Cadherin 11 promotes invasive behavior of fibroblast-like synoviocytes.
To define the expression pattern of cadherin 11 in the destructive pannus tissue of patients with rheumatoid arthritis, and to determine whether cadherin 11 expression in fibroblast-like synoviocytes controls their invasive capacity. Cadherin 11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin 11 in regulating the invasive behavior of fibroblast-like synoviocytes, we generated L cell clones expressing wild-type cadherin 11, mutant cadherin 11, and empty vector-transfected controls. The invasive capacity of L cell transfectants and cultured fibroblast-like synoviocytes treated with a blocking cadherin 11-Fc fusion protein or control immunoglobulin was determined in Matrigel invasion assays. Immunohistochemical analysis revealed that cadherin 11 is abundantly expressed in cells at the cartilage-pannus junction in rheumatoid synovitis. Assays to determine invasion demonstrated a 2-fold increased invasive capacity of cadherin 11-transfected L cells compared with L cells transfected with E-cadherin or control vector. The invasive behavior of L cells stably transfected with a cadherin 11 construct that lacked the juxtamembrane cytoplasmic domain was diminished to the level of vector control L cells. Furthermore, treatment with the cadherin 11-Fc fusion protein diminished the invasive capacity of fibroblast-like synoviocytes. The results of these in vitro studies implicate a role for cadherin 11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast-like synoviocytes in chronic synovitis and rheumatoid arthritis.


Additional mechanism for left ventricular dysfunction: chronic pulmonary regurgitation decreases left ventricular preload in patients with tetralogy of Fallot.
Right ventricular dysfunction in patients with tetralogy of Fallot and significant pulmonary regurgitation may lead to systolic dysfunction of the left ventricle due to altered ventricular interaction. We were interested in determining whether chronic pulmonary regurgitation affects the preload of the left ventricle. In addition, we wanted to study whether severe chronic pulmonary regurgitation would alter the preload of the left ventricle when compared with patients having preserved pulmonary valve annulus. The study group comprised 38 patients with tetralogy of Fallot who underwent surgical repair between 1990 and 2003. Transannular patching was required in 21 patients to reconstruct the right ventricular outflow tract. Altogether, 48 age- and gender-matched healthy volunteers were recruited. Cardiac MRI was performed on all study patients to assess the atrial and ventricular volumes and function. Severe pulmonary regurgitation (>30 ml/m2) was present in 13 patients, of whom 11 had a transannular patch, but only two had a preserved pulmonary valve annulus. The ventricular preload volumes from both atria were significantly reduced in patients with severe pulmonary regurgitation, and left ventricular stroke volumes (44.1±4.7 versus 58.9±10.7 ml/m2; p<0.0001) were smaller compared with that in patients with pulmonary regurgitation <30 ml/m2 or in controls. In patients with tetralogy of Fallot, severe pulmonary regurgitation has a significant effect on volume flow through the left atrium. Reduction in left ventricular preload volume may be an additional factor contributing to left ventricular dysfunction.


The developing heart: from The Wizard of Oz to congenital heart disease.
The heart is an essential organ with a fascinating developmental biology. It is also one of the organs that is most often affected in human disease, either during development or in postnatal life. Over the last few decades, insights into the development of the heart have led to fundamental new concepts in gene regulation, but also to genetic and mechanistic insights into congenital heart defects. In more recent years, the lessons learned from studying heart development have been applied to interrogating regeneration of the diseased heart, exemplifying the importance of understanding the mechanistic underpinnings that lead to the development of an organ.


Prospects for prevention of Haemophilus influenzae type b disease by immunization.
A vaccine consisting of the polysaccharide (PS) capsule of Haemophilus influenzae type b (Hib) has recently been licensed in the United States. This vaccine is safe and effective in preventing invasive Hib disease in children two years of age and older, but it is ineffective in younger children, the group at greatest risk of disease. The PS vaccine also may be ineffective in preventing disease in certain subgroups of the population that are genetically at increased risk of disease and show impaired antibody responses to immunization. Thus, new strategies need to be considered. Currently, several new Hib PS-protein conjugate vaccines are being evaluated. These vaccines differ in their method of preparation, carrier protein, and PS size. In contrast to the plain Hib PS vaccine, conjugate vaccines are immunogenic in infants and elicit boostable increases in antibody to PS upon reinjection of vaccine. However, some infants less than six months of age do not respond. To confer protection on all infants, it may be necessary to modify further the conjugate vaccines. One approach is to use outer membrane proteins (OMPs) as vaccine components. Five major OMPs have been purified from Hib, and three, P1 (50 kilodalton [kDa]), P2 (37 kDa), and P6 (16 kDa), contain antigens capable of eliciting strain-specific protective antibodies in experimental animals. In summary, PS-protein conjugate vaccines hold enormous promise for the prevention of Hib disease in infants, but further work is needed to define the optimal carrier protein, PS size, and method of coupling. Information is also needed on whether genetic factors influence responses to these vaccines.


Promising Strategies of Colloidal Drug Delivery-Based Approaches in Psoriasis Management.
Psoriasis is a chronic inflammatory autoimmune disorder that moderately affects social and interpersonal relationships. Conventional treatments for psoriasis have certain problems, such as poor drug penetration through the skin, hyper-pigmentation, and a burning sensation on normal and diseased skin. Colloidal drug delivery systems overcome the pitfalls of conventional approaches for psoriasis therapeutics and have improved patient safety parameters, compliance, and superior effectiveness. They also entail reduced toxicity. This comprehensive review's topics include the pathogenesis of psoriasis, causes and types of psoriasis, conventional treatment alternatives for psoriasis, the need for colloidal drug delivery systems, and recent studies in colloidal drug delivery systems for the treatment of psoriasis. This review briefly describes colloidal drug delivery approaches, such as emulsion systems-i.e., multiple emulsion, microemulsion, and nano-emulsion; vesicular systems-i.e., liposomes, ethosomes, noisomes, and transferosomes; and particulate systems-i.e., solid lipid nanoparticles, solid lipid microparticles, nano-structured lipid carriers, dendrimers, nanocrystals, polymeric nanoparticles, and gold nanoparticles. The review was compiled through an extensive search of the literature through the PubMed, Google Scholar, and ScienceDirect databases. A survey of literature revealed seven formulations based upon emulsion systems, six vesicular drug delivery systems, and fourteen particulate systems reported for antipsoriatic drugs. Based on the literature studies of colloidal approaches for psoriasis management carried out in recent years, it has been concluded that colloidal pharmaceutical formulations could be investigated broadly and have a broad scope for effective management of many skin disorders in the coming decades.


The association between drusen extent and foveolar choroidal blood flow in age-related macular degeneration.
To investigate the relationship between drusen extent and foveolar choroidal blood flow in nonexudative age-related macular degeneration. Total drusen area, average druse area, and total drusen number were determined using a computer program developed to quantify the extent of manually outlined drusen from fundus photographs of 157 patients (239 eyes) with nonexudative age-related macular degeneration. Laser Doppler flowmetry was used to assess relative choroidal blood velocity (ChBVel), volume (ChB Vol), and flow (ChBF low) in the center of the fovea. We found a significant inverse relationship between total drusen area and ChB Vol or ChB Flow. For every 1-mm2 increase in total drusen area, ChB Vol decreased by 0.0061 arbitrary units (P = 0.03) and ChBF low decreased by 0.23 arbitrary units (P = 0.049). Average druse area was also significantly inversely related to ChB Vol and ChBF low. For every 0.01-mm2 increase in average druse area, the ChB Vol decreased by 0.0149 arbitrary units (P = 0.001) and the ChB Flow decreased by 0.4951 arbitrary units (P = 0.003). Adjustment for age weakened the significance, although it remained strong for average druse area versus ChB Flow (P = 0.017) and ChB Vol (P = 0.004). The computer-aided quantification of drusen used in this study showed high intra- and intergrader agreement. In patients with nonexudative age-related macular degeneration, there is an association between increased drusen extent and decreased ChB Vol and ChB Flow. This suggests the presence of ischemia and possibly the reason why patients with high-risk drusen are prone to advanced disease.


Timing of the breath analyzer: does it make a difference?
The purpose of this article is to examine in an emergency room (ER) population the concordance of self-reports of no alcohol consumption prior to injury with breath-analyzer readings in two groups: (1) those patients from whom reports were obtained after they were breath analyzed compared to (2) patients from whom reports were obtained prior to obtaining the breath-analyzer reading. Data were collected on a probability sample of patients attending three health maintenance organization ERs. Among those sampled were 159 patients admitted for initial treatment of an injury, who were breath analyzed within 6 hours of the event and reported no drinking following the event that lead to injury. Of these, 119 were breath analyzed prior to the interview, and none who reported not drinking were positive on the breath analyzer, while of the 37 breath analyzed after the interview, only one was positive who had reported not drinking. Obtaining the breath-analyzer reading following the interview was not found to affect the rate of refusal to provide a breath-analyzer reading; however, it was found to adversely affect obtaining the breath-analyzer reading for other reasons. The data suggest that the concordance of negative self-reports of consumption with breath-analyzer readings remains high in ER populations regardless of when the breath-analyzer reading is obtained; however, it appears best to obtain the reading prior to interviewing the patient for reasons explained below.


ZEB1 Promotes Chemoresistance to Cisplatin in Ovarian Cancer Cells by Suppressing SLC3A2.
Ovarian cancer is one of the deadliest gynecological malignancies in women. Chemoresistance has been a major obstacle for ovarian cancer treatment. Zinc finger E-box-binding homeobox 1 (ZEB1) is an important regulator of tumor development in various types of cancer. Abnormal expression of SLC3A2 (CD98hc), a type 2 transmembrane cell surface molecule, has been described in several cancers. This study was designed to investigate the role of ZEB1 and SLC3A2 in the chemoresistance to cisplatin in ovarian cancer cells. We found that ZEB1 was increased in cisplatin-resistant SKOV3/DPP cells. Downregulation of ZEB1 significantly decreased cell viability in response to cisplatin, increased cis-platin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. In addition, downregulation of ZEB1 decreased the volume and weight of implanted tumors. SLC3A2 was decreased in cisplatin-resistant SKOV3/DPP cells. Upregulation of SLC3A2 significantly decreased cell viability in response to cisplatin, increased cisplatin-induced apoptosis, and decreased migration and invasion in the presence of cisplatin. Moreover, upregulation of SLC3A2 decreased the volume and weight of implanted tumors. Downregulation of ZEB1 resulted in a significant increase of SLC3A2 expression. Moreover, downregulation of SLC3A2 significantly inhibited ZEB1 knockdown-mediated inhibition of cisplatin-resistance. ZEB1-mediated regulation of SLC3A2 was involved in the chemoresistance to cisplatin in ovarian cancer cells. Overall, we provide new insights into the mechanism of chemoresistance to cisplatin in ovarian cancer cells. ZEB1/SLC3A2 may be promising therapeutic targets for enhancement of the sensitivity of ovarian cancer cells to cisplatin-mediated chemotherapy.


What can low and high technologies do for late-life mental disorders?
To identify and review the latest research in the use of low and high technology in the areas of mood disorders, psychosis, normal ageing, mild cognitive impairment and dementia. Technology use varied in type and extent of use across the different areas that have been reviewed. Telepsychiatry, internet-delivered therapy programs and bright-light therapy were used in managing symptoms associated with depression. In psychosis, multisensory therapy, reminiscence and virtual cognitive stimulation showed some benefits. Navigation aids and computerized diaries assisted in maintaining independence in the normally ageing and mildly cognitively impaired, although the benefits of cognitive stimulation are yet to be consistently established. By far, dementia technology received the most research attention. Benefits in this population included reductions in behavioural and psychological symptoms and carer burden and increased independence, task engagement and safety. Research in the use of low and high technology in late-life mental disorders continues to evolve in its scope and innovation. To progress the accessibility and acceptability of technology, involvement of stakeholders and users in the design and application, as well as examination of cost-effectiveness and robust methodologically designed studies are necessary.


The Autophagy Gene BcATG8 Regulates the Vegetative Differentiation and Pathogenicity of Botrytis cinerea.
Autophagy is a conserved degradation process that maintains intracellular homeostasis to ensure normal cell differentiation and development in eukaryotes. ATG8 is one of the key molecular components of the autophagy pathway. In this study, we identified and characterized BcATG8, a homologue of Saccharomyces cerevisiae (yeast) ATG8 in the necrotrophic plant pathogen Botrytis cinerea Yeast complementation experiments demonstrated that BcATG8 can functionally complement the defects of the yeast ATG8 null mutant. Direct physical interaction between BcAtg8 and BcAtg4 was detected in the yeast two-hybrid system. Subcellular localization assays showed that green fluorescent protein-tagged BcAtg8 (GFP-BcAtg8) localized in the cytoplasm as preautophagosomal structures (PAS) under general conditions but mainly accumulated in the lumen of vacuoles in the case of autophagy induction. Deletion of BcATG8 (ΔBcAtg8 mutant) blocked autophagy and significantly impaired mycelial growth, conidiation, sclerotial formation, and virulence. In addition, the conidia of the ΔBcAtg8 mutant contained fewer lipid droplets (LDs), and quantitative real-time PCR (qRT-PCR) assays revealed that the basal expression levels of the LD metabolism-related genes in the mutant were significantly different from those in the wild-type (WT) strain. All of these phenotypic defects were restored by gene complementation. These results indicate that BcATG8 is essential for autophagy to regulate fungal development, pathogenesis, and lipid metabolism in B. cinereaIMPORTANCE The gray mold fungus Botrytis cinerea is an economically important plant pathogen with a broad host range. Although there are fungicides for its control, many classes of fungicides have failed due to its genetic plasticity. Exploring the fundamental biology of B. cinerea can provide the theoretical basis for sustainable and long-term disease management. Autophagy is an intracellular process for degradation and recycling of cytosolic materials in eukaryotes and is now known to be vital for fungal life. Here, we report studies of the biological role of the autophagy gene BcATG8 in B. cinerea The results suggest that autophagy plays a crucial role in vegetative differentiation and virulence of B. cinerea.


Histochemical and contractile property changes during human muscle development.
When the histochemical and contractile properties of infant muscles change postnatally, and what influence muscle function has on these changes, were the focus of this study. Contractile properties were measured in the plantaflexor (PF) and dorsiflexors (DF) of 19 newborns and 36 infants aged 5-16 months. Infants were tested between one and four times at monthly intervals. Measurements included maximal twitch tension (Pt), time to peak tension (TPT), and half-relaxation times (1/2RT). TPT was similar in PF (77 ms) and DF (73 ms) at birth, remained unchanged in DF, and slowed in PF to 110-120 ms between 9 and 12 months. Type I distributions were determined at autopsy in fetal through to adult muscles. Completion of differentiation occurred in soleus at about the age that contractile properties slowed and infants started to use these muscles more. A trend of higher percentages of type I distributions was also noted in children than either newborns or adults in other muscles. The implications of these findings and the clinical use of these methods for evaluating peripheral neuromuscular function is discussed.


The malignant transformation of osteoid osteoma in the cervical spine to high-grade osteosarcoma: a case report and review of literature.
Osteoid osteoma occasionally occur in the spine, but their malignant transformation is not common. We present an extremely rare case of the malignant transformation of an osteoid osteoma to high-grade osteosarcoma that formed in the pedicle and spread to the lateral mass of the cervical spine. We report the case of an 18-year-old man who suffered from neck pain as an initial symptom. The size of the radiolucent lesion was 12 mm in diameter at the time of diagnosis. Intralesional tumour resection and autologous bone grafting were performed. The remaining tumour grew gradually for 40 months after the surgery; therefore, the tumour had grown rapidly till 51 months after the initial diagnosis. At this stage, the tumour size was approximately 6-fold larger than the initial size, and resulted in progressive paraplegia. A biopsy revealed that the tumour had transformed into a high-grade osteosarcoma. Heavy charged particle irradiation was performed to control tumour growth. There is a possibility of malignant transformation of osteoid osteoma. Patients with osteoid osteoma or osteoblastoma should be carefully observed, especially for recurrent tumours after an intralesional resection.


Free versus liposome-encapsulated muramyl tripeptide phosphatidylethanolamide in treatment of experimental Klebsiella pneumoniae infection.
The effect of free and liposome-encapsulated muramyl tripeptide phosphatidylethanolamide (MTPPE) on resistance to Klebsiella pneumoniae infection in mice was investigated. It was shown that administration of MTPPE, at 24 h before bacterial inoculation, led to a dose-dependent antibacterial resistance in terms of increased clearance of bacteria from the blood and bacterial killing in various organs. The lowest effective dose of MTPPE was 50 micrograms per mouse. Administration of liposome-encapsulated MTPPE was also effective at a dose of 25 micrograms per mouse. The time of administration of both free and liposome-encapsulated MTPPE, with respect to the appearance of bacteria in the blood, was very important and indicated that repeated administration is necessary to obtain protection for a prolonged period. In view of the toxicity of MTPPE, it was an important observation that repeated administration of MTPPE in the liposome-encapsulated form also produced antibacterial resistance. Administration of free and liposome-encapsulated MTPPE resulted in increased numbers of granulocytes, monocytes, and lymphocytes in the blood of uninfected mice and prevented leukopenia in infected mice.


Binding and screening by cations and the effect on exogenous NAD(P)H oxidation in Neurospora crassa mitochondria.
1. The uncoupled oxidation of exogenous NADH by mitochondria from Neurospora crassa has a pH optimum at 7.0. In the presence of EDTA (1 mM) the optimum is at pH 6.5; maximal inhibition (65%) occurs at pH 7.2. This is comparable to the results with higher plant mitochondria. 2. The corresponding pH optima for NADPH oxidation are 7.75 (control), 7.0 (+ EDTA) and 8.0 (effect of EDTA), respectively. NADPH oxidation is completely inhibited by EDTA at pH 8.0. These pH optima are all about 1 higher than observed in mitochondria from higher plants. 3. The inhibition of NADH oxidation by EDTA is shown to be due to the removal of Mg2+ bound to the mitochondrial membranes. 4. It is shown that 9-aminoacridine can be used to monitor the surface potential of the membranes of Neurospora mitochondria. 5. Cations stimulate NADH oxidation by Neurospora mitochondria in a manner consistent with the theory of the diffuse layer. Quantitatively, the results suggest that Neurospora mitochondria contain fewer charges per mass of protein than Jerusalem artichoke (Helianthus tuberosus) mitochondria but more than mitochondria from Arum maculatum spadices. 6. A good correlation is found between the effect of La3+ on the fluorescence of 9-aminoacridine in the presence of mitochondria and on the oxidation of NADH by the mitochondria. La3+ has different effects on mitochondria from Neurospora, Jerusalem artichoke tubers and Arum spadices. THe results indicate that the fluorescence of 9-aminoacridine can be used to monitor binding sites on biological membranes.


Accumulating experience in a child abuse clinic.
To examine the patient profile encountered in the first year of operation of the Child Abuse and Neglect Clinic of the Transvaal Memorial Institute. Record review of all cases presenting to the Clinic from May 1988 to April 1989. Females comprised just over 80% of the 227 patients. Sexual abuse was the presenting complaint in 89.8%. Most were young, 7% under 3 and 55% under 10 years of age. Almost one-third of the boys and 5.0% of the girls had chronic signs of anal abuse. Of the girls 56% had signs of chronic and 10% signs of acute vaginal abuse. Where the certainty of sexual abuse was high, 60% of the girls and 45% of the boys had suffered penetrative abuse. The perpetrators were almost invariably known to the child; biological family members accounted for 38% of perpetrators, and if all relations are included (biological, step and 'common law'), family members were the perpetrators in 66% of cases. Strangers were the perpetrators in only 7% of our cases. The majority of perpetrators were male. Behaviour problems were recorded in 73% of cases. Many different problems were noted; the most common were school problems (21%), masturbation (19%), 'clingy' behaviour (12%), and withdrawal and depression (11.5%). Certainty of diagnosis should be specified. We use four categories: proven, highly suspected, unproven but still suspected, and no abuse. For sexual abuse we also differentiate between penetrative, non-penetrative, 'type uncertain' and no abuse. Training of other health personnel in child abuse management is now a priority in our setting.


Evidence-based rationale for offloading treatment modalities.
Diabetic foot ulcers (DFU) are a common co-morbidity affecting patients with diabetes. A variety of factors, including diabetic peripheral neuropathy, altered gait, and increased pressure on certain regions of the foot, can over time result in a diabetic foot wound. Reducing pressure at the site of the ulcer can promote healing and prevent further ulceration. Offloading is an evidence-based treatment modality for patients with DFUs and is part of the standard protocol for treatment. We discuss here the most common offloading modalities, placing them in the context of relevant medical and compliance issues that affect their use and success.


Application of hormonal treatment in hypogonadotropic hypogonadism: more than ten years experience.
To demonstrate the efficacy of hormone treatment on the patients with hypogonadotropic hypogonadism (HH), we summarized our more than 10 years experience. A total of 242 male patients (age range 15-52 years old) with HH including two Kallmann syndrome treated at the andrology outpatient clinics of university hospital in the past 10 years were reviewed retrospectively. The patients were divided into three groups based on the different treatment strategy. There were 84 patients treated with human chorionic gonadotropin (hCG) (group 1, hCG treatment group), 74 patients treated with hCG plus human menopause gonadotropin (hMG) (group 2, hCG + hMG treatment group), and 84 patients treated with testosterone (group 3, T treatment group). Sex characteristics, testicular volume, and sperm production were determined before and after the treatments. The therapeutic effects in the three groups were analyzed statistically. In total, 42 patients of group 1 (50.0%) and 56 of group 2 (75.7%) had their testicular volumes increased after 6-18 months treatment, from 2.0 ± 1.1 to 6.8 ± 3.2 mL and 2.1 ± 1.1 to 8.8 ± 3.9 mL, respectively. Only six patients of group 3 had their testicular volumes increased but no statistically significant. Among the patients with testes growth, 34 patients of group 1 and 48 patients of group 2 achieved spermatogenesis, and three of them made their wives pregnant naturally. During the follow-up after treatment, there were 36 patients finally defined as delayed puberty, and 204 patients defined as idiopathic hypogonadotropic hypogonadism. For the hormonal treatment of HH, testosterone therapy could not stimulate testes growth and spermatogenesis, but HCG therapy and hCG/hMG combination therapy both are effective, while hCG/hMG combination therapy could achieve better therapeutic effects.


Interaction of IL-13 and C10 in the pathogenesis of bleomycin-induced pulmonary fibrosis.
The initial stimulus for inflammatory cell recruitment and the mechanisms responsible for the perpetuation and evolution of chronic inflammation, granulation tissue formation, and fibrosis have not been fully elucidated. Although interleukin (IL)-13, a Th2 cytokine, has been shown to have direct effects on fibroblasts that support fibroproliferation, it is also a potent inducer of a novel CC chemokine, C10, which is chemotactic for mononuclear phagocytes. The macrophage/mononuclear phagocyte has been shown to have a role in the pathogenesis of pulmonary fibrosis, serving as an important source of growth factors that regulate extracellular matrix synthesis. In this study we demonstrate that IL-13 and C10 are elevated in the pathogenesis of bleomycin-induced pulmonary fibrosis. Neutralization of IL-13, but not IL-4, attenuated bleomycin-induced pulmonary fibrosis and levels of C10, suggesting that IL-13 has an important role in the development of pulmonary fibrosis. IL-13 is a potent inducer of C10 in vivo, and neutralization of C10 attenuated bleomycin-induced pulmonary fibrosis and intrapulmonary macrophage numbers. This suggests that IL-13 has a role in the development of pulmonary fibrosis that is independent of its direct effect on fibroblasts and is evidence for an interaction between Th2 cytokines and specific CC chemokines.


Lemierre's Syndrome Associated with Periodontal Injury-derived Odontogenic Infection that Did Not Respond to Meropenem.
A 33-year-old previously healthy man injured his gums and subsequently developed dyspnea and fever. A chest X-ray showed nodules and infiltrates in both lungs, and the patient was initially diagnosed with pneumonia and administered meropenem hydrate, although his symptoms did not improve. A blood culture identified Fusobacterium necrophorum, and thrombophlebitis in the internal jugular vein of the neck was observed on computed tomography and ultrasound scans. We replaced the meropenem with clindamycin, sulbactam/ampicillin and metronidazole, and the patient's symptoms improved.


Molecular machinery: synthesis of a "nanodragster".
The synthesis and imaging by scanning tunneling microscopy of a mixed wheeled nanovehicle composed of a p-carborane small-wheeled short front axle and a C(60) large-wheeled long rear axle that has been termed a nanodragster due to the structural relation to a dragster are reported. This nanodragster is expected to exhibit motion at a lower temperature than pure C(60)-wheeled nanocars and should allow the investigation of the role played by p-carborane wheels in directional motion.


Decoding the Consequences of Increasing the Size of Self-Assembling Tricarboxamides on Chiral Amplification.
A complete series of experimental and theoretical investigations on the supramolecular polymerization of chiral (1 and 2) and achiral (3) oligo(phenylene ethynylene) tricarboxamides (OPE-TAs) is reported. The performance of seargents-and-soldiers (SaS) and majority rules (MR) experiments has allowed deriving a full set of thermodynamic parameters, including the helix reversal penalty (HRP) and the mismatch penalty (MMP). The results described illustrate the influence exerted by the number of stereogenic centers per monomeric unit and the temperature on the chiral amplification phenomenon. While the HRP decreases upon decreasing the number of chiral side chains, the MMP follows an opposite trend. The experimental trend observed in MR experiments contrasts with that reported for benzenetricarboxamides (BTAs), for which the chiral amplification ability increases by lowering the number of stereogenic centers or increasing the temperature. Theoretical calculations predict that the rotational angle between adjacent monomeric units in the stack (ca. 18°) gradually decreases when decreasing the number of branched chiral side chains and leads to higher MMP values, in good accord with the experimental trend. The reduction of the rotational angle gives rise to less efficient H-bonding interactions between the peripheral amide functional groups and is suggested to provoke a decrease of the HRP as experimentally observed. In BTAs, increasing the number of stereogenic centers per monomeric unit results in a negligible change of the rotation angle between adjacent units (ca. 65°), and, consequently, the steric bulk increases with the number of chiral side chains, leading to higher MMP values. The data presented herein contribute to shed light on the parameters controlling the transfer and amplification of chirality processes in supramolecular polymers, highlighting the enormous influence exerted by the size of the self-assembling unit on the final helical outcome.


Effects of docosahexaenoic and eicosapentaenoic acid on lipid metabolism, eicosanoid production, platelet aggregation and atherosclerosis in hypercholesterolemic rats.
Exogenously hypercholesterolemic (ExHC) rats were fed on an atherogenic diet supplemented with 1% each of either ethyl ester docosahexaenoic acid [EE-DHA, 22:6(n-3)], ethyl ester eicosapentaenoic acid [EE-EPA, 20:5(n-3)] or safflower oil (SO) for 6 months. The rats fed on the diets containing EE-EPA or EE-DHA, compared with those fed on SO, had lower serum cholesterol and triacylglycerol levels, less aggregation of platelets and slower progress of intimal thickening in the ascending aorta. Relative to the SO-fed rats, both of the (n-3) fatty acid-fed rats had a significantly reduced proportion of arachidonic acid in the platelet and aortic phospholipids, and lower production of thromboxane A2 by platelets and of prostacyclin by the aorta. These results suggest that EPA and DHA are similarly involved in preventing atherosclerosis development by reducing hypercholesterolemia and modifying the platelet functions.


A novel pathway for sequential transformation of 7-dehydrocholesterol and expression of the P450scc system in mammalian skin.
Following up on our previous findings that the skin possesses steroidogenic activity from progesterone, we now show widespread cutaneous expression of the full cytochrome P450 side-chain cleavage (P450scc) system required for the intracellular catalytic production of pregnenolone, i.e. the genes and proteins for P450scc enzyme, adrenodoxin, adrenodoxin reductase and MLN64. Functionality of the system was confirmed in mitochondria from skin cells. Moreover, purified mammalian P450scc enzyme and, most importantly, mitochondria isolated from placenta and adrenals produced robust transformation of 7-dehydrocholesterol (7-DHC; precursor to cholesterol and vitamin D3) to 7-dehydropregnenolone (7-DHP). Product identity was confirmed by comparison with the chemically synthesized standard and chromatographic, MS and NMR analyses. Reaction kinetics for the conversion of 7-DHC into 7-DHP were similar to those for cholesterol conversion into pregnenolone. Thus, 7-DHC can form 7-DHP through P450scc side-chain cleavage, which may serve as a substrate for further conversions into hydroxy derivatives through existing steroidogenic enzymes. In the skin, 5,7-steroidal dienes (7-DHP and its hydroxy derivatives), whether synthesized locally or delivered by the circulation, may undergo UVB-induced intramolecular rearrangements to vitamin D3-like derivatives. This novel pathway has the potential to generate a variety of molecules depending on local steroidogenic activity and access to UVB.


Relation between Kaufman Brief Intelligence Test and WISC-III scores of children with RD.
Concurrent validity of the Kaufman Brief Intelligence Test (K-BIT) with the Wechsler Intelligence Scale for Children-Third Edition (WISC-III) was evaluated, as well as the K-BIT's accuracy as a predictor of WISC-III scores, in a sample of young children with reading disabilities. The two measures were administered to 65 children from Atlanta, Boston, and Toronto who ranged from 6-5 to 7-11 years of age at testing. Correlations between the verbal, nonverbal, and composite scales of the K-BIT and WISC-III were .60, .48, and .63, respectively. Mean K-BIT scores ranged from 1.2 to 5.0 points higher than the corresponding WISC-III scores. Standard errors of estimation ranged from 10.0 to 12.3 points. In individual cases, K-BIT scores can underestimate or overestimate WISC-III scores by as much as 25 points. Results suggest caution against using the K-BIT exclusively for placement and diagnostic purposes with young children with reading disabilities if IQ scores are required.


E proteins and Notch signaling cooperate to promote T cell lineage specification and commitment.
The helix-loop-helix protein, E47, is essential for both B- and T-lineage development. Here we demonstrate that in vitro E47 and Notch signaling act in concert to promote T cell development from fetal hematopoietic progenitors and to restrain development into the natural killer and myeloid cell lineages. The expression of an ensemble of genes associated with Notch signaling is activated by E47, and additionally, Notch signaling and E47 act in parallel pathways to induce a T lineage-specific program of gene expression. Enforced expression of the intracellular domain of Notch rescues the developmental arrest at the T cell commitment stage in E2A-deficient fetal thymocytes. Finally, we demonstrate that regulation of Hes1 expression by Notch signaling and E47 is strikingly similar to that observed during Drosophila melanogaster sensory development. Based on these observations, we propose that in developing fetal thymocytes E47 acts to induce the expression of an ensemble of genes involved in Notch signaling, and that subsequently E47 acts in parallel with Notch signaling to promote T-lineage maturation.


Dipolar Crystals: The Crucial Role of the Clinohexagonal Prism Phase.
We report a new phase called clinohexagonal prism (CHP) that accounts for all the ground states of dipolar hard spheres prepared at any density. This phase merely consists of an oblique prismatic lattice with a hexagonal base. Our calculations show that at intermediate densities, a special close packed body-centered orthorhombic phase coincides with the CHP phase in the ground state for a wide density window. In the high packing regime, i.e., in the vicinity of the density of the hexagonal close packed phase, it is a limiting case of the CHP phase with vanishing obliquity that emerges. These findings provide a unified and clarified view of the solid-solid transitions occurring at zero temperature in dipolar systems and should be relevant in other related molecular or soft matter systems governed by anisotropic (and possibly isotropic) soft potentials.


[Determination of tributyl phosphate in the air of workplace by gas chromatography].
Objective: To establish a practical method forsampling and detectingtributyl phosphate intheworkplace. Methods: The samples were extracted by glass fiber membrane, eluted with ether, separated by gas chromatography, and detected by flame photometric detector. Results: There were good linear relationship in the minimum detection concentration was 7.2-720.0 μg/ml, and the correlation coefficient was 0.999 92. The detection limit was 0.86 μg/ml, and the minimum detection concentration was 0.14 mg/m(3) (sample volume was 30 L) . Recovery rates were 99.8%-100.2%. The with-in relative standard deviations were 4.0%-5.4% and the between relative standard deviations were 2.0%-5.5%, and average samplingefficiency was about 99.1%-100.0%. Conclusion: This method conforms with the requirements of "Standardization of Methods for Determination of Toxic Substance in Workplace" . Tributyl phosphate in air could be determined accurately using this method.


Capture of a Transition State Using Molecular Dynamics: Creation of an Intercalation Site in dsDNA with Ethidium Cation.
The mechanism of intercalation and the ability of double stranded DNA (dsDNA) to accommodate a variety of ligands in this manner has been well studied. Proposed mechanistic steps along this pathway for the classical intercalator ethidium have been discussed in the literature. Some previous studies indicate that the creation of an intercalation site may occur spontaneously, with the energy for this interaction arising either from solvent collisions or soliton propagation along the helical axis. A subsequent 1D diffusional search by the ligand along the helical axis of the DNA will allow the ligand entry to this intercalation site from its external, electrostatically stabilized position. Other mechanistic studies show that ethidium cation participates in the creation of the site, as a ligand interacting closely with the external surface of the DNA can cause unfavorable steric interactions depending on the ligands' orientation, which are relaxed during the creation of an intercalation site. Briefly, such a site is created by the lengthening of the DNA molecule via bond rotation between the sugars and phosphates along the DNA backbone, causing an unwinding of the dsDNA itself and separation between the adjacent base pairs local to the position of the ligand, which becomes the intercalation site. Previous experimental measurements of this interaction measure the enthalpic cost of this part of the mechanism to be about -8 kcal/mol. This paper reports the observation, during a computational study, of the spontaneous opening of an intercalation site in response to the presence of a single ethidium cation molecule in an externally bound configuration. The concerted motions between this ligand and the host, a dsDNA decamer, are clear. The dsDNA decamer AGGATGCCTG was studied; the central ...GATG... site was the intercalation site.


Viral hepatitis infection and insulin resistance: a review of the pathophysiological mechanisms.
Viral hepatitis is a common cause of morbidity in Mexico. Insulin resistance (IR) is related to the liver damage caused by some viral infections, especially chronic infections. Chronic viral infection is an important risk factor for the development of type 2 diabetes mellitus, disease that is currently among the 10 main causes of morbidity and the most common cause of mortality. Although several studies have reported an association between IR and hepatitis B virus or hepatitis C virus (HCV) infection, the pathophysiology has been studied thoroughly only for the association between IR and HCV infection. It is thought that HCV infection causes direct damage through the action of the core proteins, which induces an inflammatory state characterized by secretion of proinflammatory cytokines that interfere with normal insulin signaling and disturb glucose, lipid and protein metabolism. This review summarizes the mechanisms by which viral infection is thought to induce IR.


[Biomedical and social-hygienic risk factors of disability in rural children].
The importance of the problem of disability of children causes no doubts. The author defines the term "inability" which is recommended for wide use. The data of comprehensive studies of the life style and life conditions of the rural families with disabled children are summed up. The totality of factors affecting a child's health is analyzed. Subjective requirements of children with limited potentialities in medical care are investigated. Probable approaches to decrease of children's disability are discussed.


Snack Package Size and Variety Differentially Influence Energy Intake and Food Choices in Healthy Adults.
While energy and nutritional content of snacks can contribute to overconsumption, other factors within the modern food environment may also influence the amount and types of snacks consumed. The aim was to examine whether snack package size and variety influence free-living snacking behavior in healthy adults. The impact of intuitive eating score on snacking behavior was also examined. Thirty adults [age: 23.6 ± 0.8 y; BMI (kg/m2): 22.8 ± 0.5] participated in a randomized crossover-design study. Participants were provided, in randomized order, with the following isocaloric snack exposures to consume for 3 d/exposure-1) CONTROL: highly appealing/appetizing snacks (e.g., dessert snacks, candy, savory snacks, fruits and vegetables, protein snacks); 2) LARGE-PACKAGE: similar snacks as CONTROL but in larger package sizes; and 3) VARIETY: larger variety of snacks. The primary outcomes included the 3-d average ad libitum snack energy, macronutrient content, and food choices for each snack exposure. The secondary outcome was the intuitive eating score and snacking behavior. LARGE-PACKAGE increased snack intake by 11.9% (1150 ± 81 kcal) compared with CONTROL (1030 ± 71 kcal, P = 0.04), whereas VARIETY snack intake (1030 ± 69 kcal) was no different from CONTROL (P = 1.0). LARGE-PACKAGE increased consumption of desserts compared with CONTROL (P = 0.03) and VARIETY (P = 0.02). Alternately, VARIETY increased consumption of fruits and vegetables compared with LARGE-PACKAGE (P = 0.01) and CONTROL (P = 0.01). Intuitive eating score was not significantly associated with snack intake or snack choice (all, P > 0.05). Snack package size and variety differentially influence energy intake and food choices in healthy adults. This trial was registered atclinicaltrials.gov (NCT03940105).


Digoxin, hypercalcaemia, and cardiac conduction.
The cardiac effects of hypercalcaemia are usually manifest as a shortening of the QT-interval. Hypercalcaemia is infrequently associated with a clinically manifest arrhythmia. However, concomitant therapy with digoxin or underlying cardiac disease can potentiate the arrhythmogenic effects of hypercalcaemia, leading to a symptomatic rhythm disorder. We describe a symptomatic arrhythmia, which developed in a patient with hypercalcaemia secondary to squamous cell carcinoma of the bronchus. The patient was on digoxin therapy at the time. The arrhythmia did not recur after discontinuation of digoxin therapy and correction of the hypercalcaemia. Because of its effect on cardiac conduction, hypercalcaemia should be considered in the evaluation of any patient with an unexplained bradyarrhythmia. Conversely, patients with hypercalcaemia should discontinue digoxin therapy and be evaluated for the presence of rhythm disorders while receiving appropriate treatment for hypercalcaemia.


23-gauge vitrectomy assisted by combined endoscopy and a wide-angle viewing system for retinal detachment with severe penetrating corneal injury: a case report.
We report a case of traumatic retinal detachment in an eye with severe corneal opacity that was successfully treated using 23 gauge (G) transconjunctival vitrectomy assisted by endoscope and a wide-angle viewing system. A 22-year-old Japanese man was referred to our hospital with the suspicion of traumatic retinal detachment of the right eye, 1 month after an open globe eye injury due to fireworks. At the time of his first visit, his best-corrected visual acuity was hand motion in the right eye. A 23 G three port pars plana vitrectomy was conducted in combination with ophthalmic endoscope and a wide-angle viewing system. Endoscopy revealed a retinal detachment in the inferior quadrant with tiny retinal breaks. Primary reattachment of the retina was achieved by tamponade of SF₆ gas. Five months after the vitrectomy, penetrating keratoplasty was performed and visual acuity recovered to 0.02. Optical coherent tomography revealed thinning of the retina, which might be the cause of the remaining poor vision. 23 G vitrectomy assisted by combined endoscopy and a wide-angle viewing system could be advantageous in managing visualization constraints due to penetrating trauma.


Ectopic Hepatocellular Carcinoma Arising in the Left Triangular Ligament of the Liver.
Hepatocellular carcinoma (HCC) rarely originates in extrahepatic liver tissue. Laparoscopic resection is widely used to treat HCC. This report presents a case of a patient with ectopic HCC arising in the left triangular ligament of the liver that was successfully treated by laparoscopic resection. A 59-year-old female presented with an elevated serum alpha-fetoprotein (AFP) level (2,508 ng/ml). Dynamic computed tomography demonstrated a tumor measuring 20 mm in diameter below the left diaphragm just adjacent to the spleen. The tumor showed contrast enhancement in the hepatic arterial phase and became less dense than the liver parenchyma in the portal phase. The patient was diagnosed with ectopic HCC arising in the left diaphragm and laparoscopic surgery was performed. The tumor was located in the left triangular ligament of the liver and had a stalk between the tumor and the liver. The tumor was resected, and the final diagnosis was moderately differentiated ectopic HCC arising in the left triangular ligament of the liver. The patient had an uneventful postoperative recovery and has experienced no recurrence over 18 months after the operation.


Intraoperative electromyography.
Intraoperative electromyography (EMG) provides useful diagnostic and prognostic information during spine and peripheral nerve surgeries. The basic techniques include free-running EMG, stimulus-triggered EMG, and intraoperative nerve conduction studies. These techniques can be used to monitor nerve roots during spine surgeries, the facial nerve during cerebellopontine angle surgeries, and peripheral nerves during brachial plexus exploration and repair. However, there are a number of technical limitations that can cause false-positive or false-negative results, and these must be recognized and avoided when possible. The author reviews these basic electrophysiologic techniques, how they are applied to specific surgical situations, and their limitations.


Fertility History, Children's Gender, and Post-Reproductive Survival in a Longevous Population.
The question of whether mothers' fertility history influences their post-reproductive survival has been addressed frequently in the scientific literature. Using data from Villagrande Strisaili, Sardinia, where longevity is higher than anywhere else in Europe, we analyzed the relationship between the fertility pattern of mothers who survived past age 50 (n = 539) and their post-reproductive lifespan. We find that, after adjustment for potential confounders (mothers' birth cohort, survival of spouse), the mothers who on average delivered their children later displayed a reduced mortality risk (‒2.9 percent for each additional year), supporting previously reported findings. We also find that a male-skewed offspring ratio was associated with decreased mortality risk of mothers, with longer survival of mothers who delivered their sons above age 35 (p = 0.005), a result not found for daughters. So far, no biological explanation has been suggested for the positive effect of delivering sons later in life. We conjecture that in our dataset stronger nonbiological factors such as gender-specific sociocultural and economic factors may have masked the negative effect reported in other populations, for which a biological explanation was proposed.


SKP-ing TAp63: stem cell depletion, senescence, and premature aging.
The p53 family member p63 comprises multiple isoforms and is critical for stratified epithelial development. In this issue of Cell Stem Cell, by generating isoform-specific knockout mice, Su et al. (2009) reveal pivotal roles for TAp63 in the maintenance of dermal and epidermal precursors, genomic stability, and organismal longevity.


Bronchiolitis obliterans following lung transplantation: early detection using computed tomographic scanning.
Computed tomographic (CT) scanning may enable earlier diagnosis of chronic lung allograft dysfunction than forced expiratory volume in 1 second (FEV1). A study was undertaken to determine intra-observer and inter-observer agreement of composite and air trapping CT scores, to examine the association of FEV1 with the composite and air trapping CT score, and to relate the baseline composite CT score to changes in FEV1 and changes in the composite CT score over 1 year. Lung function and baseline CT scans following transplantation and at subsequent annual follow ups were analysed in 38 lung transplant recipients. Scans were randomly scored by two observers for bronchiectasis, mucus plugging, airway wall thickening, consolidation, mosaic pattern, and air trapping, and re-scored after 1 month. CT scores were expressed on a scale of 0-100 and correlated with FEV1 as a percentage of the post-transplant baseline value. The mean (SD) interval between baseline and follow up CT scans was 11.2 (4.7) months. Inter-observer and intra-observer agreement was good for both the composite and air trapping CT scores. There was a significant association between FEV1 and the composite CT score, with each unit of worsening in the baseline composite CT score predicting a 1.55% and 1.37% worsening in FEV1 over the following year (p<0.0001) and a 1.25 and 1.12 unit worsening in the composite CT score (p<0.0001) for observers 1 and 2, respectively. These findings indicate a potential role for a composite CT scoring system in the early detection of bronchiolitis obliterans.


Ontogenic profile of brain lipids following perinatal exposure to cadmium.
Uniparous female rats were exposed to 10 ppm cadmium (as Cd(CH3COO)2) in drinking water, ad libitum, from day 0 of pregnancy; neonates exposed to Cd gestationally and lactationally were separated from their mothers at 21 days of age and were given 10 ppm Cd in drinking water up to 45 days of age. The sequential analysis of brain lipids during development showed a significant reduction in the total lipid levels at 15, 21, 30 and 45 days of age compared to the respective controls. No change in the triglyceride levels was observed in the Cd-exposed group, except for a slight but statistically significant increase (12%, p < 0.05) at day 15 of postnatal life. Metallic exposure also decreased the cholesterol content of brain at different time intervals in comparison to its levels in age-matched control rats. The analysis of sialic acid content of the total gangliosides revealed elevated levels of this group of glycolipids at 21 (25%), 30 (17%) and 45 (23%) days of age compared to their counterpart controls. However, a remarkable reduction in the concentration of brain galactosylceramide (30-43%) and 3'-sulphogalactosylceramide (24-37%) at 21, 30 and 45 days of age was observed following pre- and postnatal exposure of cadmium in comparison to the respective controls. The ontogenic profile of different brain phospholipids in the Cd-exposed group showed an increase in the levels of phosphatidylethanolamine at 21 (31%), 30 (25%) and 45 (19%) days of age; the phosphatidylcholine contents increased at day 21 (14%), followed by a significant decrease at 30 (14%) and 45 (19%) days compared to age-matched controls. Brain phosphatidylinositol, phosphatidylserine and sphingomyelin did not show any alteration at early periods of exposure but decreased significantly following continued exposure by 34%, 45% and 21%, respectively, at 45 days of age. Metal analysis in the brain showed a reduction in zinc and copper levels at 15 and 21 days of age in Cd-exposed animals; however, iron levels remained comparable with control values throughout the experiment. It may be concluded that an early exposure of Cd may produce alteration in the development of different lipids, which may produce CNS dysfunctions with a possibility of being manifested even in later life.


External Quality Assessment for Rubella Virus RNA Detection Using Armored RNA in China.
Although tremendous efforts have been made to reduce rubella incidence, there are still 300 new cases of congenital rubella syndrome daily; thus, rubella infections remain one of the leading causes of preventable congenital birth defects. An effective surveillance system, which could be achieved and maintained by using an external quality assessment program, is critical for prevention and control of this disease. Armored RNAs, which are noninfectious and RNase-resistant, were used for encapsulation of the E1 gene of rubella virus and for preparation of a 10-specimen panel for external quality assessment. Thirty-two laboratories across mainland China that used nucleic acid tests for rubella virus RNA detection were included in the external quality assessment program organized by the National Center for Clinical Laboratories of China. Different kinds of commercial kits were used by the laboratories for nucleic acid extraction and TaqMan real-time reverse-transcription PCR for rubella virus RNA detection; 99.2% sensitivity and 100% specificity were achieved in this external quality assessment program. Most of the participating laboratories obtained accurate results for rubella nucleic acid tests, thereby achieving the quality required for regional rubella and congenital rubella syndrome elimination.


Osteoid osteoma: CT-guided percutaneous excision confirmed with immediate follow-up scintigraphy in 16 outpatients.
To evaluate treatment of osteoid osteoma with computed tomography (CT)-guided percutaneous excision and immediate follow-up scintigraphy. Sixteen consecutive adolescent and adult patients underwent CT-guided percutaneous excision of a nidus with 14-gauge biopsy cutting needles, with local anesthesia. After the presence of nidus was confirmed at immediate follow-up scintigraphy, curettage of the bored cavity was performed to remove any residual fragments of the nidus. Scintigraphic and histologic findings were correlated. The nidus was removed successfully in 14 of the 16 patients, with no complications (mean follow-up, 15 months; range, 3-25 months). In five of the 14 patients, immediate follow-up scintigraphy showed incomplete resection of the nidus and immediate second resection was successful. Surgical resection was necessary in two of the 16 patients. CT-guided percutaneous excision with immediate follow-up scintigraphy was safe and effective for localization and removal of osteoid osteoma in outpatients.


Isolation from opossum serum of a metalloproteinase inhibitor homologous to human alpha 1B-glycoprotein.
Fractionation of opossum (Didelphis virginiana) serum with (NH4)2SO4, followed by chromatography on DEAE-Sepharose, phenyl-Sepharose, and Mono Q HR 5/5, has resulted in the isolation in homogeneous condition of a metalloproteinase inhibitor designated oprin (opossum proteinase inhibitor). Oprin is a single-chain glycoprotein (26% carbohydrate) with an estimated Mr = 52,000, pI = 3.5, and E(1%/1 cm) = 11. Oprin inhibited snake venom metalloproteinases, but showed no activity on venom serine proteinases or on bacterial metalloproteinases. Incubation of Crotalus atrox alpha-proteinase (EC 126.96.36.199) with oprin, and analysis of the reaction products by chromatography on Mono Q HR 5/5 and by electrophoresis under nondenaturing conditions, indicated formation of an inactive enzyme/inhibitor complex. The complex dissociated during SDS/polyacrylamide gel electrophoresis. An opossum liver cDNA library was immunoscreened, and clones containing cDNA encoding for part of the open reading frame for oprin were isolated. The cDNA inserts contained nucleotide sequences corresponding to two internal amino acid sequences of oprin which had been separately determined by protein sequence analysis. Protein database screening using a 211 amino acid sequence deduced from one of the cDNA inserts showed no significant homology to known proteinase inhibitors. There was, however, a 36% identity with human alpha 1B-glycoprotein, a plasma protein of unknown function related to the immunoglobulin supergene family. In addition, the amino-terminal sequence of oprin showed 46% identity with human alpha 1B-glycoprotein in a 26 amino acid residue overlap.(ABSTRACT TRUNCATED AT 250 WORDS)


Acoustic effects of medical, cloth, and transparent face masks on speech signals.
Face masks muffle speech and make communication more difficult, especially for people with hearing loss. This study examines the acoustic attenuation caused by different face masks, including medical, cloth, and transparent masks, using a head-shaped loudspeaker and a live human talker. The results suggest that all masks attenuate frequencies above 1 kHz, that attenuation is greatest in front of the talker, and that there is substantial variation between mask types, especially cloth masks with different materials and weaves. Transparent masks have poor acoustic performance compared to both medical and cloth masks. Most masks have little effect on lapel microphones, suggesting that existing sound reinforcement and assistive listening systems may be effective for verbal communication with masks.


Fabrication of disposable topographic silicon oxide from sawtoothed patterns: control of arrays of gold nanoparticles.
Disposable topographic silicon oxide patterns were fabricated from polymeric replicas of sawtoothed glass surfaces, spin-coating of poly(dimethylsiloxane) (PDMS) thin films, and thermal annealing at certain temperature and followed by oxygen plasma treatment of the thin PDMS layer. A simple imprinting process was used to fabricate the replicated PDMS and PS patterns from sawtoothed glass surfaces. Next, thin layers of PDMS films having different thicknesses were spin-coated onto the sawtoothed PS surfaces and annealed at 60 degrees C to be drawn the PDMS into the valley of the sawtoothed PS surfaces, followed by oxygen plasma treatment to fabricate topographic silicon oxide patterns. By control of the thickness of PDMS layers, silicon oxide patterns having various line widths were fabricated. The silicon oxide topographic patterns were used to direct the self-assembly of polystyrene-block-poly(2-vinylpyridine) (PS-b-P2VP) block copolymer thin films via solvent annealing process. A highly ordered PS-b-P2VP micellar structure was used to let gold precursor complex with P2VP chains, and followed by oxygen plasma treatment. When the PS-b-P2VP thin films containing gold salts were exposed to oxygen plasma environments, gold salts were reduced to pure gold nanoparticles without changing high degree of lateral order, while polymers were completely degraded. As the width of trough and crest in topographic patterns increases, the number of gold arrays and size of gold nanoparticles are tuned. In the final step, the silicon oxide topographic patterns were selectively removed by wet etching process without changing the arrays of gold nanoparticles.


Keeping in shape: exercise fundamentals for the midlife patient.
The typical physiologic effects of aging on the musculoskeletal system can be impeded with regular exercise and diet. Common orthopedic problems in sedentary midlife patients are shoulder impingement, low back pain, and plantar fasciitis. Although the responsibility for maintaining an exercise program rests with the individual, the primary care physician can play an important role as coach, cheerleader, and respected advisor. The key is to encourage patients to initiate a program of regular, moderate exercise 30 minutes a day, three times a week, and to eat a balanced, nutritious diet. The best exercise and diet regimen is one that is custom-designed to accommodate the individual patient's needs and objectives.


Prothrombotic changes in diabetes mellitus.
Although our understanding of vascular pathology has greatly improved in recent years, the cellular and molecular mechanisms underlying the enhanced thrombotic propensity in type 2 diabetes mellitus (T2DM) remain incompletely characterized. Detrimental interactions between activated vascular cells (i.e., platelets, leukocytes, endothelial cells) and the vulnerable atheromatous plaque are a major determinant of the increased atherothrombotic burden in T2DM patients. Endothelial damage and accelerated senescence, impairment of the endothelial progenitor cell repair system, plaque neovascularization and inflammation, decreased clearance of detrimental molecules within the plaque, and increased expression of matrix metalloproteinases may collectively contribute to intraplaque hemorrhage and subsequent rupture. Notably, recent data demonstrates the central importance of the tissue factor-microparticle-mediated pathway in diabetic thrombophilia and cardiovascular complications. Acting as detrimental amplifiers of various biological responses (including thrombogenicity and plaque remodeling), microparticles have also emerged as a key marker of global vascular damage in T2DM patients. Available evidence suggests that targeting the tissue factor-microparticle pathway may be a promising approach for reducing the burden of the atherosclerotic complications of diabetes.


How well do caregivers detect mild cognitive change in Parkinson's disease?
Using the Cambridge Behavior Inventory-Revised, this study evaluated the relationship between caregiver ratings of cognitive change and neuropsychological performance. In sixty-one nondemented patients with Parkinson's Disease (PD; mean age = 64.5 years, MMSE = 28.7), 62% met criteria for mild cognitive impairment. This group were rated as having more overall change as well as memory and behavior change. Caregiver ratings were related to poorer psychomotor speed, learning/memory, language, and executive functioning. The capacity for caregivers to rate mild cognitive change in PD may be useful to assist in early screening and intervention approaches.


Mucosal IgA response to repeated wingate tests in females.
The purpose of this study was to examine the effect of repeated bouts of brief, intermittent, maximal effort exercise on the concentration of secretory IgA (S-IgA) and incidence of upper respiratory tract infection (URTI) in females. Twenty-six non-smoking, active, adult females participated in this study. The exercise intervention consisted of three consecutive, all-out 30-second Wingate leg cycling tests (0.075 kg/kg body mass), which were separated by three minutes of recovery. Unstimulated saliva was collected prior to (PRE) and five minutes after completion (POST) of the exercise testing protocol. IgA, protein and osmolality were measured, and secretory IgA (SIgA), IgA:Protein, and IgA: Osmolality were calculated. In addition, subjects completed standard logs indicating signs and symptoms of upper respiratory tract infection (URTI) for three weeks following the test. Saliva flow rates (478.5 +/- 50; 345.4 +/- 50 microl/min), S-IgA (55.8 +/- 4.7; 35.4 +/- 3.6 microg/min), and IgA: Protein ratio (30.7 +/- 3.0; 17.5 +/- 1.8 microg IgA/mg protein) were significantly lower POST compared to PRE (P < 0.05). No significant differences were observed for raw IgA, protein, osmolality, and IgA: osmolality. The results of this study show that brief, intermittent, maximal effort exercise results in an acute decrease in S-IgA in healthy adult females in less than eight minutes. However, this exercise induced transient decrease did not appear to be associated with an increase in clinical symptoms of URTI in the weeks following the exercise test intervention.


Drug addiction and periodontal diseases.
The prevalence of drug addiction is increasing globally. Drug abuse damages many parts of the body such as oral cavity, lungs, liver, brain, heart etc., Addicts suffer from physical, psychological, emotional and behavioral problems. Their nutrition is also compromised. There is certainly an impact of all these factors on the health of periodontium. Dentists should be aware of the effects of drugs while treating the drug addicts. This article correlates the studies done on the impact of abused drugs such as alcohol, tobacco, opiates, cannabis, amphetamines etc., on general and periodontal health.


One-day protocol for imaging of the nigrostriatal dopaminergic pathway in Parkinson's disease by [123I]FPCIT SPECT.
Parkinson's disease is characterized by degeneration of dopaminergic neurons, resulting in loss of dopamine transporters in the striatum. Recently, the tracer 1231-N-omega-fluoropropyl-2beta-carbomethoxy-3beta-(4-iodoph enyl)nortropane (FPCIT) was developed for imaging dopamine transporters with SPECT. The purpose of this study was to develop an [123I]FPCIT SPECT protocol for routine clinical studies. We examined the time course of [123I]FPCIT binding to dopamine transporters in 10 healthy volunteers and 19 patients with Parkinson's disease. We found that the time of peak specific striatal [123I]FPCIT binding was highly varied among subjects, but specific binding peaked in all controls and patients within 3 h postinjection. Between 3 and 6 h, the ratio of specific-to-nonspecific striatal [123I]FPCIT binding was stable in both groups, although, as expected, it was significantly lower in patients. In the patients, [123I]FPCIT binding in the putamen was lower than in the caudate nucleus, and contralateral striatal binding was significantly lower than ipsilateral striatal binding. The subgroup of patients with hemi-Parkinson's disease showed loss of striatal dopamine transporters, even on the ipsilateral side. For routine clinical [123I]FPCIT SPECT studies, we recommend imaging at a single time point, between 3 and 6 h postinjection, and using a tissue ratio as the outcome measure. The [123I]FPCIT SPECT technique is sensitive enough to distinguish control subjects from patients with Parkinson's disease, even at an early stage of the disease.


Allelic loss of selected tumor suppressor genes in acute lymphoblastic leukemia in children.
Defect in function of tumor suppressor genes may lead to initiation/progression of leukemias. RB1, CDKN2A and TP53 gene alterations are found in acute lymphoblastic leukemia (ALL) in children. Data showing a contribution of these alterations to the pathomechanism of leukemias are contradictory and their impact on a disease course still remains undefined. The main aim of the study was to identify and the characterize of RB1, CDKN2A and TP53 allele loss in ALL children patients at diagnosis. 46 children with de novo ALL were examined. Fluorescent in situ hybridization was performed on bone marrow smear preparations. We demonstrated that at least one of three investigated deletions occurred statistically more frequently in T-lineage leukemia patients (p = 0.044); this was the most frequent in respect to RB1 gene (p = 0.054). Additionally, at least one of the examined deletions was observed statistically more frequently in patients with WBC above 20 000/µl (p = 0.043), this was the most frequent for CDKN2A gene (p = 0.066). Presented results seem to give an evidence that deletions of RB1 and CDKN2A genes may contribute to the development of hyperleukocytic type of T-lineage ALL in children, nevertheless this observation needs further investigations.


Comparison of isoflurane with propofol on respiratory cilia.
We have investigated the effects of two techniques of clinical anaesthesia on human respiratory cilia by measuring cilia beat frequency of nasal tissue. In a randomized, controlled study, 13 patients undergoing either inhalation anaesthesia with isoflurane or total i.v. anaesthesia with propofol and alfentanil had nasal ciliated epithelial samples removed at the beginning and after 1 h of anaesthesia. Mean cilia beat frequency in the group anaesthetized with isoflurane changed significantly from 11.5 (95% confidence interval (CI) 10.7-12.2) Hz to 9.1 (8.1-10.1) Hz after anaesthesia whereas in the group anaesthetized with propofol and alfentanil there was a change from 11.5 (10.7-12.2) Hz to 11.0 (10.2-11.8) Hz (ns). The difference between the anaesthetic agents on cilia beat frequency was significant (MANOVA, P < 0.01). These data suggest that different anaesthetic agents may impair respiratory defence mechanisms to differing extents.


Optic nerve ultrasound for the detection of elevated intracranial pressure in the hypertensive patient.
We sought to determine whether dilation of the optic nerve sheath diameter (ONSD), as detected at the bedside by emergency ultrasound (US), could reliably correlate with patient blood pressure and whether there was a blood pressure cutoff point where you would start to see abnormal dilation in the ONSD. This was a single-blinded, prospective, observational trial from September 2010 to April 2011. One hundred fifty patients presenting to the emergency department were enrolled. There were 3 arms to the study with 50 patients in each arm: (1) ONSD in normotensive/asymptomatic patients; (2) ONSD in hypertensive/asymptomatic patients; and (3) ONSD in hypertensive/symptomatic patients. Ocular US was conducted on all subjects. Neither the number of symptoms nor the type of symptom present in the hypertensive/symptomatic group was able to significantly predict the average ONSD before treatment (P = .818 and .288, respectively). There was a significant correlation between both systolic blood pressure (SBP) and diastolic blood pressure (DBP) with the ONSD in all hypertensive patients. The best SBP and DBP cutoff point for abnormal ONSD was 166/82 mm Hg. Decrease in ONSD observed after blood pressure treatment was not statistically significant (P = .073). In conclusion, our study shows that practitioners can use bedside ocular US and a blood pressure cutoff point to help predict whether patients require more aggressive management of their symptomatic hypertension. Knowing the SBP and DBP readings that lead to increased ONSD and increased intracranial pressure can help guide management and treatment decisions at the bedside.


A model and typology of collaboration between professionals in healthcare organizations.
The new forms of organization of healthcare services entail the development of new clinical practices that are grounded in collaboration. Despite recent advances in research on the subject of collaboration, there is still a need for a better understanding of collaborative processes and for conceptual tools to help healthcare professionals develop collaboration amongst themselves in complex systems. This study draws on D'Amour's structuration model of collaboration to analyze healthcare facilities offering perinatal services in four health regions in the province of Quebec. The objectives are to: 1) validate the indicators of the structuration model of collaboration; 2) evaluate interprofessional and interorganizational collaboration in four health regions; and 3) propose a typology of collaboration A multiple-case research strategy was used. The cases were the healthcare facilities that offer perinatal services in four health regions in the province of Quebec (Canada). The data were collected through 33 semi-structured interviews with healthcare managers and professionals working in the four regions. Written material was also analyzed. The data were subjected to a "mixed" inductive-deductive analysis conducted in two main stages: an internal analysis of each case followed by a cross-sectional analysis of all the cases. The collaboration indicators were shown to be valid, although some changes were made to three of them. Analysis of the data showed great variation in the level of collaboration between the cases and on each dimension. The results suggest a three-level typology of collaboration based on the ten indicators: active collaboration, developing collaboration and potential collaboration. The model and the typology make it possible to analyze collaboration and identify areas for improvement. Researchers can use the indicators to determine the intensity of collaboration and link it to clinical outcomes. Professionals and administrators can use the model to perform a diagnostic of collaboration and implement interventions to intensify it.


Estimation of the Driving Style Based on the Users' Activity and Environment Influence.
New models and methods have been designed to predict the influence of the user's environment and activity information to the driving style in standard automotive environments. For these purposes, an experiment was conducted providing two types of analysis: (i) the evaluation of a self-assessment of the driving style; (ii) the prediction of aggressive driving style based on drivers' activity and environment parameters. Sixty seven h of driving data from 10 drivers were collected for analysis in this study. The new parameters used in the experiment are the car door opening and closing manner, which were applied to improve the prediction accuracy. An Android application called Sensoric was developed to collect low-level smartphone data about the users' activity. The driving style was predicted from the user's environment and activity data collected before driving. The prediction was tested against the actual driving style, calculated from objective driving data. The prediction has shown encouraging results, with precision values ranging from 0.727 up to 0.909 for aggressive driving recognition rate. The obtained results lend support to the hypothesis that user's environment and activity data could be used for the prediction of the aggressive driving style in advance, before the driving starts.


Identification of developmentally regulated expression of MuSK in astrocytes of the rodent retina.
One of the master regulators of postsynaptic neuromuscular synaptogenesis is the muscle-specific receptor tyrosine kinase (MuSK). In mammals prominent MuSK expression is believed to be restricted to skeletal muscle. Upon activation by nerve-derived agrin MuSK-dependent signalling participates in both the induction of genes encoding postsynaptic components and aggregation of nicotinic acetylcholine receptors (AChR) in the subsynaptic muscle membrane. Strikingly, expression of certain isoforms of nerve-derived agrin can also be detected in the CNS. In this study, we examined the expression of MuSK in the brain and eye of rodents. In the retina MuSK was expressed in astrocytes between postnatal days 7 and 14, i.e. at the time when the eyes open. We found that agrin was localized adjacent to MuSK-expressing astrocytes which in turn were detected close to the inner limiting membrane of the rodent retina. In summary, the presence of MuSK on retinal astrocytes suggests a novel role of MuSK signalling pathways in the CNS.


Behavioral preference for viewing drug v. pleasant images predicts current and future opioid misuse among chronic pain patients.
The USA is currently enduring an opioid crisis. Identifying cost-effective, easy-to-implement behavioral measures that predict treatment outcomes in opioid misusers is a crucial scientific, therapeutic, and epidemiological goal. The current study used a mixed cross-sectional and longitudinal design to test whether a behavioral choice task, previously validated in stimulant users, was associated with increased opioid misuse severity at baseline, and whether it predicted change in opioid misuse severity at follow-up. At baseline, data from 100 prescription opioid-treated chronic pain patients were analyzed; at follow-up, data were analyzed in 34 of these participants who were non-misusers at baseline. During the choice task, participants chose under probabilistic contingencies whether to view opioid-related images in comparison with affectively pleasant, unpleasant, and neutral images. Following previous procedures, we also assessed insight into choice behavior, operationalized as whether (yes/no) participants correctly self-reported the image category they chose most often. At baseline, the higher choice for viewing opioid images in direct comparison with pleasant images was associated with opioid misuse and impaired insight into choice behavior; the combination of these produced especially elevated opioid-related choice behavior. In longitudinal analyses of individuals who were initially non-misusers, higher baseline opioid v. pleasant choice behavior predicted more opioid misuse behaviors at follow-up. These results indicate that greater relative allocation of behavior toward opioid stimuli and away from stimuli depicting natural reinforcement is associated with concurrent opioid misuse and portends vulnerability toward future misuse. The choice task may provide important medical information to guide opioid-prescribing practices.


Granulomatous Myositis Associated with Myasthenia Gravis: A Rare Case.
Myasthenia gravis (MG) is an immune-mediated disease of the neuromuscular junction mediated by anti-acetylcholine receptor (AChR) antibodies (Ab). Granulomatous Myositis (GrM) is a histological diagnosis characterized by the presence of epithelioid granuloma in striated muscles. Few cases describing the presence of concomitant thymoma and non-thymoma-related MG with GrM have been reported. This present case is an addition to the literature describing the presence of concomitant thymoma and non-thymoma-related MG with GrM. The patient described is a 77-year-old male who started developing weakness and atrophy involving the musculature of the bilateral lower and upper extremities. Initial laboratory workup showed an elevated level of serum creatine phosphokinase (CPK) of 1,231 U/ L (reference range: 22 to 198 U/L). The right quadriceps muscle biopsy performed showed inflammatory infiltrates containing eosinophils, plasma cells, and lymphocytes forming multinucleate giant cells consistent with a diagnosis of GrM. Detailed laboratory and imaging work conducted to rule out an underlying cause of GrM showed elevated titers of AChR Ab (79.50 nmol/L, reference range: <0.02 nmol/L) and striational Ab (titer: 1:320, reference range < 1:120). A positive repetitive nerve stimulation test for the left ulnar nerve (decrement in the amplitude of muscle action potential by 13%) further confirmed the diagnosis of MG concomitant with GrM. Computed tomography of the chest was negative for the presence of a thymoma. The patient was started on treatment with oral prednisone and mycophenolate mofetil, which resulted in an improvement of symptoms and the downward trending of serum CPK level.


[Study of effects of copper deficiency on internal organ through a copper deficiency model in rat].
To establish copper deficiency model in rats, and observe the damnification on internal organ of copper deficiency rats. 27 male weanling SD rats with 5-week-old were randomized into 3 groups (n = 9), i.e., control group 1, control group2 and copper deficiency group (CuD). The rats of the control group 1 were fed commercial feed with copper level of 7.0 mg/kg, the rats of the control group 2 and the copper deficiency group were fed half-purified diet with copper level of 0.73 mg/kg. In afternoons, rats were orally perfused copper sulphate solution with copper concentration 0 (control group 1), 0.133 (control group 2) and 0 mg/ml (copper deficiency group), respectively, the volume was 1% of body weight, so theory copper level of the feed in the control group2 was 11.37 mg/kg. All of rats had free access to both food and de-ionized water. Rats were sacrificed at the end of test feeding on the 42nd day, blood was sampled for analyzing the plasma ceruloplasmin activity (PCP) and its content (PPD), and erythrocyte Cu-Zn SOD (EC Cu-Zn SOD); liver was sampled for analyzing the content of Metallothionein (MT), and liver copper (LC). The organic tissues of kidney, brain, heart, liver, spleen, lung and testes are sampled for histopathologic examination. The PCP and EC Cu-Zn SOD, PPD, LC and LMT of rats in copper deficiency group was significantly lower than those of rats in control group1 and control group2 (except EC Cu-Zn SOD) (P < 0.01). The cardiac muscle fibers of a part of rats in copper deficiency group were broken and eosinophilic. The endothelial cell of a coronary artery branch was presented proliferation and swelling, subendothelial space was broadened. An arteriole in the lung was showed thickening of the wall, and presented obliteration of the lumen. No obvious pathological changes of other internal organ were found. Copper deficiency model in rats is successfully established after rats ingesting diet of low copper for 42 days. Slightly pathologic changes in the cardiovascular tissues of part of rats in copper deficiency groups are observed.


Kv2.1 ablation alters glucose-induced islet electrical activity, enhancing insulin secretion.
Voltage-gated potassium currents (Kv), primarily due to Kv2.1 channels, are activated by glucose-stimulated pancreatic beta cell depolarization, but the exact role (or roles) of this channel in regulating insulin secretion remains uncertain. Here we report that, compared with controls, Kv2.1 null mice have reduced fasting blood glucose levels and elevated serum insulin levels. Glucose tolerance is improved and insulin secretion is enhanced compared to control animals, with similar results in isolated islets in vitro. Isolated Kv2.1(-/-) beta cells have residual Kv currents, which are decreased by 83% at +50 mV compared with control cells. The glucose-induced action potential (AP) duration is increased while the firing frequency is diminished, similar to the effect of specific toxins on control cells but substantially different from the effect of the less specific blocker tetraethylammonium. These results reveal the specific role of Kv2.1 in modulating glucose-stimulated APs of beta cells, exposing additional important currents involved in regulating physiological insulin secretion.


Expression of p53 as predictor for the development of esophageal cancer in achalasia patients.
Patients with longstanding achalasia have an increased risk of developing esophageal cancer. Surveillance is hampered by chronic stasis. We investigated whether aberrant expressions of tumor suppressor gene p53 and proliferation marker ki67 are early predictors for progression to malignancy. In 399 achalasia patients, 4% died of esophageal cancer despite surveillance. We performed a cohort study, using surveillance biopsies from 18 patients (11 carcinoma, one high-grade dysplasia [HGD], and six low-grade dysplasia [LGD]) and 10 controls (achalasia patients without cancer or dysplasia development). One hundred sixty-four biopsies were re-evaluated and studied for p53 and ki67 expression using immunohistochemistry. Eighty-two percent of patients with cancer/HGD showed p53 overexpression in surveillance biopsies at a mean of 6 (1-11) years prior to cancer development. In 67% of patients with LGD and only in 10% of the controls p53 overexpression was present. The proportion of samples with p53 overexpression increased with increasing grades of dysplasia. We found no difference for ki67 overexpression. p53 overexpression may identify achalasia patients at increased risk of developing esophageal carcinoma. Further study is needed to determine if patients with p53 overexpression would benefit from intensive surveillance to detect esophageal neoplasia at a potential curable stage.


The histone fold: a ubiquitous architectural motif utilized in DNA compaction and protein dimerization.
The histones of all eukaryotes show only a low degree of primary structure homology, but our earlier crystallographic results defined a three-dimensional structural motif, the histone fold, common to all core histones. We now examine the specific architectural patterns within the fold and analyze the nature of the amino acid residues within its functional segments. The histone fold emerges as a fundamental protein dimerization motif while the differentiations of the tips of the histone dimers appear to provide the rules of core octamer assembly and the basis for nucleosome regulation. We present evidence for the occurrence of the fold from archaebacteria to mammals and propose the use of this structural motif to define a distinct family of proteins, the histone fold superfamily. It appears that evolution has conserved the conformation of the fold even through variations in primary structure and among proteins with various functional roles.


Cellular mono(ADP-ribosyl) transferase inhibits protein synthesis.
A reticulocyte translation system was depleted of functional EF-2 by treatment with diphtheria toxin (DT) fragment A and NAD. After dialysis to remove NAD, the system was reconstituted using preparations of EF-2 derived from pyBHK cells. Untreated and reconstituted lysates permitted similar rates of translation. As expected, when DT-treated EF-2 was used to reconstitute the system, no translation occurred. Furthermore EF-2, reacting with the endogenous ADP-ribosyl transferase from pyBHK cells, was also unable to restore protein synthesis in the reconstituted system. These studies suggest that eukaryotic cellular ADP-ribosyl transferases may play a role in regulating protein synthesis.


Reactivated and latent varicella-zoster virus in human dorsal root ganglia.
Ganglia obtained at autopsy were examined by in situ hybridization from one patient with zoster (also called herpes zoster or shingles), two varicella-zoster virus (VZV)-seropositive patients with clinical evidence of zoster, one VZV-seronegative child, and one fetus. Ganglia positive for VZV had a hybridization signal in both neuronal and nonneuronal satellite cells. Ganglia obtained from the fetus and from the seronegative infant were consistently negative for VZV. Two striking observations were evident regarding the presence of VZV DNA in ganglia obtained from the individual with zoster at the time of death. First, ganglia innervating the sites of reactivation and ganglia innervating adjacent sites yielded strongly positive signals in neurons and satellite cells, whereas ganglia from distant sites were rarely positive. Second, VZV DNA was found in both the nuclei and the cytoplasm of neurons innervating areas of zoster. However, in neurons innervating zoster-free areas, VZV DNA was found only in the nucleus of neurons and their supporting satellite cells. Immunohistochemistry with a fluorescent monoclonal antibody to the VZV glycoprotein gpI, a late virus protein, revealed a positive signal in the cytoplasm of ganglia with clinical evidence of reactivation. These results illustrate that both neuronal and satellite cells become latently infected following primary VZV infection. The presence of VZV DNA and gpI in the cytoplasm of neurons demonstrates productive infection following reactivation at the site of latency.


Effect of the drug combination of magnesium sulfate and phentolamine on homocysteine and C-reactive protein in the serum of patients with pregnancy-induced hypertension syndrome.
Effect and clinical efficacy of magnesium sulfate combined with phentolamine on homocysteine and C-reactive protein in the serum of patients with pregnancy-induced hypertension syndrome were investigated. A total of 96 patients with pregnancy-induced hypertension syndrome who were diagnosed and treated in Jining No. 1 People's Hospital from February 2016 to January 2018 were retrospectively analyzed. The patients were grouped according to the dosage regimen. The patients who received the combination treatment of magnesium sulfate and phentolamine on the basis of magnesium sulfate were included in the observation group, and the patients who were treated with the intravenous infusion of magnesium sulfate alone were included in the control group. Mean arterial pressure (MAP), the content of 24 h urine protein, systolic blood pressure (SBP), diastolic blood pressure (DBP), Hcy, and CRP of the pregnant women were observed. MAP and the content of 24 h urine protein, SBP and DBP of the patients in the observation group after the treatment were significantly lower than those of the patients in the control group (P<0.001). Hcy and CRP of the patients in the observation group after the treatment were significantly lower than those of the patients in the control group (P<0.001). The total effective rate of the patients in the observation group was significantly higher than that of the patients in the control group (P<0.05). In conclusion, the meliorative effect of magnesium sulphate combined with phentolamine on the level of MAP, the content of 24 h urine protein, SBP, DBP, Hcy and CRP in pregnant woman had a greater impact than that of the single use of the intravenous infusion of magnesium sulfate in the treatment of pregnancy-induced hypertension syndrome, and the clinical efficacy of magnesium sulphate combined with phentolamine was better, thus worthwhile to promote widely in clinic.


Mitochondrial function is not affected by renal morphological changes in diabetic goto-kakizaki rat.
Renal disease is a common complication of diabetes mellitus. The pathogenesis of diabetic nephropathy is not well understood, but hyperglycemia seems to be a crucial factor. Recent evidence indicates that the overproduction of reactive oxygen species, observed in both clinical and experimental diabetes, and mitochondrial dysfunction are key factors in pathogenic process. The objective of this investigation was to test the hypothesis of whether hyperglycemia could affect kidney morphology and mitochondrial bioenergetics as well as susceptibility to oxidative stress in 12-month-old diabetic Goto-Kakizaki (GK) rats, a model of type 2 diabetes mellitus. We observed that there were no significant differences in the kidney respiratory function and phosphorylation capacity between GK and age-matched control Wistar rats. Mitochondria from kidneys of diabetic rats were equally susceptible to in vitro oxidative damage as those from normal rats, while coenzyme Q and alpha -tocopherol concentrations were similar in both types of preparations. However, the kidney of GK rats presented in most glomerulus a capillary basement membrane thickening with mesangial widening, in evolution to segmental glomerular sclerosis, and, in some interlobular arteries, excessive deposition of PAS-positive material at the tunica intima. The results show that the mild prolonged hyperglycemia and the kidney structural changes observed in GK rats are not sufficient to cause renal dysfunction and were not associated with functional and biochemical alterations in mitochondria.


Effects of pertussis toxin treatment of rats on estradiol-induced adenohypophyseal growth reaction and on adrenergic lipolysis.
After long-lasting administration of estradiol (4-6 weeks) in the presence or absence of pertussis toxin treatment we followed up the changes in body weight and adenohypophyseal weight in rats subjected to this treatment. The most striking effect was the potentiating effect of pertussis toxin on the estradiol-induced adenohypophyseal growth reaction. Adenylyl cyclase activity in the adenohypophysis was significantly increased in the estradiol-treated group and the addition of pertussis toxin did not further increase this enzyme activity. The lipolytic activity in adipose tissue exhibited a similar response as adenohypophyseal growth. Adrenergic lipolysis stimulated by pertussis toxin was highly significantly increased in tissues of rats treated with pertussis toxin. Our results show that the estrogen-induced adenohypophyseal growth reaction is highly potentiated by the treatment of rats with pertussis toxin and that this effect is in many aspects similar to that observed in adrenergic lipolysis. It thus seems that both processes might be mediated via a pertussis toxin-sensitive G protein which is involved in inhibitory regulation of adenylyl cyclase.


Long non-coding RNA PVT1 activates hepatic stellate cells through competitively binding microRNA-152.
Epithelial-mesenchymal transition (EMT) process is considered as a key event in the activation of hepatic stellate cells (HSCs). Hedgehog (Hh) pathway is known to be required for EMT process. Long non-coding RNAs (lncRNAs) have been reported to be involved in a wide range of biological processes. Plasmacytoma variant translocation 1 (PVT1), a novel lncRNA, is often up-regulated in various human cancers. However, the role of PVT1 in liver fibrosis remains undefined. In this study, PVT1 was increased in fibrotic liver tissues and activated HSCs. Depletion of PVT1 attenuated collagen deposits in vivo. In vitro, PVT1 down-regulation inhibited HSC activation including the reduction of HSC proliferation, α-SMA and type I collagen. Further studies showed that PVT1 knockdown suppressed HSC activation was through inhibiting EMT process and Hh pathway. Patched1 (PTCH1), a negative regulator factor of Hh pathway, was enhanced by PVT1 knockdown. PTCH1 demethylation caused by miR-152 was responsible for the effects of PVT1 knockdown on PTCH1 expression. Notably, miR-152 inhibitor reversed the effects of PVT1 knockdown on HSC activation. Luciferase reporter assays and pull-down assays showed a direct interaction between miR-152 and PVT1. Collectively, we demonstrate that PVT1 epigenetically down-regulates PTCH1 expression via competitively binding miR-152, contributing to EMT process in liver fibrosis.


[Effectiveness of antihypertensive medications in patients with preeclampsia].
The presented study is retrospective and prospective in design. It is based on the medical records of Maternity hospital "Majchin dom" and planned studies during the period 1994-2005. 544 preeclamptic patients with singleton pregnancies were included. 334 (61.3%) of them were diagnosed with mild preeclampsia and 210 (38.7%) had severe preeclampsia. Blood pressure was monitored at least four times daily, depending on the severity of the case with mechanical manometer. In special cases cardiopulsometry was applied. In order to compare the effectiveness of different antihypertensive medications, administered orally, either alone, or in combination (no antihypertensive medication, Methyldopa, Nifedipin, beta-blockers and combinations between them), patients were divided in seven groups. The mean values of systolic and diastolic blood pressure, measured before delivery were compared. No statistically significant difference between the groups was noticed. We were not also able to find statistically significant difference in blood pressure measurements before delivery, between patients with severe preeclampsia, treated with parenteral Nepresol or Chlofazolin.


Metabolic Studies on Intermediates in the myo-Inositol Oxidation Pathway in Lilium longiflorum Pollen: I. Conversion to Hexoses.
The myo-inositol oxidation pathway was investigated in regard to its role as a source of carbon for products of hexose monophosphate metabolism in germinated pollen of Lilium longiflorum Thunb., cv. Ace. myo-[2-(14)]Inositol and d-[1-(14)C]glucuronate had similar distributions of radioactivity, contributing about three times more label to polysaccharide-bound glucose than myo-[2-(3)H]inositol. In the course of glucogenesis label from the latter appeared as tritiated water in the medium. This exchange could be enhanced by supplying d-[5R,5S-(3)H]xylose instead of myo-[2-(3)H]inositol. When the former was administered, [(3)H]glucose was the only labeled sugar residue found in polysaccharide products. The soluble constituents of d-[5R,5S-(3)H]xylose-labeled pollen contained no traces of labeled xylose despite massive uptake and utilization.l-[1-(14)C]- and l-[5-(14)C]Arabinose produced similar labeling patterns in germinated pollen including incorporation of arabinosyl units into pollen tube polysaccharides and substantial glucogenesis which led to utilization of arabinose for respiration and further incorporation of labeled glucosyl units into pollen tube polysaccharides.d-[5-(3)H]Galacturonate was rapidly taken up by germinated pollen but slowly utilized, without conversion to other sugars, for incorporation into pollen tube polysaccharides. l-[6-(14)C]Gulonate was not taken up by pollen.Results strongly support a scheme of conversion from myo-inositol to hexose monophosphate and subsequent products of glucose metabolism that involves the myo-inositol oxidation pathway.