The σ-hole phenomenon of halogen atoms forms the structural basis of the strong inhibitory potency of C5 halogen substituted glucopyranosyl nucleosides towards glycogen phosphorylase b.
C5 halogen substituted glucopyranosyl nucleosides (1-(β-D-glucopyranosyl)-5-X-uracil; X=Cl, Br, I) have been discovered as some of the most potent active site inhibitors of glycogen phosphorylase (GP), with respective K(i) values of 1.02, 3.27, and 1.94 μM. The ability of the halogen atom to form intermolecular electrostatic interactions through the σ-hole phenomenon rather than through steric effects alone forms the structural basis of their improved inhibitory potential relative to the unsubstituted 1-(β-D-glucopyranosyl)uracil (K(i) =12.39 μM), as revealed by X-ray crystallography and modeling calculations exploiting quantum mechanics methods. Good agreement was obtained between kinetics results and relative binding affinities calculated by QM/MM-PBSA methodology for various substitutions at C5. Ex vivo experiments demonstrated that the most potent derivative (X=Cl) toward purified GP has no cytotoxicity and moderate inhibitory potency at the cellular level. In accordance, ADMET property predictions were performed, and suggest decreased polar surface areas as a potential means of improving activity in the cell.


The moderating effect of parenthood in the relationship between posttraumatic stress disorder symptoms and lateral preference in Israeli reserve combat troops.
The present study examined the relationship between posttraumatic stress disorder (PTSD) and lateral preference, as reflected by handedness, in Israeli reserve combat troops. Data were gathered from 147 right-handed reserve combat personnel who filled out the Edinburgh Handedness Inventory, a questionnaire examining the severity of PTSD symptoms according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria and a questionnaire on the details of military service and familial status. The participants without children exhibited significantly more PTSD symptoms compared with the participants with children but did not differ in lateral preference levels. Multiple linear regression analysis revealed an altered pattern in the relationship between PTSD symptoms severity and lateral preference between the two groups. This alternation could suggest that being a parent might compel a reservist to inhibit the use of avoidance mechanisms for coping with intrusive memories, resulting in reduction of visible symptoms of PTSD while respectively contributing to their synchronization to lateral preference.


Allogeneic transplantation for lymphoma: long-term outcome.
In the last 20 years, allogeneic stem cell transplantation (alloSCT) has been increasingly applied in lymphoma patients, due to the shift towards reduced intensity and nonmyeloablative conditioning. This review reports on the most significant long-term results of allografted lymphoma patients coming from both prospective studies and retrospective analyses. AlloSCT can cure 40-60% of aggressive B-cell lymphomas, but an unfavourable outcome has been observed in case of chemorefractory and active disease at the time of allografting. Indolent lymphoma displays the best outcome, and reduced-intensity alloSCT should be always considered in patients relapsing after an autologous SCT and in cases of chemorefractory disease. Most recent findings in Hodgkin's and T-cell lymphoma are also encouraging. Although the nonrelapse mortality has been reduced and survival curves show a plateau, the analysis of the long-term outcome reveals that a significant proportion of patients still experiences disease relapse and delayed morbidity and mortality. At the best of our knowledge, the process of decision-making should be based on lymphoma subtype, chemosensitivity, disease status and patient comorbidities at the time of allografting. To answer some of the still open questions, physicians should try to improve the enrolment of patients in multicentre prospective clinical trials.


[Pulmonary pathology in HIV seropositive children. 4 clinical cases].
Pulmonary infections in children with acquired immunodeficiency syndrome are very common. The lung, having a very important immunological function (because in it a very important part of the secretory immunological system is present), is one of the more involved apparatus in the course of AIDS. We report 4 cases of pulmonary disease (one case of Cytomegalovirus pneumonia, one case of Pneumocystis Carinii pneumonia, and two cases of interstitial lymphoid pneumonia) found in HIV positive children followed at the 5th Pediatric Department - Regional Center, Milan.


Management of hormone refractory prostate cancer.
This review highlights the most interesting developments and outstanding issues surrounding the management of hormone-refractory prostate cancer published in the medical literature during the past year. Recent research has reported poor health-related quality-of-life outcomes for patient with hormone-refractory prostate cancer treated in standard clinical practices. In addition, age-related differences in survival appear to exist for patients with hormone-refractory prostate cancer. Two potential future therapies for hormone-refractory prostate cancer, sipuleucel-T and the combination regimen of docetaxel and DN-101, demonstrate promising preliminary clinical data in terms of improving survival while minimizing toxicity. A variety of novel agents has been tested for hormone-refractory prostate cancer, including pertuzumab and BMS-275291, which may stabilize disease with minimal toxicity. In terms of bone-related health, skeletal-related events have been found to be associated with worse survival and health-related quality of life outcomes. Data reported during the past year have implications for future research directions. This direction includes the need for continued exploration of health-related quality of life and age-related outcomes, further study of the disease-stabilizing effects of novel therapies and their translation into improved survival, as well as directed efforts to continue preventing skeletal-related events, which may impact survival and health-related quality of life.


BODIPY-pyrene donor-acceptor sensitizers for triplet-triplet annihilation upconversion: the impact of the BODIPY-core on upconversion efficiency.
Triplet-triplet annihilation upconversion (TTA-UC) is an important type of optical process with applications in biophotonics, solar energy harvesting and photochemistry. In most of the TTA-UC systems, the formation of triplet excited states takes place via spin-orbital interactions promoted by heavy atoms. Given the crucial role of heavy atoms (especially noble metals, such as Pd and Pt) in promoting intersystem crossing (ISC) and, therefore, in production of UC luminescence, the feasibility of using more readily available and inexpensive sensitizers without heavy atoms remains a challenge. Here, we investigated sensitization of TTA-UC using BODIPY-pyrene heavy-atom-free donor-acceptor dyads with different numbers of alkyl groups in the BODIPY scaffold. The molecules with four and six alkyl groups are unable to sensitize TTA-UC in the investigated solvents (tetrahydrofuran (THF) and dichloromethane (DCM)) due to negligible ISC. In contrast, the dyad with two methyl groups in the BODIPY scaffold and the dyad with unsubstituted BODIPY demonstrate efficient intersystem crossing (ISC) of 49-58%, resulting in TTA-UC with quantum yields of 4.7% and 6.9%, respectively. The analysis of the elementary steps of the TTA-UC process indicates that heavy-atom-free donor-acceptor dyads are less effective than their noble metal counterparts, but may equal them in the future if the right combination of solvent, donor-acceptor sensitizer structure, and new luminescent molecules as TTA-UC emitters can be found.


Decreased GRK3 but not GRK2 expression in frontal cortex from bipolar disorder patients.
Overactivation of G-protein-mediated functions and altered G-protein regulation have been reported in bipolar disorder (BD) brain. Further, drugs effective in treating BD are reported to up-regulate expression of G-protein receptor kinase (GRK) 3 in rat frontal cortex. We therefore hypothesized that some G-protein subunits and GRK levels would be reduced in the brain of BD patients. We determined protein and mRNA levels of G-protein beta and gamma subunits, GRK2, and GRK3 in post-mortem frontal cortex from 10 BD patients and 10 age-matched controls by using immunoblots and real-time RT-PCR. There were statistically significant decreases in protein and mRNA levels of G-protein subunits beta and gamma and of GRK3 in BD brain but not a significant difference in the GRK2 level. Decreased expression of G-protein subunits and of GRK3 may alter neurotransmission, leading to disturbed cognition and behaviour in BD.


How often does spirometry testing induce cardiac arrhythmias?
To describe the frequency and type of arrhythmia induced by forced expiratory and inspiratory flow-volume loop manoeuvres. 735 subjects (548 men) aged from 10 to 98 years old (mean 54 years, SD +/- 15) were submitted to a conventional medical examination and spirometry testing prior to a maximal cardiopulmonary exercise test (CPET). A continuous digital electrocardiogram (ECG) was recorded during spirometry and CPET, and later reviewed and interpreted by the same physician (who supervised all the procedures). 470 subjects (64%) had cardiac arrhythmias during one or both procedures. About 60% of the arrhythmias were supraventricular, but 35 subjects (5%) presented more complex arrhythmias including frequent premature ventricular beats (n=31) or non-sustained ventricular tachycardia (n=4). While arrhythmias were more often exposed by the CPET (p<0.01), in 68 cases (10% of the total sample) arrhythmias were only induced by spirometry; these included four cases of non-sustained supraventricular tachycardia (n=4). Spirometry is a safe procedure with regard to induction of cardiac arrhythmias. Spirometry-induced arrhythmias tend to be simple and were always short-lasting. In some cases, ECG recording during spirometry showed arrhythmias that would not be induced by a progressive maximal exercise test.


Current developments in and importance of high-performance computing in drug discovery.
A number of current trends that are being adopted to reshape the field of high-performance computing exist, including multi-core systems, accelerators, and software frameworks for large-scale intrinsically parallel applications. These trends intersect with recent developments in computational chemistry to provide new capabilities for computer-aided drug discovery. Although this review focuses primarily on the application domains of molecular modeling and biomolecular simulation, these computing changes are relevant for other computationally intensive tasks, such as instrument data processing and chemoinformatics.


Comparison of the organophosphorus hydrolase surface display using InaVN and Lpp-OmpA systems in Escherichia coli.
The purpose of this study was to compare the ability of an engineered Escherichia coli to degrade chlorpyrifos (Cp) using an organophosphorus hydrolase enzyme by employing the Lpp-OmpA chimera and the N-terminal domain of the ice nucleation protein as anchoring motifs. Tracing of the expression location of the recombinant protein using SDS-PAGE showed the presentation of OPH by both anchors on the outer membrane. This is the first report on the presentation of OPH on the cell surface by Lpp-OmpA under the control of the T7 promoter. The results showed cell growth in the presence of Cp as the sole source of energy, without growth inhibition, and with higher whole-cell activity for both cells harboring plasmids pENVO and pELMO, at approximately 10,342.85 and 10,857.14 U/mg, respectively. Noticeably, the protein displayed by pELMO was lower than the protein displayed by pENVO. It can be concluded that Lpp-OmpA can display less protein, but more functional OPH protein. These results highlight the high potential, of both engineered bacteria, for use in the bioremediation of pesticide-contaminated sources in the environment.


Influenza surveillance in England and Wales: October 1999 to May 2000.
The period of increased influenza activity in England and Wales in the winter of 1999/2000 was associated with considerable morbidity and mortality and well-publicized pressure on hospital services. The influenza activity coincided with the regular annual increase in respiratory syncytial virus infections and the Christmas and New Year holiday period. Consultation rates with general practitioners for influenza-like illness did not reach 'epidemic' levels but were higher than seen in many winters and comparable with those seen in two out of the previous three winters. In common with those winters, attack rates for influenza-like illness and acute bronchitis were especially high in elderly people among whom complications of acute infection and hospital admissions increased. Excess mortality due to influenza during this period appeared to be substantial but was not as high as seen in the last epidemic (1989/90).


Circadian rhythms in exercise performance: implications for hormonal and muscular adaptation.
Almost all physiological and biochemical processes within the human body follow a circadian rhythm (CR). In humans, the suprachiasmatic nucleus regulates sleep- wake cycle and other daily biorhythms in line with solar time. Due to such daily physiological fluctuations, several investigations on neuromuscular performance have reported a distinct CR during exercise. Generally, peak performances have been found to occur in the early evening, at approximately the peak of core body temperature. The increase in core body temperature has been found to increase energy metabolism, improve muscle compliance and facilitate actin-myosin crossbridging. In addition, steroidal hormones such as testosterone (T) and cortisol (C) also display a clear CR. The role of T within the body is to maintain anabolism through the process of protein synthesis. By contrast, C plays a catabolic function and is involved in the response of stress. Due to the anabolic and catabolic nature of both T and C, it has been postulated that a causal relationship may exist between the CR of T and C and muscular performance. This review will therefore discuss the effects of CR on physical performance and its implications for training. Furthermore, this review will examine the impact of muscular performance on CR in hormonal responses and whether could variations in T and C be potentially beneficial for muscular adaptation. Key pointsA distinct CR can be observed in physical performance.CR of exercise performance is highly associated with CR in core body temperatureBoth T and C display a clear CR, however, the current evidence does not show a clear relationship with neuromuscular adaptations.TST is able to induce changes in physical performance variables at the particular time point, but not for the circadian profile of T and C.


Neurological Complications and Cataract in a Child With Thalassemia Major Treated With Deferiprone.
The oral iron chelator deferiprone is associated with various side effects including agranulocytosis, arthropathy, and deranged liver function tests. Rarely, neurological and visual side effects have been reported with high doses. The authors describe rare neurological manifestations of cerebellar ataxia, hypertonia, and bilateral cataract in an 11-year-old boy with thalassemia major on recommended therapeutic doses of deferiprone. The neurological abnormalities resolved with stoppage of deferiprone. Central nervous system toxicity and lenticular opacities may be attributed to the low molecular weight of deferiprone and its ability to cross the blood-brain and blood-ocular barrier, respectively. Clinicians should be alert to the possibility of neurological abnormalities that may occur during deferiprone therapy.


Health risk behaviors and mental health problems as mediators of the relationship between childhood abuse and adult health.
We examined the relationship between childhood abuse and adult health risk behaviors, and we explored whether adult health risk behaviors or mental health problems mediated the relationship between childhood abuse and adult health problems and health care utilization. We used logistic regression to analyze data from the Mental Health Supplement of the Ontario Health Survey, a representative population sample (N = 8116) of respondents aged 15 to 64 years. We found relationships between childhood sexual abuse and smoking (odds ratio [OR] = 1.52; 95% confidence interval [CI] = 1.16, 1.99), alcohol problems (OR = 2.44; 95% CI = 1.74, 3.44), obesity (OR = 1.61; 95% CI = 1.14, 2.27), having more than 1 sexual partner in the previous year (OR = 2.34; 95% CI = 1.44, 3.80), and mental health problems (OR = 2.26; 95% CI = 1.78. 2.87). We also found relationships between these factors (with the exception of obesity) and childhood physical abuse. Mediation analysis suggested that health risk behaviors and particularly mental health problems are partial mediators of the relationship between childhood abuse and adult health. Public health approaches that aim to decrease child abuse by supporting positive parent-child relationships, reducing the development of health risk behaviors, and addressing children's mental health are likely to improve long-term population health.


Combining a weed traits database with a population dynamics model predicts shifts in weed communities.
A functional approach to predicting shifts in weed floras in response to management or environmental change requires the combination of data on weed traits with analytical frameworks that capture the filtering effect of selection pressures on traits. A weed traits database (WTDB) was designed, populated and analysed, initially using data for 19 common European weeds, to begin to consolidate trait data in a single repository. The initial choice of traits was driven by the requirements of empirical models of weed population dynamics to identify correlations between traits and model parameters. These relationships were used to build a generic model, operating at the level of functional traits, to simulate the impact of increasing herbicide and fertiliser use on virtual weeds along gradients of seed weight and maximum height. The model generated 'fitness contours' (defined as population growth rates) within this trait space in different scenarios, onto which two sets of weed species, defined as common or declining in the UK, were mapped. The effect of increasing inputs on the weed flora was successfully simulated; 77% of common species were predicted to have stable or increasing populations under high fertiliser and herbicide use, in contrast with only 29% of the species that have declined. Future development of the WTDB will aim to increase the number of species covered, incorporate a wider range of traits and analyse intraspecific variability under contrasting management and environments.


Mutants of basic fibroblast growth factor identify different cellular response programs.
Mutations, expected to affect the intracellular routing, i.e. additional nuclear localization sequences (NLS; the natural 23 kDa isoform and a 17D27R mutant) and/or a deletion of amino acids 26-29 (23 delta 26-29 and 17 delta 26-29), were introduced in basic fibroblast growth factor (bFGF). The mutants were assayed for their mitotic activity and their capacity to induce a tissue-specific response in human umbilical vein endothelial cells [HUVECs; induction of urokinase plasminogen activator receptor (u-PAR)], or in rat lens epithelial cells (fibre cell differentiation). In HUVECs, the 17D27R mutant had wild type activity, the 23 kDa and the delta 26-29 proteins were impaired in the induction of both mitosis and u-PAR. The delta 26-29 proteins, but not the 23 kDa protein or 17D27R mutant, were also impaired in receptor binding in that they bound only to a subset of receptors. The concentration of 17 kDa bFGF required for half maximal u-PAR response was 30 fold higher than for the half maximal 3H-thymidine incorporation. Addition of an NLS to bFGF strongly inhibited the induction of fibre cell differentiation, though it had little effect on the stimulation of DNA synthesis. The 17 delta 26-29 kDa mutant had wild type differentiation activity but was a poor mitogen for lens epithelial cells.


Best medical practice in practice: measuring efficiency in mammography screening.
Breast cancer, screening and mammography have caused considerable debate in several countries. This article explores the concept of best medical practice in the context of mammographic screening for breast cancer. Maximizing the use of technology, ignores the risks intrinsic to technological intervention. To do no harm in modern medical practice means largely doing nothing. Best medical practice, therefore, requires a balancing of benefits and risks so that best practice is that which does more good than harm. At the same time, not all interventions that do more good than harm can be funded out of the current health care budget. Thus, best medical practice is economically efficient practice. From the conceptual notion of what is best medical practice, this article turns to the problem of what that means in practical terms. Can we recognize best medical practice when it occurs? The identification, measurement and valuation of costs and benefits are discussed as a specific case study, in the context of breast cancer screening. Many of the difficulties involved here, particularly on the benefit side, are highlighted, especially in the context of QALYs. Yet, whatever the difficulties involved they have to be seen in the context of otherwise settling for something less i.e. inefficient medical practice.


The association between whole blood viscosity and high thrombus burden in patients with non-ST elevation myocardial infarction.
Prior studies showed that patients with elevated whole blood viscosity (WBV) had a higher risk of arterial thrombosis, acute stent thrombosis, and left ventricular apical thrombus presence after acute coronary syndrome. This investigation aimed to determine the association between WBV and high thrombus burden (HTB) in non-ST elevation myocardial infarction (NSTEMI) patients treated with percutaneous coronary intervention (PCI). This retrospective cohort investigation included data from consecutive 290 NSTEMI patients who received PCI at a tertiary institution. Patients with grade 1-3 thrombus burden were categorized as having low thrombus burden (LTB) (n = 178), whereas those with grade 4-5 thrombus burden were classified as having HTB (n = 112). WBV at high shear rate (HSR) and low shear rate (LSR) were estimated using hematocrit (HTC) and total protein levels. Patients with HTB had higher WBV at both LSR and HSR. In HTB patients, the frequency of infarct-related artery (IRA) reference vessel diameter, distal embolization, and no-reflow was also higher. Multivariable logistic regression models indicated that WBV at LSR (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.014-1.043; P < 0.001) and HSR (OR, 1.606; 95% CI, 1.334-1.953; P < 0.001) were independent predictors of HTB in NSTEMI patients. Notably, the area under the curve value of WBV at both shear rates was greater than that of its components, including total protein and HTC. This is the first study showing that WBV at both shear rates is a significant predictor of HTB in NSTEMI patients.


Serum levels of vitamin D3 and 25-hydroxyvitamin D3 in elderly and young adults.
Serum levels of vitamin D3, 25(OH)D3, and vitamin D binding protein (DBP) were measured in a group of elderly subjects (71-96 years) and a group of young adults (22-40 years). The mean serum levels of vitamin D3, 25(OH)D3 and DBP were significantly lower in the elderly subjects compared to the young adults. The mean molar ratio of 25(OH)D3 to vitamin D3 was significantly higher in the elderly compared to the young adults. A parabolic relationship was found between the serum levels of 25(OH)D3 and vitamin D3 in both groups. This relationship gives a higher ratio of the serum levels of 25(OH)D3 to vitamin D3 in the lower part of the vitamin D3 range. Our data do not indicate impaired hepatic 25-hydroxylation of vitamin D3 in the elderly.


Caught between ideals and reality: Phenomenological-hermeneutic study of healthcare providers' experiences while interacting with mechanically ventilated patients.
This study aimed to explore healthcare providers' experiences of their communication and interaction with conscious patients on mechanical ventilation in intensive care. Nurses, physicians, and physiotherapists were interviewed after they had been video recorded in naturally occurring interactions with patients. The interviews were analyzed using a phenomenological-hermeneutical approach. Three themes were identified: The willingness to engage and understand the mechanically ventilated patient, the potential risk of neglecting the patient in the encounters, and provider interdependence as the core of intensive care. The themes elicited how providers handled the dissonance between their own personal ideals of care and their real-world encounters with patients and other professionals. The healthcare providers were aware of how easily patients could be neglected while being non-vocal, and therefore invested time and effort communicating with the patients. Based on their personal ideals of patient participation and autonomy, it was difficult to perform procedures, such as weaning off the ventilator or mobilization, to which the patient was opposed. Interprofessional collaboration was valued by the providers in such situations. The study revealed that providers need to consider the communication barriers that exist on the individual and team levels when interacting with patients on mechanical ventilation.


Dietary interventions to prevent high-fructose diet-associated worsening of colitis and colitis-associated tumorigenesis in mice.
Diet is believed to be an important factor in the pathogenesis of inflammatory bowel disease. High consumption of dietary fructose has been shown to exacerbate experimental colitis, an effect mediated through the gut microbiota. This study evaluated whether dietary alterations could attenuate the detrimental effects of a high-fructose diet (HFrD) in experimental colitis. First, we determined whether the procolitic effects of a HFrD could be reversed by switching mice from a HFrD to a control diet. This diet change completely prevented HFrD-induced worsening of acute colitis, in association with a rapid normalization of the microbiota. Second, we tested the effects of dietary fiber, which demonstrated that psyllium was the most effective type of fiber for protecting against HFrD-induced worsening of acute colitis, compared with pectin, inulin, or cellulose. In fact, supplemental psyllium nearly completely prevented the detrimental effects of the HFrD, an effect associated with a shift in the gut microbiota. We next determined whether the protective effects of these interventions could be extended to chronic colitis and colitis-associated tumorigenesis. Using the azoxymethane/dextran sodium sulfate model, we first demonstrated that HFrD feeding exacerbated chronic colitis and increased colitis-associated tumorigenesis. Using the same dietary changes tested in the acute colitis setting, we also showed that mice were protected from HFrD-mediated enhanced chronic colitis and tumorigenesis, upon either diet switching or psyllium supplementation. Taken together, these findings suggest that high consumption of fructose may enhance colon tumorigenesis associated with long-standing colitis, an effect that could be reduced by dietary alterations.


Investigating ozone-induced decomposition of surface-bound permethrin for conditions in aircraft cabins.
The reaction of ozone with permethrin can potentially form phosgene. Published evidence on ozone levels and permethrin surface concentrations in aircraft cabins indicated that significant phosgene formation might occur in this setting. A derivatization technique was developed to detect phosgene with a lower limit of detection of 2 ppb. Chamber experiments were conducted with permethrin-coated materials (glass, carpet, seat fabric, and plastic) exposed to ozone under cabin-relevant conditions (150 ppb O(3), 4.5/h air exchange rate, <1% relative humidity, 1700 ng/cm(2) of permethrin). Phosgene was not detected in these experiments. Reaction of ozone with permethrin appears to be hindered by the electron-withdrawing chlorine atoms adjacent to the double bond in permethrin. Experimental results indicate that the upper limit on the reaction probability of ozone with surface-bound permethrin is approximately 10(-7). Extrapolation by means of material-balance modeling indicates that the upper limit on the phosgene level in aircraft cabins resulting from this chemistry is approximately 1 microg/m(3) or approximately 0.3 ppb. It was thus determined that phosgene formation, if it occurs in aircraft cabins, is not likely to exceed relevant, health-based phosgene exposure guidelines. Phosgene formation from ozone-initiated oxidation of permethrin in the aircraft cabin environment, if it occurs, is estimated to generate levels below the California Office of Environmental Health Hazard Assessment acute reference exposure level of 4 microg/m(3) or approximately 1 ppb.


Ameliorative effect of black ginseng extract against oxidative stress-induced cellular damages in mouse hepatocytes.
Oxidative stress induces the production of reactive oxygen species (ROS), which play important causative roles in various pathological conditions. Black ginseng (BG), a type of steam-processed ginseng, has drawn significant attention due to its biological activity, and is more potent than white ginseng (WG) or red ginseng (RG). We evaluated the protective effects of BG extract (BGE) against oxidative stress-induced cellular damage, in comparison with WG extract (WGE) and RG extract (RGE) in a cell culture model. Ethanolic extracts of WG, RG, and BG were used to evaluate ginsenoside profiles, total polyphenols, flavonoid contents, and antioxidant activity. Using AML-12 cells treated with H2O2, the protective effects of WGE, RGE, and BGE on cellular redox status, DNA, protein, lipid damage, and apoptosis levels were investigated. BGE exhibited significantly enhanced antioxidant potential, as well as total flavonoid and polyphenol contents. ATP levels were significantly higher in BGE-treated cells than in control; ROS generation and glutathione disulfide levels were lower but glutathione (GSH) and NADPH levels were higher in BGE-treated cells than in other groups. Pretreatment with BGE inhibited apoptosis and therefore protected cells from oxidative stress-induced cellular damage, probably through ROS scavenging. Collectively, our results demonstrate that BGE protects AML-12 cells from oxidative stress-induced cellular damages more effectively than WGE or RGE, through ROS scavenging, maintenance of redox status, and activation of the antioxidant defense system.


Study of Energy Storage Processes in Bundle Sheath Cells of Zea mays.
Photochemical energy storage in isolated bundle sheath cells from Zea mays was examined. Photoacoustic spectroscopy was used in this study to monitor energy storage processes. The presence of methyl viologen or addition of substrates which activated carbon fixation, prevented energy storage processes through the electron transport system. The energy storage was inhibited completely by dibromothymoquinone (DBMIB) and DCMU, inhibitors of noncyclic electron flow. However, the reductants such as dithiothreitol and ascorbate increased the energy storage. It was concluded that photosystem (PS) I may be reduced by some electron donor(s) other than water and that PSII only partially participates in PSI reduction. It is postulated that the role of PSII is to regulate PSI electron transport and prevent its overoxidation. In the presence of high level of malate, photoacoustic spectroscopy indicated a low energy storage which may be due to induction of energy utilization in carbon assimilation.


Mucinous cystic neoplasms of the pancreas.
Since their initial description, mucinous cystic neoplasms have been difficult to classify. This article attempts to clarify histological, clinical, and genetic criteria so that the pathologist can categorize each mucinous cystic neoplasm into 1 of 4 possible categories. Mucinous cystadenomas contain a single layer of mucin-producing, columnar epithelium lacking significant atypia. Borderline mucinous cystic neoplasms contain cells with moderate atypia. Mucinous cystic neoplasms with in situ carcinoma show significant architectural and cytological atypia. When invasive carcinoma is present in association with a mucinous cystic neoplasm, then the diagnosis of invasive mucinous cystadenocarcinoma should be made. The categorization of mucinous cystic neoplasms into these groups is essential because it accurately predicts outcome, provided that the tumor has been sampled and examined thoroughly. Completely removed mucinous cystadenomas, borderline mucinous cystic neoplasms, and mucinous cystic neoplasms with in situ carcinoma follow benign courses. Partial resection should be avoided as evidence suggests that mucinous cystic neoplasms can progress from adenomas to borderline lesions to carcinomas in situ to invasive carcinomas over time; partial resection should be avoided if possible. Modern molecular genetic techniques are helping to unravel the origins of rare variants of mucinous cystic tumors, such as the mucinous cystic tumor with an associated osteoclast-like giant cell tumor and the mucinous cystic tumor with sarcomatous stroma.


Use of Venous Excess UltraSound (VExUS) score in hyponatraemia management in critically ill patient.
Hyponatraemia is the most prevalent electrolyte disorder in the neurocritical care setting and is associated with a significant morbimortality. Cerebral salt wasting and inappropriate antidiuretic hormone secretion syndrome have been classically described as the two most frequent entities responsible for hyponatraemia in neurocritical care patients. An accurate aetiological diagnosis of hypotonic hyponatraemia requires a proper volume status assessment. Nevertheless, determination of volume status based on physical examination, laboratory findings and imaging modalities have several limitations and can lead to improperly diagnosis and hyponatraemia mismanagement. Point-of-care ultrasound (POCUS), specifically Venous Excess UltraSound (VExUS) score, is a fast and valuable tool to evaluate venous congestion at the bedside and identify hypervolaemia, helping the physicians in therapeutic decision making in a patient with hyponatraemia. We report a case where the use of POCUS, and more specifically VExUS, can be helpful in volume status assessment, complementing the complex management of multifactorial hyponatraemia in a neurocritical patient.


[Myringoplasty: our results].
Tympanoplasty is the surgical technique used to restore the anatomy and function of the middle ear. The tympanoplasty type I or myringoplasty is performed when the ear only has a perforation of the tympanic membrane without any ossicular damage. We present a retrospective study started in 1997 and finished in 2000 with a total of 118 cases who had undergone a myringoplasty along this period of time. The percentage of closure was 85.59% (n = 101). The techniques used were underlay in a 60.16% of the patients (n = 71), overlay in 34.74% (n = 41) and sandwich in 5.08% (n = 6). In the paediatric patients (under 14 years of age) the percentage of a successful graft following surgery was 88% and in the adults 83.87%. More than fifty years have passed. Since Zöllner and Wullstein described for the first time this type of surgery important because of its good results.


Selection and evaluation of new reference genes for RT-qPCR analysis in Epinephelus akaara based on transcriptome data.
Groupers are an economically important fish species in world fishery markets. Because many studies using RT-qPCR have addressed gene expression in groupers, appropriate reference genes are required to obtain reliable and accurate results. In this study, the most suitable reference genes were identified from eleven candidate genes of one of the most valuable species, Epinephelus akaara, in a range of different experimental conditions. Using the software packages geNorm, NormFinder, BestKeeper and refFinder, three traditionally used reference genes, β-actin (β-ACT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and beta-2-microglobulin (B2M), were identified as not suitable for E. akaara gene expression studies, whereas two newly identified reference genes, conserved oligomeric Golgi complex subunit 5 (Cog5) and brefeldin a-inhibited guanine nucleotide-exchange protein 1 (ARFGEF1), could be universally applied under all the tested conditions. These data provide the foundation for more precise results in RT-qPCR studies of gene expression in E. akaara and other Epinephelus species.


The Correction of Aphakia Using Anterior Chamber Intraocular Lens.
Senile cataract is the leading cause of severe vision loss and blindness worldwide, affecting approximately 20 million people. Anterior chamber intraocular lens (AC IOLs) remain a surgical option for visual rehabilitation required after surgical extraction of the cataract lens. Relevant publications in the PUBMED database were searched for articles regarding the types, visual outcomes and the complications followed the surgical implantation of AC IOLs. AC IOLs, which can be iris- (iris-claw) or angle-supported, increase visual acuity in most patients. However, complications, such as raised intraocular pressure, hyphaema, distorted pupil shape, iris pigment precipitates, endothelial cell loss, corneal oedema, neovascular glaucoma, retinal detachment and cystoid macular oedema, can unfavorably affect the surgical outcome. Although AC IOLs have been found to improve the visual acuity of patients with cataract, they have been also implicated in several complications.


History and systems of cognitive rehabilitation.
In a rapidly evolving field such as Cognitive Rehabilitation Therapy (CRT), it is important for practitioners to be fully acquainted with the history and efficacy of their discipline. This review traces the development of Cognitive Rehabilitation over the past century and describes the status of CRT today. The authors describe various methods of Cognitive Remediation that are in current use along with several developmental issues that have influenced the field over the years. Other issues such as the efficacy of CRT and who these techniques are designed to help are also addressed. The conclusion is that Cognitive Remediation has developed to the point where it can now provide efficacious treatment for a variety of different cognitive disorders.


Efficacy and Safety of 2 Fingolimod Doses vs Glatiramer Acetate for the Treatment of Patients With Relapsing-Remitting Multiple Sclerosis: A Randomized Clinical Trial.
Doses of fingolimod lower than 0.5 mg per day were not investigated during the fingolimod clinical development program. Whether lower doses of fingolimod might retain efficacy with fewer safety risks remains unknown. To evaluate the efficacy and safety of fingolimod, 0.5 mg, and fingolimod, 0.25 mg, compared with glatiramer acetate and to assess whether these doses of fingolimod show superior efficacy to glatiramer acetate in adult patients with relapsing-remitting multiple sclerosis. Fingolimod, 0.5 mg, or fingolimod, 0.25 mg, orally once per day or glatiramer acetate, 20 mg, subcutaneously once per day. The Multiple Sclerosis Study Evaluating Safety and Efficacy of Two Doses of Fingolimod Versus Copaxone (ASSESS) was a phase 3b multicenter randomized rater-blinded and dose-blinded 12-month clinical trial conducted between August 9, 2012, and April 30, 2018 (including the time required to recruit participants). A total of 1461 patients aged 18 to 65 years with relapsing-remitting multiple sclerosis were screened, and 1064 participants were randomized. These participants had at least 1 documented relapse during the previous year or 2 documented relapses during the previous 2 years and an Expanded Disability Status Scale score of 0 to 6 at screening. Data were analyzed between September and November 2018. The superiority of the fingolimod doses was tested hierarchically, with fingolimod, 0.5 mg, vs glatiramer acetate, 20 mg, tested first, followed by fingolimod, 0.25 mg, vs glatiramer acetate, 20 mg. The primary end point was the reduction in annualized relapse rate (ARR). Magnetic resonance imaging parameters, safety, and tolerability were also assessed. Of 1461 adult patients screened, 1064 participants (72.8%) were randomized (mean [SD] age, 39.6 [11.0] years; 792 women [74.4%]) to 3 treatment groups: 352 participants received fingolimod, 0.5 mg, 370 participants received fingolimod, 0.25 mg, and 342 participants received glatiramer acetate, 20 mg. In total, 859 participants (80.7%) completed the study. Treatment with fingolimod, 0.5 mg, was superior to treatment with glatiramer acetate, 20 mg, in reducing ARR (40.7% relative reduction); the relative reduction with fingolimod, 0.25 mg, was 14.6%, which was not statistically significant (for fingolimod, 0.5 mg, ARR, 0.15; 95% CI, 0.11-0.21; for fingolimod, 0.25 mg, ARR, 0.22; 95% CI, 0.17-0.29; for glatiramer acetate, 20 mg, ARR, 0.26; 95% CI, 0.20-0.34). Treatment with both fingolimod doses (0.5 mg and 0.25 mg) significantly reduced new or newly enlarging T2 and gadolinium-enhancing T1 lesions compared with treatment with glatiramer acetate. Adverse events were reported in similar proportions across treatment groups (312 participants [90.4%] in the fingolimod, 0.5 mg, group, 323 participants [88.3%] in the fingolimod, 0.25 mg, group, and 283 participants [87.3%] in the glatiramer acetate group). Fingolimod, 0.5 mg, demonstrated superior clinical efficacy compared with glatiramer acetate, 20 mg, and had a superior benefit-risk profile compared with fingolimod, 0.25 mg, in adult participants with relapsing-remitting multiple sclerosis. ClinicalTrials.gov Identifier: NCT01633112.


The effects of halothane on ventricular tachycardia in intact dogs.
Halothane has either proarrhythmic or antiarrhythmic effects in a variety of clinical circumstances. This investigation tested the hypothesis that halothane would display different effects on ventricular tachycardia (VT) produced by different electrophysiologic mechanisms in intact dogs. Four models of VT produced by abnormal automaticity, reentry, delayed-afterdepolarization-induced triggered activity, and early-afterdepolarization-induced triggered automaticity (groups 1-4, respectively) were studied. In groups 1 and 2, the left anterior descending coronary artery (LAD) was ligated. In group 1 (n = 5), 24 h after LAD ligation and infarction, all dogs demonstrated incessant VT with 94.7 +/- 2.3% of beats of ventricular origin. This ectopy presumably was due to abnormal automaticity. Halothane reduced the frequency of ventricular ectopy until at 2% halothane only 34.8 +/- 15% of beats were of ventricular origin. One week after LAD ligation, programmed stimulation produced nonstimulated extrasystoles of presumably reentrant origin in six dogs. In three, halothane 1% abolished extrasystoles while increasing the ventricular refractory period by 23 +/- 3.8% (P less than 0.05). In the three other dogs, halothane had no effect (two dogs) or worsened the severity of VT (one dog), while the refractory period increased by 7.7% (P greater than 0.05). In group 3 dogs, ouabain was infused until VT secondary to triggered activity occurred. Halothane restored sinus rhythm in 4 of 5 dogs. Overall the percentage of sinus beats increased from 11.1 +/- 2.8 to 97.4 +/- 2.6% when halothane 2% was added during ouabain toxicity. Cesium chloride infusion increased the QT interval and produced complex VT in 5 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)


[Preoperative differential diagnosis of cystic adnexal tumors: double-contrast MRT].
Preoperative assessment of adnexal lesions as benign or malignant by MRI with gastrointestinal and intravenous contrast. 46 patients with benign (n = 42) and malignant (n = 4) cystic adnexal tumours underwent MRI of the pelvis. Transaxial and coronal images were acquired using conventional T1- and T2-weighted SE-sequences after oral administration of superparamagnetic iron oxide particles (Ferristene). Additional T1-weighted SE-images were obtained immediately following gadodiamide (Gd DTPA-BMA) injection. MRI correctly classified the four malignant lesions, whereas nine histologically benign lesions were misdiagnosed as malignant. Intravenous contrast yielded a superior delineation of intratumor architecture. Due to exclusion of solid structures. MRI with oral and i.v. contrast enables to dismiss suspected malignity in cystic adnexal lesions. Because of the non-specificity of the macroscopic criteria of dignity, the MR diagnosis "malignity" is of limited value.


Trigeminocardiac reflex during maxillary third molar extraction: Our experience.
Trigeminocardiac reflex (TCR) is a cascade of physiological response secondary to the stimulation of any of the sensory divisions of the trigeminal nerve, which is the largest cranial nerve and provides sensory supply to the face, scalp, mucosa of the nose, and mouth. This response usually presents as a triad including bradycardia, apnea, and gastric motility changes. On the another side, transient loss of consciousness or vasovagal syncope, a well-known phenomenon in dentomaxillofacial surgery with its pathophysiology fully elucidated, is thought to be mediated by TCR and sometimes termed as dentocardiac reflex. Thus, it is imperative to know about TCR and its association with routine dental and maxillofacial surgery procedures. It can potentially happen during any minor or major oral surgical procedures ranging from simple third molar extractions, soft tissue surgeries, root canal treatments, or management of maxillofacial fractures. This paper presents two case reports demonstrating TCR which presented during maxillary third molar extraction and author(s) own experience in managing the same.


[Effects of peroxisome proliferators-activated receptor gamma agonists on transforming growth factor-beta1 and Smads signal pathway: experiment with rat renal fibroblasts].
To study the effects of peroxisome proliferators-activated receptor gamma (PPARgamma) agonists on transforming growth factor (TGF)-beta1-induced fibrotic responses in renal fibroblasts, so as to investigate its effects in prevention of tubulointerstitial fibrosis. Rat renal fibroblasts of the line NRK/49F were cultured and divided into groups. In group 1 TGFbeta1 of the concentrations of 0, 1, 2, 5, and 10 ng/ml was added and co-cultured for 24 h. In group 2 TGFbeta1 of the concentration of 5 ng/ml was added and co-cultured for 0, 6, 12, and 24 h respectively. Groups 3, 4, and 5 were pretreated with 10 micromol/L15d-PGJ2, PPARgamma ligand, 10 micromol/L troglitazone, agonist of, and 10 micromol/L ciglitazone, both PPARgamma agonists, respectively for 2 h, then treated with 5 ng/ml TGFbeta1. A blank control group was set up. The cultured cells were collected. RT-PCR was used to detect the mRNA expression of TGF-beta1-indued fibronectin (FN). Western blotting was used to detect the expression of TGF-beta1-induced FN, Smad, and phosphorylated Smad (p-Smad) proteins. TGF-beta1 enhanced the FN mRNA expression in a dose- and time-dependent manner. The FN mRNA expression of the 5 ng/ml TGF-beta1 group was 3.7 times that of the control group (P < 0.05). The FN mRNA expression of the 15d-PGJ2, troglitazone-, and ciglitazone-pretreated groups were lower than that of the 5 ng/ml TGF-beta1 group by 37.3%, 41.5%, and 22.7% respectively (all P < 0.05). The p-Smad2/3 protein expression levels of the TGF-beta1 group began to increase 15 minutes after stimulation, increased in a time-dependent manner, peaked 1 hour after, and began to decrease 2 hours later. However, the levels of protein expression of total Smad2 and Smad3 did not change significantly in all groups. Both 2 ng/ml TGFbeta1 and 5 ng/ml TGFbeta1 significantly induced the increase of protein expression of p-Smad2/3 (all P < 0.05). The levels of protein expression of p-Smad2 and p-Smad3 of the 5 ng/ml TGFbeta1 group were 3.42 and 0.97 times those of the 2 ng/ml TGFbeta1 (both P < 0.05). The levels of protein expression of p-Smad2/3 of the 15d-PGJ2, troglitazone-, and ciglitazone-pretreated groups were all significantly lower than that of the 5 ng/ml TGFbeta1 group by 61.2%, 53.0%, and 59.5% (all P < 0.05), However, there was no significant difference among different drug-treated groups (all P > 0.05). Possibly through abrogating TGF-beta1/Smads signaling pathway, PPARgamma agonists inhibit TGF-beta1-induced renal fibroblast extracellular matrix synthesis and may play a potential role in preventing tubulointerstitial fibrosis as a novel approach to prevent the progress of end stage renal dysfunction.


Beyond cells - The virome in the human holobiont.
Viromics, or viral metagenomics, is a relatively new and burgeoning field of research that studies the complete collection of viruses forming part of the microbiota in any given niche. It has strong foundations rooted in over a century of discoveries in the field of virology and recent advances in molecular biology and sequencing technologies. Historically, most studies have deconstructed the concept of viruses into a simplified perception of viral agents as mere pathogens, which demerits the scope of large-scale viromic analyses. Viruses are, in fact, much more than regular parasites. They are by far the most dynamic and abundant entity and the greatest killers on the planet, as well as the most effective geo-transforming genetic engineers and resource recyclers, acting on all life strata in any habitat. Yet, most of this uncanny viral world remains vastly unexplored to date, greatly hindered by the bewildering complexity inherent to such studies and the methodological and conceptual limitations. Viromic studies are just starting to address some of these issues but they still lag behind microbial metagenomics. In recent years, however, higher-throughput analysis and resequencing have rekindled interest in a field that is just starting to show its true potential. In this review, we take a look at the scientific and technological developments that led to the advent of viral and bacterial metagenomics with a particular, but not exclusive, focus on human viromics from an ecological perspective. We also address some of the most relevant challenges that current viral studies face and ponder on the future directions of the field.


Pd(II) coordinated deprotonated diphenyl phosphino amino pyridine: reactivity towards solvent, base, and acid.
The reactivity and stability of P(III)-N and P(III)≈N bonds will be different towards various solvents, bases, and acids because of their difference in bond strength due to different N-pπ-P-dπ donor bonding. For this, a P≈N containing Pd(II) complex, [Pd(DPAP)2] (C1), was synthesized from the reaction between PdCl2(COD) (COD = 1,4-cyclooctadiene) and 2 equiv. DPAP (diphenyl phosphino amino pyridine) ligand, followed by deprotonation of the N-H proton of the coordinated DPAP. The reactivity and stability of coordinated P≈N in complex C1 were determined in various protic and aprotic solvents, bases, and acids. The inertness of coordinated P=N towards various solvents and bases was observed, whereas protonation occurs at the nitrogen of P=N in the presence of an acid to form P-NH, with the generation of dicationic palladium complexes (C2). The dicationic complex C2 is found to be stable in the presence of bulky monoanionic Sn(IV) reagents, whereas, in the presence of more nucleophilic anions like Br(-) or I(-), dissociation of one DPAP ligand from dicationic Pd(II) complexes C2 leads to the generation of Pd(DPAP)X2 (X = Br(-), I(-)). Finally, the utility of the complexes towards Suzuki coupling of various aryl bromides and aryl or heteraryl boronic acids has been checked.


Antecedents of posttraumatic stress disorder: wasn't being raped enough? A brief communication.
Many rape victims, like those traumatized by war, accidents, and natural disasters, are able to recover from their ordeal with supportive, crisis-oriented treatment. For others, however, symptoms may persist and require more intensive treatment. Hypnosis allows a modulated re-experiencing and abreaction of the traumatic event that can help to provide the victim with a relieving sense of mastery, and it fosters a receptive context for reassurance and interpretation regarding the irrational or exaggerated thoughts and feelings involved. 2 case examples are presented in which earlier conflicts appeared to play a role in perpetuating the patients' symptoms. Detecting and addressing these antecedents resulted in complete alleviation of long-standing problems through relatively brief treatment using hypnosis.


The role of HLA antigens in the aetiology of psoriasis.
To investigate the association of the HLA-C allele with psoriasis. Methods Twenty five type I psoriasis patients with 25 healthy controls participated in this study. PCR-SSP was preferred for HLA-C typing. The patients were questioned for age at onset and family history and examined for severity and area of involvement of the disease and presence of articular, nail and scalp involvement. PCRSSP method was preferred for HLA-C typing. Statistical analyses were made using the Chi-square test. Relative risk was assessed to determine the association between disease and HLA antigen. The increase prevalence of HLA-Cw6 antigen among type I psoriasis vulgaris patients (p=0.0047) compared with healthy controls was noticed, but not in the prevalence of other HLA-C alleles. Among psoriasis patients, 14 (56%) had a positive family history. Among all patients, eight (32%) had articular symptoms, 19 (76%) had nail involvement, and all subjects had scalp involvement. Onset of disease was 6.7 years earlier in patients with positive family history compared with negative family history. No significant association was found between HLA-C alleles and family history, clinical findings or severity of the disease. Our findings are consistent with previous studies that have shown association between HLA-Cw6 antigen and early onset of the disease. Clarifying the role of HLA-Cw6 antigen in the etiopathogenesis provides important advances in gene therapy for psoriasis.


Research ethics in Canada: experience of a group operating a human embryo and fetal tissue bank.
A Canadian research group is establishing a human embryo and fetal tissue bank. Its purpose is to provide researchers with frozen or fixed tissue specimens for use in protein and gene expression studies. Several legal and ethical issues have arisen, including questions about consent, use of these rare tissues, cost recovery, and profit-making. These issues are discussed here in light of the present lack of legislation in Canada. We make recommendations in these areas, and suggest that the bank's operations could legally fall under the jurisdiction of the Human Tissue Gift Act.


Nutritional advice for obesity management and health.
Obesity is one of the fastest developing public health problems in the world and is associated with increased risks in morbidity and mortality. Any treatment programme for overweight and obese people should place equal importance on weight reduction and the maintenance of the weight loss. The National Service Framework for Coronary Heart Disease (Department of Health, 2000) identified the vital role of primary care teams in tackling overweight and obesity. The aim of this article is to give a basic overview of some of the issues and principles of weight management in primary care and to ensure nurses are equipped to provide good quality, evidence-based nutritional advice on weight management.


Monitoring device acceptance in implantable cardioverter defibrillator patients using the Florida Patient Acceptance Survey.
Patient device acceptance might be essential in identifying patients at risk for adverse patient-reported outcomes following implantation of an implantable cardioverter defibrillator (ICD). We examined the validity and reliability of the Florida Patient Acceptance Scale (FPAS) and identified correlates of device acceptance in a Dutch cohort of ICD patients. Patients with a first-time ICD (N = 272, mean age = 59.2 ± 11.9, 82% men) recruited from the Erasmus Medical Center, Rotterdam, or the Medisch Spectrum Twente, Enschede, The Netherlands completed the FPAS, the Type D Scale, and the Hospital Anxiety and Depression Scale. Exploratory and confirmatory factor analyses indicated that eliminating three items from the FPAS, leaving 12 items contributing to three factors, is equivalent to the original four-factor version of the FPAS. The abbreviated FPAS had a high internal consistency both for the total scale and all subscales, with Cronbach's alphas ranging from 0.76 to 0.82. Anxiety (odds ratio [OR]: 9.75; 95% confidence interval [CI]: 2.38-39.87; P = 0.002), depression (OR: 2.96; 95% CI: 0.98-8.93; P = 0.05), and the distressed (Type D) personality (OR: 5.04; 95% CI: 1.50-16.92; P = 0.01), but not demographic and clinical factors including shocks, were significant independent correlates of poor device acceptance. A shortened 12-item, three-factor version of the FPAS was shown to be a valid and internally consistent instrument to assess device acceptance in Dutch ICD patients. Psychological but not clinical factors were the primary correlates of device acceptance, which underlines the importance of taking into account the patient's psychological profile when seeking to identify patients at risk for adjustment difficulties after ICD implantation.


Autoradiographic analysis of vasoactive neuropeptide uptake by rabbit megakaryocytes and platelets.
Autoradiographic analysis has been performed to determine whether or not platelets and megakaryocytes can take up in vitro vasoactive neuropeptides such as [3H]angiotensin II, [3H]neuropeptide Y, [3H]substance P and [3H]vasopressin. Light microscope autoradiography has revealed the active uptake of [3H]angiotensin II by megakaryocytes. [3H]angiotensin II uptake by platelets has also been confirmed by electron microscope autoradiography. Silver grains are preferentially associated with the dense bodies of platelets. Neither megakaryocytes nor platelets show any active uptake of [3H]neuropeptide Y or [3H]substance P. Megakaryocytes are slightly labelled after incubation with [3H]vasopressin.


Absolute Quantification of Pure Free Radical Reagents by Combination of the Effective Magnetic Moment Method and Quantitative Electron Paramagnetic Resonance Method.
An absolute quantitative analysis of free radicals by combining the effective magnetic moment method and the quantitative electron paramagnetic resonance [qEPR] method is proposed. This combined method utilizes the advantages of both the analytical methods and compensates for their disadvantages. In the effective magnetic moment method, the magnetic moment under a constant magnetic field is measured accurately using a superconducting quantum interference device. The qEPR method compares a "primary standard sample" and "secondary standard sample". The effective magnetic moment method was used to determine the purity of the primary standard sample. The qEPR method realizes a simple purity analysis of free-radical reagents with traceability to the International System of Units (SI). The purity of the free radicals by the qEPR method for pure 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl benzoate [4HTB], 1-oxyl-2,2,6,6-tetramethyl-4-hydroxypiperidine [TEMPOL], and di(phenyl)-(2,4,6-trinitrophenyl)iminoazanium [DPPH] reagents was obtained with a relative expanded uncertainty of 0.7% for 4HTB to 1.5% for the DPPH. These small uncertainties were almost equal to those of the purity of the primary standard samples and were achieved by adopting in-plane positioning of the measured sample perpendicular to the cylindrical axis of the sample space of the superconducting quantum interference device. Some purity values of the free radicals for these reagents differed from those stated by the manufacturers. This combined method enables short-time quality control of pure radical reagents, instead of quality control by separation analytical methods or titrations.


Acute management of clavicle fractures. A long term functional outcome study.
The purpose of this study was to evaluate the long-term results after acute treatment of clavicle fractures. We reviewed 139 patients with an average age of 39.3 years (range: 18 to 74) who sustained a clavicle fracture either isolated or as part of a polytrauma. Besides demographic data, both clinical result and residual symptoms were also recorded. The average follow-up was 7.2 years (range: 4 to 13). The fracture showed a higher prevalence in young men and older women. The most frequent mechanism of injury was a fall (39.6%) and coexisting injuries were found in 12.9% of patients. Conservatively treated fractures united in 96.9% of cases and the time to union was no different with a sling or figure-of-eight bandage. Fracture location did not influence the functional outcome. One third of patients were still complaining of mild pain and discomfort during overhead activities and polytrauma patients had a lower Constant score.


Tropical calcific pancreatitis: strong association with SPINK1 trypsin inhibitor mutations.
Tropical calcific pancreatitis (TCP) is a chronic pancreatitis unique to developing countries in tropical regions. The cause of TCP is obscure. Whereas environmental factors, such as protein energy malnutrition and ingestion of cassava, have been implicated, a genetic predisposition to the disease also may be important. In the present study we report on mutations in the serine protease inhibitor, Kazal type 1 (SPINK1) gene in north Indian patients with TCP. We studied 66 unrelated TCP patients (44 men, 49 with diabetes, and 6 with family history of TCP), 25 relatives, and 92 healthy control subjects. Samples were analyzed for SPINK1 variants (-53C>T, L14P, N34S, P55S, and 272T>C) and cationic trypsinogen (PRSS1) variants (A16V, K23R, N29I, and R122H) by melting curve analysis. Twenty-nine patients (44%) carried the N34S missense mutation, of whom 9 (14%) were homozygotes. In contrast, only 2 (2.2%) control subjects were N34S heterozygotes (prevalence ratio 20.2; 95% confidence interval 5.0-81.8; P < 0.0001 vs. TCP). The severity of pancreatitis did not differ between TCP patients with or without N34S, or among those heterozygous or homozygous for N34S. Among TCP patients with or without diabetes, the frequency of N34S carriers (43% vs. 47%) and N34S homozygotes (14% vs. 12%) was similar. TCP is highly associated with the SPINK1 N34S mutation. The high prevalence of N34S in TCP patients with and without diabetes suggests that these 2 subtypes have a similar genetic predisposition. The genetic predisposition to TCP resembles, at least in part, the idiopathic chronic pancreatitis found in industrialized countries.


Cerebellar preference of luminal A and B type and basal ganglial preference of HER2-positive type breast cancer-derived brain metastases.
The purpose of the current study was to investigate the hypothesis that the spatial distribution of brain metastases could be affected by the biological subtypes of breast cancer. CT (n=1) or MRI (n=66) images of 67 patients with a total of 437 treatment-naive brain metastases from breast cancer were retrospectively reviewed. Patients were grouped according to the biological subtype of the tumor [luminal A, 28; luminal B, 9; human epidermal growth factor receptor 2 (HER2) positive, 14; triple-negative breast cancer (TNBC), 16]. All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. The distribution pattern of brain metastases after image standardization was analyzed. The cerebellum and the frontal lobe were more commonly affected by breast cancer brain metastases. Brain metastases from luminal A and B types of breast cancer arose more often in the cerebellum. Brain metastases from HER2-positive type breast cancer occurred more often in the putamen and the thalamus and less frequently in the cerebellum than other types (P=0.0057). The subtypes of breast cancer are related to differences in the spatial distributions of their brain metastases. These differences may be utilized to plan different cranial irradiation strategies according to the breast cancer subtypes.


Plant protein hydrolysates (plant peptones) as substitutes for animal proteins in embryo culture medium.
The aim of the present study was to improve the sanitary quality of in vitro-produced bovine embryos by using plant protein hydrolysates (plant peptones) as substitutes for animal proteins. Peptones were compared with bovine serum albumin (BSA) as the protein source in synthetic oviduct fluid medium and the quality of the resulting embryos was determined. Two batches of peptones (wheat and cotton) were selected on the basis of their anti-oxidant properties. When added to the culture medium, both peptones (at 0.56 mg mL(-1) for cotton peptone and at 0.18 mg mL(-1) for wheat peptone) led to similar developmental and hatching rates compared with 4 mg mL(-1) BSA and embryos were equally resistant to freezing and able to elongate after transfer. Surprisingly, a significant decrease in reduced glutathione (GSH) content was observed when embryos were produced with plant peptone instead of BSA. Supplementation of the culture medium with precursors of GSH (cysteine and beta-mercaptoethanol) significantly increased the GSH content. A shift of the sex ratio towards male embryos was seen for Day 8 embryos cultured with wheat peptone, whereas no shift was observed for embryos cultured in the presence of BSA or polyvinylpyrrolidone. In conclusion, culture with plant peptones enables embryos to be obtained at a similar rate and of similar quality to that seen following the use of BSA. The use of the plant peptones increased the sanitary quality of the embryos and decreased the cost of embryo production.


Morphological differentiation of bipolar cells in the ferret retina.
Bipolar cells are not only important for visual processing but input from these cells may underlie the reorganization of ganglion cell dendrites in the inner plexiform layer (IPL) during development. Because little is known about the development of bipolar cells, here we have used immunocytochemical markers and dye labeling to identify and follow their differentiation in the neonatal ferret retina. Putative cone bipolar cells were immunoreacted for calbindin and recoverin, and rod bipolar cells were immunostained for protein kinase C (PKC). Our results show that calbindin-immunoreactive cone bipolar cells appear at postnatal day 15 (P15), at which time their axonal terminals are already localized to the inner half of the IPL. By contrast, recoverin-immunoreactive cells with terminals in the IPL are present at birth, but many of these cells may be immature photoreceptors. By the second postnatal week, recoverin-positive cells resembling cone bipolar cells were clearly present, and with increasing age, two distinct strata of immunolabeled processes occupied the IPL. PKC-containing rod bipolar cells emerged by the fourth postnatal week and at this age have stratified arbors in the inner IPL. The early bias of bipolar axonal arbors in terminating in the inner or outer half of the IPL is confirmed by dye labeling of cells with somata in the inner nuclear layer. At P10, several days before ribbon synapses have been previously observed in the ferret IPL, the axon terminals of all dye-labeled bipolar cells were clearly stratified. The results suggest that bipolar cells could provide spatially localized interactions that are suitable for guiding dendritic lamination in the inner retina.


Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice.
It is well known that the intake of paraquat (PQ), an herbicide, causes severe lung injury at chronic phases. We examined the intrapulmonary gene expression of cytokines and growth factors after PQ administration. To induce lung injury, C57BL/6 mice were intraperitoneally injected twice a week with 20 mg/kg of PQ. Histopathologically, at the early phase, lots of alveolar spaces contained edematous fluid. At 3 weeks after PQ challenge, a marked thickening of the alveolar walls with the accumulation of macrophages and T cells was found. Azan staining revealed the patchy distribution of collagen accumulation, indicating pulmonary fibrosis. Consistently, intrapulmonary hydroxyproline contents were significantly elevated, compared with the controls. Semi-quantitative RT-PCR analysis demonstrated that the gene expression of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 were significantly increased at 3 weeks after PQ challenge compared with the controls. The mRNA expression of macrophage inflammatory protein (MIP)-1alpha and MIP-2 was significantly enhanced at 1 and 2 weeks after PQ treatment, respectively. Moreover, PQ-treated mice showed enhanced gene expression of fibrogenic growth factors such as transforming growth factor-beta, platelet-derived growth factor-A, acidic fibroblast growth factor, and hepatoctyte growth factor at 2 and/or 3 weeks after PQ challenge. The synergistic effects of these molecules are presumed to cause pulmonary fibrosis due to PQ challenge.


Multisensory Integration as a Window into Orderly and Disrupted Cognition and Communication.
During our everyday lives, we are confronted with a vast amount of information from several sensory modalities. This multisensory information needs to be appropriately integrated for us to effectively engage with and learn from our world. Research carried out over the last half century has provided new insights into the way such multisensory processing improves human performance and perception; the neurophysiological foundations of multisensory function; the time course for its development; how multisensory abilities differ in clinical populations; and, most recently, the links between multisensory processing and cognitive abilities. This review summarizes the extant literature on multisensory function in typical and atypical circumstances, discusses the implications of the work carried out to date for theory and research, and points toward next steps for advancing the field.


Training of medical students in resuscitation at the University of Ljubljana.
The Faculty of Medicine in Ljubljana has been offering formal training in cardiopulmonary resuscitation (CPR) to its students since 1988. The CPR courses are taught mostly by anaesthesiologists. To determine whether our training programme provides the students with adequate skills and knowledge in CPR we analyzed the results of the examinations, tests, questionnaires and interviews of all students who had received CPR training at our Faculty of Medicine in 1994. We found that all the 1st year students passed the skill test immediately after the basic life support (BLS) course and that the majority of these students showed good knowledge in the written exam at the end of the year. These students were generally satisfied with the first-aid lecture course and BLS course. The 4th year lecture courses, however, were less effective because only a few of the students were present at each lecture. The 6th year students ended the advanced cardiac life support (ACLS) courses and practice in the operating theatre with both satisfactory basic theoretical knowledge and also practical skills in CPR. Thus in the oral examination at the end of the 6th year the success rate at first attempt was high, and the interviews with these students showed that they had been given the opportunities to practice airway management, breathing support and venous cannulation. These findings suggest that the education programme provides our students with both a sound basic knowledge and adequate practical skills in CPR for postgraduate training in emergency medicine.


The proper role of evidence in complementary/alternative medicine.
In this article we explore the role evidence ought to play in complementary and alternative medicine (CAM). First, we consider the claim that evidence in the form of randomized controlled trials (RCTs) cannot be obtained for CAMs. Second, we consider various claims to the effect that there are ways of obtaining evidence that do not make use of RCTs. We argue that there is no good reason why CAM should be exempted from the general requirement that treatments undergo evaluation by RCT. Third, we consider two implications for health care policy. First, many activities in conventional medicine have never been rigorously evaluated and are widely in use nonetheless. We argue that this fails to provide a reason for exempting CAM from a demand for evidence. Second, CAM use may be compared to a choice of lifestyle, and this has a significant impact on which requirements of evidence can reasonably be imposed.


[Habits and problems of sleep in adolescent students].
The evaluation of sleep habits and sleep related problems in high school adolescent students in the Athens area and the assessment of these problems' relation to demographic and other variables was investigated by the Athens Insomnia Scale - 5 item version (AIS-5), which was administered to 713 adolescent Senior High School students in the Greater Athens Area. Data such as age, sex, school records, and time spent per week in school-related and extracurricular activities were collected. The sample's mean sleep duration was 7,5 hours, mean bedtime 12:20 am and wake-up time 7:15 am. Total sleep time was not affected by gender, but was influenced by time spent in various activities. Sleep complaints were related to delayed sleep, onset latency and insufficient total duration of sleep. Girls complained more than boys, while correlations showed that students with lower academic per formance and those in second grade were more likely to have higher AIS-5 scores. The results show that sleep time of high school students is dependent on practical matters such as school schedule and other activities, while sleep complaints are related to female gender, bad school performance as well as to the second grade. The difference between actual sleep time and sleep complaints should be considered when studying the sleep of adolescents.


How Do Clinicians Judge Fluency in Aphasia?
Aphasia fluency is multiply determined by underlying impairments in lexical retrieval, grammatical formulation, and speech production. This poses challenges for establishing a reliable and feasible tool to measure fluency in the clinic. We examine the reliability and validity of perceptual ratings and clinical perspectives on the utility and relevance of methods used to assess fluency. In an online survey, 112 speech-language pathologists rated spontaneous speech samples from 181 people with aphasia (PwA) on eight perceptual rating scales (overall fluency, speech rate, pausing, effort, melody, phrase length, grammaticality, and lexical retrieval) and answered questions about their current practices for assessing fluency in the clinic. Interrater reliability for the eight perceptual rating scales ranged from fair to good. The most reliable scales were speech rate, pausing, and phrase length. Similarly, clinicians' perceived fluency ratings were most strongly correlated to objective measures of speech rate and utterance length but were also related to grammatical complexity, lexical diversity, and phonological errors. Clinicians' ratings reflected expected aphasia subtype patterns: Individuals with Broca's and transcortical motor aphasia were rated below average on fluency, whereas those with anomic, conduction, and Wernicke's aphasia were rated above average. Most respondents reported using multiple methods in the clinic to measure fluency but relying most frequently on subjective judgments. This study lends support for the use of perceptual rating scales as valid assessments of speech-language production but highlights the need for a more reliable method for clinical use. We describe next steps for developing such a tool that is clinically feasible and helps to identify the underlying deficits disrupting fluency to inform treatment targets. https://doi.org/10.23641/asha.19326419.


In vitro evaluation of inhibitory effects of antidiabetic and antihyperlipidemic drugs on human carboxylesterase activities.
Human carboxylesterase (CES) 1A is responsible for the biotransformation of angiotensin-converting enzyme (ACE) inhibitors such as imidapril and temocapril. Because antidiabetic or antihyperlipidemic drugs are often coadministered with ACE inhibitors in clinical pharmacotherapy, the inhibitory effect of these drugs on CES1A1 enzyme activity was investigated. In addition, the inhibitory effect on CES2 enzyme activity was evaluated to compare it with that on CES1A1. The inhibitory effects were evaluated with 11 antidiabetic and 12 antihyperlipidemic drugs. The imidapril hydrolase activity by recombinant CES1A1 was substantially inhibited by lactone ring-containing statins such as simvastatin and lovastatin and thiazolidinediones such as troglitazone and rosiglitazone. The activity in human liver microsomes was also strongly inhibited by simvastatin and troglitazone (K(i) = 0.8 ± 0.1 and 5.6 ± 0.2 μM, respectively). However, statins containing no lactone ring such as pravastatin and fluvastatin did not show strong inhibition. 7-Ethyl-10-[4-(1-piperidono)-1-piperidono]carbonyloxycamptothecin hydrolase activity by recombinant human CES2 was substantially inhibited by fenofibrate (K(i) = 0.04 ± 0.01 μM) as well as by simvastatin (0.67 ± 0.09 μM). Other fibrates such as clinofibrate and bezafibrate did not show strong inhibition. Thus, the inhibitory effects of the thiazolidinediones and fenofibrate on CES1A1 and CES2 were different. Some statins such as simvastatin and lovastatin, thiazolidinediones, and fenofibrate might attenuate the drug efficacy of prodrugs biotransformed by CES1A and CES2.


The Drosophila ribosomal protein S6 gene includes a 3' triplication that arose by unequal crossing-over.
Ribosomal protein S6 (rpS6) is the major phosphoprotein of the small ribosomal subunit of eukaryotes and is phosphorylated in response to treatment with mitogens and other stimuli. We have examined the organization of the rpS6 gene of Drosophila melanogaster. Comparisons of a cDNA with genomic DNA identify a transcription unit including three exons. Two tandem repeats downstream of this transcription unit reiterate divergent copies of the third exon and flanking regions. Comparisons of these three repeats with respect to nucleotide base substitutions and deletions or insertions show clearly that they arose via a duplication and subsequent crossing-over between misaligned copies. Although no direct evidence exists that the downstream exons are transcribed, the maintenance of open reading frames in spite of extensive genetic changes is consistent with a protein-coding function.


[The relationship between work and vision in a preventive medicine context: the initial guidelines for a correct ergonomic ophthalmological approach proposed by the Italian Group for the Study of the Relationships between Work and Vision (G.I.L.V.). I. The presentation].
Modern technology poses numerous and complex problems concerning the implications for health in the work/vision relationship. While many of the hypotheses made in the past about the possibility of serious eye alterations in non-industrial workers have not been confirmed by recent investigations, considerable attention is at present being addressed to the short- and long-term effects of office work, especially in the case of tasks requiring prolonged visual effort "at near point". The prevalence of asthenopia in such workers is rather high, between 40 and 80%. The considerable specificity of the symptoms and the shortcomings in assessment of exposure in most of the research done so far has meant that no clear and unequivocal causal relationship between work involving intense visual effort and onset of asthenopia has been established. Nevertheless, from an analysis of the literature three main guidelines for a correct ergophthalmologic assessment can be identified: a) ophthalmologic assessments that will detect any transitory inefficiencies of the accommodation and convergence system; b) specific analysis of the technical and illumination conditions with special attention to the distribution of the natural and artificial light sources; c) quantification of airborne pollutants that have a potential irritative effect on the "ocular surface". Other environmental parameters that could be considered are electric and magnetic fields in the vicinity of VDTs and PCs and the microclimate of the workplace.


Algorithmic Multimodality Approach to Diagnosis and Treatment of Spinal CSF Leak and Venous Fistula in Patients With Spontaneous Intracranial Hypotension.
Spontaneous intracranial hypotension (SIH) is a disorder of CSF dynamics that causes a complex clinical syndrome and severe disability. SIH is challenging to diagnose because of the variability of its presenting clinical symptoms, the potential for subtle imaging findings to be easily overlooked, and the need for specialized diagnostic testing. Once SIH is suggested by clinical history and/or supported by initial neuroim-aging, many patients may undergo initial nontargeted epidural blood patching with variable and indefinite benefit. However, data suggest that precise localization of the CSF leak or CSF-venous fistula (CVF) can lead to more effective and durable treatment strategies. Leak localization can be achieved using a variety of advanced diagnostic imaging techniques, although these may not be widely performed at nontertiary medical centers, leaving many patients with the potential for inadequate workup or treatment. This review describes imaging techniques including dynamic fluoroscopic and CT myelography as well as delayed MR myelography and treatment options including percutaneous, endovascular, and surgical approaches for SIH. These are summarized by an algorithmic framework for radiologists to approach the workup and treatment of patients with suspected SIH. The importance of a multidisciplinary approach is emphasized.


[Magnetic resonance axonography by diffusion weighted echo planar imaging].
Anisotropy of apparent diffusivities of water molecules is known to be an excellent means for elucidating detailed information regarding neuronal fiber direction and density in live subjects. The recent development of magnetic resonance axonography (MRX) utilizing three dimensional anisotropy contrast(3DAC), using Echo Planar Imaging(EPI), a new algorithm for the treatment of apparent diffusion tensor, has provided an unprecedented opportunity for visualizing anatomic detail of the human brain. In this study, we applied the 3DAC method in normal human brain. The results clearly demonstrated that 3DAC is highly sensitive to orientation of fiber tracts. Considering the rather simple implementational process and high anatomic resolution, MRX based on the 3DAC method appears to be the ideal non-invasive imaging technique for assessment of the human brain in biomedicine.


Primary cutaneous angioplasmocellular hyperplasia.
Angioplasmocellular hyperplasia is a rare clinical condition with blood vessel proliferation and a reactive plasma cell infiltrate. To the best of our knowledge fewer than 20 cases of cutaneous angioplasmocellular hyperplasia have been published in English literature. We report a case of a 65-year-old man who presented with a long standing asymptomatic flesh colored ulcerated nodule on the back. Histopathological examination revealed a dermal vascular proliferation with polyclonal plasma cell infiltration. A diagnosis of angioplasmocellular hyperplasia was established. This entity is rare and we would like to emphasize the importance of clinico-pathological correlation to differentiate it from various other conditions of cutaneous plasma cell infiltration.


Closed-circuit system for the depuration of mussels experimentally contaminated with hepatitis A virus.
In Italy, the consumption of raw or slightly cooked mussels represents the most important risk factor for the transmission of hepatitis A virus (HAV). Although there exist effective methods for the bacterial depuration of contaminated mussels, these methods are poorly effective on enteric viruses. The objective of the present study was to evaluate the effectiveness of a closed-circuit depuration system that uses both ozone and UV light for disinfecting water and that allows salinity and temperature, important parameters for the metabolism of mussels (Mytilus galloprovincialis), to be maintained at constant levels. The results showed that this depuration method decreased the viral load (from 1.72 log 50% tissue culture infective dose [TCID50] ml(-1) to <1 log TCID50 ml(-1) within 24 h and from 3.82 log TCID50 ml(-1) to <1 log TCID50 ml(-1) within 48 h). However, in both cases, after 120 h of depuration, a residual amount of virus capable of replicating in cells was detected. These results show that depuration, even if performed with advanced systems, may not guarantee the absence of virus.


Intrinsically Disordered Flanking Regions Increase the Affinity of a Transcriptional Coactivator Interaction across Vertebrates.
Interactions between two proteins are often mediated by a disordered region in one protein binding to a groove in a folded interaction domain in the other one. While the main determinants of a certain interaction are typically found within a well-defined binding interface involving the groove, recent studies show that nonspecific contacts by flanking regions may increase the affinity. One example is the coupled binding and folding underlying the interaction between the two transcriptional coactivators NCOA3 (ACTR) and CBP, where the flanking regions of an intrinsically disordered region in human NCOA3 increases the affinity for CBP. However, it is not clear whether this flanking region-mediated effect is a peculiarity of this single protein interaction or if it is of functional relevance in a broader context. To further assess the role of flanking regions in the interaction between NCOA3 and CBP, we analyzed the interaction across orthologs and paralogs (NCOA1, 2, and 3) in human, zebra fish, and ghost shark. We found that flanking regions increased the affinity 2- to 9-fold in the six interactions tested. Conservation of the amino acid sequence is a strong indicator of function. Analogously, the observed conservation of increased affinity provided by flanking regions, accompanied by moderate sequence conservation, suggests that flanking regions may be under selection to promote the affinity between NCOA transcriptional coregulators and CBP.


Oncogenes and antioncogenes in lung tumorigenesis.
The role of oncogenes and antioncogenes in lung tumorigenesis is discussed in this review, with particular emphasis on their prognostic significance. Mutations in the ras family of oncogenes, overexpression of the myc and neu families of oncogenes, and mutations of p53, the recessive tumor suppressor gene, occur with differing frequencies in small cell lung cancer and non-small cell lung cancer, and are usually associated with a poor prognosis. Loss of heterozygosity, notably on chromosomes 3p, 5q, 9p, 13q, and 17p, is a common feature in lung carcinomas and its importance is also discussed.


[A case of cervico-mediastinal abscess, secondary to acute tonsillitis: investigation of the treatments].
No other infectious diseases in the field of otolaryngology cause rapid and lethal course than cervical abscess. A case of cervicomediastinal abscess secondary to acute tonsillitis was presented. The patient was a 43-year-old male with liver cirrhosis and primarily had the treatment of tonsillitis. The complication of duodenal perforation caused marked general deteriotation, and cervical abscess occured. Immediately after transfer to our department, he was treated by cervical drainage, laparotomy and chemotherapy. However, hepatic failure occured, and he died of sepsis on the 16th day after the onset of tonsillitis. Cervicomediastinal abscesses were classified according to severity in Stage 1-4. 34 cases of advanced cervical abscess were reported in Japan from 1976 to 1989. These cases were analyzed statistically in terms of primary focus of infection, surgical procedures, clinical isolates and chemotherapy, etc., and following results were obtained. 1) Primary focus; approximately 50% was due to the infection of the tonsills and the pharynx occupied about 50%, and the odontogenic infections, approximately 40%. 2) Surgical procedures; the neck doranaige approaching through the vertical incision resulted more effective. 3) Clinical isolates; aerobes and anaerobes accounted for 50% each of all strains. alpha-Streptococcus was predominant among aerobes, and Peptostreptococcus and Bacteroides were predominant among anaerobes. In order to confirm pathogenic bacteria of cervical abscess, clinical isolates of peritonsiller abscess and mandibular ostesis were compared with those of cervical abscess, because these infections are primary infectious diseases of cervical abscess.(ABSTRACT TRUNCATED AT 250 WORDS)


Measuring progressive independence with the resident supervision index: empirical approach.
A Resident Supervision Index (RSI) developed by our research team quantifies the intensity of resident supervision in graduate medical education, with the goal of testing for progressive independence. The 4-part RSI method includes a survey instrument for staff and residents (RSI Inventory), a strategy to score survey responses, a theoretical framework (patient centered optimal supervision), and a statistical model that accounts for the presence or absence of supervision and the intensity of patient care. The RSI Inventory data came from 140 outpatient encounters involving 57 residents and 37 attending physicians during a 3-month period at a Department of Veterans Affairs outpatient clinic. Responses are scored to quantitatively measure the intensity of resident supervision across 10 levels of patient services (staff is absent, is present, participated, or provided care with or without a resident), case discussion (resident-staff interaction), and oversight (staff reviewed case, reviewed medical chart, consulted with staff, or assessed patient). Scores are analyzed by level and for patient care using a 2-part model (supervision initiated [yes or no] versus intensity once supervision was initiated). All resident encounters had patient care supervision, resident oversight, or both. Consistent with the progressive independence hypothesis, residents were 1.72 (P = .019) times more likely to be fully responsible for patient care with each additional postgraduate year. Decreasing case complexity, increasing clinic workload, and advanced nonmedical degrees among attending staff were negatively associated with supervision intensity, although associations varied by supervision level. These data are consistent with the progressive independence hypothesis in graduate medical education and offer empirical support for the 4-part RSI method to quantify the intensity of resident supervision for research, program evaluation, and resident assessment purposes. Before informing policy, however, more scientific research in actual teaching settings is needed to better understand the relationships among patient outcomes, clinic workload, case complexity, and graduate medical education experience in resident supervision and professional development.


BBMerge - Accurate paired shotgun read merging via overlap.
Merging paired-end shotgun reads generated on high-throughput sequencing platforms can substantially improve various subsequent bioinformatics processes, including genome assembly, binning, mapping, annotation, and clustering for taxonomic analysis. With the inexorable growth of sequence data volume and CPU core counts, the speed and scalability of read-processing tools becomes ever-more important. The accuracy of shotgun read merging is crucial as well, as errors introduced by incorrect merging percolate through to reduce the quality of downstream analysis. Thus, we designed a new tool to maximize accuracy and minimize processing time, allowing the use of read merging on larger datasets, and in analyses highly sensitive to errors. We present BBMerge, a new merging tool for paired-end shotgun sequence data. We benchmark BBMerge by comparison with eight other widely used merging tools, assessing speed, accuracy and scalability. Evaluations of both synthetic and real-world datasets demonstrate that BBMerge produces merged shotgun reads with greater accuracy and at higher speed than any existing merging tool examined. BBMerge also provides the ability to merge non-overlapping shotgun read pairs by using k-mer frequency information to assemble the unsequenced gap between reads, achieving a significantly higher merge rate while maintaining or increasing accuracy.


Studies on the absorption and distribution of doxycycline in normal patients and in patients with severely impaired renal function.
Doxycycline, a recently synthesized analogue of tetracycline, was given to 16 patients with normal renal function and to 14 patients with severely impaired renal function. Serum concentrations in the two groups following a single dose were followed after absorption. The rate of clearance from the plasma following a single dose did not differ significantly in the two groups despite low urinary concentrations in patients with renal failure. No accumulation of doxycycline occurred in the serum of three normal patients or of nine patients with renal failure when treated with either 200 mg. daily or 200 mg. initially followed by 100 mg. daily for up to 15 days.


Cognitive and Affective Uses of a Thoracic Outlet Syndrome Facebook Support Group.
There are currently many disease-specific groups on Facebook in which patients may take an active part (Greene, Choudhry, Kilabuk, & Shrank, 2011). Although uses and gratifications of patient-disease groups have begun to be identified for chronic diseases, rare diseases have been omitted, even though they collectively affect roughly 30 million people in the United States and 350 million people worldwide. This study is a content analysis of one Facebook rare disease patient group, the Thoracic Outlet Syndrome (TOS) Awareness group. All wall posts were recorded and content analyzed for cognitive and affective categories and subcategories between October 9, 2011 (date of site origin), and May 1, 2012. Analysis of cognitive needs indicated TOS patients used the site more to share information about their own TOS symptoms and journey with diagnosis than to seek information. Analysis of affective needs found patients were more likely to use the site to give support and encouragement to others than to express concerns and complaints. The complaints they did express were primarily related to their frustration with the general medical community's perceived inability to diagnose and understand their disease or to question a specific doctor's diagnosis/recommendation. Results point to needs specific to TOS patients that uses and gratifications research can help clarify.


Reconstruction of chronic ruptures of the distal biceps tendon with use of an achilles tendon allograft.
Chronic ruptures of the distal biceps tendon are uncommon and are complicated by the retraction and poor quality of the muscle and tendon. Surgical procedures that have been described for the treatment of this injury are limited by the quality and availability of the structures used for augmentation. The purpose of the present study was to describe the surgical technique for reconstruction of the tendon with an Achilles tendon allograft and to report our preliminary experience with this procedure. An Achilles tendon allograft was used to reconstruct a chronic rupture of the distal biceps tendon in four patients. The patients were evaluated with regard to subjective satisfaction, pain, range of motion, and strength in flexion and supination. The results were graded with use of the Mayo elbow performance score. After an average duration of follow-up of 2.8 years (range, 2.0 to 3.7 years), all four patients had a satisfactory subjective result, a full range of motion, and an excellent Mayo elbow performance score. The strength of flexion and supination was comparable with that on the contralateral side in two patients and was slightly decreased in the other two. Reconstruction of chronic disruptions of the distal biceps tendon with an Achilles tendon allograft appears to offer a satisfactory technical solution for this challenging problem and has provided satisfactory clinical results to date.


Residual and sound limb hip strength distinguish between sedentary and nonsedentary adults with transtibial amputation.
Following a transtibial amputation (TTA), physical activity has known benefits for health and quality of life. Adults post-TTA, however, demonstrate reduced physical activity, predisposing them to adverse health outcomes. Identifying adults at the risk of sedentarism post-TTA via commonly used, objective clinical measures may enhance clinical decisions, including prosthesis prescription. The study's purpose was to determine whether residual and sound limb hip strength distinguishes between sedentary and nonsedentary adults post-TTA. A secondary analysis of a cross-sectional dataset (n = 44) was conducted. Participant residual and sound limb hip flexion, extension, abduction and adduction strength were assessed via handheld dynamometry. Physical activity was monitored for 7 days and participants were classified as sedentary (<5000 steps/day; n = 13) or nonsedentary (≥5000 steps/day; n = 31). Receiver operating curves revealed that residual and sound limb hip extension, abduction and adduction strength distinguished between sedentary and nonsedentary adults post-TTA (P < 0.050). Preliminary cut-points for hip strength measures to classify adults at the risk of sedentarism were determined. A hip strength composite score (0-6) estimates a 2.2× increased odds of being sedentary with each additional hip strength deficit. Post-TTA, residual and sound limb hip strength can help identify adults at risk of sedentarism to aid clinical decision making, including prosthesis prescription.