Effect of stabilization splint therapy on pain during chewing in patients suffering from myofascial pain.
Masticatory myofascial pain (MFP) condition is a musculoskeletal disorder that compromises the functional capacities of the masticatory system. As such, the incorporation of an intensive chewing test as a discriminatory exercise for the diagnosis of this condition and evaluation of treatment success has considerable potential. Various splint designs have been used successfully, which have posed a question of whether the therapeutic effect of the splint is a placebo or has some other curative properties. The purpose of this study was to evaluate the efficacy of the stabilization appliance to reduce signs and symptoms in MFP patients and to compare the pain experience during the chewing test between two groups of patients, with and without splints. Myofascial pain patients (n = 37) who reported exacerbation of pain in function participated in the study. Patients perfomed a 9-min chewing test, followed by 9-min rest and marked their pain intensity on a visual analogue scale every 3 min. Of the 37 patients, 21 received a stabilization flat occlusal splint for night use and 16 were equally monitored clinically without a splint. At the end of 8 weeks, a second clinical examination and chewing test were performed. Student's t-test was used to analyse differences between study groups. Analysis of variance and covariance (ancova) with repeated measures was applied to analyse the effect of treatment. Level of pain at baseline prior to the chewing test (P0) was introduced as a co-variant. At baseline both groups showed relatively high scores of pain intensity and did not show any significant differences among the collected variables. At the end of the experiment, the splint group had a statistically significant reduction in pain intensity, in mean muscle sensitivity to palpation and in the pain experience during the chewing test compared with no change in the controls. A stabilization splint has a therapeutic value beyond its placebo effects. Thus, it should be an integral part of the treatment modalities in MFP disorder patients. An intensive chewing test is an effective tool to evaluate the treatment modality efficacy in MFP patients.


Perfluoroalkylated substances in the global tropical and subtropical surface oceans.
In this study, perfluoroalkylated substances (PFASs) were analyzed in 92 surface seawater samples taken during the Malaspina 2010 expedition which covered all the tropical and subtropical Atlantic, Pacific and Indian oceans. Nine ionic PFASs including C6-C10 perfluoroalkyl carboxylic acids (PFCAs), C4 and C6-C8 perfluoroalkyl sulfonic acids (PFSAs) and two neutral precursors perfluoroalkyl sulfonamides (PFASAs), were identified and quantified. The Atlantic Ocean presented the broader range in concentrations of total PFASs (131-10900 pg/L, median 645 pg/L, n = 45) compared to the other oceanic basins, probably due to a better spatial coverage. Total concentrations in the Pacific ranged from 344 to 2500 pg/L (median = 527 pg/L, n = 27) and in the Indian Ocean from 176 to 1976 pg/L (median = 329, n = 18). Perfluorooctanesulfonic acid (PFOS) was the most abundant compound, accounting for 33% of the total PFASs globally, followed by perfluorodecanoic acid (PFDA, 22%) and perfluorohexanoic acid (PFHxA, 12%), being the rest of the individual congeners under 10% of total PFASs, even for perfluorooctane carboxylic acid (PFOA, 6%). PFASAs accounted for less than 1% of the total PFASs concentration. This study reports the ubiquitous occurrence of PFCAs, PFSAs, and PFASAs in the global ocean, being the first attempt, to our knowledge, to show a comprehensive assessment in surface water samples collected in a single oceanic expedition covering tropical and subtropical oceans. The potential factors affecting their distribution patterns were assessed including the distance to coastal regions, oceanic subtropical gyres, currents and biogeochemical processes. Field evidence of biogeochemical controls on the occurrence of PFASs was tentatively assessed considering environmental variables (solar radiation, temperature, chlorophyll a concentrations among others), and these showed significant correlations with some PFASs, but explaining small to moderate percentages of variability. This suggests that a number of physical and biogeochemical processes collectively drive the oceanic occurrence and fate of PFASs in a complex manner.


FAM13A is associated with non-small cell lung cancer (NSCLC) progression and controls tumor cell proliferation and survival.
Genome-wide association studies (GWAS) associated Family with sequence similarity 13, member A (FAM13A) with non-small cell lung cancer (NSCLC) occurrence. Here, we found increased numbers of FAM13A protein expressing cells in the tumoral region of lung tissues from a cohort of patients with NSCLC. Moreover, FAM13A inversely correlated with CTLA4 but directly correlated with HIF1α levels in the control region of these patients. Consistently, FAM13A RhoGAP was found to be associated with T cell effector molecules like HIF1α and Tbet and was downregulated in immunosuppressive CD4+CD25+Foxp3+CTLA4+ T cells. TGFβ, a tumor suppressor factor, as well as siRNA to FAM13A, suppressed both isoforms of FAM13A and inhibited tumor cell proliferation. RNA-Seq analysis confirmed this finding. Moreover, siRNA to FAM13A induced TGFβ levels. Finally, in experimental tumor cell migration, FAM13A was induced and TGFβ accelerated this process by inducing cell migration, HIF1α, and the FAM13A RhoGAP isoform. Furthermore, siRNA to FAM13A inhibited tumor cell proliferation and induced cell migration without affecting HIF1α. In conclusion, FAM13A is involved in tumor cell proliferation and downstream of TGFβ and HIF1α, FAM13A RhoGAP is associated with Th1 gene expression and lung tumor cell migration. These findings identify FAM13A as key regulator of NSCLC growth and progression.


Proteomics study on the protective mechanism of soybean isoflavone against inflammation injury of bovine mammary epithelial cells induced by Streptococcus agalactiae.
This study aimed to verify the anti-inflammatory effect of soybean isoflavones (SI) on the inflammatory response induced by Streptococcus agalactiae (S. agalactiae) of bovine mammary epithelial cells (bMECs) and to elucidate its possible mechanism. BMECs were pretreated with SI of different concentrations (20, 40, 60, 80, 100 μg/mL) for 0.5, 3, 6, 9, 12, 15, 18, 24 h. And then, S. agalactiae was used to infect bMECs for 6 h (MOI = 50:1) to establish the inflammation model. Cell viability, growth curves of S. agalactiae, cytotoxicity, and S. agalactiae invasion rate were determined. A proteomics technique was used to further detect differential proteins and enrichment pathways. SI (40 μg/mL) improved the viability of bMECs at 12 h (p < 0.05) and 60 and 80 μg/mL of SI greater (p < 0.01). Moreover, 60 μg/mL of SI protects cells from bacterial damage (p < 0.05). SI could inhibit S. agalactiae growth and internalization into bMECs in a time- and dose-dependent manner. In addition, proteomics results showed that 133 proteins were up-regulated and 89 proteins were down-regulated significantly. The differentially significantly expressed proteins (DSEPs) were mainly related to cell proliferation, differentiation, apoptosis, and migration. GO annotation showed that 222 DSEPs were divided into 23 biological processes (BP) terms, 14 cell components (CC) terms, and 12 molecular functions (MF) terms. DSEPs were significantly enriched in 10 pathways, of which the immune pathway was the main enrichment pathway.


Psychopathy, attention and emotion.
Psychopathy is a developmental disorder marked by emotional hypo-responsiveness and an increased risk for antisocial behavior. Influential attention-based accounts of psychopathy have long been made; however, these accounts have made relatively little reference to general models of attention in healthy individuals. This review has three aims: (1) to summarize current cognitive neuroscience data on differing attentional systems; (2) to examine the functional integrity of these attentional systems in individuals with psychopathy; and (3) to consider the implications of these data for attention and emotion dysfunction accounts of psychopathy.


Tumors sound the alarmin(s).
Recent evidence suggests that inflammatory molecules play critical roles in the development and progression of numerous tumors. However, one specific group of inflammatory molecules whose importance has been established in host immune responses, termed alarmins, has been largely overlooked in cancer biology. The function of several alarmins-including the defensins, LL-37, and HMGB1-in tumor development, progression, or suppression is discussed here. Taken together, these studies indicate that alarmins represent potential new targets for manipulation in a variety of tumors.


Pharmacological and genetical evidence supporting nitric oxide requirement for 2,4-epibrassinolide regulation of root architecture in Arabidopsis thaliana.
Brassinosteroids (BRs) regulate various physiological processes, such as tolerance to stresses and root growth. Recently, a connection was reported between BRs and nitric oxide (NO) in plant responses to abiotic stress. Here we present evidence supporting NO functions in BR signaling during root growth process. Arabidopsis seedlings treated with BR 24-epibrassinolide (BL) show increased lateral roots (LR) density, inhibition of primary root (PR) elongation and NO accumulation. Similar effects were observed adding the NO donor GSNO to BR-receptor mutant bri1-1. Furthermore, BL-induced responses in the root were abolished by the specific NO scavenger c-PTIO. The activities of nitrate reductase (NR) and nitric oxide synthase (NOS)-like, two NO generating enzymes were involved in BR signaling. These results demonstrate that BR increases the NO concentration in root cells, which is required for BR-induced changes in root architecture.


Management of antimicrobial use in the intensive care unit.
Indications for the use of antimicrobials in critically ill patients are similar to those for other hospitalised patients. However, the selection of agents depends on the particular characteristics of patients in the intensive care unit (ICU), the form of presentation of infection, the type of infection and the bacteriological features of the causative pathogens. The use of antimicrobials in patients admitted to medical-surgical ICUs varies between 33 and 53%. The selection of empirical antimicrobials to be included in treatment protocols of the most common infections depends on the strong interrelationship between patient characteristics, predominant pathogens in each focus. and antimicrobials used for treatment. Epidemiological studies carried out in the past have identified the microorganisms most frequently responsible for community-acquired and nosocomial infections in patients admitted to ICUs. Susceptibility to antimicrobial agents may be different between each geographical area, between each hospital and even within the same hospital service. In addition, susceptibility patterns may change temporarily in relation to the use of particular antimicrobials or in association with other unknown factors so that assessment of endemic antimicrobial resistance patterns is very useful in order to tailor the antimicrobial regimens of therapeutic protocols. Antimicrobial use should not be a routine procedure. The clinical course of the patient (an indicator of effectiveness) should be closely monitored as well as the possible appearance of adverse effects and/or multiresistant pathogens. Controls are based on the assessment of plasma drug concentrations and microbiological surveillance to detect the presence of multiresistant strains or new antibacterial-resistant pathogens. Prevention of the development of multiresistant pathogens is the main goal of the ICU antimicrobial policy. Although a series of general strategies to reduce the presence of multiresistant pathogens have been proposed, the implementation of these recommendations in ICUs requires the cooperation of a member of the intensive care team.


Inhibitory effects of steroidal timosaponins isolated from the rhizomes of Anemarrhena asphodeloides against passive cutaneous anaphylaxis reaction and pruritus.
To investigate the antiallergic effect of the rhizome of Anemarrhena asphodeloides (AA, family Liliaceae), which was found to inhibit the mouse passive cutaneous anaphylaxis (PCA) reaction induced by the antigen-immunoglobulin E (IgE) complex in preliminary experiments, main steroidal saponins, timosaponins AIII, BIII, and D, were isolated and their inhibitory effects against PCA reaction and scratching behaviors investigated in mice. Oral administration of three main steroidal sapogenins blocked the PCA reaction and scratching behaviors, timosaponin AIII was the most potent. However, intraperitoneal administration of timosaponin AIII showed weak inhibition. To understand its metabolism and antiallergic mechanism, timosaponin AIII was anaerobically incubated with human intestinal microflora to afford a main metabolite, sarsasapogenin. Intraperitoneal administration of sarsasapogenin inhibited allergic reaction more potently than timosaponin AIII. In addition, sarsasapogenin more potently inhibited degranulation and IL-4 protein expression of RBL-2H3 cells induced by IgE-antigen complex than timosaponin AIII. On the basis of these findings, antiallergic effect of AA may be due to those of its steroidal constituents, and that of timosaponin AIII may be activated by using intestinal microflora.


Site of action of chlorsulfuron: inhibition of valine and isoleucine biosynthesis in plants.
The sulfonylurea herbicide chlorsulfuron blocks the biosynthesis of the amino acids valine and isoleucine in plants. Addition of these two amino acids to excised pea root (Pisum sativum L. var Alaska) cultures incubated in the presence of chlorsulfuron completely alleviates herbicide-induced growth inhibition. The site of action of chlorsulfuron is the enzyme acetolactate synthase which catalyzes the first step in the biosynthesis of valine and isoleucine. This enzyme is extremely sensitive to inhibition by chlorsulfuron having I(50) values ranging from 18 to 36 nanomolar. In addition, acetolactate synthase from a wide variety of tolerant and sensitive plants species is highly sensitive to inhibition by chlorsulfuron.


Sieving coefficients for small solutes during experimental peritoneal dialysis in rats.
A single 4-hour experimental peritoneal dialysis was performed in 6 normal Sprague-Dawley rats to investigate sieving coefficients (S) for small solutes during peritoneal dialysis. A modified 3.86% Dianeal solution with approximately the same concentrations of urea, sodium, and potassium as in the rat plasma (isochratic solution) was used to avoid diffusion of investigated solutes and to achieve sufficient ultrafiltration. As a control, a 4-hour peritoneal dialysis in 7 normal Sprague-Dawley rats was performed using the conventional 3.86% Dianeal solution. The infusion volume was 30 ml. A dilution of radioiodinated serum albumin was used to determine the intraperitoneal dialysate volume. S was calculated (1) from the mass and volume balances for the initial 30 min of the exchange with the isochratic solution (SI, isochratic method) and (2) by using a membrane model based on the thermodynamic theory of mass transport (SM). The diffusive mass transport coefficient KBD for the solutes investigated was estimated using the membrane model. The SI values for urea, sodium, and potassium were similar with the isochratic solution. For urea and sodium, the S values were within the physiological range 0-1, whereas the S values for glucose were close to 0 and for potassium were negative. SM for glucose, urea, and sodium using the conventional solution did not differ from the values obtained with the isochratic solution; however, SM for potassium was significantly lower than with the isochratic solution. SI and SM for potassium and sodium were correlated. The KBD values for glucose, urea, and sodium using the isochratic solution did not differ from the values obtained with the conventional solution, whereas the KBD values for potassium were significantly higher with the isochratic solution as compared with the conventional solution. We conclude that the net sieving coefficients SI and SM for urea and sodium were lower than unity in the rats dialyzed with the two solutions and did not differ from the previously reported S values measured in continuous ambulatory peritoneal dialysis patients with the isochratic solution. However, the transport of potassium was abnormal with the isochratic solution, suggesting mechanisms other than passive diffusive and convective potassium transport.


Genomic and Epigenomic Landscape of Juvenile Myelomonocytic Leukemia.
Juvenile myelomonocytic leukemia (JMML) is a rare myelodysplastic/myeloproliferative neoplasm of early childhood. Most of JMML patients experience an aggressive clinical course of the disease and require hematopoietic stem cell transplantation, which is currently the only curative treatment. JMML is characterized by RAS signaling hyperactivation, which is mainly driven by mutations in one of five genes of the RAS pathway, including PTPN11, KRAS, NRAS, NF1, and CBL. These driving mutations define different disease subtypes with specific clinico-biological features. Secondary mutations affecting other genes inside and outside the RAS pathway contribute to JMML pathogenesis and are associated with a poorer prognosis. In addition to these genetic alterations, JMML commonly presents aberrant epigenetic profiles that strongly correlate with the clinical outcome of the patients. This observation led to the recent publication of an international JMML stratification consensus, which defines three JMML clinical groups based on DNA methylation status. Although the characterization of the genomic and epigenomic landscapes in JMML has significantly contributed to better understand the molecular mechanisms driving the disease, our knowledge on JMML origin, cell identity, and intratumor and interpatient heterogeneity is still scarce. The application of new single-cell sequencing technologies will be critical to address these questions in the future.


Measuring and monitoring illegal use of natural resources.
Illegal use of natural resources is a threat to biodiversity globally, but research on illegal activities has methodological challenges. We examined 100 studies that empirically identify targeted resources, techniques used to procure resources illegally, locations of illegal activities, characteristics of typical violators, incentives driving illegal use of resources, magnitude of the problem of illegal use (e.g., quantities used), or frequency of illegal activity. We based our evaluation of the methods used in these studies on their ability to provide these empirical data, relative labor demands, training and technology requirements, and levels of uncontrollable bias. We evaluated eight different methods: law-enforcement records, indirect observation, self-reporting, direct observation, direct questioning, randomized response technique (a survey method designed to improve accuracy of responses to sensitive questions), forensics, and modeling. Different situations favored different methods, each with distinct advantages and limitations. Six context-specific factors-location of resource use (in situ vs. ex situ), budget, technology and training capacity, ease of detection of illegal activity, scope of illegal activity (limited vs. widespread), and researchers' willingness to accept bias in results-help narrow the choice of methods. Several methodological concerns applied to any study of illegal resource use: regular monitoring can detect trends; modeling can incorporate sampling error and data uncertainties; researchers must manage levels of bias that vary between methods; triangulation of results from multiple methods can improve accuracy. No method is a panacea, but a combination of techniques can help address the lack of data on illegal activity. Researchers empirically compared results from different methods in only four studies, and no one has compared more than two methods simultaneously. Conservation would benefit from more research focused on: methods comparisons that include cost effectiveness, time efficiency, and statistical rigor; unique applications of the eight techniques currently in use; and testing of new methods.


UVB-induced cell death signaling is associated with G1-S progression and transcription inhibition in primary human fibroblasts.
DNA damage induced by ultraviolet (UV) radiation can be removed by nucleotide excision repair through two sub-pathways, one general (GGR) and the other specific for transcribed DNA (TCR), and the processing of unrepaired lesions trigger signals that may lead to cell death. These signals involve the tumor suppressor p53 protein, a central regulator of cell responses to DNA damage, and the E3 ubiquitin ligase Mdm2, that forms a feedback regulatory loop with p53. The involvement of cell cycle and transcription on the signaling to apoptosis was investigated in UVB-irradiated synchronized, DNA repair proficient, CS-B (TCR-deficient) and XP-C (GGR-deficient) primary human fibroblasts. Cells were irradiated in the G1 phase of the cell cycle, with two doses with equivalent levels of apoptosis (low and high), defined for each cell line. In the three cell lines, the low doses of UVB caused only a transient delay in progression to the S phase, whereas the high doses induced permanent cell cycle arrest. However, while accumulation of Mdm2 correlated well with the recovery from transcription inhibition at the low doses for normal and CS-B fibroblasts, for XP-C cells this protein was shown to be accumulated even at UVB doses that induced high levels of apoptosis. Thus, UVB-induced accumulation of Mdm2 is critical for counteracting p53 activation and apoptosis avoidance, but its effect is limited due to transcription inhibition. However, in the case of XP-C cells, an excess of unrepaired DNA damage would be sufficient to block S phase progression, which would signal to apoptosis, independent of Mdm2 accumulation. The data clearly discriminate DNA damage signals that lead to cell death, depending on the presence of UVB-induced DNA damage in replicating or transcribing regions.


Mitochondrial mislocalization underlies Abeta42-induced neuronal dysfunction in a Drosophila model of Alzheimer's disease.
The amyloid-beta 42 (Abeta42) is thought to play a central role in the pathogenesis of Alzheimer's disease (AD). However, the molecular mechanisms by which Abeta42 induces neuronal dysfunction and degeneration remain elusive. Mitochondrial dysfunctions are implicated in AD brains. Whether mitochondrial dysfunctions are merely a consequence of AD pathology, or are early seminal events in AD pathogenesis remains to be determined. Here, we show that Abeta42 induces mitochondrial mislocalization, which contributes to Abeta42-induced neuronal dysfunction in a transgenic Drosophila model. In the Abeta42 fly brain, mitochondria were reduced in axons and dendrites, and accumulated in the somata without severe mitochondrial damage or neurodegeneration. In contrast, organization of microtubule or global axonal transport was not significantly altered at this stage. Abeta42-induced behavioral defects were exacerbated by genetic reductions in mitochondrial transport, and were modulated by cAMP levels and PKA activity. Levels of putative PKA substrate phosphoproteins were reduced in the Abeta42 fly brains. Importantly, perturbations in mitochondrial transport in neurons were sufficient to disrupt PKA signaling and induce late-onset behavioral deficits, suggesting a mechanism whereby mitochondrial mislocalization contributes to Abeta42-induced neuronal dysfunction. These results demonstrate that mislocalization of mitochondria underlies the pathogenic effects of Abeta42 in vivo.


Giant cells lepromatous leprosy. Diffuse dermatitis with exuberant foreign body giant cells in treated lepromatous leprosy
Patients with lepromatous leprosy that have received treatment for many years usually get follow up biopsies for persistent skin lesions or positive bacilloscopy even if the values are lower than in the initial bacilloscopy. We report the case of a 48-year old woman with long-standing lepromatous leprosy of 15 years of evolution, with a bacterial index of 4 in the direct smear and the initial skin biopsy. The patient was treated with multidrug therapy for 32 months although the treatment recommended by the World Health Organization (WHO) is only for 12 months. A skin biopsy was taken to determine if there was an active disease. We observed a diffuse dermal inflammation with numerous foreign body giant cells and vacuolated macrophages (Virchow´s cells). These cells contained granular acid-fast material that was also positive with immunohistochemistry for BCG. There were fragmented bacilli and the BI was 2. These cells were also strongly positive for CD68. The biopsy was interpreted as a residual form of lepromatous leprosy that did not require further multidrug therapy. We have observed similar histological profiles in several cases. The lack of clinical data makes it a histological challenge. The accumulation of lipids in these giant cells is due to bacillary destruction and fusion of vacuolated macrophages. We discuss here the role of bacillary and host lipids in the pathogenesis of lepromatous leprosy. We concluded that there was no need to extend the 12-month multidrug therapy recommended by WHO.


Analysis of 20-Year Trends in Medicare Reimbursement for Reconstructive Microsurgery.
Microsurgery is being increasingly utilized across surgical specialties, including plastic surgery. Microsurgical techniques require greater time and financial investment compared with traditional methods. This study aimed to evaluate 20-year trends in Medicare reimbursement and utilization for commonly billed reconstructive microsurgery procedures from 2000 to 2019. Microsurgical procedures commonly billed by plastic surgeons were identified. Reimbursement data were extracted from The Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services for each current procedural terminology (CPT) code. All monetary data were adjusted for inflation to 2019 U.S. dollars. The average annual and total percentage changes in reimbursement were calculated based on these adjusted trends. To assess utilization trends, CMS physician/supplier procedure summary files were queried for the number of procedures billed by plastic surgeons from 2010 to 2018. After adjusting for inflation, the average reimbursement for all procedures decreased by 26.92% from 2000 to 2019. The greatest mean decrease was observed in CPT 20969 free osteocutaneous flaps with microvascular anastomosis (-36.93%). The smallest mean decrease was observed in repair of blood vessels with vein graft (-9.28%). None of the included procedures saw an increase in reimbursement rate over the study period. From 2000 to 2019, the adjusted reimbursement rate for all procedures decreased by an average of 1.35% annually. Meanwhile, the number of services billed to Medicare by plastic surgeons across the included CPT codes increased by 42.17% from 2010 to 2018. This is the first study evaluating 20-year trends in inflation-adjusted Medicare reimbursement and utilization in reconstructive microsurgery. Reimbursement for all included procedures decreased over 20% during the study period, while number of services increased. Increased consideration of these trends will be important for U.S. policymakers, hospitals, and surgeons to assure continued access and reconstructive options for patients.


Brain injury rehabilitation settings: a gold mine for student and staff learning.
This article explores cognitive, psychomotor, and affective learning relative to the professional development of senior nursing students and staff in a long-term brain injury rehabilitation setting. Valuable opportunities for learning exist in this environment. Nursing students acquire a much different perspective toward caring for patients in rehabilitation settings than in acute care; they also gain tremendous opportunities to strengthen the clinical judgement and psychomotor skills applicable to most clinical work environments following graduation. In addition, they assume professional attitudes toward and interest in caring for long-term brain-injured patients as they work closely with expert rehabilitation nurses. When staff nurses interact with students, they receive reciprocal benefits. Staff nurses profit by refining and broadening the scope of their own practice; they also develop a positive self-image and a feeling of pride in their work. More importantly, staff nurses in a long-term brain injury rehabilitation setting regain the feeling that their daily efforts are really worthwhile.


System of monitoring the environmental impact on population health of the Czech Republic.
The data collected in the System of monitoring the environmental impact on population health of the Czech Republic in 1994 and 1995 were obtained routinely and in a stabilized manner in six subsystems: health consequences and risks related to air pollution, drinking water quality, noise, human dietary exposure, human exposure to toxic pollutants from the environment and the monitoring of the health state and evaluation of selected indicators of demographic and health statistics. They represent a useful and comprehensive background for providing objective information on the health status of the Czech population and on pollution of different components of the environment in the Czech Republic to other countries in Europe and worldwide to facilitate their commercial and cultural contacts. The results of the calendar year 1995 show that no critical situation needing urgent countermeasures to be taken appeared in the localities monitored. However, some results are indicative of the necessity to take certain remedial measures to maintain all population exposure burdens as low as reasonably possible from the economical and social points of view. The set of problems was identified as important also in 1994. Generally, the limit values and exposure standards are exceeded only sporadically in some localities while for most contaminants monitored only very low values compared to the admissible limits can be found.


Granulomatous Lobular Mastitis: Antituberculous Treatment and Outcome in 22 Patients.
Granulomatous lobular mastitis (GLM) is a rare chronic inflammatory condition of the breast. The purpose of this study was to describe antituberculous treatment of GLM and the long-term follow-up outcome. This retrospective study included 22 patients who had been histopathologically diagnosed with GLM at the Second Hospital of Shandong University from January 2011 to March 2015. Clinical characteristics, ultrasonography and mammography findings, laboratory tests, treatment regimens, follow-up information, and recurrences were recorded. All patients were female with a median age of 29 (range 23-44) years. The most common symptom was a breast mass with or without pain. Large irregular hypoechoic masses could be found in the breast ultrasounds of 13 patients. All patients received triple antituberculous therapy. During a median follow-up period of 40 months, 3 patients were lost to follow-up; of the remaining 19 patients, 18 achieved clinical complete remission and no recurrences were observed. GLM is an unusual benign breast condition that mimics breast carcinoma in its clinical and imaging presentation. Antituberculous therapy seems to be an effective alternative option in the treatment of GLM.


Preparation and measurement of tunable high-power sub-Poissonian light using twin beams.
Widely frequency tunable bright sub-Poissonian field preparation has been experimentally achieved with quantum-correlated twin beams in the continuously variable regime. The noise of the sub-Poissonian field is reduced to more than 2 dB below the shot-noise level throughout the entire wavelength-tunable range of 7.4 nm. A maximum noise reduction of 45% (2.6 dB) is observed. The statistical distribution of a sub-Poissonian field is also obtained.


A Highly Triflated Rare-Earth Ion in [Eu(O3SCF3)8](5-).
The reaction of Eu2O3 with fuming nitric acid, trifluormethanesulfonic acid, and its anhydride in torch-sealed glass ampoules at 120 °C gave the europium compound (NO)5[Eu(O3SCF3)8] (orthorhombic, Fddd, Z = 16, a = 1932.69(4), b = 2878.44(7), c = 2955.12(7) pm, V = 16439.7(7) Å(3)). The compound exhibits the [Eu(O3SCF3)8](5-) anion showing for the first time a lanthanide ion that is exclusively coordinated by eight triflate anions. The anion has been further investigated by DFT calculations, which also allowed clear assignment of the vibrational spectra. Moreover, magnetochemical and luminescence measurements gave additional insight into the properties of this complex. The luminescence spectra revealed that the Eu(3+) ions are in a pseudo D4d symmetric environment.


An analysis of the mechanism by which cetiedil inhibits the Gardos phenomenon.
Energy depletion in the human erythrocyte causes a rise in intracellular calcium. This in turn accelerates the transmembrane movement of potassium and chloride, resulting in cell dehydration. This process, known as the Gardos phenomenon, is inhibited by cetiedil. The present study examines the mechanism by which cetiedil inhibits the Gardos phenomenon. The ability of cetiedil to retard the initial step in the Gardos phenomenon, a rise in intracellular calcium, was first tested. Cetiedil did not prevent calcium accumulation. Cetiedil's ability to inhibit anion movement was next evaluated, as cetiedil could appear to be blocking K movement when in fact it was preventing the movement of its accompanying anion. No inhibitory effect on anion movement was seen. Since cetiedil prevented neither calcium accumulation nor anion movement, it must inhibit the Gardos phenomenon by preventing the opening of the K-specific gate in the erythrocyte membrane. The fact that cetiedil's effect on the Gardos phenomenon could not be removed with repeated cell washing indicates that this effect is irreversible.


Statins and risk of new-onset diabetes mellitus: is there a rationale for individualized statin therapy?
Statins (hydroxymethylglutaryl-coenzyme-A reductase inhibitors) are first-line agents for the management of hyperlipidemia in patients at high risk of cardiovascular (CV) events, and are the most commonly prescribed CV drugs worldwide. Although safe and generally well tolerated, there is growing evidence to suggest that statins are associated with an elevated occurrence of new-onset diabetes mellitus (DM). Recent experimental and clinical data have prompted the US Food and Drug Administration to add information to statin labels regarding the increased risk of development of type 2 DM. The main purpose of this review is to critically discuss the clinical evidence regarding the association of statin use with new-onset DM, the CV benefit/risk ratio with statins, and the rationale for individualized statin therapy.


Univariate and Multivariate Analysis of Phosphorus Element in Fertilizers Using Laser-Induced Breakdown Spectroscopy.
Rapid detection of phosphorus (P) element is beneficial to the control of compound fertilizer production process and is of great significance in the fertilizer industry. The aim of this work was to compare the univariate and multivariate analysis of phosphorus element in compound fertilizers and obtain a reliable and accurate method for rapid detection of phosphorus element. A total of 47 fertilizer samples were collected from the production line; 36 samples were used as a calibration set, and 11 samples were used as a prediction set. The univariate calibration curve was constructed by the intensity of characteristic line and the concentration of P. The linear correlation coefficient was 0.854 as the existence of the matrix effect. In order to eliminate the matrix effect, the internal standardization as the appropriate methodology was used to increase the accuracy. Using silicon (Si) element as an internal element, a linear correlation coefficient of 0.932 was obtained. Furthermore, the chemometrics model of partial least-squares regression (PLSR) was used to analysis the concentration of P in fertilizer. The correlation coefficient was 0.977 and 0.976 for the calibration set and prediction set, respectively. The results indicated that the LIBS technique coupled with PLSR could be a reliable and accurate method in the quantitative determination of P element in complex matrices like compound fertilizers.


Endoscopic ultrasonography in patients with gastrinomas.
Placing the endoscopic ultrasound transducer in the descending duodenum, the duodenal bulb and the stomach, all the pancreas can be imaged. Endoscopic ultrasonography is a sophisticated imaging technique able to accurately diagnose and localize primary endocrine tumours of the pancreas (mostly insulinoma and gastrinoma) which may not be detectable with other imaging modalities. Furthermore, endoscopic ultrasonography-guided fine needle aspiration allows cytology and/or biopsy specimens to be obtained, that are crucial for clinicians in decision making. In the case of extrapancreatic endocrine tumours, which are often localized in the second and third part of the duodenum, endoscopic ultrasonography may have difficulty in localizing small and flat lesions. In this case, the initial step would be identification of duodenal nodules by duodenoscopy and thereafter, a catheter echoprobe can be inserted to identify the extent of submucosal lesion. Then gastroduodenal nodules found by endoscopy and confirmed by endoscopic ultrasonography can be removed endoscopically using the technique of mucosectomy. In the case of large pancreatic lesions, endoscopic tattoo with dye-India ink or methylene blue may become helpful for the surgeon to perform local resection via duodenostomy.


Can a humid storage environment of surgical instruments before reprocessing increase patient safety and durability of instruments?
National and international guidelines recommend reprocessing of medical instruments to commence as soon as possible post-surgery; furthermore, they recommend that transport and storage of surgical instruments postoperatively occurs in a moist, humid atmosphere. The concern is that a dry storage environment results in deterioration of instruments. To evaluate whether residual protein or corrosion is associated with storage environment (dry or humid), holding time or number of treatment cycles. The range of protein residue and corrosion were tested on surgical instruments contaminated with human blood amended Enterococcus faecalis ATCC 29212. Subsequently instruments were stored for 6, 12 and 24 h in dry or humid conditions. After one, 25 and 50 reprocessing cycles, instruments were examined for protein residues using the o-phthaldialdehyde (OPA) method or corrosion using stereomicroscopy, scanning electron microscopy and energy dispersive spectroscopy. Protein residue found on instruments was 21.5-54.0 μg and corrosion corresponded to 0-5% of the inspected area. No associations between storage environment and protein residue (adjusted mean difference = 0.48, 95% confidence interval: -0.42, 1.37, P=0.30) or corrosion (P=0.20) were identified. Higher numbers of treatment cycles showed higher amounts of corrosion (mean: 1cycle = 0.06%, 25cycles = 0.52% and 50cycles = 1.45%). In contrast, higher numbers of treatment cycles showed lower amounts of protein residue (P<0.001). We found both lower protein residue concentration and lower corrosion rating at 12 h compared with 6 and 24 h holding time. Cleanliness and durability of instruments before reprocessing seems not to be affected by storage environment or holding time but instead by number of treatment cycles.


Post-traumatic massive hand lymphedema fully cured by vascularized lymph node flap transfer.
Post-traumatic localized hand lymphedema is a rare situation and its diagnosis may be difficult, causing lack of care leading to failure of care. Our case study is of two young women with massive post-traumatic hand lymphedema who were treated for algodystrophy for 2 years, and whose bandages and physiotherapy were unsuccessful. Major social and psychological consequences due to difficulty with diagnosis and management resulting in inappropriate tests and therapeutic treatment were prescribed due to these issues. Noncontrast magnetic resonance lymphography revealed complete lymphatic vessel blockage in the hand and wrist. A vascularized lymph node flap harvested at the groin level was transferred to the elbow level 1 month after local dermolipectomy. These procedures resulted in the restoration of lymphatic flow. Both patients were definitely cured, and they returned to normal life within 6 months after surgery. Lymph node flap transfer associated with dermolipectomy may cure massive localized lymphedema in selected cases.


Serum lithium concentration can be used to assess dietary compliance in adults.
With dietary intervention studies, it is important to ensure that subjects adhere to the test diet. Current methods to monitor adherence have substantial limitations. Therefore, a dose-response test curve was constructed to determine whether small differences in serum Li could be detected in response to ingestion of variable Li doses indicative of full or partial dietary compliance. During 3 separate weeks, subjects consumed a test meal that included a single food containing Li citrate daily for 4 d. Doses of 250, 213, or 175 micromol Li were used each week to approximate compliance levels of 100, 85, and 70%. On d 4, blood samples were taken before and 1, 2, 3, 5, 7, 9, and 24 h after ingesting the test meal. Compared with the 100% dose, serum Li was significantly lower at all times after the 70% dose and at most times after the 85% dose. Data were analyzed to determine a cutoff value so that if a subject's serum Li was below that value, they would be declared noncompliant. The probability that a subject was declared to be noncompliant when in fact they were compliant was set to 0.05 (specificity was set to 0.95) and the probability of noncompliance (sensitivity) was estimated. Test performance was best in the 3- to 9-h range, for which 90-95% of subjects "noncompliant" at the 70% dose were identified. Li can be used as a biomarker to determine dietary compliance. Measuring serum Li 3-9 h after the last dose provides the highest sensitivity and specificity for noncompliance at doses <70%.


Flow pattern of four pulmonary veins in a case with prolapsing left atrial myxoma. A case report.
The authors report the flow pattern of the four pulmonary veins in a case with prolapsing left atrial myxoma. The early systolic flow was reversed, midsystolic forward flow was diminished, and diastolic forward flow was augmented and decelerated rapidly in all four pulmonary veins. This phenomenon is attributed to the dynamic movement of the myxoma.


Pest sequences in EF-hand calcium-binding proteins.
Calcium binding proteins are subdivided into two major families: the EF-family and the Annexin family. The EF-hand family is distinguished by the characteristic helix-loop-helix motif which consists of two alpha-helices separated by a loop. The EF-hand Ca2+(-)binding protein family contain subfamilies rich in proline, glutamic acid, serine and threonine residues (called PEST sequences) and non PEST-containing subfamilies. A few of the Ca2+(-)binding proteins contain KFERQ-like sequences which are thought to be possible signals for lysosomal degradation. Arginine pairs (RR) which have also been suggested to act as signals for proteolysis were found to be few or absent. However, most EF-hand proteins were found to possess lysine pairs (KK) which may also act as signals for proteolysis.


Temporal Changes in Deceased Kidney Donor Characteristics in Australia.
Demand for deceased donor kidneys has exceeded supply in Australia over the past 2 decades. With a desire to use as many donor organs as possible, the health characteristics of accepted donors may have changed over time. All deceased kidney donors actually transplanted in Australia between January 1, 1994, and December 31, 2013, were retrospectively analyzed, using data from the Australian and New Zealand Organ Donor Registry. Of 4172 deceased donors, 57% were men. Mean donor age increased from 37.2 ± 16.8 years to 46.1 ± 17.7 years over time, and donor numbers increased from 162 in 1994 to 334 in 2013. As the primary cause of death, motor vehicle accidents decreased from 27% to 12%, whereas cerebral pathology persisted at 50%. There was an increase in the proportion of donors with hypertension (12% to 24%), diabetes (2% to 7%), and an increase in mean body mass index (24.4 ± 4.4 kg/m2 to 27.5 ± 6.3 kg/m2) between 1994 and 2013. These changes were reflected by an increase in the median kidney donor risk index from 1.08 (interquartile range, 0.85-1.25) to 1.32 (interquartile range, 0.95-1.53). The proportion of medically higher risk donors increased over time. Because deceased kidney donor numbers have increased, the range of donor quality has broadened, with an increase in both the proportion and number of high-risk donors, as well as a decline in donor quality. These data highlight the need for kidney allocation algorithms to evolve to ensure appropriate allocation of deceased donor kidneys.


Is Anti-NXP2 Autoantibody a Risk Factor for Calcinosis and Poor Outcome in Juvenile Dermatomyositis Patients? Case Series.
Juvenile dermatomyositis (JDM) has a wide spectrum of clinical presentations. In the last decade, several myositis-specific antibodies have been identified in patients with JDM and connected with specific organ involvement or specific clinical picture. It has been published that the presence of anti-NXP2 autoantibodies presents a risk for calcinosis in patients with JDM. We aimed to investigate the prevalence of calcinosis and response to the treatment in JDM patients with anti-NXP2. In a retrospective, multinational, multicenter study, data on 26 JDM (19 F, 7 M) patients with positive anti-NXP2 were collected. The mean age at disease presentation was 6.5 years (SD 3.7), the median diagnosis delay was 4 months (range 0.5-27 months). Patients were divided into two groups (A and B) based on the presence of calcinosis, which occurred in 42% of anti-NXP2 positive JDM patients (group A). Four patients already had calcinosis at presentation, one developed calcinosis after 4 months, and 6 developed calcinosis later in the disease course (median 2 years, range 0.8-7.8). The differences in laboratory results were not statistically significant between the groups. The mean age at disease presentation (5.2/7.5 years) trended toward being younger in group A. Children with calcinosis were treated with several combinations of drugs. In four cases, rituximab and, in one case, anti-TNF alpha agents were used successfully. Disease outcome (by evaluation of the treating physician) was excellent in four, good in two, stable in two, and poor in three patients. None of the patients from group B had a poor disease outcome. In conclusion, JDM patients with anti-NXP2 are prone to develop calcinosis, especially if they present with the disease early, before 5 years of age. The development of calcinosis is associated with worse disease outcomes. The combination of several immunomodulatory drugs and biologic drugs can stop calcinosis progression; however, there are no evidence-based therapies for treating calcinosis in JDM patients.


[Therapy of multiple myeloma]
Multiple myeloma (MM) is a haematological malignancy characterised by the clonal expansion of malignant plasma cells within the bone marrow. It accounts for 10% of all haematological malignant diseases and 1% of all malignancies. The median age of patients at the time of the diagnosis is 70 years. The characteristic clinical features of MM are bone marrow failure, susceptibility to infections, bone pain, pathological bone fractures, hypercalcaemia, and renal failure. Though MM is currently incurable, the important progress in chemotherapy has resulted in an improvement in survival from a median of 7 months in the 1950-ies to about 3 years today. Advances in the diagnosis and in supportive treatment of infections, hypercalcaemia, and renal failure also contributed to the prolongation of survival. For decades, the gold standard of treatment had been oral melphalan alone or in combination with prednisolone. Combination chemotherapy has not improved overall survival (OS), but these regimens have led to the prolongation of event-free survival (EFS) and also to a better quality of life. High-dose chemotherapy with haemopoietic stem cell rescue resulted in a great improvement in EFS as well as OS. For those very few who have an HLA-compatible donor and are under 55, allogeneic bone marrow transplantation offers the best hope of survival but comes at a greatly increased risk of toxicity. There are conflicting data in the literature concerning the role of interferon-alpha; it seems to be able to prolong the duration of the plateau phase. Current treatment is moving towards an approach using sequential therapy. This involves induction therapy proceeding to high-dose chemotherapy with some form of stem-cell rescue. Bisphosphonates reduce hypercalcaemia, bone pain and can inhibit bone destruction. They also possess a direct antitumor activity. The better understanding of the pathomechanism of the disease gives the opportunity of the application of new therapeutic modalities such as antagonising the effect of interleukin-6 (IL-6), or idiotypic vaccination.


Green biocide for mitigating sulfate-reducing bacteria influenced microbial corrosion.
In the present investigation, Polyalthia longifolia plant extract (PLAE) was used as biocide to control corrosion in the presence of sulfate-reducing bacteria (SRB). Transmission electron microscopy showed the damage of SRB outer cell membrane which lead to cell destruction and disturbed membrane permeability. The scanning electron microscopy also confirmed the cell shrinkage due to green biocide, and energy-dispersive Fourier transform infra-red spectroscopy indicated the decrease in sulfide concentration in the presence of biocide. Potentiodynamic polarization of mild steel showed the lower in corrosion rate due to the decrease in cathodic reduction kinetics of SRB in the presence of biocide PLAE. The gravimetric mass loss also showed corrosion rate dropped from 0.064 millimeter per year (mm/year) to 0.013 mm/year with and without biocide. The present study showed that P. longifolia extract could be a novel biocide against the growth of the SRB to control corrosion in oil and gas industries.


Effect of low protein diet on manganese neurotoxicity: III. Brain neurotransmitter levels.
The effect of concurrent low protein (10% casein) diet and manganese (Mn) exposure (3 mg/ml drinking water) on brain levels of dopamine (DA), norepinephrine (NE) and 5-hydroxytryptamine (5-HT) were investigated in Fo-growing (90 days exposure), Fo-diet rehabilitated (low----normal protein diet-28 days) and F1-weaned rats. Mn exposure in either diet group resulted in a significant increase in the DA and NE levels but a decrease in the 5-HT level. These effects were more pronounced in the rats fed the low protein diet, especially in the F1-offsprings. Diet rehabilitation reduced the effects of Mn exposure.


Lipase activities in scutella of maize lines having diverse kernel lipid content.
The maize lines, Illinois High Oil, Illinois Low Oil, and their F(1) generation contained about 18%, 0.5%, and 10%, respectively, of kernel lipids, which were present mostly in the scutella. We explored to see if the activities of gluconeogenic enzymes which appeared in postgerminative growth were proportional to the lipid content in each maize line. This proportionality was found to be valid in lipase, but the two glyoxysomal enzymes, catalase and isocitrate lyase, were the same in the three maize lines irrespective of the lipid content. The results suggest a difference in the genetic control of the gluconeogenic enzymes and a co-selection for high lipid content and high lipase activity through breeding.


Trend of air pollution and its effect on human health in Hiroshima Prefecture--a retrospective study in the cities of Otake, Kure, Mihara, Takehara, Fukuyama and Kaita Town, 1977-1992.
The evaluation of adverse health effects resulting from exposure to relatively low levels of ambient air pollution is currently a major concern. By using methodology that directly addressed the time series nature of data, this study investigated the association between ambient air pollution and respiratory symptoms and eye, nose, throat irritation symptoms. Health effects were determined by using the air quality data from ambient monitoring stations located within the Hiroshima Prefecture area. The air pollution data chosen for this study were the mean of annual average concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), suspended particulate matter (SPM) and photochemical oxidants (Ox). The health data were extracted from the Hiroshima Community Health Study conducted in the cities of Otake, Kure, Takehara, Mihara, Fukuyama and Kaita Town during 1977-1992. The Community Health Study data were obtained by using a Japanese translation of the British Medical Research Council (BMRC) Questionnaire. The analysis was limited to the investigation of the health symptoms reported by subjects and the mean annual average concentrations of ambient air pollution in each study area. The results indicated a significant association between SO2 levels and lacrimacy symptoms (p < 0.05), runny nose (p < 0.05) and cough symptoms (p < 0.05). This study also found a significant association between O(x) and phlegm symptoms reported by the subjects (p < 0.01). In contrast, the results found that there was a negative correlation between NO2 levels and phlegm symptoms reported by subjects. In conclusion, moderate annual changes in SO2 and O(x) levels induce a significant increase of health symptoms in the local community.


What can be learnt from a snail?
The marine snail Littorina saxatilis is a common inhabitant of intertidal shores of the north Atlantic. It is amazingly polymorphic and forms reproductively isolated ecotypes in microhabitats where crabs are either present and wave action is less furious, or where waves are strong and crabs are absent. Decades of research have unveiled much of the ecological and demographic context of the formation of crab- and wave-ecotype snails showing important phenotypic differences being inherited, differential selection being strong over adjacent microhabitats, local dispersal being restricted, and long-distance transports of individuals being rare. In addition, strong assortative mating of ecotypes has been shown to include a component of male mate preference based on female size. Several studies support ecotypes being diverged locally and under gene flow in a parallel and highly replicated fashion. The high level of replication at various levels of independence (from local to pan-European scale) provides excellent opportunities to investigate the detailed mechanisms of microevolution, including the formation of barriers to gene flow. Current investigations benefit from a draft reference genome and an integration of genomic approaches, modelling and experiments to unveil molecular and ecological components of speciation and their interactions.


Muscle strength differences in healthy young adults with and without generalized joint hypermobility: a cross-sectional study.
Generalized joint hypermobility (GJH), in the absence of symptoms, is a common clinical finding. The joint instability present due to excessive musculoskeletal flexibility in hypermobile joints impairs the external force production during muscle contraction. However, whether GJH is associated with muscle weakness is unclear. This study evaluated differences in upper and lower limb muscle strengths among asymptomatic young adults with and without GJH. One hundred six young adults (53 hypermobile, i.e. 25 male (mean age 22 ± 1.8); 28 female (mean age 21 ± 1.8), and 53 non-hypermobile, i.e. 25 male (mean age 19 ± 1.06); 28 female (mean age 20 ± 1.4) were selected using a cut-off ≥ 4 on Beighton and Horan Joint Mobility Index. Isometric strength of elbow and knee extensors was measured using an isokinetic dynamometer. Independent sample t- tests were done to compare the muscle strengths of hypermobile and non-hypermobile participants. One-way ANCOVA was applied to control the effect of height and body mass on muscle strength. Male hypermobile participants had significantly less strength than non-hypermobile males in the right (71.7 Nm, SD = 23.1, vs 97.6 Nm, SD = 47.4, p = 0.006*) and left (74.8 Nm, SD = 24.3, vs 97.7 Nm, SD = 45.5, p = 0.007*) elbow extensors and right knee extensors (188.7 Nm, SD = 83.3, vs 228.3 Nm, SD = 106.7, p = 0.03*). In females, both elbow extensors (right: 51.9 Nm, SD = 16.2 vs 48.8 Nm, SD = 17.8, p = 0.4; left: 48.9 Nm, SD = 17.2, vs 44.7 Nm, SD = 15.1, p = 0.2) and knee extensors (right: 161.3 Nm, SD = 74.9 vs 145.5 Nm, SD = 75.8, p = 0.3; left: 155.2 Nm, SD = 73 vs 124.3 Nm, SD = 69.6, p = 0.07) strength were not statistically different between hypermobile and non-hypermobile participants. The findings indicate that male participants with GJH have less isometric muscle strength in both elbow extensors and right knee extensors compared to non-hypermobile male participants. Female hypermobile participants did not show any significant differences in muscle strength compared to non-hypermobile female participants.


Paraganglioma of the vulva.
A case of vulvar paraganglioma is reported. Following presentation with vulvar pain, a 1-cm nodule was excised from the labium minus of a 58-year-old woman. Histologically, the tumor was composed of nests of round eosinophilic cells with moderately pleomorphic nuclei, beneath an intact squamous epithelium. Ultrastructural studies indicated two cell types within the neoplasm: chief cells with numerous small neurosecretory granules and peripheral slender sustentacular cells. A reticulin stain confirmed the "zellballen" nature of the neoplasm, and the neoplastic cells showed moderate argyrophilia on a Grimelius stain. The immunoperoxidase stains for chromogranin and neuron-specific enolase were strongly positive in the neoplastic chief cells. Immunostaining using anti-S-100 antibody confirmed the finding of sustentacular cells by identifying many slender cellular processes among the chief cells. These light and electron microscopic findings are diagnostic of paraganglioma, an entity not previously reported in the vulva to our knowledge.


Sonographic monitoring of ovarian follicular development.
Serial sonographic examinations were performed on 15 volunteers five days during the expected midcycle. The 75 sonographic studies were evaluated in a nonbiased manner, and the following features were assessed: 1) the presence or absence of a follicle within the ovary; 2) if present, the average dimension of the follicle; 3) the ability to delineate both ovaries; and 4) the presence of associated changes, such as involution of the follicle, echogenic texture within the follicle, or fluid in the cul-de-sac. The sonographic findings were correlated with serial leutinizing hormone (LH) assays as well as basal body temperature charts. As defined in the study, the correlation between the sonographic findings and hormonal determination were considered excellent in 70% of the cases, good in 20%, and poor in 10%. Both ovaries were delineated in 73% of the examinations performed, thus substantiating the ability of sonography to detect maturing ovarian follicles.


CaMKII plays a part in the chondrogenesis of bone marrow-derived mesenchymal stem cells.
The purpose of the study is to observe the functions of calcium/calmodulin dependent protein kinase II (CaMKII) in the induced chondrogenic differentiation of bone marrow derived mesenchymal stem cells (BMSCs). BMSCs was in vitro isolated and cultured for induced chondrogenesis. Western blot was used to ascertain the expression of CaMKII and phosphorylated CaMKII (PCaMKII, activatory CaMKII) in chondrogenic induced BMSCs. MTT method was utilized to observe the impact of CaMKII on the proliferation of BMSCs. The generation of cartilage matrix in BMSCs cells was detected by toluidine blue staining. The levels of cartilage marker genes COL2A1, Aggrecan and SOX9 in BMSCs were gained by real-time fluorescence quantitative polymerase chain reaction (RT-QPCR). Finally, BMSCs proliferation, cartilage matrix generation and the changes of COL2A1, Aggrecan and SOX9 were surveyed after CaMKII being blocked by CaMKII inhibitor KN93. Expression of CaMKII and PCaMKII could be found in chondrogenic induced BMSCs. CaMKII had no significant influence on BMSCs proliferation, but the toluidine blue staining was obviously lighter, indicating a significant decline in the expression of COL2A1, Aggrecan and SOX9. As one of the factors influencing the chondrogenic capacity of BMSCs, CaMKII does not impact on BMSCs proliferation, but it can inhibit the chondrogenic ability of BMSCs by influencing its differentiation.


Purification and characterization of rat ovarian 20 alpha-hydroxysteroid dehydrogenase.
To investigate the regulatory mechanism of 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) (EC 22.214.171.124) activity in ovarian tissue, the enzyme was purified from ovaries of normal mature female rats. Column chromatography of the cytosolic fraction from ovaries on DEAE-Toyopearl 650M revealed two peaks of the 20 alpha-HSD activity at different ionic strengths. These peaks were designated HSD1 and HSD2, respectively. Each of the active fractions was further purified to homogeneity by dye-affinity chromatography using Matrex Green A and AF Red-Toyopearl. Both the fractions appeared as a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (at Mr = 33,000 under reducing conditions). Under non-reducing conditions, similar values were obtained on gel-exclusion HPLC, indicating that the enzyme fractions were single-stranded, monomeric polypeptides. Homogeneous HSD1 and HSD2 were purified 361-fold and 509-fold, respectively, and differed in their substrate preference. The two enzyme fractions had Km values of 4.75 microM and 5.16 microM for 20 alpha-dihydroprogesterone, respectively, and showed almost the same RF values on reverse-phase HPLC and free-zone capillary electrophoresis. However, amino acid composition was slightly different, i.e. lysin content was higher in HSD1 than HSD2. Thus, it was clarified that two types of 20 alpha-HSD with very similar molecular structures are present in the rat ovary.


Geminivirus C4 antagonizes the HIR1-mediated hypersensitive response by inhibiting the HIR1 self-interaction and promoting degradation of the protein.
Tomato leaf curl Yunnan virus (TLCYnV)-encoded C4 protein induces the upregulation of the hypersensitive induced reaction 1 (HIR1) gene but interferes with the HIR1-mediated hypersensitive response (HR). HIR1 self-interaction is essential for the HIR1-induced HR. TLCYnV C4 impairs the HIR1 self-interaction and concomitantly increases the amount of Leucine-Rich Repeat protein 1 (LRR1), a modulator of HIR1, which binds to HIR1. LRR1 promotes the degradation of HIR1, compromising the HIR1-mediated HR. This study provides new insights into the mechanisms employed by a viral protein to counter host resistance through the cooption of the host regulatory system.


[Glucosamine as a pain-modifying drug in osteorthritis. What's new in 2006].
Glucosamine is widely used as a symptom-modifying drug in osteoarthritis. New clinical trials, from Europe and the United-States bring some clarification regarding the optimal formulation and doses to be used in knee osteoarthritis. Their results are supported by new pharmacokinetic and preclinical studies, explaining the mode of action of glucosamine in osteoarthritis.


Stimulation of mesothelial cells proliferation by endogenous growth factor(s).
We have attempted to determine whether human mesothelial cells (MC) have the power to influence their own proliferation. A serum-free medium was conditioned with the mesothelial monolayer for 24 hours and then applied to proliferating MC. Conditioned medium increased proliferation rate of MC. When the medium was heated at 60 degrees C for 60 minutes, the growth-promoting activity of the conditioned medium decreased by 50%, suggesting that MC produce at least 2 growth factors, 1 heat-labile and the other heat-stable. When MC were exposed continuously to a medium containing 90 mM glucose growth factor, production was decreased by 35%. However, when the cells were exposed to glucose only on alternate days, growth-factor production was similar to that in the control medium. On the other hand, MC exposed continuously for 10 days to 90 mM of glucose exhibited a weaker response to endogenous growth factor, even in a normotonic medium with low glucose concentration. Our results suggest that MC synthesize factor(s), which stimulate their own proliferation, and that high glucose concentrations interfere with this production and the subsequent action of growth factor.


[Evaluation of the glucose screening retest during pregnancy].
To evaluate of the glucose screening retest for gestational diabetes mellitus (GDM) during pregnancy. A retrospective analysis of 714 pregnant women screened for GDM, between December 1, 2001, and December 31, 2002, was performed. The first glucose challenge test (GCT) was performed in 16 - 27 week and retested in 28 - 38 week. Diagnosis of GDM was based on the criteria of Dong. NDDG criteria was also discussed. (1) 1-hour glucose value of 50 g GCT >or= 7.8 mmol/L was set as abnormal. The first 50 g GCT abnormal rate was 26.6% (190/714), and the retest abnormal rate was 35.2% (225/639). The mean age of pregnant women in 50 g GCT positive group was significantly higher than that in the negative group (P < 0.05), but there was no significant difference in family history and body mass index (BMI) between the two groups. Both the mean birth weight and the incidence of macrosomia of second 50 g GCT abnormal group were significantly higher than those in the normal group (P < 0.05). (2) By the criteria of Dong, 28 women were found to have GDM and 40 have IGT (impaired glucose tolerance) by the first 50 g GCT. New added cases included 15 GDM and 27 IGT by the retest 50 g GCT. By NDDG criteria, 14 GDM and 24 IGT cases were diagnosed by the first 50 g GCT, 5 GDM and 14 IGT cases by retest GCT. (3) The 1-hour blood glucose value [(7.3 +/- 1.6) mmol/L] in second 50 g GCT were significantly higher than those in first 50 g GCT [(6.9 +/- 1.8) mmol/L]. The results of 50 g GCT of two times were consistent in 68.1% women (normal/normal and abnormal/abnormal). There were 376 (52.7%) women whose 1-hour glucose value of the first 50 g GCT <or= 6.8 mmol/L. Among them neither GDM nor IGT were found by retest GCT. If the 1-hour glucose value of first 50 g GCT < 7.8 mmol/L (n = 524), there were 4 cases GDM and 17 cases IGT by the criteria of Dong by retest of 50 g GCT, but no GDM and only 7 cases IGT were found by NDDG criteria. (1) Screening for GDM should be done for all pregnant women especially in big city. (2) If the NDDG criteria were used, the retest should be done for the women whose first 50 g GCT >or= 7.8 mmol/L, and the 75 g OGTT should be done directly. (3) Maternal age appears to be the most important risk factor for GDM.


Prognostic relevance of silver-stained nucleolar proteins in sarcomatoid carcinomas of the breast.
Fourteen cases of sarcomatoid carcinomas of breast were evaluated by means of a silver technique that selectively stains proteins located in the nucleolar organizer regions (Ag-NORs). The mean area of Ag-NORs (MNORA) was in each case quantitatively analyzed by means of an automated image analyzer. Patients who died early of the disease had a higher MNORA than patients who survived longer than 3 years. The difference was statistically significant. Ag-NORs might be a novel parameter of prognostic relevance in specific cases.


Brochothrix thermosphacta bacteriophages feature heterogeneous and highly mosaic genomes and utilize unique prophage insertion sites.
Brochothrix belongs to the low-GC branch of Gram-positive bacteria (Firmicutes), closely related to Listeria, Staphylococcus, Clostridium, and Bacillus. Brochothrix thermosphacta is a nonproteolytic food spoilage organism, adapted to growth in vacuum-packaged meats. We report the first genome sequences and characterization of Brochothrix bacteriophages. Phage A9 is a myovirus with an 89-nm capsid diameter and a 171-nm contractile tail; it belongs to the Spounavirinae subfamily and shares significant homologies with Listeria phage A511, Staphylococcus phage Twort, and others. The A9 unit genome is 127 kb long with 11-kb terminal redundancy; it encodes 198 proteins and 6 tRNAs. Phages BL3 and NF5 are temperate siphoviruses with a head diameter of 56 to 59 nm. The BL3 tail is 270 nm long, whereas NF5 features a short tail of only 94 nm. The NF5 genome (36.95 kb) encodes 57 gene products, BL3 (41.52 kb) encodes 65 products, and both are arranged in life cycle-specific modules. Surprisingly, BL3 and NF5 show little relatedness to Listeria phages but rather demonstrate relatedness to lactococcal phages. Peptide mass fingerprinting of viral proteins indicate programmed -1 translational frameshifts in the NF5 capsid and the BL3 major tail protein. Both NF5 and BL3 feature circularly permuted, terminally redundant genomes, packaged by a headful mechanism, and integrases of the serine (BL3) and tyrosine (NF5) types. They utilize unique target sequences not previously described: BL3 inserts into the 3' end of a RNA methyltransferase, whereas NF5 integrates into the 5'-terminal part of a putative histidinol-phosphatase. Interestingly, both genes are reconstituted by phage sequence.


[In vitro activity of beta-lactam antibiotics in combination with sulbactam against enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter. Results of a multicenter study].
The in vitro antimicrobial activity of ticarcillin (TICAR), mezlocillin (MEZLO), piperacillin (PIPER), cefoperazone (CPZ), cefotaxime (CTX) and ceftazidime (CAZ), alone and in combination with 8 micrograms/ml of sulbactam (SULB), was studied by agar dilution against TICAR resistant strains isolated in 8 hospitals over a period of 3 months in 1989 (747 enterobacteria, 110 Ps. aeruginosa and 48 Acinetobacter sp.). SULB did not modify the activity of beta-lactam antibiotics against Ps. aeruginosa. The 6 beta-lactam antibiotics SULB combinations were only active for 27% of Acinetobacter SULB sensitive. SULB restored the activity of: MEZLO, PIPER, CPZ in Enterobacteria producing a penicillinase; PIPER, CTX and CAZ in Enterobacteria producing a broad-spectrum beta-lactamase; MEZLO, PIPER, CTX and CAZ in M. morganii producing a derepressed cephalosporinase.


Integrating structural and epidemiological research to inform the classification of psychopathology.
Given the enormous influence of classification on the major clinical, research, and administrative activities of mental health professionals, understanding the true number and nature of disorders and the reasons for their comorbidity is an important public health priority. However, while studies of latent structure have yielded valuable information about disorder boundaries, their reliance on non-representative samples and failure to evaluate the practical implications of structural findings has limited their ability to effect nosological change. Conversely, community epidemiology studies, which inform classification by assessing the implications of diagnostic criteria in representative samples, have been limited by their focus on mental disorders as they are currently conceptualized by the field rather than on correlates and consequences of these disorders as they actually exist in nature. I consider the potential value of integrating systematically the methods of structural research with the methods of epidemiological research, exploring five ways in which these largely independent traditions may profitably be combined to inform the next classifications of mental disorders. By capitalizing on the complementary strengths of structural and epidemiological research, an integrated approach has significant potential to advance understanding of the nature of psychopathology and improve the validity and utility of its diagnosis.


Holographic Lenses in an Environment-Friendly Photopolymer.
In this paper, we theoretically and experimentally evaluated the quality of volume phase transmission lenses stored in an environmentally friendly photopolymer. Holographic lenses (HLs) were obtained using symmetrical and asymmetrical experimental setups with the same positive and negative focal length and pupil diameter. The image quality was evaluated from the calculation of the modulation transfer function (MTF) by capturing the point spread function (PSF) with a charge-coupled device (CCD). A maximum frequency of 14 L/mm, reaching an MTF value of 0.1, was obtained for a negative asymmetrically recorded HL, evaluated at 473 nm wavelength. A theoretical study of aberrations was carried out to qualitatively evaluate the experimental results obtained.


Selective saturation NMR imaging.
The application of selective saturation (or solvent suppression) techniques in nuclear magnetic resonance (NMR) imaging offers the opportunity to significantly expand the range of NMR studies. Data acquired at 1.44 T are presented using a two-dimensional spin-echo sequence preceded by a selective (saturating) radiofrequency pulse. Individual water or lipid proton resonances were eliminated (greater than 90% reduction in signal intensity) resulting in images of H2O or -CH2- distribution with resolution and imaging time equivalent to conventional proton images. Data are also presented demonstrating the feasibility of using selective saturation to image proton metabolites at low concentrations with a three-dimensional chemical shift imaging approach. Lactate was investigated because of its importance in the pathophysiology of ischemic insult. Phantom studies without solvent suppression failed to detect lactate at 80 mM; however, with solvent suppression, lactate at 40 mM was imaged in a reasonable time (approximately 50 min). With the favorable NMR characteristics of the methyl protons of lactate and with improvements in imaging systems, this technique may play an important role in the noninvasive evaluation of tissue ischemia using 1H NMR.


EANM procedure guideline for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds.
Primary liver tumours (i.e. hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)) are among the most frequent cancers worldwide. However, only 10-20% of patients are amenable to curative treatment, such as resection or transplant. Liver metastases are most frequently caused by colorectal cancer, which accounts for the second most cancer-related deaths in Europe. In both primary and secondary tumours, radioembolization has been shown to be a safe and effective treatment option. The vast potential of personalized dosimetry has also been shown, resulting in markedly increased response rates and overall survival. In a rapidly evolving therapeutic landscape, the role of radioembolization will be subject to changes. Therefore, the decision for radioembolization should be taken by a multidisciplinary tumour board in accordance with the current clinical guidelines. The purpose of this procedure guideline is to assist the nuclear medicine physician in treating and managing patients undergoing radioembolization treatment. PREAMBLE: The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide among individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. These guidelines are intended to assist practitioners in providing appropriate nuclear medicine care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by medical professionals taking into account the unique circumstances of each case. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set out in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine involves not only the science but also the art of dealing with the prevention, diagnosis, alleviation and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognised that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.


Spatial analysis of factors impacting lower limb major amputation rates in Hungary: Is geography partially destiny?
Background: Lower limb major amputations represent a substantial public health burden in Hungary, where previous research revealed markedly high rates with significant spatial variations. Therefore, we aimed to assess to what extent healthcare and socio-economic factors in the local environment explain the regional disparity. Patients and methods: In a retrospective cohort analysis, based on the healthcare administrative data of the Hungarian population, lower limb major amputations were identified from 1st of January 2017 to 31st of December 2019. The permanent residence of the amputees on the local administrative level (197 geographic units) was used to identify potential healthcare (outpatient care, revascularisation activity) and socio-economic (educational attainment, local infrastructure and services, income and employment) determinants of amputations. Spatial effects were modelled using the spatial Durbin error regression model. Results: 10,209 patients underwent 11,649 lower limb major amputations in the observational period. In our spatial analysis, outpatient care was not associated with local amputation rates. However, revascularisation activity in a geographic unit entailed an increased rate of amputations, while revascularisations in the neighbouring areas were associated with a lower rate of amputations, resulting in an overall neutral effect (β=-0.002, 95% CI: -0.05 - 0.04, p=0.96). The local socio-economic environment had a significant direct inverse association with amputations (β=-7.45, 95% CI: -10.50 - -4.42, p<0.0001) . Our spatial model showed better performance than the traditional statistical modelling (ordinary least squares regression), explaining 37% of the variation in amputations rates. Conclusions: Regional environmental factors explain a substantial portion of spatial disparities in amputation practice. While the socio-economic environment shows a significant inverse relationship with the regional amputation rates, the impact of the local healthcare-related factors (outpatient care, revascularisation activity) is not straightforward. Unravelling the impact of the location on amputation practice requires complex spatial modelling, which may guide efficient healthcare policy decisions.


Improving the solubility, activity, and stability of reteplase using in silico design of new variants.
Reteplase (recombinant plasminogen activator, r-PA) is a thrombolytic agent recombined from tissue-type plasminogen activator (t-PA), which has several prominent features such as strong thrombolytic ability and E. coli expressibility. Despite these outstanding features, it demonstrates reduced fibrin binding affinity, reduced stimulation of protease activity, and lower solubility, hence higher aggregation propensity, compared to t-PA. The present study was devoted to design r-PA variants with comparable structural stability, enhanced biological activity, and high solubility. For this purpose, computational molecular modeling techniques were utilized. The supercharging technique was applied for r-PA to designing new species of the protein. Based on the results from in silico evaluation of selected mutations in comparison to the wild-type r-PA, the designed supercharged mutant (S7 variant) exhibited augmented stability, decreased solvation energy, as well as enhanced binding affinity to fibrin. The data also implied increased plasminogen cleavage activity of the new variant. These findings have implications to therapies which involve removal of intravascular blood clots, including the treatment of acute myocardial infarction.


Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2.
The Chk2 Ser/Thr kinase plays crucial, evolutionarily conserved roles in cellular responses to DNA damage. Identification of two pro-oncogenic mutations within the Chk2 FHA domain has highlighted its importance for Chk2 function in checkpoint activation. The X-ray structure of the Chk2 FHA domain in complex with an in vitro selected phosphopeptide motif reveals the determinants of binding specificity and shows that both mutations are remote from the peptide binding site. We show that the Chk2 FHA domain mediates ATM-dependent Chk2 phosphorylation and targeting of Chk2 to in vivo binding partners such as BRCA1 through either or both of two structurally distinct mechanisms. Although phospho-dependent binding is important for Chk2 activity, previously uncharacterized phospho-independent FHA domain interactions appear to be the primary target of oncogenic lesions.


Measurement of influenza virus-antibody reaction by quantitative electron microscopy.
Measurement of the weight of individual virus particles from untreated and antibody-treated populations was made by quantitative electron microscopy. The weight of antibody bound depended on the concentration of antibody in solution. One population of viruses exposed to an antibody concentration which resulted in 95% inhibition of hemagglutination showed a mass increase of 55%, corresponding to an absolute increase of 9.0 x 10(-17) g in the median value. Another population, whose hemagglutination inhibition assay was 64%, showed a 39% increase in mass corresponding to an absolute median increase of 7.3 x 10(-17) g. The larger viruses in each population bound a greater absolute amount of antibody than did the smaller ones, but the latter bound relatively more antibody in proportion to their mass. No cross-reactivity was found between the antibody to influenza A/PR8 and the influenza strain B/LEE. Influenza A/PR8 controls exposed to nonspecific gamma-globulin displayed a significant weight loss, at least in part owing to loss from the core, as judged from the electron micrographs.


An aggressive childhood tumor mimicking pleural empyema: pleuropulmonary blastoma.
We report a case of pleuropulmonary blastoma in a child initially diagnosed with encysted pleural empyema. She was treated with combination chemotherapy including ifosfamide, etoposide, vincristine, adriamycin, actinomycin-D, and cyclophosphamide after surgical excision.


Cystic Progression of a Cavernous Malformation at the Level of the Trigeminal Root Entry Zone Presenting With Sudden Onset of Trigeminal Neuralgia.
Cavernous malformations (CM) in the cerebellopontine angle (CPA) are rare, and most of them are solid and extend from the internal auditory canal into the CPA. In contrast, cystic CM arising in the CPA and not involving the internal auditory canal and dura of the skull base are extremely rare. The authors present an uncommon large cystic progression of a cavernous malformation at the level of the trigeminal root entry zone evolving to severe trigeminal neuralgia and brainstem compression. A 62-year-old female presented a sudden onset of left trigeminal neuralgia, caused by a large cystic lesion at the level of the root entry zone of the left 5th nerve. On neurological examination, she showed slight gait ataxia and hypoesthesia on the left hemiface (on the first and second trigeminal branches). Other cranial nerves were in order. Magnetic resonance imaging showed a large cystic intracranial mass, with a small solid portion, leading to brainstem compression. Microsurgical removal of the lesion was performed via retrosigmoid approach, with intraoperative monitoring of somato-sensory evoked potentials, facial, and cochlear nerves. The posterior-medial portion of the lesion was solid, whereas the main portion was cystic, containing xanthochromic fluid. The small solid lesion continued with a thin capsule of a large cyst adherent to brainstem, cerebellar hemisphere, and trigeminal nerve entry zone. A big draining vein arising from the solid part of the lesion runned parallel to brainstem. The mass was piecemeal totally removed.After surgery the patient recovered both left trigeminal neuralgia and hypoesthesia; ataxia was significantly relieved too. Postoperative magnetic resonance imaging confirmed the total removal. Histopathological features were consistent with a CM. At 6-month follow-up, patient's symptoms at the presentation had resolved. The authors present a very rare patient of large cystic cavernous malformation at the level of the trigeminal root entry zone presenting with sudden onset of trigeminal neuralgia. Even if it has not established imaging features, a cystic cavernoma of the cerebello-pontine angle may be suspected when a cystic mass is present, not involving the internal acoustic meatus nor the skull base dura mater. Careful microneurosurgical technique and monitoring of cranial nerves allow good long-term results.


Acute hyperoxaluria, renal injury and calcium oxalate urolithiasis.
Single intraperitoneal injections of three, seven, or 10 mg. of sodium oxalate per 100 gm. of rat body weight were administered to male Sprague-Dawley rats. At various times after the injection, urine samples were analyzed for oxalate, and urinary enzymes, alkaline phosphatase, leucine aminopeptidase, gamma-glutamyl transpeptidase, and N-acetyl-beta-glucosaminidase. The kidneys were processed for light microscopy and renal calcium and oxalate determination. Oxalate administration resulted in an increase in urinary oxalate and formation of calcium oxalate crystals in the kidneys. The amount and duration of urinary excretion of excess oxalate and retention of crystals in the kidneys correlated with the dose of sodium oxalate administered. At a low oxalate dose of three mg./100 gm., crystals moved rapidly down the nephron and cleared the kidneys. At higher doses crystals were retained in kidneys and at a dose of 10 mg./100 gm. were still there seven days post-injection. Crystal retention was associated with enhanced excretion of urinary enzymes indicating renal tubular epithelial injury.


Electron tunneling in azurin: the coupling across a beta-sheet.
We would like to understand how electron flow is controlled in biological molecules. Standard theories calculate the rate for long distance electron transfer (ET) as the product of electronic coupling (the square of the electron tunneling matrix element) and nuclear (Franck-Condon) factors. Much attention has been directed to the role of protein secondary and tertiary structure in the tunneling coupling, focusing on the interplay between different types of chemical bonds. Here we have evaluated the relative contributions of covalent bonds, hydrogen bonds and through-space jumps in coupling through a beta-strand or across a beta-sheet section of a blue copper protein, azurin. We have analyzed four distant electronic couplings in azurin. Each coupling is between the copper atom and a Ru(bpy)2(im) complex attached to a histidine on the protein surface. In three experiments the intervening medium was a simple beta-strand, while in the fourth experiment it was a section of beta-sheet. We have shown that electron tunneling in a protein can be broken down into ET 'tubes' of pathways through specific covalent and hydrogen bonds. These ET tubes encapsulate trivial interference effects and can expose crucial inter-tube interference effects. In coupling through a beta-sheet, hydrogen bonds are as important as covalent links, and are the primary source for tube interference.


Prognostic factors for survival in metastatic renal cell carcinoma: update 2008.
A variety of prognostic factor models to predict survival in patients with metastatic renal cell carcinoma have been developed. Diverse populations of patients with variable treatments have been used for these analyses. A variety of clinical, pathologic, and molecular factors have been studied, but current models use predominantly easily obtained clinical factors. These approaches are reviewed, and current approaches to further refine and develop these techniques are reviewed.


Expression of telomerase RNA, telomerase activity, and telomere length in human gliomas.
To understand the mechanisms of telomere maintenance in human gliomas, telomerase activity, telomerase RNA expression and telomere length of surgically excised glioma samples were analyzed. Sixty-five percent of gliomas exhibited telomerase activity, the occurrence of which was not related to their histological malignancy scale. Not only the telomerase-positive gliomas, but also the telomerase-negative gliomas and normal brain expressed telomerase RNA, suggesting that the presence of telomerase RNA component does not indicate the presence of telomerase activity. Compared with telomerase-positive gliomas, telomerase-negative gliomas had long heterogeneous telomeric terminal restriction fragments. These data suggest that in addition to the telomerase-dependent mechanism, a telomerase-independent mechanism for telomere maintenance may be present in human gliomas.


Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.
Transient receptor potential vanilloid 1 (TRPV1) -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R)-induced acute kidney injury (AKI). However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist) and using Trpv1-/- mice. Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight) or capsazepine (50 mg/kg body weight). Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL) abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE) or epoxyeicosatrienoic acids (EETs) are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.


Flavonoids in atherosclerosis: an overview of their mechanisms of action.
Polyphenols are composed of a wide variety of molecules that are classified into several categories, according to their chemical type such as phenolic acids, flavonoids, stilbenes, and lignans. Many studies have proven the beneficial effects of flavonoids in atherosclerosis progression and cardiovascular disease. Dietary flavonoids reduce oxidative stress and exert anti-inflammatory actions. Moreover, flavonoids have the ability to avoid the thrombus formation, improve endothelial function, modify lipid levels and regulate glucose metabolism. In the context of this evidence in this review article we summarize the so far acquired knowledge of the most important mechanisms of action of flavonoids in atherosclerosis progression.


Minimal requirements for ejaculates used for in vitro fertilization.
Minimal requirements for ejaculates to be used for in vitro fertilization of human oocytes are defined. Experimental results obtained a total concentration of at least 5 X 10(6) spermatozoa per ml are required, with at least 30% of the sperm showing normal motility and normal morphology in the differential spermiocytogram. The total volume of ejaculate should not be less than 1 ml. A total of 140 ejaculates from patients taking part in the in vitro fertilization program were examined. In 60 ejaculates (42.9%) bacteria concentrations of greater than 10(5)/ml were found. Eighty (57.1%) of the probes were negative or had bacteria concentrations less than 10(4)/ml. Mycoplasma was found in 30 of the examined ejaculates (21.4%) and the second most frequent group of microorganisms were enterococci found in 15 patients (10.7%). Anaerobic organisms in concentrations of more than 10(5)/ml were not detected. After insemination of one or more pelviscopically obtained oocytes with sperm of the husband in 14 out of 22 cases (63.6%) with bacteria concentrations greater than 10(5)/ml the cleavage of at least one oocyte occurred leading to an embryo-transfer rate of 63.6%. In 14 of 31 ejaculates with negative bacteriological findings (45.2%) at least one of the inseminated oocytes was fertilized. Direct effect of microorganism contaminated sperm on the human in vitro fertilization system resulting in reduced fertilization rates cannot be demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)


Stereocontrolled synthesis of the oxathiabicyclo[3.3.1]nonane core structure of tagetitoxin.
Tagetitoxin is an unusually densely functionalized natural product, consisting of an unprecedented oxathiabicyclo[3.3.1]nonane ring system possessing acetate, phosphate, amide, carboxylic acid, and amine groups with six contiguous asymmetric centers. A fully functionalized core structure of tagetitoxin was synthesized from tri-O-acetyl-D-galactal in a highly stereoselective manner.


Transvaginal ultrasound assessment of women presenting with infertility and menstrual irregularity in Calabar, Nigeria.
This study was designed to document the Transvaginal Scan (TVS) findings in women presenting with infertility and menstrual irregularities at the University of Calabar Teaching Hospital. Subjects were women of reproductive age presenting at the University of Calabar Teaching Hospital with menstrual irregularities and infertility over a two year period, February 2011-January 2013. As part of their management, transvaginal scans were done and findings included a substantial number with polycystic ovarian cysts. Therefore the ovaries were further analysed with controls. Out of seventy-one women with age distribution of 22 to 46years, twenty- four(33.8%) presented with infertility, the rest presented with either menstrual irregularity alone or in combination with infertility. Polycystic ovaries (PCO), chronic pelvic inflammatory disease and fibroids were the main pathologies seen. PCO was by far the commonest. Ovarian volumes and follicular numbers were significantly higher in women with PCO than in controls, whereas their average follicular sizes were lower. PCO is the major finding in women with menstrual irregularity and infertility in the Calabar area. This hitherto poorly recorded pathology should be actively investigated in women representing with these symptoms by the use of TVS.


Hurler Scheie Disease.
We present a very rare case of mucopolysaccharidosis type I (MPS I) which presented to us with respiratory distress. Our patient had short stature, coarse facial features, claw hands and clouding of both corneae. This article highlights the salient features present in a case of mucopolysaccharidosis type I.


T cell receptor beta chain RFLP in Chinese, Indians and Malays from Singapore.
Restriction fragment length polymorphism (RFLP) of the gene encoding the beta chain of the human T cell receptor (TcR) was studied in three ethnic groups in Singapore by Southern blotting. Polymorphism in the beta chain gene was identified in BglII-digested DNA samples using a 770-bp TcR beta cDNA clone containing the joining and constant region segments. The TcR beta/BglII polymorphism was studied in 136 Chinese, 93 Indian and 88 Malay samples. The frequency of the less frequent allele (TcR beta*2) in all the ethnic groups was significantly lower (0.15-0.29, p < 0.01) than that in the Caucasians (0.46). Indians had a significantly lower frequency of this allele (0.15) than the Chinese (0.29) and Malays (0.26).


[Ubiquitous perfluorinated compounds].
Perfluorinated compounds are derivatives of hydrocarbons, in which all or most of hydrogen atoms are substitiuted by fluorine atoms. These compounds are commonly used in many branches of industry. Perfluorinated compounds are in the limelight because of numerous reports concerning their toxicity and negative effects on human health as well as contradictory information about their cancerogenic effect. The above compounds are used in production of many commonly used products including such brand names as Gore-Tex, Teflon, Stainmaster. The most common ways of penetrating these compounds into a human organism are: via food, inhalation and skin contact. Perfluorooctanesulfonate (PFOS) has been added to the list of persistent organic pollutants (POPs).