Evaluation of average glandular dose (AGD) in screening and diagnostic digital mammography and digital breast tomosynthesis (DBT) towards establishing a reference dose range band (DRB): a developing country experience.
This study represents the first national survey conducted in Sri Lanka to establish national diagnostic reference levels (NDRLs) for screening and diagnostic acquisitions in digital mammography (2D-DM) and digital breast tomosynthesis (DBT). Additionally, the study investigated the relationship between average glandular dose (AGD) and compressed breast thickness (CBT) and introduced a novel concept called dose range bands (DRBs) as a tool for optimizing radiation dose in mammography. DICOM metadata was used to extract dose data and exposure parameters from women undergoing either screening (350) or diagnostic (750) DM. The analysis included both craniocaudal and mediolateral oblique views of each breast, acquired using 2D-DM and DBT imaging techniques. The NDRL (AGD per view) was 1.97 mGy and 2.01 mGy for diagnostic DM and DBT, respectively. The corresponding NDRLs for screening acquisition were 2.44 mGy and 2.30 mGy. The mean DBT/DM AGD ratio was 1.39 and 0.97 for diagnostic and screening, respectively. Further, the association between the average glandular AGD per view and CBT is stronger in DBT than in 2D-DM. The study findings highlight the need for standardisation of compression practices, considering factors such as the radiographer's experience, imaging equipment, breast density, age, breast size, and pain threshold.


Activation and cleavage of the N-N bond in side-on bound [L₂M-NN-ML₂] (L = NH₂, NMe₂, N(i)Pr₂, C₅H₅, C₅Me₄H) dinitrogen complexes of transition metals from groups 4 through 9.
The activation and cleavage of the N-N bond in side-on bound [L₂M-NN-ML₂] (L = NH₂, NMe₂, N(i)Pr₂, C₅H₅, C₅Me₄H) dinitrogen complexes of transition metals in groups 4 through 9 have been investigated using density functional theory. Emphasis has been placed on Ti, Zr, and Hf (group 4) complexes due to their experimental relevance. Calculations on these species have shown that for cases when the structural configuration corresponds to the terminal [ML₂] fragments adopting a perpendicular orientation with respect to the central [N-N] unit, a considerably higher degree of N-N activation is predicted relative to that observed in the experimentally characterized cyclopentadienyl analogues and in related systems involving end-on dinitrogen coordination. An examination of the orbital interactions between the metal-based fragments and the dinitrogen unit shows that both σ and π bonding are important in the side-on binding mode, in contrast to the end-on mode where metal-nitrogen π interactions are dominant. This analysis also reveals that the model amide systems possess the orbital properties identified as necessary for successful N-N hydrogenation. A significant result obtained for the amide complexes containing metals from groups 5 (V, Nb, Ta), 6 (Cr, Mo, W), and 7 (Mn, Tc, Re), is the presence of metal-metal bonding in configurations that are considerably distorted from planarity. As a consequence, these complexes exhibit strongly enhanced stability relative to species where metal-metal bonding is absent. In contrast, the d² metal-based configurations in the group 4 complexes of Ti, Zr, and Hf are unable to provide the six electrons required for complete reductive cleavage of the dinitrogen unit which is necessary to allow the metal centres to approach one another sufficiently for metal-metal bond formation.


COX-2 inhibition versus gastroprotection with dual COX inhibitors: an evidence-based approach.
Highly selective inhibitors of cyclooxygenase-2 (COX-2i) were introduced to minimize peptic ulcers and their complications caused by dual COX inhibitors (COXi). Co-prescribing a (generally cheap) dual COXi with a gastroprotectant is an alternative strategy, proven to reduce the incidence of NSAID-associated endoscopic ulcers. This review compares the efficacies of these two strategies and makes some estimates of their relative cost-effectiveness. In standard risk patients, endoscopic ulcers are reduced to about the same extent (around 70-80%) by either co-prescribing omeprazole or lansoprazole with a dual COXi or preferring a COX-2i alone. COX-2i reduced ulcer complications by a weighted mean of around 60% in comparative studies with dual COXi. There is little information about the influence of PPI on this endpoint, although one study using H. pylori treatment as a possible surrogate for placebo intervention found 77% protection against recurrent upper gastrointestinal bleeding by co-administered omeprazole. One direct comparison of the two strategies in high-risk patients (recent ulcer bleed) found quite high rates of re-presentation with bleeding ulcer using either strategy, and the differences between them were not significant. Drug costs in four Western countries were compared for each strategy. In one, the costs were similar, but in the others the combination of a cheap dual COXi with omeprazole was usually more expensive than using a COX-2i. The safest strategy in highest risk patients may be to co-prescribe a gastroprotectant with a COX-2i, with resulting higher drug costs but possibly offset by savings in other health costs. The efficacy and cost-benefit of this alternative approach warrants investigation.


Biliary transport of glutathione disulfide studied with isolated rat-liver canalicular-membrane vesicles.
Canalicular plasma membrane vesicles isolated from rat liver (right side out) were used to study glutathione disulfide (GSSG) transport. GSSG is transported into an osmotically sensitive compartment. Extrapolation to an external osmolarity of infinity indicates 35% binding after 10 min of incubation, e.g. as mixed disulfides between glutathione and SH-groups in membrane proteins. Glutathione disulfide uptake occurred with equal rates in the presence of KCl or NaCl. After equilibration, no significant GSSG concentration gradient across the canalicular membrane was found. The temperature dependence of uptake is consistent with a carrier-mediated transport for GSSG (Q10 X 1.6) and seems to exclude simple diffusion. Concentration dependence of GSSG uptake shows Michaelis-Menten kinetics at concentrations up to 1 mM; a Km of 0.4 mM and a V of 1.1 nmol X min-1 X mg protein-1 is calculated. At higher concentrations a linear dependence is observed without saturation kinetics. It is concluded that transport of glutathione disulfide is mediated by a carrier present in the canalicular membrane of the hepatocyte.


Height matters-from monogenic disorders to normal variation.
Height is a classic polygenic quantitative trait with a high level of heritability. As it is a simple and stable parameter to measure, height is a model for both common, complex disorders and monogenic, Mendelian disease. In this Review, we examine height from the perspective of monogenic and complex genetics and discuss the lessons learned so far. We explore several examples of rare sequence variants with large effects on height and compare these variants to the common variants identified in genome-wide association studies that have small effects on height. We discuss how copy number changes or genetic interactions might contribute to the unidentified aspects of the heritability of height. We also ask whether information derived from genome-wide association studies on specific loci in the vicinity of genes can be used for further research in clinical paediatric endocrinology. Furthermore, we address key challenges that remain for gene discovery and for the transition of moving from genomic localization to mechanistic insights, with an emphasis on using next-generation sequencing to identify causative variants of people at the extremes of height distribution.


Cellular and molecular mechanisms of acute exposure to sulfur mustard: a systematic review.
Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury. In this systematic review, more than 1200 (2000-2014) articles focusing on gross or molecular pathological reports in the acute phase of the respiratory injury after SM exposure were reviewed, followed by two different layers of gross and molecular pathological data (clinic and laboratory) integrated together in a spatio-temporal order. Role of epithelial, neutrophil and macrophage cells and three signaling pathways of inflammation, oxidative stress and cell death are covered in details. Our results propose a critical role of interleukin-17 producing cells in acute and chronic inflammatory responses.


Repeated evolution of identical domain architecture in metazoan netrin domain-containing proteins.
The majority of proteins in eukaryotes are composed of multiple domains, and the number and order of these domains is an important determinant of protein function. Although multidomain proteins with a particular domain architecture were initially considered to have a common evolutionary origin, recent comparative studies of protein families or whole genomes have reported that a minority of multidomain proteins could have appeared multiple times independently. Here, we test this scenario in detail for the signaling molecules netrin and secreted frizzled-related proteins (sFRPs), two groups of netrin domain-containing proteins with essential roles in animal development. Our primary phylogenetic analyses suggest that the particular domain architectures of each of these proteins were present in the eumetazoan ancestor and evolved a second time independently within the metazoan lineage from laminin and frizzled proteins, respectively. Using an array of phylogenetic methods, statistical tests, and character sorting analyses, we show that the polyphyly of netrin and sFRP is well supported and cannot be explained by classical phylogenetic reconstruction artifacts. Despite their independent origins, the two groups of netrins and of sFRPs have the same protein interaction partners (Deleted in Colorectal Cancer/neogenin and Unc5 for netrins and Wnts for sFRPs) and similar developmental functions. Thus, these cases of convergent evolution emphasize the importance of domain architecture for protein function by uncoupling shared domain architecture from shared evolutionary history. Therefore, we propose the terms merology to describe the repeated evolution of proteins with similar domain architecture and discuss the potential of merologous proteins to help understanding protein evolution.


Molecular zinc phosphonates: synthesis and X-ray crystal structures of [[(ZnMe)4(THF)2][tBuPO3]2] and [[(ZnEt)3(Zn(THF))3][tBuPO3]4[mu3-OEt]].
The reactions of zinc alkyls with tert-butylphosphonic acid in 2 : 1 and 1 : 1 molar ratios afforded [[(ZnMe)(4-)(THF)2][tBuPO3]2] (2) and [[(ZnEt)3(Zn(THF))3][tBuPO3]4[mu3-OEt]] (3), respectively. Compounds 2 and 3 have been fully characterised by means of spectroscopic and analytical methods. Single-crystal X-ray diffraction studies revealed that zinc phosphonates 2 and 3 are tetra- and hexa-nuclear, respectively. This is in contrast to the dodecanuclear zinc phosphonate [[Zn2(THF)2(ZnEt)6Zn4(mu4-O)][(tBuPO3)8]] (1) obtained in a 1.5 : 1 reaction between zinc alkyls and tBuP(O)(OH)2.


Oral Candida colonization in oral cancer patients and its relationship with traditional risk factors of oral cancer: a matched case-control study.
Candida, an opportunistic fungal pathogen, has been implicated in oral and oesophageal cancers. This study aimed to examine oral Candida carriage in 52 oral cancer patients and 104 age-, gender- and denture status-matched oral cancer-free subjects. We assessed general health, smoking and alcohol drinking habits, use of alcohol-containing mouthwash and periodontal status (community periodontal index of treatment needs). Yeasts were isolated using oral rinse technique and genetically identified via Real-Time PCR-High resolution melting curve analysis of conserved ribosomal DNA. Conditional and binary logistic regressions were used to identify explanatory variables that are risk factors for oral cancer. The frequencies of oral yeasts' presence and high oral colonization were significantly higher in oral cancer than non-oral cancer patients (p=001; p=0.033, respectively). No significant difference in the isolation profile of Candida species was found between the two groups, except C. parapsilosis was more frequent in non-oral cancer group. Differences were noticed in the incidence of C. albicans strains where significantly more C. albicans genotype-A was isolated from cancer patients and significantly more C. albicans genotype-B isolated from non-cancer patients. Multiple regression analyses showed significant association with cancer observed for alcohol drinking (OR=4.253; 95% CI=1.351, 13.386), Candida presence (OR=3.242; 95% CI=1.505, 6.984) and high oral colonization (OR=3.587; 95% CI=1.153, 11.162). These results indicate that there is a significant association between oral cancer occurrence and Candida oral colonization and that the observed genotypic diversity of C. albicans strains may play a role in oral carcinogenesis.


Enzymatic determination of free glutamic acid in dried soups and in minced sausages: NMKL collaborative study.
An enzymatic method for the determination of free glutamic acid in meat products and dried soups was collaboratively studied in 11 laboratories. In the presence of the enzyme glutamate dehydrogenase, L-glutamic acid is oxidatively deaminated by nicotinamide adenine dinucleotide (NAD) to 2-oxoglutarate. In a reaction catalyzed by diaphorase, the NADH thus formed converts 2-(p-iodophenyl)-3-(p-nitrophenyl)-5-phenyltetrazolium chloride to a formazan, which is measured in the visible range at 492 nm. Fourteen samples (7 samples of minced sausage and 7 samples of dried cauliflower soup) with glutamate contents varying between 0.4 and 16 g/kg were included in the study. Materials were distributed to participants as blind duplicates and as split level pairs. The mean relative standard deviation (RSDR) for reproducibility for the dried soup material containing glutamate between 7 and 16 g/kg was 4.6%. RSDR values for samples of minced sausage containing glutamate at lower levels (0.4-1.3 g/kg) were between 12 and 16%.


Dynamics of progesterone and estrogen receptor alpha in the ventromedial hypothalamus.
Cyclic fluctuations of estradiol and progesterone in females influence neuronal activity in the ventrolateral division of the ventromedial hypothalamic nucleus (VMNvl), through the activation of progesterone receptors (PRs) and estrogen receptors (ERs). The expression of ER and PR in the VMNvl is influenced by their cognate ligands and is a central upstream trigger in the pathway of VMNvl-dependent modulation of endocrine responses. By studying the role played by estradiol and progesterone in PR and ERa expression in the VMNvl along the estrous cycle and how the two receptors interact in the same neuron, we aim to evaluate the synergistic action of both ovarian hormones in the regulation of VMNvl activity. In animals at all phases of the estrous cycle, the number of VMN neurons expressing PR or ERa was estimated by stereological methods, and the percentage, and rostro-caudal distribution, of neurons simultaneously expressing both receptors was determined. The highest number of PR-immunoreactive neurons was seen at proestrus, and of ERa-immunoreactive neurons was seen at proestrus and metestrus. The ERa/PR co-localization is increased at caudal levels. Approximately half the neurons expressing PR co-express ERa, a proportion that stays constant along the estrous cycle. The percentage of ERa neurons co-expressing PR changes from 60% at proestrus to 40% at metestrus. Fluctuations in circulating ovarian hormone levels promote coordinated changes in PR and ERa expression and co-localization. This may be an important mechanism in the regulation of input relayed by the VMNvl, allowing a precise modulation of endocrine responses.


Alectinib as a treatment option following recovery from crizotinib-induced interstitial lung disease in patients with anaplastic lymphoma kinase-positive advanced non-small-cell lung cancer.
Crizotinib is a tyrosine kinase inhibitor that displays antitumor activity against anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer. However, crizotinib-associated interstitial lung disease (ILD) has been reported as an infrequent, but potentially fatal complication. We herein describe the case of a 63-year-old male patient with ALK-rearranged advanced lung adenocarcinoma. Chest computed tomography (CT) revealed extensive bilateral ground-glass opacity and airspace consolidation with traction bronchiectasis on day 27 of crizotinib therapy. No signs of infection or left heart failure were identified and we considered the lesions to be consistent with crizotinib-induced ILD. Following corticosteroid treatment and discontinuation of crizotinib, CT revealed improvement of ILD, but also showed regrowth of the tumor. Alectinib, a novel alternative ALK inhibitor, was initiated, and has been successfully continued, with neither disease progression nor recurrence of ILD. The present case indicates that alectinib may be considered as an alternative agent in cases of crizotinib-induced ILD, irrespective of the pattern of ILD, i.e., a diffuse alveolar damage (DAD) or non-DAD pattern, with careful observation.


[Biomechanical prerequisites for examining the stability of osteosynthesis procedures of the spine].
Basic reflections on biomechanical tests of spinal implants are reviewed. Four different pedicle screw systems are compared during loading in extension, flexion, side-bending, and rotation. The thoracolumbar and the lumbar spine were tested. Stability against rotation forces was lowest in all systems. Because of this, a cross-connector is recommended in highly unstable situations. All tests were done in cadaver spines with normal bone mineral density (measured before the tests). The first series of tests was done without destroying the cadavers. A second series was done with maximal load until the implants or the bony bed of the screws failed. The results show that rigid implants more often led to pedicle fractures. An unstable screw rod interface led to implant failure. Cadaver tests can provide answers about the primary stability characteristic only. Fatigue tests are not possible in cadaver spines because they become autolytic before enough cycles can be applied.


Factors associated with serum IgM concentrations: a general adult population study.
To investigate the influence of common factors on serum immunoglobulin M (IgM) concentrations in adults, and clinical associations with high and low values. We measured serum IgM levels using immunonephelometry in a random sample of 1510 individuals (aged 18-91 years, 44.7% male). We obtained data defining metabolic syndrome from all participants, defined atopy by skin prick tests to aeroallergens, and assessed lifestyle factors by questionnaire. Women showed higher IgM concentrations than men; 95 (6.3%, mostly male) individuals showed low (<0.40 g/L) IgM values, and 64 (4.2%, mostly female) showed high (>2.30 g/L) IgM values. Individuals with abnormal IgM concentrations had no history of opportunistic infections nor a different atopy prevalence. Serum IgM concentrations decreased with age, and obesity was negatively associated with IgM concentrations. Alcohol consumption, smoking, physical activity, and metabolic syndrome had no significant influence in the multivariate analyses. Many adults in the general population show abnormally high or low IgM concentrations with no evidence of immunodeficiency-associated diseases. Sex and age should be considered when defining reference IgM concentrations.


Nuclear DNA content of fine needle aspirates of invasive ductal carcinomas of the breast.
Patients with aggressive breast cancers benefit from chemotherapy prior to surgery. If the biology of the breast cancers were better characterised pre-operatively, more patients at risk could be offered chemotherapy. We have assessed nuclear DNA content of fine needle aspirates (FNA) of 103 invasive ductal breast cancers and compared this to tumour size, node status and histological grade. Median follow-up was 18 months so no prognostic studies were made. Diploid and non-diploid tumours were distributed equally in node negative and positive patients. However non-diploidy status increased in line with known prognostic markers of tumour size and histological grade. This suggests that ploidy might contribute to the pre-operative assessment of prognosis. We conclude that nuclear DNA of breast cancer FNAs may be of value in the pre-operative biological assessment of breast cancer patients.


Evidence-based pain management and palliative care in Issue One for 2008 of the Cochrane Library.
The Cochrane Library is published quarterly. Issue 1, 2008, contains 3,385 complete reviews, 1,786 protocols for reviews in production, and 7,048 one-page summaries of systematic reviews published in the general medical literature. In addition there are citations of 527,000 randomized controlled trials, and 10,000 cited papers in the Cochrane methodology register. The health technology assessment database contains 7,177 citations. This edition of the Library contains 86 new reviews of which 7 have potential relevance for practitioners in pain and palliative medicine.


Amoxicillin/clavulanate for infections in infants and children: past, present and future.
Chemical synthesis of the penicillin nucleus in the 1950s made introduction of a broad array of new and important antimicrobials, including ampicillin and amoxicillin, possible. Ampicillin was introduced in 1962 in oral and parenteral forms as the first of the semisynthetic penicillins to provide increased activity against Gram-negative bacteria. Amoxicillin replaced oral ampicillin beginning in 1974 because amoxicillin resulted in higher and more prolonged serum concentrations than did equivalent doses of ampicillin. Amoxicillin/clavulanate (Augmentin) was introduced in the United States in 1984 to enhance the activity of amoxicillin by addition of the beta-lactamase inhibitor, clavulanic acid. During the past 20 years, amoxicillin/clavulanate has proven effective for a variety of pediatric infectious diseases, particularly acute otitis media (AOM). In 2001, a new pediatric formulation, high dose amoxicillin/clavulanate (Augmentin ES-600) was approved for use in the United States. The high dose preparation addressed the needs of pediatricians by providing greater amounts of amoxicillin while maintaining the same daily dose of clavulanic acid as the regular strength formulation. Doubling the dose of amoxicillin for management of recurrent and persistent AOM was recommended in 1999 by the Centers for Disease Control and Prevention because of concern about the increased incidence of nonsusceptible strains of Streptococcus pneumoniae. The original formulation combined amoxicillin/clavulanate in a 4:1 ratio and was followed by a 7:1 ratio formulation. The high dose formulation (600 mg of amoxicillin per 5 ml) provides a 14:1 ratio of amoxicillin to clavulanate. Although management of AOM will likely undergo changes in the coming years, amoxicillin is expected to remain first line therapy for AOM. For children who fail initial therapy with amoxicillin, high dose amoxicillin/clavulanate, an oral cephalosporin or parenteral ceftriaxone is recommended.


Preoperative and operative considerations in malignant hyperpyrexia.
Malignant hyperpyrexia is a condition characterized by fever and often by skeletal muscle rigidity usually triggered by the administration of general anesthetic agents. A review of the current literature is given to emphasize preoperative and operative considerations. An uncomplicated case is presented to illustrate the special care that these individuals require.


HIV prevalence no higher among female drug injectors also involved in prostitution.
To assess the prevalence of HIV infection among female drug injectors involved in prostitution and female drug injectors not involved in prostitution, survey-based interviews were undertaken with 308 female drug injectors in 1990 and 1991. Confirmed saliva test results show 12.9% HIV prevalence among female drug injectors involved in prostitution and 14.4% HIV prevalence among drug injectors not involved in prostitution. This gives an HIV prevalence rate of 14.2% among female drug injectors overall. Findings also show that women not involved in prostitution were less likely to be in contact with a drug treatment or helping agency and were less likely to report having had an HIV test. Respondents in contact with a treatment agency and respondents involved in prostitution were more likely to be aware of their HIV status, and 72% of non-prostitute women confirmed HIV positive were unaware of their positive status. These findings of no higher HIV prevalence among female drug injectors also involved in prostitution lend some support to emerging evidence which associates HIV transmission among women prostitutes with an involvement in injecting drug use rather than with an involvement in prostitution per se. Findings also strengthen the need for greater expansion and greater accessibility of HIV testing, counselling and prevention facilities in community locales where drug injection and prostitution is prevalent.


Effect of lengthening along the anatomical axis of the femur and its clinical impact.
To review and study the effect of lengthening along the anatomical axis of long bones and its relation to the mechanical axis deviation. We try in this review to calculate and discuss the exact clinical impact of lengthening along the anatomical axis of the femur on affecting the limb alignment. Also we used a trigonometric formula to predict the change of the femoral distal anatomical mechanical angle (AMA) after lengthening along the anatomical axis. Lengthening along the anatomical axis of the femur by 10% of its original length results in reduction in the distal femoral AMA by 0.57 degrees. There is no objective experimental scientific data to prove that the Mechanical axis is passing via the center of the hip to the center of the knee. There is wide variation in normal anatomical axis for different populations. In deformity correction, surgeons try to reproduce the normal usual bone shape to regain normal function, which is mainly anatomical axis. Lengthening of the femur along its anatomical axis results in mild reduction of the distal femoral AMA. This may partially compensate for the expected mechanical axis lateralisation and hence justify its minimal clinical impact.


Extending the preoxygenation period from 4 to 8 mins in critically ill patients undergoing emergency intubation.
To determine the effectiveness of increasing the preoxygenation period with 100% oxygen in the critically ill patient from 4 to 8 mins in preparation for emergency tracheal intubation. Nonrandomized, controlled trial. Large, level one trauma center, tertiary care intensive care unit. Critically ill patients failing noninvasive respiratory support techniques who required tracheal intubation followed by mechanical ventilation. A baseline arterial blood gas was obtained on noninvasive passive therapy and at 4, 6, and 8 mins of active preoxygenation efforts with 100% oxygen therapy with a noncollapsing resuscitator bag and mask. Best effort to achieve a tight fitting mask seal was pursued coupled with other mask ventilation maneuvers to optimize noninvasive oxygenation and ventilation. Thirty-four patients consecutively intubated by the author during the 7-month study period were studied. The baseline PaO2 (mean +/- SD) with concurrent noninvasive support was 61.9 +/- 14.6 mm Hg (range: 44-109 mm Hg) and increased a mean of 22 mm Hg to 83.8 +/- 51.5 mm Hg after 4 mins of preoxygenation (p < 0.01). Continued preoxygenation efforts (6 mins) increased the PaO2 to 88.2 mm Hg +/- 48.5 and after 8 mins to 92.7 mm Hg +/- 55.2. At the 8-min mark, 5 of 34 patients achieved > 10% increase in their PaO2 and only two patients increased their 4-min PaO2 by > or = 50 mm Hg after the additional 4 mins of preoxygenation. One quarter of the patients experienced a reduction in their PaO2 from the 4 to the 8-min time period. Nearly, 50% of the patients met the criteria for desaturation during the intubation procedure. Extending the preoxygenation period from the customary 4 mins to either 6 or 8 min seems to be marginally effective in the majority of patient suffering from cardiopulmonary deterioration and such an extension may jeopardize oxygenation efforts in some patients.


The action of clonidine on the baroreflex control of heart rate in conscious animals and man, and on single aortic baroreceptor discharge in the rabbit.
Changes in mean arterial pressure (M.A.P.) have been produced in conscious rabbits by inflation of balloon cuffs previously implanted round the inferior vena cave and aorta; Sigmoid stimulus/response curves (M.A.P./Heart Period, H.P.) were constructed. Clonidine caused a striking dose dependent increase in gain of the reflex arc in both normal rabbits and rabbits with renal hypertension. The largest effect was upon vagal motorneurones but a similar but smaller effect was present in vagotomised animals. Similar changes in the baro-reflex arc were produced by injection of very much smaller doses of clonidine into the lateral cerebral ventricle. Recordings made from single aortic baroreceptor fibres in anaesthetised rabbits showed again a dose dependeent sensitisation. These results suggest that the bradycardia caused by clonidine is largely mediated via an action in the brain on the baroreflex arc, with an additional action on the baroreceptors themselves. Preliminary results in normal man show a similar increase in the gain of this reflex after intravenous clonidine (150 mug).


Residual protein contamination of ProSeal laryngeal mask airways after two washing protocols.
The risk of prion protein cross-infection has focussed attention on the potential hazards of protein contamination of re-usable medical devices. This study determined the frequency of protein contamination of ProSeal laryngeal mask airways (PLMA) after two cleaning procedures and tested the hypothesis that the combination of hand- and machine-washing removes protein contamination more effectively than hand-washing alone. After clinical use fifty-four PLMAs were randomly allocated to be washed by hand or by hand then machine. All PLMAs were then autoclaved at 134 degrees C for 4 minutes. After processing, each PLMA was immersed in a 1.2% solution of erythrosin B and examined for uptake of stain. The site (outer surface, bowl and edges of the cuff airway and drain tube, finger strap) and severity (nil/mild/moderate/severe) of staining was scored by a blinded observer. There were no differences in the site or severity of staining between the two cleaning procedures. Staining was detected on 89% of PLMAs that were hand-washed and 78% of PLMAs that were hand-, then machine-washed (P=0.27). When staining occurred, it was mild in 98%, moderate in 2% and was never severe. Staining was more frequent on the edge than at any other location (all comparisons: P < or = 0.01). The strap never had any staining. We conclude that residual contamination of PLMAs with protein deposits is common even when machine-washing is used to augment hand-washing before autoclaving. The infection risk associated with these deposits remains to be determined.


13-valent pneumococcal vaccine: 50 years of age and older.
In adults, the 13-valent pneumococcal conjugate vaccine seems to be more immunogenic than the 23-valent polysaccharide pneumococcal vaccine for most of the 12 shared serotypes. However, in mid-2012, routine vaccination of adults has no proven efficacy.


Target model of nucleosome particle for track structure calculations and DNA damage modelling.
A non-homogeneous target model of nucleosome particle for track structure calculations and biophysical modelling of radiation-induced DNA damage was developed together with a sampling method for non-homogeneous targets. The model allows one to distinguish energy deposited in the histone core, primary hydration shell and nucleosome DNA. Illustrative results for low energy electrons are presented and compared with results obtained with simpler models of a nucleosome particle.


Transgenerational retention and maternal transfer of selenium in Daphnia magna.
We examined transgenerational retention and maternal transfer of selenium (Se) in three consecutive generations (F0, F1, and F2) of Daphnia magna. The F0 generation was exposed to dietary selenium (as selenite) only, and the F1 and F2 generations received only the maternally derived selenium from F0 and F1, respectively. Algal food Scenedesmus obilquus was radiolabeled with 0.56 microM Se, and the finial Se concentration in the algae was 115.6 microg Se/g dry weight. After 10 d feeding, the initial Se concentration in the F0 prior to depuration was 0.72 microg Se/g wet weight. The Se retention within the same generation was comparable at different food concentrations, but it increased across the consecutive generations regardless of the food concentration, suggesting that Se elimination was dependent on the source of Se accumulation (dietary vs maternally derived). Retention was also comparable among different batches of offspring within the same generation. Reproduction rate increased with increasing food concentration but decreased across the successive batches in F1. The 10-d overall maternal transfer efficiency increased with increasing food concentration in all generations. Approximately 19 to 24% of Se in F0 was transferred maternally to F1 during reproductive events, but the-efficiency decreased considerably from F1 to F2. Maternal transfer also decreased in the later batches of F1. The transfer efficiency to each neonate showed a negative relationship with food concentration in both F0 and F1, suggesting that the Se transfer to the offspring was compromised by the reproduction rate. We concluded that dietary-derived Se (from F0) was more efficiently transferred to the offspring (F1) than the maternally derived Se (from F1) transferred to F2; thus it is necessary to separate the dietary and maternal contributions to the overall Se accumulation in Daphnia.


The functional architectures of addition and subtraction: Network discovery using fMRI and DCM.
The neuronal mechanisms underlying arithmetic calculations are not well understood but the differences between mental addition and subtraction could be particularly revealing. Using fMRI and dynamic causal modeling (DCM), this study aimed to identify the distinct neuronal architectures engaged by the cognitive processes of simple addition and subtraction. Our results revealed significantly greater activation during subtraction in regions along the dorsal pathway, including the left inferior frontal gyrus (IFG), middle portion of dorsolateral prefrontal cortex (mDLPFC), and supplementary motor area (SMA), compared with addition. Subsequent analysis of the underlying changes in connectivity - with DCM - revealed a common circuit processing basic (numeric) attributes and the retrieval of arithmetic facts. However, DCM showed that addition was more likely to engage (numeric) retrieval-based circuits in the left hemisphere, while subtraction tended to draw on (magnitude) processing in bilateral parietal cortex, especially the right intraparietal sulcus (IPS). Our findings endorse previous hypotheses about the differences in strategic implementation, dominant hemisphere, and the neuronal circuits underlying addition and subtraction. Moreover, for simple arithmetic, our connectivity results suggest that subtraction calls on more complex processing than addition: auxiliary phonological, visual, and motor processes, for representing numbers, were engaged by subtraction, relative to addition. Hum Brain Mapp 38:3210-3225, 2017. © 2017 Wiley Periodicals, Inc.


Versatility of RNA-Binding Proteins in Cancer.
Posttranscriptional gene regulation is a rapid and efficient process to adjust the proteome of a cell to a changing environment. RNA-binding proteins (RBPs) are the master regulators of mRNA processing and translation and are often aberrantly expressed in cancer. In addition to well-studied transcription factors, RBPs are emerging as fundamental players in tumor development. RBPs and their mRNA targets form a complex network that plays a crucial role in tumorigenesis. This paper describes mechanisms by which RBPs influence the expression of well-known oncogenes, focusing on precise examples that illustrate the versatility of RBPs in posttranscriptional control of cancer development. RBPs appeared very early in evolution, and new RNA-binding domains and combinations of them were generated in more complex organisms. The identification of RBPs, their mRNA targets, and their mechanism of action have provided novel potential targets for cancer therapy.


Thermodynamic Consideration of the Solid Saponin Extract Drop-Air System.
The aim of this research was to elucidate the surface active properties of Saponaria officinalis (soapwort) extract containing the plant surfactants saponins. To this end, the advancing contact angle (θ) of water, formamide and diiodomethane on the glass, as well as θ of the aqueous solution of S. officinalis extract fractions on PTFE, PMMA and glass, were studied. Based on the obtained results, the wetting behaviour of saponins was considered with regard to the surface tension components and parameters of the solutions and solids. The investigations also involved the description of the θ isotherms, the dependences between the cosine of contact angle and/or the adhesion of the solution to the solid surfaces and solution surface tension, as well as the critical surface tension of PTFE, PMMA and glass wetting. These dependences were studied based on the saponin adsorption at the different interfaces, which was deduced from the dependence between the adhesion and surface tension of the solution, as well as using the Gibbs and Frumkin isotherm equations. This proved that the saponins are poor wetting agents and that the contact angle isotherm can be described by the exponential function of the second order as well as the Szyszkowski equation, but only for PTFE.


Fifty years on: Serotonin and depression.
It has been over 50 years since the original serotonin hypothesis was proposed by the British Psychiatrist Alec Coppen. Recently, some authors have questioned the validity of the hypothesis. In this narrative review, we summarise the evidence for the serotonin hypothesis of depression, focusing on psychopharmacology and molecular imaging, as well as systems-level neuroscience.


Multicyclic Peptides as Scaffolds for the Development of Tumor Targeting Agents.
The lack of specificity of traditional cytotoxic drugs triggers the development of anticancer agents with high selectivity to tumor-specific proteins. The unveiling of target structures such as EGFR or Her2 allows the focused development of novel therapies and has strongly advanced tumor treatment. Tumor-specific high-affinity ligands can be identified by using display techniques such as phage, yeast surface, ribosome and mRNA display. These techniques enable the screening of huge libraries, consequently providing a valuable alternative to rational drug development. In recent years, miniproteins and multicyclic peptides have become the preferred ligands expressed by these libraries. Due to their favorable pharmacokinetics and the ease of their synthesis, peptidic ligands overcome disadvantages of antibody derived therapeutics. Peptides that are structurally defined by a rigid scaffold are ideally suited for the use in display techniques. These molecules feature high stability and excellent affinities while offering the opportunity to randomize partial sequences to be used as binding sites. Structurization of the peptide scaffold can be achieved by different approaches, of which cyclization is one of the most commonly used. The favored cyclization strategies are based on amide or disulfide bridging and the use of synthetic braces or chemical linkers. The use of multicyclic peptides allows the simultaneous presentation of several different binding loops. Semisynthetic approaches enable the introduction of unnatural amino acids, increasing the diversity of the resulting peptide libraries. Given that, miniprotein scaffolds offer a wide range of potential applications and facilitate efficient screening of novel high-affinity ligands to be used in precise diagnosis and highly efficient cancer therapy.


Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson's Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line.
The movement disorder Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and is associated with aging, the environment, and genetic factors. The intracellular aggregation of α-synuclein and the loss of dopaminergic neurons in the substantia nigra pars compacta are the pathological hallmark of PD. At present, there is no successful treatment for PD. Maackiain (MK) is a flavonoid extracted from dried roots of Sophora flavescens Aiton. MK has emerged as a novel agent for PD treatment that acts by inhibiting monoamine oxidase B. In this study, we assessed the neuroprotective potential of MK in Caenorhabditis elegans and investigated possible mechanism of this neuroprotection in the human SH-SY5Y cell line. We found that MK significantly reduced dopaminergic neuron damage in 6-hydroxydopamine (6-OHDA)-exposed worms of the BZ555 strain, with corresponding improvements in food-sensing behavior and life-span. In transgenic worms of strain NL5901 treated with 0.25 mM MK, the accumulation of α-synuclein was diminished by 27% (p < 0.01) compared with that in untreated worms. Moreover, in worms and the SH-SY5Y cell line, we confirmed that the mechanism of MK-mediated protection against PD pathology may include blocking apoptosis, enhancing the ubiquitin-proteasome system, and augmenting autophagy by increasing PINK1/parkin expression. The use of small interfering RNA to downregulate parkin expression in vivo and in vitro could reverse the benefits of MK in PD models. MK may have considerable therapeutic applications in PD.


Fine needle aspiration cytology diagnosis of paravertebral extraosseus Ewing's sarcoma.
Extraskeletal Ewing's sarcoma (EES) is a rare tumor. Paravertebral Ewing's sarcoma requires more extensive therapy as compared to Ewing's sarcoma of bone. Fine needle aspiration cytology (FNAC) plays an important role in the early diagnosis of these cases. We present a case where paravertebral extraosseous Ewing's sarcoma was diagnosed on FNAC in a 19-year-old girl.


Psychological treatment for depression and anxiety associated with dementia and mild cognitive impairment.
Depression and anxiety are commonly associated with cognitive impairment. A systematic review of psychological treatments that appears in this issue of the Journal highlights the current paucity of good-quality data, but suggests these interventions hold promise. Given the increasing burden of dementia in our community, novel adequately powered randomised controlled trials in this area are urgently needed.


Influence of litter size on metabolic status and reproductive axis in primiparous sows.
This study on primiparous sows was designed to 1) determine the impact of nursing a large litter on LH secretion and follicular development, and 2) investigate the metabolic adaptations by which milk yield increases with litter size. At farrowing, crossbred, primiparous sows were assigned to 1 of 3 experimental groups differing in litter size and feed allowance. Sows with 13 or 14 piglets (13AL, n = 7) were fed ad libitum. Sows with 7 piglets were fed ad libitum (7AL, n = 6) or were feed-restricted (7R, n = 8). The restriction was based on the estimated energy deficiency for the 13AL sows. On d 9 +/- 1 of lactation, a jugular catheter was surgically implanted. Serial blood samplings and glucose tolerance tests were performed in mid- and late lactation. Sows were slaughtered 3 d after weaning, and ovarian characteristics were recorded. During lactation, the 7AL sows lost no or little body reserves, and their estimated energy balance was near zero. The 13AL and 7R sows exhibited similar negative energy balances and similar losses of backfat and estimated lipid content. Litter growth rate was greater (P < 0.05) in the 13AL than in the 7AL and 7R groups. After weaning, the volume of the largest 14 follicles was smaller (P < 0.05) in sows nursing 13 or 14 piglets than in sows with 7 piglets. Plasma concentrations of LH and LH pulse frequency did not differ between groups (P > 0.1). The longer glucose half-life on d 16 than on d 27 of lactation (22.5 vs. 18.8 min; P < 0.05) indicated a lower glucose tolerance in mid- than in late lactation. The area under the insulin curve was greater in the 7AL than in the 13AL sows (P = 0.08) and intermediate in the 7R group, with no differences in glucose profiles. This led to the suggestion that the 7AL sows were more resistant to insulin than the 13AL sows. In all groups of sows, follicular development after weaning was correlated with LH secretion in midlactation. Active follicular development was associated with prolonged secretion of insulin in response to glucose challenge. Our results show that besides litter size, a sow's metabolic status in lactation influences follicular maturation after weaning and also indicate that the metabolic adaptations by which primiparous sows nursing large litters increase litter growth rate and body reserve mobilization do not involve an accentuated peripheral insulin resistance.


A review of potential applications of MR-guided focused ultrasound for targeting brain tumor therapy.
Magnetic resonance-guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.


The association of uveitis with hepatitis B and hepatitis C viruses: a large-scale population-based study.
To examine the association of uveitis with hepatitis B (HBV) and hepatitis C (HCV) chronic infections METHOD: This is a population-based cross-sectional study. The study encompassed 13,183 consecutive patients with uveitis and 65,331control subjects. The prevalence of chronic HBV and HCV infections was compared between patients diagnosed with uveitis and age-, sex-, and ethnicity-matched controls. Lifetime prevalence rates of HBV and HCV were calculated for patients with uveitis and control individuals. Odds ratio (OR) for HBV and HCV was evaluated across different strata. The lifetime prevalence rate of chronic HBV infection was greater in patients with uveitis than in controls (1.2% vs. 0.8%, respectively; P < 0.001). The association of HBV with uveitis was statistically significant among individuals older than 40 years of age, both sexes, and individuals of Jewish ethnicity. The lifetime prevalence of HCV was comparable between patients with uveitis and controls (0.8% vs. 0.7%, respectively; P = 0.189). Thus, no independently significant association was found between uveitis and HCV (fully-adjusted OR, 1.15; 95% CI, 0.93-1.42; P = 0.211). Uveitis is associated with HBV. The association was more prominent among older and Jewish patients. Patients with uveitis may benefit from screening for HBV. An association between uveitis and HCV has not been found.


State-Specific Barriers to Methadone for Opioid Use Disorder Treatment.
Opioid agonist treatment, including methadone, is the safest and most effective method for treating opioid use disorders and reduces opioid overdose deaths. While access to methadone is highly regulated by federal law, a substantial portion of states impose stricter barriers.


Identification of a human group C rotavirus in Malaysia.
Stool specimens from 334 infants and young children hospitalized with diarrhea in the General Hospital, Kuala Lumpur, Malaysia between August and November, 1987 were analyzed for the presence of rotavirus double-stranded (ds) RNA by polyacrylamide gel electrophoresis. Of the 334 specimens analyzed, 32 (9.6%) were positive for rotavirus RNA. One specimen (designated G147) exhibited a ds RNA electropherotype profile characteristic of Group C rotavirus and was selected for further characterization. In Northern blot hybridization studies, the gene 5 segment of strain G147 hybridized with a cDNA probe generated from the cloned gene 5 (which encodes the VP6 inner capsid protein that is group specific) of porcine Group C rotavirus strain Cowden, confirming the classification of strain G147 in Group C. The association of Group C rotavirus with diarrheal illness in Malaysia is consistent with earlier studies that suggest a global distribution of this virus and supports the need for additional epidemiologic studies.


A review of the therapeutic potential of histone deacetylase inhibitors in rhabdomyosarcoma.
This review aims to summarize the putative role of histone deacetylases (HDACs) in rhabdomyosarcoma (RMS) and the effects of HDAC inhibitors (HDACi) on RMS by elucidating and highlighting known oncogenic pathways, mechanisms of resistance, and the synergistic potential of histone deacetylase inhibitors. We searched two databases (PubMed and Google Scholar) for the keywords "Rhabdomyosarcoma, histone deacetylase, histone deacetylase inhibitors." We excluded three publications that did not permit access to the full text to review and those that focus exclusively on pleiomorphic RMS in adults. Forty-seven papers met the inclusion criteria. This review highlights that HDACi induce cytotoxicity, cell-cycle arrest, and oxidative stress in RMS cells. Ultimately, HDACi have been shown to increase apoptosis and the cessation of embryonal and alveolar RMS proliferation in vivo and in vitro, both synergistically and on its own. HDACi contain potent therapeutic potential against RMS. This review discusses the significant findings and the biological mechanisms behind the anti-cancer effects of HDACi. Additionally, this review highlights important clinical trials assessing the efficacy of HDACi in sarcomas.


Design of Lead(II) Metal-Organic Frameworks Based on Covalent and Tetrel Bonding.
Three solid materials, [Pb(HL)(SCN)2 ]⋅CH3 OH (1), [Pb(HL)(SCN)2 ] (2), and [Pb(L)(SCN)]n (3), were obtained from Pb(SCN)2 and an unsymmetrical bis-pyridyl hydrazone ligand that can act both as a bridging and as a chelating ligand. In all three the lead center is hemidirectionally coordinated and is thus sterically optimal for participation in tetrel bonding. In the crystal structures of all three compounds, the lead atoms participate in short contacts with thiocyanate sulfur or nitrogen atoms. These contacts are shorter than the sums of the van der Waals radii (3.04-3.47 Å for Pb⋅⋅⋅S and 3.54 Å for Pb⋅⋅⋅N) and interconnect the covalently bonded units (monomers, dimers, and 2D polymers) into supramolecular assemblies (chains and 3D structures). DFT calculations showed these contacts to be tetrel bonds of considerable energy (6.5-10.5 kcal mol(-1) for Pb⋅⋅⋅S and 16.5 kcal mol(-1) for Pb⋅⋅⋅N). A survey of structures in the CSD showed that similar contacts often appear in crystals of Pb(II) complexes with regular geometries, which leads to the conclusion that tetrel bonding plays a significant role in the supramolecular chemistry of Pb(II) .


Basic science and research in renal cell carcinoma: from workbench to bedside.
Renal cell carcinoma represents the third most common cancer in men. Radical surgery remains the only curative approach, and the 5-year survival rate once the cancer has metastasized rarely exceeds 20% despite systemic therapy. It becomes evident that an improvement in outcome might only be achieved if (1) there is early diagnosis, (2) there is accurate prediction of progression and response, and (3) new treatment options reflecting the molecular pathogenesis and progression are developed. The detection of circulating cancer cells by reverse transcriptase/polymerase chain reaction techniques for the MN/CAIX gene, the identification of specific genetic alterations in circulating tumor DNA, as well as the demonstration of somatic von Hippel-Lindau mutations and extracellular matrix proteins in urine of high-risk patients might be clinically useful in improving early diagnosis and treatment. The signal transducer and activator of transcription has been shown to significantly correlate with relapse patterns following radical surgery. Heterozygosity or homozygosity for class II haplotypes DQA1 and DQB1 accurately predicts response and survival following cytokine-based therapy and may be helpful in patient selection. In terms of treatment, the use of monoclonal antibody derivates against the epidermal growth factor receptor and the vascular endothelial growth factor receptor has shown promising clinical results. Antisense oligodeoxynucleotide therapy has shown significant therapeutic effects in in-vitro and in-vivo studies. Recent developments in the clinical application of proteasome inhibitors have opened the door to exciting, highly specific and effective molecular treatment options for metastatic renal cell carcinoma. Recent developments in research on renal cell carcinoma have identified various clinically useful diagnostic and therapeutic options reflecting the molecular basis of the pathogenesis and progression of the disease.


NMR imaging of pulmonary arteriovenous fistulae .
The nuclear magnetic resonance (NMR) imaging of pulmonary arteriovenous fistulae is reported, and the value of NMR in separating vascular from nonvascular lesions in the lung and mediastinum is discussed.


Functionalized liposomes: an enticing nanocarrier for management of glioma.
Glioma is one of the most severe central nervous systems (CNS)-specific tumors, with rapidly growing malignant glial cells accounting for roughly half of all brain tumors and having a poor survival rate ranging from 12 to 15 months. Despite being the most often used technique for glioma therapy, conventional chemotherapy suffers from low permeability of the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB) to anticancer drugs. When it comes to nanocarriers, liposomes are thought of as one of the most promising nanocarrier systems for glioma treatment. However, owing to BBB tight junctions, non-targeted liposomes, which passively accumulate in most cancer cells primarily via the increased permeability and retention effect (EPR), would not be suitable for glioma treatment. The surface modification of liposomes with various active targeting ligands has shown encouraging outcomes in the recent times by allowing various chemotherapy drugs to pass across the BBB and BBTB and enter glioma cells. This review article introduces by briefly outlining the landscape of glioma, its classification, and some of the pathogenic causes. Further, it discusses major barriers for delivering drugs to glioma such as the BBB, BBTB, and tumor microenvironment. It further discusses modified liposomes such as long-acting circulating liposomes, actively targeted liposomes, stimuli responsive liposomes. Finally, it highlighted the limitations of liposomes in the treatment of glioma and the various actively targeted liposomes undergoing clinical trials for the treatment of glioma.


Norepinephrine and epinephrine release and adrenergic mediation of smoking-associated hemodynamic and metabolic events.
We studied the effects of cigarette smoking, sham smoking and smoking during adrenergic blockade in 10 subjects to determine whether smoking released the sympathetic neurotransmitter norepinephrine, as well as the adrenomedullary hormone epinephrine, and whether smoking-associated hemodynamic and metabolic changes were mediated through adrenergic mechanisms. Smoking-associated increments in mean (+/- S.E.M.) plasma norepinephrine (227 +/- 23 to 324 +/- 39 pg per milliliter, P less than 0.01) and epinephrine (44 +/- to 113 +/- 27 pg per milliliter, P less than 0.05) were demonstrated. Smoking-associated increments in pulse rate, blood pressure, blood glycerol and blood lactate/pyruvate ratio were prevented by adrenergic blockade; increments in plasma growth hormone and cortisol were not. Since significant smoking-associated increments, in pulse rate, blood pressure and blood lactate/pyruvate ratio, preceded measurable increments in plasma catecholamine concentrations, but were adrenergically mediated, these changes should be attributed to norepinephrine released locally from adrenergic axon terminals within the tissues rather than to increments in circulating catecholamines.


Distinction of B cell maturation factors from lymphokines affecting B cell growth and viability.
Supernatants from S26.5 helper T cells, autoimmune viable motheaten (mev/mev) mouse spleen cells, EL4 lymphoma cells, and recombinant DNA-derived interferon gamma (IFN-gamma), all of which display B cell maturation factor (BMF) activity, were assayed for effects on B cell proliferation alone and with Dextran Sulfate (DxS) and anti-immunoglobulin antibodies (alpha-Ig). Both EL4 and S26.5 supernatants showed BCGF-II (DxS co-stimulator) activity, whereas only EL4 supernatant had BCGF-I (alpha-Ig co-stimulator or BSF-I) activity. Supernatants from mev/mev spleen cells and recombinant DNA-derived IFN-gamma showed no activity in either assay. Fractionation of S26.5 supernatant by chromatofocusing showed a divergence of BMF activity (BMF-T, pIa of 6.0) from BCGF-II activity (pIa of 5.4), providing evidence for their physical nonidentity. IFN-gamma, which decreases B cell viability in culture, was separable from BMF-T by phenyl-Sepharose chromatography. BMF-T from S26.5 supernatant was separated from IFN-gamma and BCGF-II and was shown to induce B cell maturation without affecting B cell proliferation. The molecular characteristics of the purified BMF-T were pIa 6.0, Mr 55,000 by G-75 gel filtration, and Mr 16,000 by SDS-PAGE. These data demonstrate that several lymphokines (BMF) exist that mediate the maturation of B cells to active Ig secretion without stimulating B cell proliferation.


Brain representation of hemifield stimulation in poststroke visual field defects.
Plasticity in extended, parallel, or reciprocal operating networks is well recognized. Changes in neuronal activity after lesions to distinct localized structures, such as the primary visual cortex, are less well characterized. We investigated the cortical reorganization in patients with poststroke visual field defects using blood oxygen level-dependent functional MRI. Brain activation was measured in 7 patients with a single occipital cortical lesion and partially recovered hemianopia and in 7 age-matched control subjects. Differences in activation between rest and visual hemifield stimulation were assessed with statistical parametric mapping (SPM'99). In normal subjects, significant activation was found in the contralateral primary visual cortex and bilaterally in the extrastriate cortex. During hemifield stimulation of the unaffected side of stroke patients, a similar pattern was found compared with that seen in control subjects. During stimulation of the hemianopic side, bilateral activation was seen within the extrastriate cortex, stronger in the ipsilateral hemisphere. The primary visual cortex was not significantly activated in either hemisphere during stimulation of the hemianopic side. Visual field defects after stroke are associated with bilateral activation of the extrastriate visual cortex. This pattern of activation indicates altered neuronal activity in the visual system. Further investigation is necessary to determine the relationship between functional reorganization and recovery of lost visual function after poststroke hemianopia.


Induction of apoptosis by 1,4-phenylenebis(methylene)selenocyanate in cultured human colon cancer cells.
Using a cultured human colon cancer cell line (Col 2), a structurally diverse group of chemopreventive agents was evaluated for their potential to induce apoptosis. As a result, 1,4-phenylenebis(methylene)selenocyanate (p-xylylselenocyanate; p-XSC) was found to be active in this process. p-XSC, a synthetic organoselenium compound, has been shown to inhibit tobacco-specific 4-(methylnitrosoamino)-(3-pyridyl)-1-butanone-induced tumorigenesis in A/J mouse lung, rat tongue carcinogenesis and colon cancer. Known chemopreventive mechanisms include inhibition of DNA methylation, inhibition of thymidine kinase and reduction of oxidative DNA damage. In order to assess apoptosis induction, the cells were exposed to various concentrations of test substances for 48 hours. Enrichment of mono- and oligonucleosomes in the cytoplasm was monitored as an indication of apoptosis using an ELISA kit. As a result, p-XSC caused dose-dependent enrichment of fragmented nucleosomes. In further studies, p-XSC was found to induce DNA laddering in a dose-dependent manner, while apoptotic cells accumulated in a time-dependent manner up to 96 hours. The apoptotic peaks after treatment of p-XSC were also found as confirmed by the flow cytometric analysis of cell cycle distribution. In an additional study, however, p-XSC-mediated apoptosis was not shown to be dependent on p53 expression. Taken together, these results suggest that induction of apoptosis is one possible mechanism for the cancer chemopreventive activity mediated by p-XSC.


Product Studies and Mechanistic Analysis of the Reaction of Methylglyoxal with Deoxyguanosine.
Methylglyoxal (MG) is a highly reactive electrophile produced endogenously as a byproduct of glucose metabolism and protein catabolism and exogenously as a food contaminant. MG reacts spontaneously with proteins, lipids, and nucleic acids to form advanced glycation end products (AGEs), modifying or inhibiting their function. Protein AGEs are associated with pathological complications of diabetes, cancer, and neurodegenerative diseases, while the physiological impact of DNA, RNA, and lipid AGE formation is less well explored. Conflicting reports in the literature on the biologically significant DNA-AGE product distribution and mechanisms of formation prompted a re-examination of the reaction products of MG with dG, oligonucleotides, and plasmid DNA under varying conditions of MG:dG stoichiometry, pH, and reaction time. Major products identified using sequential mass fragmentation and authentic standards were N2-(1-carboxyethyl)-2'-dG (CEdG), N2-(1-carboxyethyl)-7-1-hydroxy-2-oxopropyl-dG (MG-CEdG), and 1,N2-(1,2-dihydroxy-2-methyl)ethano-2'-dG (cMG-dG). CEdG and MG-CEdG were observed in all DNA substrates, although cMG-dG was not detected to any significant extent in oligomeric or polymeric DNA. Product analyses of reactions under conditions of diminished water activity as well as results from H218O labeling indicated that MG hydration equilibria plays an important role in controlling product distribution. In contrast to previous reports, our data support independent mechanisms of formation of CEdG and cMG-dG, with the latter kinetic product undergoing reversible formation under physiological conditions.


Tracking reorganization of large-scale effective connectivity in aphasia following right hemisphere stroke.
In this paper we demonstrate the application of new effective connectivity analyses to characterize changing patterns of task-related directed interaction in large (25-55 node) cortical networks following the onset of aphasia. The subject was a left-handed woman who became aphasic following a right-hemisphere stroke. She was tested on an auditory word-picture verification task administered one and seven months after the onset of aphasia. MEG/EEG and anatomical MRI data were used to create high spatiotemporal resolution estimates of task-related cortical activity. Effective connectivity analyses of those data showed a reduction of bilateral network influences on preserved right-hemisphere structures, and an increase in intra-hemispheric left-hemisphere influences. She developed a connectivity pattern that was more left lateralized than that of right-handed control subjects. Her emergent left hemisphere network showed a combination of increased functional subdivision of perisylvian language areas and recruitment of medial structures.


Cross talk between the gut microbiome and host immune response in ulcerative colitis: nonpharmacological strategies to improve homeostasis.
Ulcerative colitis (UC) is a chronic disease that is characterized by diffuse inflammation of the colonic and rectal mucosa. The burden of UC is rising globally with significant disparities in levels and trends of disease in different countries. The pathogenesis of UC involves the presence of pathogenic factors including genetic, environmental, autoimmune, and immune-mediated components. Evidence suggests that disturbed interactions between the host immune system and gut microbiome contribute to the origin and development of UC. Current medications for UC include antibiotics, corticosteroids, and biological drugs, which can have deleterious off-target effects on the gut microbiome, contributing to increased susceptibility to severe infections and chronic immunosuppression. Alternative, nonpharmacological, and behavioral interventions have been proposed as safe and effective treatments to alleviate UC, while also holding the potential to improve overall life quality. This mini-review will discuss the interactions between the immune system and the gut microbiome in the case of UC. In addition, we suggest nonpharmacological and behavioral strategies aimed at restoring a proper microbial-immune relationship.


Thermal transformations of self-assembled gold glyconanoparticles probed by combined nanocalorimetry and X-ray nanobeam scattering.
Noble metal nanoparticles with ligand shells are of interest for applications in catalysis, thermo-plasmonics, and others, involving heating processes. To gain insight into the structure-formation processes in such systems, self-assembly of carbohydrate-functionalized gold nanoparticles during precipitation from solution and during further heating to ca. 340 °C was explored by in situ combination of nanobeam SAXS/WAXS and nanocalorimetry. Upon precipitation from solution, X-ray scattering reveals the appearance of small 2D domains of close-packed nanoparticles. During heating, increasing interpenetration of the nanoparticle soft shells in the domains is observed up to ca. 81 °C, followed by cluster formation at ca. 125 °C, which transform into crystalline gold nuclei at around 160 °C. Above ca. 200 °C, one observes the onset of coalescence and grain growth resulting in gold crystallites of average size of about 100 nm. The observed microstructural changes are in agreement with the in situ heat capacity measurements with nanocalorimetry.


Advanced Cd(II) complexes as high efficiency co-sensitizers for enhanced dye-sensitized solar cell performance.
This work reports on two new complexes with the general formula [Cd3(IBA)3(Cl)2(HCOO)(H2O)]n (1) and {[Cd1.5(IBA)3(H2O)6]·3.5H2O}n (2), which can be synthesized by the reaction of Cd(II) with rigid linear ligand 4-HIBA containing imidazolyl and carboxylate functional groups [4-HIBA = 4-(1H-imidazol-1-yl)benzoic acid]. Single-crystal X-ray diffraction analyses indicate that complex 1 is a 2D "wave-like" layer structure constructed from trinuclear units and complex 2 is just a mononuclear structure. Surprisingly, both complexes 1 and 2 appear as a 3D supramolecular network via intermolecular hydrogen bonding interactions. What's more, due to their strong UV-visible absorption, 1 and 2 can be employed as co-sensitizers in combination with N719 to enhance dye-sensitized solar cell (DSSC) performance. Both of them could overcome the deficiency of the ruthenium complex N719 absorption in the region of ultraviolet and blue-violet, and the charge collection efficiency is also improved when 1 and 2 are used as co-sensitizers, which are all in favor of enhancing the performance. The DSSC devices using co-sensitizers of 1/N719 and 2/N719 show an overall conversion efficiency of 8.27% and 7.73% with a short circuit current density of 17.48 mA cm(-2) and 17.39 mA cm(-2), and an open circuit voltage of 0.75 V and 0.74 V, respectively. The overall conversion efficiency is 27.23% and 18.92% higher than that of a device solely sensitized by N719 (6.50%). Consequently, the prepared complexes are high efficiency co-sensitizers for enhancing the performance of N719 sensitized solar cells.


Passive vectoring of entomopathogenic fungus Beauveria bassiana among the wax moth Galleria mellonella larvae by the ectoparasitoid Habrobracon hebetor females.
Females of the ectoparasitoid Habrobracon hebetor attack and envenomate numerous host individuals during oviposition. The vectoring of the entomopathogenic fungus Beauveria bassiana during the adhesion stage by ectoparasitoid females among the wax moth larvae Galleria mellonella was explored under laboratory conditions. Vectoring occurred both from infected parasitoids to wax moth larvae and from infected to healthy wax moth larvae by parasitoids. The efficacy of vectoring in both cases was dose dependent. Parasitoid females were unable to recognize infected larvae in a labyrinth test. In addition, the presence of H. hebetor females significantly (1.5-13 fold) increased the mycoses level in clusters of G. mellonella, with 40% of the larvae infected with fungal conidia. Envenomation by H. hebetor increased conidia germination on the cuticles of the wax moth larvae by 4.4 fold. An enhanced germination rate (2 fold) was registered in the n-hexane epicuticular extract of envenomated larvae compared to that of healthy larvae. Both envenomation and mycoses enhanced the phenoloxidase (PO) activity in the integument of G. mellonella and, in contrast, decreased the encapsulation rate in hemolymphs. We hypothesize that changes in the integument property and inhibition of cellular immunity provide the highest infection efficacy of entomopathogenic fungi with H. hebetor.


Implications of the Incidental Finding of a MYCN Amplified Adrenal Tumor: A Case Report and Update of a Pediatric Disease Diagnosed in Adults.
MYCN is a well-known oncogene overexpressed in different human malignancies including neuroblastoma, rhabdomyosarcoma, medulloblastoma, astrocytoma, Wilms' tumor, and small cell lung cancer. While neuroblastoma is one of the most common childhood malignancies, in adults it is extremely rare and its treatment is based on pediatric protocols that take into consideration stage and genotypic features, such as MYCN amplification. Although neuroblastoma therapy has evolved, identification of early stage patients who need chemotherapy continues to pose a therapeutic challenge. The emerging prognostic role of MYCN phenotype of this disease is currently under investigation as it may redefine MYCN amplified subgroups. We describe an unusual case of adult neuroblastoma with MYCN amplification diagnosed incidentally and discuss possible therapeutic dilemmas.


Transcriptome profiling of lentil (Lens culinaris) through the first 24 hours of Ascochyta lentis infection reveals key defence response genes.
Ascochyta blight, caused by the fungus Ascochyta lentis, is one of the most destructive lentil diseases worldwide, resulting in over $16 million AUD annual loss in Australia alone. The use of resistant cultivars is currently considered the most effective and environmentally sustainable strategy to control this disease. However, little is known about the genes and molecular mechanisms underlying lentil resistance against A. lentis. To uncover the genetic basis of lentil resistance to A. lentis, differentially expressed genes were profiled in lentil plants during the early stages of A. lentis infection. The resistant 'ILL7537' and susceptible 'ILL6002' lentil genotypes were examined at 2, 6, and 24 h post inoculation utilising high throughput RNA-Sequencing. Genotype and time-dependent differential expression analysis identified genes which play key roles in several functions of the defence response: fungal elicitors recognition and early signalling; structural response; biochemical response; transcription regulators; hypersensitive reaction and cell death; and systemic acquired resistance. Overall, the resistant genotype displayed an earlier and faster detection and signalling response to the A. lentis infection and demonstrated higher expression levels of structural defence-related genes. This study presents a first-time defence-related transcriptome of lentil to A. lentis, including a comprehensive characterisation of the molecular mechanism through which defence against A. lentis is induced in the resistant lentil genotype.


Relative Validity of a Beverage Frequency Questionnaire Used to Assess Fluid Intake in the Autosomal Dominant Polycystic Kidney Disease Population.
Maintaining hydration sufficient to reduce levels of arginine vasopressin has been hypothesised to slow kidney cyst growth in autosomal dominant polycystic kidney disease (ADPKD). The semi-quantitative beverage frequency questionnaire (BFQ) was designed to measure usual fluid intake over the past month. The aim of this study was to assess the validity and reliability of the BFQ compared with the 24-h urine biomarkers. Participants with ADPKD (18⁻67 years; estimated glomerular filtration rate (eGFR) ≥ 30 mL/min1.73 m²) completed the BFQ. Serum creatinine, eGFR, 24-h urine volume, and osmolality were measured. Pearson correlation coefficients, paired t test, and Bland⁻Altman plots were used to evaluate agreement between the methods. A subset repeated the BFQ to assess reliability. A total of 121 participants (54% male, 43 ± 11 years; mean ± SD) completed the BFQ and at least one 24-h urine collection. The correlation between the BFQ and the 24-h urine volume was moderate (r = 0.580) and weaker with the 24-h urine osmolality (r = -0.276). The Bland⁻Altman plots revealed good agreement between the BFQ and the 24-h urine volume with no obvious bias; however, the limits of agreement were wide (-1517⁻1943 mL). The BFQ1 and BFQ2 were strongly correlated (r = 0.799, p < 0.001) and were not significantly different (p = 0.598). The BFQ is a valid and reliable tool to assess the usual fluid intake of the ADPKD population.


On the presence of bilirubin in the ocular humors of premature infants.
The yellow pigments observed in the ocular humors of premature infants were identified as the plasma pigments bilirubin and oxyhemoglobin. The blood/vitreous humor barrier to bilirubin was estimated to be (1/0.11) for total bilirubin and (1/0.25) for direct-acting bilirubin. Hall method histochemical staining for bilirubin in sections of premature infant eyes was highly positive for the vitreous humor, and suggestive of uptake of bilirubin by the neural-retinal cells.


Use of Complementary and Alternative Medicine in Children with Neuromuscular Disorders Followed at Penn State Health Pediatric Muscular Dystrophy Association Care Center Clinic.
The exact prevalence of complementary and alternative medicine (CAM) use is not known in pediatric patients with neuromuscular diseases followed by any of the 150 Muscular Dystrophy Association (MDA) Care Center Clinics nationwide. This study describes the prevalence and variety of CAM usage in this population, while also assessing the prevalence of caregiver disclosure of CAM use and caregiver perception of provider support for CAM. Fifty-two caregivers of pediatric patients seen at Penn State Health's Pediatric MDA Care Center Clinic completed our online survey. Overall, 19.2% of caregivers reported CAM use by their child. Less than half of caregivers reported discussing CAM use with their child's neurologist (41.5%); however, a majority of respondents reported interest in using CAM for their child in the future (52.8%). Understanding the prevalence of CAM usage and disclosure in pediatric MDA clinics may facilitate safer use of CAM in this community.


Teratogenic responses of zebrafish embryos to decabromodiphenyl ether (BDE-209) in the presence of nano-SiO2 particles.
This study investigated the influence of nano-SiO2 particles (nSiO2) on the teratogenic responses of zebrafish embryos to decabromodiphenyl ether (BDE-209). Zebrafish embryos were exposed to BDE-209 in the absence and presence of nSiO2 for 96 h post fertilization (hpf). Results showed that formation of nSiO2-BDE-209 associates promoted both extracellular and intracellular uptake of BDE-209 by zebrafish embryos, thereby increasing the bioconcentration of BDE-209 on the chorion surface and the embryos. Results also showed embryos delay hatching temporarily when co-exposure to BDE-209 and nSiO2 at 60 hpf. Furthermore, there was heartbeat decline (28.3 beats/10s) and increase in irregular heartbeat (45.8%) in zebrafish larvae at 96 hpf, compared to the sole exposure to BDE-209 (32.7 beats/10s and 0%). Malformation in terms of spinal curvature (SC), pericardial edema (PE) and yolk sac edema (YSE) were observed on zebrafish larvae at 33.9, 23.4, and 18%, respectively. Overall, abnormal development of zebrafish was apparent when co-exposure to BDE-209 and nSiO2. All relevant evidence considered, nSiO2 could facilitate the transport of BDE-209 towards zebrafish embryos and negatively impact the development of zebrafish.


The Glyoxalase System and Methylglyoxal-Derived Carbonyl Stress in Sepsis: Glycotoxic Aspects of Sepsis Pathophysiology.
Sepsis remains one of the leading causes of death in intensive care units. Although sepsis is caused by a viral, fungal or bacterial infection, it is the dysregulated generalized host response that ultimately leads to severe dysfunction of multiple organs and death. The concomitant profound metabolic changes are characterized by hyperglycemia, insulin resistance, and profound transformations of the intracellular energy supply in both peripheral and immune cells. A further hallmark of the early phases of sepsis is a massive formation of reactive oxygen (ROS; e.g., superoxide) as well as nitrogen (RNS; e.g., nitric oxide) species. Reactive carbonyl species (RCS) form a third crucial group of highly reactive metabolites, which until today have been not the focus of interest in sepsis. However, we previously showed in a prospective observational clinical trial that patients suffering from septic shock are characterized by significant methylglyoxal (MG)-derived carbonyl stress, with the glyoxalase system being downregulated in peripheral blood mononuclear cells. In this review, we give a detailed insight into the current state of research regarding the metabolic changes that entail an increased MG-production in septicemia. Thus, we point out the special role of the glyoxalase system in the context of sepsis.


Projecting the medical costs of AIDS and ARC in the United States.
We projected the direct medical costs of acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) for the United States during the period 1987-1991, by applying current epidemiologic projections to state-of-the-art medical decision algorithms for diagnosis and treatment of AIDS-related illnesses. We included the cost of azidothymidine (AZT) therapy, as well as other therapeutic innovations likely to be approved by the FDA, and estimated average ARC patient treatment costs. By combining prospective study data on rates of progression to AIDS with current AIDS incidence data, we arrived at human immunodeficiency virus (HIV) seroprevalence and AIDS incidence projection that were considerably lower than those of the Public Health Service. We estimated the average total medical costs per patient for AIDS in the 1990s at $27,950-$40,455 and for ARC at $3,621-$4,913 per year (1987 U.S. dollars). We projected the medical costs of AIDS and ARC at $2-4 billion annually by 1991, substantially lower than previous estimates. We projected that Pneumocystis carinii pneumonia and other pulmonary complications would account for the largest share (over 40%) of AIDS medical costs, and that AZT therapy and medication would account for more than 25% of total ARC/AIDS treatment costs by 1991. In our estimates, the total medical costs of treating ARC patients could approach one-half of the costs of treating AIDS patients by 1991, primarily due to costs associated with AZT.


EGF-dependent growth inhibition in MDA-468 human breast cancer cells is characterized by late G1 arrest and altered gene expression.
The MDA-468 human breast cancer cell line displays the unusual phenomenon of growth inhibition in response to pharmacological concentrations of EGF. This study was initiated with the objective of elucidating the cellular mechanisms involved in EGF-induced growth inhibition. Following EGF treatment the percentage of MDA-468 cells in G1 phase increased, together with a concomitant depletion in S and G2/M phase populations, as revealed by flow cytometry of DNA content. The apparent G1 block in the cell cycle was confirmed by treating the cells with vinblastine. DNA synthesis was reduced to about 35% of that measured in control, untreated cells after 48 h of EGF treatment, as measured by the incorporation of [3H]thymidine. DNA synthesis returned to normal following the removal of EGF from the growth-arrested cells. In order to locate the EGF-induced event responsible for the G1 arrest more precisely, we examined the expression of certain cell cycle-dependent genes by Northern blot analysis. EGF treatment did not alter either the induction of the early G1 marker, c-myc, or the expression of the late G1 markers, proliferating cell nuclear antigen, and thymidine kinase. However, EGF-treated cells revealed down regulation of p53 and histone 3.2 expression, which are expressed at the G1/S boundary and in S phase, respectively. These results indicate that EGF-induced growth inhibition in MDA-468 human breast cancer cells is characterized by a reversible cell cycle block at the G1/S boundary.


[Results of hallux valgus therapy after initial surgical correction].
Authors present own experience after use surgical correction technique in order to heal the complex hallux valgus deformity. In period 1999-2002 we used this technique on 5 patients (4 females, 1 male) with 6 surgical procedures (1 female had bilateral treatment). Indications for surgical treatment were functional problems and x-ray angle between the first and second metatarsals as well as valgus angle of the first metatarsophalangeal joint which were much higher. Pre-surgical, possibility of correction angle was exact by x-ray planing. The same examination was done after surgical treatment. After surgical care and rehabilitation program all patients had well biomechanical foot relation and they had not previous functional problems.


A selective coronary indicator dilution technique with fiberoptic recording.
A new method of accurately measuring myocardial circulation times is described: dye injections were made selectively into the left coronary artery while the passage of dye was recorded instantaneously in the coronary sinus with a fiberoptic catheter. The appearance time was found to be shorter than previously estimated (2.2 +/- 0.8 sec). The mean transit time in patients with left coronary artery disease and/or myocardial disease was significantly prolonged (p less than 0.01) and was found in all patients to shorten with increasing heart rate (p less than 0.01). Deformed dyd dilution curves were only obtained with stenotic lesions of the left coronary artery.


Real-time dosimetry with Yb-doped silica optical fibres.
Over the years, many efforts have been made to develop radiation detectors to handle the complex issues of small field dosimetry and achieve the increasing accuracy, precision and in vivo dose monitoring required by the new advanced treatment modalities. In this context, interest has surged in the development of sensors based on scintillating optical fibres. In this paper, the near-infrared radioluminescence and dosimetric properties of Yb-doped silica optical fibres, coupled with a laboratory prototype based on an avalanche photodiode, were studied by irradiating the fibres with photons and electron beams generated by a Varian Trilogy accelerator. The performance of the system in standard and small field sizes has also been investigated, comparing the output factor, percentage depth dose and off-axis ratio measurements of the prototypal detector with other commercial sensors, including the Exradin W1 scintillator. The results of this study demonstrate that the drawback due to the stem effect in Yb-doped silica optical fibres can be managed in a simple but effective way by optical filtering. The robustness of the system in complex dosimetric scenarios and the accuracy and precision achieved by Yb-doped fibres in relative dose assessments suggest an effective use of the system for real-time in vivo dosimetry applications.


Effects of a knee extension constraint brace on selected lower extremity motion patterns during a stop-jump task.
Small knee flexion angle during landing has been proposed as a potential risk factor for sustaining noncontact ACL injury. A brace that promotes increased knee flexion and decreased posterior ground reaction force during landing may prove to be advantageous for developing prevention strategies. Forty male and forty female recreational athletes were recruited. Three-dimensional videographic and ground reaction force data in a stop-jump task were collected in three conditions. Knee flexion angle at peak posterior ground reaction force, peak posterior ground reaction force, the horizontal velocity of approach run, the vertical velocity at takeoff, and the knee flexion angle at takeoff were compared among conditions: knee extension constraint brace, nonconstraint brace, and no brace. The knee extension constraint brace significantly increased knee flexion angle at peak posterior ground reaction force. Both knee extension constraint brace and nonconstraint brace significantly decreased peak posterior ground reaction force during landing. The brace and knee extension constraint did not significantly affect the horizontal velocity of approach run, the vertical velocity at takeoff, and the knee flexion angle at takeoff. A knee extension constraint brace exhibits the ability to modify the knee flexion angle at peak posterior ground reaction force and peak posterior ground reaction force during landing.


Pharmacokinetics of sirolimus in stable renal transplant patients after multiple oral dose administration.
In this 2-week, ascending dose study, the pharmacokinetic activity of sirolimus was examined in 40 stable renal transplant patients treated with cyclosporine and prednisone. Nine dose levels (range, 0.5-6.5 mg/m2/12 hr) of sirolimus were studied in a parallel design. Mean values for the pharmacokinetic parameters of sirolimus calculated in all dose groups were as follows: time to peak blood concentration, 1.4 +/- 1.2 hours; terminal half-life, 62 +/- 16 hours; oral dose clearance, 208 +/- 95 mL/h/kg; apparent oral steady-state volume of distribution, 12 +/- 5 L/kg; and blood/plasma ratio, 38 +/- 13. The intersubject variabilities in dose clearance, steady-state volume of distribution, and blood/plasma ratio were 4.5-fold. Preliminary assessments suggests linear dose proportionality. An excellent correlation existed between area under the concentration-time curve and trough blood concentration at steady state. Sirolimus did not produce any significant changes in area under the concentration-time curve of cyclosporine. Preliminary analysis suggested that values for the pharmacokinetic parameters of sirolimus vary among races (black versus nonblack) but not among genders.


The Effect of Preserved Residual Renal Function on Left Ventricular Structure in Non-Anuric Peritoneal Dialysis Patients.
Residual renal function (RRF) has been shown to influence survival of peritoneal dialysis (PD) patients. This study examined the relations between RRF and left ventricular hypertrophy (LVH) before switching on dialysis treatment and observed during 18 months on PD treatment. A prospective longitudinal study was performed in 50 non-anuric (defined as >200 mL urine output in a 24-hour period) PD patients. Echocardiography, RRF and other known risk factors for the increase of LV mass index (LVMi) were determined at study baseline and the end of follow-up. There was 78% patients with LVH in end-stage renal disease (ESRD) baseline and 60% at the end of follow-up. RRF at the start of the study showed no significant difference between patients with normal and increased LVMi, as well as in daily collection of urine. After 18 months, patients with decreased LVMi had better RRF, lower CRP and better Kt/V compared to patients with increased LVMi (p < 0.001). Patients with better preserved RRF not only had significantly higher total Kt/V, but were less anemic and hypoproteinemic and lesser presence of LVH. PD in non-anuric ESRD patients the first 18 months has a positive effect on the preservation of RRF and partial regression of left ventricular remodeling.


Juxtaglomerular cell tumor of the kidney.
The authors describe a juxtaglomerular cell tumor (JGCT) which caused severe hypertension in a 58-year-old man. Light microscopy showed a circumscribed tumor composed of interlacing cords and occasional nodules of relatively uniform cells with no mitotic activity. Rhomboid crystals characteristic of "prerenin" were present within the cytoplasm of tumor cells, and there was a close relationship between the tumor and unmyelinated nerve axons. Intracytoplasmic renin was demonstrated by immunofluorescence, and tumor granules were shown to contain zinc by electron-beam microanalysis. Review of 14 prior cases, with additional follow-up of 9, showed that no patient had developed recurrence, metastasis, or another tumor. Four patients, however, are hypertensive but probably because of secondary tumor effects rather than recurrent hyperreninism. The distinction of JGCT from hemangiopericytoma with renal involvement is important because of the high mortality associated with the latter. The authors conclude that JGCT is benign, but patients with JGCT may remain hypertensive postnephrectomy because of hypertensive angiopathy.


Encrusted Cystitis with Suspected Ureteral Obstruction Following Cystoscopic-Guided Laser Ablation of Ectopic Ureters in a Dog.
A 1 yr old 30 kg spayed female Labrador retriever presented for stranguria and hematuria 3 wk after cystoscopic laser ablation for ectopic ureters. Encrusted cystitis was diagnosed based on ultrasonography, cystoscopy, urinalysis, and culture of Corynebacterium urealyticum from the urine. Unilateral hydronephrosis and hydroureter were suspected to be secondary to obstruction at the trigone. The dog was treated with focal debridement of plaques at the left ureter, urinary acidification, and long-term antibiotic therapy with complete recovery. This is the first report of encrusted cystitis as a complication of cystoscopic-guided laser ablation for ectopic ureters, and suggests cystoscopic debridement may be useful if ureteral obstruction occurs.


[Russian Medical Society for Arterial Hypertension expert consensus. Resistant hypertension: detection and management].
The diagnosis of resistant arterial hypertension allows us to single out a separate group of patients in whom it is necessary to use special diagnostic methods and approaches to treatment. Elimination of reversible factors leading to the development of resistant arterial hypertension, such as non-adherence to therapy, inappropriate therapy, secondary forms of arterial hypertension, leads to an improvement in the patient's prognosis. Most patients with resistant hypertension should be evaluated to rule out primary aldosteronism, renal artery stenosis, chronic kidney disease, and obstructive sleep apnea. The algorithm for examining patients, recommendations for lifestyle changes and a step-by-step therapy plan can improve blood pressure control. It is optative to use the most simplified treatment regimen and long-acting combined drugs. For a separate category of patients, it is advisable to perform radiofrequency denervation of the renal arteries.


Burnout: co-workers' perceptions of signs preceding workmates' burnout.
This paper is a report of a study to describe co-workers' perceptions of signs preceding workmates' burnout. Burnout engenders emotional and economic suffering, both individual and societal. It is therefore important to learn to recognize early signs to prevent burnout and co-workers, who have opportunities to recognize such signs, are valuable resources in this context. Fifteen interviews were conducted with nursing and medical staff in Sweden who had worked with a person who developed burnout. The interviews took place in 2004 and were analysed using a thematic content analysis. The narratives were obtained when co-workers already knew that their workmates were on sick leave because of burnout or had left their employment after sick leave because of burnout. The findings show that co-workers retrospectively recalled a multiplicity of signs. They perceived that the people concerned were struggling to manage alone, showing self-sacrifice, struggling to achieve unattainable goals, becoming distanced and isolated, and showing signs of falling apart. Some of the signs preceding workmates' burnout may be difficult to interpret as signs of burnout, because they may be regarded as qualities which are to some extent encouraged in the prevailing culture. The findings provide a complex picture of these signs that will hopefully increase our awareness of and ability to recognize such signs to facilitate the possibilities of our helping in time. The sub-themes and themes in the present study may also serve as a basis for supervisors involved in supporting clinical staff.


The intertwine of nanotechnology with the food industry.
The past decade has proven the competence of nanotechnology in almost all known fields. The evolution of nanotechnology today in the area of the food industry has been largely and has had a lot of contribution in the food processing, food package, and food preservation. The increasing global human population has come with growing population to be fed, and food production is not adjusted to at par with the growing population. This mismatch has shown the real essence of food preservation so that food products can reach to people on a global scale. The introduction of nanotechnology in the food industry has made it easy to transport foods to different parts of the world by extending the shelf-life of most food products. Even with this beneficial aspect of nanotechnology, it has not been proven an entire full-proof measure, and the field is still open to changing technology. It suffices to note that nanotechnology has to a big extent succeed in curbing the extent of food wastage due to food spoilage by the microbial infestation. Nanotechnology has focused on fresh foods, ensuring a healthier food by employing nano-delivery systems in the process. The delivery systems are the ones, which carries the food supplements. However, these are certain sets of regulations that must be followed to tame or control the health related risks of nanotechnology in food industries. This paper outlines the role of nanotechnology at different levels of the food industry including, packaging of food, processing of food and the various preservation techniques all aiming to increase the shelf life of the food products.


Understanding the toxicity of buried radioactive waste and its impacts.
The oral ingestion toxicities of buried high level radioactive waste from nuclear power plants and of the natural radioactivity in the ground are calculated and expressed as cancer doses, the number of fatal cancers predicted by the linear no-threshold theory if all of the material were fed to people. Unless the size of the U.S. nuclear power industry is greatly expanded, there will probably never be more than 2 trillion cancer doses (CD) in U.S. repositories, as compared with 31 trillion CD in the ground above them. Measurements of the uranium, thorium, and radium in human bodies indicate that the latter cause 500 deaths per year in U.S. The great majority of this material is derived from the top few meters of soil that are penetrated by plant roots. It is concluded that the annual number of U.S. deaths from buried nuclear wastes will be about 1.0 (or less), orders of magnitude less than the number from coal burning electricity generation, the principal competitor of nuclear power.