia coli infection. C. rodentium infection causes an initial decrease in mucus layer thickness, followed by an increase during clearance. We aimed to identify the cause of these changes and to utilize this naturally occurring mucus stimulus to decrease pathogen impact and inflammation. We identified that mucin production and speed of transport from Golgi to secretory vesicles at the apical surface increased concomitantly with increased mucus thickness. Of the cytokines differentially expressed during increased mucus thickness, IFN-γ and TNF-α decreased the mucin production and transport speed, whereas IL-4, IL-13, C. rodentium and E. coli enhanced these aspects. IFN-γ and TNF-α treatment in combination with C. rodentium and pathogenic E. coli infection negatively affected mucus parameters in vitro, which was relieved by IL-4 treatment. The effect of IL-4 was more pronounced than that of IL-13, and in wild type mice, only IL-4 was present. Increased expression of Il-4, Il-4-receptor α, Stat6 and Spdef during clearance indicate that this pathway contributes to the increase in mucin production. In vivo IL-4 administration initiated 10 days after infection increased mucus thickness and quality and decreased colitis and pathogen contact with the epithelium. Thus, during clearance of infection, the concomitant increase in IL-4 protects and maintains goblet cell function against the increasing levels of TNF-α and IFN-γ. Furthermore, IL-4 affects intestinal mucus production, pathogen contact with the epithelium and colitis. IL-4 treatment may thus have therapeutic benefits for mucosal healing.


Effects of Hard Water Boiling on Chalky Rice in Terms of Texture Improvement and Ca Fortification.
In the present paper, we investigated the characteristics of chalky rice grains generated by ripening under high temperature and compared them with whole grains. We evaluated 14 unpolished Japonica rice grains harvested in Japan in 2021, and these samples (original grains) were divided into two groups (a whole grain group and a chalky grain one). We found that not only activities of endogenous amylase and proteinase, but also cell wall-degrading enzymes, such as xylanase and cellulase, changed markedly between chalky grains and whole grains. Using rice grains blended with 30% of chalky grains as the material, we compared the sugar and mineral contents and textural properties of the rice grains soaked and boiled in either ordinary water or hard water, such as Evian or Contrex. It was shown that xylanase, in addition to amylase and proteinase, may play an important role in changing the texture of the boiled chalky rice grains. For the sake of preventing the above-mentioned deterioration in the texture of boiled grains of chalky rice, we tried to use hard water, such as Evian or Contrex, to soak and cook the chalky rice grains. It was shown that the hard water was useful for the prevention of texture deterioration of the boiled rice grains due to inhibition of the activities of endogenous hydrolytic enzymes, such as α-amylase, β-amylase, proteinase, and xylanase. Furthermore, we found that the hard water was useful in increasing the calcium absorption through the meal by 2.6 to 16.5 times.


[Bullous dermatoses with special reference to the symptomatology of the eyelids in pemphigus vulgaris].
Among the bullous dermatoses the pemphigus group, the pemphigoids have to be distinguished from the hereditary epidermolyses. Immune-histological examinations are of paramount importance for the differential diagnosis between pemphigus vulgaris and cicatricial pemphigoid. This paper describes symmetrical erosions of the edges of the eyelids and adjacent skin which have their origin in transient vesicle formations, and classifies them as a partial symptom of the overall pemphigus vulgaris complex. High doses of cortison can re-epithelialize these troublesome and cosmetically unpleasant erosions.


Metabolic pathways in Anopheles stephensi mitochondria.
No studies have been performed on the mitochondria of malaria vector mosquitoes. This information would be valuable in understanding mosquito aging and detoxification of insecticides, two parameters that have a significant impact on malaria parasite transmission in endemic regions. In the present study, we report the analyses of respiration and oxidative phosphorylation in mitochondria of cultured cells [ASE (Anopheles stephensi Mos. 43) cell line] from A. stephensi, a major vector of malaria in India, South-East Asia and parts of the Middle East. ASE cell mitochondria share many features in common with mammalian muscle mitochondria, despite the fact that these cells are of larval origin. However, two major differences with mammalian mitochondria were apparent. One, the glycerol-phosphate shuttle plays as major a role in NADH oxidation in ASE cell mitochondria as it does in insect muscle mitochondria. In contrast, mammalian white muscle mitochondria depend primarily on lactate dehydrogenase, whereas red muscle mitochondria depend on the malate-oxaloacetate shuttle. Two, ASE mitochondria were able to oxidize proline at a rate comparable with that of alpha-glycerophosphate. However, the proline pathway appeared to differ from the currently accepted pathway, in that oxoglutarate could be catabolized completely by the tricarboxylic acid cycle or via transamination, depending on the ATP need.


Detection of human sperm acrosome reaction: comparison between methods using double staining, Pisum sativum agglutinin, concanavalin A and transmission electron microscopy.
The acrosome reaction is an important marker for human sperm function. Since different laboratory techniques may be used for the detection of this exocytotic process, the purpose of the present study was to compare three common markers [Pisum sativum agglutinin (PSA), concanavalin A (ConA), double staining] and transmission electron microscopy for identification of acrosomal changes. Preliminary findings had demonstrated that similar results were achieved with Trypan Blue and Hoechst 33258 staining. Therefore, supravital stainings were omitted. In various experiments, human spermatozoa were treated with two concentrations (10 and 3.3 microM) of calcium ionophore A23187 for 15, 30 and 60 min after capacitation for 3 and 6 h at 37 degrees C. The percentages of spermatozoa with acrosomal loss detected by fluorescein isothiocyanate (FITC)-ConA were consistently lower than those obtained by double staining or FITC-PSA, which showed comparable results. Following 6 h of capacitation and incubation with 10 microM ionophore for 1 h at 37 degrees C, 25.9 +/- 15.7% of all spermatozoa showed almost complete loss of the acrosomal content. Binding of FITC-ConA to the acrosomal region was observed in 27.0 +/- 13.2% of spermatozoa obtained from the same sample. FITC-ConA and double staining or FITC-PSA detect different stages of the acrosome reaction and may be helpful for a differentiated evaluation of this sperm function.


Transition metal vinylidene complexes as supramolecular building blocks: nucleobase-mediated self-assembly of crystals with hexagonal symmetry.
Reaction of the ruthenium half sandwich compound RuCl(eta(5)-C(5)H(5))(PPh(3))(2) with the uracil (Ur) substituted alkyne HC[triple bond, length as m-dash]CUr in the presence of halide scavengers NH(4)X (X = PF(6), BF(4), OTf) results in the formation of the vinylidene complexes [Ru([double bond, length as m-dash]C[double bond, length as m-dash]CHUr)(eta(5)-C(5)H(5))(PPh(3))(2)][X] which crystallize in the hexagonal space group P6(3)/m. The hexagonal symmetry inherent to the system is due to the formation of a hydrogen bonded array mediated by the two sets of donor-acceptor units on the uracil, resulting in the formation of a cyclic "rosette" containing six ruthenium cations. In solution the (1)H and (31)P{(1)H} NMR spectra of the vinylidene complexes are both concentration and temperature dependent, in accord with the presence of monomer-dimer equilibria in which the rate of rotation of the vinylidene group is fast on the NMR timescale in the monomeric species, but slow in the dimers. The isoelectronic molybdenum-containing vinylidene complex [Mo(eta(7)-C(7)H(7))(dppe)([double bond, length as m-dash]C[double bond, length as m-dash]CHUr)][BF(4)] (dppe = 1,2-bis(diphenylphosphino)ethane) has also been prepared, but forms symmetric dimers in the solid state.


Quantitative trait loci with sex-specific effects for internal organs weights and hematocrit value in a broiler-layer cross.
Rapid growth in broilers is associated with susceptibility to metabolic disorders such as pulmonary hypertension syndrome (ascites) and sudden death. This study describes a genome search for QTL associated with relative weight of cardio respiratory and metabolically important organs (heart, lungs, liver and gizzard), and hematocrit value in a Brazilian broiler-layer cross. QTL with similar or different effects across sexes were investigated. At 42 days of age after fasted for 6 h, the F2 chickens were weighed and slaughtered. Weights and percentages of the weight relative to BW42 of gizzard, heart, lungs, liver and hematocrit were used in the QTL search. Parental, F1 and F2 individuals were genotyped with 128 genetic markers (127 microsatellites and 1 SNP) covering 22 linkage groups. QTL mapping analyses were carried out using mixed models. A total of 11 genome-wide significant QTL and five suggestive linkages were mapped. Thus, genome-wide significant QTL with similar effects across sexes were mapped to GGA2, 4 and 14 for heart weight, and to GGA2, 8 and 12 for gizzard %. Additionally, five genome-wide significant QTL with different effects across sexes were mapped to GGA 8, 19 and 26 for heart weight; GGA26 for heart % and GGA3 for hematocrit value. Five QTL were detected in chromosomal regions where QTL for similar traits were previously mapped in other F2 chicken populations. Seven novel genome-wide significant QTL are reported here, and 21 positional candidate genes in QTL regions were identified.


Mitotane and Carney Complex: ten years follow-up of a low-dose mitotane regimen inducing a sustained correction of hypercortisolism.
Primary pigmented nodular adrenocortical disease (PPNAD), an uncommon cause of Cushing's syndrome, is frequently associated with a wider clinical spectrum, the Carney complex (CC), a multiple endocrine neoplasia syndrome. We evaluated a low-dose mitotane regimen for treating severe hypercortisolism in a 27-year-old woman with CC. She presented with severe hypercortisolism and a history of surgeries for breast ductal adenoma, atrial cardiac myxomas with cerebral and peripheral arterial embolism, and near-total thyroidectomy because of an oxyphilic adenoma. The patient refused further surgery for adrenalectomy. During the first 7 months of mitotane (Lysodren, HRA Pharma, Paris, France), the daily oral dose was progressively increased from 0.5 to 4 g/day and then stopped because of the appearance of sustained signs of hypoadrenalism, that required a replacement therapy with 5 mg of prednisone o.d. A 10-month mitotane off-therapy follow-up was performed and when an increase in urine free cortisol (UFC) was noted, the mitotane regimen was restarted at lower doses (0.750-1 g/day). Serum morning cortisol levels and UFC were then maintained within the normal range, with plasma mitotane ranging between 2 and 4 mg/L. A sustained regression of Cushing's features without inducing hypoadrenalism was achieved, which still persists after 122 months of follow-up. Minimal initial gastric discomfort was the only side effect of which the patient complained and only during the first higher dose mitotane course. Long-term administration of a low maintenance dose of mitotane may be suggested as treatment for hypercortisolism in CC patients who refuse or are at high risk for surgical adrenalectomy.


Effects of Drought Stress on Non-Structural Carbohydrates in Different Organs of Cunninghamia lanceolata.
The Chinese fir Cunninghamia lanceolata (Lamb.) Hook. is an important timber conifer species in China. Much has been studied about Chinese fir, but the distribution of non-structural carbohydrates (NSCs) among different organs (needles, branch, stem, and roots) under drought stress remains poorly understood. In this study, we used one-year-old C. lanceolata plantlets to evaluate the effects of simulated drought under four water regimes, i.e., adequate water or control, light drought, moderate drought, and severe drought stress corresponding to 80%, 60%, 50%, and 40%, respectively of soil field maximum capacity on various NSCs in the needles, branch, stem and roots. The degree and duration of drought stress had significant effects on fructose, glucose, sucrose, soluble sugar, starch, and NSC content in various organs (p < 0.05). Fructose content increased in stem xylem, stem phloem, and leaves. Glucose and sucrose content declined in stem and branch xylem under light drought stress and moderate drought stress, and increased under severe drought stress conditions. Soluble sugars content declined, and starch content increased in leaf and branch phloem, but the latter could not compensate for soluble sugar consumption in the whole plant, and therefore, total NSCs decreased. Correlation analysis showed that a significant positive correlation existed in the soluble sugar content between leaves and roots, and between xylem and phloem in the stems and branches. Chinese fir appears to have different NSCs distribution strategies in response to drought stress, viz., allocating more soluble sugars to fine roots and increasing starch content in the needles, as well as ensuring osmosis to prevent xylem embolism. Our study may broaden the understanding of the various mechanisms that Chinese fir and other plants have to enhance their tolerance to drought stress.


Overexpression of mitogen-activated protein kinase kinase (MAPKK) and its mutants in NIH 3T3 cells. Evidence that MAPKK involvement in cellular proliferation is regulated by phosphorylation of serine residues in its kinase subdomains VII and VIII.
Mitogen-activated protein kinase kinase (MAPKK) is a dual specificity protein kinase that exhibits a high degree of specificity toward its downstream target, mitogen-activated protein kinase (MAPK). In this study, we used stable overexpression of MAPKK and its mutants in NIH 3T3 cells to study effects on downstream components of the MAPK signaling cascade and to correlate them to physiological responses. We have mutated the potential regulatory serine residue 222 to alanine (S222A) or to glutamate (S222E) and serines 212 and 218 together to alanine residues (S212A,S218A). Lysine 97 was mutated to alanine (K97A) to provide an inactive enzyme. Overexpression of the wild type MAPKK had no effect on any of the parameters examined. The K97A and S222A mutants served as dominant negatives by suppressing MAPKK, MAPK, and p90rsk activation in vivo. S222E enhanced all of these activities, and S212A,S218A had a small inhibitory effect. A similar trend was observed when cellular proliferation was examined and the different effects were accompanied by altered cellular shape. Taken together, our results demonstrate a direct linkage between the MAPK signaling pathway and the control of cellular proliferation and morphology and also establish that phosphorylation of serine 222 is essential for MAPKK activation together with the phosphorylation of an additional serine(s) (probably serine 218).


BTBR ob/ob mouse model of type 2 diabetes exhibits early loss of retinal function and retinal inflammation followed by late vascular changes.
Diabetic retinopathy is increasing in prevalence worldwide and is fast becoming a global epidemic and a leading cause of visual loss. Current therapies are limited, and the development of effective treatments for diabetic retinopathy requires a greater in-depth knowledge of disease progression and suitable modelling of diabetic retinopathy in animals. The aim of this study was to assess the early pathological changes in retinal morphology and neuronal, inflammatory and vascular features consistent with diabetic retinopathy in the ob/ob mouse model of type 2 diabetes, to investigate whether features similar to those in human diabetic retinopathy were present. Male and female wild-type (+/+), heterozygous (+/-) and homozygous (-/-) BTBR ob/ob mice were examined at 6, 10, 15 and 20 weeks of age. Animals were weighed and blood glucose was measured. TUNEL and brain-specific homeobox/POU domain protein 3A (BRN3A) markers were used to examine retinal ganglion cells. We used immunostaining (collagen IV and platelet endothelial cell adhesion molecule [PECAM]/CD31) to reveal retinal vessel degeneration. Spectral domain optical coherence tomography was used to reveal changes in the thickness and structure of the retinal layer. Vitreous fluorophotometry was used to investigate vascular permeability. A-waves, b-waves and oscillatory potentials were measured under photopic and scotopic conditions. Concanavalin A leucostasis and immunostaining with glial fibrillary acidic protein (GFAP) and ionised calcium-binding adapter molecule 1 (IBA-1) identified differences in inflammatory status. Paraffin sections and transmission electron microscopy were used to reveal changes in the thickness and structure of the retinal layer. Following the development of obesity and hyperglycaemia in 2-week-old and 3-week-old ob-/ob- mice, respectively (p < 0.001), early functional deficits (p < 0.001) and thinning of the inner retina (p < 0.001) were identified. Glial activation, leucostasis (p < 0.05) and a shift in microglia/macrophage phenotype were observed before microvascular degeneration (p < 0.05) and elevated vascular permeability occurred (p < 0.05). The present characterisation of the development of diabetic retinopathy in the ob/ob mouse represents a platform that will enable the development of new therapies, particularly for the early stages of disease.


From genome to proteome: great progress in the domesticated silkworm (Bombyx mori L.).
As the only truly domesticated insect, the silkworm not only has great economic value, but it also has value as a model for genetics and molecular biology research. Genomics and proteomics have recently shown vast potential to be essential tools in domesticated silkworm research, especially after the completion of the Bombyx mori genome sequence. This paper reviews the progress of the domesticated silkworm genome, particularly focusing on its genetic map, physical map and functional genome. This review also presents proteomics, the proteomic technique and its application in silkworm research.


Renal progenitors: an evolutionary conserved strategy for kidney regeneration.
Following kidney injury, repair can result in functional tissue becoming a patch of cells and disorganized extracellular matrix--a scar--or it can recapitulate the original tissue architecture through the process of regeneration. Regeneration can potentially occur in all animal species and humans. Indeed, the repair of portions of the existing nephron after tubular damage, a response that has been designated classically as cellular regeneration, is conserved in all animal species from the ancestral phases of evolution. By contrast, another type of regenerative response--nephron neogenesis--has been described in lower branches of the animal kingdom, but does not occur in adult mammals. Converging evidence suggests that a renal progenitor system is present in the adult kidney across different stages of evolution, with renal progenitors having been identified as the main drivers of kidney regenerative responses in fish, insects, rodents and humans. In this Review, we describe similarities and differences between the renal progenitor systems through evolution, and propose explanations for how progressive kidney adaptation to environmental changes both required and permitted neonephrogenesis to be given up and for cellular regeneration to be retained as the main regenerative strategy. Understanding the mechanisms that drive renal progenitor growth and differentiation represent the key step for modulating this potential for therapeutic purposes.


Computer-Assisted Flagging of Individuals at High Risk of Colorectal Cancer in a Large Health Maintenance Organization Using the ColonFlag Test.
To evaluate in a sample of adults who had been noncompliant with colorectal cancer (CRC) screening whether screening could be enhanced by an automated patient recall system based on identifying high-risk individuals using the ColonFlag test and an electronic medical record database. A total of 79,671 individuals who were determined to be noncompliant with current screening recommendations were identified in the Maccabi Health Services program in Israel. Their cancer risk was determined by ColonFlag using information on age, sex, and CBC results. Doctors of individuals who were flagged as high risk were notified and asked to follow up with their patients. The ColonFlag identified 688 men and women who scored in the highest 0.87 percentile. Of these individuals, 254 had colonoscopies performed by Maccabi physicians, and 19 CRCs (7.5%) were found. An additional 15 cancers primarily identified outside of Maccabi were found through code matching. The ColonFlag test is a rapid, efficient, and inexpensive test that can be applied to scan electronic medical records to identify individuals at high risk of CRC who would otherwise avoid screening.


[A patient with adult T cell leukemia in smoldering stage expressing an aberrant phenotype of CD3- and CD4+].
This report is of a patient with adult T cell leukemia (ATL) in the smoldering stage showing expression an aberrant phenotype of CD3-, CD4+ and CD8-. A 71-year-old woman was admitted to our hospital in December 1992, because of skin eruption and persistent low grade fever. Laboratory examination showed a leukocyte count of 7,000/microliter with 29% abnormal lymphocytes. The diagnosis of ATL was made by the detection of serum anti-HTLV-I antibody and the monoclonal integration of HTLV-I proviral DNA in abnormal lymphocytes. ATL cells at diagnosis were CD3+, CD4+ and CD8+. However, one month later ATL cells lacked CD3 and CD8. Three color analysis showed that most of the CD25+ cells were CD3- and CD4+.


Group sequential multi-arm multi-stage survival trial design with treatment selection.
Multi-arm trials are increasingly of interest because for many diseases; there are multiple experimental treatments available for testing efficacy. Several novel multi-arm multi-stage (MAMS) clinical trial designs have been proposed. However, a major hurdle to adopting the group sequential MAMS routinely is the computational effort of obtaining stopping boundaries. For example, the method of Jaki and Magirr for time-to-event endpoint, implemented in R package MAMS, requires complicated computational efforts to obtain stopping boundaries. In this study, we develop a group sequential MAMS survival trial design based on the sequential conditional probability ratio test. The proposed method is an improvement of the Jaki and Magirr's method in the following three directions. First, the proposed method provides explicit solutions for both futility and efficacy boundaries to an arbitrary number of stages and arms. Thus, it avoids complicated computational efforts for the trial design. Second, the proposed method provides an accurate number of events for the fixed sample and group sequential designs. Third, the proposed method uses a new procedure for interim analysis which preserves the study power.


Polyol pathway metabolites in human cataracts. Correlation of circulating glycosylated hemoglobin content and fasting blood glucose levels.
Circulating glycosylated hemoglobin (Hb A1) and/or fasting blood glucose (FBG) levels, measures of the extent to which diabetes is clinically controlled, were correlated with the contents of fructose, sorbitol, glucose, and inositol in 27 cataracts removed by intracapsular extraction. In the series of patients studied, Hb A1 levels ranged from 6.0% to 15.5% of the total hemoglobin value. The levels of fructose and sorbitol (micromoles per gram of lens) in their cataracts ranged from 0 to 8.4 and 0 to 10.2 mumole/g, respectively, with correlation coefficients greater than .8. Similar correlations were noted with FBG. The Hb A1 correlated with lens glucose (r = .58) and not with inositol. However, FBG had no correlation with either lens glucose or inositol. The observed correlation of the polyol pathway metabolites with both Hb A1 and FBG suggests that the lens can synthesize substantial quantities of sorbitol and fructose in response to the excess glucose available to lenses of human diabetics. A synergistic role of the polyol pathway in the cause of senile cataracts is thus possible.


MicroRNA-194 reciprocally stimulates osteogenesis and inhibits adipogenesis via regulating COUP-TFII expression.
Osteoblasts and adipocytes are differentiated from common mesenchymal stem cells (MSCs) in processes which are tightly controlled by various growth factors, signaling molecules, transcriptional factors and microRNAs. Recently, chicken ovalbumin upstream promoter-transcription factor II (COUP-TFII) was identified as a critical regulator of MSC fate. In the present study, we aimed to identify some microRNAs (miR), which target COUP-TFII, and to determine the effects on MSCs fate. During osteoblastic or adipocytic differentiation from MSCs lineage cells, miR-194 expression was found to be reversal. In the cultures of mesenchymal C3H10T1/2 and primary bone marrow stromal cells, osteogenic stimuli increased miR-194 expression with accompanying decreases in COUP-TFII expression, whereas adipogenic stimuli reduced miR-194 expression with accompanying increases in COUP-TFII expression. A luciferase assay with COUP-TFII 3'-untranslated region (UTR) reporter plasmid, including the miR-194 binding sequences, showed that the introduction of miR-194 reduced the luciferase activity. However, it did not affect the activity of mutated COUP-TFII 3'-UTR reporter. Enforced expression of miR-194 significantly enhanced osteoblast differentiation, but inhibited adipocyte differentiation by decreasing COUP-TFII mRNA and protein levels. In contrast, inhibition of the endogenous miR-194 reduced matrix mineralization in the MSCs cultures, promoting the formation of lipid droplets by rescuing COUP-TFII expression. Furthermore, overexpression of COUP-TFII reversed the effects of miR-194 on the cell fates. Taken together, our results showed that miR-194 acts as a critical regulator of COUP-TFII, and can determinate the fate of MSCs to differentiate into osteoblasts and adipocytes. This suggests that miR-194 and COUP-TFII may be good target molecules for controlling bone and metabolic diseases.


Tissue culture studies of contact lenses.
Standard methylmethacrylate hard contact lenses and several available soft (HEMA) contact lenses were studied in tissue culture using secondary rabbit kidney cells. No toxic constituents were found but the cells were readily destroyed by a keratoprosthesis which was found to be toxic in culture. The tissue culture technique should assist in determining which plastics are most suitable for in vivo use and make conclusions concerning mechanical or metabolic effects of lenses more meaningful.


Volumetric assessment of tissue changes following combined surgical therapy of peri-implantitis: A pilot study.
To assess volumetric tissue changes at peri-implantitis sites following combined surgical therapy of peri-implantitis over a 6-month follow-up period. Twenty patients (n = 28 implants) diagnosed with peri-implantitis underwent access flap surgery, implantoplasty at supracrestally or bucally exposed implant surfaces and augmentation at intra-bony components using a natural bone mineral and application of a native collagen membrane during clinical routine treatments. The peri-implant region of interest (ROI) was intra-orally scanned pre-operatively (S0), and after 1 (S1) and 6 (S2) months following surgical therapy. Digital files were converted to standard tessellation language (STL) format for superimposition and assessment of peri-implant volumetric variations between time points. The change in thickness was assessed at a standardized ROI, subdivided into three equidistant sections (i.e. marginal, medial and apical). Peri-implant soft tissue contour area (STCA) (mm2 ) and its corresponding contraction rates (%) were also assessed. Peri-implant tissues revealed a mean thickness change (loss) of -0.11 and -0.28 mm at 1 and 6 months. S0 to S1 volumetric variations pointed to a thickness change of -0.46, 0.08 and 0.4 mm at marginal, medial and apical regions, respectively. S0 to S2 analysis exhibited corresponding thickness changes of -0.61, -0.25 and -0.09 mm, respectively. The thickness differences between the areas were statistically significant at both time periods. The mean peri-implant STCA totalled to 189.2, 175 and 158.9 mm2 at S0, S1 and S2, showing a significant STCA contraction rate of 7.9% from S0 to S1 and of 18.5% from S0 to S2. Linear regression analysis revealed a significant association between the pre-operative width of keratinized mucosa (KM) and STCA contraction rate. The peri-implant mucosa undergoes considerable volumetric changes after combined surgical therapy. However, tissue contraction appears to be influenced by the width of KM.


Immunoregulatory functions of BCG-elicited alveolar macrophages in cell-mediated immune responses.
The pulmonary alveolar macrophage (AM) has been shown to play an important role in maintenance of the lung. However, the function of AM in specific cell-mediated immune responses has not been studied in detail. By employing both functional and immunologic assays, the present studies were undertaken to investigate the accessory and immunoregulatory functions of BCG-elicited AM in cell-mediated immune responses in vitro. AM, at concentrations of from 1.0 to 10%, could replace the accessory function of splenic adherent cells in the biological and functional activation of purified T-lymphocyte populations stimulated by mitogen and allogeneic cells as well as for the generation of cytotoxic effector cells. In unfractionated lymphoid cell cultures, AM were found to exert pronounced dose-dependent suppressive effects on mitogen and allogeneic cell stimulation. AM-mediated suppression of cell-mediated immune responses required metabolically active AM, but it did not require direct physical contact between AM and the stimulated lymphocytes. Furthermore, kinetic studies suggested that AM-mediated suppression was a time-dependent event that affected the afferent phase of T-cell activation by arresting the development of a primary activation signal. Moreover, the biological manifestation of suppression was characterized by inhibition of blast transformation, a decline in interleukin-2 receptor expression, as well as decreased proliferation and differentiation of precursors into effector cells (cytotoxic T-lymphocytes). These results suggest that BCG-elicited AM are capable of both accessory and regulatory functions in cell-mediated immunity.