A xanthine-derivative K(+)-channel opener protects against serotonin-induced cardiomyocyte hypertrophy via the modulation of protein kinases.
This study investigated whether KMUP-1, a xanthine-derivative K(+) channel opener, could prevent serotonin-induced hypertrophy in H9c2 cardiomyocytes via L-type Ca(2+) channels (LTCCs). Rat heart-derived H9c2 cells were incubated with serotonin (10 μM) for 4 days. The cell size increased by 155.5%, and this was reversed by KMUP-1 (≥1 μM), and attenuated by the LTCC blocker verapamil (1 μM) and the 5-HT2A antagonist ketanserin (0.1 μM), but unaffected by the 5-HT2B antagonist SB206553. A perforated whole-cell patch-clamp technique was used to investigate Ca(2+) currents through LTCCs in serotonin-induced H9c2 hypertrophy, in which cell capacitance and current density were increased. The LTCC current (ICa,L) increased ~2.9-fold in serotonin-elicited H9c2 hypertrophy, which was attenuated by verapamil and ketanserin, but not affected by SB206553 (0.1 μM). Serotonin-increased ICa,L was reduced by KMUP-1, PKA and PKC inhibitors (H-89, 1 μM and chelerythrine, 1 μM) while the current was enhanced by the PKC activator PMA, (1 μM) but not the PKA activator 8-Br-cAMP (100 μM), and was abolished by KMUP-1. In contrast, serotonin-increased ICa,L was blunted by the PKG activator 8-Br-cGMP (100 μM), but unaffected by the PKG inhibitor KT5823 (1 μM). Notably, KMUP-1 blocked serotonin-increased ICa,L but this was partially reversed by KT5823. In conclusion, serotonin-increased ICa,L could be due to activated 5-HT2A receptor-mediated PKA and PKC cascades, and/or indirect interaction with PKG. KMUP-1 prevents serotonin-induced H9c2 cardiomyocyte hypertrophy, which can be attributed to its PKA and PKC inhibition, and/or PKG stimulation.


Structural analysis of lipoprotein E particles.
Apolipoprotein E (apoE) is a key regulator of cholesterol homeostasis. Human apoE has three common isoforms, each with different risk implications for cardiovascular and neurodegenerative disease. Neither the structure of lipoprotein E particles nor the structural consequences of the isoform differences are known. In this investigation, synthetic lipoprotein particles were prepared by complexing phospholipids with full-length apoE isoforms, or with truncated N-terminal and C-terminal domains of apoE. These particles were examined with calorimetry, electron microscopy, circular dichroism spectroscopy, and internal reflection infrared spectroscopy. Results indicate that particles made with the three full-length apoE isoforms are discoidal in shape, and structurally indistinguishable. Thus, differences in their pathological consequences are not due to gross differences in particle structure. Although apoE is predominantly helical, and the axes of the helices are parallel to the flat surfaces of the particles, the orientational order of lipid acyl chains is low and inconsistent with the belt model of lipoprotein A-I structure. Instead, the data suggest that there are at least two different types of apoE-lipid interactions within lipoprotein E particles. One type occurs between apoE helices and the edge of the lipid bilayer as in the belt model, while a second type involves apoE helices that situate in the plane of the membrane and disturb acyl chain order. These interactions allow LpE particles to form with different protein/lipid ratios, and they account for the structure of LpE particles made with only the truncated domains.


The Effectiveness of the Association of Chlorhexidine with Mechanical Treatment of Peri-Implant Mucositis.
(1) Background: The aim of the study was to evaluate the benefit of combining chlorhexidine with the mechanical treatment of peri-implant mucositis. (2) Methods: Articles from 2016 to 2021 included in the PubMed and Scopus databases were analyzed, following the PICOS criteria and the randomized controlled study model that used chlorhexidine in various forms in the treatment of peri-mucositis. According to the established criteria, a limited number of studies were selected. These studies had as their criteria of evaluation for the effectiveness of chlorhexidine, plaque indices, bleeding indices and depth probing indices. Chlorhexidine has been used after mechanical debridement as a solution, with different concentrations of 0.06%/0.12%/0.2% alone or in a concentration of 0.03%, in combination with 0.05% cetylpyridinium chloride, as well as in the form of a gel with a concentration of 0.2%. (3) Results: The results were assessed to a placebo or other substances, and showed a significant reduction in the indices with a follow-up period ranging from 3 months to 1 year. (4) Conclusions: The association of chlorhexidine with the mechanical treatment of peri-implant mucositis has a role in reducing inflammation, although a complete remission was not obtained in all cases, and the results were not statistically significantly different from the use of other antiseptics.


The atrophy of white and gray matter volume in patients with comitant strabismus: Evidence from a voxel-based morphometry study.
To compare the difference in white matter volume (WMV) and gray matter volume (GMV) between the comitant strabismus (CS) patients and health controls by voxel-based morphometry (VBM) and the relationship with behavioral performance. A total of 20 patients with comitant strabismus (10 males and 10 females), and 20 healthy subjects (10 males and 10 females) with matched age, sex status underwent magnetic resonance examination. The authors analyzed the original 3D T1 brain images using the VBM module. The comitant strabismus groups were compared with the control groups for the GMW and WMV of the entire brain. Correlation analysis was performed to investigate the relationship between the GMV and WMV altered areas and the behavioral performance in comitant strabismus. CS patients were distinguishable from the healthy controls (HCs) by receiver operating characteristic curves. Results of the VBM analysis demonstrated that the CS groups had decreased GMV in the brain regions of the left middle temporal pole, left cerebellum posterior lobe, right posterior cingulate cortex, left cuneus and right premotor cortex. Meanwhile, the WMV was significantly decreased in the brain regions of the left middle temporal gyrus, right middle temporal gyrus, left middle temporal gyrus, right precuneus and right premotor cortex in the comitant strabismus patients compared with HCs. Furthermore, the duration of CS was negatively correlated with the GMV values of the left middle temporal pole (r=-0.486, P=0.030). CS caused GMV and WMV atrophy in many brain regions, which may indicate the neural mechanisms of the ocular motility disorders in CS patients.


Mobile Health for Caregivers of Young Adults With Early Psychosis: A Survey Study Examining User Preferences.
Caregivers play a key role in supporting the recovery of young adults with early psychosis. This role often involves considerable responsibilities and burden. Despite the considerable needs of caregivers, troubling service gaps addressing these needs remain. Digital technologies may increase caregivers' access to supportive resources; however, technologies developed specifically for caregivers lag far behind those developed for their relatives affected by early psychosis. In particular, little is known about the mobile health (mHealth) features that may be most acceptable to caregivers. The authors surveyed a sample of 43 caregivers on their interests regarding various features of a proposed mHealth intervention. Caregivers of young adults with early psychosis were highly interested in a caregiver-facing mHealth intervention, specifically one providing information about psychosis, treatments, and communication with their affected family member. Future caregiver-focused mHealth intervention interventions may be highly acceptable to this population and may address pressing service gaps.


Pretreatment of glial cell-derived neurotrophic factor and geranylgeranylacetone ameliorates brain injury in Parkinson's disease by its anti-apoptotic and anti-oxidative property.
The aim of the present study was to determine the combined effects of glial cell-derived neurotrophic factor (GDNF) and geranylgeranylacetone (GGA) on neuron apoptosis and oxidative stress in Parkinson's disease (PD). A mouse MPTP model of PD and cellular models of H2 O2 and MPP+ -treated PC12 cells were established. Swimming, pole, and traction tests were used to detect behavioral impairment. Tyrosine hydroxylase (TH) immunohistochemistry was used to evaluate the neuron loss. TUNEL and flow cytometer method were used to identify the neuron apoptosis. MDA levels and activities of antioxidant enzymes were used to detect the oxidative damage. The PD model of mice received GDNF and GGA exhibited a significant recovery in their swim, pole, and traction scores. Moreover, the combined treatment significantly reduced the neuron apoptosis in the substantia nigra (SN) of PD mice or in H2 O2 or MPP+ -induced PC12 cells compared with the single drug group. In addition, significant reduction of MDA levels and improvement of activities of CAT, SOD, and GSH-px were observed after GDNF and GGA treatment in the PD model and H2 O2 or MPP+ -induced PC12 cells. The combination of GDNF and GGA ameliorated neural apoptosis and oxidative damage in PD.


Analysis of material parameter uncertainty propagation in preoperative flap suture simulation.
Skin flap transplantation is the most commonly used method to repair tissue defect and cover the wound. In clinic, finite element method is often used to design the pre-operation scheme of flap suture. However, the material parameters of skin flap are uncertain due to experimental errors and differences in body parts. How to consider the influence of material parameter uncertainty on the mechanical response of flap suture in the finite element modeling is an urgent problem to be solved at present. Therefore, the influence of material parameter uncertainty propagation in skin flap suture simulation was studied, Firstly, the geometric model of clinical patient's hand wound was constructed by using reverse modeling technology, the patient's three-dimensional wound was unfolded into a flat surface by using curved surface expansion method, yielding a preliminary design contour for the patient's transplant flap. Based on the acquired patient wound geometry model, the finite element model of flap suture with different fiber orientations and different sizes was constructed in Abaqus, and the uncertainty propagation analysis method based on Monte Carlo simulation combined with surrogate model technology was further used to analyze the stress response of flap suture considering the uncertainty of material parameters. Results showed that the overall stress value was relatively lower when the average fiber orientation was 45°. which could be used as the optimal direction for the flap excision. when the preliminary design contour of the flap was scaled down within 90%, the stress value after flap suturing remained within a safe range.


[Vesiculo-bullous erythrasma of the feet (author's transl)].
7 Cases of vesiculo-bullous erythrasma of the feet are reported. Wood's light, microbiology and histology permit to separate this entity from dysidrotic eczema and dermatophytosis.


Recent advances in personalized lung cancer medicine.
The identification of molecular subtypes of non-small-cell lung cancer has transformed the clinical management of this disease. This is best exemplified by the clinical success of targeting the EGFR or ALK with tyrosine kinase inhibitors in the front-line setting. Our ability to further improve patient outcomes with biomarker-based targeted therapies will depend on a more comprehensive genetic platform that can rationally interrogate the cancer genome of an individual patient. Novel technologies, including multiplex genotyping and next-generation sequencing are rapidly evolving and will soon challenge the oncologist with a wealth of genetic information for each patient. Although there are many barriers to overcome, the integration of these genetic platforms into clinical care has the potential to transform the management of lung cancer through improved molecular categorization, patient stratification, and drug development, thereby, improving clinical outcomes through personalized lung cancer medicine.


[Urinary undiversion; Bricker to Studer. With regard of two cases].
We present two cases of urinary undiversion from an ileal loop (Bricker) to an orthotopic neobladder. Due to miss adaptation to the stoma, two patients demanded reconversion to a continent urinary diversion. We proceed to change their urinary diversion to an ileal neobladder (Studer), one by open surgery and the other by laparoscopic surgery. In both cases immediate postoperative went uneventful. Both patients are continent, satisfied with their new situation, and without metabolic complications. Urinary undiversion from an ileal conduit to an orthotopic neobladder is technically feasible by open or laparoscopic surgery. It is a valid alternative for patients with complications due to their urinary diversion or miss adaptation to the cutaneous stoma.


Optimization of flow cytometry parameters for high-throughput screening of spores of the filamentous fungus Trichoderma reesei.
Flow cytometry (FCM) is a powerful technique still little used to study filamentous fungi due to physical constraints: the hyphae are too large to enter the FCM fluidic system, unless spores can be analyzed at a very early stage of germination. The technique nevertheless has strong potential for the study of these micro-organisms (spore sorting, viability, characterization etc.). This study focused on the investigation of several parameters, ranging from germination and storage conditions of T. reesei spores through to FCM gating, to detect their fluorescence during the first 24 h of germination. Fluorescent spores were first obtained after aerobic germination at 25 °C and monitored over 24 h using FCM, to screen for nine promoters controlling a green fluorescent protein gene. The fluorescence signal (FL1) was then acquired, in addition to the growth characterization of the spores, based on the size signal or Forward Scatter (FSC). They were combined to identify the best candidate(s) from among the nine promoters for the strongest- and earliest-possible fluorescence emission, which resulted in the following ranking: pTEF > pPKI > pGPD > pPDC. There are numerous possible applications of this work, ranging from molecular biology to monitoring fermentation.


Congenital diverticulum of the vermiform appendix: a rare finding of a routine operation.
Congenital diverticulum of the appendix as well as diverticulitis of the vermiform appendix remain a rare, mainly retrospective diagnosis, reported by the pathologist, post-appendicectomy. In clinical practice, however, it is important to be aware of this entity, the different types, diagnosis, association with malignancy and treatment options. We are presenting a young female case of pathologically proved true diverticulum of the appendix with associated uncomplicated appendicitis and an overview of the literature.


Intact artificial grammar learning in patients with cerebellar degeneration and advanced Parkinson's disease.
In an artificial grammar learning task, subjects were asked to memorise short lists of letter strings formed according to complex rules for letter order. After an interval they were unexpectedly asked to discriminate new grammatical strings from strings which used the same letters but violated the sequential constraints of the grammar. Artificial grammar learning can be mastered successfully by amnesic patients and is considered to be an implicit learning task independent of declarative learning and memory mechanisms. In this study, 10 patients with cerebellar degeneration (CD), 21 Parkinson's disease (PD) and 15 control subjects were tested on artificial grammar learning. Additionally PD patients with advanced disease were examined under adequate medication and dopaminergic withdrawal. All patient groups showed intact artificial grammar learning. Neither cerebellar damage nor basal ganglia dysfunction nor dopaminergic medication impairs or affects artificial grammar learning. Although the patients showed significant executive dysfunction, implicit learning remains intact. The conclusion is that cerebellar and basal ganglia circuits play no essential part in this kind of implicit learning. The results suggest that artificial grammar learning is a cortically mediated function comparable to the mechanism of visual priming.


Particle-by-particle quantification of protein adsorption onto poly(ethylene glycol) grafted surfaces.
The use and advantage of flow cytometry as a particle-by-particle, low sampling volume, high-throughput screening technique for quantitatively examining the non-specific adsorption of proteins onto surfaces is presented. The adsorption of three proteins: bovine serum albumin (BSA), immunoglobulin gamma (IgG) and protein G, incubated at room temperature for 2 h onto organosilica particles modified with poly(ethylene glycol) (PEG) of increasing MW (2000, 3400, 6000, 10,000 and 20,000 g mol(-1)) and grafted amounts (0.14-1.4 mg m(-2)) was investigated as a model system. Each protein exhibited Langmuir-like, high affinity monolayer limited adsorption on unmodified particles with the proteins reaching surface saturation at 1.8, 4.0 and 2.5 mg m(-2) for BSA, IgG and protein G, respectively. Protein adsorption on PEG-modified surfaces was found to decrease with increasing amounts of grafted polymer. PEG grafting amounts >0.6 mg m(-2) effectively prevented the adsorption of the larger two proteins (BSA and IgG) while a PEG grafting amount >1.3 mg m(-2) was required to prevent the adsorption of the smaller protein G.


Prognostic value of nuclear hepatoma-derived growth factor (HDGF) localization in patients with breast cancer.
Hepatoma-derived growth factor (HDGF) plays an important role in tumor progression. Highly expressed HDGF has been found to indicate poor prognosis in many cancers. However, no information is available regarding the prognostic value of nuclear or cytoplasmic HDGF staining level in breast cancer. In the present study, the nuclear or cytoplasmic HDGF staining level was investigated in 86 patients with primary breast cancer by immunohistochemistry; the relationship between nuclear or cytoplasmic HDGF staining level and clinicopathological parameters was examined by Two-tailed Mann-Whitney U-test or Krustal-Wallis. The prognostic value of nuclear or cytoplasmic HDGF staining level in disease-free survival and overall survival was analyzed by Kaplan-Meier methods and log-rank test. We found that the percentage of cases with strong nuclear HDGF staining level was significantly higher in the cases with high tumor grade, high stage, high proliferation index (Ki-67 index>20%), as well as in those with lymph node invasion and recurrence (p<0.05) compared to those without. No significant correlation was found between cytoplasmic HDGF expression and any clinicopathological variables. In addition, disease-free survival and overall survival were significantly lower in patients with high nuclear HDGF expression (level 2) than in those with low nuclear HDGF expression (level 0 and level 1). Further Cox multivariate analysis showed that high nuclear HDGF expression is an independent factor for indicating poor prognosis in breast cancer patients. No significant difference in disease-free survival rate and overall survival was found between different cytoplasmic HDGF staining levels. All these findings suggest that increased nuclear HDGF expression is involved in tumor progression and might be used as a new prognosticator for breast cancer.


Interleukin-17 positive cells accumulate in renal allografts during acute rejection and are independent predictors of worse graft outcome.
Interleukin-17 (IL-17) plays an important role in the regulation of cellular and humoral immune responses. Recent studies suggest a role for IL-17 in transplantation. Our study investigated whether quantifying IL-17(+) cells in renal transplant biopsies during acute rejection could have additional prognostic value for better stratifying patients at risk for nonresponsiveness to anti-rejection therapy and future graft dysfunction. Forty-nine renal biopsies with acute rejection were double immunostained and quantitatively analyzed for IL-17 and CD3 (IL-17(+) T-lymphocytes), tryptase (IL-17(+) mast cells) or CD15 (IL-17(+) neutrophils). Total IL-17(+) cell count correlated with total percentage of inflamed biopsy and estimated GFR during rejection. Most IL-17(+) cells were mast cells and neutrophils. We could hardly find any IL-17(+) T-lymphocytes. IL-17(+) mast cells correlated with interstitial fibrosis/tubular atrophy (IF/TA). None of the IL-17(+) cell counts had an additional prognostic value for response to anti-rejection treatment. Multivariate analysis correcting for C4d positivity and time from transplantation to biopsy showed that total IL-17(+) cell count independently predicts graft dysfunction at the last follow-up, which was validated in an independent cohort of 48 renal biopsies with acute rejection. We conclude that intragraft IL-17(+) cell count during acute allograft rejection could have an additional value for predicting late graft dysfunction.


Identification of novel indigenous Bacillus thuringiensis isolates.
Internally Transcribed Spacers (ITS) characterization and distribution of Repetitive Extragenic Palindromic (REP) sequences were studied in the genome of 223 field isolates of Bacillus thuringiensis from Madurai, India. They were characterized by morphological, biochemical and molecular methods. One hundred and twenty four of a total 223 isolates fitted ITS characterization of B. thuringiensis varieties known. Significant genomic variation was observed among seven isolates using REP primers. The ITS PCR product (EMBL accession number AJ639659) exhibited 98% nucleotide sequence homology with B. thuringiensis and placed the origin of indigenous isolate LDC-7 closer to B. thuringiensis on the basis of phylogenetic analysis.


U21, a novel small nucleolar RNA with a 13 nt. complementarity to 28S rRNA, is encoded in an intron of ribosomal protein L5 gene in chicken and mammals.
Following a search of sequence data bases for intronic sequences exhibiting structural features typical of snoRNAs, we have positively identified by Northern assays and sequence analysis another intron-encoded snoRNA, termed U21. U21 RNA is a 93 nt. long, metabolically stable RNA, present at about 10(4) molecules per HeLa cell. It is encoded in intron 5 of the ribosomal protein L5 gene, both in chicken and in the two mammals studied so far, human and mouse. U21 RNA is devoid of a 5'-trimethyl-cap and is likely to result from processing of intronic RNA. The nucleolar localization of U21 has been established by fluorescence microscopy after in situ hybridization with digoxigenin-labeled oligonucleotide probes. Like most other snoRNAs U21 contains the box C and box D motifs and is precipitated by anti-fibrillarin antibodies. By the presence of a typical 5'-3' terminal stem, U21 appears more particularly related to U14, U15, U16 and U20 intron-encoded snoRNAs. Remarkably, U21 contains a long stretch (13 nt.) of complementarity to a highly conserved sequence in 28S rRNA. Sequence comparisons between chicken and mammals, together with Northern hybridizations with antisense oligonucleotides on cellular RNAs from more distant vertebrates, point to the preferential preservation of this segment of U21 sequence during evolution. Accordingly, this complementarity, which overlaps the complementarity of 28S rRNA to another snoRNA, U18, could reflect an important role of U21 snoRNA in the biogenesis of large ribosomal subunit.


Monitoring of girls undergoing medical therapy for isosexual precocious puberty.
We evaluated the use of sonography in monitoring the efficacy of suppressive therapy with a gonadotropin releasing hormone analogue in girls being treated for isosexual precocious puberty. Ten girls 5 to 9 years of age underwent serial sonography and hormonal stimulation tests on the same day. Sonographic trends of decreasing ovarian volume and uterine length indicated early suppression even when absolute values were above threshold. Changes in ovarian volume were the most sensitive predictor of pituitary-gonadal suppression. Sonography is a sensitive and accurate method of monitoring medical therapy; ovarian volume and analysis of interval change are the most sensitive barometers of change.


The Spindle: Integrating Architecture and Mechanics across Scales.
The spindle segregates chromosomes at cell division, and its task is a mechanical one. While we have a nearly complete list of spindle components, how their molecular-scale mechanics give rise to cellular-scale spindle architecture, mechanics, and function is not yet clear. Recent in vitro and in vivo measurements bring new levels of molecular and physical control and shed light on this question. Highlighting recent findings and open questions, we introduce the molecular force generators of the spindle, and discuss how they organize microtubules into diverse architectural modules and give rise to the emergent mechanics of the mammalian spindle. Throughout, we emphasize the breadth of space and time scales at play, and the feedback between spindle architecture, dynamics, and mechanics that drives robust function.


Efficient Secretion of Recombinant Proteins from Rice Suspension-Cultured Cells Modulated by the Choice of Signal Peptide.
Plant-based expression systems have emerged as a competitive platform in the large-scale production of recombinant proteins. By adding a signal peptide, αAmy3sp, the desired recombinant proteins can be secreted outside transgenic rice cells, making them easy to harvest. In this work, to improve the secretion efficiency of recombinant proteins in rice expression systems, various signal peptides including αAmy3sp, CIN1sp, and 33KDsp have been fused to the N-terminus of green fluorescent protein (GFP) and introduced into rice cells to explore the efficiency of secretion of foreign proteins. 33KDsp had better efficiency than αAmy3sp and CIN1sp for the secretion of GFP from calli and suspension-cultured cells. 33KDsp was further applied for the secretion of mouse granulocyte-macrophage colony-stimulating factor (mGM-CSF) from transgenic rice suspension-cultured cells; approximately 76%-92% of total rice-derived mGM-CSF (rmGM-CSF) was detected in the culture medium. The rmGM-CSF was bioactive and could stimulate the proliferation of a murine myeloblastic leukemia cell line, NSF-60. The extracellular yield of rmGM-CSF reached 31.7 mg/L. Our study indicates that 33KDsp is better at promoting the secretion of recombinant proteins in rice suspension-cultured cell systems than the commonly used αAmy3sp.


A comparison between the two methods of chest compression in infant and neonatal resuscitation. A review according to 2010 CPR guidelines.
The quality of chest compression (CC) delivered during neonatal and infant cardiopulmonary resuscitation (CPR) is identified as the most important factor to achieve the increase of survival rate without major neurological deficit to the patients. The objective of the study was to systematically review all the available studies that have compared the two different techniques of hand placement on infants and neonatal resuscitation, from 2010 to 2015 and to highlight which method is more effective. A review of the literature using a variety of medical databases, including Cochrane, MEDLINE, and SCOPUS electronic databases. The following MeSH terms were used in the search: infant, neonatal, CPR, CC, two-thumb (TT) technique/method, two-finger (TF) technique/method, rescuer fatigue, thumb/finger position/placement, as well as combinations of these. Ten studies met the inclusion criteria; nine observational studies and a randomized controlled trial. All providers performed either continuous TF or TT technique CCs and the majority of CPR performance was taken place in infant trainer manikin. The majority of the studies suggest the TT method as the more useful for infants and neonatal resuscitation than the TF.


[Molecular typing of Shiga-toxin producing Escherichia coli O157:H7 isolated in China with pulsed field gel electrophresis].
To type and group the Shiga-toxin producing Escherichia coli O157:H7 strains isolated recent years in China to understand the epidemiological features caused by the pathogen. Pulsed field gel electrophoresis of large restriction fragments of bacterial chromosomal DNA was used. The 51 isolates of E. coli O157:H7 collected in recent years in China could be divided into 8 Pulsed Field Gel Electrophoresis (PFGE) types based on the size and number of restriction fragments and patterns, that were digested by XbaI. Strains isolated from Ningxia province showed only two types- PFGE1 and PFGE2. Strains isolated in Xuzhou of Jiangsu province had 6 PFGE types. Isolates identified between 1986 - 1988 belonged to PFGE7. Strains isolated from patients in 1999 - 2000 were PFGE5 and PFGE3. Strains isolated from stool samples of domestic animal, food and vegetable were PFGE3 - 6, of which the predominant type was PFGE5. All of the 5 strains isolated from patients with diarrhea and hemolytic uremic syndrome (HUS) belonged to PFGE type 5, which was the dominant type of the isolates from stool samples of domestic animal and samples of food and vegetable contaminated. Data suggested that the cluster patients with diarrhea and HUS might have been related to the pathogens from domestic animas and contaminated food or vegetables. The distribution of PFGE types also varied in different provinces of China.


[The Development of Psychiatric and Mental Health Nursing in Taiwan: Reflection From the Perspective of Recovery].
Evidence-based nursing science has identified psychological recovery, partnership, and medication adherence as factors that have influenced the development of mental health care. This article discusses the process by which mental health care has developed from a medical / rehabilitation-focused model to a model that focuses on patient empowerment. The current model aims to assist patients to achieve self-awareness and to develop coping skills that enhance their motivation to transform. Medical advances have improved the control of psychiatric symptoms. Following the introduction of 2nd generation antipsychotics, patients were invited to establish decisions related to these prescription medications. Under the principles of patient-centered service, Taiwanese mental health professionals have changed their relationship with patients from a therapeutic model to a mutual-partnership model. Furthermore, investigations of the therapeutic care of patients with mental illness have used the needs of patients as their starting point and emphasized various aspects of patient and caregiver needs. Taiwanese mental health professionals are searching for a model of mental health care that is superior to the traditional operative framework of medical authority.


Maternal Behavior Modifications during Pretense and Their Long-Term Effects on Toddlers' Understanding of Pretense.
Recent studies indicate the need to investigate the sources of toddlers' understanding of another person's pretense. The present study is a cultural and longitudinal extension of the work of Lillard and Witherington (2004), who claimed that mothers modify their behaviors during pretense and that the some of these behavior modifications help their toddlers understand maternal pretense. Experiment 1 investigated whether mothers would change their behaviors during pretense with a sample of 31 Japanese mother-infant pairs. Experiment 2, with a subsample of 20 mother-child pairs who had participated in Experiment 1, examined whether the maternal behavior modifications at 18 months predicted their toddlers' understanding of pretense at 24 months. The results of Experiment 1 indicated that Japanese mothers smiled more frequently, gazed at their toddlers longer, used sound effects more frequently, and engaged in more frequent snack-related actions in a "pretense condition" than in a "real condition." In addition, some of these behaviors were significantly related to their toddlers' apparent understanding of pretense. Experiment 2 showed that both the frequency of maternal smiles and the number of sound effects in the pretense condition at 18 months predicted toddlers' understanding of the pretense enacted by a strange adult at 24 months. This research indicates the impact of maternal behavior modifications during pretense on the development of symbolic thought in the 2nd year of life.


[Cytotoxic nucleoside analogues--metabolism, activity and resistance].
Cellular resistance is an increasing problem in the treatment of haematological malignancies and solid tumours with cytotoxic nucleoside analogues. Studies on cellular models and clinical samples have allowed insight into the mechanisms behind this resistance. An overview of cytotoxic nucleoside analogues, their metabolism and their mechanism of action is presented. Studies on resistance to nucleoside analogues are reviewed. Results were collected from the literature in the PubMed database and from research in our laboratory. Variations in the activity of nucleoside transporters and proteins of the intracellular metabolism are implicated in the result of treatment with nucleoside analogues. These proteins are kinases, 5'-nucleotidases and deaminases. Mechanisms identified in cell models or in samples from non-responding patients should be validated in treated patients. These mechanisms are prognostic factors for the clinical outcome in nucleoside analogue-treated patients.


Room temperature, nanosecond, 60 mJ/pulse Fe:ZnSe master oscillator power amplifier system operating at 3.8-5.0 µm.
We report on a RT gain-switched Fe:ZnSe master oscillator power amplifier (MOPA) system tunable over 3.8-5.0 µm pumped by radiation of Er:YAG laser operating at 2.94 µm. The mechanically Q-switched Er:YAG laser with output energy up to 220 mJ was used as a pump source for a master oscillator and three-stage power amplifier. The maximum output energies in 200 ns pulses exceeded 60, 56, and 48 mJ at 4.4, 4.3, and 4.1 µm, respectively, under 220 mJ of pump energy. The extraction energy efficiencies were measured to be 25, 30, and 40% at the first, second, and third stages, respectively.


The differences in characteristics between health-care users and non-users: implication for introducing community-based health insurance in Burkina Faso.
The purposes of this study are to describe the characteristics of different health-care users, to explain such characteristics using a health demand model and to estimate the price-related probability change for different types of health care in order to provide policy guidance for the introduction of community-based health insurance (CBI) in Burkina Faso. Data were collected from a household survey using a two stage cluster sampling approach. Household interviews were carried out during April and May 2003. In the interviewed 7,939 individuals in 988 households, there were 558 people reported one or more illness episodes; two-thirds of these people did not seek professional care. Health care non-users display lower household income and expenditure, older age and lower perceived severity of disease. The main reason for choosing no-care and self-care was 'not enough money'. Multinomial logistic regression confirms these observations. Higher household cash-income, higher perceived severity of disease and acute disease significantly increased the probability of using western care. Older age and higher price-cash income ratio significantly increased the probability of no-care or self-care. If CBI were introduced the probability of using western care would increase by 4.33% and the probability of using self-care would reduce by 3.98%. The price-related probability change of using western care for lower income people is higher than for higher income although the quantity changed is relatively small. In conclusion, the introduction of CBI might increase the use of medical services, especially for the poor. Co-payment for the rich might be necessary. Premium adjusted for income or subsidies for the poor can be considered in order to absorb a greater number of poor households into CBI and further improve equity in terms of enrollment. However, the role of CBI in Burkina Faso is rather limited: it might only increase utilisation of western health care by a probability of 4%.


Probing the binding of insecticide permethrin to calf thymus DNA by spectroscopic techniques merging with chemometrics method.
The binding of permethrin (PE) with calf thymus DNA (ctDNA) in physiological buffer (pH 7.4) was investigated by ultraviolet-visible (UV-vis) absorption, fluorescence, circular dichroism (CD), and Fourier transform infrared (FT-IR) spectroscopy merging with multivariate curve resolution-alternating least-squares (MCR-ALS) chemometrics approach. The MCR-ALS was applied to resolve the combined spectroscopic data matrix, which was obtained by UV-vis and fluorescence methods. The concentration profiles of PE, ctDNA, and PE-ctDNA complex and their pure spectra were then successfully obtained. The PE molecular was found to be able to intercalate into the base pairs of ctDNA as evidenced by decreases in resonance light-scattering signal and iodide-quenching effect and increase in ctDNA viscosity. The results of FT-IR spectra indicated that PE was prone to bind to G-C base pairs of ctDNA, and the molecular docking studies were used to validate and clarify the specific binding. The observed changes in CD signals revealed that the DNA turned into a more highly wound form of B-conformation. The calculated thermodynamic parameters, enthalpy change (ΔH°) and entropy change (ΔS°), suggested that hydrogen bonds and van der Waals forces played a predominant role in the binding of PE to ctDNA.


Aqueous two-phase extraction and characterization of thermotolerant alkaliphilic Cladophora hutchinsiae xylanase: biochemical properties and potential applications in fruit juice clarification and fish feed supplementation.
Xylanase finds extensive applications in diverse biotechnological fields such as biofuel production, pulp and paper industry, baking and brewing industry, food and feed industry, and deinking of waste paper. Here, polyethylene glycol (PEG)-phosphate aqueous two-phase system (ATPS) was applied for the purification of an alkaline active and thermotolerant xylanase from a marine source, Cladophora hutchinsiae (C. hutchinsiae). In the purification process, the effects of some experimental factors such as PEG concentration and PEG molar mass, potassium phosphate(K2HP04) concentration, and pH on xylanase distribution were systematically investigated. Relative enzymatic activity and purification factor obtained were 93.21% and 7.18, respectively. A single protein band of 28 kDa was observed on SDS-PAGE. The optimum temperature and pH of xylanase with beechwood xylan were 30 °C and 9.0, respectively. The Lineweaver-Burk graph was utilized to determine the Km (4.5 ± 0.8 mg/mL), Vmax (0.04 ± 0.01 U) and kcat (0.001 s-1) values of the enzyme. It was observed that the purified xylanase maintained 70% of its activity at 4 °C and was found stable at pH 4.0 by retaining almost all of its activity. Enzymatic activity was slightly enhanced with Na+, K+, Ca2+ and acetone. The highest increase in the reducing sugar amount was 53.6 ± 3.8, for orange juice at 50 U/mL enzyme concentration.


Bioactive glass versus autologous platelet-rich fibrin for treating periodontal intrabony defects: A comparative clinical study.
To compare treatment modalities: Open flap debridement (OFD) alone (Group I), OFD in combination with PerioGlas® (Group II), and OFD in combination with autologous platelet-rich fibrin (PRF) (Group III) for periodontal intrabony defects (IBDs). To evaluate on clinical and radiographic basis, effectiveness of PerioGlas®, and PRF in treating IBDs. IBDs selected on the basis of the inclusion criteria were randomly assigned to Groups I, II, and III by coin toss method. The study was conducted on patients reporting to the department of periodontology and oral implantology. Thirty-eight patients with ninety periodontal IBDs of moderate to severe periodontitis were selected and assigned to Groups I, II, and III. In each patient, a minimum number of two sextants were present with pocket depths ≥5 mm in at least three teeth. Statistical analysis based on mean values, standard deviation, and P values. Compared to baseline, 9 months postoperatively: (1) mean probing pocket depth reduction for Group I was 3.68 mm ± 0.72, for Group II was 5.57 mm ± 1.10, and for Group III was 6.11 mm ± 0.92. (2) The mean relative attachment level gain for Group I was 4.14 mm ± 0.76, for Group II was 6.57 mm ± 1.45, and for Group III was 6.74 mm ± 1.55. (3) Mean radiographic IBD fill for Group I was 69.29% mm ± 7.73, for Group II was 74.44% mm ± 8.57, and for Group III was 75.01% mm ± 7.85. This study shows marked improvements in the clinical parameters and radiographic outcomes with both PerioGlas® and autologous PRF to treat periodontal IBDs as compared to OFD alone.


Application of a deductive database system to search for topological and similar three-dimensional structures in protein.
A deductive database system PACADE (Protein Atomic Coordinate Analyzer with Deductive Engine) has been developed for protein structure analysis. With this system, super-secondary structures described in logical and declarative rules can be retrieved effectively. For protein structure analysis, comparison of local structures in different proteins is a necessary mean. A function to search for similar structures has, therefore, been added to the PACADE system. We describe herein the result of searches for the same topological structures and three-dimensionally similar ones. A user of PACADE can select these two levels of similarity by changing parameters. This function enables the inference system to retrieve similar structures, according to the restraints of variables defined by the user. Similar super-secondary structures among proteins can be searched for automatically, which is useful for protein structure analysis. The retrieved similar super-secondary structures can serve as criteria for protein spatial alignment.


Thermodynamic and computational analyses reveal the functional roles of the galloyl group of tea catechins in molecular recognition.
Catechins, biologically active polyphenols in green tea, exhibit various biological activities, such as anticancer and antiviral activities, arising from interactions with functional proteins. However, the molecular details of these interactions remain unclear. In this study, we investigated the interactions between human serum albumin (HSA) and various catechins, including some with a galloyl group, by means of isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC), and docking simulations. Our results indicate that the galloyl group was important for recognition by HSA and was responsible for enthalpic gains derived from a larger buried surface area and more van der Waals contacts. Thus, our thermodynamic and computational analyses suggest that the galloyl group plays important functional roles in the specific binding of catechins to proteins, implying that the biological activities of these compounds may be due in part to the physicochemical characteristics of the galloyl group.


Highly stereoselective and efficient synthesis of functionalized cyclohexanes with multiple stereocenters.
Chiral 7-oxo-2-enimides 2, which were readily obtained through a silyloxy-Cope rearrangement of syn-aldol products 1, have proved to be versatile substrates for a one-step, highly efficient and stereoselective synthesis of functionalized cyclohexanes. Organocopper and organoaluminum reagents have been employed as nucleophiles that underwent a conjugate addition to the enimide structure of the Cope products. The enolates formed in situ attacked the aldehyde or iminium ion in an intramolecular aldol or Mannich reaction, respectively, to directly yield cyclohexanols 3 and 4 and cyclohexylamines 5, respectively, in moderate to good yields and with excellent stereocontrol.


Microbial factors in contact lens fitting.
As contact lens practitioners, optometrists work in a nonsterile environment and on a nonsterile part of the human body. Our report describes 10 cases of eye infection related to contact lens wear. Practitioners need to be aware of the problems which can occur when a thoroughly sterilized contact lens is placed on an unsterile and biologically complex eye. We recommend taking swabs of the conjuctiva in all eyes where ocular inflammation is present. In those areas in which the professions of optometry and medicine meet, cooperation should exist. Improving our knowledge and skills in microbiology helps to facilitate such cooperation. Our experience has been most rewarding and interaction in this field with medical practitioners has been positive. The use of a high quality slitlamp is essential.


Benefits of early glycemic control by insulin on sensory neuropathy and cataract in diabetic rats.
While there is an emphasis on the early glycemic control for its long-term benefits in preventing microvascular complications of diabetes, the biochemical mechanisms responsible for the long-lasting effects are not clearly understood. Therefore the impact of early insulin (EI) versus late insulin (LI) treatment on diabetic sensory neuropathy and cataract in streptozotocin-induced diabetic Wistar male rats were evaluated. EI group received insulin (2.5 IU/animal, once daily) treatment from day 1 to 90 while LI group received insulin from day 60 to 90. Early insulin treatment significantly reduced the biochemical markers like glucose, triglyceride, glycated hemoglobin, thiobarbituric acid reactive substances, advanced glycation end products and ratio of reduced glutathione and oxidized glutathione in diabetic rats. The late insulin treatment failed to resist the biochemical changes in diabetic rats. Diabetic rats developed sensory neuropathy as evidenced by mechanical and thermal hyperalgesia and showed a higher incidence and severity of cataract as revealed by slit lamp examination. Early insulin treatment protected the rats from the development of neuropathy and cataract, but late insulin administration failed to do so. The results demonstrate the benefits of early glycemic control in preventing neuropathy and cataract development in diabetic rats.


The effect of a low molecular weight inhibitor of lipid peroxidation on ultrastructural alterations to ischemia-reperfusion in the isolated rat heart.
The effects of H290/51, a novel indenoindole derivative inhibitor of lipid peroxidation, on ultrastructural changes during cardiac ischemia-reperfusion injury were investigated. Langendorff-perfused rat hearts were exposed to 30 minutes of global ischemia followed by 20 minutes of reperfusion: Group A: Control hearts with standard buffer perfusion with vehicle added. Group B: H290/51 (10(-6) mol/l) added to buffer throughout stabilisation and reperfusion. In an additional Group C, where hearts were given H290/51, but not subjected to ischemia, the ultrastructure was preserved till the end of reperfusion. Absolute volumes and calculated volume fractions (Vv) of tissue and subcellular components were assessed with quantitative stereologic morphometry. After ischemia the increase in volume of extracellular interstitium was inhibited by H290/51 (247 +/- 80 vs. 159 +/- 50 microl, mean +/- SD, groups A and B, respectively, p<0.05). The Vv (interstitium/myocard) was higher in control hearts (0.318 +/- 0.062 vs. 0.206 +/- 0.067, p<0.05). Vv (cell edema/myocyte) was higher in the control group (0.144 +/- 0.07 vs. 0.083 +/- 0.033, p<0.05). Vv (myocyte/myocard) was higher in group B after ischemia than in the control group (0.622 +/- 0.071 vs. 0.707 +/- 0.052, p<0.05). The decreased Vv (capillary/myocard) after ischemia was inhibited by H290/51. After reperfusion there was no difference between groups. Treatment with H290/51 reduced edema and ensured better preserved sarcolemmal membrane structure during ischemia. The effect was no longer present after reperfusion.


Pharmacotherapy of xerostomia in primary Sjögren's syndrome.
We reviewed the current literature concerning the treatment of dry mouth in patients with primary Sjögren's syndrome (SJS). Computerized MEDLINE search engines were used with the terms Sjögren, xerostomia, dry mouth, and treatment. References from key articles were searched, and all pertinent articles were procured and reviewed. Primary SJS is an uncommon but serious disorder. Dry mouth caused by SJS can lead to dental erosion, dysphagia, oral infections, and discomfort. Preventing these complications is of paramount importance. Pharmacotherapy is limited to topical saliva substitutes, which are considered first, followed by muscarinic stimulators such as pilocarpine or cevimeline, if required. Immunosuppressive therapy is being investigated. Patients should have regular oral and dental examinations to detect complications. Satisfaction with the efficacy and tolerability of treatment should be monitored frequently. The clinician may have to use a trial-and-error approach to determine a successful regimen.


Purification of glycogen phosphorylase from bovine brain and immunocytochemical examination of rat glial primary cultures using monoclonal antibodies raised against this enzyme.
The physiological function in brain of glycogen and the enzyme catalyzing the rate-limiting step in glycogenolysis, glycogen phosphorylase (EC 126.96.36.199), is unknown. As a first step toward elucidating such a function, we have purified bovine brain glycogen phosphorylase isozyme BB 1,700-fold to a specific activity of 24 units/mg protein. When analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and subsequent silver staining, a single major protein band corresponding to an apparent molecular mass of 97 kDa was observed. Mouse monoclonal antibodies raised against the enzyme were purified and shown to be monospecific as indicated by immunoblotting. Immunocytochemical examination of astroglia-rich primary cultures of rat brain cells revealed a colocalization of glycogen phosphorylase with the astroglial marker glial fibrillary acidic protein in many cells. The staining for the enzyme appeared at two levels of intensity. There were other cells in the culture showing no specific staining under the experimental conditions employed. Neurons in neuron-rich primary cultures did not show positive staining. The data suggest that glycogen phosphorylase may be predominantly an astroglial enzyme and that astroglia cells play an important role in the energy metabolism of the brain.


[From the history of Roger commentators].
The biblical manuscript A 12, preserved in Duesseldorf's Federal and University Library (Universitaets- und Landesbibliothek Duesseldorf), dates from the mid-13th century. In the course of its scholarly analysis, a piece of parchment was found in the interior board, where a fragment of a surgical text is written on. Judging from the writing, the original manuscript came from southern France (Montpellier) and dates from the late 13th century. Several pas- sages quote "M[agister] W[ilhelmus] de Congenis", but the text bears only a vague resem- blance to Pagel's (1891) and Sudhoff s (1918) editions. Upon the other hand, the author was guided by Roger Frugardi's 'Chirurgia', which presumably gave the structure for Wilhelm's lectures. The edition of the fragmentary text presents a yet unknown example of student notes referring to William of Congenis and illustrates the complex history of Roger commentaries.


Numerical study of wave propagation in uniaxially anisotropic Lorentzian backward-wave slabs.
The propagation and refraction of a cylindrical wave created by a line current through a slab of backward-wave medium, also called left-handed medium, is numerically studied with a finite-difference time-domain method. The slab is assumed to be uniaxially anisotropic. Several sets of constitutive parameters are considered and comparisons with theoretical results are made. Electric field distributions are studied inside and behind the slab. It is found that the shape of the wave fronts and the regions of real and complex wave vectors are in agreement with theoretical results.


Effects of DNA minor groove binding agents on global gene expression.
The capacity of two minor groove binding agents that differ in their DNA sequence selectivity to modulate gene expression in human leukaemia cells was investigated. The chosen compounds were the chromomycin A3, a GC selective minor groove binder, and alkamin, an AT selective minor groove binder. As revealed by DNA microarray analysis of 6000 genes, at equitoxic doses, 5×IC(50) values for growth inhibition, the two drugs disturbed transcription, resulting in both up- and down-regulation of many hundreds of genes, 24 h after drug exposure. Direct comparisons between the most affected genes and also the cluster analysis indicated a relatively low degree of similarity between the tow expression profiles. Moreover, the ontological and the pathway responses also indicated a distinguished biological responses. Chromomycin treatment was characterized by many negative impacts on the important cellular functions and by the activation for those functions that usually take the cells towards apoptosis. In the second biological profile, the domination of many positive functions might indicate that the cells were attempting to overcome and repair the alkamin assault. Examples of these functions are positive regulation of gene expression, positive regulation of macromolecule biosynthetic processes, the cell cycle pathway and DNA repair.


Serum level of intact parathyroid hormone and other markers of bone metabolism in dialyzed patients.
In the present study, we evaluated and compared serum markers of bone turnover in dialyzed patients with serum intact parathyroid hormone (iPTH) < 100 pg/mL (LBT group, n = 9), 100-150 pg/mL (MIX group, n = 6), and iPTH > 150 pg/mL (non-LBT group, n = 15). Laboratory parameters included iPTH; cyclase activating parathyroid hormone (CAP); osteoprotegerin (OPG); OPG ligand (OPGL); inorganic phosphates; total Ca, urea, and creatinine; alkaline phosphatase activity; and blood pH. Cyclase inactive parathyroid hormone (CIP) was calculated by subtraction of CAP from iPTH. When results were adjusted for sex, age, dialysis modality, and dialysis duration, only CAP and CIP were significantly different between the groups. For the LBT MIX, and non-LBT groups respectively, mean serum values for CAP were 20.3 pg/mL (range: 6.53-50.7 pg/mL), 79.3 pg/mL (range: 53.4-99.0 pg/mL), and 343.3 pg/mL (range: 102.1-887.9 pg/mL) and for CIP they were 7.74 pg/mL (range: 2.41-48.4 pg/mL), 50.2 pg/mL (range: 29.5-68.0 pg/mL), and 129.0 pg/mL (range: 62.4-399.0 pg/mL). In a selection of dialyzed patients, serum CAP and CIP concentrations--but not CAP/CIP ratio, OPG, OPGL, and OPGL/OPG ratio--can, like iPTH values, be used to categorize those suspected of having adynamic bone.


Metastasis to parotid gland from non Head and Neck tumors.
Most primary tumors spreading metastasis to the parotid gland are usually located in the head and neck region, nonetheless, rarely, parotid gland can also be the target of metastatic localization site of distant primary tumors. The purpose of this study was to describe a clinical series of metastasis to the parotid gland from distant primary tumors (non Head & Neck). The clinical databases of parotid tumors in two academic centers have been analyzed and 11 cases of parotid metastatic cancers from distant primary tumors were found. Primary tumor was lung cancer in 8 cases, and breast cancer, gastric carcinoma and pancreatic carcinoma in one case each. Parotid metastases can be the first clinical manifestation of a malignant tumor from a distant site and can manifest years after curative-intent treatment of the distant primary. Histopathology and immunohistochemistry can help in the identification of the primary site. Parotidectomy with complete excision of the parotid lesion may have diagnostic and/or loco-regional control and/or curative intent, however there is still no international consensus about the therapy of parotid malignant metastasis.


Coombs-positive hemolytic uremic syndrome.
Two children presenting typical clinical features of the hemolytic-uremic syndrome had a positive direct Coombs test that remained positive throughout the illness. It is probable that an upper respiratory tract infection precipitated an antigen-antibody reaction that caused the autoimmune hemolytic anemia and immune-complex glomerulonephritis.


Consumption of partially hydrolysed guar gum stimulates Bifidobacteria and butyrate-producing bacteria in the human large intestine.
Partially hydrolysed guar gum (PHGG) is a water-soluble dietary fibre that is non-digestible in the upper gastrointestinal tract. It is believed that PHGG benefits the health of hosts by altering the colonic microbiota and stimulating short-chain fatty acid (SCFA) production. However, it remains unclear which bacteria ferment PHGG in the human large intestine. In this study, the effect of PHGG on faecal bacteria was analysed to specify the bacteria that contribute to the fermentation of PHGG in the human large intestine. Ten healthy volunteers consumed PHGG (6 g/day) for 2 weeks. Faeces were collected at 2 weeks prior to consumption, at the end of 2 weeks of consumption, and 2 weeks after consumption of PHGG. Bacterial DNA was extracted from these collected faeces and subjected to real-time PCR using bacterial group- or species-specific primers. The copy number of the butyryl-CoA CoA-transferase gene and the 16S rRNA gene copy numbers of Bifidobacterium, the Clostridium coccoides group, the Roseburia/ Eubacterium rectale group, Eubacterium hallii, and butyrate-producing bacterium strain SS2/1 were significantly increased by the intake of PHGG. Other bacteria and bacterial groups were not significantly influenced by the intake of PHGG. It was believed that the Roseburia/E. rectale group bacteria, Bifidobacterium, the lactate-utilising, butyrate-producing bacteria, E. hallii and bacterium strain SS2/1, would contribute to the fermentation of PHGG in the human large intestine. PHGG may benefit health by stimulating Bifidobacterium and butyrate-producing bacteria in the human large intestine.


Role of tissue factor in thrombosis. Coagulation-inflammation-thrombosis circuit.
Tissue factor (TF) plays a role in thrombogenesis. TF initiates blood coagulation resulting in the generation of protease coagulant mediators (FVIIa, FXa, and FIIa) and fibrin production. TF hypercoagulablility directly contributes to thrombus formation resulting from the major events of fibrin deposition and FIIa-induced platelet activation/aggregation. In addition, blood coagulation indirectly promotes thrombogenicity via the coagulation-inflammation cycle in which TF plays a diverging and converging role. As the consequence of coagulation-dependent inflammation in which protease-activated receptor (PAR) mediates the coagulant signaling to elicit cytokines, selectins, and growth factors, such inflammation facilitates thrombosis by platelet aggregation and leukocyte recruitment. As TF hypercoagulability concerned, anti-thrombotic strategies involve the prevention by anticoagulation and PAR antagonism. Anticoagulants block the direct and indirect thrombotic contributions, while PAR antagonists arrest coagulation-dependent inflammation. With respect to both thrombosis and inflammation being cardiovascular risk factors, such strategies offer diverse benefits to cardioprotection.


Genistein decreases A549 cell viability via inhibition of the PI3K/AKT/HIF‑1α/VEGF and NF‑κB/COX‑2 signaling pathways.
Genistein is an important chemopreventive agent against atherosclerosis and cancer. However, whether genistein is effective in the treatment of lung cancer, and its underlying mechanism, remains to be determined. The present study demonstrated that genistein treatment of A549 lung cancer cells decreased viability in a dose‑ and time‑dependent manner, and induced apoptosis. Additionally, A549 cells exhibited significantly increased reactive oxygen species formation and cytochrome‑c leakage, and activated caspase‑3, B‑cell lymphoma 2‑associated X protein and apoptosis inducing factor expression levels, which are involved in the mitochondrial apoptosis pathway. Furthermore, the phosphatidylinositol‑4,5‑biphosphate 3‑kinase (PI3K)/protein kinase B (AKT)/hypoxia‑inducible factor‑1α (HIF‑1α) and nuclear factor‑κB (NF‑κB)/cyclooxygenase‑2 (COX‑2) signaling pathways were significantly downregulated by genistein treatment. In conclusion, reduced proliferation and increased apoptosis in A549 lung cancer cells was associated with inhibition of the PI3K/AKT/HIF‑1α/ and NF‑κB/COX‑2 signaling pathways, which implicates genistein as a potential chemotherapeutic agent for the treatment of lung cancer.


Nasopharyngeal polyp causing sensory disturbances: a case report.
Nasopharyngeal polyps are benign abnormal mucosal protrusions associated with nasal and pharyngeal mucosa. They are commonly found in all age groups with various symptoms. This paper presents a case of a 52-year-old male who presented with constant numbness over the dental midline and extending along the right side of the maxilla for the past few weeks. The patient also reported difficulty in breathing, especially lying down. After a comprehensive head and neck examination, including muscle palpation and temporomandibular joint examination, all within normal limits, a CNS lesion was suspected. A cranial nerve screening examination disclosed hyposensitivity in the area of teeth # 7 to 10. A panoramic radiograph demonstrated right sinus abnormality. We determined the need for additional diagnostic testing, including cone beam computed tomography, which showed a thickened sinus membrane with a polypoid structure (extending posterior from the right inferior concha into the oropharynx). The patient was referred to an ear, nose, and throat (ENT) specialist for further evaluation. The ENT diagnosis was a nasal polyp, and the patient was prescribed a steroid spray to be used three times daily. On follow-up, the patient's symptoms were reduced from constant numbness to intermittent "fading sensation" with no breathing difficulties lying down. Ancillary diagnostic testing, such as Cone Beam CT, is useful and may be required for the diagnosis of sensory disturbances in the Orofacial region.


Glassy dynamics of convex polyhedra.
Self-assembly of polyhedral-shaped particles has attracted huge interest with the advent of new synthesis methods that realize these faceted particles in the lab. Recent studies have shown that polyhedral-shaped particles exhibit a rich phase behavior by excluded volume interactions alone; some of these particles are even alleged to show a transition to a glass phase by quenching the liquid sufficiently fast beyond the glass transition (supercooling), such that the formation of structures with long-range order is suppressed. Despite the recent progress, no study has been made on the glass formation of polyhedral-shaped particles. Here, we study the glass behavior of polyhedral particles using advanced Monte Carlo methods. We investigate the formation of a glass of monodisperse hard polyhedral-shaped particles, namely, octahedra, tetrahedra, and triangular cupola, using simulations. Finally, the fragility of these particles is determined and compared to that of a polydisperse hard-sphere system.


[Calcineurin inhibitors and mechanisms that are responsible for the appearance of post-transplant diabetes mellitus].
Calcineurin (CaN), a calmodulin-dependent heterodimer, is, together with NAF-T, involved in the regulation of the Ca++ pump and in the transmission of the activation signal of the immune response. The CaN inhibitor drugs, such as cyclosporin A (CyA), carried by cyclophillin, and tacrolimus, carried by FK-binding protein-12 (FKBP-12), inhibit the binding with the regulatory subunit CaNB. A meta-analysis, comparing tacrolimus with cyclosporin A, has evidenced that tacrolimus significantly increases the diabetes prevalence one year after renal transplant. The diabetogenic effect is due to a direct effect of both drugs on the beta pancreatic cell, in particular on intracellular Ca++ metabolism, which is involved in the insulin secretion and in the reduction of the number of the secretor granules. Some immunological-hystochemical studies, performed on murine pancreas, have evidenced that the FKBP-12 content is higher in beta cells than in alpha cells. This fact allows a high intracellular store of tacrolimus, and a consequently more toxic effect, inside the insulin secreting structures. On the contrary, the low FKBP-12 content of alpha cells involves a higher content of calcineurin and a higher resistance to toxic effects. Finally, an increased incidence of islet cell antibodies (ICA) has been evidenced in patients treated with tacrolimus, as opposed to those treated with CyA.


[Pharmacoepidemiological study of the course of influenza and other acute respiratory viral infections in risk groups].
To identify risk factors (RFs) for the development of bacterial complications and the prolonged course of influenza and other acute respiratory viral infections (ARVIs) among inpatients treated in Russian healthcare facilities in the post-pandemic period; to determine the clinical presentation of the disease (flu-like syndrome) in risk-group people and to evaluate the efficacy of antiviral therapy with arbidol (umifenovir). The investigators retrospectively analyzed randomly selected medical records of inpatients with influenza and other ARVI in 88 hospitals from 50 regions of the Russian Federation: those of 3532 and 1755 patients in the 2010-2011 and 2014-2015 seasons, respectively, by applying parametric and nonparametric statistical methods. The built database of patients with influenza-like syndrome contained data from the histories of 2072 men and 2537 women, of whom there were 317 (12.49%) pregnant women; gender evidence was not given in the medical records for 678 patients. 382 (7.2%) were vaccinated against influenza. 1528 (28.9%) people were admitted to hospital with various complications. Information on laboratory tests was available in 1691 (31.98%) patients; of these, 1291 (76.4%) were detected to have influenza and other respiratory viruses. Influenza viruses were found in 1026 (60.7%) examinees; influenza A viruses in 712 (42.1%) people while pandemic strain of swine influenza A/H1N1 and A/H3N2 viruses was detected in 487 (28.8%) and 107 (6.3%) patients, respectively; influenza A subtype was indicated in 118 (7%) persons with laboratory-confirmed influenza virus. Influenza B viruses were found in 314 (18.6%) examinees. Other types of respiratory viruses were detected in 265 (15.7%) patients. The body mass index exceeded 30 kg/m2 in 227 (4.3%) patients. Single-factor analysis of variance revealed factors influencing the course of flu-like syndrome and identified risk groups: children younger than 2 years old and adults over 65, pregnant women, and people with chronic somatic diseases and obesity. The high-risk groups exhibited a more severe course of flu-like syndrome than did the patients outside the risk groups. The incidence of complications was higher, especially in the under 2-year-year-old children and in patients with endocrine, metabolic, or respiratory diseases, with a large proportion of complications being pneumonia. The efficacy of antiviral therapy was higher in the elderly, patients with chronic diseases, and pregnant women than in patients not at risk. In patients treated with umifenovir (provided that it was administered in the first 48 hours after disease onset), the duration of fever and frequency of complications proved to be lower than those in patients who did not receive antiviral therapy. The FRs for influenza and ARVI complications are patient's age (children under 3 years of age and adults older than 65 years), the presence of chronic somatic diseases, and pregnancy. Patients with endocrine, eating, metabolic (including obesity), circulatory, and respiratory disorders are at high risk for influenza and ARVI complications. Umifenovir therapy substantially reduces the duration of fever and risk of complications, especially in patients with laboratory-confirmed influenza infection.


A systematic review of recommendations and guidelines for the management of osteoarthritis: The chronic osteoarthritis management initiative of the U.S. bone and joint initiative.
Although a number of osteoarthritis (OA) management guidelines exist, uptake has been suboptimal. Our aim was to review and critically evaluate existing OA management guidelines to better understand potential issues and barriers. A systematic review of the literature in MEDLINE published from January 1, 2000 to April 1, 2013 was performed and supplemented by bibliographic reviews, following PRISMA guidelines and a written protocol. Following initial title and abstract screening, 2 authors independently reviewed full-text articles; a third settled disagreements. Two independent reviewers extracted data into a standardized form. Two authors independently assessed guideline quality using the AGREE II instrument; three generated summary recommendations based on the extracted guideline data. Overall, 16 articles were included in the final review. There was broad agreement on recommendations by the various organizations. For non-pharmacologic modalities, education/self-management, exercise, weight loss if overweight, walking aids as indicated, and thermal modalities were widely recommended. For appropriate patients, joint replacement was recommended; arthroscopy with debridement was not recommended for symptomatic knee OA. Pharmacologic modalities most recommended included acetaminophen/paracetamol (first line) and NSAIDs (topical or oral, second line). Intra-articular corticosteroids were generally recommended for hip and knee OA. Controversy remains about the use of acupuncture, knee braces, heel wedges, intra-articular hyaluronans, and glucosamine/chondroitin. The relative agreement on many OA management recommendations across organizations indicates a problem with dissemination and implementation rather than a lack of quality guidelines. Future efforts should focus on optimizing implementation in primary care settings, where the majority of OA care occurs.


Alteration of enzymatic activities implicating neuronal degeneration in the spinal cord of the motor neuron degeneration mouse during postnatal development.
Oxidative stress is suggested as a significant causative factor for pathogenesis of neuronal degeneration on spinal cord of human ALS. We measured some enzymic activities implicating neuronal degeneration process, such as cytochrome c oxidase (CO), superoxide dismutase (SOD), and transglutaminase (TG) in spinal cord of an animal model of ALS, motor neuron degeneration (Mnd) mouse, a mutant that exhibits progressive degeneration of lower spinal neurons during developmental growth, and compared them with age-matched control C57BL/6 mice. CO activity in Mnd spinal cord decreased during early postnatal period, while SOD activity reduced in later stage. In Mnd tissue, TG activity in lumbar cord was increasing during early stage, but tended to decline in later period gradually. These biochemical alterations became evident prior to the appearance of clinical motor dysfunction which were observed in later stages of development in Mnd spinal cord.


Counting and Surveying Homeless Youth: Recommendations from YouthCount 2.0!, a Community-Academic Partnership.
Communities across the United States are increasing efforts to find and count homeless youth. This paper presents findings and lessons learned from a community/academic partnership to count homeless youth and conduct an in depth research survey focused on the health needs of this population. Over a 4 week recruitment period, 632 youth were counted and 420 surveyed. Methodological successes included an extended counting period, broader inclusion criteria to capture those in unstable housing, use of student volunteers in health training programs, recruiting from magnet events for high risk youth, and partnering with community agencies to disseminate findings. Strategies that did not facilitate recruitment included respondent driven sampling, street canvassing beyond known hotspots, and having community agencies lead data collection. Surveying was successful in gathering data on reasons for homelessness, history in public systems of care, mental health history and needs, sexual risk behaviors, health status, and substance use. Youth were successfully surveyed across housing types including shelters or transitional housing (n = 205), those in unstable housing such as doubled up with friends or acquaintances (n = 75), and those who were literally on the streets or living in a place not meant for human habitation (n = 140). Most youth completed the self-report survey and provided detailed information about risk behaviors. Recommendations to combine research data collection with counting are presented.


Electroconvulsive shock increases alpha 1b- but not alpha 1a-adrenoceptor binding sites in rat cerebral cortex.
Repeated administration of electroconvulsive shock (ECS) increases [3H]prazosin binding to alpha 1-adrenoceptors in rat cerebral cortex. In contrast, [3H]WB4101 binding in cortex has been reported to be unchanged after ECS. [3H]Prazosin labels two alpha 1-adrenoceptor subtypes, termed alpha 1a and alpha 1b, whereas [3H]WB4101 labels the alpha 1a subtype preferentially. The purpose of this study was to determine whether ECS increases one or both alpha 1-adrenoceptor subtypes in rat cerebral cortex. We found that treatment of rats with ECS once daily for 10-12 days increased [3H]prazosin binding in cortex by about 25% but did not significantly alter [3H]WB4101 binding to alpha 1-adrenoceptors. Measurement of alpha 1a and alpha 1b receptors by competition analysis of the selective alpha 1a antagonist 5-methylurapidil against [3H]prazosin and measurement of [3H]prazosin binding in homogenates preincubated with chlorethylclonidine, which alkylates alpha 1b binding sites, also indicated that the ECS-induced increase in alpha 1-adrenoceptors is confined to the alpha 1b subtype. In contrast to its effect on [3H]prazosin binding, ECS did not increase phosphoinositide hydrolysis as measured by [3H]inositol 1-phosphate accumulation in slices of rat cerebral cortex stimulated by either norepinephrine or phenylephrine. The failure of ECS to increase [3H]inositol 1-phosphate accumulation stimulated by phenylephrine, which is a partial agonist for this response, suggests that spare receptors do not account for the apparent absence of effect of ECS on alpha 1-adrenoceptor-mediated phosphoinositide hydrolysis.


Unusual Localisation for Onychomatricoma on the 5th Toenail: A Case Report and Review of the Literature.
Onychomatricoma is a rare and benign tumour of the nail matrix but originates rarely from the ventral portion of the proximal nail fold. This tumour is characterised by fingerlike projections that invade the nail plate. This lesion, of unknown aetiology, is typically asymptomatic with slow progression. Localisation on the finger is the most frequently described. We report the case of a 68-year-old woman who has an onychomatricoma in an unusual location, the fifth toe of the left foot. Due to its clinical appearance, the tumour can be confused with and treated as onychomycosis. However, if it is resistant to an oral antifungal well behaved treatment, one must consider onychomatricoma diagnosis.


Boosting Tunable Syngas Formation via Electrochemical CO2 Reduction on Cu/In2O3 Core/Shell Nanoparticles.
In this work, monodisperse core/shell Cu/In2O3 nanoparticles (NPs) were developed to boost efficient and tunable syngas formation via electrochemical CO2 reduction for the first time. The efficiency and composition of syngas production on the developed carbon-supported Cu/In2O3 catalysts are highly dependent on the In2O3 shell thickness (0.4-1.5 nm). As a result, a wide H2/CO ratio (4/1 to 0.4/1) was achieved on the Cu/In2O3 catalysts by controlling the shell thickness and the applied potential (from -0.4 to -0.9 V vs reversible hydrogen electrode), with Faraday efficiency of syngas formation larger than 90%. Specifically, the best-performing Cu/In2O3 catalyst demonstrates remarkably large current densities under low overpotentials (4.6 and 12.7 mA/cm2 at -0.6 and -0.9 V, respectively), which are competitive with most of the reported systems for syngas formation. Mechanistic discussion implicates that the synergistic effect between lattice compression and Cu doping in the In2O3 shell may enhance the binding of *COOH on the Cu/In2O3 NP surface, leading to the enhanced CO generation relative to Cu and In2O3 catalysts. This report demonstrates a new strategy to realize efficient and tunable syngas formation via rationally designed core/shell catalyst configuration.


Repair of regional osteoporosis after removal of rigid fixing plate. An experimental investigation.
Twenty-four New Zealand white rabbits were plated on their intact left tibiae with stainless steel plates and 4 animals served as controls. The plates were removed 2 months after implantation in 20 plated animals. Of them, 4 were sacrificed immediately after plate removal and the other 16 were killed in successive groups with 4 in each group 1,2,3 and 4 months after plate removal respectively. The remaining 4 plated animals were killed at 6 months after implantation. Bone samples under the plates were harvested and prepared for polarized light microscopy to investigate the repair of the regional osteoporosis induced by rigid implant. The results indicated that the regional osteoporosis could recover gradually after plate removal. The repair process manifested itself mainly as the repair of resorption cavities and the remodeling of collagen fibers. The orientation of the collagen fibers remained disorganized when the resorption cavities had been repaired. It is suggested that delayed restoration of bone structure might be one of the potential causes of refracture after removal of the rigid implant.


BisGMA/TEGDMA dental nanocomposites containing glyoxylic acid-modified high-aspect ratio hydroxyapatite nanofibers with enhanced dispersion.
The purpose of this research was to investigate the influence of the glyoxylic acid (GA) modification of hydroxyapatite (HAP) nanofibers on their dispersion in bisphenol A glycidyl methacrylate (BisGMA)/triethylene glycol dimethacrylate (TEGDMA) dental composites and also to investigate the mechanical properties, water absorption and water solubility of the resulting dental resins and composites. Scanning/transmission electron microscopy images showed that microsized HAP nanofiber bundles could be effectively broken down into individual HAP nanofibers with an average length of ∼15 µm after the surface modification process. Fourier transform infrared spectroscopy, x-ray photoelectron spectroscopy and thermal gravimetric analysis characterization confirmed that GA was chemically grafted on the HAP nanofiber surface, hypothetically by reacting with the amine group on the HAP nanofiber surface. The enhanced dispersion of HAP nanofibers in the dental matrix led to increased biaxial flexural strength (BFS) compared with the corresponding dental resins and composites filled with untreated HAP nanofibers. In addition, impregnation of small mass fractions of the GA-modified HAP nanofibers into the BisGMA/TEGDMA dental resins (5 wt%, 10 wt%) or composites (2 wt%, 3 wt%) could also substantially improve the BFS in comparison with the controls (pure resins or dental composites filled with silica particles alone). Larger mass fractions could not increase the mechanical property further or even degraded the BFS values. Water behavior testing results indicated that the addition of the GA-modified HAP nanofibers resulted in higher water absorption and water solubility values, which are not preferred for clinical application. In summary, well-dispersed HAP nanofibers and their dental composites with enhanced mechanical properties have been successfully fabricated, but the water absorption and water solubility of such dental composites need to be further improved.


Whole blood staining in suspension for nonspecific esterase and alkaline phosphatase analyzed with a Technicon H-1.
We adapted previously published methods for nonspecific esterase and alkaline phosphatase staining of white blood cells in suspension for use on a Technicon H-1 hematology analyzer. The objective was to develop a semiautomated method using whole blood that could be employed on a large scale for hematology laboratory applications, including toxicology studies, measurement of neutrophil left shift, and cytochemical classification of myeloid leukemias. The nonspecific esterase method uses the pararosaniline stain, generating the unstable substrate from two stable precursors. Whole blood is added to the substrate plus dye mix. Next, acid lysis and fixation steps destroy red cells and stabilize the monocyte staining. The alkaline phosphatase stain employs a stable naphthyl phosphate substrate and fast blue B coupling dye. The red cells are lysed with a pH 10.3 propanediol buffer, and the white blood cells are then stabilized with formalin fixation. For both methods the staining is performed off-line, and the sample is then diluted with propanediol to match the refractive index of the sheath on the H-1 analyzer, before aspiration into the direct cytometry port. A cytogram of scattered versus absorbed light is obtained. The number of cells staining and the intensity of the stain can be quantified from the cytogram.


eHealth tools to assess the neurological function for research, in absence of the neurologist - a systematic review, part I (software).
Neurological disorders remain a worldwide concern due to their increasing prevalence and mortality, combined with the lack of available treatment, in most cases. Exploring protective and risk factors associated with the development of neurological disorders will allow for improving prevention strategies. However, ascertaining neurological outcomes in population-based studies can be both complex and costly. The application of eHealth tools in research may contribute to lowering the costs and increase accessibility. The aim of this systematic review is to map existing eHealth tools assessing neurological signs and/or symptoms for epidemiological research. Four search engines (PubMed, Web of Science, Scopus & EBSCOHost) were used to retrieve articles on the development, validation, or implementation of eHealth tools to assess neurological signs and/or symptoms. The clinical and technical properties of the software tools were summarised. Due to high numbers, only software tools are presented here. A total of 42 tools were retrieved. These captured signs and/or symptoms belonging to four neurological domains: cognitive function, motor function, cranial nerves, and gait and coordination. An additional fifth category of composite tools was added. Most of the tools were available in English and were developed for smartphone device, with the remaining tools being available as web-based platforms. Less than half of the captured tools were fully validated, and only approximately half were still active at the time of data collection. The identified tools often presented limitations either due to language barriers or lack of proper validation. Maintenance and durability of most tools were low. The present mapping exercise offers a detailed guide for epidemiologists to identify the most appropriate eHealth tool for their research. The current study was funded by a PhD position at the University of Groningen. No additional funding was acquired.


Riems influenza a typing array (RITA): An RT-qPCR-based low density array for subtyping avian and mammalian influenza a viruses.
Rapid and sensitive diagnostic approaches are of the utmost importance for the detection of humans and animals infected by specific influenza virus subtype(s). Cascade-like diagnostics starting with the use of pan-influenza assays and subsequent subtyping devices are normally used. Here, we demonstrated a novel low density array combining 32 TaqMan(®) real-time RT-PCR systems in parallel for the specific detection of the haemagglutinin (HA) and neuraminidase (NA) subtypes of avian and porcine hosts. The sensitivity of the newly developed system was compared with that of the pan-influenza assay, and the specificity of all RT-qPCRs was examined using a broad panel of 404 different influenza A virus isolates representing 45 different subtypes. Furthermore, we analysed the performance of the RT-qPCR assays with diagnostic samples obtained from wild birds and swine. Due to the open format of the array, adaptations to detect newly emerging influenza A virus strains can easily be integrated. The RITA array represents a competitive, fast and sensitive subtyping tool that requires neither new machinery nor additional training of staff in a lab where RT-qPCR is already established.


The structure of Fcp1, an essential RNA polymerase II CTD phosphatase.
Kinases and phosphatases regulate mRNA synthesis and processing by phosphorylating and dephosphorylating the C-terminal domain (CTD) of the largest subunit of RNA polymerase II. Fcp1 is an essential CTD phosphatase that preferentially hydrolyzes Ser2-PO(4) of the tandem YSPTSPS CTD heptad array. Fcp1 crystal structures were captured at two stages of the reaction pathway: a Mg-BeF(3) complex that mimics the aspartylphosphate intermediate and a Mg-AlF(4)(-) complex that mimics the transition state of the hydrolysis step. Fcp1 is a Y-shaped protein composed of an acylphosphatase domain located at the base of a deep canyon formed by flanking modules that are missing from the small CTD phosphatase (SCP) clade: an Fcp1-specific helical domain and a C-terminal BRCA1 C-terminal (BRCT) domain. The structure and mutational analysis reveals that Fcp1 and Scp1 (a Ser5-selective phosphatase) adopt different CTD-binding modes; we surmise the CTD threads through the Fcp1 canyon to access the active site.


Tilted Bragg gratings in step-index polymer optical fiber.
We report the first slightly tilted Bragg gratings photo-inscription in polymer optical fiber (POF). For this, we make use of trans-4-stilbenemethanol-doped photosensitive step-index poly(methyl methacrylate) (PMMA) POFs. Tilted fiber Bragg gratings (TFBGs) are inscribed in the near-infrared wavelength range using the scanning phase mask technique with a tilted phase mask in the plane perpendicular to the laser beam direction. The transmitted amplitude spectrum evolution of a 3° TFBG is analyzed as a function of the surrounding refractive index. A maximum sensitivity close to 13 nm/RIU (refractive index unit) is obtained in the range 1.42-1.49.


Human blood platelet elastase and proelastase.
Platelet elastase has been differenciated from various protein fractions into a trypsin dependent form and a trypsin independent form. Trypsin independent elastase has been purified by affinity chromatography on cellulose elastin column as a pure protein raction of molecular weight: 26,000 ou SDS acrylamide gels. Trypsin dependent elastase has been purified by preparative acrylamide disc gel electrophoresis. This fraction, proteolysed (limited proteolysis) and activated by trypsin into active elastase, has been identified as the precursor (platelet proelastase) of platelet elastase. Its molecular weight is 28,000 before trypsin and 26,000 after trypsin.


Y chromosome STR haplotypes of Tibetan Living Tibet Lassa.
Allele frequencies and haplotypes of the 17 Y-chromosome STRs loci, namely DYS19, DYS385a/b, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635 (YGATA C4), and YGATA H4 were determined in a sample of 131 healthy unrelated males from the Lassa area of Tibet Autonomy Region of China (SW China). In 131 samples 106 different haplotypes were encountered, of which 105 were observed only once. The overall haplotype diversity was 0.9998. The results demonstrate that these loci will be very useful for human identification in forensic cases and paternity tests in the Lassa region.


Synthetic peptides as substrates and inhibitors of human immune deficiency virus-1 protease.
Retroviruses code for a virus-specific protease which is essential for polyprotein processing and viral infectivity. The human immune deficiency virus-1 protease is an aspartic protease of 9 kDa which was synthesized by recombinant DNA technology and arises by autocatalytic processing from a polyprotein precursor which has recently been demonstrated by use of a protease-specific monoclonal antibody. The protease was shown to form dimers. Here we demonstrate that synthetic peptides can be used as both model substrates as well as inhibitors for investigation of the protease. 14 synthetic peptides, 7-18 amino acids in length, containing putative protease cleavage sites of the viral polyprotein gag and pol precursors, have been analyzed with the partially purified protease by the use of high performance liquid chromatography. In seven cases, where cleavage was observed, the length of the peptides did not significantly influence the cleavage efficiencies, heptapeptides being large enough as model substrates. No cleavage was observed with a protein preparation purified in parallel from control bacteria not expressing the human immune deficiency virus-1 protease. The protease was not only able to cut next to a proline but also between other peptides indicating that the proline is not a prerequisite. Three peptides with either reduced bonds at the cleavage site or a substitution by statin were inhibitory while another uncleaved substrate was not. The usefulness of small model substrates for characterization of the protease is further demonstrated by determination of a kinetic optimum pH (3.5-5.5) and incubation temperature (37 degrees C).


Prospective pilot intervention study to prevent medication errors in drugs administered to children by mouth or gastric tube: a programme for nurses, physicians and parents.
Drug administration in children is an error-prone task for nurses and parents because individual dose adjustment is often necessary, and suitable formulations for children are frequently lacking. Hence, in the absence of measures for their prevention, medication errors are likely to occur. To assess the error prevalence in drug administration by mouth or gastric tube before and after implementing a programme for quality improvement for nurses and parents. Prospective, two-period cohort intervention study on a paediatric neurology ward of a university hospital where drug administration procedures of nurses and parents were consecutively monitored during the routine drug administration hours. Prevalence of administration errors before and after implementing instructions for appropriate drug administration, and a teaching and training programme supported by information pamphlets. Altogether, 1164 predefined administration tasks were assessed, 675 before and 489 after the intervention. Of these, 95.7% (after the 92.6%) were performed by nurses. Errors addressed by the intervention were reduced from 261/646 tasks (40.4%) to 36/453 (7.9%, p<0.001) in nurses and from 28/29 (96.6%) to 2/36 (5.6%, p<0.001) in parents. Errors in predefined categories concerning tablet dissolution, tablet storage, oral liquids, tablet splitting, administration by gastric tube and others were all considerably less frequent after the intervention (each p<0.001). Errors of drug administration by mouth and gastric tube represent a considerable and often neglected drug-related problem in paediatric inpatients. Targeted quality-improvement programmes can substantially and rapidly reduce error prevalence. Appropriate teaching and training of both nurses and parents supported by pamphlets was a highly efficient way to reduce error prevalence.


Electroporation-Induced Stress Response and Its Effect on Gene Electrotransfer Efficacy: In Vivo Imaging and Numerical Modeling.
Skin is an attractive target tissue for gene transfer due to its size, accessibility, and its immune competence. One of the promising delivery methods is gene delivery by means of electroporation (EP), i.e., gene electrotransfer (GET). To assess the importance of different effects of electroporation for successful GET we investigated: stress response and transfection efficacy upon different pulse protocols. Moreover, numerical modeling was used to explain experimental results and to test the agreement of experimental results with current knowledge about GET. Double transgenic mice Hspa1b-LucF (+/+) Hspa1b-mPlum (+/+) were used to determine the level of stress sensed by the cell in the tissue in vivo that was exposed to EP. The effect of five different pulse protocols on stress levels sensed by the exposed cells and their efficacy for gene electrotransfer for two plasmids pEGFP-C1 (EGFP) and pCMV-tdTomato was tested. Quantification of the bioluminescence signal intensity shows that EP, regardless of the electric pulse parameters used, increased mean bioluminescence compared to the baseline bioluminescence signal of the non-exposed skin. The results of numerical modeling indicate that thermal stress alone is not sufficient to explain the measured bioluminescence signal. Of the tested pulse protocols, the highest expression of EGFP and tdTomato was achieved with HV-MV (high voltage - medium voltage) protocols, which agrees also with numerical model. Although EP is widely used as a method for gene delivery, we show that the field could benefit from the use of mathematical modeling by introducing additional parameters such as EP induced stress and electrophoretic movement of plasmids.


Catecholamine-induced Takotsubo syndrome: a case series.
Catecholamine-induced Takotsubo Syndrome (cat-TS) is a type of secondary Takotsubo syndrome, characterized by rapid onset of symptoms, high rate of complications during the acute phase, good short-term prognosis, and frequent apical sparing at echocardiogram. We present two clinical cases of cat-TS treated in our department. Case one: 78-year-old man, admitted to Ear Nose and Throat Unit for surgical removal of oral squamous cellular carcinoma. During surgery, the occurrence of hypotensive episode was treated with catecholamines. After surgery, the occurrence of atrial fibrillation was followed by evidence of phasic increase of troponin levels and akinesia of midventricular segments. Angiography showed the absence of significant coronary stenoses, and during hospital stay, we observed rapid recovery of wall motion abnormalities. Case two: 64-year-old woman, admitted for hysteropexy surgery, during which cardiac arrest occurred, treated with epinephrine i.v.1 mg and DC shock. Two hours after resuscitation, the patient developed pulmonary oedema, troponin levels increased progressively, and the echocardiogram demonstrated hypokinesia in all midventricular segments with apical sparing. Afterwards, an urgent angiography highlighted normal coronary anatomy. Cardiac magnetic resonance imaging (MRI) revealed oedema corresponding to hypokinetic areas. On the seventh day, echocardiogram showed a complete remission of wall motion abnormalities. These cases warn the physicians about the importance of routinely screening myocardial impairment through clinical assessment, electrocardiogram (ECG) monitoring, and serial cardiac troponin testing after catecholamine i.v. bolus administration. In case of alterations of these exams, performing a prompt echocardiogram allows early detection of cat-TS, to provide immediate suitable medical support and avoid complications.


Dose variations with varying calculation grid size in head and neck IMRT.
Ever since the advent and development of treatment planning systems, the uncertainty associated with calculation grid size has been an issue. Even to this day, with highly sophisticated 3D conformal and intensity-modulated radiation therapy (IMRT) treatment planning systems (TPS), dose uncertainty due to grid size is still a concern. A phantom simulating head and neck treatment was prepared from two semi-cylindrical solid water slabs and a radiochromic film was inserted between the two slabs for measurement. Plans were generated for a 5,400 cGy prescribed dose using Philips Pinnacle(3) TPS for two targets, one shallow ( approximately 0.5 cm depth) and one deep ( approximately 6 cm depth). Calculation grid sizes of 1.5, 2, 3 and 4 mm were considered. Three clinical cases were also evaluated. The dose differences for the varying grid sizes (2 mm, 3 mm and 4 mm from 1.5 mm) in the phantom study were 126 cGy (2.3% of the 5,400 cGy dose prescription), 248.2 cGy (4.6% of the 5,400 cGy dose prescription) and 301.8 cGy (5.6% of the 5,400 cGy dose prescription), respectively for the shallow target case. It was found that the dose could be varied to about 100 cGy (1.9% of the 5,400 cGy dose prescription), 148.9 cGy (2.8% of the 5,400 cGy dose prescription) and 202.9 cGy (3.8% of the 5,400 cGy dose prescription) for 2 mm, 3 mm and 4 mm grid sizes, respectively, simply by shifting the calculation grid origin. Dose difference with a different range of the relative dose gradient was evaluated and we found that the relative dose difference increased with an increase in the range of the relative dose gradient. When comparing varying calculation grid sizes and measurements, the variation of the dose difference histogram was insignificant, but a local effect was observed in the dose difference map. Similar results were observed in the case of the deep target and the three clinical cases also showed results comparable to those from the phantom study.