Discovery of novel cell proliferation-enhancing gene by random siRNA library based combinatorial screening.
Bone remodeling is tightly controlled by the actions of osteoblast and osteoclast. Impaired osteoblast proliferation and differentiation may disrupt the balance and lead to pathological symptom such as osteoporosis. To help understand the molecular mechanism of osteoblast proliferation, we performed a phenotype-driven high throughput screening with a random siRNA library, in search of novel genes that can accelerate murine preosteoblast MC3T3-E1 cell proliferation. Three siRNAs screened from the library were able to enhance MC3T3-E1 cell proliferation significantly. One of the proliferation-enhancing siRNAs (B7) was further subjected to expression profiling to pinpoint genes that putatively act down stream of it. A number of genes were regulated in response to proliferation-enhancing siRNA B7. Among these genes, Tmed2, which has never been reported yet in cell proliferation, was verified to be able to enhance MC3T3-E1 cell proliferation when over-expressed. Our screening process with random siRNA library provided an alternative strategy in addition to gene-specific siRNA library, in search of novel functional genes in genome scale.


Reevaluating the Role of Polarizability in Ion Mobility Spectrometry.
With the expanding commercial availability of gas-phase separation systems that incorporate gas-phase mobility, there is a concurrent rise in efforts to cast the gas-phase mobility coefficient in terms of an ion-neutral collision cross-section (CCS). The motivating factors for this trend are varied, but many aim to complement experimental results with computationally generated CCS values from in silico structural approximations. Unfortunately, the current paradigm for relating experimental mobility results to computationally derived structures relies upon empirical approaches, including a myriad of variables that do not realistically bound the comparison. In this Critical Insight, we advocate for the development of a self-consistent experimental and computational framework that uses laboratory results to constrain the scope of the modeling effort. This paper aims to prompt discussion, challenge assumptions, and promote the development of more efficient, accurate computational techniques within the gas-phase ion measurement community. Specifically, we postulate whether experimental deviations from Langevin's polarization limit (Kpol) are suitable to estimate the relative contributions of hard-sphere collisions and long-range interactions within CCS values. Not surprisingly, different molecule classes exhibit different trends in the K/Kpol ratio when normalized for reduced mass, and the most common IMS calibrants (e.g., tune mix, polyalanine, tetraalkylammonium salts) follow different polarizability trends than many of the analytes probed in the literature. Succinctly, if gas-phase ion structure is largely invariant based upon the colliding neutral and newly developed experimental efforts can quantitatively capture ion polarizability, then modeling efforts describing a target analyte must be self-consistent as the collision neutral is changed in silico.


YiQiFuMai Powder Injection Ameliorates Cerebral Ischemia by Inhibiting Endoplasmic Reticulum Stress-Mediated Neuronal Apoptosis.
YiQiFuMai (YQFM) powder injection as a modern preparation derived from Sheng Mai San, a traditional Chinese medicine, has been widely used in the treatment of cardiovascular and cerebrovascular diseases. However, its neuroprotective effect and underlying mechanism in cerebral ischemia remain to be explored. The present study was designed to investigate the neuroprotective effect of YQFM on endoplasmic reticulum (ER) stress-mediated neuronal apoptosis in the permanent middle cerebral artery occlusion- (MCAO-) injured mice and the oxygen-glucose deprivation- (OGD-) induced pheochromocytoma (PC12) cells. The results showed that single administration of YQFM (1.342 g/kg, i.p.) could reduce the brain infarction and improve the neurological deficits and the cerebral blood flow (CBF) after MCAO for 24 h in mice. Moreover, incubation with YQFM (100, 200, and 400 μg/mL) could increase the cell viability, decrease the caspase-3 activity, and inhibit the cell apoptosis in OGD-induced PC12 cells for 12 h. In addition, YQFM treatment could significantly modulate cleaved caspase-3 and Bcl-2 expressions and inhibit the expressions of ER stress-related marker proteins and signaling pathways in vivo and in vitro. In conclusion, our findings provide the first evidence that YQFM ameliorates cerebral ischemic injury linked with modulating ER stress-related signaling pathways, which provided some new insights for its prevention and treatment of cerebral ischemia diseases.


High Pressure Deuterium Passivation of Charge Trapping Layer for Nonvolatile Memory Applications.
In this study, the deuterium passivation effect of silicon nitride (Si3N4) on data retention characteristics is investigated in a Metal-Nitride-Oxide-Silicon (MNOS) memory device. To focus on trap passivation in Si3N4 as a charge trapping layer, deuterium (D2) high pressure annealing (HPA) was applied after Si3N4 deposition. Flat band voltage shifts (ΔVFB) in data retention mode were compared by CV measurement after D2 HPA, which shows that the memory window decreases but charge loss in retention mode after program is suppressed. Trap energy distribution based on thermal activated retention model is extracted to compare the trap density of Si3N4. D2 HPA reduces the amount of trap densities in the band gap range of 1.06-1.18 eV. SIMS profiles are used to analyze the D2 profile in Si3N4. The results show that deuterium diffuses into the Si3N4 and exists up to the Si3N4-SiO2 interface region during post-annealing process, which seems to lower the trap density and improve the memory reliability.


Transplacental transfer of acetaminophen in pregnant rats.
Acetaminophen is among the most widely used analgesics; however, the proportion and mechanism of transplacental transfer of unbound acetaminophen with actual pharmacological activity remain unknown. Our hypothesis is that acetaminophen gradually penetrates the blood-placenta barrier to reach the fetus. A multiple microdialysis coupled to liquid chromatography with photodiode array detection method was developed to monitor acetaminophen levels in the maternal blood, placenta, fetus, and amniotic fluid of a pregnant rat and investigate this hypothesis. The pharmacokinetic data indicates that acetaminophen exhibits a nonlinear behavior in the maternal blood within the dosage regimen of 100 and 300 mg/kg. In addition, acetaminophen penetrates the placenta, fetus, and amniotic fluid during treatment. The transplacental transfer ratio represented by the area under the concentration curve (AUC) ratio for the conceptus (the collective term for the fetus, placenta, and amniotic fluid) and maternal blood (AUCtissue/AUCblood) was approximately 11-23 % after acetaminophen (100 and 300 mg/kg) administration. However, the transporter of multidrug resistance-associated protein (MRP) inhibitor MK-571 did not significantly change the transplacental transfer ratio. This basic study provides constructive information for the clinical application of acetaminophen in pregnant women.


Endovascular repair of ruptured abdominal and thoracic aortic aneurysms.
Management of acute pathology remains one of the most challenging clinical entities, with a persistently high mortality rate both prior to and upon arrival to a hospital. Responding to the distinct advantages of endovascular approaches to aortic disease, many high-volume cardiovascular centers have focused on endovascular therapies for managing patients with ruptured or leaking aortic aneurysms and other acute aortic syndromes. Nonetheless, similar to outcomes for other surgical emergencies, time and efficiency are critical in managing these conditions. Early diagnosis, transport to an appropriate acute care facility, rapid institution of optimal medical management, availability of cardiovascular anesthesia and intensive care, and appropriate and timely surgical intervention continue to be the keys to success. This article discusses the endovascular approach to ruptured abdominal and thoracic aortic aneurysms.


Automated measurement of amylase isoenzymes by a double kinetic assay with "blocked" beta-2-chloro-4-nitrophenyl maltopentaoside as substrate and with wheat germ inhibitor.
We evaluated the enzymic mechanism by which 3-keto butylidene-beta-2-chloro-4-nitrophenyl maltopentaoside (3KB-G5-CNP) serves as a substrate for serum pancreatic (p-) and salivary (s-) amylases. In aliquots of the reaction mixture, three kinds of beta-2-chloro-4-nitrophenyl oligosaccharides (glucose, maltoside, and maltotrioside) were separated from the substrate by high-performance liquid chromatography. Both isoenzymes behaved nearly identically and produced almost the same products. We automated a double kinetic procedure for determining total (t-) and p-amylase with use of a selective inhibitor from wheat germ in a single channel on the Hitachi 7050 analyzer. Within- and between-run CVs were, respectively, 0.5% and 1.7% for t-amylase (240 U/L), and 0.7% and 2.3% for p-amylase (230 U/L). The test results varied linearly with concentrations up to approximately 2000 U/L for t- and p-amylase activities. p/s ratios varied from 0.2 to 5.0. Results correlated well with those obtained by the monoclonal inhibition method (r = 0.992).


Differential expressions of nNOS and iNOS in the rostral ventrolateral medulla induced by electroacupuncture in acute myocardial ischemia rats.
Increasing lines of evidence has been accumulated that nitric oxide (NO) and nitric oxide synthase (NOS) distribute plentifully in the rostral ventrolateral medulla (RVLM) and contribute to cardiovascular regulation. In the present study, the expressions of neuronal and inducible isoform of NOS (nNOS and iNOS) were observed in the RVLM of acute myocardial ischemia (AMI) Wistar rats experienced electroacupuncture (EA) treatment, thereby the cardiovascular effects of NO in the RVLM were investigated and the mechanism of acupuncture effect on AMI was inferred. The results indicated that in the AMI rats, cardiac functions were markedly attenuated with high serum level of brain natriuretic peptide (BNP) and norepinephine (NE), the number of nNOS-immunoreactive cells and nNOS mRNA exprossion in the RVLM area were increased, while those of iNOS were lowered. EA at "Neiguan" acupoints (Pe 6) 30 min daily for successive 5 d resulted in an improvement of the cardiac functions, decreases in NE and BNP levels; it also increased the expression of iNOS and decreased the expression of nNOS in the RVLM. These results suggest that the curative effect of acupuncture on AMI is possibly attributable to the differential regulation of NOS/NO in the RVLM, leading to decreased sympathetic outflow and improvement of cardiac functions.


Accuracy of vaginal symptom self-diagnosis algorithms for deployed military women.
Deployed military women have an increased risk for development of vaginitis due to extreme temperatures, primitive sanitation, hygiene and laundry facilities, and unavailable or unacceptable healthcare resources. The Women in the Military Self-Diagnosis (WMSD) and treatment kit was developed as a field-expedient solution to this problem. The primary study aims were to evaluate the accuracy of women's self-diagnosis of vaginal symptoms and eight diagnostic algorithms and to predict potential self-medication omission and commission error rates. Participants included 546 active duty, deployable Army (43.3%) and Navy (53.6%) women with vaginal symptoms who sought healthcare at troop medical clinics on base.In the clinic lavatory, women conducted a self-diagnosis using a sterile cotton swab to obtain vaginal fluid, a FemExam card to measure positive or negative pH and amines, and the investigator-developed WMSD Decision-Making Guide. Potential self-diagnoses were "bacterial infection" (bacterial vaginosis [BV] and/or trichomonas vaginitis [TV]), "yeast infection" (candida vaginitis [CV]), "no infection/normal," or "unclear." The Affirm VPIII laboratory reference standard was used to detect clinically significant amounts of vaginal fluid DNA for organisms associated with BV, TV, and CV. Women's self-diagnostic accuracy was 56% for BV/TV and 69.2% for CV. False-positives would have led to a self-medication commission error rate of 20.3% for BV/TV and 8% for CV. Potential self-medication omission error rates due to false-negatives were 23.7% for BV/TV and 24.8% for CV. The positive predictive value of diagnostic algorithms ranged from 0% to 78.1% for BV/TV and 41.7% for CV. The algorithms were based on clinical diagnostic standards. The nonspecific nature of vaginal symptoms, mixed infections, and a faulty device intended to measure vaginal pH and amines explain why none of the algorithms reached the goal of 95% accuracy. The next prototype of the WMSD kit will not include nonspecific vaginal signs and symptoms in favor of recently available point-of-care devices that identify antigens or enzymes of the causative BV, TV, and CV organisms.


Surfactant-free synthesis of mesoporous and hollow silica nanoparticles with an inorganic template.
A surfactant-free synthesis of mesoporous and hollow silica nanoparticles is reported in which boron acts as the templating agent. Using such a simple and mild procedure as a treatment with water, the boron-rich phase is selectively removed, affording mesoporous pure silica nanoparticles with wormhole-like pores or, depending on the synthetic conditions, silica nanoshells.


[Complexity of the phenomenon of life - the challenge for medicine].
The human organism presents a complex biological system that has hierarchical organization. The lowest, basal hierarchical level is composed of chemical molecules. The system's structure as "the whole" is maintained by complex interactions of its parts (molecules). New forms and functions, not present in molecules themselves emerge from their orchestrated and coordinated interaction, creating the novel "whole". The "whole" is not a simple summation of its parts. Therefore, on the basis of reductionist analysis and solely on the list of component elements of biological systems it is not possible to predict the future form and function of the "whole". The information included in genes is not directly or proportionally expressed as the phenotype. The phenotype is based on secondary information and arises from the complex interaction of component elements of the system. On a basal (molecular) level, biological systems function according to self-organization rules. No central regulatory device is providing instruction for molecular interaction. Regulatory centers that coordinate the system are dispersed all over the system from molecular level up, keeping it in order and preventing a system to enter the chaos space. Advances in biology and development of new research technologies, as well as bioinformatics, computer sciences and mathematical modeling have enabled research on interaction of cellular macromolecules (proteins, DNA, RNA, etc.) that in a living cell are organized into large dynamic network. Some rules of a structural and functional networks' properties, as well as their organization were discovered. The above research area is regarded as a new academic field termed systems biology. Based on systems biology, many new concepts in medicine, particularly the mechanisms of biogenesis and development of diseases have emerged have potential application for early diagnostics and therapy.


Comparison of EMG activity and blood flow during graded exertion in the orbicularis oris muscle of adult subjects with and without lip incompetence: a cross-sectional survey.
The peri-oral muscles-including orbicularis oris-are critical in maintaining equilibrium in tooth position. Lip incompetence (LI) can thus be a factor in malocclusion. We therefore aimed to validate a technique to evaluate not only muscle activity via electromyography (EMG) but also muscle endurance and fatigue via blood flow (BF) for LI. Subjects were classified into increased muscle tension/lip incompetent (experimental) and normal muscle tension/lip competent (control) groups. Each subject then exerted force on a custom-made traction plate connected to a tension gauge. Using laser speckle imaging and electromyographic measurements, we characterized muscle activity and corresponding BF rates in these subjects in various states of resting, loading, and recovery. Results showed a significant difference between the experimental and control groups, notably in the rate of change in BF to the inferior orbicularis oris muscle under conditions of increasing load (graded exertion). Furthermore, the data suggested that the muscles in the control group undergo a more prolonged (and therefore presumably more complete) recovery than muscles in the experimental group. These factors of reduced BF and short recovery may combine to accelerate muscle fatigue and produce LI. The sample used here was controlled for malocclusion (including open bite) to eliminate this type of confounding effect. From these findings, we conclude that reduced BF and inadequate recovery in the orbicularis oris muscles may be more significant than EMG activity in the assessment of LI.


Transcriptomic and proteomic analyses of pericycle cells of the maize primary root.
Each plant cell type expresses a unique transcriptome and proteome at different stages of differentiation dependent on its developmental fate. This study compared gene expression and protein accumulation in cell-cycle-competent primary root pericycle cells of maize (Zea mays) prior to their first division and lateral root initiation. These are the only root cells that maintain the competence to divide after they leave the meristematic zone. Pericycle cells of the inbred line B73 were isolated via laser capture microdissection. Microarray experiments identified 32 genes preferentially expressed in pericycle versus all other root cells that have left the apical meristem; selective subtractive hybridization identified seven genes preferentially expressed in pericycle versus central cylinder cells of the same root region. Transcription and protein synthesis represented the most abundant functional categories among these pericycle-specific genes. Moreover, 701 expressed sequence tags (ESTs) were generated from pericycle and central cylinder cells. Among those, transcripts related to protein synthesis and cell fate were significantly enriched in pericycle versus nonpericycle cells. In addition, 77 EST clusters not previously identified in maize ESTs or genomic databases were identified. Finally, among the most abundant soluble pericycle proteins separated via two-dimensional electrophoresis, 20 proteins were identified via electrospray ionization-tandem mass spectrometry, thus defining a reference dataset of the maize pericycle proteome. Among those, two proteins were preferentially expressed in the pericycle. In summary, these pericycle-specific gene expression experiments define the distinct molecular events during the specification of cell-cycle-competent pericycle cells prior to their first division and demonstrate that pericycle specification and lateral root initiation might be controlled by a different set of genes.


Vibrio cholerae was found in cultured bullfrog.
Bullfrog is one of the most important economic aquatic animals in China that is widely cultured in southern China and is a key breed recommended as an industry of poverty alleviation in China. During recent years, a fatal bacterial disease has often been found in cultured bullfrogs. The clinical manifestations of the diseased bullfrogs were severe intestinal inflammation and an anal prolapse. A bacterial pathogen was isolated from the diseased bullfrog intestines. The bacterium was identified as Vibrio cholerae using morphological, biochemical and 16S rRNA phylogenetic analysis. In this study, V. cholerae was isolated and identified in diseased bullfrogs for the first time, providing a basis for the diagnosis and control of the disease. Therefore, attention should be paid to the modes of transmission of V. cholerae from bullfrog and formulate reasonable safety measures.


Support, information, and integration of genetics for children with congenital lower limb deficiencies in British Columbia, Canada.
Children and families affected by congenital limb deficiencies (CLD) require a unique level of emotional support from diagnosis through to adolescence. The following study aims to collect data on Canadian paediatric patients affected by a CLD followed at BC Children's Hospital (BCCH), Department of Orthopaedics. Parents of children with a CLD were asked to complete a written questionnaire examining their experiences. Qualitative and quantitative data were collected concerning parent satisfaction with patient referrals, emotional support, and knowledge of their child's diagnosis. Twenty-five completed questionnaires were returned. Fifty per cent of the parents reported they were either very satisfied, or satisfied, with the emotional support provided by health care providers (HCPs). Twenty-five per cent of the parents were unsatisfied with the emotional support received by HCPs. Forty-eight per cent of the parents could not recall the specific name of their child's diagnosis; 20% of the parents reported their child did not have diagnosis. All the patients in our study had received a clinical diagnosis. Twenty-eight per cent of the parents in this study were also seen in medical genetics. Families require additional resources for emotional support, peer support, and referrals to support organizations. Gaps in parent knowledge regarding their child's CLD suggest the need for formalized communication strategies for HCPs. Furthermore, patients with CLDs and their families may benefit from improved communication between orthopaedic and medical genetic services at the time of diagnosis. Integration of genetic counsellors may improve emotional supports and education for families with regards to testing and reproductive planning.


Adjuvant Docetaxel and Cyclophosphamide (DC) with prophylactic granulocyte colony-stimulating factor (G-CSF) on days 8 &12 in breast cancer patients: a retrospective analysis.
Four cycles of docetaxel/cyclophosphamide (DC) resulted in superior survival than doxorubicin/cyclophosphamide in the treatment of early breast cancer. The original study reported a 5% incidence of febrile neutropenia (FN) recommending prophylactic antibiotics with no granulocyte colony-stimulating factor (G-CSF) support. The worldwide adoption of this protocol yielded several reports on substantially higher rates of FN events. We explored the use of growth factor (GF) support on days 8 and 12 of the cycle with the original DC protocol. Our study included all consecutive patients with stages I-II breast cancer who were treated with the DC protocol at the Institute of Oncology, Davidoff Center (Rabin Medical Center, Petah Tikva, Israel) from April, 2007 to March, 2012. Patient, tumor characteristics, and toxicity were reported. In total, 123 patients received the DC regimen. Median age was 60 years, (range, 25-81 years). Thirty-three patients (26.8%) were aged 65 years and older. Most of the women (87%) adhered to the planned G-CSF protocol (days 8 &12). 96% of the patients completed the 4 planned cycles of chemotherapy. Six patients (5%) had dose reductions, 6 (5%) had treatment delays due to non-medical reasons. Thirteen patients (10.6%) experienced at least one event of FN (3 patients had 2 events), all requiring hospitalization. Eight patients (6.5%) required additional support with G-CSF after the first chemotherapy cycle, 7 because of FN and one due to neutropenia and diarrhea. Primary prophylactic G-CSF support on days 8 and 12 of the cycle provides a tolerable option to deliver the DC protocol. Our results are in line with other retrospective protocols using longer schedules of GF support.


Knockdown of E-cadherin expression of endometrial epithelial cells may activate Wnt/β-catenin pathway in vitro.
E-cadherin, a transmembrane glycoprotein mediating Ca2+-independent homotypic cell-cell adhesion in epithelial cell, plays an essential role in metastasis. It has been postulated that E-cadherin downregulation is a crucial mechanism in the pathogenesis of endometriosis. To evaluate the effect on the cell behavior after knockdown of E-cadherin gene (CDH1) in cultured human endometrial epithelial cells (EECs) isolated from normal endometrium. EECs were isolated from the endometrial tissues of fertile woman who underwent total hysterectomy due to cervical intraepithelial neoplasia III. CDH1 expression was knocked down by small hairpin RNA. The EECs transfected with empty vector served as control. Transwell assay was used to test EECs migration or invasion. qRT-PCR and western blot were used to detect mRNA and protein levels. The results showed that knockdown of E-cadherin expression can increase cell migration and invasion, and up-regulate mRNA and protein levels of β-catenin, cyclinD1, and c-myc. Down-regulation of E-cadherin expression may activate the Wnt/β-catenin pathway in endometrial cells, which may together participate in the occurrence of endometriosis.


Primary microRNA processing assay reconstituted using recombinant Drosha and DGCR8.
In animals, the Microprocessor complex cleaves primary transcripts of microRNAs (pri-miRNAs) to produce precursor microRNAs in the nucleus. The core components of Microprocessor include the Drosha ribonuclease and its RNA-binding partner protein DiGeorge critical region 8 (DGCR8). DGCR8 has been shown to tightly bind an Fe(III) heme cofactor, which activates its pri-miRNA processing activity. Here we describe how to reconstitute pri-miRNA processing using recombinant human Drosha and DGCR8 proteins. In particular, we present the procedures for expressing and purifying DGCR8 as an Fe(III) heme-bound dimer, the most active form of this protein, and for estimating its heme content.


Pulse Oximetry Is Unreliable in Patients on Veno-Venous Extracorporeal Membrane Oxygenation Caused by Unrecognized Carboxyhemoglobinemia.
Continuous bedside pulse oximetry (SpO2) is universally used to monitor oxygenation for patients supported on veno-venous extracorporeal membrane oxygenation (VV-ECMO). Yet, elevated carboxyhemoglobin (COHb), a known event in VV-ECMO, diminishes the reliability of SpO2. This retrospective cohort study aims to assess the accuracy of SpO2 compared with oxyhemoglobin (SaO2) and quantify COHb levels by co-oximetry in the VV-ECMO population. Forty patients on VV_ECMO from 2012 to 2017 underwent 1,119 simultaneous SaO2 and SpO2 measurements. Most patients were male (60%) with average age of 46 years. SpO2 overestimated SaO2 values by 2.35% at time of cannulation and 0.0061% for each additional hour on VV-ECMO (p < 0.0001). Twenty-nine (72.5%) patients developed elevated COHb (>3% of hemoglobin saturation) at least once during VV-ECMO support and 602 (40.2%) arterial blood gases yielded elevated COHb levels. Mean duration for ECMO with elevated COHb was 244 hours compared with 98 hours in patients without (p < 0.0048). Patients who developed COHb were younger (mean age 40 vs. 55 years, p < 0.024) and had single-site double-lumen cannulation (odds ratio = 4.5, p = 0.23). At time of cannulation, mean COHb was 2.18% and increased by 0.0054% for each additional hour (p < 0.0001). For every 1% increase in COHb, SaO2 decreased by 1.1% (p < 0.0001). During VV-ECMO, SpO2 often overestimates SaO2 by substantial margins. This is attributable to rising COHb levels proportional to duration on VV-ECMO. In this population where adequate oxygen delivery is often marginal, clinicians should be wary of the reliability of continuous pulse oximetry to assess oxygenation.


Acute combined exposure to heavy metals (Zn, Cd) blocks memory formation in a freshwater snail.
The effect of heavy metals on species survival is well documented; however, sublethal effects on behaviour and physiology are receiving growing attention. Measurements of changes in activity and respiration are more sensitive to pollutants, and therefore a better early indicator of potentially harmful ecological impacts. We assessed the effect of acute exposure (48 h) to two heavy metals at concentrations below those allowable in municipal drinking water (Zn: 1,100 μg/l; Cd: 3 μg/l) on locomotion and respiration using the freshwater snail, Lymnaea stagnalis. In addition we used a novel assessment method, testing the ability of the snail to form memory in the presence of heavy metals in both intact snails, and also snails that had the osphradial nerve severed which connects a chemosensory organ, the osphradium, to the central nervous system. Aerial respiration and locomotion remained unchanged by acute exposure to heavy metals. There was also no effect on memory formation of these metals when administered alone. However, when snails were exposed to these metals in combination memory formation was blocked. Severing the osphradial nerve prevented the memory blocking effect of Zn and Cd, indicating that the snails are sensing these metals in their environment via the osphradium and responding to them as a stressor. Therefore, assessing the ability of this species to form memory is a more sensitive measure of heavy metal pollution than measures of activity, and indicates that the snails' ability to demonstrate behavioural plasticity may be compromised by the presence of these pollutants.


List of essential drugs for primary care in Lebanon.
In 1966, Lebanon had around 19,000 drug formulations registered in the Ministry of Public Health. The government decreased that number to 5400 in 1992 through numerous interventions. In 1995 and in an effort to rationalize drug prescribing, the Lebanese government organized an ad hoc committee of medical and pharmaceutical experts to review the 1992 list and create a list of essential drugs for primary care (LEDPC). This report describes the process and the studies used to update the 1992 list by the ad hoc committee.


Highly efficient removal of chromium(VI) from aqueous solution using polyaniline/sepiolite nanofibers.
Polyaniline/sepiolite (PANI/sepiolite) nanofibers were prepared by in situ chemical oxidation polymerization in the presence of sepiolite. The effect of aniline/sepiolite weight ratio on the nanostructure of PANI/sepiolite composites was investigated by field-emission scanning electron microscopy. The adsorption of Cr(VI) onto the PANI/sepiolite nanofibers was highly dependent on pH values. The pseudo-second-order and Langmuir isothermal models can well describe the adsorption kinetics and adsorption isotherm, respectively. The maximum adsorption capacity of the PANI/sepiolite nanofibers for Cr(VI) was up to 206.6 mg/g at 25 °C and increased with the increase in temperature. Desorption experiments indicated that PANI/sepiolite can be regenerated and reused for two consecutive cycles with no loss of its removal efficiency. PANI/sepiolite nanofibers can be used as a highly efficient and economically viable adsorbent for Cr(VI) removal due to their excellent adsorption characteristics.


Cellular site of expression and genetic interaction of the rd and the rds loci in the retina of the mouse.
In the retina of mice, the two genes, rd and rds, produce retinal degeneration. Depending on allelic combination and gene dosage at these loci, four different genotypes with distinct phenotypic traits and rates of photoreceptor cell loss are recognized. The cellular site of gene action and the nature of interaction, resulting in the variegation of the retinal phenotypes have been analyzed by comparing gene expression in the retina of pure line (unigenotypic) mice, and in the retina of chimaeric mice, experimentally produced by aggregating embryos of different genotypic constitution. The findings suggest that both rd and rds genes act intracellularly within the photoreceptor cells. The primary expression of the genes, producing specific phenotypic alterations of the photoreceptor cells, are invariant and are not affected by extracellular factors. The lethal effects of the genes, on the other hand, resulting in specified rates of photoreceptor cell death, are influenced by both genetic (intracellular), and environmental factors.


Analysis of the Intracellular Localization of Transiently Expressed and Fluorescently Labeled Copper-Containing Amine Oxidases, Diamine Oxidase and N-Methylputrescine Oxidase in Tobacco, Using an Agrobacterium Infiltration Protocol.
The intracellular localization of enzymes provides key information for understanding complex metabolic pathways. Based on enzyme localization data, the involvement of multiple organelles and the movement of metabolites between cellular compartments have been suggested for a number of pathways. Transient expression of fluorescently tagged proteins in the leaves of Nicotiana benthamiana through Agrobacterium infiltration is a simple and versatile way to examine the intracellular localization of proteins of interest. Here, this method was applied to demonstrate the peroxisomal localization of a pair of homologous copper-containing amine oxidases (CuAOs) from tobacco with distinct substrate preferences: diamine oxidase (DAO), which mediates polyamine catabolism, and N-methylputrescine oxidase (MPO), which is involved in nicotine biosynthesis. Our results demonstrate that the Agrobacterium infiltration protocol can be effectively used to study the intracellular localization of oxidases that localize to the peroxisome.


A huge infiltrating squamous cell carcinoma of the neck 46 years after radiotherapy of a haemangioma.
There is a higher risk for malignant tumours in patients who underwent any kind of radiotherapy. An 87-year-old patient with an extended squamous cell carcinoma of the neck was referred to our hospital. The large ulcerated tumour showed a deep infiltration of the para-vertebral muscles and the spinal processes C6-C7. The tumour was known since about six years and appeared about 46 years after low-dose radiotherapy of a cervical haemangioma of the neck in 1961. The large dimension of the tumour leaded to a radical surgical removal and a sufficient fast reconstruction strategy. The extended defect was covered by a pedicled lower musculocutaneous trapezius flap. No postoperative complications like partial necrosis, infection or movement disorders of the shoulder or a shoulder drop syndrome were seen. Ten weeks after the operation the patient showed a good functional and aesthetic result with no limitation of arm mobility. Two and a half years after radical intended surgery the patient was still alive and showed no recurrence of the tumour. In conclusion there is a need for a life-time lasting dermatological supervision in patients with a history of radiotherapy in the past, because the handling of patients with such an enlarged tumour is complicated.


[Studies of the effectiveness and optimal administration of repeated intraperitoneal chemotherapy for peritoneal dissemination from gastric cancer].
The optimal interval for drug administration was examined for repeated intraperitoneal chemotherapy (IPC). The subjects were 31 patients who underwent curative surgical resection excluding P1 or CY1 factor, followed by IPC. IPC was carried out 180 times in total, and the intervals were divided into three groups: 2-week interval 45 times, 3-week interval 10 times and 4-week or greater interval 94 times. The optimal method of drug administration was evaluated from the therapeutic outcome and the development of adverse effects with each interval time. The cytology of ascites obtained via an i.p. port was examined before each drug administration, and those with a negative change (CY0) were judged as responders. The adverse effects in the patients receiving drugs at 2-week intervals were grade 1 or 2, although the incidence was high compared with other patients. All responders obtained a negative change in CY within six courses. At present, we conclude that it is reasonable for IPC to be carried out six times at 2-week intervals.


Erythromycin and phenoxymethylpenicillin (penicillin V) in the treatment of respiratory tract infections as related to microbiological findings and serum C-reactive protein.
Respiratory tract pathogens (beta-haemolytic streptococci groups A, C and G, Haemophilus influenzae, Branhamella catarrhalis or pneumococci), were isolated from nasopharyngeal and/or throat swabs in 73/138 (53%) patients greater than 10 years of age with a clinical diagnosis of acute sinusitis, acute tonsillitis, purulent nasopharyngitis or acute bronchitis. Serological evidence of a viral infection (influenza A and B, parainfluenza 1, 2 and 3, respiratory syncytial virus, adenovirus) or Mycoplasma pneumoniae infection was found in 10% of the patients. The serum content of C-reactive protein (S-CRP) was increased (greater than 12 mg/l) in 26/33 (79%) patients with streptococci and in 22/59 (37%) patients without respiratory tract bacteria. In patients with a serological evidence of a virus tonsillitis, the S-CRP was also high (32-64 mg/l). At follow-up 10-12 days after the first visit, the clinical effect of erythromycin and penicillin V was judged to be similar (90% clinical effect). Relapse or re-infection with group A streptococci were seen in 7 patients (4 on erythromycin, 3 on penicillin). In another 6 patients (3 on erythromycin, 3 on penicillin), antibiotic treatment was switched owing to persisting symptoms, probably due to H. Influenzae infection in 3 cases. The patients' own estimates of their symptoms suggested treatment with erythromycin to have a more rapid effect than treatment with penicillin.


[Mental atony in children].
The paper considers the phenomenon of «mental atony» in children with developmental delay, intellectual disability and autism. The condition of mental atony is a congenital or early acquired even decrease in mental tone, manifested by the reduced ability to concentrate attention, a decline of the targeted activity, difficulties in contacting, weakening of unconditioned reflexes, lack of instinctive manifestations, «mobilization» of mental functions by persistent verbal and tactile stimulation. The article provides the history of the «mental atony» theory, as well as clinical features, epidemiology, etiology, pathogenesis and nosological specificity of the condition. Moreover, the criteria for the differential diagnosis between the atonic form of intellectual disability and autism are discussed in detail. Based on the analysis of literature and the results of own clinical observations, the authors conclude that a thorough differential analysis between childhood autism and atonic form of intellectual disability in children is necessary, otherwise, there is a risk of overdiagnosis of autistic disorders. The authors also point to the role of the brain lesion, particularly in the area of reticular formation, in the occurrence of phenomena of mental atony.


Comprehensive Perspectives on Experimental Models for Parkinson's Disease.
Parkinson's disease (PD) ranks second among the most common neurodegenerative diseases, characterized by progressive and selective loss of dopaminergic neurons. Various cross-species preclinical models, including cellular models and animal models, have been established through the decades to study the etiology and mechanism of the disease from cell lines to nonhuman primates. These models are aimed at developing effective therapeutic strategies for the disease. None of the current models can replicate all major pathological and clinical phenotypes of PD. Selection of the model for PD largely relies on our interest of study. In this review, we systemically summarized experimental PD models, including cellular and animal models used in preclinical studies, to understand the pathogenesis of PD. This review is intended to provide current knowledge about the application of these different PD models, with focus on their strengths and limitations with respect to their contributions to the assessment of the molecular pathobiology of PD and identification of the therapeutic strategies for the disease.


Stereoselective synthesis of highly functionalized hydroindoles as building blocks for rostratins B-D and synthesis of the pentacyclic core of rostratin C.
The stereoselective synthesis of a variety of functionalized hydroindoles suitable as building blocks for thiodiketopiperazine natural products such as rostratins B-D is reported. The key precursor for all transformations is a previously reported hexahydroindole compound. All functional groups were installed with the desired stereochemistry and the feasibility of the synthetic strategy was exemplified by dimerization of two hydroindole units to form the pentacyclic C2 -symmetric scaffold of rostratin C.


Maternal nutritional status and the risk for orofacial cleft offspring in humans.
Periconceptional folate and folic acid intake prevents orofacial clefts (OFC) in the offspring. It has been suggested that other nutrients also play a role. We investigated the preconceptional intake of macronutrients (protein, fat, carbohydrate, fiber, and cholesterol), vitamins (vitamin A, retinol, beta-carotene, ascorbic acid, and alpha-tocopherol), minerals (calcium, phosphorus, iron, magnesium, and zinc) and food groups in mothers of OFC children and controls. At approximately 14 mo after the index pregnancy, 206 mothers of a child with a nonsyndromic OFC and 203 control mothers completed a FFQ on current food intake and a general questionnaire. After exclusion of pregnant and lactating mothers, mothers who reported a change in diet compared with the preconceptional period, and those for whom periconceptional folic acid supplement use was unclear, 182 OFC mothers and 173 control mothers were evaluated. Macronutrient, vitamin, mineral, and food group intakes were compared. After adjustment for energy, quintiles of dietary nutrient intake and odds ratios with 95% CI were calculated. The preconceptional intake of all macronutrients, vitamins, minerals, and food groups with the exception of milk (products), potatoes, pies/cookies were lower in OFC mothers than in controls. The energy-adjusted intakes of vegetable protein, fiber, beta-carotene, ascorbic acid, alpha-tocopherol, iron, and magnesium were significantly lower in cases compared with controls. Increasing intakes of vegetable protein, fiber, ascorbic acid, iron, and magnesium decreased OFC risk. In conclusion, a higher preconceptional intake of nutrients predominantly present in fruits and vegetables reduces the risk of offspring affected by OFC.


Post-exposure prevention of HIV-1 infection.
Post-exposure prevention of human immunodeficiency virus type 1 (HIV-1) infection involves a combined modality approach to subjects exposed to the HIV-1 virus through sexual or occupational contact or intravenous drug use. Identification of those at highest risk of transmission, which involves patient factors as well as the infectivity of the partner and the local prevalence of HIV-1, will help to determine appropriate candidates for post-exposure treatment. Early institution of therapy (within 72 h) should be followed with education and counselling to help maximize therapeutic adherence while reinforcing safer behaviour for the future.


[Analysis of dental care provided to the adult population with infectious diseases in in-patient departments].
The purpose of the study was to analyze the types and volumes of treatment and prophylactic services provided to the adult population with infectious diseases in the dental office of a multidisciplinary hospital. The types and volumes of dental care provided to the adult population with infectious diseases in a multidisciplinary hospital have been analyzed. The study showed that dentists use 49 types of services when treating adults with infectious diseases, which corresponds to 29.88% of the compulsory medical insurance classifier in Moscow. Provided services can be conditionally divided into 4 groups: consultation, diagnostic, preventive and medicinal manipulations. The share of consulting services corresponds to 18.16±0.41% of the total volume of services provided; on average patients made 320.8 visits to the dentist's doctors per year, which corresponds to 2.38 visits for each patient. The proportion of medicinal manipulations, diagnostic and preventive services corresponds to 68.64±0.49%, 7.02±0.27% and 6.17±0.26%, respectively. Services related to the diagnosis and treatment of diseases of the oral mucosa and salivary glands dominate with 69.3%, on average 5.51 services are provided per visit. The compulsory medical insurance program for the city of Moscow should provide services for the diagnosis, treatment and prevention of dental diseases, provided by doctors specializing in «dentistry», for patients with infectious diseases who are undergoing treatment in inpatient conditions.


Large Riedel's lobe and atrophic left liver in a donor - Accept for transplant or call off?
In context of suboptimal liver utilisation, grafts with various risk factors are under consideration today. For example, impaired vascularity with severe arterial calcifications and modified liver shapes are no longer contraindications and their use depends on the centre policy and experience of the surgical team. Riedel liver lobes represent a tongue-like liver shape with inferior projection in the right liver lobe. Such development modifications were initially described when patients developed a lesion and subsequently presented with symptoms. We here present the first case report in the literature, where such livers with anatomical variations were used for transplantation. We describe here two cases of adult human liver transplantation, where we have accepted two donor livers with modified shape. The technical considerations for transplantation of such livers, found with enlarged right lobes, or Riedel shape, and hypo-trophic left lateral segment are highlighted. Both recipients experienced immediate liver function and overall good outcomes with a minimum follow up of 1 year. We also provide detailed pictures and outcome analysis in combination with a literature review. The utilisation of donor livers with modified shape, such as Riedel's Lobe appears safe and will increase the donor pool.


Bandgap Engineering in 2D Lateral Heterostructures of Transition Metal Dichalcogenides via Controlled Alloying.
2D heterostructures made of transition metal dichalcogenides (TMD) have emerged as potential building blocks for new-generation 2D electronics due to their interesting physical properties at the interfaces. The bandgap, work function, and optical constants are composition dependent, and the spectrum of applications can be expanded by producing alloy-based heterostructures. Herein, the successful synthesis of monolayer and bilayer lateral heterostructures, based on ternary alloys of MoS2(1- x ) Se2 x -WS2(1- x ) Se2 x , is reported by modifying the ratio of the source precursors; the bandgaps of both materials in the heterostructure are continuously tuned in the entire range of chalcogen compositions. Raman and photoluminescence (PL) spatial maps show good intradomain composition homogeneity. Kelvin probe measurements in different heterostructures reveal composition-dependent band alignments, which can further be affected by unintentional electronic doping during the growth. The fabrication of sequential multijunction lateral heterostructures with three layers of thickness, composed of quaternary and ternary alloys, is also reported. These results greatly expand the available tools kit for optoelectronic applications in the 2D realm.


Carotid artery stenting for high-risk patients.
Carotid artery stenting is being increasingly considered as a treatment option for high-risk patients with internal carotid artery atherosclerosis or vasculopathies. Since carotid endarterectomy is a procedure with a longer track record, some clinicians consider stenting to be appropriate only in high-risk conditions such as patients with severe medical comorbidities, recurrent stenosis following previous endarterectomy, or radiation-induced stenosis. The application of stenting in these areas is discussed, as well as the potential role for stenting in patients with acute ischemic stroke.


Diagnosis of unexposed tumours using endobronchial ultrasonography with a guide sheath and a thin transbronchial needle.
Transbronchial diagnosis of unexposed lung tumours is challenging in clinical practice. Although modified transbronchial needle aspiration (TBNA) is used for this purpose, the diagnostic yield is unsatisfactory. In such cases, conventional endobronchial ultrasonography with a guide sheath and transbronchial biopsy (TBB) is also ineffective. We found TBB was feasible by placing a guide sheath with a thin transbronchial needle into the tumours. We report two cases of unexposed tumours diagnosed successfully with this technique. Case 1 presents a typical carcinoid in the peripheral lung. Case 2 presents a squamous cell carcinoma at the third bifurcation of the right lung. TBB samples obtained this way were larger than TBNA samples. Moreover, multiple TBBs were possible once the guide sheath was inserted intratumourally. In the modern era of precision medicine, larger amounts of tissues are required for multiple downstream analyses. This novel technique will make a significant contribution towards diagnosing unexposed lung tumours.


Guanylyl cyclase-A inhibits angiotensin II type 1A receptor-mediated cardiac remodeling, an endogenous protective mechanism in the heart.
Guanylyl cyclase (GC)-A, a natriuretic peptide receptor, lowers blood pressure and inhibits the growth of cardiac myocytes and fibroblasts. Angiotensin II (Ang II) type 1A (AT1A), an Ang II receptor, regulates cardiovascular homeostasis oppositely. Disruption of GC-A induces cardiac hypertrophy and fibrosis, suggesting that GC-A protects the heart from abnormal remodeling. We investigated whether GC-A interacts with AT1A signaling in the heart by target deletion and pharmacological blockade or stimulation of AT1A in mice. We generated double-knockout (KO) mice for GC-A and AT1A by crossing GC-A-KO mice and AT1A-KO mice and blocked AT1 with a selective antagonist, CS-866. The cardiac hypertrophy and fibrosis of GC-A-KO mice were greatly improved by deletion or pharmacological blockade of AT1A. Overexpression of mRNAs encoding atrial natriuretic peptide, brain natriuretic peptide, collagens I and III, transforming growth factors beta1 and beta3, were also strongly inhibited. Furthermore, stimulation of AT1A by exogenous Ang II at a subpressor dose significantly exacerbated cardiac hypertrophy and dramatically augmented interstitial fibrosis in GC-A-KO mice but not in wild-type animals. These results suggest that cardiac hypertrophy and fibrosis of GC-A-deficient mice are partially ascribed to an augmented cardiac AT1A signaling and that GC-A inhibits AT1A signaling-mediated excessive remodeling.


Circulating progenitor and mature endothelial cells in deep vein thrombosis.
Mature circulating endothelial cells (CEC) and circulating endothelial progenitor cells (EPC) have been described in several conditions associated with endothelial injury. Their role in deep vein thrombosis (DVT) has not been previously evaluated. In this pilot study we evaluated the time course of CEC and EPC release after vena cava experimental DVT in mice, using the FeCl3 model. We also evaluated their presence in patients with DVT at different phases of the disease (acute and chronic phase). CEC and EPC were evaluated by Flow Cytometry. In mice, both CEC and EPC were increased 24 hours after DVT induction, peaking 48 hours thereafter. After 72 hours, CEC counts decreased sharply, whereas EPC counts decreased less substantially. In DVT patients we observed a significant increase in CEC counts immediately after DVT compared to healthy individuals. Patients with chronic disease also presented a significant elevation of these cell count. In a subgroup of patients for whom serial samples were available, CEC counts decreased significantly after 9-15 months of the acute event. Our results suggest the participation of these cells in the reparative processes that follows DVT, both at immediate and late time-points. The different kinetics of CEC and EPC release in experimental DVT suggests a heterogeneous role for these cells in the reparative events after DVT.


The effect and recovery of long-term H2O2 exposure on lens morphology and biochemistry.
Oxidative stress has long been speculated to play an important role in cataractogenesis. In the H2O2-induced cataract model, rat lens showed extensive biochemical damage but very mild morphological changes after being exposed to H2O2 (0.5 mM) for 24 hr in culture. This damage included reduced glutathione (GSH) depletion, protein-GSH mixed disulfide (PSSG) elevation but not protein-protein disulfide (PSSP) formation. In order to understand the role of protein-thiol mixed disulfide formation in relation to the sequence of events during cataract induction, we conducted a long term H2O2 exposure study for up to 96 hr to monitor the dynamic changes in GSH and PSSG levels, the formation of PSSP aggregate, protein solubility, and the progression in lens opacity. Rat lenses were cultured in 0.5 mM H2O2 and harvested at intervals of 24, 48, 72 and 96 hr for the examination of morphological and biochemical changes. Contralateral lenses cultured in H2O2-free media were used as controls. It was found that the lenses had only patchy opacity at the equator after 24 hr, but became hydrated suddenly at 48 hr (31% heavier than the control), with an opacity which involved the entire outer cortical region. By 72 hr incubation, the nucleus was opacified. Lens GSH progressively decreased with time of H2O2 exposure, 40% was lost by 24 hr and over 95% by 48 hr. There was a concomitant elevation of PSSG, 16-fold over the controls by 24 hr and 45-fold by 48 hr followed by a decline to 34-fold after 72 hr. In addition, the level of protein-cysteine mixed disulfide (PSSC) was elevated after 48 hr incubation in H2O2. At this time point, PSSP aggregates began to appear both in water soluble (WS) and urea soluble (US) fractions along with a drastic reduction in protein solubility. Western blot analysis of the protein fractions identified beta and gamma, but not alpha-crystallin in the disulfide-containing aggregates. The lens clarity and biochemical changes partially recovered if the oxidant was removed within 24 hr, indicating a potential therapeutic role for antioxidants. The complete normalization of PSSG level under this recovery condition signifies that cells may have a natural defense system for controlling PSSG elevation.


Calcium antagonists and the stunned myocardium.
"Stunned myocardium" is defined as the prolonged but transient contractile dysfunction of viable myocardium salvaged by reperfusion. For example, a brief 15-min episode of coronary artery occlusion does not result in myocyte necrosis, yet contractile function of the previously ischemic tissue remains profoundly depressed at 0-30% of baseline values for hours to days following reflow. This phenomenon, first characterized in the experimental canine model, has more recently been documented in clinical instances of angina, following cardiac surgery, after angioplasty, and following successful reperfusion for the treatment of acute myocardial infarction. Considerable evidence indicates that calcium antagonists administered prior to coronary occlusion attenuate postischemic stunning in the canine model: verapamil, diltiazem, and amlodipine have been shown to restore contractile function to 50-100% of baseline values during the initial hours following relief of ischemia. Furthermore, both verapamil and nifedipine improved systolic contraction of stunned myocardium even when treatment was "delayed"--i.e., when the agents were administered 30 min after reflow had been established. This improved recovery of contractile function associated with calcium antagonist treatment may be due in part to the well-documented afterload reducing and coronary vasodilatory properties of these agents. However, as low doses of intracoronary nifedipine infused after reperfusion restored systolic contraction to 75-90% of baseline values in the absence of afterload reduction or increases in coronary blood flow, these data suggest that calcium antagonists may act in part by favorably modulating calcium flux within the stunned, previously ischemic myocytes.(ABSTRACT TRUNCATED AT 250 WORDS)


Ground-state cooling of an oscillator in a hybrid atom-optomechanical system.
We investigate a hybrid quantum system combining cavity quantum electrodynamics and optomechanics, where a photon mode is coupled to a four-level tripod atom and to a mechanical mode via radiation pressure. We find that within the single-photon optomechanics and Lamb-Dicke limit, the presence of the tripod atom alters the optical properties of the cavity radiation field drastically, and gives rise to completely quantum destructive interference effects in the optical scattering. The heating rate can be dramatically suppressed via utilizing the completely destructive interference involving atom, photon and phonon, and the obtained result is analogous to that of the resolved sideband regime. The heating process is only connected to the scattering of cavity damping path, which is also far-off resonance. Meanwhile, the cooling rate assisted by the atomic transitions can be significantly enhanced, where the cooling process occurs through the cavity and atomic dissipation paths. Finally, the ground-state cooling of the movable mirror is achievable and even more robust to heating process and thermal noise.


Fasting-induced down-regulation of NADPH-diaphorase in the magnocellular PVN of rats.
In this study, we examined if glucocorticoids are required for the fasting-induced decrease of neuronal nitric oxide synthase (nNOS) in the magnocellular division of the paraventricular nucleus (PVN). Rats were adrenalectomized, subjected to 48 h of food deprivation with/without dexamethasone (5 mg/ kg, 4 subcutaneous injections with 12 h intervals), and the brain slices were processed for NADPH-diaphorase (NADPH- d) staining, a histochemical marker for nNOS in neuronal cells. In food deprived adrenalectomized rats, but not in free fed intact rats, dexamethasone significantly decreased NADPH-d staining in the magnocellular PVN. We previously reported that food deprivation decreases nNOS in the magnocellular PVN of intact rats. Thus, the present results together with our previous report suggest that although glucocorticoids are required for fasting-induced nNOS down-regulation in the magnocellular PVN, glucocorticoids may not be directly involved and some other molecular signals produced by food deprivation may play a pivotal role over glucocorticoid in the regulatory pathway for nNOS expression in this brain region.


Shape of a cracking whip.
The crack of a whip is produced by a shock wave created by the supersonic motion of the tip of the whip in the air. A simple dynamical model for the propagation and acceleration of waves in the motion of whips is presented. The respective contributions of tension, tapering, and boundary conditions in the acceleration of an initial impulse are studied theoretically and numerically.


Does education plays a role in meeting the human rights needs of Indian women with mental illness?
Globally women are one of the vulnerable populations and women without education and with mental illness are doubly disadvantaged. To find out the role of education in meeting the human rights needs of women with mental illness at family and community levels. A descriptive design was carried out among randomly selected recovered women (N = 100) with mental illness at a tertiary care center. Data was collected through face-to-face interview using a structured questionnaire. Our findings revealed that human rights needs in physical needs dimension, i.e. access to safe drinking water (χ(2) = 7.447, P < 0.059) and serving in the same utensils (χ(2) = 10.866, P < 0.012), were rated higher in women with illiteracy. The human rights needs in emotional dimension, i.e. afraid of family members (χ(2) = 13.266, P < 0.004), not involved in making decisions regarding family matters (χ(2) = 21.133, P < 0.00) and called with filthy nicknames (χ(2) = 8.334, P < 0.040), were rated higher in literate women. The human rights needs in religious needs dimension, i.e. allowed to go to temple, church, mosque etc. (χ(2) = 9.459, P < 0.024), were not satisfied by the illiterate women. Similarly, literate women felt that they were discriminated by community members due to their illness (χ(2) = 9.823, P < 0.044). The findings of the present study suggested that women without education were more deprived of human rights needs than literate women. Thus, there is an urgent need to improve literacy of women and to strengthen the legal framework to protect the rights of the women with mental illness.


Role of barium meal examination in diagnosis of peptic ulcer.
Peptic ulcer is a sore in the protective lining (mucosal lining) of the gastrointestinal tract and develops when the lining is damaged. The objectives of this Descriptive Validational study were to determine the validity of Barium Meal examination in the diagnosis of peptic ulcer disease in comparison to the gold standard, i.e., endoscopic evaluation in peptic ulcer disease. The study was conducted at Radiology Department Khyber Teaching Hospital Peshawar from November 2000 to March 2004. A total of 115 patients with signs and symptoms of peptic ulcer disease were selected for this study and were subjected for this diagnostic modality. The diagnosis of benign/malignant peptic ulcer was made by barium meal examinations. In all these patients the diagnosis was later on confirmed by endoscopy and or surgery. Of the 115 patients, 80 were male and 35 were female patients. Their ages ranged from 27-75 years with mean age of 49 years. Fifty two patients had duodenal ulcer, 30 patients gastric ulcer, and 33 patients had normal radiological findings. In 6 out of 30 patients with gastric ulcer had radiological evidence of malignant gastric ulcer. Efficiency of Barium meal examination in diagnosis of peptic ulcer is good and most of peptic ulcers can be diagnosed by this method.


The value of MMP-9 for breast and non-small cell lung cancer patients' survival.
Matrix metalloproteinases (MMPs) are implicated in cancer cells invasion and metastasis processes and have been investigated as potential cancer biomarkers. In this study MMP-9 gene expression and MMP-9 -1562 C/T polymorphism in breast and non-small cell lung cancer patients' blood and tumor samples and its correlation with clinicopathological parameters were investigated. MMP-9 gene expression was assessed by reverse transcription - polymerase chain reaction method in 108 cancer patients' blood and tumor samples. MMP-9 -1562 C/T polymorphism was determined by the polymerase chain reaction - based restriction fragment length polymorphism method. Significant relationship of MMP-9 gene expression and tumor differentiation grade was found only between groups with G1 and G3 breast tumors. Low survival rates were identified among positive MMP-9 expression in blood and ductal carcinoma of the breast (p=0.01) and negative progesterone receptor reaction (p=0.04). Significant differences in the distribution among genotypes were found between groups with stage I and stages III/IV (p=0.005) as well as between groups with lymph node status N0 and N1 (p<0.001). Breast cancer patients with tumor differentiation grade G3 and identified CC variant had a longer survival time (p=0.014). Shorter survival time was found among positive MMP-9 expression in tumor and stage I non-small cell lung cancer patients with negative lymph node (p=0.012) and squamous cell carcinoma (p=0.019). Expression of MMP-9 in blood and tumor together indicates worse prognosis for breast cancer patients.


Cell-cycle-specific interaction of nuclear DNA-binding proteins with a CCAAT sequence from the human thymidine kinase gene.
Induction of thymidine kinase parallels the onset of DNA synthesis. To investigate the transcriptional regulation of the thymidine kinase gene, we have examined whether specific nuclear factors interact in a cell-cycle-dependent manner with sequences upstream of this gene. Two inverted CCAAT boxes near the transcriptional initiation sites were observed to form complexes with nuclear DNA-binding proteins. The nature of the complexes changes dramatically as the cells approach DNA synthesis and correlates well with the previously reported transcriptional increase of the thymidine kinase gene.


Long-term vaginal antibody delivery: delivery systems and biodistribution.
Topical delivery systems can provide prolonged delivery of antibodies to the vaginal mucosal surface for long-term protection against infectious diseases. We examined the biodistribution of antibodies during 30 days of vaginal antibody delivery in mice. Different antibody preparations (including monoclonal IgG and IgM, as well as several different (125)I-labeled IgGs) were administered by polymer vaginal rings, which were designed to provide continuous antibody delivery. Antibody concentrations remained high in the vaginal secretions for up to 30 days after disk insertion; radiolabeled antibody was also found, at approximately 100 times lower concentration, in the blood and other tissues. The measured concentrations agreed reasonably well with a simple pharmacokinetic model, which was used to calculate mucosal and systemic concentrations as a function of antibody delivery and elimination rates. Results from the model were consistent with previously reported antibody pharmacokinetic measurements: the half-life for antibody elimination for the vagina was approximately 3 h; the half-life for IgG(1) clearance from the blood was >1 day; and the overall permeability constant for vaginal uptake of IgG was approximately 0.01 to 0.03 h(-1). These results provide important information for the design of controlled antibody delivery devices for vaginal use, and suggest that high-dose, long-term vaginal administration of antibodies may be a reasonable approach for achieving sustained mucosal and systemic antibody levels.


[The discriminative stimulus properties of naloxone during dissociative learning in a Y maze in morphine-dependent rats].
The study was dedicated to evaluation of discriminative stimulus properties of opiate withdrawal syndrome precipitated by naloxon. The possibility of naloxon-appropriate reaction significantly increased in a dose-dependent manner (0-1.0 mg/kg, ED50 = 0.03 mg/kg) and was observed during the period of morphine withdrawal (8-96 h, peak at 24 h). Naloxone stimulus effects were antagonized by morphine (10-100.mg/kg), thus providing the experimental evidence for competitive and saturatable nature of interaction with opiate receptors. The probability of naloxone-appropriate reaction decreased during administration of the conditioned stimulus associated with morphine injection. Ligands of peripheral opiate receptors failed to either substitute for naloxone (methylnaloxon, 0.1-3.0 mg/kg) or attenuate naloxone stimulus effects (loperamide, 1-30 mg/kg).


Human newborns' perception of male voices: preference, discrimination, and reinforcing value.
Human newborns were tested with an operant choice procedure to determine whether they would prefer their fathers' voices to that of another male. No preference was observed. Subsequent testing revealed that they could discriminate between the voices but that the voices lacked reinforcing value. These results contrast sharply with newborns' perception of their mothers' voices, in particular, and female voices, in general. The data were interpreted as supporting an hypothesis that prenatal experience significantly influences human newborns' earliest voice preferences.


Drivers of healthcare costs associated with the episode of care for surgical aortic valve replacement versus transcatheter aortic valve implantation.
Transcatheter aortic valve implantation (TAVI) is generally more expensive than surgical aortic valve replacement (SAVR) due to the high cost of the device. Our objective was to understand the patient and procedural drivers of cumulative healthcare costs during the index hospitalisation for these procedures. All patients undergoing TAVI, isolated SAVR or combined SAVR+coronary artery bypass grafting (CABG) at 7 hospitals in Ontario, Canada were identified during the fiscal year 2012-2013. Data were obtained from a prospective registry. Cumulative healthcare costs during the episode of care were determined using microcosting. To identify drivers of healthcare costs, multivariable hierarchical generalised linear models with a logarithmic link and γ distribution were developed for TAVI, SAVR and SAVR+CABG separately. Our cohort consisted of 1310 patients with aortic stenosis, of whom 585 underwent isolated SAVR, 518 had SAVR+CABG and 207 underwent TAVI. The median costs for the index hospitalisation for isolated SAVR were $21 811 (IQR $18 148-$30 498), while those for SAVR+CABG were $27 256 (IQR $21 741-$39 000), compared with $42 742 (IQR $37 295-$56 196) for TAVI. For SAVR, the major patient-level drivers of costs were age >75 years, renal dysfunction and active endocarditis. For TAVI, chronic lung disease was a major patient-level driver. Procedural drivers of cost for TAVI included a non-transfemoral approach. A prolonged intensive care unit stay was associated with increased costs for all procedures. We found wide variation in healthcare costs for SAVR compared with TAVI, with different patient-level drivers as well as potentially modifiable procedural factors. These highlight areas of further study to optimise healthcare delivery.


Preconception Counseling: Identifying Ways to Improve Services.
Objective The aim of this retrospective study was to evaluate the maternal conditions for which preconception services are provided and the routine services and recommendations offered through the Maternal Fetal Medicine group at the University of Colorado (CU). The study sought to determine how services and recommendations differ by maternal condition, demographics, and reproductive health history. Materials and Methods Charts of patients who received preconception counseling through the CU MFM department during 2018 were reviewed to evaluate maternal conditions and the type of counseling patients received. Patients were grouped by their referral reason and subsequently by counseling recommendations to either proceed with immediate conception, defer immediate conception pending completion of further recommendations or to not conceive. Results Of the fifty-nine patients referred to preconception counseling, 52% ( n = 31) of the women were referred for maternal disease, 40% ( n = 24) for infertility, 32% ( n = 19) for previous poor obstetric outcomes, 30% ( n = 18) for advanced maternal age and finally, 15% ( n = 9) for gynecologic anatomic abnormalities. Conclusion During the initial evaluation, 58% ( n = 34) of patients were determined to have no concern for immediate conception while 7% ( n = 4) were ultimately advised to not conceive. Using this data, we identified areas of preconception counseling that standardization will improve by ensuring patients receive comparable services and advice.


[SEPTIC CARDIOMYOPATHY].
Septic cardiomyopathy is a reversible myocardial dysfunction in patients with sepsis. Depression in myocardial contractility is detected in more than 40% of patients with severe sepsis or septic shock. Sepsis-induced myocardial dysfunction (SIMD) is one of the main predictors of poor outcome in patients with sepsis. Mortality rate in patients with sepsis and SIMD is 70%-90%, while it is only 20% in patients without SIMD. SIMD is characterized by ventricular dilatation, decreased ejection fraction, less response to fluid replacement and catecholamines. It is reversible within 7-10 days. Many extracellular and intracellular mechanisms and mediators included in the regulation of the heart muscle cell contraction may contribute to septic cardiomyopathy. The underlying cause is disorder in communication between the intracellular contractile apparatus and extracellular matrix, resulting in attenuation of the myocardial contraction. Hemodynamic monitoring, ECG, transthoracic and transesophageal echocardiography, and various laboratory tests are used in the diagnostic work-up. There are several therapeutic interventions such as infection control, optimization of hemodynamic parameters, adequate volume resuscitation, inotropic drugs, transfusion of blood derivatives, and statins. However, for now, there is no efficient therapy for septic cardiomyopathy. The management of SIMD includes cardio-protective therapy, etiologic treatment of sepsis and septic shock, and supportive measures.


Spondyloepiphyseal Dysplasia Congenita: A Rare Cause of Respiratory Distress.
Spondyloepiphysal dysplasia (SED) is an inheritable dysplasia of the bone due to a defect in collagen. It has a prevalence of 3.4 per million. It has two important types, congenita and tarda, which are differentiated by the age presentation and heritage mode. SED congenita can present a significant reduction in the upper segment to a lower segment ratio. Collagen mutation results in abnormal growth and development of spine and limb bones. The complex pattern of craniofacial anomalies is due to defective ossification and connective tissue problem. We here present the case of a three-hour-old girl with a short trunk and craniofacial anomalies that brought in respiratory distress to the neonatal intensive care unit. This condition is rare and thus poses a major diagnostic challenge at an early stage.


The norwegian version of the psoriasis disability index--a validation and reliability study.
The aim of this study was to translate the Psoriasis Disability Index (PDI) into Norwegian and validate it in a Norwegian setting. The PDI is a measure that was developed to assess the impact of psoriasis on the patient's life. Two hundred and eighty-two patients with psoriasis were included in the study (80% outpatients, and 20% hospitalized). Face and content validity were assessed as satisfactory. The PDI seems to capture issues of importance to patients. The results indicate that the PDI does not capture a unidimensional concept. A factor analysis (principal component with orthogonal rotation) resulted in three factors (physical, social, and hygienic) that were substantially different. All three factors had satisfactory internal consistency. Altogether they explained 58% of the variance. In addition, there were differing patterns of correlations with external criteria, such as dimensions of SF-36, as well as with sex, age, and education. The PDI has been found to have acceptable reliability in this study. However, further validation is necessary to estimate the sensitivity to change.


Intraocular pressure and the intrastromal corneal ring.
The intrastromal corneal ring is a refractive surgery device placed in the peripheral cornea at 2/3 depth, and it has the potential to correct both myopia and hyperopia. This study examined whether intraocular pressure (IOP) could be accurately measured with the ring in place and whether intraocular pressure was altered as a result of surgery. Fifteen eye bank eyes were attached to a manometric device to control pressure (10 to 40 mm Hg) which was measured over the range before and after placement of the ring with a pneumotonometer. A paired t-test showed no significant difference in pressure, pre- vs postoperative. To determine the effect of the ring on IOP in vivo, ring implantation was performed on 10 rabbit eyes and pressure measured before and after surgery. At 24 and 48 hours postoperatively, there was no significant change in IOP (3 +/- 2 mm Hg, P greater than .05, and 9 +/- 8 mm Hg, P greater than .20 respectively) and facility of outflow calculated from tonography showed no significant change.


Early treatment of Class II, division 1 malocclusion--comparison of alternative treatment modalities.
The purpose of this paper was to compare the findings from three randomized clinical trials that investigated alternative treatments of Class II, division 1 malocclusion in young children. The trials were conducted at the University of North Carolina, the University of Florida, and the University of Pennsylvania. The appliances investigated in each center were a functional appliance versus a headgear. Variations in the specific aims and the working hypotheses were noted. The types of appliances, length of treatment, and methods of evaluation were also different. A general comparison of selected clinically relevant findings reveals similarities and differences in conclusions, but underlines the importance of assessing each study on the basis of its original hypothesis. The separate and combined contribution of these studies to the state of knowledge and research is discussed.


Properties of Bacillus cereus hemolysin II: a heptameric transmembrane pore.
The gene encoding hemolysin II (HlyII) was amplified from Bacillus cereus genomic DNA and a truncated mutant, HlyII(DeltaCT), was constructed lacking the 94 amino acid extension at the C terminus. The proteins were produced in an E. coli cell-free in vitro transcription and translation system, and were shown to assemble into SDS-stable oligomers on rabbit erythrocyte membranes and liposomes. The hemolytic activity of HlyII was measured with rabbit erythrocytes yielding an HC(50) value of 1.64 ng mL(-1), which is over 15 times more potent than staphylococcal alpha-hemolysin. HlyII(DeltaCT) was about eight times less potent than HlyII in this assay. Limited proteolysis of the oligomers formed by HlyII and HlyII(DeltaCT) on red cell membranes showed that the C-terminal extension is sensitive to digestion, while HlyII(DeltaCT) is protease resistant and migrates with an electrophoretic mobility similar to that of digested HlyII. HlyII forms moderately anion selective, rectifying pores (I(+80)/I(-80) = 0.57, 1 M KCl, pH 7.4) in planar lipid bilayers of diphytanoylphosphatidylcholine with a unitary conductance of 637 pS (1 M KCl, 5 mM HEPES, pH 7.4) and exhibits no gating over a wide range of applied potentials (-160 to +160 mV). In addition, it was demonstrated that HlyII forms a homoheptameric pore by using gel shift electrophoresis aided by a genetically encoded oligoaspartate tag. Although they share limited primary sequence identity (30%), these data confirm that HlyII is a structural and functional homolog of staphylococcal alpha-hemolysin.


The nuclear factor of activated T cells (NFAT) transcription factor NFATp (NFATc2) is a repressor of chondrogenesis.
Nuclear factor of activated T cells (NFAT) transcription factors regulate gene expression in lymphocytes and control cardiac valve formation. Here, we report that NFATp regulates chondrogenesis in the adult animal. In mice lacking NFATp, resident cells in the extraarticular connective tissues spontaneously differentiate to cartilage. These cartilage cells progressively differentiate and the tissue undergoes endochondral ossification, recapitulating the development of endochondral bone. Proliferation of already existing articular cartilage cells also occurs in some older animals. At both sites, neoplastic changes in the cartilage cells occur. Consistent with these data, NFATp expression is regulated in mesenchymal stem cells induced to differentiate along a chondrogenic pathway. Lack of NFATp in articular cartilage cells results in increased expression of cartilage markers, whereas overexpression of NFATp in cartilage cell lines extinguishes the cartilage phenotype. Thus, NFATp is a repressor of cartilage cell growth and differentiation and also has the properties of a tumor suppressor.


Osteoporosis Is Associated With High Risk for Coronary Heart Disease: A Population-Based Cohort Study.
We employed a population-based cohort sample to explore the risk of coronary heart disease (CHD) in relation to osteoporosis in an Asian population.We designed a retrospective population-based cohort study from 2000 to 2010 with data obtained from Taiwan's Longitudinal Health Insurance Database. A total of 19,456 patients aged 45 years or older who had no history of CHD and had a diagnosis of osteoporosis were identified as the osteoporosis cohort. The patients in the comparison cohort were randomly selected and frequency matched according to age, sex, and year of index date at a 1:1 ratio. Both cohorts were followed from the index date until a new diagnosis of CHD was made. Baseline variables, comorbidities, and bisphosphonate and estrogen prescriptions were collected.The overall incidence of CHD was 23.5 (per 1000 person-years) for the osteoporosis cohort and 16.7 for the comparison cohort, with a mean follow-up of 6.54 years and 6.63 years, respectively. The hazard ratio (HR) for developing CHD during follow-up was 1.30 (95% confidence interval [CI], 1.23-1.38) for the osteoporosis cohort compared with the comparison cohort after adjusting for age, sex, comorbidities, and estrogen medication. Patients with osteoporosis who received treatment with bisphosphonates or with both bisphosphonates and estrogen exhibited a significantly lower risk for CHD (adjusted HR = 0.37 and 0.23) than those who did not receive either of these 2 medications.The results support an association between osteoporosis and CHD in Asian population.


Efficiency of an Online Health-Promotion Program in Individuals with At-Risk Mental State during the COVID-19 Pandemic.
Mental health issues caused by the COVID-19 pandemic greatly impact people's daily lives. Individuals with an at-risk mental state are more vulnerable to mental health issues, and these may lead to onset of full psychotic illnesses. This study aimed to develop and evaluate an online health-promotion program for physical and mental health of the individuals with at-risk mental state during the COVID-19 pandemic. A single group study with pre- and post-tests was conducted in 39 young adults with at-risk mental state. The participants were provided with the online health-promotion program after completing the pretest. Via social media, the online counseling program released one topic of material (about 15-20 min) every two weeks and provided interactive counseling for specific personal health needs on the platform. Study questionnaires, physiological examination, and blood serum examination were completed at both pre- and post-tests. The participants showed significant improvements in mental risk, anxiety, and physical activity after participating in the program. Furthermore, those who did not complete the program had significantly more severe negative symptoms. These results imply that the online health-promotion program is effective and accessible under certain barriers such as the COVID-19 pandemic, but not for individuals with higher risk of more negative mental health symptoms.


[Nitrogen retention in germ-free and conventional mice reared on an antigen-free diet and the significance of the appearance of protein nitrogen in their feces].
The nutritional state of animals removed from as much antigenic stimuli as possible--germ-free mice on an antigen-free liquid diet--was compared with that of conventional mice through assessment of their protein metabolism. Both the germ-free and conventional mice reared on the antigen-free liquid diet for 7 weeks exhibited relatively stable body weight throughout the experimental period. Although the nitrogen retention rate was generally higher for the conventional mice, even in the germ-free mice with the exception of one observation in a male, positive nitrogen retention rates were observed, and this suggests nutritional adequacy of the diet. The amount of protein-nitrogen excreted in the feces due to the physiological processes, such as the digestive tract cell turnover, digestive juice secretions, etc, (4.2-5.3 mg/mouse/week), and the amount that was influenced by the presence of intestinal bacteria and due to bacterial protein per se (2.3-4. 4 mg /mouse/week) could be estimated through the comparison of the fecal protein values obtained from germ-free and conventional mice reared on the antigen-free liquid diet.


Lisfranc fractures.
Injuries of the tarsometatarsal, or Lisfranc, joint are rarely seen. Lisfranc fractures and fracture dislocations are among the most frequently misdiagnosed foot injuries in the emergency department. A misdiagnosed injury may have severe consequences including chronic pain and loss of foot biomechanics. Evaluation of a foot injury should include a high level of suspicion of a Lisfranc injury, and a thorough work-up is needed for correct diagnosis.


Vitamin D Enhanced the Osteogenic Differentiation of Cell Spheroids Composed of Bone Marrow Stem Cells.
Background and Objectives: Vitamin D is a bone modulator widely used in regenerative medicine. This study aimed to analyze the effects of vitamin D on the osteogenic differentiation and mineralization of human mesenchymal stem cells. Materials and Methods: Spheroids were fabricated using human bone marrow-derived stem cells, and were cultured in the presence of vitamin D at concentrations of 0, 0.1, 1, 10, and 100 nM. Stem cell spheroids were fabricated and the morphological evaluation was conducted on days 1, 3, 7 and 14. Determination of qualitative cellular viability was performed with Live/Dead Kit assay on days 1 and 7. Quantitative cellular viability was evaluated with Cell Counting Kit-8 on days 1, 3, 7, and 14. To analyze the osteogenic differentiation of cell spheroids, alkaline phosphatase activity assays were performed with commercially available kit on days 7 and 14. Real-time polymerase chain reaction was used to determine the expression levels of RUNX2, BSP, OCN, and COL1A1 on days 7 and 14. Results: The stem cells produced well-formed spheroids, and addition of vitamin D did not result in any noticeable changes in the shape. The addition of vitamin D did not significantly change the diameter of the spheroids at 0, 0.1, 1, 10, or 100 nM concentrations. Quantitative cell viability results from days 1, 3, 7 and 14 showed no significant difference between groups (p > 0.05). There was significantly higher alkaline phosphatase activity in the 0.1 nM group when compared with the control group on day 14 (p < 0.05). Real-time polymerase chain reaction results demonstrated that the mRNA expression levels of RUNX2, OCN, and COL1A1 were significantly increased when vitamin D was added to the culture. Conclusions: Based on these findings, we concluded that vitamin D could be applied to the increased osteogenicity of stem cell spheroids.


Mitochondrial Dysfunction, Macrophage, and Microglia in Brain Cancer.
Glioblastoma (GBM) is the most common malignant brain cancer. Increasing evidence suggests that mitochondrial dysfunction plays a key role in GBM progression as mitochondria is essential in regulating cell metabolism, oxidative stress, and cell death. Meanwhile, the immune microenvironment in GBM is predominated by tumor-associated macrophages and microglia (TAM), which is a heterogenous population of myeloid cells that, in general, create an immunosuppressive milieu to support tumor growth. However, subsets of TAMs can be pro-inflammatory and thereby antitumor. Therapeutic strategies targeting TAMs are increasingly explored as novel treatment strategies for GBM. The connection between mitochondrial dysfunction and TAMs phenotype in the tumor microenvironment is unclear. This review aims to provide perspectives and discuss possible molecular mechanisms mediating the interplay between glioma mitochondrial dysfunction and TAMs phenotype in shaping tumor immune microenvironment.


An electrostatic autoresonant ion trap mass spectrometer.
A new method for ion extraction from an anharmonic electrostatic trap is introduced. Anharmonicity is a common feature of electrostatic traps which can be used for small scale spatial confinement of ions, and this feature is also necessary for autoresonant ion extraction. With the aid of ion trajectory simulations, novel autoresonant trap mass spectrometers (ART-MSs) have been designed based on these very simple principles. A mass resolution approximately 60 is demonstrated for the prototypes discussed here. We report also on the pressure dependencies, and the (mV) rf field strength dependencies of the ART-MS sensitivity. Importantly the new MS designs do not require heavy magnets, tight manufacturing tolerances, introduction of buffer gases, high power rf sources, nor complicated electronics. The designs described here are very inexpensive to implement relative to other instruments, and can be easily miniaturized. Possible applications are discussed.


What is the purpose of launching the World Journal of Psychiatry?
The first issue of World Journal of Psychiatry (WJP), whose preparatory work was initiated on May 18, 2011, will be published on December 31, 2011. The WJP Editorial Board has now been established and consists of 103 distinguished experts from 32 countries. Our purpose of launching WJP is to publish peer-reviewed, high-quality articles via an open-access online publishing model, thereby acting as a platform for communication between peers and the wider public, and maximizing the benefits to editorial board members, authors and readers.


[Ventricular assist system].
Despite the recent remarkable advances in the medical treatment for severe end-stage heart failure, we still need a more powerful therapy to save patients presenting with cardiogenic shock or progressive cardiac deterioration. The implantation of ventricular assist system (VAS) is one of the available strategies in such patients and it has been used as a bridge to recovery or a bridge to transplantation. Because of the severe shortage of brain -dead donors, the role of VAS is now expanding into an alternative to transplantation, which is called a destination therapy. This review summarizes the current application and the future direction of VAS therapy for end -stage heart failure in Japan.


Transport mechanisms for long-chain polyunsaturated fatty acids in the human placenta.
To understand the placental role in the processes responsible for the preferential accumulation of maternal long-chain polyunsaturated fatty acids (LCPUFAs) in the fetus, we investigated fatty acid uptake and metabolism in the human placenta. A preference for LCPUFAs over nonessential fatty acids has been observed in isolated human placental membranes as well as in BeWo cells, a human placental choriocarcinoma cell line. A placental plasma membrane fatty acid binding protein (p-FABP(pm)) with a molecular mass of approximately 40 kDa was identified. The purified p-FABP(pm) preferentially bound with essential fatty acids (EFAs) and LCPUFAs over nonessential fatty acids. Oleic acid was taken up least and docosahexaenoic acid (DHA) most by BeWo cells, whereas no such discrimination was observed in HepG2 liver cells. Studies on the distribution of radiolabeled fatty acids in the cellular lipids of BeWo cells showed that DHA is incorporated mainly into the triacylglycerol fraction, followed by the phospholipid fraction; the reverse is true for arachidonic acid (AA). The greater cellular uptake of DHA and its preferential incorporation into the triacylglycerol fraction suggests that both uptake and transport modes of DHA by the placenta to the fetus are different from those of AA. p-FABP(pm) antiserum preferentially decreased the uptake of LCPUFAs and EFAs by BeWo cells compared with preimmune serum. Together, these results show the preferential uptake of LCPUFAs by the placenta that is most probably mediated via the p-FABP(pm).


Feasibility and acceptance of telemedicine for wound care in patients with chronic leg ulcers.
We examined the feasibility and acceptance of teledermatology for wound management of patients with chronic leg ulcers by home-care nurses. Forty-one chronic leg ulcers of different origin in 14 patients were included. After an initial in-person visit in which leg ulcers were assessed and classified, and underlying diseases noted, follow-up visits were done by home-care nurses. Once a week 1-4 digital images of the wound and surrounding skin and relevant clinical information were transmitted via a secure Website to an expert at the wound care centre. The experts provided an assessment of wound status and therapeutic recommendations. In 89% of the 492 teleconsultations, the quality of images was sufficient or excellent and the experts were confident giving therapeutic recommendations. Treatment modalities were changed or adapted in one-third of the consultations. There was a significant decrease in visits to a general physician or the wound care centre. The acceptance of teledermatology was high in patients, home-care nurses and wound experts. Teledermatology offers great potential for chronic wound care and seems to be accepted both by patients and health-care persons.


[Risk factors in the development of bleeding peptic ulcer].
Gastric or duodenal peptic ulcer is the most common cause of bleeding from upper parts of the alimentary tract. Although there is a great number of these patients in the clinical practice, there are some contradictory characteristics in regard to the age of patient, localization of ulcer, the diameter of ulcer and Helicobacter pylori infection as possible risk factors in development of bleeding peptic ulcer. The aim of this work is evaluation of risk factors in our patients. During this research we examened two groups of patients: a) first group consisted of patients with acute gastric or duodenal bleeding peptic ulcer, b) the second group consisted of patients without peptic ulcer bleeding. In both groups of patients we examined the most common risk factors for development of bleeding. This research took place in the Clinic for Surgery "Dr Dragisa Misović" in the period from January to December 1997. In both groups we had male predominance. Patients with bleeding peptic ulcers are statistically older when compared with the non-bleeding group (52.2 +/- 7.3:65.3 +/- 8.1). In both groups the anterior wall of the duodenum is the most common localization. In the group of bleeding ulcers we had high frequency of patients with localization of ulcers in the back wall of the duodenal bulb (20%). In this group of patients there was a high percentage of penetrating ulcers (62.5%) with active arterial bleeding (Forrest I a). Ulcers on the front wall of duodenal bulb and in small bend of stomach, as most common (over 50%), gave small peptic ulcers (under l cm) with capillary bleeding (oozing-Forrest I b) without haemodynamic complications. The presence of Helicobacter pylori infection is statistically significantly higher in the group of patients with bleeding peptic ulcers. The age of patients and localization of ulcer are very important and well known risk factors for development of bleeding peptic ulcer. However, in the last ten years Helicobacter pylori infection has become one of the most important risk factors. All Helicobacter pylori positive patients were treated with three component eradicational therapy for Helicobacter pylori. In this way we restricted the number of recurrent bleeding. In our opinion the age of patient, localization of ulcer, diameter and Helicobacter pylori infection are very important risk factors for development of bleeding peptic ulcer.


Counselling, care in infertility: the ethic of care.
Infertility is a health-care problem which has very definite physiological, psychological and social implications. Infertile couples are continually reminded of their plight--the structure of society is based on the family unit; simple activities such as shopping are a constant reminder, the shops being geared to the family; the neighbours fill their cars with all the paraphernalia which accompanies children--the stigma of infertility often leads to mental disharmony, marital difficulties, divorce, and in some cultures to ostracism. The suffering experienced by infertile people is very real. We need to remind ourselves that we are treating 'people who are infertile' rather than 'infertility'. Our care goes beyond their physical treatment--their stresses and strains are our concern and we must be careful not to add additional stress to their existing problems. Successful treatment can transform their lives: 'They are bright, healthy, beautiful children--a dream come true. Our lives are transformed and complete. Thank you a million times.' Failure after years of trying is all the more painful. The availability of effective, informed, independent and involved counselling is essential.


Further evidence of Mycobacterium tuberculosis in the sputum of culture-negative pulmonary tuberculosis suspects using an ultrasensitive molecular assay.
Rapid diagnosis of pulmonary tuberculosis (TB) is critical to TB control. However, many patients with paucibacillary TB disease remain undiagnosed. Current TB elimination goals require new tools to diagnose early disease. We evaluated performance of the Totally Optimized PCR (TOP) TB assay, a novel ultrasensitive molecular test. We assessed analytical specificity against nontuberculous mycobacteria (NTM), and estimated the diagnostic accuracy of TOP in a pilot study in Brazil (n = 46) and a cross-sectional study in Boston (n = 60). We compared TOP results to culture and a composite reference standard (CRS). TOP exhibited no cross-reactivity against NTM. We tested 132 respiratory specimens from 106 patients with suspected pulmonary TB. The pilot demonstrated feasibility and 100% (95% CI 85-100) sensitivity in predominantly smear-positive specimens; TOP's specificity against solid media culture was low (58%, 37-77) but improved against a CRS (93%, 68-100). Similarly, when using the CRS in the Boston study, TOP (88%, 1-99) had greater sensitivity than solid or liquid media culture (25%, 3-65) and similar specificity (both 100%, 93-100). The TOP assay enables detection of M. tuberculosis in culture-negative paucibacillary disease. While the use of TOP for the diagnosis of paucibacillary disease will require further clinical validation, its high sensitivity indicate a more immediate utility as a rule out TB test.