Fluorides in groundwater and its impact on health.
Fluoride is a naturally occurring toxic mineral present in drinking water and causes yellowing of teeth, tooth problems etc. Fluorspar, Cryolite and Fluorapatite are the naturally occurring minerals, from which fluoride finds its path to groundwater through infiltration. In the present study two groundwater samples, Station I and Station II at Hyderabad megacity, the capital of Andhra Pradesh were investigated for one year from January 2001 to December 2001. The average fluoride values were 1.37 mg/l at Station I and 0.91 mg/l at Station II. The permissible limit given by BIS (1983) 0.6-1.2 mg/l and WHO (1984) 1.5 mg/l for fluoride in drinking water. The groundwaters at Station I exceeded the limit while at Station II it was within the limits. The study indicated that fluoride content of 0.5 mg/l is sufficient to cause yellowing of teeth and dental problems.


Osteoblastoma of the lumbar spine as a cause of chronic low back pain.
We report a case of osteoblastoma in the uncommon location of the L5 lumbar vertebra, detailing the clinical and radiologic aspects. Although the plain radiographs of the patient were normal, computed tomographic scans of the lumbar region confirmed the diagnosis of osteoblastoma or osteoid osteoma of the L5 vertebra. The patient was referred to the orthopedic department for operation. Histologic examination revealed osteoblastoma of the L5 vertebra. Following surgery, the patient's pain resolved completely. Although osteoblastoma is extremely rare in the spine, it should be included in the differential diagnosis as a cause of chronic back pain, especially in young males with painful scoliosis and/or radicular-type leg pain. The tumor is often not readily apparent on plain radiographs. Therefore, advanced radiological investigation is necessary to establish the correct diagnosis.


Regulation of dopaminergic markers expression in response to acute and chronic morphine and to morphine withdrawal.
Dopamine (DA) is thought to represent a teaching signal and has been implicated in the induction of addictive behaviours. Dysfunction of DA homeostasis leading to high or low DA levels is causally linked to addiction. Previously, it has been proposed that the transcription factors Nurr1 and Pitx3, which are critical for transcription of a set of genes involved in DA metabolism in the mesolimbic pathway, are associated with addiction pathology. Using quantitative real-time polymerase chain reaction, immunofluorescence and Western blotting, we studied the effects of single morphine administration, morphine dependence and withdrawal on the DA markers DA transporters (DAT), vesicular monoamine transporters (VMAT2) and DA 2 receptor subtype (DRD2), DA 1 receptor subtype as well as tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and/or nucleus accumbens (NAc). In addition, Nurr1 and Pitx3 expression was also measured. Present data showed a high degree of colocalization of Nurr1 and Pitx3 with TH(+) neurons in the VTA. We found that the increased Nurr1 and/or Pitx3 levels during morphine dependence and in morphine-withdrawn rats were associated to an increase of DAT, VMAT2 and DRD2. Altogether, present data indicate that morphine dependence and withdrawal induced consistent alterations of most of the DA markers, which was correlated with transcription factors involved in the maintenance of DA neurons in drug-reward pathways, suggesting that Nurr1 and Pitx3 regulation might be associated with controlling adaptation to chronic morphine and to morphine withdrawal-induced alterations of DA neurons activity in the mesolimbic pathway.


Identification of the purC gene product of Escherichia coli.
The purC region of the Escherichia coli chromosome was isolated from in vivo-derived lambda transducing bacteriophages and cloned in high-copy-number plasmids. The product of the purC gene, phosphoribosylaminoimidazolesuccinocarboxamide synthetase, was identified as a protein with an Mr of ca. 27,000. The level of the protein is increased by more than 60-fold in strains carrying the gene on a high-copy-number plasmid. Purine addition represses the enzyme level in both plasmid- and non-plasmid-containing strains.


Intrarenal angiotensin II and angiotensinogen augmentation in chronic angiotensin II-infused mice.
The objectives of this study were to determine the effects of chronic angiotensin II (ANG II) infusions on ANG II content and angiotensinogen expression in the mouse kidney and the role of the angiotensin II type 1 receptor (AT(1)R) in mediating these changes. C57BL/6J male mice were subjected to ANG II infusions at doses of 400 or 1,000 ng.kg(-1).min(-1) either alone or with an AT(1)R blocker (olmesartan; 3 mg.kg(-1).day(-1)) for 12 days. Systolic and mean arterial pressures were determined by tail-cuff plethysmography and radiotelemetry. On day 13, blood and kidneys were collected for ANG II determinations by radioimmunoanalysis and intrarenal angiotensinogen expression studies by quantitative RT-PCR, Western blotting, and immunohistochemistry. ANG II infusions at the low dose elicited progressive increases in systolic blood pressure (135 +/- 2.5 mmHg). In contrast, the high dose induced a rapid increase (152 +/- 2.5, P < 0.05 vs. controls, 109 +/- 2.8). Renal ANG II content was increased by ANG II infusions at the low dose (1,203 +/- 253 fmol/g) and the high dose (1,258 +/- 173) vs. controls (499 +/- 40, P < 0.05). Kidney angiotensinogen mRNA and protein were increased only by the low dose to 1.13 +/- 0.02 and 1.26 +/- 0.10, respectively, over controls (1.00, P < 0.05). These effects were not observed in mice infused at the high dose and those receiving olmesartan. The results indicate that chronic ANG II infusions augment mouse intrarenal ANG II content with AT(1)R-dependent uptake occurring at both doses, but only the low dose of infusion, which elicited a slow progressive response, causes an AT(1)R-dependent increase in intrarenal angiotensinogen expression.


Beyond regulatory T cells: the potential role for IL-2 to deplete T-follicular helper cells and treat autoimmune diseases.
Low-dose IL-2 administration suppresses unwanted immune responses in mice and humans, thus evidencing the potential of IL-2 to treat autoimmune disorders. Increased Tregs activity is one of the potential mechanisms by which low-dose IL-2 immunotherapy induces immunosuppression. In addition, recent data indicate that IL-2 may contribute to prevent unwanted self-reactive responses by preventing the developing of T-follicular helper cells, a CD4(+) T-cell subset that expands in autoimmune disease patients and promotes long-term effector B-cell responses. Here we discuss the mechanisms underlying the clinical benefits of low-dose IL-2 administration, focusing on the role of this cytokine in promoting Treg-mediated suppression and preventing self-reactive T-follicular helper cell responses.


A twofold interpenetrating three-dimensional heterometallic metal-organic framework with pcu topology based on 2-methylbiphenyl-4,4'-dicarboxylic acid.
The 2-methylbiphenyl-4,4'-dicarboxylate (mbpdc2-) ligand has versatile coordination modes and can be used to construct multinuclear structures. Despite this, reports of the synthesis of coordination complexes involving this ligand are scarce. The title compound, poly[[triaquadi-μ3-hydroxido-hexakis(μ4-2-methylbiphenyl-4,4'-dicarboxylato)calcium(II)hexazinc(II)] monohydrate], {[CaZn6(C15H10O4)6(OH)2(H2O)3]·H2O}n, has been prepared by the hydrothermal assembly of Zn(NO3)2·6H2O, CaCl2 and 2-methylbiphenyl-4,4'-dicarboxylic acid. Two ZnII atoms adopt a four-coordinated distorted tetrahedral geometry by bonding to three O atoms from three different 2-methylbiphenyl-4,4'-dicarboxylate (mbpdc2-) dianionic ligands and one bridging hydroxide O atom. For the remaining ZnII atom, a five-coordinate environment is completed half the time by one carboxylate O atom, and then the same carboxylate O atom and an aqua O atom are present the other half of the time, giving a six-coordinate environment. The CaII atom is coordinated by six O atoms to give an octahedral coordination geometry. The supramolecular secondary building unit (SBU) is a hamburger-like heptanuclear unit (Zn6CaO30) and these units are interconnected through mbpdc2- carboxylate groups to generate a three-dimensional framework with the pcu topology. The single net leaves voids that are filled by mutual interpenetration of an independent equivalent framework in a twofold interpenetrating architecture. The title compound shows thermal stability up to 673 K. The excitation and luminescence data showed the emission of a bright-blue fluorescence.


Reconfigurable Multifunctional van der Waals Ferroelectric Devices and Logic Circuits.
Emerging reconfigurable devices are fast gaining popularity in the search for next-generation computing hardware, while ferroelectric engineering of the doping state in semiconductor materials has the potential to offer alternatives to traditional von-Neumann architecture. In this work, we combine these concepts and demonstrate the suitability of reconfigurable ferroelectric field-effect transistors (Re-FeFETs) for designing nonvolatile reconfigurable logic-in-memory circuits with multifunctional capabilities. Modulation of the energy landscape within a homojunction of a 2D tungsten diselenide (WSe2) layer is achieved by independently controlling two split-gate electrodes made of a ferroelectric 2D copper indium thiophosphate (CuInP2S6) layer. Controlling the state encoded in the program gate enables switching between p, n, and ambipolar FeFET operating modes. The transistors exhibit on-off ratios exceeding 106 and hysteresis windows of up to 10 V width. The homojunction can change from Ohmic-like to diode behavior with a large rectification ratio of 104. When programmed in the diode mode, the large built-in p-n junction electric field enables efficient separation of photogenerated carriers, making the device attractive for energy-harvesting applications. The implementation of the Re-FeFET for reconfigurable logic functions shows how a circuit can be reconfigured to emulate either polymorphic ferroelectric NAND/AND logic-in-memory or electronic XNOR logic with a long retention time exceeding 104 s. We also illustrate how a circuit design made of just two Re-FeFETs exhibits high logic expressivity with reconfigurability at runtime to implement several key nonvolatile 2-input logic functions. Moreover, the Re-FeFET circuit demonstrates high compactness, with an up to 80% reduction in transistor count compared to standard CMOS design. The 2D van de Waals Re-FeFET devices therefore exhibit promising potential for both More-than-Moore and beyond-Moore future of electronics, in particular for an energy-efficient implementation of in-memory computing and machine learning hardware, due to their multifunctionality and design compactness.


Small conductance calcium-activated potassium channels of trout CNS: molecular structure, developmental expression, and partial biophysical characterization.
Two small conductance calcium-activated potassium channels that exhibited amino acid similarity with mammalian SK2 and SK3, respectively, were PCR cloned from the CNS of trout and sequenced. Upon heterologous expression in Sf21 insect cells trout SK2 (termed tSK2) produced a calcium-dependent, voltage-insensitive, and non-inactivating current with a single unit conductance of about 11 pS. This current was half maximally activated by 0.76 microM Ca(2+) and blocked by picomolar concentrations of apamin but not by TEA. Transcripts of both SK-related channels possessed a widespread distribution in the mature brain tissue of trout and outside the nervous system were detectable in muscle tissue as well as in liver. As revealed by RT-PCR analysis transcripts encoding tSK2 and tSK3 channels were early detectable during brain development (stage 30, shortly after hatching).


[General hydro galvanic baths in the treatment of patients with lumbosacral radiculopathy].
Hydrogalvanic baths are a hydrotherapy method based on the combined effect of electric current and fresh water on the body. Scientific evidence and evaluation of the effectiveness of use of general hydrogalvanic baths in the treatment of patients with lumbosacral radiculopathy with the background of degenerative spinal disorder. A randomized comparative clinical trial included 84 patients. The 1st (active) group included 43 patients, the 2nd (control) had 41 patients. Patients of the 1st group received general hydrogalvanic baths. Patients in the control group - drug treatment, including NSAIDs, muscle relaxants, anticonvulsants. The assessment was carried out before treatment, at the end of the course (on the 14th day) and 3 months after the end of treatment according to the results of neurological examination, VAS questionnaires, Pain DETECT, Beck scale, Oswestry scale, SF-36 scales, electroneuromyography (nerve conduction study). In patients receiving general hydrogalvanic baths, in comparison with the control group, there was an improvement in sensitivity (the incidence of hypesthesia decreased from 77 to 11%, p=0.008) and conductivity in peripheral sensory fibers. A decrease in pain was observed in both groups, however, a decrease in neuropathic pain was recorded only in patients receiving drug treatment. In the 1st group during therapy, an improvement in the emotional state in patients and a decrease in the level of depression were revealed. An analysis of long-term results showed that the delayed effect of non-drug treatment significantly increased in patients of the 1st group in comparison with the control group (p<0.05). Exposure to general hydrogalvanic baths is an effective way to treat lumbosacral radiculopathy, the main registered effects are: improvement of sensitivity, reduction of pain and stabilization of the emotional background. However, the studied method does not affect neuropathic pain.


An appreciation of the maximum tolerated dose: an inadequately precise decision point in designing a carcinogenesis bioassay?
Cancers arise in specific tissues. One difficulty with the present definitions of the Maximum Tolerated Dose (MTD), as they pertain to the rodent cancer bioassay, is that they base MTD on relatively crude parameters associated with the well-being of the entire animal rather than with the lack of specific tissue toxicity. Additional factors that could be included in the MTD definition, or could be separately determined, are addressed. Many of these factors refer to toxic behavior in one or a few tissues and, if used in setting the MTD, may mask more relevant events occurring at higher dose levels in other tissues. Reducing the MTD to a level that fails to take into account pesticide or drug-related toxicity may lead to the loss of relevant information in the bioassay. It is concluded, therefore, that there are two possible approaches to a more appropriate use of the MTD. The highest dose of the test agent (MTD) may be chosen (i) to lie below the thresholds of carcinogenicity-related non-genotoxic toxicity or (ii) the present high level MTD may continue to be used and tumors that arise may be classified as being irrelvant to humans at some or all exposure levels. The latter approach is to be preferred. It has the potential to avoid missing high level effects of the test agent that may be relevant to the human population.


Vedolizumab Induces Long-term Mucosal Healing in Patients With Crohn's Disease and Ulcerative Colitis.
Vedolizumab has proven efficacy in inflammatory bowel disease [IBD], but long-term mucosal healing in Crohn's disease [CD], as well as the incidence of colorectal neoplasia in IBD, among patients treated with vedolizumab have not been studied. We aimed to document mucosal healing and to explore the risk of colorectal neoplasia with vedolizumab maintenance therapy. Surveillance colonoscopy was prospectively scheduled for patients with longstanding ulcerative coltis [UC] or CD at a tertiary referral centre, in the open-label extension phase (vedolizumab 300 mg intravenously [IV] every 4 weeks) of the Gemini studies [GEMINI LTS, study number NCT00790933]. Mayo score ≤ 1 or ulcer disappearance [in CD] was defined as mucosal healing. Targeted biopsies were graded for inflammation and dysplasia. Of 68 patients [29 CD/39 UC] treated for ≥ 1 year [median 3.2 years, range 1.1-6.1], 58 [24 CD/34 UC] were endoscopically monitored. Durable endoscopic healing corrected by non-responder imputation was found in 7/24, 29% [CD] and 17/34, 50% [UC]. Combined histological and mucosal healing was observed in 5/24 [CD] and 11/34 [UC] of those with endoscopic healing. Low-grade dysplasia was detected in 10% of patients and high-grade dysplasia in the resection specimen of one patient with biopsy-proven low-grade dysplasia. Long-term endoscopic and histological healing was observed in a proportion of patients treated with vedolizumab long-term. The dysplasia risk with vedolizumab deserves further study.


GABAergic inhibitory neurons as therapeutic targets for cognitive impairment in schizophrenia.
Schizophrenia is considered primarily as a cognitive disorder. However, functional outcomes in schizophrenia are limited by the lack of effective pharmacological and psychosocial interventions for cognitive impairment. GABA (gamma-aminobutyric acid) interneurons are the main inhibitory neurons in the central nervous system (CNS), and they play a critical role in a variety of pathophysiological processes including modulation of cortical and hippocampal neural circuitry and activity, cognitive function-related neural oscillations (eg, gamma oscillations) and information integration and processing. Dysfunctional GABA interneuron activity can disrupt the excitatory/inhibitory (E/I) balance in the cortex, which could represent a core pathophysiological mechanism underlying cognitive dysfunction in schizophrenia. Recent research suggests that selective modulation of the GABAergic system is a promising intervention for the treatment of schizophrenia-associated cognitive defects. In this review, we summarized evidence from postmortem and animal studies for abnormal GABAergic neurotransmission in schizophrenia, and how altered GABA interneurons could disrupt neuronal oscillations. Next, we systemically reviewed a variety of up-to-date subtype-selective agonists, antagonists, positive and negative allosteric modulators (including dual allosteric modulators) for α5/α3/α2 GABAA and GABAB receptors, and summarized their pro-cognitive effects in animal behavioral tests and clinical trials. Finally, we also discuss various representative histone deacetylases (HDAC) inhibitors that target GABA system through epigenetic modulations, GABA prodrug and presynaptic GABA transporter inhibitors. This review provides important information on current potential GABA-associated therapies and future insights for development of more effective treatments.


A peroxynitrite decomposition catalyst prevents mechanical allodynia and NMDA receptor activation in the hind-paw ischemia reperfusion injury rats.
The contributions of superoxide and nitric oxide to ischemia/reperfusion (I/R)-induced neuropathic pain have previously been demonstrated in an animal model that mimics the symptoms of complex regional pain syndrome type I (CRPS I). Targeting peroxynitrite, which is the product of their interaction, may provide effective treatments for I/R-induced neuropathic pain. In this study, the effect of the peroxynitrite decomposition catalyst FeTMPyP [5,10,15,20-tetrakis (N-methyl-4'-pyridyl)porphyrinato iron (III)], administered at doses of 1, 3 and 10 mg/kg via intraperitoneal injection 30 min prior to reperfusion, was evaluated in rats with chronic post-ischemic pain. The pain behavior of the rats was tested with a von Frey filament. Phosphorylation of N-methyl-D-aspartate (NMDA) receptors in the L4/6 section of the spinal cord was measured on the third day following reperfusion by western blotting. The rats treated with 3 or 10 mg/kg FeTMPyP demonstrated significant increases in their paw withdrawal thresholds and decreased levels of phosphorylated NMDA receptor subunit 1 compared with those of the vehicle group (all P<0.001). These findings suggest that nitrosative stress, specifically that associated with peroxynitrite, may be involved in the mechanical allodynia and central sensitization that are associated with CRPS I and may provide a rationale for CRPS I treatment strategies using peroxynitrite decomposition catalysts.


Practices and Attitudes of Michigan-Based Occupational Physicians Regarding Adult Immunization.
To assess practices and barriers regarding adult immunizations, among occupational and environmental physicians in Michigan. A 10-item multiple choice web based questionnaire was designed after reviewing the Centers for Disease Control and Prevention recommendations and the current literature on adult immunization standards. Assessing immunization status is common practice for 62% of respondents. 92% of respondents recommend the annual influenza vaccination, unless contraindicated. The most commonly reported barriers included the cost of providing immunizations and the prioritization of acute over preventative care. Use of standing order vaccinations and reminder-recall systems were popular strategies used to improve vaccination rates. Occupational physicians frequently recommend influenza, tetanus, and hepatitis B vaccines when indicated, but are less likely to order other vaccines for patients. Promotion of a more comprehensive assessment of immunity needs in the workplace may improve national vaccine coverage.


Comparing racial and ethnic populations based on Healthy People 2010 objectives.
Objective - The Healthy People 2010 initiative (HP2010) specified objectives for improving the health of the nation, established baseline values, and set specific targets to be achieved by 2010. HP2010 objectives are based on two overarching goals: First, to increase years and quality of life, and second, to eliminate disparities among subgroups of the population. In this report racial and ethnic populations are compared based on progress toward targets, the size of disparities, and changes in disparity for specific sets of objectives. Methods - Progress is measured in terms of movement toward or away from the target between the HP2010 baseline and the most recent data point. Disparities are measured as the percent difference between the rate for the racial and ethnic population with the best or most favorable rate and the rates for the other racial and ethnic populations. Changes in disparity are measured in terms of the percentage point change in the percent difference from the best group rate between the baseline and the most recent data point. Some comparisons can be made based on objectives with data for five populations (American Indian or Alaska Native, Asian, Hispanic or Latino, non-Hispanic black, and non-Hispanic white). Additional comparisons can be made for objectives with data for the three larger populations (Hispanic or Latino, non-Hispanic black, and non-Hispanic white). Results - Differences between populations in progress toward the targets for HP2010 objectives are observed; however, the majority of objectives was moving toward or had reached their targets for each population. Greater differences between racial and ethnic populations are evident in the size of disparities. Disparities for the American Indian or Alaska Native, the Hispanic or Latino and non-Hispanic black populations are greater than those for the Asian and non-Hispanic white populations. Between the baseline and the most recent data point, the number of objectives with increasing disparities was similar to the number of objectives with decreasing disparities and there was no change in disparity for most objectives. In order to achieve the two goals of HP2010, rates must improve and relative differences between populations must be reduced.


Resin-infiltrated-dentine--a FE-ESEM microscopy investigation.
The formation of a hybrid layer is essential for bonding of dental composites to dentine. The objective of this study was to examine the effects of various etchants/conditioners and dentine bonding systems on dentine surfaces utilising a Field Emission Environmental SEM (FE-ESEM). Twenty one, freshly extracted human molar teeth were utilised. Dentine without resin application was initially observed both wet and dried in the following conditions: (1) fractured surface, (2) smear layer, and (3) smear layer removed with 37% phosphoric acid. Resin infiltration into dentine was then studied after applying Scotchbond 1, Optibond Solo, Prime & Bond NT, or Prompt L-Pop systems. Scotchbond 1, Optibond Solo, and Prime & Bond NT resins penetrated the dentine tubules and created hybrid layers; although, in some cases Prime & Bond NT only created a partially filled hybrid layer. No polymerised resin or hybrid layer was observed for Prompt L-Pop. The FE-ESEM permitted observation of specimens at near in-vivo wet conditions.


Quercetin nanoparticles display antitumor activity via proliferation inhibition and apoptosis induction in liver cancer cells.
Quercetin is a potent cancer therapeutic agent and dietary antioxidant present in fruit and vegetables. Quercetin prevents tumor proliferation by inducing cell cycle arrest and is a well known cancer therapeutic agent and autophagy mediator. Recent studies showed that drug delivery by nanoparticles have enhanced efficacy with reduced side effects. In this regard, gold-quercetin into poly(DL-lactide-co-glycolide) nanoparticles was examined. In this study, we explored the role and possible underlying mechanisms of quercetin nanoparticle in regulation of antitumor activity in liver cancer cells. Treatment with quercetin nanoparticle effectively inhibited the liver cancer cell proliferation, cell migration and colony formation, thus suppressing liver cancer progression. Quercetin nanoparticle also upregulated apoptosis markedly. Further study suggested that quercetin nanoparticle accelerated the cleavage of caspase-9, caspase-3, and induced the up-releasing of cytochrome c (Cyto-c), contributing to apoptosis in liver cancer cells. Quercetin nanoparticles also promoted telomerase reverse transcriptase (hTERT) inhibition through reducing AP-2β expression and decreasing its binding to hTERT promoter. In addition, quercetin nanoparticle had an inhibitory role in cyclooxygenase 2 (COX-2) via suppressing the NF-κB nuclear translocation and its binding to COX-2 promoter. Quercetin nanoparticle also inactivated Akt and ERK1/2 signaling pathway. Taken together, our results suggested that quercetin nanoparticle had an antitumor effect by inactivating caspase/Cyto-c pathway, suppressing AP-2β/hTERT, inhibiting NF-κB/COX-2 and impeding Akt/ERK1/2 signaling pathways. Our results provided new mechanistic basis for further investigation of quercetin nanoparticles to find potential therapeutic strategies and possible targets for liver cancer inhibition.


Hepatitis B Vaccination Status among Japanese Travelers.
This study clarified the characteristics of travelers who received hepatitis B vaccinations. Subjects were 233 Japanese travelers who visited our clinic prior to travel. We summarized the characteristics of the clients and performed two comparative studies: first, we compared a hepatitis B-vaccinated group with an unvaccinated group; second, we compared a group that had completed the hepatitis B vaccine series with a group that did not complete the series. The hepatitis B vaccine was administered to 152 clients. Factors positively associated with the hepatitis B vaccination (after adjusting for age and sex) included the following: travel for business or travel as an accompanying family member; travel to Asia; travel for a duration of a month or more; and, inclusion of the vaccine in a company or organization's payment plan. Meanwhile, factors negatively associated with the vaccination were travel for leisure or education, and travel to North America or Africa. Among 89 record-confirmed cases, only 53 completed 3 doses. The completion rate was negatively associated with the scheduled duration of travel if it was from a month to less than a year (after adjusting for age and sex). The present study provides a basis for promoting vaccination compliance more vigorously among Japanese adults.


Biomarkers for HER2-positive metastatic breast cancer: Beyond hormone receptors.
The overexpression of human epidermal growth factor receptor-2 (HER2) results in a biologically and clinically aggressive breast cancer (BC) subtype. Since the introduction of anti-HER2 targeted agents, survival rates of patients with HER2-positive metastatic BC have dramatically improved. Currently, although the treatment decision process in metastatic BC is primarily based on HER2 and hormone-receptor (HR) status, a rapidly growing body of data suggests that several other sources of biological heterogeneity may characterize HER2-positive metastatic BC. Moreover, pivotal clinical trials of new anti-HER2 antibody-drug conjugates showed encouraging results in HER2-low metastatic BC, thus leading to the possibility, in the near future, to expand the pool of patients suitable for HER2-targeted treatments. The present review summarizes and puts in perspective available evidence on biomarkers that hold the greatest promise to become potentially useful tools for optimizing HER2-positive metastatic BC patients' prognostic stratification and treatment in the next future. These biomarkers include HER2 levels and heterogeneity, HER3, intrinsic molecular subtypes by PAM50 analysis, DNA mutations, and immune-related factors. Molecular discordance between primary and metastatic tumors is also discussed.


Serum thyroglobulin level after radioiodine therapy (Day 3) to predict successful ablation of thyroid remnant in postoperative thyroid cancer.
The utility of serum thyroglobulin (Tg) level, 3 days after radioactive iodine (RAI) therapy, was assessed as a means of predicting successful ablation of thyroid remnant in patients with postoperative thyroid cancer. A total of 152 patients with thyroid cancer (mean age = 44.9 ± 13.7 year) undergoing RAI therapy after total thyroidectomy were included. Levels of TSH-stimulated Tg prior to ablation (stimTg) and serum Tg sampled immediately after RAI therapy (Day 3) were measured (immTg). ImmTg samples were collected during patient hospital visits for scheduled follow-up of radioiodine scans. Successful ablation was determined by the second time stimulated Tg levels (≤1 ng/ml) and negative radioiodine uptake at thyroid bed after 6.1 ± 1.1 months of RAI therapy. Univariate and multivariate analyses were done for immTg, stimTg, change in Tg levels (deltaTg: immTg - stimTg), immTg:stimTg ratio (ratioTg), and other potential clinical and pathologic markers of successful ablation. Of selected laboratory variables, ratioTg was a significant predictor of successful ablation. StimTg, tumor diameter, metastatic lymph node (LN) numbers, lymphatic invasion were possible clinical markers of successful ablation by univariate analysis. By multivariate analysis, ratioTg (odds ratio = 7.851), stimTg (odds ratio = 16.819), metastatic LN numbers (odds ratio with stimTg = 6.732) proved significant results. Furthermore, combining high ratioTg and low stimTg provided added predictive value. High ratioTg (reflecting extensive release of Tg to the blood after RAI therapy) and low stimTg (reflecting small remnant thyroid tissue) constitute the indices of successful ablation after RAI therapy. Immediate Tg level could give an useful information on RAI ablation of postoperative thyroid remnant.


Levodopa: is toxicity a myth?
Whether a drug such as levodopa, which is prescribed for long periods, may be toxic is a legitimate and even indispensable question. The problem is no different from that posed by other drugs-such as calcium antagonists, antihypertensives, or hormones-normally prescribed for chronic diseases. What, however, is meant in this context by "toxic" (from the Greek toxicon, meaning poison)? Irrevocable damage such as cell loss should not be confused with reversible side effects resulting from cell dysfunction. Clinically or experimentally, levodopa has not been shown to accelerate neurodegeneration or cause permanent impairment of cell function in a manner that would result in irreversible side effects. These data have been reasonably well established in vivo in animals and humans, although preliminary studies suggesting that levodopa is a trophic factor remain unconfirmed. Like oxygen or calcium, levodopa can be toxic in vitro when it is present in high concentrations or in the absence of glial cells. However, glial cells are much more numerous than neurons in vivo, so these conditions cannot simply be extrapolated to three-dimensional brain structures in which protective interactions with the cellular environment abound. Because levodopa remains the most effective treatment available for Parkinson's disease, questions regarding timing or manner of administration of the drug should arise not because levodopa is toxic to nerve cells, but because it causes reversible side effects. When the elementary rules of substitutive therapy to provide maximum comfort while limiting side effects are followed, we need not fear that levodopa is dangerous unless the contrary is proven.


[Abnormal liver tests during pregnancy - emergency department decision making].
Abnormal liver biochemical and function tests is common problem among patients in emergency department and can result from many different pathologies. In pregnant women, causes are sometime life-threating for the mother and the fetus. The role of emergency physician is : 1) to differentiate between serious (HELPPS syndrome, pre-eclampsia and eclampsia, acute fatty liver of pregnancy) and minor (intrahepatic cholestasis, hyperemesis gravidarum) pregnancy related liver disease and 2) to recognize non-pregnancy related liver disease.


A novel technique of STEM observation of TEM section using LVSEM and application of pathological diagnosis of renal biopsy.
The usefulness of the transmission electron microscope (TEM) for pathological diagnosis is apparent. However, high operating costs and other disadvantages have limited the ability to maintain and operate a TEM. In recent years, a general-purpose benchtop low-vacuum scanning electron microscope (LVSEM), which is inexpensive and easy to operate, has been developed and is expected to be applied in electron microscopic pathological diagnosis. To date, we have previously observed TEM ultrathin sections of Immunoglobulin A (IgA) nephropathy with a benchtop LVSEM using an ultra variable-pressure detector (UVD) and a newly developed holder for observing scanning transmission electron microscope (STEM) images (UVD-STEM holder) and compared the images with those obtained with typical TEM observations. We reported the results in the 53rd Annual Meeting of the Japanese Society for Clinical Molecular Morphology and the 64th Symposium of The Japanese Society of Microscopy and discussed the validity of the methods in the pathological diagnosis of IgA nephropathy and other renal diseases. As a result, we demonstrated the potential for pathological diagnosis using benchtop LVSEM. In this study, we similarly examined typical kidney diseases such as membranous nephropathy, lupus nephritis and amyloidosis. We could obtain sufficient data for the pathological diagnosis of IgA nephropathy, membranous nephropathy and lupus nephritis. However, it is difficult to detect amyloid fibres that are characteristic of amyloidosis. The development of this method is expected to expand the possibilities for pathological diagnosis using electron microscopy, including its application to other diseases.


A Rapid Biochemical and Radiological Response to the Concomitant Therapy with Temozolomide and Radiotherapy in an Aggressive ACTH Pituitary Adenoma.
Background and Importance. In the last eight years temozolomide (TMZ) has been used as the last-line treatment modality for aggressive pituitary tumors to be applied after the failure of surgery, medical therapy, and radiotherapy. The objective was to achieve a rapid control of tumor growth and hormone normalization with concurrent chemoradiotherapy in a patient with very aggressive ACTH pituitary adenoma. Clinical Presentation. We describe a patient with an aggressive ACTH-producing adenoma treated with concurrent temozolomide and radiotherapy. The patient suffered from an aggressive ACTH adenoma resistant to surgical and medical treatment. After two months of concurrent temozolomide and radiotherapy, cortisol normalization and significant tumor shrinkage were observed. After 22 months of follow-up, there is still no evidence of tumor recurrence. Conclusion. Concurrent treatment with temozolomide and irradiation appears to be highly effective in the achievement of the tumor volume control as well as in the control of ACTH secretion in aggressive ACTH adenoma.


Modulation of transmembrane pressure in manufacturing scale tangential flow filtration N-1 perfusion seed culture.
Mammalian cells were grown to high density in a 3,000 L culture using perfusion with hollow fibers operated in a tangential flow filtration mode. The high-density culture was used to inoculate the production stage of a biomanufacturing process. At constant permeate flux operation, increased transmembrane pressures (TMPs) were observed on the final day of the manufacturing batches. Small scale studies suggested that the filters were not irreversibly fouled, but rather exposed to membrane concentration polarization that could be relieved by tangential sweeping of the hollow fibers. Studies were undertaken to analyze parameters that influence the hydrodynamic profile within hollow fibers; including filter area, cell density, recirculation flow rate, and permeate flow rate. Results indicated that permeate flow rate had the greatest influence on modulating TMP. Further evaluation showed a significant decrease in TMP when permeate flow was reduced, and this occurred without any negative effect on cell growth or viability. Hence, a 30% reduction of permeate flow rate was implemented at manufacturing scale. A stable operation was achieved as TMP was successfully reduced by 75% while preserving all critical factors for performance in the perfusion bioreactor.


Eosinophilic angiocentric fibrosis : a sino-orbital masquerader.
A 58-year-old Caucasian male presented with left periorbital oedema extending to the nasal area for 1 year along with nasal discharge for 1 month. Lab work was significant for positive cytoplasmic antineutrophil cytoplasmic antibodies. CT scan showed solid mass along the nasal soft tissue with bony nasal destruction. A CT scan of the thorax was performed to rule out granulomatosis with polyangiitis and showed multiple pulmonary nodules. Biopsies of the nasal mass and lung nodule were performed which showed fragments of fibrosis with spindle cell proliferation consistent with eosinophilic angiocentric fibrosis (EAF). EAF is a very rare disease, recently described as a subtype of immunoglobulin G4-related disease. A few rare cases of EAF involving the structures of the orbit have been reported in the literature.


Review of petroleum toxicity in marine reptiles.
Worldwide petroleum exploration and transportation continue to impact the health of the marine environment through both catastrophic and chronic spillage. Of the impacted fauna, marine reptiles are often overlooked. While marine reptiles are sensitive to xenobiotics, there is a paucity of petroleum toxicity data for these specialized fauna in peer reviewed literature. Here we review the known impacts of petroleum spillage to marine reptiles, specifically to marine turtles and iguanas with an emphasis on physiology and fitness related toxicological effects. Secondly, we recommend standardized toxicity testing on surrogate species to elucidate the mechanisms by which petroleum related mortalities occur in the field following catastrophic spillage and to better link physiological and fitness related endpoints. Finally, we propose that marine reptiles could serve as sentinel species for marine ecosystem monitoring in the case of petroleum spillage. Comprehensive petroleum toxicity data on marine reptiles is needed in order to serve as a foundation for future research with newer, unconventional crude oils of unknown toxicity such as diluted bitumen.


[Progress in studies of glutathione S-transferase P1 and prostate cancer].
Prostate cancer ( PCa) is an important genitourinary malignancy with increasing morbidity and mortality. Glutathione S-transferase P1 ( GSTP1) , as a phrase- II enzyme, has an important role in the activation and detoxification of carcinogens. There is a close association between GSTP1 gene polymorphisms and the risk of Pca. GSTP1 CpG island hypermethylation can reliably distinguish Pca from benign prostatic hyperplasia( BPH) and promises to be an important molecular marker for the diagnosis of Pca. This paper summarizes the association of GSTP1 with the diagnosis and risk of Pca.


Hemorrhagic corpus luteum mimicking heterotopic pregnancy.
Hemorrhagic corpus luteum (CL) is clinically known to simulate a number of medical, surgical and gynecologic conditions that cause acute abdomen. One such case is hereby presented that mimicked ectopic pregnancy clinically and heterotopic pregnancy on ultrasound. Laparoscopy was decisive.


Improved Electrocatalytic Activity and Stability by Single Iridium Atoms on Iron-based Layered Double Hydroxides for Oxygen Evolution.
Full understanding to the origin of the catalytic performance of a supported nanocatalyst from the points of view of both the active component and support is significant for the achievement of high performance. Herein, based on a model electrocatalyst of single-iridium-atom-doped iron (Fe)-based layered double hydroxides (LDH) for oxygen evolution reaction (OER), we reveal the first completed origin of the catalytic performance of such supported nanocatalysts. Specially, besides the activity enhancement of Ir sites by LDH support, the stability of surface Fe sites is enhanced by doped Ir sites: DFT calculation shows that the Ir sites can reduce the activity and enhance the stability of the nearby Fe sites; while further finite element simulations indicate, the stability enhancement of distant Fe sites could be attributed to the much low concentration of OER reactant (hydroxyl ions, OH- ) around them induced by the much fast consumption of OH- on highly active Ir sites. These new findings about the interaction between the main active components and supports are applicable in principle to other heterogeneous nanocatalysts and provide a completed understanding to the catalytic performance of heterogeneous nanocatalysts.


Hypothesis: ROBOPHERA, a phosphatase and tensin homolog-targeted antineoplastic therapy.
Phosphatase and tensin homolog (PTEN) is a protein that regulates cellular response to growth/antigrowth signals, cell survival, apoptosis, proliferation, angiogenesis, and cellular migration. Impairments in these processes are the main hallmarks of cancer, and reduced expression, activity, or stability of PTEN are among the most common etiologies of diverse types of sporadic cancers. Rosiglitazone (RO), bortezomib (BO), phosphatidylserine (PH), ethanol (E), and radiotherapy (RA) (ROBOPHERA) stimulate the expression and increase the activity of PTEN. Here, it is hypothesized that the synergistic effects of these medications on cancerous cells may stimulate differentiation of cancer stem cells toward non-stem-cancer cells, hinder progression and metastasis of the cancer, sensitize cancerous cells to antineoplastic therapies, and increase the efficacy and the rate of success of current treatments.


When is the physician "Playing God"?
In the author's opinion, the medical profession is committed to the preservation and prolongation of life through use of all ordinary remedies, but is not obliged ethically or morally to apply extraordinary measures when there is no realistic hope of recovery. In addition to the proper medical therapy, the care given during the dying phase of life by the physician includes the responsibility of deciding whether the geriatric patient should be allowed to die in a dignified manner. The question of who should bear this responsibility is discussed.


Changes in the superior longitudinal fasciculus and anterior thalamic radiation in the left brain are associated with developmental dyscalculia.
Developmental dyscalculia is a neurodevelopmental disorder specific to arithmetic learning even with normal intelligence and age-appropriate education. Difficulties often persist from childhood through adulthood lowering the individual's quality of life. However, the neural correlates of developmental dyscalculia are poorly understood. This study aimed to identify brain structural connectivity alterations in developmental dyscalculia. All participants were recruited from a large scale, non-referred population sample in a longitudinal design. We studied 10 children with developmental dyscalculia (11.3 ± 0.7 years) and 16 typically developing peers (11.2 ± 0.6 years) using diffusion-weighted magnetic resonance imaging. We assessed white matter microstructure with tract-based spatial statistics in regions-of-interest tracts that had previously been related to math ability in children. Then we used global probabilistic tractography for the first time to measure and compare tract length between developmental dyscalculia and typically developing groups. The high angular resolution diffusion-weighted magnetic resonance imaging and crossing-fiber probabilistic tractography allowed us to evaluate the length of the pathways compared to previous studies. The major findings of our study were reduced white matter coherence and shorter tract length of the left superior longitudinal/arcuate fasciculus and left anterior thalamic radiation in the developmental dyscalculia group. Furthermore, the lower white matter coherence and shorter pathways tended to be associated with the lower math performance. These results from the regional analyses indicate that learning, memory and language-related pathways in the left hemisphere might be related to developmental dyscalculia in children.


Visual recognition and visually guided action after early bilateral lesion of occipital cortex: a behavioral study of a 4.6-year-old girl.
We report the case of a 4.6-year-old girl born pre-term with early bilateral occipital damage. It was revealed that the child had non-severely impaired basic visual abilities and ocular motility, a selective perceptual deficit of figure-ground segregation, impaired visual recognition and abnormal navigating through space. Even if the child's visual functioning was not optimal, this was the expression of adaptive anatomic and functional brain modifications that occurred following the early lesion. Anatomic brain structure was studied with anatomic MRI and Diffusor Tensor Imaging (DTI)-MRI. This behavioral study may provide an important contribution to understanding the impact of an early lesion of the visual system on the development of visual functions and on the immature brain's potential for reorganisation related to when the damage occurred.


Effects of dietary mixture of protease and probiotics on growth performance, blood constituents, and carcass characteristics of growing-finishing pigs.
This study was conducted to evaluate the effects of dietary mixture of protease and probiotics on growth performance, blood constituents, and carcass characteristics of growing-finishing pigs. A total of 48 growing pigs were randomly allotted into 2 dietary (6 pigs/pen; 4 replicates/treatment). The treatments were a diet based on corn and soybean meal (CON) and CON supplemented with 0.01% of dietary mixture of protease and probiotics (MULTI). No differences were found on growth performance (average daily gain, ADG; overall, 874.06 vs. 881.14 g/d; p > 0.05), blood constituents (white blood cell, WBC; phase I, 17.51 vs. 19.96 × 103 /μL; phase II, 19.65 vs. 21.95 × 103 /μL; p > 0.05), and carcass characteristics during overall experimental period between CON and MULTI. In conclusion, the addition of dietary mix-ture of protease and probiotics in growing-finishing pig diet did not have any beneficial effects.


Accidental transmission of HCV and treatment with interferon.
Accidental transmission of contagious pathogens, especially hepatitis C virus (HCV), by needlestick or other means as an occupational hazard for medical staff is of concern. We retrospectively analysed cases of work-related accidental injury with pathogens such as hepatitis B virus (HBV), HCV, syphilis and human immunodeficiency virus (HIV) reported to the centres for disease control at 15 hospitals (total 5776 beds) in the Gunma prefecture, Japan, from December 1990 to August 1993 (24.7 months). There were 416 such cases (16.8 cases/month), with an incidence of 0.2-3.5 accidents per month per hospital. Such accidents occurred in 297 (71.2%) nurses, 98 (23.5%) medical doctors, 13 (3%) laboratory technicians, four (1.0%) hospital maintenance workers, one (0.2%) assistant nurse, one secretary and two others. There were 323 (77.6%) injuries caused by needlestick, 42 (10.1%) from suture needles or surgical knife cuts, 17 (4.1%) from blood splatters from patients into the eyes or mouth, 10 (2.4%) from contact with injured skin and 24 (5.8%) simple skin contacts. Of the pathogens, 60.3% were HCV, 22.6% HBV, 5.8% syphilis, 0.7% HIV and 10.6% were of unknown origin. Four cases (1.6%) of HCV infection were found and treated with one or two courses of interferon therapy, and HCV was subsequently cleared. All four patients were cured with interferon therapy. None of the HBV-injured cases resulted in infection, possibly because of prophylaxis with HB immunoglobulin and HB vaccine. No HIV or syphilis infection was contracted. In summary, chronic HCV infection acquired as an occupational hazard can be cured by appropriate treatment, such as with interferon, after early detection of the infection.


Natural history of benign prostate hyperplasia.
Benign prostate hyperplasia is one of the most common diseases affecting the health of the aging males. Watchful waiting is an acceptable management strategy for benign prostate hyperplasia in which the patient is monitored by the physician but receives no active intervention. The epidemiological data on this are lacking in China. Our study was designed to evaluate the changes of signs and symptoms of patients with benign prostate hyperplasia during management by watchful waiting in China. One hundred and forty-five patients with benign prostate hyperplasia aged > 50 years were enrolled in management by watchful waiting. All the patients were visited every 6 months and were given an International Prostate Symptom Score and Quality of Life questionnaire to complete. They also had uroflowmetry and were assessed using ultrasonography to get the volume of prostate, transition zone and amount of residual urine. The Student's t test, the Chi-square test, and variance analysis were used in the statistical analysis. All patients were visited after 6 months, the mean volume of transitional zone was found to have increased by 1.6 ml (P < 0.01), International Prostate Symptom Score was increased by 0.8 (P < 0.01) and Quality of Life was increased by 0.2 (P < 0.01), and there was no statistical change in other data. Among these patients, 17.9% (26/145) visited again after 12 months when the data failed to show a statistically significant difference among the three groups (0, 6, and 12 months). After one year's follow-up, the progression of benign prostate hyperplasia was slow and the clinical data did not undergo much change.


Acute cell damage after low Mg2+-induced epileptiform activity in organotypic hippocampal slice cultures.
Upon perfusion with Mg2+-free artificial cerebrospinal fluid (ACSF) organotypic hippocampal slice cultures develop seizure-like events and tonic recurrent discharges in which areas CA3 and CA1 and, in contrast to acute slices, also the dentate gyrus (DG) participate. Using the fluorescent dye propidium iodide (PI) we show that sustained epileptic activity causes cell death in the DG and pyramidal cell layer particularly evident in the granule cell layer of the DG. This correlates with the decrease of the electrophysiological responses to hilar stimulation. Interestingly, perfusion with carbogenated serum-free ACSF also induces some cell death which is, however, mild compared with low magnesium treated slice cultures.


Serum neutrophil gelatinase-associated lipocalin levels are correlated with the complexity and the severity of atherosclerosis in acute coronary syndrome.
Neutrophil gelatinase-associated lipocalin (NGAL) is a novel inflammatory marker that is released from neutrophils. In this study, we evaluated the correlation between serum NGAL level and clinical and angiographic risk scores in patients diagnosed with non-ST elevation acute coronary syndrome (NSTE-ACS). Forty-seven random NSTE-ACS patients and 45 patients with normal coronary arteries (NCA) who underwent coronary angiography were enrolled in the study. GRACE risk score and SYNTAX and Gensini risk scores were used, respectively, for the purpose of clinical risk assessment and angiographic risk scoring. Serum NGAL level was measured via ELISA in peripheral blood samples obtained from the patients at the time of admission. Serum NGAL level was significantly higher in the NSTE-ACS group compared to the control group (112.3±49.6 ng/mL vs. 58.1±24.3 ng/mL, p<0.001). There was a significant positive correlation between serum NGAL levels and the GRACE (r=0.533 and p<0.001), SYNTAX (r=0.395 and p=0.006), and Gensini risk scores (r=0.575 and p<0.001). The intermediate-high SYNTAX (>22) group had statistically significantly higher serum NGAL levels compared to the low SYNTAX (≤22) group (143±29.5 ng/mL vs. 98.7±43.2 ng/mL, p=0.001). NGAL level was positively correlated with lesion complexity and severity of coronary artery disease in patients with NSTE-ACS. Serum NGAL levels on admission are associated with increased burden of atherosclerosis in patients with NSTE-ACS.


Does outdoor air pollution induce new cases of asthma? Biological plausibility and evidence; a review.
It is widely accepted that air pollution can exacerbate asthma in those who already have the condition. What is less clear is whether air pollution can contribute to the initiation of new cases of asthma. Mechanistic evidence from toxicological studies, together with recent information on genes that predispose towards the development of asthma, suggests that this is biologically plausible, particularly in the light of the current understanding of asthma as a complex disease with a variety of phenotypes. The epidemiological evidence for associations between ambient levels of air pollutants and asthma prevalence at a whole community level is unconvincing; meta-analysis confirms a lack of association. In contrast, a meta-analysis of cohort studies found an association between asthma incidence and within-community variations in air pollution (largely traffic dominated). Similarly, a systematic review suggests an association of asthma prevalence with exposure to traffic, although only in those living very close to heavily trafficked roads carrying a lot of trucks. Based on this evidence, the U.K.'s Committee on the Medical Effects of Air Pollutants recently concluded that, overall, the evidence is consistent with the possibility that outdoor air pollution might play a role in causing asthma in susceptible individuals living very close to busy roads carrying a lot of truck traffic. Nonetheless, the effect on public health is unlikely to be large: air pollutants are likely to make only a small contribution, compared with other factors, in the development of asthma, and in only a small proportion of the population.


Accuracy of colon tumor localization: Computed tomography scanning as a complement to colonoscopy.
To determine the utility of computed tomography (CT) scanning in localizing colon tumors. At a single tertiary care teaching hospital, a retrospective chart review was conducted on patients who underwent surgery for colon malignancies between January 2004 and May 2006. One hundred and four charts containing all of the following data were reviewed: preoperative colonoscopy report, preoperative CT report, surgical operative report, tumor pathology report. The colon was divided into five segments from the cecum to the sigmoid and the location of the lesions was categorized into one of these areas. The tumor location was considered "erroneous" if its location determined during surgery differed from the location determined by colonoscopy or CT. Over all, tumor location was accurately determined via colonoscopy in 83/104 cases (79.8%) and erroneously in 21/104 (20.2%) of cases. CT scan accurately localized colon tumors in 52/104 (50.0%) of cases, incorrectly localized tumors in 18/104 (17.3%) of cases, and did not detect known tumors in 34/104 (32.7%) of cases. Of the 21 tumors erroneously located by colonoscopy, 11 (52.4%) were accurately localized by CT scan. The average tumor size for all patients in this study was 5.72 (+/- 3.11) cm. The average size of tumors properly located by colonoscopy and CT was 5.39 (+/- 3.34) cm and 6.79 (+/- 3.48) cm, respectively. The average size of the tumors not detected by CT was 3.98 (+/- 1.75) cm. CT scanning may be used in concert with colonoscopy to help localize colon tumors.


Association of high sensitivity C-reactive protein and abdominal aortic aneurysm: a meta-analysis and systematic review.
To evaluate the association of high sensitivity C-reactive protein (hsCRP) with the presence of abdominal aortic aneurysm (AAA). Medline, Cochrane, Embase, and Google Scholar databases were searched until 22 June 2016 using the keywords predictive factors, biomarkers, abdominal aortic aneurysm, prediction, high sensitivity C-reactive protein, and hsCRP. Prospective studies, retrospective studies, and cohort studies were included. Twelve case-control studies were included in the meta-analysis with a total of 8345 patients (1977 in the AAA group and 6368 in the control group). The pooled results showed that AAA patients had higher hsCRP value than the control group (difference in means = 1.827, 95% CI = 0.010 to 3.645, p = .049). Subgroup analysis found AAA patients with medium or small aortic diameter (<50 mm) had higher hsCRP plasma levels than the control group (difference in means = 1.301, 95% CI = 0.821 to 1.781, p < .001). In patients with large aortic diameter (≥50 mm), no difference was observed in hsCRP levels between the AAA and control groups (difference in means = 1.769, 95% CI = -1.387 to 4.925, p = .272). Multi-regression analysis found the difference in means of hsCRP plasma levels between AAA and control groups decreased as aortic diameter increased (slope = -0.04, p < .001), suggesting that hsCRP levels may be inversely associated with increasing aneurysm size. Our findings suggest that hsCRP levels may possibly be used as a diagnostic biomarker for AAA patients with medium or small aortic diameter but not for AAA patients with large aortic diameter. The correlation between serum hsCRP level and AAA aneurysm is not conclusive due to the small number of included articles and between-study heterogeneity.


Hydrolysis by human alpha-amylase of p-nitrophenyloligosaccharides containing four to seven glucose units.
Kinetic and "high-pressure" liquid-chromatographic studies were performed on the reaction of human pancreatic and salivary alpha-amylase (EC 126.96.36.199) with p-nitrophenyloligosaccharides containing four to seven glucose units. The kinetic studies indicate that, as the temperature increases from 25 to 37 degrees C, the apparent Km of the enzyme for a given substrate increases slightly. However, as the number of glucose units in the substrate increases, the apparent Km decreases. The apparent Vmax increases as the temperature increases, and decreases as the number of glucose units in the substrate increases. In contrast, chromatographic data indicate that the relative rate of hydrolysis by alpha-amylase is pG7 greater than pG6 greater than pG5 greater than pG4. The differences between the kinetic and the chromatographic results are discussed. p-Nitrophenyl-alpha-maltopentaoside and p-nitrophenyl-alpha-maltohexaoside are superior to the other p-nitrophenyloligosaccharides as substrates for determining alpha-amylase activity in an alpha-glucosidase-coupled assay system.


Causes and Risk Factors for Absenteeism among Medical Staff in German Specialized Lung Clinics during the COVID Pandemic.
Staff shortages pose a major challenge to the health system. The objective of this study was to clarify the role of different causative factors we investigated on staff absenteeism during the COVID pandemic. The prospective multicentre cohort study assessed the private and professional impact of the pandemic on health care workers (HCWs) using a specially developed questionnaire. HCWs from 7 specialist lung clinics throughout Germany were surveyed from December 1 to December 23, 2021. The current analysis addresses pandemic-related absenteeism. 1,134 HCW (55% female; 18.4% male, 26.3% not willing to provide information on age or gender) participated. 72.8% had received at least one vaccination dose at the time of the survey, and 9.4% reported a COVID infection. Of those with positive tests, 98% reported home quarantine for median (IQR) 14 (12-17) days; 10.3% of those who ultimately tested negative also reported quarantine periods of 14 (7-14) days. 32.2% of vaccinated respondents reported absenteeism due to vaccine reactions of 2 (1-3) days. Overall, 37% (n = 420) of HCW reported pandemic-related absenteeism, with 3,524 total days of absenteeism, of which 2,828 were due to illness/quarantine and 696 to vaccination effects. Independent risk factors for COVID-related absenteeism ≥5 days included already having COVID, but also concern about long-term effects of COVID (OR 1,782, p = 0.014); risk factors for vaccine-related absenteeism ≥2 days included concerns of late effects of vaccination (OR 2.2, 95% CI: 1.4-3.1, p < 0.000). Staff shortages due to quarantine or infections and vaccine reactogenicity have put a strain on German respiratory specialists. The fact that staff concerns also contributed to absenteeism may be helpful in managing future pandemic events to minimize staff absenteeism.


Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304.
Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).


Inhibition of vagally mediated immune-to-brain signaling by vanadyl sulfate speeds recovery from sickness.
To the ill patient with diabetes, the behavioral symptoms of sickness such as fatigue and apathy are debilitating and can prevent recuperation. Here we report that peripherally administered insulin-like growth factor 1 (IGF-1) attenuates LPS-dependent depression of social exploration (sickness) in nondiabetic (db/+) but not in diabetic (db/db) mice. We show that the insulin/IGF-1 mimetic vanadyl sulfate (VS) is effective at augmenting recovery from sickness in both db/+ and db/db mice. Specifically, peak illness was reached at 2 h for both VS and control animals injected with LPS, and VS mice recovered 50% faster than non-VS-treated animals. Examination of the mechanism of VS action in db/+ mice showed that VS paradoxically augmented peritoneal macrophage responsivity to LPS, increasing both peritoneal and ex vivo macrophage production of IL-1beta and IL-6 but not TNF-alpha. The effects of VS in promoting recovery from sickness were not restricted to LPS, because they were also observed after direct administration of IL-1beta. To explore the possibility that VS impairs immune-to-brain communication via vagal afferents, the vagally mediated satiety-inducing effects of cholecystokinin 8 were tested in db/+ mice. Cholecystokinin decreased food intake in saline-injected mice but not in VS-treated mice. VS also inhibited LPS-dependent up-regulation of IL-1beta and IL-6 mRNA in the brain, while increasing by 50% the cerebral expression of transcripts of the specific antagonist of IL-1 receptors IL-1RA and IL-1R2. Taken together, these data indicate that VS improves recovery from LPS-induced sickness by blocking vagally mediated immune-to-brain signaling and by up-regulating brain expression of IL-1beta antagonists.


The origin of symptoms in patients with chronic heart failure.
Severe shortness of breath is a prominent symptom in acute heart failure (pulmonary oedema) and is related to left atrial pressure. A reduction of this pressure almost always leads to an improvement in symptoms. Patients with chronic heart failure complain of both shortness of breath and tiredness even when fluid overload has been corrected by the appropriate use of diuretics. Shortness of breath under these circumstances is not related simply to central haemodynamics but is determined more by the interaction of changes in respiratory pattern and the metabolic consequences of reduced perfusion of exercising skeletal muscle. An important clinical consequence is that when such patients are optimally treated with diuretics, further improvement of symptoms would not be expected from drugs which merely alter central haemodynamics without influencing other factors such as skeletal muscle blood flow on exercise, or lung perfusion.


The importance and role of intracluster correlations in planning cluster trials.
There is increasing recognition of the critical role of intracluster correlations of health behavior outcomes in cluster intervention trials. This study examines the estimation, reporting, and use of intracluster correlations in planning cluster trials. We use an estimating equations approach to estimate the intracluster correlations corresponding to the multiple-time-point nested cross-sectional design. Sample size formulae incorporating 2 types of intracluster correlations are examined for the purpose of planning future trials. The traditional intracluster correlation is the correlation among individuals within the same community at a specific time point. A second type is the correlation among individuals within the same community at different time points. For a "time x condition" analysis of a pretest-posttest nested cross-sectional trial design, we show that statistical power considerations based upon a posttest-only design generally are not an adequate substitute for sample size calculations that incorporate both types of intracluster correlations. Estimation, reporting, and use of intracluster correlations are illustrated for several dichotomous measures related to underage drinking collected as part of a large nonrandomized trial to enforce underage drinking laws in the United States from 1998 to 2004.


Fever of Unknown Origin With Normal Inflammatory Markers Due to Latent Pulmonary Embolism and Deep Vein Thrombosis: A Case Report.
An 86-year-old woman who was hospitalized due to cerebral hemorrhage developed an intermittent fever of up to 39.3°C. A computed tomography angiography of the chest with venous runoff to the legs showed pulmonary embolism (PE) and deep vein thrombosis (DVT) of the legs. Intravenous heparin rapidly reduced the fever, indicating that these thrombi were the primary cause of her fever. During her course, white blood cell count and serum C-reactive protein levels were always within normal limits. This case suggested that latent PE and DVT can be a cause of intermittent fever with normal inflammatory markers.


Healthy lifestyle and leukocyte telomere length in U.S. women.
Whether a healthy lifestyle may be associated with longer telomere length is largely unknown. To examine healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, in relation to leukocyte telomere length. Cross-sectional analysis in the Nurses' Health Study (NHS). The population consisted of 5,862 women who participated in multiple prospective case-control studies within the NHS cohort. Z scores of leukocyte telomere length were derived within each case-control study. Based on prior work, we defined low-risk or healthy categories for five major modifiable factors assessed in 1988 or 1990: non-current smoking, maintaining a healthy body weight (body mass index in 18.5-24.9 kg/m(2)), engaging in regular moderate or vigorous physical activities (≥150 minutes/week), drinking alcohol in moderation (1 drink/week to <2 drinks/day), and eating a healthy diet (Alternate Healthy Eating Index score in top 50%). We calculated difference (%) of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest. Although none of the individual low-risk factors was significantly associated with larger leukocyte telomere length z scores, we observed a significant, positive relationship between the number of low-risk factors and the z scores. In comparison with women who had zero low-risk factors (1.9% of the total population) and were, therefore, considered the least healthy group, the leukocyte telomere length z scores were 16.4%, 22.1%, 28.7%, 22.6%, and 31.2% (P for trend = 0.015) higher for women who had 1 to 5 low-risk factors, respectively. Adherence to a healthy lifestyle, defined by major modifiable risk factors, was associated with longer telomere length in leukocytes.


Born to Code: Does the Portrayal of Computer Scientists as Geniuses Undermine Adolescent Youths' Motivational Beliefs?
Introduction: Computer scientists are often stereotyped as geniuses who are naturally gifted in pSTEM (physical Sciences, Technology, Engineering, and Math). Prior correlational research found that this genius stereotype is negatively related to students' pSTEM motivation. However, the effect has not been explored experimentally to evaluate possible casual influences. Using situated expectancy-value theory as a framework, the present experiment tested whether media invoking the genius stereotype negatively impacts high school students' expectancy and value beliefs regarding pSTEM. Methods: The sample comprised of 213 U.S. high school students (53% boys, 46% Asian). Participants read one of two versions of an article profiling a student majoring in computer science. The genius condition emphasized the student's natural talent and the importance of being gifted for success in computer science, whereas the control condition did not mention these attributes. Pre- and post-test measures of pSTEM expectancy and value beliefs were assessed. Results and Conclusions: Students in the genius condition, but not the control condition, demonstrated a significant decline in pSTEM value beliefs. There was no effect on expectancy beliefs. Thus, popular stereotypes of persons in pSTEM as geniuses may contribute to students devaluing of pSTEM subjects. These stereotypes may be especially threatening to girls and students from minoritized backgrounds. Implications are discussed, including the need to address genius stereotypes in pSTEM classrooms.


Chemical PARP inhibition enhances growth of Arabidopsis and reduces anthocyanin accumulation and the activation of stress protective mechanisms.
Poly-ADP-ribose polymerase (PARP) post-translationally modifies proteins through the addition of ADP-ribose polymers, yet its role in modulating plant development and stress responses is only poorly understood. The experiments presented here address some of the gaps in our understanding of its role in stress tolerance and thereby provide new insights into tolerance mechanisms and growth. Using a combination of chemical and genetic approaches, this study characterized phenotypes associated with PARP inhibition at the physiological level. Molecular analyses including gene expression analysis, measurement of primary metabolites and redox metabolites were used to understand the underlying processes. The analysis revealed that PARP inhibition represses anthocyanin and ascorbate accumulation under stress conditions. The reduction in defense is correlated with enhanced biomass production. Even in unstressed conditions protective genes and molecules are repressed by PARP inhibition. The reduced anthocyanin production was shown to be based on the repression of transcription of key regulatory and biosynthesis genes. PARP is a key factor for understanding growth and stress responses of plants. PARP inhibition allows plants to reduce protection such as anthocyanin, ascorbate or Non-Photochemical-Quenching whilst maintaining high energy levels likely enabling the observed enhancement of biomass production under stress, opening interesting perspectives for increasing crop productivity.


Sijin Li.
"A key experience in my career was the complete biosynthesis of opium poppy-derived noscapine in yeast … I advise my students to explore as much as they can in the first years and focus as deeply as they can in the later years." Find out more about Sijin Li in her Introducing … Profile.


Effect of bovine serum albumin concentration and source on sperm capacitation in the golden hamster.
Since virtually all experiments on sperm capacitation routinely include serum albumin in the culture media, the relative effect of BSA concentration on sperm capacitation was investigated. The fertile life of hamster sperm, as measured by the ability to penetrate the zona pellucida, decreased from 5 to 3 h as the concentration of BSA was increased from 3 to 18 mg/ml. To determine the extent of sperm capacitation in sperm populations that resulted in 100% penetration, the rate and timing of sperm penetration through the zona pellucida was determined. For each insemination, the rate of sperm penetration (%/min), the time when 50% of the eggs were zona-penetrated (T50), and the sperm capacitation index (T50/rate) were calculated. The extent of sperm capacitation as measured by all three parameters increased as the duration of preincubation or the BSA concentration was increased. The data on the duration of preincubation and the BSA concentration matrix indicated two properties of the effect of BSA on sperm capacitation: 1) the extent of sperm capacitation after the first hour of preincubation was independent of BSA concentration; and 2) when sperm were preincubated for two or more hours, the capacitating effectiveness of BSA was saturable; the saturating concentration of BSA decreased as the duration of preincubation increased. To determine whether the first hour of preincubation is independent of BSA, sperm were preincubated for 1 h without BSA and then 2 h with BSA. The extent of sperm capacitation of these sperm was equal to that of the 3-h control sperm; thus the first hour of capacitation is independent of BSA.(ABSTRACT TRUNCATED AT 250 WORDS)


Screening Tests for Depression in Older Black vs. White Patients.
Thirty-nine psychiatric patients age 50 and older with diagnoses of depression participated in a study of the reliability of screening instruments in the identification of depression. All patients had a diagnosis of affective disorder confirmed by a SCID interview. Forty-nine percent of the depressed patients were black, 51% were 70-92 years old, 77% were women, and 51% were widowed. When the Center for Epidemiologic Studies-Depression Scale (CES-D) was administered to these depressed patients, its sensitivity in black patients was 71% and in white patients was 85%. The sensitivity of the Geriatric Depression Scale (GDS) was 53% in black patients and 65% in white patients. The CES-D was significantly better than the GDS in the identification of depressive symptoms in this sample. These data suggest that the CES-D and the GDS may not be equally effective in identifying depression among older American black and white patients. Further studies with larger samples of SCID-diagnosed, depressed, older black and white patients are needed to confirm these findings.


Enterotoxigenic bacteria in the sudden infant death syndrome.
Faecal samples from 123 infants who died with sudden infant death syndrome (SIDS) and from a comparative group of 52 age-matched babies were analysed for toxigenic bacteria and their toxins. Serum samples from the SIDS infants were also analysed for these toxins. A significantly higher proportion of toxigenic bacteria and their toxins were found in faecal samples of SIDS babies than in samples from the comparative group. These toxins were also found in serum from the SIDS babies. Clostridium perfringens was found in 54 (45.4%) of 119 SIDS cases compared with 10 (19.6%) of 51 healthy babies (chi 2 = 10.1, p < 0.01); C. difficile in 33 (27.7%) of 119 SIDS cases compared with 8 (14.8%) of 54 healthy babies (chi 2 = 3.43ns, p < 0.1); Staphylococcus aureus in 12 (27.3%; 66.7% enterotoxigenic) of 44 SIDS cases compared with 12 (85.7%; non-enterotoxigenic) of 14 healthy babies (chi 2 = 14.9, p < 0.001); C. botulinum in 6 (5.0%) of 120 SIDS cases compared with 0 of 53 healthy babies (chi 2 = 2.74, p < 0.1). Campylobacter jejuni, Yersinia enterocolitica, Vibrio parahaemolyticus, salmonellae and Bacillus cereus were not detected. Heat-labile toxin, lethal to mice (HLML) was found in 32 (27.1%) of 118 SIDS faecal samples compared with 5 (10.6%) of 47 healthy babies (chi 2 = 5.24, p < 0.05); cytotoxins in 38 (30.9%) of 123 SIDS faecal samples compared with 0 of 21 of healthy babies (chi 2 = 8.8, p < 0.01) and 24 (27.6%) of 87 SIDS serum samples. C. perfringens enterotoxin was detected in 33 (34.4%) of 96 SIDS faecal extracts compared with 0 of 23 of healthy babies (chi 2 = 10.94, p < 0.001), and in 27 (24.5%) of 110 SIDS serum samples. C. perfringens alpha-toxin (presumptive) was detected in 14 (17.5%) of 80 SIDS faecal extracts compared with 0 of 17 from healthy babies (chi 2 = 3.5ns, p congruent to 0.05) and in 2 (2.3%) of 87 SIDS serum samples. C. difficile toxin was detected in four SIDS faecal samples and two serum samples. C. botulinum toxin was detected in only one of 120 SIDS faecal samples compared with none of 49 from healthy babies. Staphylococcal enterotoxins were detected in 8 (19.5%) of 41 SIDS faecal samples compared with 0 of 19 from healthy babies (chi 2 = 4.278, p < 0.05), and in 4 (10.8%) of 37 SIDS serum samples.(ABSTRACT TRUNCATED AT 400 WORDS)


Rostro-Caudal Organization of Connectivity between Cingulate Motor Areas and Lateral Frontal Regions.
According to contemporary views, the lateral frontal cortex is organized along a rostro-caudal functional axis with increasingly complex cognitive/behavioral control implemented rostrally, and increasingly detailed motor control implemented caudally. Whether the medial frontal cortex follows the same organization remains to be elucidated. To address this issue, the functional connectivity of the 3 cingulate motor areas (CMAs) in the human brain with the lateral frontal cortex was investigated. First, the CMAs and their representations of hand, tongue, and eye movements were mapped via task-related functional magnetic resonance imaging (fMRI). Second, using resting-state fMRI, their functional connectivity with lateral prefrontal and lateral motor cortical regions of interest (ROIs) were examined. Importantly, the above analyses were conducted at the single-subject level to account for variability in individual cingulate morphology. The results demonstrated a rostro-caudal functional organization of the CMAs in the human brain that parallels that in the lateral frontal cortex: the rostral CMA has stronger functional connectivity with prefrontal regions and weaker connectivity with motor regions; conversely, the more caudal CMAs have weaker prefrontal and stronger motor connectivity. Connectivity patterns of the hand, tongue and eye representations within the CMAs are consistent with that of their parent CMAs. The parallel rostral-to-caudal functional organization observed in the medial and lateral frontal cortex could likely contribute to different hierarchies of cognitive-motor control.


A critical role for NF2 and the Hippo pathway in branching morphogenesis.
Branching morphogenesis is a complex biological process common to the development of most epithelial organs. Here we demonstrate that NF2, LATS1/2 and YAP play a critical role in branching morphogenesis in the mouse kidney. Removal of Nf2 or Lats1/2 from the ureteric bud (UB) lineage causes loss of branching morphogenesis that is rescued by loss of one copy of Yap and Taz, and phenocopied by YAP overexpression. Mosaic analysis demonstrates that cells with high YAP expression have reduced contribution to UB tips, similar to Ret(-/-) cells, and that YAP suppresses RET signalling and tip identity. Conversely, Yap/Taz UB-deletion leads to cyst-like branching and expansion of UB tip markers, suggesting a shift towards tip cell identity. Based on these data we propose that NF2 and the Hippo pathway locally repress YAP/TAZ activity in the UB to promote subsequent splitting of the tip to allow branching morphogenesis.


The strength of plant-pollinator interactions.
Recent studies of plant-animal mutualistic networks have assumed that interaction frequency between mutualists predicts species impacts (population-level effects), and that field estimates of interaction strength (per-interaction effects) are unnecessary. Although existing evidence supports this assumption for the effect of animals on plants, no studies have evaluated it for the reciprocal effect of plants on animals. We evaluate this assumption using data on the reproductive effects of pollinators on plants and the reciprocal reproductive effects of plants on pollinators. The magnitude of species impacts of plants on pollinators, the reciprocal impacts of pollinators on plants, and their asymmetry were well predicted by interaction frequency. However, interaction strength was a key determinant of the sign of species impacts. These results underscore the importance of quantifying interaction strength in studies of mutualistic networks. We also show that the distributions of interaction strengths and species impacts are highly skewed, with few strong and many weak interactions. This skewed distribution matches the pattern observed in food webs, suggesting that the community-wide organization of species interactions is fundamentally similar between mutualistic and antagonistic interactions. Our results have profound ecological implications, given the key role of interaction strength for community stability.


Corn silage management I: effects of hybrid, maturity, and mechanical processing on chemical and physical characteristics.
Two experiments were conducted to evaluate the effects of hybrid, maturity, and mechanical processing of whole plant corn on chemical and physical characteristics, particle size, pack density, and dry matter recovery. In the first experiment, hybrid 3845 whole plant corn was harvested at hard dough, one-third milkline, and two-thirds milkline with a theoretical length-of-cut of 6.4 mm. In the second experiment, hybrids 3845 and Quanta were harvested at one-third milkline, two-thirds milkline, and blackline stages of maturity with a theoretical length-of-cut of 12.7 mm. At each stage of maturity, corn was harvested with and without mechanical processing by using a John Deere 5830 harvester with an onboard kernel processor. The percentage of intact corn kernels present in unprocessed corn silage explained 62% of variation in total tract starch digestibility. As the amount of intact kernels increased, total tract starch digestibility decreased. Post-ensiled vitreousness of corn kernels within the corn silage explained 31 and 48% of the variation of total tract starch digestibility for processed and unprocessed treatments, respectively. For a given amount of vitreous starch in corn kernels, total tract starch digestibility was lower for cows fed unprocessed corn silage compared with processed corn silage. This suggests that processing corn silage disrupts the dense protein matrix within the corn kernel where starch is embedded, therefore making the starch more available for digestion. Particle size of corn silage and orts that contained corn silage was reduced when it was processed. Wet pack density was greater for processed compared with unprocessed corn silage.


Structural variability versus structural flexibility. A case study of Eu9Cd4+xSb9 and Ca9Mn4+xSb9 (x ≈ (1)/2).
The focus of this article is on the synthesis and structural characterization of the new ternary antimonides Eu(9)Cd(4+x)Sb(9) and Ca(9)Mn(4+x)Sb(9) (x ≈ (1)/2). Although these compounds have analogous chemical makeup and formulas, which may suggest isotypism, they actually belong to two different structure types. Eu(9)Cd(4.45(1))Sb(9) is isostructural with the previously reported Eu(9)Zn(4.5)Sb(9) (Pbam), and its structure has unit cell parameters a = 12.9178(11) Å, b = 23.025(2) Å, and c = 4.7767(4) Å. Ca(9)Mn(4.41(1))Sb(9) crystallizes in the orthorhombic space group Pnma with unit cell dimensions a = 12.490(2) Å, b = 4.6292(8) Å, and c = 44.197(8) Å and constitutes a new structure type. The two structures are compared and contrasted, and the structural relationships are discussed. Exploratory work aimed at the arsenic-based analogues of either type led to the identification of Ca(9)Zn(4.46(1))As(9), forming with the latter structure [a = 11.855(2) Å, b = 4.2747(8) Å, and c = 41.440(8) Å]. Differential thermal analysis and electrical resistivity measurements, performed on single crystals of Ca(9)Zn(4+x)As(9), indicate high thermal stability and semiconducting behavior. Magnetic susceptibility measurements on Eu(9)Cd(4+x)Sb(9) samples confirm the expected Eu(2+) ([Xe]4f(7)) ground state.


Specification and Diversification of Pericytes and Smooth Muscle Cells from Mesenchymoangioblasts.
Elucidating the pathways that lead to vasculogenic cells, and being able to identify their progenitors and lineage-restricted cells, is critical to the establishment of human pluripotent stem cell (hPSC) models for vascular diseases and development of vascular therapies. Here, we find that mesoderm-derived pericytes (PCs) and smooth muscle cells (SMCs) originate from a clonal mesenchymal progenitor mesenchymoangioblast (MB). In clonogenic cultures, MBs differentiate into primitive PDGFRβ+CD271+CD73- mesenchymal progenitors, which give rise to proliferative PCs, SMCs, and mesenchymal stem/stromal cells. MB-derived PCs can be further specified to CD274+ capillary and DLK1+ arteriolar PCs with a proinflammatory and contractile phenotype, respectively. SMC maturation was induced using a MEK inhibitor. Establishing the vasculogenic lineage tree, along with identification of stage- and lineage-specific markers, provides a platform for interrogating the molecular mechanisms that regulate vasculogenic cell specification and diversification and manufacturing well-defined mural cell populations for vascular engineering and cellular therapies from hPSCs.


Detection of uracil within DNA using a sensitive labeling method for in vitro and cellular applications.
The role of uracil in genomic DNA has been recently re-evaluated. It is now widely accepted to be a physiologically important DNA element in diverse systems from specific phages to antibody maturation and Drosophila development. Further relevant investigations would largely benefit from a novel reliable and fast method to gain quantitative and qualitative information on uracil levels in DNA both in vitro and in situ, especially since current techniques does not allow in situ cellular detection. Here, starting from a catalytically inactive uracil-DNA glycosylase protein, we have designed several uracil sensor fusion proteins. The designed constructs can be applied as molecular recognition tools that can be detected with conventional antibodies in dot-blot applications and may also serve as in situ uracil-DNA sensors in cellular techniques. Our method is verified on numerous prokaryotic and eukaryotic cellular systems. The method is easy to use and can be applied in a high-throughput manner. It does not require expensive equipment or complex know-how, facilitating its easy implementation in any basic molecular biology laboratory. Elevated genomic uracil levels from cells of diverse genetic backgrounds and/or treated with different drugs can be demonstrated also in situ, within the cell.


Influence of interleukin-6 on the invasiveness of human colorectal carcinoma.
Plasma interleukin-6 (IL-6) level correlates with patient survival in colorectal carcinoma and is regarded as a prognostic factor. In this study, the role of IL-6 in colorectal carcinoma proliferation, chemotaxis and invasion was investigated. Proliferation and invasion were measured in four colorectal carcinoma cell lines. The effect of IL-6 (10, 50, 100 ng/ml) on progression (the ability to grow, adhere, chemotax and invade) was also measured. Physiological (10 ng/ml) and pharmacological (50 and 100 ng/ml) concentrations of IL-6 did not significantly affect growth. However, IL-6 (10 ng/ml) significantly increased attachment to basement membrane (p < 0.05). IL-6 (50 ng/ml) significantly increased the chemotaxis, anchorage-independent growth and invasiveness of SW-480 (one of the four cell lines) (p < 0.05). IL-6 (100 ng/ml) resulted in negative feedback inhibition of these effects. IL-6 plays an important role in the progression of colorectal carcinoma.


Hormone profiling, including anti-Müllerian hormone (AMH), for the diagnosis of polycystic ovary syndrome (PCOS) and characterization of PCOS phenotypes.
Objective was to evaluate serum anti-Müllerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and in its different phenotypes in relation to clinical, endocrine and metabolic parameters using a new automated VIDAS® method and to compare it with the Gen II method. Study design was multi-center study including 319 PCOS women and 109 healthy controls. Serum AMH levels measured using VIDAS® were significantly higher in PCOS women than controls (p < .001), and they correlated with those measured using the AMH Gen II method. An AMH cutoff value of 42.1 pmol/L distinguished PCOS women from controls with 67% sensitivity and 83% specificity. The PCOS women with three Rotterdam criteria or hyperandrogenism displayed significantly higher AMH levels compared with those with two Rotterdam criteria or normoandrogenism. In PCOS, AMH levels correlated positively with luteinizing hormone (LH), androgen and sex hormone-binding globulin (SHBG) levels and negatively with BMI, abdominal obesity, follicle-stimulating hormone (FSH), fasting glucose and insulin, and insulin resistance. In conclusion, AMH evaluated using the VIDAS® method distinguished PCOS patients from healthy controls relatively well, especially in those with more severe phenotypes. Further studies are needed to establish whether AMH measurements can distinguish PCOS patients with different metabolic risk factors.


Thermally driven interfacial dynamics of metal/oxide bilayer nanoribbons.
Solid-solid interfacial processes greatly affect the performance of electronic and composite materials, but probing the dynamics of buried interfaces is challenging and often involves lengthy or invasive sample preparation. We show that bilayer nanoribbons-made here of tin dioxide and copper-are convenient structures for observing as-made interfaces as they respond to changing temperature in a transmission electron microscope (TEM). At low temperatures (<200 degrees C), differential thermal expansion causes the bilayers to bend when heated or cooled, with the motion determined by the extent of Cu-SnO(2) epitaxy. At higher temperatures, we are able to watch-in real time and with nanometer resolution-a progression of grain growth, interdiffusion, island formation, solid-state chemical reactions, and melting. This novel TEM geometry is readily applicable to other nanoribbon/coating combinations and is well suited to observing interfacial phenomena driven thermally or by the application of mechanical, electrical, or magnetic forces.


Contextual Treatment of Dissociative Identity Disorder.
Evidence for the effectiveness of contextual therapy, a new approach for treating adult survivors of prolonged child abuse (PCA), is provided via case studies of three women with Dissociative Identity Disorder (DID). Contextual therapy is based on the premise that it is not only traumatic experiences that account for PCA survivors' psychological difficulties. Even more fundamentally, many survivors grow up in an interpersonal context in which adequate resources for secure attachment and acquisition of adaptive living skills are not available. As a result, they are left with lasting deficits that undermine not only their current functioning, but also their ability to cope with reliving their traumatic memories in therapy. The primary focus of this treatment approach, therefore, is on developing capacities for feeling and functioning better in the present, rather than on extensive exploration and processing of the client's trauma history or, in the case of DID, of identity fragments. Treatment of the three cases presented ranged from eight months to two and one-half years' duration, and culminated in very positive outcomes. The women's reports of achievements, such as obtaining and maintaining gainful employment, greater self-sufficiency, and the establishment of more intimate and gratifying relationships, indicated marked improvements in daily functioning. Objective test data obtained at admission and discharge, and in one case, at follow-up, documented substantial reductions in dissociative, posttraumatic stress, depressive, and other symptoms.


Reflectance confocal endomicroscope with optical axial scanning for in vivo imaging of the oral mucosa.
This paper presents the design and evaluation of a reflectance confocal laser endomicroscope using a miniature objective lens within a rigid probe in conjunction with an electrically tunable lens for axial scanning. The miniature lens was characterized alone as well as in the endoscope across a 200 µm axial scan range using the tunable lens. The ability of the confocal endoscope to probe the human oral cavity is demonstrated by imaging of the oral mucosa in vivo. The results indicate that reflectance confocal endomicroscopy has the potential to be used in a clinical setting and guide diagnostic evaluation of biological tissue.


Minimally invasive approach to Boerhaave's syndrome: a pilot study of three cases.
Boerhaave's syndrome requires urgent thoracotomy, laparotomy, or both for esophageal repair and pleuromediastinal debridement. Minimally invasive techniques may be suitable alternatives. Over a period of 12 months, three patients with spontaneous esophageal perforations after forceful vomiting were treated by a combination of minimally invasive techniques including laparoscopy, thoracoscopy, mediastinoscopy, and endoscopic stenting. Esophageal repair was performed transhiatally via laparoscopy using primary suture, primary suture reinforced by a fundic patch, and fundic patch alone in one patient each. One patient had a second perforation of the proximal esophagus, which was sutured through a cervical incision. This patient successfully underwent secondary endoscopic stenting for a persistent esophageal fistula. Mediastinal debridement was performed transhiatally and also by means of a mediastinoscope introduced via the cervical incision in one patient. One patient required secondary thoracoscopic debridement of a pleural empyema but died of sepsis after 1 month. The two other patients recovered and were discharged from the hospital after 2 and 8 weeks, respectively. Boerhaave's syndrome is amenable to minimally invasive techniques. Avoidance of a formal thoracotomy with its resulting morbidity could be of considerable benefit to these critically ill patients.


Primary appendiceal lymphoma presenting as suspected perforated acute appendicitis: clinical, sonography and CT findings with pathologic correlation.
The gastrointestinal tract is the most common site for extranodal involvement by non-Hodgkin's lymphoma. However, primary appendiceal lymphomas presenting as perforated acute appendicitis are very rare: they occur in only 0.015% of all gastrointestinal lymphoma cases. The management of this condition is still controversial, and a multimodality approach (e.g., surgery, radiation therapy, and chemotherapy) is the optimal treatment. In these cases, appendiceal non-Hodgkin's lymphomas typically manifest with acute symptoms in patients with no prior lymphoma history. Additionally, we treated our patient with a right hemicolectomy and postoperative multiagent chemotherapy.