Multi-Class UHPLC-MS/MS Method for Plant Toxins and Cyanotoxins in Food Supplements and Application for Belgian Market Samples.
The presence of plant toxins and/or cyanotoxins in food supplements implies consumer health risks. Therefore, a targeted ultra-high performance liquid chromatographic-tandem mass spectrometric method to detect/quantify 25 toxins simultaneously in food supplement formulations was developed and validated. Full validation for tablets/powders and secondary validation for a liquid and soft gel capsule indicated that most compounds were efficiently extracted (≥ 75%), while others were only partly extracted (18 - 61%). Trueness was fulfilled (70 - 120%), with some exceptions (mostly at the lowest validation level). Intralaboratory repeatability, intra- and interlaboratory reproducibility values of ≤ 20%, ≤ 25%, and ≤ 25% were obtained for most, respectively. Matrix effects were found to be significant for most compounds. Good sensitivity (µg/kg level) was observed for galegin(e), lycopsamine, lycorine, rubiadin, skimmiamine, and vascin(e), in contrast to helveticoside, lucidin, lucidin-3-primveroside, plumbagin(e), and thujone, which were detected at the mg/kg level. The other compounds were characterized by a sensitivity between 10 to 1000 µg/kg. The validated methodology was applied for 52 food supplements (tablets, capsules, liquids/syrup, etc.) purchased from the Belgian market. In more than 25% of the samples, one or more toxins were detected (concentrations determined using standard addition). Lycopsamine, microcystin LR, solamargine, thujone, and vasicin(e) were the most frequently detected toxins. A clear link between the toxins detected and the plant species on the food supplement ingredient list could not always be established. This generic "dilute-and-shoot" procedure can be used for further research on toxins in food supplements and by extension other plant/algae-based food/feed commodities (herbs, edible flowers, etc.).


MTP1-dependent Zn sequestration into shoot vacuoles suggests dual roles in Zn tolerance and accumulation in Zn-hyperaccumulating plants.
The integral membrane protein Thlaspi goesingense metal tolerance protein 1 (TgMTP1) has been suggested to play an important role in Zn hyperaccumulation in T. goesingense. Here, we show that the TgMTP1 protein is accumulated to high levels at the vacuolar membrane in shoot tissue of T. goesingense. TgMTP1 is likely to act in the transport of Zn into the vacuole, enhancing both Zn accumulation and tolerance. By specifically expressing TgMTP1 in Arabidopsis thaliana shoots, we show that TgMTP1, localized at the vacuolar membrane, can drive the enhanced shoot accumulation of Zn by initiating a systemic Zn deficiency response. The systematic response includes increased expression of Zn transporters (ZIP3, ZIP4, ZIP5 and ZIP9) in both shoot and root tissue. Furthermore, shoot-specific accumulation of TgMTP1 at the vacuolar membrane also leads to increased resistance to Zn in A. thaliana, probably through enhanced Zn compartmentalization in the vacuole. Such evidence leads to the conclusion that the high levels of TgMTP1 at the vacuolar membrane in shoot tissue of the Zn hyperaccumulator T. goesingense play a role in both Zn tolerance and enhanced Zn uptake and accumulation, via the activation of a systemic Zn deficiency response.


Phenotypic and genotypic detection of methicillin-resistant Staphylococcus aureus in hunting dogs in Maiduguri metropolitan, Borno State, Nigeria.
To determine the presence of MRSA in hunting dogs in Maiduguri metropolitan. Phenotypic methods used includes microscopic technique, colony morphology study, catalase-coagulase tests, and the use of mannitol salt agar test, oxacillin resistance screening agar base, and antibiotic susceptibility testing methods. Genotypic approach was used for deoxyribonucleic acid extraction, and the presence of nuc and mecA gene was detected using polymerase chain reaction (PCR) techniques. Examination of 416 swab samples from nasal and perineal region of dogs revealed a total of 79.5% of S. aureus, where 62.5% of the isolates were MRSA. Molecular analysis revealed that 7nuc genes specific for S. aureus from 20 presumptive MRSA assay were all mecA PCR negative. The isolates were sensitive to gentamicin and ciprofloxacin but proved resistant to cefoxitin and oxacillin. High isolation rate of MRSA was found in hunting dogs. Significant level (p<0.05) of MRSA was isolated in the nasal cavity of hunting dogs than its perineum. Only nuc genes were detected from the MRSA isolates.


Loperamide metabolite-induced cardiomyopathy and QTc prolongation.
Loperamide is an over-the-counter, peripherally acting, μ-opioid receptor agonist used for the treatment of diarrhea. In recent times users have found that at higher doses, loperamide crosses the blood-brain barrier and reaches central μ-receptors in the brain, leading to central opiate effects including euphoria and respiratory depression. We report a case of a 37-year-old female who attempted suicide with over 200 loperamide tablets. During her overdose, her QTc was significantly prolonged at >600 ms. Our case aims to add to the growing body of literature describing life-threatening ventricular arrhythmias associated with loperamide toxicity and further suggests that a metabolite of loperamide, desmethylloperamide, may play a role in the pathogenesis.


Caspase-1: A Promising Target for Preserving Blood-Brain Barrier Integrity in Acute Stroke.
The blood-brain barrier (BBB) acts as a physical and biochemical barrier that plays a fundamental role in regulating the blood-to-brain influx of endogenous and exogenous components and maintaining the homeostatic microenvironment of the central nervous system (CNS). Acute stroke leads to BBB disruption, blood substances extravasation into the brain parenchyma, and the consequence of brain edema formation with neurological impairment afterward. Caspase-1, one of the evolutionary conserved families of cysteine proteases, which is upregulated in acute stroke, mainly mediates pyroptosis and compromises BBB integrity via lytic cellular death and inflammatory cytokines release. Nowadays, targeting caspase-1 has been proven to be effective in decreasing the occurrence of hemorrhagic transformation (HT) and in attenuating brain edema and secondary damages during acute stroke. However, the underlying interactions among caspase-1, BBB, and stroke still remain ill-defined. Hence, in this review, we are concerned about the roles of caspase-1 activation and its associated mechanisms in stroke-induced BBB damage, aiming at providing insights into the significance of caspase-1 inhibition on stroke treatment in the near future.


Relationships between inhibitory activity against a cancer cell line panel, profiles of plants collected, and compound classes isolated in an anticancer drug discovery project.
In an attempt to determine the relationships between the plant profiles (country of collection, taxonomy, plant part) and the compound classes isolated with cytotoxic activity against a panel of human tumor cell lines, the data compiled from a 15-year anticancer drug-discovery project were subjected to an analysis of variance (ANOVA). The results indicate significant trends in cytotoxic activity relative to collection location, taxonomy, plant part, and compound classes isolated. Plant collections were made in tropical forests in six countries, with collections from Ecuador resulting in higher activity than those from Indonesia and Peru. Interestingly, collections from Florida were not statistically different than those from the countries with higher biodiversity. One hundred and forty-five families were represented in the collections, with the Clusiaceae, Elaeocarpaceae, Meliaceae, and Rubiaceae having low ED50 (half maximal effective dose) values. Especially active genera included Aglaia, Casearia, Exostema, Mallotus, and Trichosanthes. Roots and below-ground plant materials were significantly more active than above-ground materials. Cucurbitacins, flavaglines, anthraquinones, fatty acids, tropane alkaloids, lignans, and sesquiterpenoids were significantly more active than xanthones and oligorhamnosides. The results from this study should serve as a guide for future plant collection endeavors for anticancer drug discovery.


[Evaluation of the quality of life of chronic psychotic patients living in supportive housing].
This study concerns 46 chronically mentally ill patients living in community support systems. Their quality of life was measured with a validated questionnaire: the "Subjective Quality of Life Questionnaire" ("SQLP"). Both patients and their care givers separately completed the same version of the questionnaire. This study first shows the feasibility of such inquiries with chronically mentally ill patients. It gives a description of the patient's feeling which is different from the usual medical point of view. The life domains the patient is very satisfied with are mostly restricted to food, material conditions, and relationship with the care-givers, but exclude the other relationships. Our data also allow to estimate the degree of agreement and disagreement between the care-givers and their patients.


Rotational constants and structure of para-difluorobenzene determined by femtosecond Raman coherence spectroscopy: A new transient type.
Femtosecond Raman rotational coherence spectroscopy (RCS) detected by degenerate four-wave mixing is a background-free method that allows to determine accurate gas-phase rotational constants of non-polar molecules. Raman RCS has so far mostly been applied to the regular coherence patterns of symmetric-top molecules, while its application to nonpolar asymmetric tops has been hampered by the large number of RCS transient types, the resulting variability of the RCS patterns, and the 10(3)-10(4) times larger computational effort to simulate and fit rotational Raman RCS transients. We present the rotational Raman RCS spectra of the nonpolar asymmetric top 1,4-difluorobenzene (para-difluorobenzene, p-DFB) measured in a pulsed Ar supersonic jet and in a gas cell over delay times up to ∼2.5 ns. p-DFB exhibits rotational Raman transitions with ΔJ = 0, 1, 2 and ΔK = 0, 2, leading to the observation of J -, K -, A -, and C-type transients, as well as a novel transient (S-type) that has not been characterized so far. The jet and gas cell RCS measurements were fully analyzed and yield the ground-state (v = 0) rotational constants A0 = 5637.68(20) MHz, B0 = 1428.23(37) MHz, and C0 = 1138.90(48) MHz (1σ uncertainties). Combining the A0, B0, and C0 constants with coupled-cluster with single-, double- and perturbatively corrected triple-excitation calculations using large basis sets allows to determine the semi-experimental equilibrium bond lengths re(C1-C2) = 1.3849(4) Å, re(C2-C3) = 1.3917(4) Å, re(C-F) = 1.3422(3) Å, and re(C2-H2) = 1.0791(5) Å.


Ground and lowest-lying electronic states of CoN. A multiconfigurational study.
The lowest-lying X1Sigma+, a3Phi, b3II, c5Delta, A1Phi, and B1II electronic states of CoN have been investigated at the ab initio MRCI and MS-CASPT2 levels, with extended atomic basis sets and inclusion of scalar relativistic effects. Among the singlet states, the A1Phi and B1II states have been described for the first time. Potential energy curves, excitation energies, spectroscopic constants, and bonding character for all states are reported. Comparison with other early transition-metal nitrides (ScN, TiN, VN, and CrN), isoelectronic (NiC) and isovalent (RhN and IrN) species has been made, besides analyzing the B1II <=> X1+ electronic transition in terms of Franck-Condon factors, Einstein coefficients, and radiative lifetimes. At both levels of theory, the following energetic order has been obtained: X1Sigma+, a3Phi, b3II, c5Delta, A1Phi, and B1II, with good agreement with experimental results. In contrast, previous DFT and MRCI calculations predicted the ground state to be the 5Delta state.


Virus-Specific Antibody, Viral Load, and Disease Severity in Respiratory Syncytial Virus Infection.
Maternally derived serum antibody and viral load are thought to influence disease severity in primary respiratory syncytial virus (RSV) infection. As part of the AsPIRES study of RSV pathogenesis, we correlated various serum antibody concentrations and viral load with disease severity. Serum neutralizing antibody titers and levels of immunoglobulin G (IgG) to RSV fusion protein (F), attachment proteins of RSV group A and B, the CX3C region of G, and nasal viral load were measured in 139 full-term previously healthy infants with primary RSV infection and correlated with illness severity. Univariate analysis showed no relationship between measures of serum antibody and severity. However, a multivariate model adjusting for age at the time of infection found a significant 0.56 decrease in severity score for each 2-fold increase in antibody concentration to RSV F. The benefit of antibody was greatest in infants ≤ 2 months of age. Additionally, estimated antibody titer at birth was correlated with age at infection, suggesting that higher antibody titers delay infection. Viral load did not differ by illness severity. Our data support the concept of maternal immunization with an RSV vaccine during pregnancy as a strategy for reducing the burden of RSV infection in full-term healthy infants exposed to RSV during their first winter.


Health-risk appraisal applied to ordinary AMHTS.
The main purpose of an automatic health testing system (AMHTS) has changed from early detection to primary prevention. Health-risk appraisal is now widely available as a tool of health education aiming at the modification of unhealthy lifestyles. However, the opportunity to offer appropriate health education was less frequent for those who had no particular findings during AMHTS. The results of an AMHTS should be evaluated from the viewpoint of health-risk appraisal, because the system is expected to supply useful information regarding one's lifestyle. Our system consists of two health-risk appraisal subsystems. One subsystem estimates the degree of improvement in medical indicators after a patient's lifestyle has been modified. The other subsystem predicts the occurrence of abnormal findings in medical indicators. These health-risk appraisal subsystems provide patients with information about their health-risks, based on their AMHTS results. Our health-risk appraisal subsystems should play an important role in future health education through the application of ordinary AMHTS.


Narrowing of the Diagnostic Gap of Acute Gastroenteritis in Children 0-6 Years of Age Using a Combination of Classical and Molecular Techniques, Delivers Challenges in Syndromic Approach Diagnostics.
Twenty-five percent to 50% of acute gastroenteritis (AGE) cases remain etiologically undiagnosed. Our main aim was to determine the most appropriate list of enteric pathogens to be included in the daily diagnostics scheme of AGE, ensuring the lowest possible diagnostic gap. Two hundred ninety seven children ≤6 years of age, admitted to hospital in Slovenia, October 2011 to October 2012, with AGE, and 88 ≤6 years old healthy children were included in the study. A broad spectrum of enteric pathogens was targeted with molecular methods, including 8 viruses, 6 bacteria and 2 parasites. At least one enteric pathogen was detected in 91.2% of cases with AGE and 27.3% of controls. Viruses were the most prevalent (82.5% and 15.9%), followed by bacteria (27.3% and 10.2%) and parasites (3.0% and 1.1%) in cases and controls, respectively. A high proportion (41.8%) of mixed infections was observed in the cases. For cases with undetermined etiology (8.8%), stool samples were analyzed with next generation sequencing, and a potential viral pathogen was detected in 17 additional samples (5.8%). Our study suggests that tests for rotaviruses, noroviruses genogroup II, adenoviruses 40/41, astroviruses, Campylobacter spp. and Salmonella sp. should be included in the initial diagnostic algorithm, which revealed the etiology in 83.5% of children tested. The use of molecular methods in diagnostics of gastroenteritis is preferable because of their high sensitivity, specificity, fast performance and the possibility of establishing the concentration of the target. The latter may be valuable for assessing the clinical significance of the detected enteric, particularly viral pathogens.


Opioid use disorder treatment in rural settings: The primary care perspective.
Despite the efficacy of medications for treating opioid use disorder (OUD), they are underutilized, especially in rural areas. Our objectives were to determine the association between primary care practitioners (PCPs) rurality and concerns for patient substance use, and to identify factors associated with PCP comfort treating OUD, focusing on barriers to treatment. We developed a web-based survey completed by 116 adult-serving PCPs located in Vermont's rural and non-rural counties between April-August 2020. The instrument included PCP-identified concerns for substance use among patients, barriers to treating patients with OUD, and current level of comfort treating patients with OUD. On a scale from 0 to 10, rural PCPs reported higher concern for heroin (mean difference; Mdiff = 1.38, 95% CI: 0.13 to 2.63), fentanyl (Mdiff = 1.52, 95% CI: 0.29 to 2.74), and methamphetamine (Mdiff = 1.61, 95% CI: 0.33 to 2.90) use among patients compared to non-rural PCPs, and practitioners in both settings expressed high concern regarding their patients' use of tobacco (7.6 out of 10) and alcohol (7.0 out of 10). There was no difference in reported comfort in treating patients with OUD among rural vs. non-rural PCPs (Mdiff = 0.65, 95%CI: 0.17 to 1.46; P = 0.119), controlling for higher comfort among male PCPs and those waivered to prescribe buprenorphine (Ps < 0.05). Lack of training/experience and medication diversion were PCP-identified barriers associated with less comfort treating OUD patients, while time constraints was associated with more comfort (Ps < 0.05). Taken together, these data highlight important areas for dissemination of evidence-based training, support, and resources to expand OUD treatment capacity in rural communities.


Identification of Younger Dryas outburst flood path from Lake Agassiz to the Arctic Ocean.
The melting Laurentide Ice Sheet discharged thousands of cubic kilometres of fresh water each year into surrounding oceans, at times suppressing the Atlantic meridional overturning circulation and triggering abrupt climate change. Understanding the physical mechanisms leading to events such as the Younger Dryas cold interval requires identification of the paths and timing of the freshwater discharges. Although Broecker et al. hypothesized in 1989 that an outburst from glacial Lake Agassiz triggered the Younger Dryas, specific evidence has so far proved elusive, leading Broecker to conclude in 2006 that "our inability to identify the path taken by the flood is disconcerting". Here we identify the missing flood path-evident from gravels and a regional erosion surface-running through the Mackenzie River system in the Canadian Arctic Coastal Plain. Our modelling of the isostatically adjusted surface in the upstream Fort McMurray region, and a slight revision of the ice margin at this time, allows Lake Agassiz to spill into the Mackenzie drainage basin. From optically stimulated luminescence dating we have determined the approximate age of this Mackenzie River flood into the Arctic Ocean to be shortly after 13,000 years ago, near the start of the Younger Dryas. We attribute to this flood a boulder terrace near Fort McMurray with calibrated radiocarbon dates of over 11,500 years ago. A large flood into the Arctic Ocean at the start of the Younger Dryas leads us to reject the widespread view that Agassiz overflow at this time was solely eastward into the North Atlantic Ocean.


Uterine disorders in 50 pet rabbits.
Although the incidence of uterine disorders in pet rabbits is high there are only a few retrospective studies and case reports on genital tract disease in female rabbits. Uterine disorders were assessed in 50 pet rabbits. In 31 pet rabbits with suspected clinical uterine disease, medical records were further reviewed regarding clinical signs, diagnostic workup, treatment as well as the outcome itself. Uterine adenocarcinoma (54%) was most frequently diagnosed, followed by endometrial hyperplasia (26%). Serosanguineous vaginal discharge was the predominant clinical sign observed by the rabbit owners. In approximately 50% of the rabbits with suspected uterine disorders, abdominal palpation revealed enlarged and/or irregular masses in the caudoventral abdomen indicating uterine lesions. Out of 23 rabbits undergoing ovariohysterectomy, four were either euthanized or died shortly after surgery because they were clinically unstable. Overall, 80% of the ovariohysterectomized animals were still alive 6 mo after surgery. In female pet rabbits that are not breeding, either ovariohysterectomy should be performed at an early age or routine checks including ultrasonography of the abdomen are recommended on a regular basis.


Comparative in situ analysis of ipdC-gfpmut3 promoter fusions of Azospirillum brasilense strains Sp7 and Sp245.
Inoculation of wheat roots with Azospirillum brasilense results in an increase of plant growth and yield, which is proposed to be mainly due to the bacterial production of indole-3-acetic acid in the rhizosphere. Field inoculation experiments had revealed more consistent plant growth stimulation using A. brasilense strain Sp245 as compared with the strain Sp7. Therefore, the in situ expression of the key gene ipdC (indole-3-pyruvate decarboxylase) was examined in these two strains. Within the ipdC promoter of strain Sp245 a region of 150 bases was identified, which was missing in strain Sp7. Thus, three different translational ipdC promoter fusions with gfpmut3 were constructed on plasmid level: the first contained the part of the Sp245 promoter region homologous to strain Sp7, the second was bearing the complete promoter region of Sp245 including the specific insertion and the third comprised the Sp7 promoter region. By comparing the fluorescence levels of these constructs after growth on mineral medium with and without inducing amino acids, it could be demonstrated that ipdC expression in A. brasilense Sp245 was subject to a stricter control compared with strain Sp7. Microscopic detection of these reporter strains colonizing the rhizoplane documented for the first time an in situ expression of ipdC.


Mobile surgery: a new frontier.
At the end of the 20th Century, the world lives in the midst of a tremendous contradiction. On one side we have great scientific and technological progress, designed for the well-being of mankind, and on the other, the everyday widening gap between a few who have more than what they need and the vast majority of people who do not have enough.


Natural product for the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is related to increasing age. It is mainly characterized by progressive neurodegenerative disease, which damages memory and cognitive function. Natural products offer many options to reduce the progress and symptoms of many kinds of diseases, including AD. Meanwhile, natural compound structures, including lignans, flavonoids, tannins, polyphenols, triterpenes, sterols, and alkaloids, have anti-inflammatory, antioxidant, anti-amyloidogenic, and anticholinesterase activities. In this review, we summarize the pathogenesis and targets for treatment of AD. We also present several medicinal plants and isolated compounds that are used for preventing and reducing symptoms of AD.


The background of beta-oxidation disorders in humans. II. Laboratoy studies and clinical data.
Laboratory method for studies of clinical disorders of beta-oxidation is described. The effects of other diet components such as microelements (Cr3+ ions) and non-digestible oligofructans (inulin and oligofructose) as stimulatory factors on the activity of beta-oxidation and cholesterol and triacylglyceroles levels lowering are reported.


Challenges in HbA1c Analysis and Reporting in Patients with Variant Hemoglobins.
Hemoglobin A1c (HbA(1)c) is a well-established indicator of mean glycemia. The presence of genetic variants of hemoglobin can profoundly affect the accuracy of HbA(1)c measurements. Variants of hemoglobin especially Hemoglobin E (HbE) is prevalent in South East Asia including Bangladesh. The objective of our study is to compare the HbA(1)c values measured on high performance liquid chromatography (HPLC) and Turbidimetric Inhibition Immunoassay (TINIA) in diabetic patients with variant hemoglobins including HbE. A total of 7595 diabetic patients receiving treatment at BIRDEM General Hospital were analyzed for HbA(1)c results within a period of two months from December 2013 to January 2014. Seventy two cases out of 7595 (0.95%) had either undetectable or below normal HbA(1)c levels (males-33 and females-39; ratio = 0.82:1) by HPLC method. In 34(0.45%) cases, HbA(1)c value was undetectable by HPLC method but was in the reportable range by TINIA method. In the other 38 (0.55%) cases, HbA(1)c levels were below the reportable range (<4%) by HPLC method but were in the normal or higher range by TINIA method. TINIA method did not agree with HPLC method on Bland Altman plot in the 38 cases with below normal HbA(1)c levels, [Mean bias -5.2(-9.3 to 1.0), 95% CI] but agreed very well [mean bias -0.21 (-0.84 to 0.42), y=1.1037+0.776X; r(2)=0.30, p<0.01] in controls. In control group mean MCV was 83.80±7.48 and in study group was 73.65±10.44. Alkaline electrophoresis confirmed the variant hemoglobin to be HbE. The fasting blood sugar levels of all the 72 cases correlated strongly with TINIA method (r(2) =0.75, p<0.0001) but not with HPLC (r = 0.24, p=0.13). In our regions where populations have a high prevalence of Hb variant, proper knowledge of hemoglobin variants which affect the measurements HbA(1)c level is essential. MCV of 80fl or below may serve as a rough guide to select samples that require analysis by TINIA method. Moreover, HPLC may be a convenient and inexpensive tool for screening of hemoglobinopathies especially among diabetic population in Bangladesh. It may therefore be helpful in improving management of complications related to both anaemia and iron overload.


What Does DALL-E 2 Know About Radiology?
Generative models, such as DALL-E 2 (OpenAI), could represent promising future tools for image generation, augmentation, and manipulation for artificial intelligence research in radiology, provided that these models have sufficient medical domain knowledge. Herein, we show that DALL-E 2 has learned relevant representations of x-ray images, with promising capabilities in terms of zero-shot text-to-image generation of new images, the continuation of an image beyond its original boundaries, and the removal of elements; however, its capabilities for the generation of images with pathological abnormalities (eg, tumors, fractures, and inflammation) or computed tomography, magnetic resonance imaging, or ultrasound images are still limited. The use of generative models for augmenting and generating radiological data thus seems feasible, even if the further fine-tuning and adaptation of these models to their respective domains are required first.


Additive Antiproliferative and Antiangiogenic Effects of Metformin and Pemetrexed in a Non-Small-Cell Lung Cancer Xenograft Model.
Lung cancer is heterogeneous and challenging to cope with once it has progressed. Chemotherapy is the first step once no active driver mutation has been discovered. Non-antitumor drugs have been found to be beneficial when used as adjuvants to chemotherapy. In this study, the additive effect and mechanism of metformin combined with pemetrexed in non-small-cell lung cancer (NSCLC) cells were elucidated. Three NSCLC cell lines, A549, H1975, and HCC827, were used to analyze tumor cell proliferation, colony formation and the cell cycle in vitro when exposed to metformin alone, pemetrexed alone or their combination. We found that combination treatment in three cell lines exerted antiproliferative effects through cell cycle arrest in the S phase. An ex vivo chicken chorioallantoic membrane (CAM) assay was used to examine the antiangiogenic effect of metformin combined with pemetrexed on vascular structure formation. We further created an A549 orthotopic xenograft model with an in vivo imaging system (IVIS) and explored the associated indicators involved in the tumorigenic process. The in vitro results showed that the combination of metformin and pemetrexed exhibited an antiproliferative effect in reducing cell viability and colony formation, the downregulation of cyclin D1 and A2 and the upregulation of CDKN1B, which are involved in the G1/S phase. For antiangiogenic effects, the combination therapy inhibited the vascular structure, as proven by the CAM assay. We elucidated that combination therapy could target VEGFA and Endoglin by RT-qPCR, ELISA and histopathological findings in an A549 orthotopic NSCLC xenograft model. Our research demonstrated the additive antiproliferative and antiangiogenic effects of the combination of metformin with pemetrexed in NSCLC and could be applied to clinical lung cancer therapy.


Surgical clinical trials.
Surveys of surgical practice in the United States during the last 2 decades have documented a gradual retreat from the standard radical mastectomy for treatment of early breast cancer. During this time, clinical trials have tested traditional principles of cancer surgery, and permitted conclusions to be made regarding treatment alternatives. Modified mastectomy (total mastectomy plus axillary dissection) has proved equal to radical mastectomy in terms of survival, disease-free survival, and local tumor control in a randomized trial confined to TNM clinical Stage I and II cases. This study showed that routine removal of grossly uninvolved pectoral muscles (and apical axillary nodes) is not necessary in early cases, a result which failed to support the principle of en bloc dissection. Trials addressed to the practice of prophylactic regional node dissections have indicated that node dissections are useful for reducing regional tumor recurrence, for providing prognostic information, and for establishing the need for adjuvant treatment, but they do not improve overall survival. Metastases in lymph nodes appear to be a sign, rather than a source, of tumor dissemination. Furthermore, a recent trial indicates that routine removal of the breast may not be necessary in early cases. High-dose irradiation of the breast (after wide excision of the primary and axillary dissection) in TNM clinical Stage I cases provided local tumor control and survival comparable to that of radical mastectomy. Trials of breast preservation not yet complete address more advanced stages (TNM I and II), and the question of whether irradiation is necessary in all cases. On the basis of completed studies, it appears that TNM clinical State I and II cancers can be appropriately treated with modified mastectomy; Stage I cancers can be treated equally well with irradiation of the breast after quadrantectomy and removal of axillary lymph nodes.


Comparative accuracy of fitness tracking modalities in quantifying energy expenditure.
The purpose of this study is to compare the accuracy of wrist-worn, consumer-grade pedometers and earbud sensor technology in quantifying energy expenditure. Nineteen participants (24.6 ± 3.1 years) performed 5 min exercise stages on a treadmill (80.5 m/min, 107.3 m/min, 134.1 m/min and 160.9 m/min) while measuring energy expenditure via the Fitbit Charge pedometer and Jabra Sport Pulse Wireless Earbuds, comparing with indirect calorimetry. Paired samples t-tests were used to calculate differences and Pearson correlations to examine associations between kcals measured from the Fitbit and Jabra earbuds from indirect calorimetry. Results indicate significant underestimations of kcals for both devices at all speeds except one (Jabra earbuds at 107.3 m/min). Moderate correlations were observed for the Fitbit at 107.3 m/min and 107.3 m/min, and 134.1 m/min for the Jabra earbuds. Both devices considerably underestimated kcals, suggesting that caution be used when incorporating such data into fitness/health goals.


Hemodynamic benefits of right ventricular outflow tract pacing: comparison with right ventricular apex pacing.
To assess optimal hemodynamics in relation to stimulation site during right ventricular pacing, 17 consecutive patients who underwent cardiac catheterization were studied. In all patients, right ventricular apex and right ventricular outflow tract stimulation was performed at 85, 100, and 120 beats/min. Cardiac index at both pacing sites was compared using the left ventricular outflow tract continuous wave Doppler technique. Comparison of the two stimulation sites demonstrated that right ventricular outflow tract pacing resulted in a higher cardiac index at 85 beats/min (2.42 +/- 1.2 vs 2.04 +/- 1.0 L/min per m2, P < 0.002) at 100 beats/min (2.78 +/- 1.4 vs 2.35 +/- 1.1 L/min per m2, P < 0.001) and 120 beats/min (3.00 +/- 1.5 vs 2.61 +/- 0.9 L/min per m2, P < 0.001). From a total of 51 paired observations, 45 showed an increase in cardiac index during outflow tract pacing as compared to apex pacing. Right ventricular outflow tract pacing at 120 beats/min resulted in a lower cardiac index than right ventricular apex pacing in patients with significant coronary artery disease and/or impaired left ventricular function (ejection fraction < or = 50%), whereas right ventricular outflow tract pacing produced higher cardiac indices in the absence of these abnormalities. Right ventricular outflow tract pacing resulted in higher cardiac indices as compared to apex pacing in all other subgroups at all other pacing sites tested. It is concluded that stimulation of the right ventricular outflow tract offers a significant hemodynamic benefit during single chamber pacing as compared to conventional apex pacing, particularly in the absence of significant coronary artery disease and/or left ventricular dysfunction.


Effect of sesamin against cytokine production from influenza type A H1N1-induced peripheral blood mononuclear cells: computational and experimental studies.
In 2009, swine flu (H1N1) had spread significantly to levels that threatened pandemic influenza. There have been many treatments that have arisen for patients since the WHO first reported the disease. Although some progress in controlling influenza has taken place during the last few years, the disease is not yet under control. The development of new and less expensive anti-influenza drugs is still needed. Here, we show that sesamin from the seeds of the Thai medicinal plant Sesamum indicum has anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs) induced by 2009 influenza virus type A H1N1. In this study, the combinatorial screening method combined with the computational approach was applied to investigate the new molecular binding structures of sesamin against the 2009 influenza virus type A H1N1 (p09N1) crystallized structure. Experimental methods were applied to propose the mechanisms of sesamin against cytokine production from H1N1-induced human PBMC model. The molecular dynamics simulation of sesamin binding with the p09N1 crystallized structure showed new molecular binding structures at ARG118, ILE222, ARG224, and TYR406, and it has been proposed that sesamin could potentially be used to produce anti-H1N1 compounds. Furthermore, the mechanisms of sesamin against cytokine production from influenza type A H1N1-induced PBMCs by ELISA and signaling transduction showed that sesamin exhibits the ability to inhibit proinflammatory cytokines, IL-1β and TNF-α, and to enhance the activity of the immune cell cytokine IL-2 via downregulating the phosphorylated JNK, p38, and ERK1/2 MAPK signaling pathways. This information might very well be useful in the prevention and treatment of immune-induced inflammatory disorders.


The Trithorax-like gene encodes the Drosophila GAGA factor.
Little is known about the way higher-order chromatin structure influences gene expression and chromosome topology in general. Genetic analysis in Drosophila has led to the discovery of two classes of genes, the regulators of homeotic genes and the modifiers of position-effect variegation, which seem to be good candidates for encoding some of the factors regulating chromatin functions. The Trithorax-like gene we described here is required for the normal expression of the homeotic genes and is a modifier of position-effect variegation. We found that Trithorax-like encodes the GAGA factor which is involved in the formation of an accessible chromatin structure at promoter sequences. Our genetic analysis suggests that the chromatin modelling function of the GAGA factor is not restricted to promoter regions.


Large-scale Reconstructions and Independent, Unbiased Clustering Based on Morphological Metrics to Classify Neurons in Selective Populations.
This protocol outlines large-scale reconstructions of neurons combined with the use of independent and unbiased clustering analyses to create a comprehensive survey of the morphological characteristics observed among a selective neuronal population. Combination of these techniques constitutes a novel approach for the collection and analysis of neuroanatomical data. Together, these techniques enable large-scale, and therefore more comprehensive, sampling of selective neuronal populations and establish unbiased quantitative methods for describing morphologically unique neuronal classes within a population. The protocol outlines the use of modified rabies virus to selectively label neurons. G-deleted rabies virus acts like a retrograde tracer following stereotaxic injection into a target brain structure of interest and serves as a vehicle for the delivery and expression of EGFP in neurons. Large numbers of neurons are infected using this technique and express GFP throughout their dendrites, producing "Golgi-like" complete fills of individual neurons. Accordingly, the virus-mediated retrograde tracing method improves upon traditional dye-based retrograde tracing techniques by producing complete intracellular fills. Individual well-isolated neurons spanning all regions of the brain area under study are selected for reconstruction in order to obtain a representative sample of neurons. The protocol outlines procedures to reconstruct cell bodies and complete dendritic arborization patterns of labeled neurons spanning multiple tissue sections. Morphological data, including positions of each neuron within the brain structure, are extracted for further analysis. Standard programming functions were utilized to perform independent cluster analyses and cluster evaluations based on morphological metrics. To verify the utility of these analyses, statistical evaluation of a cluster analysis performed on 160 neurons reconstructed in the thalamic reticular nucleus of the thalamus (TRN) of the macaque monkey was made. Both the original cluster analysis and the statistical evaluations performed here indicate that TRN neurons are separated into three subpopulations, each with unique morphological characteristics.


Erythema multiforme following polymorphic light eruption: a report of two cases.
We report two patients in whom episodes of polymorphic light eruption were followed by recurrent erythema multiforme on exposed and nonexposed sites. Treating the polymorphic light eruption with prophylactic PUVA and/or oral prednisolone or cyclosporin prevented the development of erythema multiforme, suggesting that the two events are related. It is possible that erythema multiforme develops as a response to the same causative antigen as polymorphic light eruption.


Yeast partial dominance: effect of environment and background genotype.
Growth-rate mutations that were newly induced in haploid yeast by nitrosoguanidine were partially expressed in diploids heterozygous for these mutations only when the diploids were heterozygous elsewhere in the genome, and when both haploids and diploids were grown in a stress environment.


Strength of the Zn-N coordination bond in zinc porphyrins on the basis of experimental thermochemistry.
The compound, 5,10,15,20-tetrakis(4-methoxyphenyl)porphine zinc(II) (ZnTMPP), was prepared, and its thermochemical properties were experimentally established. The standard molar energy of combustion (Delta(c)U degrees m) was determined from oxygen rotating-bomb combustion calorimetry experiments. The standard molar enthalpies of combustion (Delta(c)H degrees m) and formation (Delta(f)H degrees m) were derived. The enthalpy of sublimation (Delta(cr)(g)H degrees m) was determined by Knudsen effusion at high temperatures. With these results, the standard molar enthalpies of formation and atomization (Delta(at)H degrees m) in the gas state were calculated. A summary of the results at T = 298.15 K (p degrees = 0.1 MPa) is shown in Table 1. Using these results and those previously obtained for the free ligand, 5,10,15,20-tetrakis(4-methoxyphenyl)porphine, the mean dissociation enthalpy for the Zn-N coordination bond is obtained as D(Zn-N) = (160 +/- 9) kJ.mol-1. This value is consistent with the results obtained using the same experimental approach in a similar system (5,10,15,20-tetraphenylporphine, TPP/ZnTPP) reported elsewhere. A discussion of the strength for the Zn-N coordination bond is made in terms of the structural and electronic features of the molecules involved.


Alpha7 nicotinic acetylcholine receptor mRNA expression and binding in postmortem human brain are associated with genetic variation in neuregulin 1.
Studies in cell culture and in animals suggest that neuregulin 1 (NRG1), a probable schizophrenia susceptibility gene, regulates the expression of the alpha7 nicotinic acetylcholine receptors (nAChRs). We hypothesized that schizophrenia-associated allelic variations within the NRG1 gene, via their effects on NRG1 isoform expression, would be associated with alterations in nAChR alpha7 receptor levels. We examined the effects of four disease-associated single-nucleotide polymorphisms (SNPs) in the 5' region of the NRG1 gene on nAChR alpha7 mRNA transcript expression in both the dorsolateral prefrontal cortex (DLPFC) and hippocampus of normal controls and patients with schizophrenia using quantitative real-time PCR. NRG1 risk alleles at SNPs SNP8NRG221132 and rs6994992 predicted significantly lower nAChR alpha7 mRNA expression in the DLPFC. Haplotypes containing the risk alleles at the above SNPs were also associated with lower expression of nAChR alpha7 in the DLPFC. The genotype effect for rs6994992 and the haplotype effect were more pronounced within the schizophrenic patient group. To determine whether receptor levels follow that of mRNA expression, we performed receptor binding and autoradiography using [(125)I] alpha-bungarotoxin in the DLPFC. Consistent with the mRNA findings, we found a decrease in binding in risk allele carriers of SNP8NRG221132 as compared with heterozygous individuals. Together, these results suggest that the molecular mechanism of the association between NRG1 risk alleles and schizophrenia may include down-regulation of nAChR alpha7 expression.


[New developments in hormone replacement therapy].
Hormone replacement therapy with estrogen and progesterone does not appear to protect against Alzheimer's disease and does not improve cognitive functioning. Long-term administration of estrogen as monotherapy may be associated with an increased risk of ovarian cancer.


Growth and development in the haemopoietic system: the role of lymphokines and their possible therapeutic potential in disease and malignancy.
Some cells can produce soluble factors which modify the behaviour and/or growth pattern of other cells. These 'factors' are broadly referred to as cytokines and may be further classified on the basis of the cells which were first characterized as the producer cells. For example, lymphokines are the soluble products of lymphocytes and monokines are the soluble factors released by mononuclear phagocytes. Although useful, this nomenclature is in many respects misleading since protein sequence and gene structure analysis has shown that 'lymphokines' may not only be produced by lymphocytes, but by various other types of cells as well. Fortunately, with the advent of molecular techniques, the number of cytokines has decreased drastically and what was once an increasingly large number of factors is now becoming restricted to a manageable few. What remain, however, still pose conceptual and mechanistic problems. These have mainly arisen as a result of the assay systems used to detect and define the lymphokines and the problems in extending the findings to normal physiology. Almost exclusively, lymphocytes have been stimulated to produce and export their soluble factors in response to nonphysiologic stimuli, such as lectins, and the various lymphokines have been characterized on the basis of in vitro test systems. Therefore, for reasons which will become obvious later, many of the in vitro findings have been difficult to corroborate in in vivo situations. Nonetheless, the results obtained with these factors are sufficiently intriguing to warrant serious consideration regarding their relevance in normal haemopoiesis, their possible therapeutic potential and their involvement in disease.


Enolase isoenzymes as tumour markers.
alpha- and gamma-enolase isoenzyme substance concentrations were measured in serum and plasma from healthy subjects and from 174 patients with different solid tumours. While alpha-enolase was found to be increased in the plasma of patients with tumours of quite different origin, gamma-enolase apparently reflected malignancies of the neuroendocrine system. Before the beginning of the cytotoxic therapy gamma-enolase was increased above the upper limit of the reference range (10 micrograms/l) in 27/27 patients (100%) suffering from small cell lung cancer. Most patients with squamous cell carcinoma of the lung or with prostatic cancer exhibited normal gamma-enolase, while both tumour types produced high plasma substance concentrations of the alpha-isoenzymes of enolase.


Knowledge, Beliefs, and Practices on Epilepsy among High School Students of Central Nepal.
Introduction. Epilepsy continues to increase worldwide but, unfortunately, many high school students have inadequate knowledge of and negative beliefs towards the disease. We aimed to assess the knowledge, beliefs, and practices of epilepsy among high school students of Central Nepal. Materials and Methods. A cross-sectional study was performed involving 1360 high school students from 33 private schools across Bharatpur, from June 2013 to July 2013, to assess their knowledge, beliefs, and practices (KBP) on epilepsy using a standardized questionnaire. The differences in mean KBP scores between different sexes, religions, and those personally knowing versus not knowing someone with epilepsy were assessed using independent t-tests; a Pearson correlation was calculated to assess the relationship between KBP scores and age. Results. Of 1360 participants, 79 (5.8%) students had never heard or read about epilepsy and were consequently excluded from statistical analysis. Only 261 out of 1360 (19.2%) had personally known someone with epilepsy. The mean KBP scores were 5.0/8, 7.4/12, and 1.7/3, respectively. Statistically significant differences were only observed in the knowledge component of the KBP score; female scored higher than males (p < 0.001) and, interestingly, students who had personally known a person with epilepsy actually knew less than those who had not known one (p = 0.018). We also found a significant negative correlation between knowledge and age (p = 0.003). Conclusions. The overall knowledge, beliefs, and practices appear to be inadequate, emphasizing the need for further educational intervention.


Prevalence of female pattern hair loss in postmenopausal women: a cross-sectional study.
To identify the prevalence of female pattern hair loss (FPHL), hair characteristics, and associated factors in healthy postmenopausal women. Two hundred postmenopausal women aged 50 to 65 years were recruited. Each participant was evaluated for FPHL according to Ludwig's classification using standardized global photography in all six views and trichoscopy for hair density and diameter. Three dermatologists re-evaluated all pictures for confirmation of FPHL. The time since menopause, levels of scalp sebum, serum testosterone, estradiol, thyroid stimulating hormone, and hemoglobin; family history of hair loss, as well as an evaluation of low self-esteem were evaluated. Women who underwent recent hair loss treatments were excluded. We used simple and multivariable logistic regression analysis to identify the factors affecting FPHL. In total, 178 postmenopausal women were evaluated for hair-loss patterns. The average age and time since menopause were 58.8±4.1 and 9.2 ± 5.6 years, respectively. The prevalence of FPHL was 52.2% (95% CI, 44.6-59.8). Severity of FPHL by Ludwig grades I, II, and III was 73.2% (95% CI, 62.9-81.8), 22.6% (95% CI, 14.6-32.4), and 4.3% (95% CI, 1.2-10.7), respectively. Logistic regression analysis revealed that age, time since menopause, and body mass index were all significantly associated with FPHL. After adjusting for age and family history of FPHL, only body mass index ≥25 kg/m2 was significantly associated with FPHL (adjusted OR = 2.65, 95% CI, 1.23-5.70). Conclusion: The prevalence of FPHL was high in postmenopausal women, raising the need for hair loss awareness in menopause clinics. Early detection and proper treatment of FPHL may increase the quality of life in postmenopausal women.


Comprehensive Analysis of Prognostic Value and Immune Infiltration of TFAP2 Family Members in Bladder Cancer from Database and FFPE Sample.
Background: Bladder cancer (BLCA) is one of the common malignant tumors worldwide. Recent studies have shown that Transcription factor activating protein-2(TFAP2) family proteins plays a bidirectional regulatory role in the process of tumorigenesis versus evolution by regulating the expression of tumor associated genes. However, little is known about the function of distinct TFAP2s proteins in patient with BLCA. Methods: Formalin-fixed paraffin-embedded (FFPE) sample tissues and clinical data of 240 patients with bladder cancer were collected for immunohistochemical analysis. The Human Protein Atlas, Gene Expression Profiling Interactive Analysis (GEPIA), Shiny Methylation Analysis Resource Tool (SMART), Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, TIMER and CIBERSORT were utilized to analyze differential expression, prognostic value, genetic alteration and immune cell infiltration of TFAP2 family in patients with BLCA. Results: Our study found that TFAP2 family proteins are generally expressed higher in BLCA tissues than in normal tissues. However, they show different trends in the growth, metastasis and survival prognosis of BLCA. TFAP2A and TFAP2C was associated with worse clinical stage and prognosis in BLCA patients, while TFAP2B, TFAP2D and TFAP2E showed the opposite trend. Importantly, the functions of the differentially expressed TFAP2s were primarily related to the developmental process, reproductive process, response to stimulus and immune system process, etc. Moreover, TFAP2 family was significantly correlated with the infiltration of six immune cell types and might regulate TAM polarization. Conclusion: TFAP2 family might be an important regulator of immune cell infiltration and a valuable prognostic biomarker in patients with BLCA.


Monoclonal antibodies and enzyme immunoassays specific for human interferon (IFN) omega 1: evidence that IFN-omega 1 is a component of human leukocyte IFN.
Four hybridoma cell lines secreting monoclonal IgG antibodies to human interferon (IFN) omega 1 (= IFN-alpha II 1) were developed, using spleen cells of mice immunized with IFN-omega 1 and/or a novel hybrid interferon, IFN-omega 1/alpha 2. All antibodies (OMG-2, -4, -5, and -7) neutralize the antiviral activity of IFN-omega 1 and show distinct patterns of reactivity with the hybrid proteins, IFN-omega 1/alpha 2 and IFN-alpha 2c/omega 1. However, none of the antibodies is able to neutralize human IFN-alpha, confirming earlier observations that IFN-omega 1 and IFN-alpha are antigenically unrelated. The epitope specificities of the antibodies were further characterized in direct and competitive enzyme immunoassays (ELISAs). All binary antibody combinations were tested for their suitability for a two-site ("sandwich") ELISA for IFN-omega 1, using horse radish peroxidase as the marker enzyme. A configuration employing OMG-2 for antigen capture and OMG-7 as the detector antibody resulted in the highest assay sensitivity (approximately 10 pg IFN-omega 1/ml) and was studied further. This one-step assay is highly specific for IFN-omega 1 and does not recognize human IFN-alpha, -beta, and -gamma, thus allowing for determination of IFN-omega 1 levels in natural mixtures of human IFNs. Using this ELISA, it was found that IFN-omega 1 is present in IFN preparations derived from virus-induced human peripheral blood leukocytes and may constitute as much as 15% of the total leukocyte IFN activity. IFN-omega 1 was also detected at somewhat lower levels in preparations of human "lymphoblastoid" IFN.


Change in Biotypic Diversity of Russian Wheat Aphid (Hemiptera: Aphididae) Populations in the United States.
A key component of Russian wheat aphid, Diuraphis noxia (Kurdjumov), management has been through planting resistant wheat cultivars. A new biotype, RWA2, appeared in 2003 which caused widespread damage to wheat cultivars containing the Dn4 gene. Biotypic diversity in Russian wheat aphid populations has not been addressed since 2005 when RWA2 dominated the biotype complex. Our objectives were to determine the biotypic diversity in the Central Great Plains and Colorado Plateau at regional (2010, 2011, 2013) and local (2012) levels and detect the presence of new Russian wheat aphid biotypes. Regional and within-field aphid collections were screened against Russian wheat aphid-resistant wheat genotypes containing genes Dn3, Dn4, Dn6, Dn7, Dn9, CI2401; and resistant barley STARS 9301B. In 2010, all aphid collections from Texas were avirulent to the Dn4 resistance gene in wheat. Regional results revealed Dn4 avirulent RWA6 was widespread (55-84%) in populations infesting wheat in both regions. Biotypes RWA1, 2, and 3/7 were equally represented with percentages<20% each while RWA8 was rarely detected. Combining percentages of RWA1, 6, and 8 across regions to estimate avirulence to Dn4 gene revealed high percentages for both 2011 (64-80%) and 2013 (69-90%). In contrast, the biotype structure at the local level differed where biotype percentages varied up to ≥2-fold between fields. No new biotypes were detected; therefore, Dn7, CI2401, and STARS9301B remained resistant to all known Russian wheat aphid biotypes. This study documents a shift to Dn4 avirulent biotypes and serves as a valuable baseline for biotypic diversity in Russian wheat aphid populations prior to the deployment of new Russian wheat aphid-resistant wheat cultivars.


Development and validation of genome-wide InDel markers with high levels of polymorphism in bitter gourd (Momordica charantia).
The preferred choice for molecular marker development is identifying existing variation in populations through DNA sequencing. With the genome resources currently available for bitter gourd (Momordica charantia), it is now possible to detect genome-wide insertion-deletion (InDel) polymorphisms among bitter gourd populations, which guides the efficient development of InDel markers. Here, using bioinformatics technology, we detected 389,487 InDels from 61 Chinese bitter gourd accessions with an average density of approximately 1298 InDels/Mb. Then we developed a total of 2502 unique InDel primer pairs with a polymorphism information content (PIC) ≥0.6 distributed across the whole genome. Amplification of InDels in two bitter gourd lines '47-2-1-1-3' and '04-17,' indicated that the InDel markers were reliable and accurate. To highlight their utilization, the InDel markers were employed to construct a genetic map using 113 '47-2-1-1-3' × '04-17' F2 individuals. This InDel genetic map of bitter gourd consisted of 164 new InDel markers distributed on 15 linkage groups with a coverage of approximately half of the genome. This is the first report on the development of genome-wide InDel markers for bitter gourd. The validation of the amplification and genetic map construction suggests that these unique InDel markers may enhance the efficiency of genetic studies and marker-assisted selection for bitter gourd.


Big thrombus "sitting" in an atrial septal aneurysm.
A 79 year-old-man presented three episodes of upper gastrointestinal bleeding and weight loss. Endoscopy revealed bleeding and extrinsic compression at the pyloric region. Computed tomography scan showed a pancreatic tumor, peritoneal carcinomatosis, vascular infiltration, and incidentally found a partially calcified hypodense lesion of 35 mm in the left atrium, suggesting a myxoma or a thrombus. Echocardiography revealed moderate left atrium enlargement, dilated left atrial appendage with spontaneous echo contrast, moderate dilatation and dysfunction of the left ventricle, ejection fraction was 39%, and an atrial septal aneurysm in which a piriform, mass of 35×33×25 mm, was "sitting," suggesting an organized thrombus.


Is it intestinal tuberculosis again? Case report.
This case report focuses on an immigrant admitted to the Department of Respiratory Diseases, University Hospital Brno due to suspicion of relapsing intestinal tuberculosis. The patient presented with fever, night sweat, weight loss, diarrhea, and a history of several tuberculosis attacks in the last few years. None of the examinations confirmed the presence of active tuberculosis but raised suspicion of hematological malignancy. Pancytopenia was present in the peripheral blood. However, bone marrow examination and flowcytometry excluded the presence of a hematological malignancy. The results pointed to the possibility of vitamin B12 or folate deficiency that were both confirmed consequently by serum biochemical tests. Cobalamin and folate deficiency were caused by short bowel syndrome that developed after a major intestinal resection that the patient underwent in his past. Combined treatment including vitamins, pancreatic enzymes substitution, antidiarrhoics and spasmolytics was administered. The general health status of the patient improved rapidly with restitution of hematopoiesis, weight gain, and a decrease by 80% in daily number of stools. Clinical appearance of intestinal tuberculosis, short bowel syndrome and of cobalamin and folate deficiency as well as pathophysiology, diagnosis and treatment of these uncommon or even rare diseases are discussed in this case report.Key words: intestinal tuberculosis - pancytopenia - short bowel syndrome - vitamin B12 deficiency.


Risks posed by mystery illness.
Patients may present with unknown illness caused by accidental or deliberate release of biological, chemical or radioactive material or a new/emerging disease. Nurses must be aware of the protocols to follow to ensure their own safety and that of other patients. This article discusses the national advice in dealing with incidents or outbreaks of unusual illness.


Series-coupled silicon racetrack resonators and the Vernier effect: theory and measurement.
Silicon-on-insulator racetrack resonators can be used as multiplexers in wavelength division multiplexing applications. The free spectral range should be comparable to the span of the C-band so that a maximum number of channels can be multiplexed. However, the free spectral range is inversely proportional to the length of the resonator and, therefore, bending losses can become non-negligible. A viable alternative to increase the free spectral range is to use the Vernier effect. In this work, we present the theory of series-coupled racetrack resonators exhibiting the Vernier effect. We demonstrate the experimental performance of the device using silicon-on-insulator strip waveguides. The extended free spectral range is 36 nm and the interstitial peak suppression is from 9 dB to 17 dB.


S100b protein levels in subretinal fluid in rhegmatogenous retinal detachment.
To investigate the relevance of the concentration of S100B in subretinal fluid (SRF) with the postoperative anatomical and functional success and proliferative vitreoretinopathy (PVR) formation parameters in rhegmatogenous retinal detachment (RRD). Fifty-three patients (34 male, 19 female) were included in this prospective study. Study group consisted of 46 patients who had scleral buckling (SB) surgery with the diagnosis of RRD. Control group consisted of six patients who had pars plana vitrectomy (PPV) for either full-thickness macular hole or subluxated intraocular lens. SRFs were obtained during SB surgery. Study cases were divided into three groups, corresponding to the duration of retinal detachment (DRD). Clinical characteristics including best-corrected visual acuity (BCVA), anatomical status at 6 months, the presence of postoperative PVR that resulted in recurrent detachment and any possible re-operations were recorded. The concentration of S100B was quantified by using an enzyme immunoassay test kit. The concentration of S100B in SRF increased significantly after RRD. And, S100B levels were evidently elevated in concordance with DRD. There was no correlation between the concentration of SRF - S100B with preoperative or postoperative BCVA. Again, S100B levels were not related to the extent of RRD or postoperative PVR formation. Concentration of S100B in SRF is good marker of retinal stress and increases in concordance with DRD. However it would not help to predict the possible anatomical and functional success or postoperative PVR formation.


Histochemical study on the tongue of Rana ridibunda (anuran amphibian).
A structural and histochemical study of the tongue in the Anuran Amphibian Rana ridibunda was carried out. Histochemical analysis of the filiform and fungiform papillae of the dorsal epithelium has shown a variety of cellular types which may be characterized cytochemically. All of them, except the goblet cells, show a remarkable amount of neutral mucins. The intensity of histochemical positive reaction for sulphomucins, sialomucins and protein is variable according to the cell type. Other histochemical reactions show that the lingual glands are rich in neutral mucins, but not in sialomucins. Histochemically in the component the basic proteins with sulphydryl groups are demonstrated. This sulphydryl groups are more abundant in the glands located in the deep regions.


Pathogens pulling the strings: Effectors manipulating salicylic acid and phenylpropanoid biosynthesis in plants.
During evolution, plants have developed sophisticated ways to cope with different biotic and abiotic stresses. Phytohormones and secondary metabolites are known to play pivotal roles in defence responses against invading pathogens. One of the key hormones involved in plant immunity is salicylic acid (SA), of which the role in plant defence is well established and documented. Plants produce an array of secondary metabolites categorized in different classes, with the phenylpropanoids as major players in plant immunity. Both SA and phenylpropanoids are needed for an effective immune response by the plant. To successfully infect the host, pathogens secrete proteins, called effectors, into the plant tissue to lower defence. Secreted effectors can interfere with several metabolic or signalling pathways in the host to facilitate infection. In this review, we will focus on the different strategies pathogens have developed to affect the levels of SA and phenylpropanoids to increase plant susceptibility.


Atomistic modeling of alternating access of a mitochondrial ADP/ATP membrane transporter with molecular simulations.
The mitochondrial ADP/ATP carrier (AAC) is a membrane transporter that exchanges a cytosolic ADP for a matrix ATP. Atomic structures in an outward-facing (OF) form which binds an ADP from the intermembrane space have been solved by X-ray crystallography, and revealed their unique pseudo three-fold symmetry fold which is qualitatively different from pseudo two-fold symmetry of most transporters of which atomic structures have been solved. However, any atomic-level information on an inward-facing (IF) form, which binds an ATP from the matrix side and is fixed by binding of an inhibitor, bongkrekic acid (BA), is not available, and thus its alternating access mechanism for the transport process is unknown. Here, we report an atomic structure of the IF form predicted by atomic-level molecular dynamics (MD) simulations of the alternating access transition with a recently developed accelerating technique. We successfully obtained a significantly stable IF structure characterized by newly formed well-packed and -organized inter-domain interactions through the accelerated simulations of unprecedentedly large conformational changes of the alternating access without a prior knowledge of the target protein structure. The simulation also shed light on an atomistic mechanism of the strict transport selectivity of adenosine nucleotides over guanosine and inosine ones. Furthermore, the IF structure was shown to bind ATP and BA, and thus revealed their binding mechanisms. The present study proposes a qualitatively novel view of the alternating access of transporters having the unique three-fold symmetry in atomic details and opens the way for rational drug design targeting the transporter in the dynamic functional cycle.


First molecular survey of piroplasm species in cattle from Kyrgyzstan.
Bovine piroplasmosis is a tick-borne disease caused by apicomplexan hemoparasites of the genera Theileria and Babesia. This study was carried out to assess the presence and frequency of piroplasm parasites in apparently healthy cattle in Kyrgyzstan. A total of 454 blood samples were collected from animals of various ages in eight villages located in the Chu valley and around the Lake Issyk Kul. The hypervariable V4 region of the 18S ribosomal RNA (rRNA) gene was amplified with a set of primers specific targeting members of the genera Theileria and Babesia. Amplified PCR products were hybridized onto a membrane to which generic and species-specific oligonucleotide probes were covalently linked. The results revealed the presence of three piroplasm species (Theileria orientalis, Babesia major, Theileria annulata). Theileria orientalis was the most prevalent species (32.8%; CI 28.5-37.3). Babesia major was the only species of Babesia found in any of the samples (1.3%; CI 0.5-2.8). The co-existence of Theileria annulata and T. orientalis was detected in nine animals (1.9%; CI 0.9-3.7). BLAST search revealed that the Theileria sequences shared 100% identity with the recently reported sequences for T. buffeli and T. annulata. The sequence of B. major was also 100% identical to an existing B. major sequence. This molecular survey provides important epidemiological data for control of bovine piroplasmosis caused by T. orientalis, B. major, and T. annulata in Kyrgyzstan.


[Therapeutic strategy in colorectal carcinoma].
The authors review the contemporary optimal approach in the treatment of colorectal carcinoma. They emphasize the necessity of a comprehensive therapeutic approach, i.e. a combination of surgery, radiotherapy and chemotherapy in the treatment of colorectal carcinoma. Possibilities of curative and palliative treatment are presented.


Work-related musculoskeletal disorders in the automotive industry due to repetitive work - implications for rehabilitation.
Musculoskeletal disorders (MSDs) due to repetitive work are common in manufacturing industries, such as the automotive industry. However, it's still unclear which MSDs of the upper limb are to be expected in the automotive industry in a first aid unit as well as in occupational precaution examinations. It is also unclear which examination method could be performed effectively for practical reasons and under rehabilitation aspects. Additionally, it was to discuss whether the conception of unspecific description for MSDs has advantages or disadvantages in contrast to a precise medical diagnosis. We investigated the health status of two study populations working at two automotive plants in Germany. The first part included 67 consecutive patients who were seen for acute or chronic MSDs at the forearm over a 4-month period at the plants' medical services. Information about patients' working conditions and musculoskeletal symptoms was obtained during a standardized interview, which was followed by a standardized orthopedic-chiropractic physical examination. In the second part, 209 workers with daily exposure to video display terminals (VDT) completed a standardized questionnaire and were examined with function-oriented muscular tests on the occasion of their routine occupational precaution medical check-up. The majority of the 67 patients seen by the company's medical services were blue-collar works from the assembly lines and trainees rather than white-collar workers from offices. Rates of musculoskeletal complaints were disproportionately higher among experienced people performing new tasks and younger trainees. The most common MSD in this group were disorders of flexor tendons of the forearm. By contrast, among the 209 employees working at VDT disorders of the neck and shoulders were more common than discomfort in the forearm. A positive tendency between restricted rotation of the cervical vertebrae and years worked at VDT was observed. In addition, only less than 8% of unspecific disorders of the upper limb (esp. wrist and forearm) were found. Functional tests for the upper limb seemed to be very helpful to give precise medical advice to the employees to prevent individual complaints. The results are also helpful for developing specific training programs before beginning new tasks as well as for rehabilitation reasons. There's no need to use uncertain terminology (such as RSI) as it may not be representative of the actual underlying disorders as diagnosed by more thorough physical examinations.


The microRNA signature of patients with sunitinib failure: regulation of UHRF1 pathways by microRNA-101 in renal cell carcinoma.
Molecular targeted therapy is a standard treatment for patients with advanced renal cell carcinoma (RCC). Sunitinib is one of the most common molecular-targeted drugs for metastatic RCC. Molecular mechanisms of sunitinib resistance in RCC cells is still ambiguous. The microRNA (miRNA) expression signature of patients with sunitinib failure in RCC was constructed using a polymerase chain reaction (PCR)-based array. Several miRNAs that were aberrantly expressed in RCC tissues from patients treated with sunitinib were identified in this analysis. MicroRNA-101 (miR- 101) was markedly suppressed in sunitinib treated RCC tissues. Restoration of miR-101 significantly inhibited cell migration and invasion in Caki-1 and 786-O cells. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was directly suppressed by miR-101 in RCC cells, and overexpression of UHRF1 was confirmed in sunitinib-treated RCC tissues. The pathways of nucleotide excision repair and mismatch repair were significantly suppressed by knockdown of UHRF1. Our findings showed that antitumor miR-101- mediated UHRF1 pathways may be suppressed by sunitinib treatment.


Morphology of the Nervous System of the Barnacle Cypris Larva (Balanus amphitrite Darwin) Revealed by Light and Electron Microscopy.
The central nervous system of the cypris larva of Balanus amphitrite consists of a brain and posterior ganglion. The neuropil of the brain includes protocerebral and deutocerebral divisions, with nerve roots from the protocerebrum extending to the eyes and frontal filaments, and nerve roots from the deutocerebrum extending to the first antennae (antennules) and cement glands. The neuropil of the posterior ganglion includes subesophageal and thoracic divisions, with nerve roots from subesophageal divisions extending to the gut, and nerve roots from each of the six thoracic divisions extending to their corresponding thoracic appendage. The antennular nerve is the major peripheral extension of the nervous system and is composed in part by afferent fibers that innervate setae on the antennules. The cyprid nervous system is small, containing fewer than 2000 neurons, but is well organized for coordinating a response to settlement cues.


Chemically modified collagen: a natural biomaterial for tissue replacement.
Glutaraldehyde crosslinking of native or reconstituted collagen fibrils and tissues rich in collagen significantly reduces biodegradation. Other aldehydes are less efficient than glutaraldehyde in generating chemically, biologically, and thermally stable crosslinks. Tissues crosslinked with glutaraldehyde retain many of the viscoelastic properties of the native collagen fibrillar network which render them suitable for bioprostheses. Implants of collagenous materials crosslinked with glutaraldehyde are subject long-term to calcification, biodegradation, and low-grade immune reactions. We have attempted to overcome these problems by enhancing crosslinking through bridging of activated carboxyl groups with diamines and using glutaraldehyde to crosslink the epsilon-NH2 groups in collagen and the unreacted amines introduced by aliphatic diamines. This crosslinking reduces tissue degradation and nearly eliminates humoral antibody induction. Covalent binding of diphosphonates, specifically 3-amino-1-hydroxypropane-1, 1-diphosphonic acid (3-APD), and chondroitin sulfate to collagen or to the crosslink-enhanced collagen network reduces its potential for calcification. Platelet aggregation is also reduced by glutaraldehyde crosslinking and nearly eliminated by the covalent binding of chondroitin sulfate to collagen. The cytotoxicity of residual glutaraldehyde--leaching through the interstices of the collagen fibrils or the tissue matrix--and of reactive aldehydes associated with the bound polymeric glutaraldehyde can be minimized by neutralization and thorough rinsing after crosslinking and storage in a nontoxic bacteriostatic solution.


White Lies in Hand: Are Other-Oriented Lies Modified by Hand Gestures? Possibly Not.
Previous studies have shown that the hand-over-heart gesture is related to being more honest as opposed to using self-centered dishonesty. We assumed that the hand-over-heart gesture would also relate to other-oriented dishonesty, though the latter differs highly from self-centered lying. In Study 1 (N = 79), we showed that performing a hand-over-heart gesture diminished the tendency to use other-oriented white lies and that the fingers crossed behind one's back gesture was not related to higher dishonesty. We then pre-registered and conducted Study 2 (N = 88), which was designed following higher methodological standards than Study 1. Contrary, to the findings of Study 1, we found that using the hand-over-heart gesture did not result in refraining from using other-oriented white lies. We discuss the findings of this failed replication indicating the importance of strict methodological guidelines in conducting research and also reflect on relatively small effect sizes related to some findings in embodied cognition.


Three-dimensional convective alveolar flow induced by rhythmic breathing motion of the pulmonary acinus.
Low Reynolds number flows (Re<1) in the human pulmonary acinus are often difficult to assess due to the submillimeter dimensions and accessibility of the region. In the present computational study, we simulated three-dimensional alveolar flows in an alveolated duct at each generation of the pulmonary acinar tree using recent morphometric data. Rhythmic lung expansion and contraction motion was modeled using moving wall boundary conditions to simulate realistic sedentary tidal breathing. The resulting alveolar flow patterns are largely time independent and governed by the ratio of the alveolar to ductal flow rates, Qa/Qd. This ratio depends uniquely on geometrical configuration such that alveolar flow patterns may be entirely determined by the location of the alveoli along the acinar tree. Although flows within alveoli travel very slowly relative to those in acinar ducts, 0.021%<or=Ua/Ud<or=9.1%, they may exhibit complex patterns linked to the three-dimensional nature of the flow and confirm findings from earlier three-dimensional simulations. Such patterns are largely determined by the interplay between recirculation in the cavity induced by ductal shear flow over the alveolar opening and radial flows induced by wall displacement. Furthermore, alveolar flow patterns under rhythmic wall motion contrast sharply with results obtained in a rigid alveolus, further confirming the importance of including inherent wall motion to understand realistic acinar flow phenomena. The present findings may give further insight into the role of convective alveolar flows in determining aerosol kinematics and deposition in the pulmonary acinus.


Ruffles induced by Salmonella and other stimuli direct macropinocytosis of bacteria.
Ruffles are specialized plasma membrane ultrastructures of mammalian cells though to be integral to growth, development and locomotion. Induced by growth factors, mitogens or oncogene expression, ruffles are sites of filamentous actin rearrangement and are temporally associated with enhanced pinocytosis. But the function of ruffles, their mechanism of induction and their role in pinocytosis are not understood. We have observed formation of structures resembling ruffles associated with the site of entry of invasive Salmonella typhimurium. Here we report that ruffles elicited by invasive Salmonella directly mediate internalization of non-invasive bacteria in a macropinocytotic fashion, a phenomenon we term 'passive entry'. Furthermore, ruffles induced in the absence of Salmonella also facilitate passive entry. We present evidence that ruffles, common to many signalling events, comprise the macropinocytotic machinery mediating pinocytosis and are subverted by Salmonella so as to enter mammalian cells.


Expression patterns of zebrafish nocturnin genes and the transcriptional activity of the frog nocturnin promoter in zebrafish rod photoreceptors.
Daily modulation of gene expression is critical for the circadian rhythms of many organisms. One of the modulating mechanisms is based on nocturnin, a deadenylase that degrades mRNA in a circadian fashion. The nocturnin genes are expressed broadly, but their tissue expression patterns differ between mice and the frog Xenopus laevis; this difference suggests that the extent of the regulation of nocturin gene expression varies among species. In this study, we set out to characterize the expression patterns of two zebrafish nocturnin genes; in addition, we asked whether a frog nocturnin promoter has transcriptional activity in zebrafish. We used reverse transcription (RT)-PCR, quantitative real-time PCR (qRT-PCR), and rapid amplification of cDNA ends (RACE) analysis to determine whether the nocturnin-a and nocturnin-b genes are expressed in the eye, in situ hybridization to determine the cellular expression pattern of the nocturnin-b gene in the retina, and confocal microscopy to determine the protein expression pattern of the transgenic reporter green fluorescent protein (GFP) driven by the frog nocturnin promoter. We found that the amino acid sequences of zebrafish nocturnin-a and nocturnin-b are highly similar to those of frog, mouse, and human nocturnin homologs. Only nocturnin-b is expressed in the eye. Within the retina, nocturnin-b mRNA was expressed at higher levels in the retinal photoreceptors layer than in other cellular layers. This expression pattern echoes the restricted photoreceptor expression of nocturnin in the frog. We also found that the frog nocturnin promoter can be specifically activated in zebrafish rod photoreceptors. The high level of similarities in amino acid sequences of human, mouse, frog, and zebrafish nocturnin homologs suggest these proteins maintain a conserved deadenylation function that is important for regulating retinal circadian rhythmicity. The rod-specific transcriptional activity of the frog nocturnin promoter makes it a useful tool to drive moderate and rod-specific transgenic expression in zebrafish. The results of this study lay the groundwork to study nocturnin-based circadian biology of the zebrafish retina.


Novel accessory factor-binding site required for glucocorticoid regulation of the gamma-fibrinogen subunit gene from Xenopus laevis.
Glucocorticoids induce gene expression by binding to an intracellular receptor that interacts with genomic DNA and stimulates transcription of specific genes. The consensus DNA-binding site for the glucocorticoid receptor, called a glucocorticoid response element (GRE), is GGTACAnnnTGTTCT. In the classical model, binding of the receptor as a dimer to the two halves of the GRE is required for activation of transcription. For some glucocorticoid-regulated genes, additional DNA-binding proteins called accessory factors are necessary for hormonal responsiveness. We have identified a new factor required for glucocorticoid-induced expression of the gamma-fibrinogen subunit gene from the frog Xenopus laevis. Transfection of cloned DNA fragments into primary Xenopus hepatocytes showed that the DNA between 163 and 187 bp upstream of the transcription initiation site is essential for hormonal activation. A single complex forms when this small region of DNA is incubated in vitro with Xenopus liver nuclear proteins. The protein recognition site has been narrowed to AAGAGTTAA, a sequence not previously described as a transcription factor-binding site. We have named the protein(s) bound to this sequence Xenopus glucocorticoid receptor accessory factor (XGRAF). In addition to the XGRAF-binding site, glucocorticoid regulation of the gamma-fibrinogen gene requires at least three nearby GREs, each of which is a poor match to the consensus GRE. The position of the binding site for XGRAF overlaps the putative upstream half of the most important GRE. Models are presented to show possible ways that the novel accessory factor and the glucocorticoid receptor could act through closely juxtaposed sites on the DNA.


[Treatment of diabetic nephropathy by integrative medicine: a multi-center prospective cohort study].
To assess the efficacy and safety of integrative medicine (IM) treatment for diabetic nephropathy (DN), and to explore the medication laws by Chinese medicine (CM) syndrome typing. One hundred and seventy outpatients or inpatients with DN at Dongfang Hospital of Beijing University of Chinese Medicine, Xiyuan Hospital of China Academy of Chinese Medical Sciences, and China-Japan Friendship Hospital of the Ministry of Health were recruited from March 2008 to July 2009. They were allocated into the IM group (116 cases) or the Western medicine group (54 cases) according to whether or not they were willing to receive CM syndrome typing. The incidence of endpoint events and secondary outcome measures [such as body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), urinary albumin excretion rate (UAER), 24 h urinary protein (24 hU), serum creatinine (SCr), fasting blood glucose (FBG), and glycosylated hemoglobin (HbA1c)] of two groups were observed at 3, 6, 12, 18, and 24 months respectively during the follow-ups. Patients in the IM group were syndrome typed. The CM recipes were collected to calculate the frequency of Chinese materia medica used. The liver function, blood routines, and ECG were observed and compared during the follow-ups. The follow-up period was 3 to 24 months with the mean of 14 months. Data suitable for analysis mainly covered the 3rd, 6th, 12th and 18th month of the follow-up. Both PPS and FAS analysis showed that there were no significant difference in the incidence of endpoint between two groups (11.2% vs 7.4%, P>0.05). The level of body mass index (BMI) [(25.0 +/- 3.1) kg/m2] and fasting blood glucose (FBG) [(7.9 +/- 1.5) mmol/L] in the IM group were lower than those of the Western medicine group [(28.6 +/- 4.4) kg/m2 and (8.8 +/- 2.9) mmol/L respectively] at the 6-month follow-up (P<0.05). The levels of FBG [(7.9 +/- 1.4) mmol/L] and HbA1c [(7.8 +/- 1.4)%] in the IM group were lower than those of the Western medicine group [(9.6 +/- 2.8) mmol/L and (8.5 +/- 1.6)% respectively] at the 12-month follow-up (P<0.05). There was no significant difference in other indices between the two groups at the 3- or 12-month follow-ups. The level of SCr in the IM group and the Western medicine group before follow-up were (96.8 +/- 35.2) micromol/L and (80.5 +/- 24.6) micromol/L respectively, showing statistical difference (P<0.01). There were no significance difference in SCr between the two groups at 3, 6, 12, 18-month follow-ups for center 2 (Xiyuan Hospital of China Academy of Chinese Medical Sciences) and center 3 (China-Japan Friendship Hospital of the Ministry of Health), while the level of SCr in the IM group [(82.4 +/- 25.7) micromol/L, (78.1 +/- 25.9) micromol/L, (80.3 +/- 24.0) micromol/L, respectively] were lower than that of the Western medicine group [(101.4 +/- 37.2) micromol/L, (96.5 +/- 34.1) micromol/L, (93.9 +/- 25.9) micromol/L, respectively] for center 1 (Dongfang Hospital of Beijing University of Chinese Medicine) at 3, 6, 12-month follow-ups (P<0.05). The top ten drugs used most frequently in the 237 prescriptions collected was astragali (68.4%), ophiopogonis tube (67.5%), rehmannia dried rhizome (67.1%), danshen root (49.4%), Codonopsis pilosula (41.8%), figwort root (35.4%), Chinese magnolia-vine fruit (29.5%), safflower (27.9%), peach seed (26.2%), and angelica root (25.3%). There was no abnormal liver function, blood abnormalities, and serious adverse events in two groups during the follow-ups. CM treatment based on syndrome typing in combination with routine Western medicine for DN could reduce the levels of BMI, FBG, HbA1c, and SCr at partial time points, showing favorable safety. Chinese medicinals applied in treatment based on syndrome typing for DN covered mainly supplementing qi, nourishing yin, and activating blood circulation to remove blood stasis.


Effect of muscle compensation on knee instability during ACL-deficient gait.
The purpose of this investigation was to determine whether an isolated change in either quadriceps or hamstrings muscle force (quadriceps avoidance and hamstrings facilitation, respectively) is sufficient to stabilize the ACL-deficient (ACLd) knee during gait. A three-dimensional model of the lower limb was used to calculate anterior tibial translation in the intact and ACLd knee during gait. The model was then used to predict the amount of quadriceps and hamstrings force needed to restore anterior tibial translation (ATT) in the ACLd knee to an intact or maximum allowable level. It was possible to reduce ATT in the ACLd knee to the level calculated for the intact knee by increasing the magnitude of hamstrings force (a hamstrings facilitation pattern). Although this strategy decreased the knee extensor moment calculated for walking, the effect was much less than that obtained when quadriceps force was reduced. Reducing quadriceps force to restore normal ATT resulted in complete elimination of the knee extensor moment (a quadriceps avoidance pattern); however, this strategy was insufficient to restore ATT to the level calculated for the intact knee over portions of the gait cycle. The model simulations showed that increased hamstrings force was sufficient to stabilize the ACLd knee during gait. Reduced quadriceps force was insufficient to restore normal ATT for portions of the gait cycle.


Engaged patients, engaged partnerships: singles and partners dealing with an acute cardiac event.
A few studies examine patients' (and partners') individual and relational functioning after an acute cardiac event and no research focuses on the individual and relational factors associated with the patient's engagement in his/her disease management. The present study aimed at exploring these variables in male and female patients as well as their partners. We pursued our objectives by taking advantage of a dyadic research design that involved both partners in the data collection, when present, and by including women patients in the sample. Findings showed that patients in a couple, compared to single patients, perceive that their illness had less serious consequences for their life and they were more engaged in their health care; that patients and partners showed comparable levels of distress; and that less depressed, more confident, and better informed patients were more likely to actively engage in their treatment. Findings are discussed in light of their implications for clinical practice.


Endoscopic management of massive mercury ingestion: A case report.
Ingestion of a massive amount of metallic mercury was thought to be harmless until the last century. After that, in a number of cases, mercury ingestion has been associated with appendicitis, impaired liver function, memory deficits, aspiration leading to pneumonitis and acute renal failure. Treatment includes gastric lavage, giving laxatives and chelating agents, but rapid removal of metallic mercury with gastroscopy has not been used. An 18-year-old man was admitted to our emergency department after drinking 1000 g of metallic mercury as a suicide attempt. Except from mild umbilical tenderness, he had no other symptoms. Radiography showed a metallic density in the area of the stomach. Gastroscopy was performed to remove the mercury. One large pool and several small droplets of mercury were removed from the stomach. Blood and urine mercury levels of the patient remained low during hospitalization. No symptoms of mercury intoxication developed during the follow-up period. Massive mercury ingestion may cause several symptoms, which can be prevented with prompt treatment. We used endoscopy to remove the mercury, which shortened the exposure time and minimized the risk of aspiration. This is the first case where endoscopy was used for the management of mercury ingestion.


Auxin-Responsive R2R3-MYB Transcription Factors HcMYB1 and HcMYB2 Activate Volatile Biosynthesis in Hedychium coronarium Flowers.
Auxin, an important plant hormone, induces the biosynthesis of various secondary metabolites by modulating the expression of auxin-responsive genes. In the ornamental plant Hedychium coronarium, linalool and methyl benzoate are biosynthesized by the terpene synthase (TPS) HcTPS5 and the benzoic/salicylic acid methyltransferase (BSMT) HcBSMT2, respectively. However, the transcriptional regulation of this process remains unclear. Here, we identified and functionally characterized the R2R3-MYB transcription factors HcMYB1 and HcMYB2 in regulating the biosynthesis of these floral aroma compounds. HcMYB1 and HcMYB2 are specifically expressed in flowers, their expression is correlated with the emission of volatile compounds in flowers, and is induced by auxin. Moreover, HcMYB1 and HcMYB2 interact with the HcBSMT2 promoter region. HcMYB2 activates the expression of the linalool synthase gene HcTPS5. In flowers with HcMYB1 or HcMYB2 silenced, the levels of floral scent compounds were significantly reduced, and HcBSMT2 and HcTPS5 were downregulated compared with the wild type. Moreover, HcMYB1 form protein-protein interaction with key scent-related HcIAA4 protein to regulate floral aroma production. Taken together, these results indicate that HcMYB1 and HcMYB2 play crucial roles in regulating the formation of scent compounds in Hedychium coronarium (H. coronarium) flowers in response to auxin signaling.


An international cohort study spanning five decades assessed outcomes of nephropathic cystinosis.
Nephropathic cystinosis is a rare disease secondary to recessive mutations of the CTNS gene encoding the lysosomal cystine transporter cystinosin, causing accumulation of cystine in multiple organs. Over the years, the disease has evolved from being a fatal condition during early childhood into a treatable condition, with patients surviving into adulthood. Data on cystinosis are limited by the rarity of the disease. Here, we have investigated factors associated with kidney and growth outcome in a very large cohort of 453 patients born between 1964 and 2016 and followed in Belgium, Germany, Austria, France, Italy, Spain, The Netherlands, Turkey and United Kingdom. From the 1970s to the 1990s, the median increase in kidney survival was 9.1 years. During these years, cysteamine, a cystine-depleting agent, was introduced for the treatment of cystinosis. Significant risk factors associated with early progression to end-stage kidney disease assessed by Cox proportional multivariable analysis included delayed initiation of cysteamine therapy and higher mean leucocyte cystine levels. No significant effect on kidney function was observed for gender, pathogenic variant of the CTNS gene, and the prescription of indomethacin or renin angiotensin system blockers. Significantly improved linear growth was associated with early use of cysteamine and lower leukocyte cystine levels. Thus, our study provides strong evidence in favor of early diagnosis and optimization of cystine depletion therapy in nephropathic cystinosis.


Family physician consultation patterns indicate high risk for early-onset anorexia nervosa.
There is often a delay in the recognition of early-onset anorexia nervosa. The current study aimed to determine whether there are specific patterns in the frequency and content of family physician consultations that might predict its onset. Lifetime number and type of family physician consultations were recorded for three groups: (a) an index group comprising 19 girls with anorexia nervosa, onset under 14; (b) a clinical control group comprising 19 girls with an emotional disorder; and (c) a nonclinical group comprising 19 girls with no history of mental health problems. Both clinical groups had an elevated number of consultations, particularly in the 5 years before diagnosis. The index group had a significantly higher number of eating, weight, and shape consultations (especially in the year before diagnosis), whereas the clinical control group had a greater number of psychological consultations. A single consultation about eating behaviour or weight and shape concerns is a strong predictor of the subsequent emergence of anorexia nervosa.


Pseudoephedrine use among US children, 1999-2006: results from the Slone survey.
Pseudoephedrine, a decongestant found in many cough-and-cold and allergy medications, has been associated with deaths and adverse events in young children; however, the absolute risks of pediatric pseudoephedrine use are difficult to assess because the number of children exposed on a population basis and typical patterns of use are unknown. In addition, use may be changing because of the Combat Methamphetamine Epidemic Act of 2005, which limited pseudoephedrine availability. We sought to describe the prevalence and patterns of pseudoephedrine use among US children and to assess any change since the 2005 law took effect. We analyzed data on pseudoephedrine use among 4267 children who were aged 0 to 17 years and enrolled from 1999 to 2006 in the Slone Survey, a national random-digit-dial telephone survey of medication use in the US population. Overall, 214 children took pseudoephedrine in a given week. Use was highest for children who were younger than 2 years. Sixteen children (7.5% of users) took >1 pseudoephedrine-containing product within the same week, including 6 children who were younger than 2 years. Of the pseudoephedrine products used, most were multiple-ingredient liquids (58.9%) and multiple-ingredient tablets (24.7%). Fifty-two children (25.0% of users) took pseudoephedrine for >1 week, including 7 children who were younger than 2 years. Use in 2006 (2.9%) was significantly lower than in 1999-2005 (5.2%). Pseudoephedrine exposure, mostly in the form of multiple-ingredient products, is common among US children, especially children who are younger than 2 years, who are at the highest risk for toxicity and for whom safe dosing recommendations are lacking. Concerning patterns of use include taking >1 pseudoephedrine-containing product concurrently and using pseudoephedrine for extended periods. Pediatric pseudoephedrine use seems to be declining since the institution of the 2005 Combat Methamphetamine Epidemic Act.


IDEAS internal contamination database: a compilation of published internal contamination cases. A tool for the internal dosimetry community.
In the scope of the IDEAS project to develop General Guidelines for the Assessment of Internal Dose from Monitoring data, two databases were compiled. The IDEAS Bibliography database contains references dealing with problems related to cases of internal contamination. The IDEAS Internal Contamination Database now contains more than 200 cases of internal contamination. In the near future, the IDEAS Internal Contamination database will be made available to the internal dosimetry community. The database has several potential applications, including: training, testing biokinetic models, testing software for calculating intakes and doses from bioassay data, comparison of data from a new accidental intake with that from previous exposures to similar materials. The database is by no means complete, and this presentation is also an appeal for internal contamination cases to extend and update it.