Spanish Ketogenic Mediterranean Diet: a healthy cardiovascular diet for weight loss.
Ketogenic diets are an effective healthy way of losing weight since they promote a non-atherogenic lipid profile, lower blood pressure and decrease resistance to insulin with an improvement in blood levels of glucose and insulin. On the other hand, Mediterranean diet is well known to be one of the healthiest diets, being the basic ingredients of such diet the olive oil, red wine and vegetables. In Spain the fish is an important component of such diet. The objective of this study was to determine the dietary effects of a protein ketogenic diet rich in olive oil, salad, fish and red wine. A prospective study was carried out in 31 obese subjects (22 male and 19 female) with the inclusion criteria whose body mass index and age was 36.46 +/- 2.22 and 38.48 +/- 2.27, respectively. This Ketogenic diet was called "Spanish Ketogenic Mediterranean Diet" (SKMD) due to the incorporation of virgin olive oil as the principal source of fat (> or =30 ml/day), moderate red wine intake (200-400 ml/day), green vegetables and salads as the main source of carbohydrates and fish as the main source of proteins. It was an unlimited calorie diet. Statistical differences between the parameters studied before and after the administration of the "Spanish Ketogenic Mediterranean diet" (week 0 and 12) were analyzed by paired Student's t test. There was an extremely significant (p < 0.0001) reduction in body weight (108.62 kg--> 94.48 kg), body mass index (36.46 kg/m(2)-->31.76 kg/m(2), systolic blood pressure (125.71 mmHg-->109.05 mmHg), diastolic blood pressure (84.52 mmHg--> 75.24 mmHg), total cholesterol (208.24 mg/dl-->186.62 mg/dl), triacylglicerols (218.67 mg/dl-->113.90 mg/dl) and glucose (109.81 mg/dl--> 93.33 mg/dl). There was a significant (p = 0.0167) reduction in LDLc (114.52 mg/dl-->105.95 mg/dl) and an extremely significant increase in HDLc (50.10 mg/dl-->54.57 mg/dl). The most affected parameter was the triacylglicerols (47.91% of reduction). The SKMD is safe, an effective way of losing weight, promoting non-atherogenic lipid profiles, lowering blood pressure and improving fasting blood glucose levels. Future research should include a larger sample size, a longer term use and a comparison with other ketogenic diets.


Korean medicines for poor ovarian reserve in infertility: A protocol for a multicenter observational study.
Many infertile patients have used Korean medicines (KMs) as a primary or adjuvant therapeutic method to improve in vitro fertilization success rates. The aim of this multicenter observational study is to investigate the effects of KMs on poor ovarian reserve (POR) in infertile patients. We will perform a prospective multicenter observational study. This study will recruit 50 women between 25 and 44 years of age with infertility caused by POR from among patients who visit the KM clinic. All participants will visit the KM clinic on the 2nd or 3rd day of menstruation to receive the KMs. KM treatment will be delivered for 3 menstrual cycles (3 months) and will include herbal decoction, acupuncture, or moxibustion on demand. Every participant will be assessed based on KM clinical symptoms, a quality of life questionnaire, and ovarian reserve test results. The study was approved by Institutional Review Board of Semyung University (SMU-IM-190501). The results will be published in a peer-reviewed journal and will be disseminated electronically and in print. Clinical Research Information Service: KCT0004209.


[Correlation of cyto-colpo-histology in 204 invasive carcinomas of the uterine cervix].
The combined use of colposcopy and cytology allows the diagnosis of 98.39 per cent of the cases of invasive cervical carcinoma.


Water consumption of electric power system in China: from electricity generation to consumption.
Understanding the water requirement of electricity generation is critical to the development of both electricity and water systems, while the water consumption of the whole electric power system remains unrevealed. Here, we examine the water consumption driven by electricity generation, transmission, and consumption in China, finding that 14 billion m3 of freshwater is consumed by electricity generation in 2019 and that 2.5 billion m3 of freshwater was virtually transferred via electricity transmission. Nationally, the freshwater consumption per unit of electricity generation was 1.9 m3/MWh. Based on the state-of-the-art electricity transmission data, we find that 59% of the transported electric power was from water-scarce provinces and 0.7 billion m3 of freshwater was lost due to the electricity loss in transmission lines in China. It is essential to link water resources with the whole electric power system (production, transmission, and consumption) rather than only part of the power system as in previous research.


Minor impacts of rain on methane flux from hemiboreal, boreal, and subarctic lakes.
Methane (CH4) emissions (FCH4) from northern freshwater lakes are not only significant but also highly variable in time and one driver variable suggested to be important is precipitation. Rain can have various, potentially large effects on FCH4 across multiple time frames, and verifying the impact of rain on lake FCH4 is key to understand both contemporary flux regulation, and to predict future FCH4 related to possible changes in frequency and intensity of rainfall from climate change. The main objective of this study was to assess the short-term impact of typically occurring rain events with different intensity on FCH4 from various lake types located in hemiboreal, boreal, and subarctic Sweden. In spite of high time resolution automated flux measurements across different depth zones and covering numerous commonly types of rain events in northern areas, in general, no strong impact on FCH4 during and within 24 h after the rainfall could be observed. Only in deeper lake areas and during longer rain events FCH4 was weakly related to rain (R2 = 0.29, p < 0.05), where a minor FCH4 decrease during the rain was identified, suggesting that direct rainwater input, during greater rainfall, may decrease FCH4 by dilution of surface water CH4. Overall, this study indicates that typical rain events in the studied regions have minor direct short-term effects on FCH4 from northern lakes and do not enhance FCH4 from shallow and deeper parts of lakes during and up to 24-h after the rainfall. Instead, other factors such as wind speed, water temperature and pressure changes were more strongly correlated with lake FCH4.


Extragonadal mixed germ cell tumor of the right arm: description of the first case in the literature.
Extragonadal localization of germ cell tumors (GCTs) is rare; to the best of our knowledge, a location in the soft tissue of the arm has never been previously reported in the literature. We report the case of a 37-year-old man who presented with a primary malignant mixed non-seminomatous GCT (teratocarcinoma variety) in the right arm, treated by a combination of cisplatin-based chemotherapy and surgery. After 18 months of close follow-up, no locoregional recurrence or distant metastases have been detected. A combination of chemotherapy and surgery is the most appropriate treatment strategy for extragonadal GCTs, to ensure both local and systemic control.


Munchausen's syndrome: a new variety of bleeding type-self-inflicted cheilorrhagia and cheilitis glandularis.
The unique case of a self-inflicted cheilorrhagia with clinical features of Munchausen syndrome and cheilitis glandularis is described. Attention is directed to the association of cheilitis glandularis and factitious bleeding. This constitutes a new variety of bleeding type Munchausen's syndrome.


Lack of association between the unique LMP2 gene polymorphism and the outcome of lung cancer in a population of Chinese Han nationality.
Lung cancer is characterized by a widely ranging incidence variation; it is the most common cancer in China. In this study we will assess the association of low-molecular-mass protease 2 (LMP2) gene codon 60 polymorphism with the risk of lung cancer. Genomic DNA of peripheral blood mononuclear cells was isolated from 207 patients with lung cancer and 264 healthy controls. DNA direct sequencing and polymerase chain reaction-restriction fragment length polymorphism were performed to scrutinize LMP2 gene codon 60 polymorphism. The risk of LMP2 gene polymorphism in lung cancer was assessed using an unconditional logistic regression model adjusted by the confounding factors. As a result of DNA direct sequencing, the LMP2 codon 60 polymorphic substitution of the nucleotide was CGC → TGC in Chinese individuals, not CGC → CAC as reported in other ethnic populations. In histology-specific analysis and TNM stages, there was no apparent association between this LMP2 gene polymorphism and any of the histologic types or TNM stages of lung cancer using the Arg/Arg genotypes as the reference group (all p values > 0.05). These results suggest that the polymorphic site is unique in the Chinese population of Han nationality at the LMP2 codon 60 loci (Arg60Cys), but a lack of association with lung cancer exists.


Arsenic uptake and speciation and the effects of phosphate nutrition in hydroponically grown kikuyu grass (Pennisetum clandestinum Hochst).
This work focuses on the accumulation and mobility properties of arsenic (As) and the effects of phosphate (P) on its movement in Pennisetum clandestinum Hochst (kikuyu grass), grown hydroponically under increasing arsenate (As(V)) concentrations. The uptake of both ions and the relative kinetics show that phosphate is an efficient competitive inhibitor of As(V) uptake. The P/As uptake rate ratios in roots indicate that P is taken up preferentially by P/As transporters. An arsenite (As(III)) efflux from roots was also found, but this decreased when the arsenate concentration in the solution exceeded 5 μM. Increases in both arsenite and arsenate concentrations in roots were observed when the arsenate concentration in the solution was increased, and the highest accumulation of As(III) in roots was found when plants were grown at 5 μM As(V). The low ratios of As accumulated in shoots compared to roots suggest limited mobility of the metalloid within Kikuyu plants. The results indicate that arsenic resistance in kikuyu grass in conditions of moderate exposure is mainly dependent on the following factors: 1) phosphate nutrition: P is an efficient competitive inhibitor of As(V) uptake because of the higher selectivity of membrane transporters with respect to phosphate rather than arsenate; and 2) a detoxification mechanism including a reduction in both arsenate and arsenite root efflux. The As tolerance strategy of Kikuyu limits arsenate uptake and As translocation from roots to shoots; therefore, this plant cannot be considered a viable candidate for use in the phytoextraction of arsenic from contaminated soils or water.


Quantitative measurement of adenosine deaminase from human erythrocytes.
Methods for measuring enzymatic activity of adenosine deaminase from human erythrocytes were examined and compared with each other. Determination of ADA by the method in which adenosine is converted into inosine with uric acid as the final product by the action of nucleoside phosphorylase and xanthine oxidase appears to yield the most reliable results. In the recommended assay saponin is used for lysis of erythrocytes when testing adenosine deaminase activity in red blood cells. Storage of erythrocyte samples is optimal at +4 degrees C; storage at room temperature or at -20 degrees C leads to loss of adenosine deaminase activity.


A synoptic approach to weather conditions discloses a relationship with ambulatory blood pressure in hypertensives.
Higher blood pressure (BP) values in cold than in hot months has been documented in hypertensives. These changes may potentially contribute to the observed excess winter cardiovascular mortality. However, the association with weather has always been investigated by considering the relationship with a single variable rather than considering the combination of ground weather variables characterizing a specific weather pattern (air mass (AM)). We retrospectively investigate in Florence (Italy) the relationship between BP and specific AMs in hypertensive subjects (n = 540) referred to our Hypertension Unit for 24-h ambulatory BP monitoring during the period of the year characterized by the highest weather variability (winter). Five different winter daily AMs were classified according to the combination of ground weather data (air temperature, cloud cover, relative humidity, atmospheric pressure, wind speed, and direction). Multiple variable analysis selected the AM as a significant predictor of mean 24-h BP (P < 0.01 for diastolic BP (DBP) and P < 0.05 for systolic BP (SBP)), daytime DBP (P < 0.001) and nighttime BP (P < 0.01 for both SBP and DBP), with higher BP values observed in cyclonic (unstable, cloudy, and mild weather) than in anticyclonic (settled, cloudless, and cold weather) days. When the association with 2-day sequences of AMs was considered, an increase in ambulatory BP followed a sudden day-to-day change of weather pattern going from anticyclonic to cyclonic days. The weather considered as a combination of different weather variables may affect BP. The forecast of a sudden change of AM could provide important information helpful for hypertensives during winter.


Exploring the utility and acceptability of Faecal immunochemical testing (FIT) as a novel intervention for the improvement of colorectal Cancer (CRC) surveillance in individuals with lynch syndrome (FIT for lynch study): a single-arm, prospective, multi-centre, non-randomised study.
Lynch Syndrome (LS) is an inherited cancer predisposition syndrome defined by pathogenic variants in the mismatch repair (MMR) or EPCAM genes. In the United Kingdom, people with LS are advised to undergo biennial colonoscopy from as early as 25 until 75 years of age to mitigate a high lifetime colorectal cancer (CRC) risk, though the consideration of additional surveillance intervention(s) through the application of non-invasive diagnostic devices has yet to be longitudinally observed in LS patients. In this study, we will examine the role of annual faecal immunochemical testing (FIT) alongside biennial colonoscopy for CRC surveillance in people with LS. In this single-arm, prospective, non-randomised study, 400 LS patients will be recruited across 11 National Health Service (NHS) Trusts throughout the United Kingdom. Study inclusion requires a LS diagnosis, between 25 and 73 years old, and a routine surveillance colonoscopy scheduled during the recruitment period. Eligible patients will receive a baseline OC-Sensor™ FIT kit ahead of their colonoscopy, and annually for 3 years thereafter. A pre-paid envelope addressed to the central lab will be included within all patient mailings for the return of FIT kits and relevant study documents. A questionnaire assessing attitudes and perception of FIT will also be included at baseline. All study samples received by the central lab will be assayed on an OC-Sensor™ PLEDIA Analyser. Patients with FIT results of ≥6 μg of Haemoglobin per gram of faeces (f-Hb) at Years 1 and/or 3 will be referred for colonoscopy via an urgent colonoscopy triage pathway. 16S rRNA gene V4 amplicon sequencing will be carried out on residual faecal DNA of eligible archived FIT samples to characterise the faecal microbiome. FIT may have clinical utility alongside colonoscopic surveillance in people with LS. We have designed a longitudinal study to examine the efficacy of FIT as a non-invasive modality. Potential limitations of this method will be assessed, including false negative or false positive FIT results related to specific morphological features of LS neoplasia or the presence of post-resection anastomotic inflammation. The potential for additional colonoscopies in a subset of participants may also impact on colonoscopic resources and patient acceptability. Trial Registration: ISRCTN, ISRCTN15740250 . Registered 13 July 2021.


Solid and papillary neoplasm of the pancreas: a report of an unusual pattern of calcification.
Solid and papillary neoplasms of the pancreas are very rare and occur predominantly in young women. Calcifications in the neoplasms are rarely observed radiologically. We report a case of a 48-yr-old female with this neoplasm containing prominent calcifications on the wall.


Repression of in vivo growth of Myc/Ras transformed tumor cells by Mad1.
The Myc/Max/Mad network of transcriptional regulatory proteins plays an essential role in cell proliferation, growth, apoptosis, and differentiation. Whereas Myc proteins affect cell cycle progression positively, Mad proteins are negative regulators of cell proliferation. It has been shown in several in vitro systems that Mad proteins antagonize c-Myc functions. In this report we describe the inhibition of tumor cell outgrowth in vivo by Mad1 expression. Transformed cell lines were generated by co-transfection of c-myc, c-H-ras, and a chimeric mad1ER construct into primary rat embryo cells (MRMad1ER cells). Activation of Mad1 by 4-Hydroxy-Tamoxifen (OHT) resulted in abrogation of telomerase activity, reduced cloning efficiency, and decreased proportion of cells in S phase. Injection of MRMad1ER cells into syngenic rats induced aggressively growing tumors after a short latency period. This tumor growth was inhibited by OHT-treatment of animals, with the extent of inhibition correlating with the amount of OHT injected. No effect of OHT on tumor growth was observed with similarly transformed Myc/Ras cell lines which did not express Mad1ER. These data demonstrate that Mad1 is able to suppress Myc/Ras-mediated transformation under in vivo conditions.


School Bag-Related Factors and Their Implications for Walking and Cycling to School among New Zealand Adolescents.
Excessive school bag weight may be a modifiable barrier to active transport to school. This study examined correlates of school bag weight and adolescents' perceptions of excessive school bag weight for walking and cycling to school among New Zealand adolescents living in diverse settlement types. Adolescents (n = 1512; 15.0 ± 1.3 years) completed a questionnaire and had their bag weight (n = 1190) and body weight (n = 1038) measured. Adolescents using active transport and rural adolescents had lighter school bags compared to their counterparts. One-third of adolescents reported excessive school bag weight for walking (31.2%) and cycling (37.2%) to school. Positive correlates of relative school bag weight were female gender (regression coefficient (95% CI): 0.53 (0.13, 0.93)), and underweight (2.21 (1.39, 3.02)), whereas negative correlates were Māori ethnicity (-0.87 (-1.41, -0.32)), overweight (-1.84 (-2.35, -1.34)) and obesity (-3.57 (-4.26, -2.87)), and school location in small urban areas (-2.10 (-4.19, -0.01)), and rural settlements (-3.58 (-5.66, -1.49)). Older adolescents, females, those with greater relative school bag weight, and those experiencing school bag-related pain symptoms and/or fatigue were more likely to report excessive school bag weight for both walking and cycling to school. Future initiatives should target reducing excessive school bag weight, particularly in female and urban adolescents.


[Selective embolization of the internal iliac artery: last resort in inoperable hemorrhaging prostatic cancer].
A case of profuse hemorrhage from prostatic carcinoma infiltrating the urinary bladder is presented. Angiography was performed to identify the vascular supply. Selective embolization of the internal iliac arteries is described, potential complications are discussed.


Adenovirus endopeptidase and papain are inhibited by the same agents.
Adenoviruses encode a cysteine protease (AVP) which carries out highly specific cleavages on at least seven viral proteins and two cellular proteins. Virus infectivity is dependent on this function. The three-dimensional positions of the amino acids involved in catalysis display a striking similarity to those of papain, suggesting a similar catalytic mechanism. This similarity has prompted us to compare the effect of papain inhibitors on the two enzymes. AVP and papain activity was tested on a fluorescent peptide substrate as well as on metabolically labeled adenovirus (Ad2) precursor proteins. Hep2 cells infected with Ad2 were exposed to inhibitors and assayed for, (a) infectious virus, (b) in situ Ad2 protease activity, (c) physical particle production and their polypeptide composition. We found that in both substrate systems AVP was sensitive to the papain inhibitors benzamidoacetonitrile, acetamidoacetonitrile and N-methoxyphenylalanine glycylnitrile, and that the degree of sensitivity was influenced by the substrate. Unlike papain, AVP was relatively insensitive to E64. In ex vivo tests, Hep2 cells infected with Ad2 were exposed to inhibitors and assayed for, (a) infectious virus, (b) in situ Ad2 protease activity, (c) physical particle production and their polypeptide composition. A 4-fold reduction in virus titer was obtained when the inhibitors were added between 17 and 25 h after infection. Processing of precursor proteins was also inhibited yet the production of physical particles was only reduced 2-fold. These experiments show that papain inhibitors are also capable of inhibiting the adenovirus protease both in vitro and ex vivo, thus forging a possible link between structural similarity and functionality.


CRISPR-Cas systems are present predominantly on chromosome and its relationship with MEGs in Vibrio species.
Bacteria have developed diverse strategies to counteract virus predation, one of which is the clustered regularly interspaced short palindromic repeat (CRISPR) and CRISPR associated (Cas) proteins immune defense system. In this study, the structure and function of the CRISPR-Cas system in 120 Vibrio strains were analyzed by bioinformatics methods, as well as the correlation between CRISPR and mobile genetic elements (MEGs). Only 61 Vibrio strains contained one or more CRISPR structures, and finally 102 CRISPRs were identified. The typical repeat size was 28 bp, and the total length of CRISPRs is nearly 60 bp, which was the most stable length of CRISPR in Vibrio strains. The types of CRISPR-Cas present in 61 strains were I-C, I-E, I-F, II-B, III-B, III-D and the rare type IV systems. Through principal component analysis, we found that Cas gene was most closely related to CRISPR. In addition, phages and plasmids were also highly correlated, showing negative correlation with CRISPR-Cas system. CRISPR-Cas predominantly present on chromosome within Vibrio while rarely in plasmids. Comparing the structural characteristics of plasmids containing CRISPR and without CRISPR, we found plasmid pMBL287 with CRISPR contained a bacteriophage f237, with more MGES, suggesting the diversity was greater. In addition, the same mobile genetic elements IS256 and ISL3 were found in the upstream and downstream of CRISPR. This study provides the prevalence, diversity and phylogenetic distribution of CRISPR-Cas in Vibrio, revealing which type of CRISPR-Cas system is predominant, and the factors affecting its function, as well as its relationship with mobile genetic elements.


Do sediment-bound nickel and lead affect chironomids life-history? Toxicity assessment under environmentally relevant conditions.
Metal pollution in aquatic ecosystems translates into increased concentrations of sediment-bound metals, representing a risk for benthic species. This risk might be enhanced in soft and moderately hard waters, world widely distributed, due to the protective role of hardness against metal toxicity. As lead (Pb) and nickel (Ni) are amongst the more abundant metals in aquatic systems, and since their combined effects to benthic species have been overlooked, in this study we aimed to investigate the life-cycle toxicity of Pb and Ni (using spiked sediment) to the benthic species Chironomus riparius, considering both single and mixture exposures, in moderately hard water. Environmentally relevant concentrations of each metal were used (25 and 75 mg kg-1, based on a scenario of pollution by runoff waters from burnt forests), following a full factorial design. Effects of the mixture with the highest metal concentrations (Pb 75 mg kg-1 dw + Ni 75 mg kg-1 dw) were also assessed in the second generation. In the first generation, exposure to Pb increased emergence and the weight of males, and decreased time to emergence of both males and females. Conversely, exposure to Ni delayed female emergence and decreased the weight of imagoes. Summarizing, Pb affected more endpoints but showed an apparent positive effect, whereas Ni affected less endpoints but exhibited adverse effects. Reproduction was not affected by these metals. In the second generation, the mixture Pb 75 mg kg-1 + Ni 75 mg kg-1 dw delayed emergence and reduced the emerged female fraction and their weight. These results highlight that Pb and Ni can alter the structure of C. riparius populations at environmentally relevant concentrations, which signals potential repercussions in the dynamics and functioning of freshwater ecosystems under these contamination scenarios. The findings of the present study are relevant not only for metal-polluted environments, in general, but also for fire-affected ecosystems.


Covalent immobilization of proteins for the biosensor based on imaging ellipsometry.
In the development of biosensors, the immobilization of biomolecules at interfaces played a crucial role. The feasibility of using 3-aminopropyltriethoxysilane (APTES) and glutaraldehyde (Glu) to modify silicon surface to immobilize covalently protein for immunoassay with the biosensor based on imaging ellipsometry was investigated. The higher density and stability of human IgG layer could be obtained on the silicon surface modified with APTES and Glu than that on the silicon surface modified with dichlorodimethylsilane (DDS). The human IgG molecules immobilized covalently on APTES-Glu surface bound more anti-IgG molecules than that on DDS surface, which indicated that the human IgG molecules could maintain higher binding capability on APTES-Glu surface. Tween 20 was able to block the undesirable adsorption on APTES-Glu surface, and also enhanced the recognition between human IgG and its antibody on both APTES-Glu and DDS surfaces. The combination of this protein covalent immobilization and the biosensor has the potential to be developed into a fast, simple immunoassay technique.


Serum prolactin concentration in patients taking neuroleptic drugs.
Non-tumour causes of hyperprolactinaemia, including prolactin-elevating drugs, must be excluded. There is a general view that such drugs are unlikely to raise serum PRL above 3000 mU/I, but the literature is confusing. We report 8 patients receiving treatment with neuroleptic drugs, whose serum PRL concentrations were grossly elevated. Prolactin was measured using a 2-site immunofluorometric assay (Abbott Laboratories; reference range < 500 mU/l). Seven of the eight women (age range 24-49 years) were symptomatic (galactorrhoea, oligo- or amenorrhoea). Prolactin concentrations ranged from 3600 mU/l to 7300 mU/l. All patients had a normal pituitary CT scan. Five patients were treated with bromocriptine without detriment to their mental state. Prolactin can rise to concentrations associated with prolactinomas in patients on neuroleptic drugs. As it is rarely possible to stop the drugs to see if the PRL concentration will decline to normal, neuroradiology is required in these patients to exclude a vision-threatening macroprolactinoma before deciding on medical treatment.


A high-throughput platform for interpretation of metabolite profile data from pepper (Capsicum) fruits of 13 phenotypes associated with different fruit maturity states.
Nowadays, novel tools have been developed for efficient analysis and visualization of large-scale metabolite profile data associated with metabolic pathways. A high-throughput platform using PathVisio 3 combined with multivariate analysis is proposed for the first time. Additionally, this is the first analysis of the relationships among terpenoids monoterpene, sesquiterpene, triterpene, and tetraterpene during pepper fruit ripening, and their changes. This platform was successfully applied to interpret large-scale data related to 131 metabolites from mature and immature fruits of 13 pepper phenotypes. The carotenoid-derived volatiles, such as dihydroactinidiolide and β-ionone were closely correlated with carotenoids, indicating that the synthesis and degradation of carotenoids occurred in pepper fruit mature stage. Using PathVisio 3, the metabolic changes in pathway could be presented quickly, revealing the accumulation of stress-related metabolites, such as proline, capsaicin, and phenylalanine, in the mature stage. This approach could provide useful information about comprehensive biochemical regulation of fruit ripening.


Cytauxzoonosis.
Cytauxzoon felis is a hematoprotozoan parasite with a complex life cycle involving a tick-vector and a mammalian host. The mammalian hosts are all felidae but in the bobcat reservoir host, the parasite typically causes only a brief, self-resolving illness followed by a prolonged subclinical infection. In domestic cats, however, infection often leads to an acute febrile illness characterized by severe morbidity and mortality. Diagnosis is based on microscopic identification of parasites or molecular testing. Treatment for ill cats is expensive, difficult, and often unsuccessful. Prevention is quite possible and depends on avoidance of feeding by vector ticks.


Mechano growth factor E peptide inhibits invasion of melanoma cells and up-regulates CHOP expression via endoplasmic reticulum stress.
To evaluate the effects of mechano growth factor E peptide (MGF) on the invasive properties of melanoma cells. Melanoma cells (GLL19) were treated with 10, 20 and 30 ng MGF/ml for 24 h. Their invasive properties were investigated by transwell assay. Cytoskeleton reorganization was assessed via staining with phalloidin-FITC; lysyl oxidase (LOX) family gene expression was tested by qRT-PCR, and western blotting was used to detect expression of the matrix metalloproteinases (MMPs) and endoplasmic reticulum (ER) stress. MGF decreased the invasive capabilities of melanoma cells and induced changes in cytoskeleton distribution. MGF also down-regulated the expression of MMPs and up-regulated the expression of the cell apoptosis-related protein CHOP by inducing ER stress. MGF can decrease the invasive properties of melanoma cells and induce ER stress, promoting cell apoptosis. Thus, MGF represents a novel strategy for the potential treatment of patients presenting with cutaneous melanoma.


Thyroid metastasis from small cell lung carcinoma: a case report and review of the literature.
Small cell lung carcinoma frequently metastasizes to lymph nodes, liver, adrenal glands, bone, brain and pleura. Metastasis of small cell lung cancer to the thyroid gland is extremely rare. A 55-year-old Turkish man presented with a mediastinal mass intermingled with mediastinal lymphadenopathy, measuring 11cm in total, and encasing superior vena cava and deviating his trachea, esophagus and vascular structures. He had superior vena cava syndrome. His thyroid appeared normal on computed tomography of his chest. A bronchoscopic biopsy showed small cell lung carcinoma. Chemotherapy with cisplatin and etoposide and external radiotherapy was given. Six months after the presentation, multiple brain metastases were detected on magnetic resonance imaging. Chemotherapy was changed to topotecan and cranial irradiation was performed. At the same time, a right thyroid nodule was detected on computed tomography of his chest and showed growth in size in the following 4 months. A palpable right thyroid nodule came to our attention at that time, the 10th month of presentation. Free thyroxine, free triiodothyronine, thyroid-stimulating hormone, antithyroglobulin and antithyroid peroxidase antibodies were within normal limits. Thyroid ultrasonography showed a right thyroid lobe 26.2×16.8×15.7mm hypoechoic solid nodule with irregular borders. Ultrasonography-guided thyroid fine-needle aspiration biopsy showed metastasis from small cell lung carcinoma. His cranial metastases worsened. He developed right cervical lymph node, hepatic, pancreatic and meningeal metastases and died 15 months after the initial presentation and 9 months after the detection of thyroid metastasis by computed tomography of his chest. Our case and two previously reported cases were male, 55-years old or older and had history of more than 40 pack-years of cigarette smoking. All had metastatic disease elsewhere, when the thyroid metastasis was diagnosed by fine-needle aspiration biopsy. All had poor survival, between 9 and 18 months, after thyroid metastasis was diagnosed. We conclude that in a patient with a known history of malignant disease, the finding of a new thyroid mass should be promptly evaluated with a thyroid fine-needle aspiration biopsy to search for metastatic disease. The clinical features of our and two previously reported cases were summarized.


Follicular neoplasms: the role for observation, fine needle aspiration biopsy, thyroid suppression, and surgery.
The diagnosis and management of follicular carcinoma of the thyroid gland remains a controversial topic. Fine needle aspiration, although very sensitive with other types of thyroid cancer, has limited accuracy with follicular lesions. The role of suppression combined with observation has yet to gain widespread acceptance. The extent of surgical excision of follicular carcinoma also raises several competing views. The goal of this review is to address these issues and present an algorithm for the management of follicular neoplasms of the thyroid.


Novel computed tomographic analysis demonstrates differences in patterns of bone mineral content between fracture configurations in distal condylar fractures of the third metacarpal/metatarsal bones in 97 Thoroughbred racehorses.
To evaluate bone mineral content patterns between fracture configurations using novel CT image analysis. CT images from 97 Thoroughbred racehorses with third metacarpal/tarsal condyle fractures provide the case population for analysis. Fractures were grouped by radiographic appearance. Image analysis objectively measured area of highly attenuating pixels (aHAP), areal density of highly attenuating pixels (dHAP) utilizing novel convex hull analysis, and subjective assessment of apparent attenuation intensity ranking (AAIR) for each fracture. Differences between fracture configuration groups were evaluated. Analysis of dHAP identified lower-density regions of highly attenuating pixels in propagating fractures and higher-density regions of highly attenuating pixels in unicortical fractures (P = .028). Complete and incomplete configurations were almost indistinguishable in dHAP (P = 1.000). The ratio of dHAP between fractured and nonfractured condyles revealed higher density gradients between condyles in unicortical (P = .040) and incomplete (P = .031) fractures than propagating fractures. Differences in patterns of bone mineral content were identified between propagating, bicortical (incomplete and complete), and unicortical fractures of third metacarpal/tarsal bone condyles. Computer-assisted geometric measurement of dHAP identified on CT images could help to assess fracture risk in equine athletes. This application may have greater relevance as standing CT screening becomes more available.


Role of central serotonergic systems in the development of hypertension in spontaneously hypertensive rats.
The spontaneously hypertensive rat (SHR) maintained a higher blood pressure level at and after 8 weeks old than the genetical control Wistar-Kyoto strain (WKY). At 10 weeks old, the turnover rate of 5-hydroxytryptamine (5-HT) was lower in the hypothalamus of SHR than of WKY. Following portacaval anastomosis (PCA) in SHR, the blood pressure was significantly decreased in comparison with that of sham-operated control SHR. In WKY, no significant change in the blood pressure response was observed. PCA treatment increased the 5-HT turnover including that in SHR. If the SHR with PCA was bred with food pellets containing higher concentrations of leucine and isoleucine, the blood pressure increased and the 5-HT turnover decreased. These findings suggest that the central serotonergic system is involved in the development of hypertension.


Anticoagulation variability between centres: implications for comparative prosthetic valve assessment.
One of the major determinants in the choice of a mechanical prosthetic valve is that valve's thromboembolic record but the thromboembolic (TE) rates may be substantially influenced by the levels of anticoagulation achieved. A detailed study of anticoagulation variability was undertaken in 834 patients who received one or more of a particular prosthesis (Medtronic-Hall) in one centre during a 7-year period from 1979 to 1987, but who attended 27 different anticoagulant clinics spread over a wide area. In addition, a questionnaire was sent to all 89 practising cardiac surgeons in the UK asking for their preferred range of International Normalised Ratio (INR) for patients with mechanical prosthetic valves. Both the local study (with 16,866 INR observations) and the national questionnaire (with a 53% response) revealed an enormous amount of variability. Median INR values (semi-interquartile range) varied from 2.2 to 3.9 (0.8-2.5) according to the anticoagulant clinic attended. The range of INR preferred by UK cardiac surgeons, but presumably not necessarily achieved, varied from 1.8-2.2 to 3.0-4.8, with 64% of surgeons preferring an INR less than 3.0. In comparison, standard US practice is to maintain prothrombin times equivalent to INR values of 4.0-5.0. Unless anticoagulant practice can be standardised internationally, comparison of TE complications between centres is meaningless, and casts doubt on the validity of TE rates quoted for particular prostheses, unless accompanied by a detailed analysis of anticoagulant control.


Differential Pattern of Soluble Immune Markers in Asymptomatic Dengue, West Nile and Zika Virus Infections.
Infections with dengue virus (DENV), West Nile virus (WNV) and Zika virus (ZIKV) usually present similar mild symptoms at early stages, and most infections (~80%) are asymptomatic. However, these infections may progress to severe disease with different clinical manifestations. In this study we attempted to identify unique characteristics for each infection at the presymptomatic/asymptomatic stage of infection and compared levels of soluble immune markers that have been shown to be altered during clinical course of these viral infections. Levels of soluble markers were determined by Luminex-based assays or by ELISA in plasma samples from asymptomatic blood donors who were reactive for RNA from DENV (n = 71), WNV (n = 52) or ZIKV (n = 44), and a control or non-infected (NI) group (n = 22). Results showed that even in the absence of symptoms, increased interleukin (IL) levels of IL-12, IL-17, IL-10, IL-5, CXCL9, E-Selectin and ST2/IL-1R4; and decreased levels of IL-13 and CD40 were found in all flavivirus group samples, compared to those from NI donors. DENV-infected donors demonstrated variation in expression of IL-1ra and IL-2; WNV-infected donors demonstrated variation in expression of IL-1ra, P-Selectin, IL-4 and IL-5; ZIKV-infected donors demonstrated variation in expression of IL-1ra, P-Selectin, IL-4, RANK-L, CD40L and C3a. The findings suggest that, even in the presymptomatic/asymptomatic phase of the infection, different immunomodulation profiles were associated with DENV, WNV and ZIKV infections.


Reproducibility of Novel Soft-Tissue Landmarks on Three-Dimensional Human Facial Scan Images in Caucasian and Asian.
Three-dimensional surface imaging is established in many disciplines for objective facial acquisition regarding anthropometry. Former studies addressed the validation of landmark-based measurements for single race. In order to distinguish racial difference, the reproducibility of the landmark measurements must first be validated. Our purpose is to validate the reproducibility of 46 facial soft-tissue landmarks on x, y, z axes to prove their reliability as 3D reference points. The study included 80 European Caucasian and 80 Chinese volunteers. Standardized 3D surface imaging was performed using Vectra 3D system. Two raters identified and defined 46 landmarks (138 coordinates), then repeatedly 3D-imaged volunteers' facial region in separate sessions. Coordinates' reproducibility of landmarks is divided into three categories (< 0.5 mm, < 1 mm, and >1 mm) for intra- and inter-rater reproducibility assessments. Coordinates' reproducibility of 160 samples was distributed as follows: Intra-rater: < 0.5 mm (45%), < 1 mm (42%), >1 mm (13%); inter-rater: < 0.5 mm (31.2%), < 1 mm (42%), > 1 mm (26.8%). The reproducibility of landmarks in nasal tip region differs slightly between Caucasians and Asians. Compared to females, males typically have higher landmark reproducibility in lip and chin region. However, there were no differences in the reproducibility ranking of landmarks by gender. The majority of the 46 landmarks in the 3D plane are reproducible to 1 mm, which is clinically acceptable. All selected landmarks showed strong consistency across race and gender, suggesting their potential use as reference points in prospective clinical practice. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Impacts of water-sediment regulation on spatial-temporal variations of heavy metals in riparian sediments along the middle and lower reaches of the Yellow River.
The water-sediment regulation scheme (WSRS) of dams influences the desorption, resuspension, and deposition processes of riparian sediments, which in turn affect the spatial-temporal variations of heavy metals (HMs) in riparian sediments and leads to severe degradation of soil and water quality. However, the difference between the trapping effect of dams and the redistribution effects of the WSRS on HMs in riparian sediments, as well as the consecutively seasonal change of HMs after the WSRS, are rarely reported. To fill this gap, the concentrations of six HMs including Cd, Cr, Cu, Ni, Pb, and Zn in riparian sediments along the Xiaolangdi Dam (XLD) Reservoir and its downstream reach were investigated, and the contamination level and potential ecological risk of HMs were assessed, to differentiate the effects of the XLD and its WSRS on the concentration, contamination level, and potential ecological risks of HMs. The results indicated that the mean HM concentrations in riparian sediments were higher than the background values in the study area and showed significant spatial and temporal variations. However, the regional differences of HM concentrations caused by the trapping effect of the XLD were less than the seasonal differences caused by the redistribution effects of the WSRS. The contamination and ecological risk assessment indicated that riparian sediments in the study area were contaminated by the six HMs, particularly by Cd and Pb, which overall exhibited a high and moderate ecological risk, respectively. The sources for Pb were likely agricultural inputs, while the sources for Cd should be attributed to both industrial and agricultural inputs. Overall, the trapping effect of the XLD led to the accumulation of HMs in riparian sediments along the reservoir area, while the regulation effects of the WSRS resulted in the redistribution of HMs in riparian sediments from the reservoir area to the downstream reach.


Rapid determination of apixaban concentration in human plasma by liquid chromatography/tandem mass spectrometry: application to pharmacokinetic study.
We described the development and full validation of a rapid, high throughput sensible and accurate LC method using tandem mass spectrometry detection for determining apixaban concentration with [(¹³C, ²H₇]-apixaban as internal standard in human plasma. Plasma pretreatment involved a one-step protein precipitation with methanol. The separation was performed by reverse-phase chromatography on a Luna MercuryMS C18 column (20 mm × 4 mm × 3 μm) column. The multiple reaction monitoring transitions used for quantification were m/z 460.20→443.27 and 460.20→198.99 for apixaban, 468.22→451.30 for [(¹³C, ²H₇]-apixaban in the electrospray positive ionization mode. The method was linear over the concentration range of 5-500 μg/L. The intra- and inter-day precision values were below 14% and accuracy was from 90.0 to 105.8% at all quality control levels. Sample analysis time was less than 10 min including sample preparation. The present method was successfully applied to a pharmacokinetic study following oral administration of apixaban.


Nanoemulsion-directed growth of MOFs with versatile architectures for the heterogeneous regeneration of coenzymes.
As one of the most appealing strategies for the synthesis of nanomaterials with various architectures, emulsion-directed methods have been rarely used to control the structure of metal-organic frameworks (MOFs). Herein, we report a versatile salt-assisted nanoemulsion-guided assembly to achieve continuous architecture transition of hierarchical Zr-based MOFs. The morphology of nanoemulsion can be facilely regulated by tuning the feed ratio of a dual-surfactant and the introduced amount of compatible hydrophobic compounds, which directs the assembly of MOFs with various architectures such as bowl-like mesoporous particle, dendritic nanospheres, walnut-shaped particles, crumpled nanosheets and nanodisks. The developed dendritic nanospheres with highly open and large mesochannels is successfully used as matrix for the co-immobilization of coenzymes and corresponding enzymes to realize the in situ heterogeneous regeneration of NAD+. This strategy is expected to pave a way for exploring sophisticated hierarchical MOFs which can be competent for practical applications with bulk molecules involved.


Knowledge and barriers related to prostate and colorectal cancer prevention in underserved black men.
This qualitative study examined underserved black males' perspectives about prostate and colorectal cancer screening. Black male residents of Newark, NJ, > or =18 years of age, were recruited to participate in focus groups. Two groups were conducted with a total of 24 participants. Transcripts were analyzed using an immersion/crystallization approach. Three major themes were identified, while men reflected on their experiences with prostate and colorectal cancer screening: (1) motivation for seeking screening; (2) fear associated with screenings: and (3) healthcare system barriers (e.g., patient-doctor relationships, insurance and mistrust of healthcare professionals). Participants also gave recommendations on how to increase preventive screening. Fear and past experiences with healthcare serve as motivators and demotivators of preventive screening behavior. Interventions that address motivation and fear are recommended to increase preventive screening among this population.


Protein phosphatase 2A promotes endothelial survival via stabilization of translational inhibitor 4E-BP1 following exposure to tumor necrosis factor-α.
Tumor necrosis factor-α (TNFα) may change from a stimulator of reversible activation of endothelial cells (ECs) to a killer when combined with cycloheximide (CHX). The means by which endothelial cells are destined to either the survival pathway or the apoptotic pathway are not fully understood. We investigated the role of p38 mitogen-activated protein kinase (MAPK) and protein phosphatase 2A (PP2A) activation and their regulation of 4E-BP1 stability in ECs to determine whether this pathway contributes to apoptosis induced by TNFα and CHX. Apoptosis was induced in human umbilical vein ECs (HUVECs) by treating them with a combination of TNFα and CHX (TNFα/CHX). Activation of p38 MAPK was increased in HUVECs undergoing apoptosis, which was associated with degradation of eukaryotic initiation factor 4A regulator 4E-BP1 in a p38 MAPK-dependent manner. CHX attenuated a TNFα-stimulated increase in the expression and activity of PP2A. Silencing PP2A expression with small interfering RNA transfection mimicked CHX sensitization, increasing HUVEC apoptosis with TNFα stimulation and suggesting a protective role for PP2A in the apoptotic process. Our data suggest that (1) TNFα stimulates PP2A and HUVECs elude apoptosis by PP2A-dependent dephosphorylation of p38 MAPK, and (2) CHX-induced inhibition of PP2A leads to maintenance of p38 activity and degradation of 4E-BP1, resulting in enhanced TNFα-induced apoptosis.


[Complex regional pain syndrome].
The Complex Regional Pain Syndrome (previously algodystrophy) is a rare affliction that usually affects a distal extremity (hand, foot). It occurs most frequently within weeks following a traumatic injury or stroke. It is a syndromic entity whose diagnosis is based on precise criteria, known as the Budapest criteria, excluding any disease that better explains the symptoms. The treatment must be given early. Functional restoration (physiotherapy, occupational therapy) is at the heart of the treatment, along with psychoeducation. Inappropriate disuse and avoidance, often encountered, must be combated. Bisphosphonates or steroids are first-line drugs at early stages. The evolution is often long, but the prognosis is favorable in about 75 % of cases (≤ 1 year).


Does the channel for nascent peptide exist inside the ribosome? Immune electron microscopy study.
MS2 phage RNA-directed synthesis of an N-terminal polypeptide of the phage coat protein on Escherichia coli 70 S ribosomes was initiated in a cell-free system with the N-dinitrophenyl derivative of methionyl-tRNAFMet) and performed in the absence of tyrosine, lysine, cysteine and methionine. As a result, the translating ribosomes carried peptides up to 42 amino acid residues in length with the dinitrophenyl hapten at the N-ends. Using the immune electron microscopy technique the positions of the nascent peptide N-ends on the 70 S ribosomes have been visualized. It has been found that (i) the N-ends of nascent peptides of these lengths are accessible to antibodies, (ii) the exit site of a nascent peptide is the pocket between the base of the central protuberance and the L1 ridge on the 50 S subunit, i.e. presumably its peptidyl transferase center, and (iii) the further pathway of a nascent peptide seems to proceed along the groove on the external surface of the 50 S subunit.


How a Patient Personalised Clinical Pharmacy Programme Can Secure Therapeutic Care in an Orthogeriatric Care Pathway (5P Project)?
A new model was developed for integrating a personalised clinical pharmacy programme (5P project) into the orthogeriatric care pathway. To secure the therapeutic care of orthogeriatric patients. Prospective descriptive study in a multisite teaching hospital from June 2019 to January 2020. Patients aged ≥75 years admitted for hip fracture. A prescription review was performed for all patients at inclusion. Other clinical pharmacy activities (additional prescription review, pharmaceutical interviews, medication reconciliation) were dedicated to "high-risk" patients. Potential medication errors (ME), either pharmaceutical interventions (PI) or unintentional discrepancies (UID), were recorded. The potential clinical impact of PI was evaluated by a pluriprofessional expert panel using a validated tool. In the 455 patients included, 955 potential ME were detected, that is ≥1 potential ME for 324/455 (71%) patients. In acute care, 561 PI were formulated during prescription review for 440/455 (97%) patients and 348/561 (62%) were accepted by physicians. Medication reconciliation was performed for 213 patients, 316 UID were identified. In rehabilitation units, a second prescription review was performed for 112/122 (92%) "high-risk" patients, leading to 61 PI. The clinical impact was evaluated for 519/622 (83%) PI. A consensus was obtained for 310/519 (60%) PI: 147/310 (47%) were rated as having minor clinical impact, 138/310 (45%) moderate, 22/310 (7%) major, 2/310 (0.6%) vital, and 1/310 (0.3%) null. The 5P project secured the orthogeriatric care pathway by detecting a great number of potential ME, including PI mostly considered as having a significant clinical impact.


Brain health is independently impaired by E-vaping and high-fat diet.
Tobacco smoking and high-fat diet (HFD) independently impair short-term memory. E-cigarettes produce e-vapour containing flavourings and nicotine. Here, we investigated whether e-vapour inhalation interacts with HFD to affect short-term memory and neural integrity. Balb/c mice (7 weeks, male) were fed a HFD (43% fat, 20 kJ/g) for 16 weeks. In the last 6 weeks, half of the mice were exposed to tobacco-flavoured e-vapour from nicotine-containing (18 mg/L) or nicotine-free (0 mg/L) e-fluids twice daily. Short-term memory function was measured in week 15. HFD alone did not impair memory function, but increased brain phosphorylated (p)-Tau and astrogliosis marker, while neuron and microglia levels were decreased. E-vapour exposure significantly impaired short-term memory function independent of diet and nicotine. Nicotine free e-vapour induced greater changes compared to the nicotine e-vapour and included, increased systemic cytokines, increased brain p-Tau and decreased postsynaptic density protein (PSD)-95 levels in chow-fed mice, and decreased astrogliosis marker, increased microglia and increased glycogen synthase kinase levels in HFD-fed mice. Increased hippocampal apoptosis was also differentially observed in chow and HFD mice. In conclusion, E-vapour exposure impaired short-term memory independent of diet and nicotine, and was correlated to increased systemic inflammation, reduced PSD-95 level and increased astrogliosis in chow-fed mice, but decreased gliosis and increased microglia in HFD-fed mice, indicating the inflammatory nature of e-vapour leading to short term memory impairment.


Vesicular movements in the growth cone.
Growth cones, which are the highly motile tips of extending neuronal processes in developing neurons, have many vesicles. These vesicles are likely essential for the membrane expansion that is required for nerve growth, and probably coordinate with rearrangement of the cytoskeletons. Such mechanisms are poorly understood from molecular and cell biological aspects. Recently, we used superresolution microscopic approaches and described new mechanisms that are involved in the interaction between the vesicles and F-actin in the leading edge of the peripheral domain. Vesicles mainly accumulate in the central domain of growth cones. However, the dynamics of vesicles in each domain, for example, clathrin dependency, are totally distinct from each other. Here, we discuss the diversity of the dynamics of vesicular and related proteins that play different roles in nerve growth.


Occurrence of selected antibiotics and antiretroviral drugs in Nairobi River Basin, Kenya.
In this paper, we investigated the occurrence of three antibiotics (sulfamethoxazole, trimethoprim and ciprofloxacin) and three antiretroviral (lamivudine, nevirapine and zidovudine) drugs in the Nairobi River Basin, Kenya. The analytical procedure involved extraction using solid phase extraction followed by liquid chromatography-electrospray ionization tandem mass spectrometry (SPE-LC-ESI-MS/MS). In this study, 40 sites were selected for sampling, including 38 sites along the rivers and 2 wastewater treatment effluent sites. All the studied compounds were detected with sulfamethoxazole having the highest detection frequency of 97.5% and ciprofloxacin had the lowest at 60%. The results showed that the concentration of the drugs increased in highly populated regions especially within the informal settlements. The maximum (median) concentrations in the river waters for sulfamethoxazole, trimethoprim, ciprofloxacin, lamivudine, nevirapine and zidovudine in ng/L were 13,800 (1800), 2650 (327), 509 (129), 5430 (1000), 4860 (769), and 7680 (660), respectively. The maximum concentrations in the river waters were generally higher than those of the wastewater treatment plant effluents signifying that the rivers are substantially contaminated by domestic wastewater. The environmental risk was evaluated by calculating the risk quotients (RQs) for algae, daphnia and fish based on the maximum and median concentrations of the analytes in the river basin and was expressed as the ratios of measured environmental concentrations (MEC) to predicted no effect concentrations (PNEC). The RQs ranged from 0 to 507.8 and apart from lamivudine that had a low RQ, all the other analytes had RQ>1 at maximum and median measured concentrations for at least one taxonomic group. The high RQs are indicative of possible adverse ecological effects and calls for corrective and mitigation strategies.


Inhibition of STAT-mediated cytokine responses to chemically-induced colitis prevents inflammation-associated neurobehavioral impairments.
Depression can be associated with chronic systemic inflammation, and production of peripheral proinflammatory cytokines and upregulation of the kynurenine pathway have been implicated in pathogenesis of depression. However, the mechanistic bases for these comorbidities are not yet well understood. As tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), which convert tryptophan to kynurenine, are rate-limiting enzymes of the kynurenine pathway, we screened TDO or IDO inhibitors for effects on the production of proinflammatory cytokines in a mouse macrophage cell line. The TDO inhibitor 680C91 attenuated LPS-induced pro-inflammatory cytokines including IL-1β and IL-6. Surprisingly, this effect was TDO-independent, as it occurred even in peritoneal macrophages from TDO knockout mice. Instead, the anti-inflammatory effects of 680C91 were mediated through the suppression of signal transducer and activator of transcription(STAT) signaling. Furthermore, 680C91 suppressed production of proinflammatory cytokines and STAT signaling in an animal model of inflammatory bowel disease. Specifically, 680C91 effectively attenuated acute phase colon cytokine responses in male mice subjected to dextran sulfate sodium (DSS)-induced colitis. Interestingly, this treatment also prevented the development of anxiodepressive-like neurobehaviors in DSS-treated mice during the recovery phase. The ability of 680C91 to prevent anxiodepressive-like behavior in response to chemically-induced colitis appeared to be due to rescue of attenuated dopamine responses in the nucleus accumbens. Thus, inhibition of STAT-mediated, but TDO-independent proinflammatory cytokines in macrophages can prevent inflammation-associated anxiety and depression. Identification of molecular mechanisms involved may facilitate the development of new treatments for gastrointestinal-neuropsychiatric comorbidity.


The prognosis of retinoblastoma in terms of survival. A computer assisted study. Part II.
At present there is no satisfactory classification or staging system. In order to compare the Reese classification (Reese, 1963), the Essen classification (Höpping, 1983) and a new classification, a method of evaluating different parameters was created in order to get an optimal classification of survival.


Use of the laser in the oral cavity.
Laser surgery is now commonly performed for lesions arising in the oral cavity. The laser provides certain advantages relating to the precision of tissue destruction and some hemostatic capabilities. However, it is the author's impression that it provides no special healing or cancer-killing advantages. It can be used for a wide variety of surgical procedures involving benign lesions. Its use for resection of oral cavity malignancies is restricted to verrucous cancers and smaller cancers. When the proper techniques are used to protect both the patient and the surgeon and other operating room personnel, it can be a safely performed surgical adjunct that has certain advantages over standard surgical approaches.


70K heat shock related proteins stimulate protein translocation into microsomes.
A yeast cytosol is shown to contain two distinct activities that stimulate protein translocation across microsomal membranes. One activity was purified. It consists of two constitutively expressed 70K heat shock related proteins that increase the rate of translocation. Possible mechanisms of action of these proteins are discussed.


New applications and innovations in the electrophoretic separation of proteins from the eye lens core (nucleus).
The electrophoretic separation of proteins from the eye lens core (nucleus) has been a useful procedure in population and taxonomic studies. The possibility exists that this method may be applied to obtaining behavioral, environmental, and perhaps other types of information. Because of the increasing usefulness of this approach with nuclear lens proteins, efforts to optimize the methodology are continually being made. A complete system, incorporating new developments and applied to four fish species, is described in this report.


A mutation in the tRNA(Leu)(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies.
Mitochondrial encephalomyopathies are usually divided into three distinct clinical subgroups: (1) mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS); (2) myoclonus epilepsy associated with ragged-red fibres (MERRF); and (3) chronic progressive external ophthalmoplegia (CPEO) including Kearns-Sayre syndrome. Large deletions of human mitochondrial DNA and a transition mutation at the mitochondrial transfer RNALys gene give rise to CPEO including Kearns-Sayre syndrome and MERRF, respectively. Here we report an A-to-G transition mutation at nucleotide pair 3,243 in the dihydrouridine loop of mitochondrial tRNA(Leu)(UUR) that is specific to patients with MELAS. Because this mutation creates an ApaI restriction site, we could perform a simple molecular diagnostic test for the disease. The mutation was present in 26 out of 31 independent MELAS patients and 1 out of 29 CPEO patients, but absent in the 5 MERRF and 50 controls tested. Southern blot analysis confirmed that the mutant DNA always coexists with the wild-type DNA (heteroplasmy).


Bacterial differentiation via gradual activation of global regulators.
Bacteria have evolved to adapt to various conditions and respond to certain stress conditions. The ability to sense and efficiently reply to these environmental effects involve versatile array of sensors and global or specific regulators. Interestingly, modulation of the levels of active global regulators enables bacteria to respond to diverse signals via a single central transcriptional regulator and to activate or repress certain differentiation pathways at a spatio-temporal manner. The Gram-positive Bacillus subtilis is an ideal bacterium to study how membrane bound and cytoplasmic sensor kinases affect the level of phosphorylated global regulator, Spo0A which in response activates genes related to sliding, biofilm formation, and sporulation. In addition, other global regulators, including the two-component system DegS-DegU, modulate overlapping and complementary genes in B. subtilis related to surface colonization and biofilm formation. The intertwinement of global regulatory systems also allows the accurate modulation of differentiation pathways. Studies in the last decade enable us to get a deeper insight into the role of global regulators on the smooth transition of developmental processes in B. subtilis.


Outcome of treatment at a psycho-educational day unit for young children.
The outcome of treatment at the psychiatric day centre of the Red Cross War Memorial Children's Hospital in Cape Town is described. Forty-five children were followed up for 2-6 years after discharge--12 were asymptomatic, 22 moderately improved and 11 unimproved. Possible means of improving outcome are discussed.


Differentiating organic and conventional sage by chromatographic and mass spectrometry flow injection fingerprints combined with principal component analysis.
High-performance liquid chromatography (HPLC) and flow injection electrospray ionization with ion trap mass spectrometry (FIMS) fingerprints combined with principal component analysis (PCA) were examined for their potential in differentiating commercial organic and conventional sage samples. The individual components in the sage samples were also characterized with an ultraperformance liquid chromatograph with a quadrupole-time-of-flight mass spectrometer (UPLC Q-TOF MS). The results suggested that both HPLC and FIMS fingerprints combined with PCA could differentiate organic and conventional sage samples effectively. FIMS may serve as a quick test capable of distinguishing organic and conventional sages in 1 min and could potentially be developed for high-throughput applications, whereas HPLC fingerprints could provide more chemical composition information with a longer analytical time.


Impact of margin ablation after EMR of large nonpedunculated colonic polyps in routine clinical practice.
Owing to its simplicity, effectiveness, and safety, EMR is the preferred treatment for the majority of large (≥20 mm) nonpedunculated colonic polyps (LNPCPs); however, residual and recurrent adenomas (RRAs) encountered during surveillance constitute a major limitation. Thermal ablation of the post-EMR mucosal defect margin has been shown to be highly efficacious in reducing RRA in a randomized trial setting, but data on effectiveness in clinical practice are scarce. We aimed to determine the effectiveness of this technique for reducing RRAs in routine clinical practice. We analyzed data collected in 3 hospitals in Israel: Prospective data were available in 2 hospitals where margin thermal ablation with snare-tip soft coagulation (STSC) is routinely performed after EMR of LNPCP (TA-EMR). Only retrospective data were available from the third center, which exclusively did not perform STSC (standard EMR] [S-EMR]), during the study period. Surveillance was performed 4 to 6 months after resection. RRA was assessed endoscopically with high-definition white light and optical chromoendoscopy. The primary endpoint was RRA at first surveillance colonoscopy. Data from 764 patients with 824 LNPCPs were analyzed. The patient and lesion characteristics were similar between the groups. Four hundred sixty-four LNPCPs were treated by TA-EMR and 360 LNPCPs by S-EMR. RRA at first surveillance colonoscopy was detected in 14 (3.6%) of lesions in the TA-EMR group compared with 96 (31.6%) in the S-EMR group (P < .001; RR = .14; 95% CI, .07-.29). Adverse events were comparable between the 2 groups. TA-EMR leads to a significant reduction in post-EMR recurrence in routine clinical practice.


Convergent effects from vestibulospinal tract and primary cutaneous afferent fibers on motoneurons to proximal lower limb flexor and extensor muscles in humans.
In human subjects, the latency and magnitude of cutaneomuscular test reflexes, evoked by stimulation of the sural nerve in the contralateral and ipsilateral quadricep and hamstring muscles, were investigated during static tilts in the pitch axis. The ANOVA demonstrated a highly significant, tilt-dependent modulation of the magnitude of the test reflex for the initial phase of both ipsilateral quadriceps and ipsilateral hamstrings. These results are consistent with results from a similar study on human ankle muscles and provide further evidence that the tilt-dependence of these cutaneomuscular reflexes originates from activity in the otolith receptors.


Interplays between pre- and post-natal environments affect early-life mortality, body mass and telomere dynamics in the wild.
Early-life conditions are crucial determinants of phenotype and fitness. The effects of pre- and post-natal conditions on fitness prospects have been widely studied but their interactive effects have received less attention. In birds, asynchronous hatching creates challenging developmental conditions for the last-hatched chicks, but differential allocation in last-laid eggs might help to compensate this initial handicap. The relative importance and potential interaction between pre- and post-hatching developmental conditions for different fitness components remains mostly unknown. We manipulated hatching order in wild pied flycatchers (Ficedula hypoleuca), creating three groups: natural asynchrony (last-laid eggs hatching last), reversed asynchrony (last-laid eggs hatching first) and hatching synchrony (all eggs hatching at once). We examined the effects of these manipulations on early-life survival, growth and telomere length, a potential cellular biomarker of fitness prospects. Mortality was mostly affected by hatching order, with last-hatched chicks being more likely to die. Early-life telomere dynamics and growth were influenced by the interplays between laying and hatching order. Last-laid but first-hatched chicks were heavier but had shorter telomeres 5 days after hatching than their siblings, indicating rapid early growth with potential adverse consequences on telomere length. Synchronous chicks did not suffer any apparent cost of hatching synchronously. Impaired phenotypes only occurred when reversing the natural hatching order (i.e. developmental mismatch), suggesting that maternal investment in last-laid eggs might indeed counterbalance the initial handicap of last-hatched chicks. Our experimental study thus highlights that potential interplays between pre- and post-natal environments are likely to shape fitness prospects in the wild.


Effect of aflatoxin B1 on hepatic polyribosomes and protein synthesis in the rat.
This study was concerned with the effect of aflatoxin B1 on protein synthesis in rat liver. Specifically, the effect of the administration of aflatoxin B1 (6.0 mg/kg body weight) on hepatic polyribosomes (free and membranebound), protein synthesis in vitro, and initiation factors activity of rats within 3-12 h was investigated. The results revealed that aflatoxin B1 rapidly led to disaggregation of free and membrane-bound polyribosomes, to inhibition of in vitro protein synthesis by both populations of polyribosomes, to little or no effect on the activities of initiation factors, and to defective ribosomes, particularly the 60S ribosomal subnits, of both types of polyribosomes. Comparative studies on the effects of aflatoxin B1 and actinomycin D revealed progressive disaggregation by both hepatic free and membrane-bound polyribosomes after aflatoxin B1 but not only of the free polyribosomes after actinomycin D.


Implementation of telemedicine screening for retinopathy of prematurity in rural areas in Guatemala.
To report findings of a telemedicine retinopathy of prematurity (ROP) screening program in six neonatal units in rural areas of Guatemala, using a portable, noncontact, 40° field digital fundus camera (Pictor Plus) operated by trained technicians. National ROP Program Guidelines screening criteria were used: gestational age <36 weeks and/or birth weight (BW) <2000 g, or GA <36 weeks but BW ≥2000 g, with qualifying medical history. Retinal images were obtained by two technicians and graded by ophthalmologists experienced in ROP. Infants with signs of pre-plus or plus disease in one or both eyes were referred for clinical examination. Screening was stopped when retinal vessels in anterior zone II were normal on two successive evaluations or the infant had reached 45 week's postmenstrual age. A total of 418 of 1,890 eligible infants (22.1%) were screened. Mean GA was 33.9 ± 2.2 weeks (range, 27-36), and mean BW 1728.3 ± 379.3 g (range, 840-2830 g). Thirty-three infants (8.6%) developed plus or pre-plus disease, and 19 (58%) underwent ophthalmologic examination. Fifteen infants were confirmed with type 1 ROP, and 14 were treated. Mean GA of treated infants treated was 33.6 ± 3.0 weeks (range, 32-34.9), and mean BW was 1,646 ± 245.8 g (range, 1100-1774.1 g). Imaging with a noncontact fundus camera can facilitate detection of treatable ROP in countries with limited resources. Strengthening the health systems, including motivation and continued training of neonatal intensive care personnel is essential to improve and maintain program effectiveness. Reasons for, and interventions to address the low uptake of screening need to be explored to extend coverage of ROP screening to district hospitals in Guatemala.


Can medical simulation and team training reduce errors in labor and delivery?
Patient safety is one of the most pressing challenges in health care today, and there is no question that medical errors occur and that patients are worried about them. Currently, there is a belief that the availability of medical simulations and the knowledge gained from the science of team training may improve patient outcomes, and there is a paradigm shift occurring in many universities and training programs. This article discusses two strategies that, when combined, may reduce medical error in the labor and delivery suite: team training and medical simulation.


Occurrence of bacterial indicators and bacteriophages infecting enteric bacteria in groundwater in different geographical areas.
The aim of this research was to determine the suitability of coliphages (bacteriophages) for assessing the microbial quality of groundwater. The number of several bacterial indicators (faecal coliforms, Escherichia coli, enterococci and spores of sulfite-reducing clostridia) and bacteriophages (somatic coliphages, F-specific RNA bacteriophages and bacteriophages infecting Bacteroides fragilis) were determined in groundwater of aquifers in various geographical areas. Results show that the relative abundance, determined as percentages of positive detections, of the bacterial indicators and bacteriophages varies depending on the aquifer. A single bacterial indicator may not be enough to assess microbiological quality in certain aquifers. One bacterial indicator and a bacteriophage parameter provide more information than two bacterial indicators. Coliphages (CPH) provide different information from that provided by bacterial indicators on the microbial quality of groundwater in different geographical areas. Easy, fast and inexpensive methods for the detection of CPH are feasible in both industrialized and developing countries.


Health factors in colostrum.
Colostrum is a breast milk produced after the birth of the newborn and lasts for 2-4 days. Colostrum is very important part of breast milk and lays down the immune system and confers growth factors and other protective factors for the young ones in mammals. This is the source of passive immunity achieved by the mother and is transferred to the baby. This is the major source of secretory IgA and gives protection against gastrointestinal infections. In view of so many health factors through colostrum, the use of colostrum has been extended to so many health problems of mankind. Human and bovine colostrums have many similarities barring that bovine colostrum can be obtained in large quantity, so bovine colostrum has been used in various disorders in human beings. This is the nature's gift that is for the young ones to grow as well as for the treatment of many health problems in older age group.


Exclusion of birds from bilberry stands: impact on insect larval density and damage to the bilberry.
The bilberry (Vaccinium myrtillus L.), is the dominant plant in the field layer of many boreal forests in northern Sweden. It is utilized by several herbivorous insect larvae as food (i.e. Lepidoptera: Geometridae, Tortricidae and Hymenoptera: Symphyta). Total density of insect larvae was 63% lower where birds had access to larvae compared to exclosures. Larvae with a feeding behaviour which exposes them to birds (geometrids and sawflies) showed a pronounced reduction in density when exposed to bird predators. Density of larvae with a concealed feeding behaviour (tortricids) was unaffected by birds. The frequency of larval damage to bilberry annual shoots was significantly higher in areas where larval density was high due to exclusion of birds. I concluded that birds have the potential to heavily modify the interaction between bilberry and insect larvae.


[3D-ultrasound: a valuable adjunct for therapy planning and follow-up of head and neck tumours].
The three-dimensional visualization of orofacial tumours and adjacent organs at risk of infiltration is an important requirement for staging, therapy planning and follow-up. Artifacts from the mandible or metal implants often reduce the diagnostic power of computed tomography (CT). The value of 3D-ultrasound (3D-US) in respect to the standard methods CT and magnetic resonance imaging (MRI) was therefore analyzed. Between 9/97 and 10/99 the visualization of orofacial tumours in 243 patients by 3D-US was examined, classified on a five-point scale and compared to the corresponding CT and MRI scans. Complete visualization of the tumours was possible in 85.6 % by 3D-US, whereas the rates of MRI and CT were lower with 77.4 % and 61.3 % respectively, mainly because of artifacts. The best combinations of methods, 3D-US + CT (96.7 %) and 3D-US + MRI (95.1 %) gave almost equivalent results, whereas CT + MRI (83.5 %) was inferior. In 2.5 % of the cases none of the methods produced adequate results. By free selection of sectional planes and direct correlation to the clinical findings 3D-ultrasound can improve staging, therapy planning and follow-up of orofacial tumours, especially in the case of small tumour size, dental crowns/inlays, metal implants or contraindications to MRI.


A diagnosis of prediabetes when combined with lifestyle advice and support is considered helpful rather than a negative label by a demographically diverse group: A qualitative study.
The aim of this study was to explore the experience and perceptions of a diagnosis of prediabetes among a demographically diverse sample of New Zealanders who had, and had not, regressed to normoglycaemia following participation in a primary care nurse-delivered intervention for 6 months. The sample included Indigenous Māori who have high rates of diabetes and associated co-morbidities. A purposefully selected sample of 58 people with prediabetes and BMI >25 kg/m2, stratified by male/female, Māori/non-Māori, and those who had/had not regressed to normoglycaemia, after completing 6-months of a prediabetes intervention were interviewed. Interviews were audio-recorded and transcribed. Data were analysed by thematic analysis. Most participants recalled being shocked when told they had prediabetes, but they did not perceive the diagnosis to be a label in a negative sense, and some, described the diagnosis as helpful. Participants appreciated knowing that prediabetes could be reversed, and the opportunity to be able to take supported action and make lifestyle changes through the nurse-delivered prediabetes lifestyle intervention. Participants' clear preference was to take control and make dietary changes, not to take Metformin. Prediabetes was not considered a negative label, but an opportunity, when coupled with a primary care nurse-delivered dietary intervention.


Conservative and surgical treatment of acute posttraumatic tracheobronchial injuries.
Acute posttraumatic tracheobronchial lesions are rare events associated with significant morbidity and mortality. They are caused by blunt and penetrating trauma, or they are iatrogenic, appearing after intubation or tracheotomy. Although surgery has traditionally been considered the treatment of choice for these injuries, recent reports show that conservative treatment can be effective in selected patients. The aim of this study was to evaluate the role of surgical and conservative management of these lesions, differentiated on the basis of clinical and endoscopic criteria. From January 1993 to October 2010, a total of 50 patients with acute posttraumatic tracheobronchial lesions were referred for treatment to our department. In all, 36 patients had iatrogenic injuries of the airway, and 14 had lesions resulting from blunt or penetrating trauma. Of the 30 patients who underwent surgery, the lesion was repaired with interrupted absorbable sutures in 29; the remaining patient, with an associated tracheoesophageal fistula, underwent single-stage tracheal resection and reconstruction and closure of the fistula. In all, 20 patients were treated conservatively: clinical observation in 5 patients, airway decompression with a mini-tracheotomy cannula in 4 spontaneously breathing patients, and tracheotomy with the cuff positioned distal to the lesion in 11 mechanically ventilated patients. One surgical and one conservatively-managed patient died after treatment (4% overall mortality). Complete recovery and healing were achieved in all the remaining patients. Surgery remains the treatment of choice for posttraumatic lesions of the airway. However, conservative treatment based on strict clinical and endoscopic criteria-stable vital signs; effective ventilation; no esophageal injuries, signs of sepsis, or evidence of major communication with the mediastinal space-enables favorable results to be achieved in selected patients.


Genotoxicity of complex mixtures: strategies for the identification and comparative assessment of airborne mutagens and carcinogens from combustion sources.
Two strategies for assessment of the toxicity of complex mixtures are described and illustrated with examples from genotoxicity studies of complex combustion mixtures. The first, a strategy for identifying biologically active compounds or compound classes in complex mixtures, is called bioassay-directed fractionation and characterization. The identification and assessment of mutagens and potential carcinogens in complex mixtures has been significantly advanced by the use of short-term genetic bioassays. Bioassay-directed fractionation coupled with new analytical characterization methods has provided the tools needed to more efficiently identify potential carcinogens in complex combustion emissions and urban air samples. These studies have shown that a significant portion of the mutagenicity in combustion emissions and urban air is found in fractions more polar than polynuclear aromatic hydrocarbons (PAHs). A second strategy, the comparative potency method, provides an approach to evaluating the relative toxicities of a series of mixtures. The comparative mutagenicity and carcinogenicity of a series of combustion emissions has been assessed using dose-response studies in bacteria, mammalian cells, and rodents. Comparative mutagenic and tumorigenic emission rates or emission factors provide a means to directly compare the relative hazard of the sources. This data base has also been used to develop a comparative risk assessment methodology for combustion emissions.


Antiatherosclerotic effects of oral cicaprost in experimental hypercholesterolemia in rabbits.
The efficacy of the oral prostacyclin mimetic cicaprost in preventing atheromatous plaque formation was studied in an in vivo model of experimental hypercholesterolemia. New Zealand white rabbits were fed either standard chow or a cholesterol-enriched (1%) diet for 12 weeks. Cicaprost was added to the drinking water in a non-hypotensive dose (5 micrograms/kg/day) and withdrawn 3 days prior to studying platelet, leukocyte and endothelial function. In cholesterol-fed rabbits, oral cicaprost reduced the aortic intimal surface covered by atheromatous lesions from 84 to 63% (P < 0.05). There was no major difference in serum lipid composition between cicaprost- and vehicle-treated animals. In hyper-cholesterolemic rabbits there was a significant impairment of endothelium-dependent relaxations. Cicaprost treatment considerably improved this endothelial function but had no effect in rabbits receiving standard diet. In addition, platelet and leukocyte hyperreactivity, as seen in hypercholesterolemic rabbits, were largely reduced by cicaprost treatment. These data are the first to demonstrate marked antiatherosclerotic effects of long-term oral prostacyclin treatment. The mechanism may be related to improved endothelial function and subsequent prevention of secondary platelet and neutrophil hyperreactivity.


Amelioration of beta654-thalassemia in mouse model with the knockdown of aberrantly spliced beta-globin mRNA.
Large amounts of aberrantly spliced mRNA from the beta(654) allele was present in erythroid cells, which might impair the erythropoiesis. A therapeutic strategy for beta-thalassemia was explored by knocking down the aberrantly spliced mRNA of beta-globin. Lentiviral vector with siRNA fragment targets on the specific portion of beta(654)-globin aberrantly spliced pre-mRNA was constructed. In HeLa beta(654) cells, the siRNA vector could reduce approximately 60% of aberrantly spliced mRNA, which was assessed by RT-PCR and qRT-PCR. Furthermore, a disease model of beta(654) thalassemia mice with lentiviral-mediated siRNA was produced by subzonal injection (named Hbetai-Hbb(th-4)/Hbb(+) transgenic mice). Our results showed that the hemotological parameters were improved in Hbetai-Hbb(th-4)/Hbb(+) transgenic mice. This study provides a potential way for beta(654)-thalassemia therapy by knocking down the aberrantly spliced beta-globin mRNA, whilst supporting that the aberrantly spliced beta-globin mRNA may aggravate the disease.


Identification of a C-terminal regulatory motif in hepatitis C virus RNA-dependent RNA polymerase: structural and biochemical analysis.
The NS5B RNA-dependent RNA polymerase encoded by the hepatitis C virus (HCV) is a key component of the viral replicase. Reported here is the three-dimensional structure of HCV NS5B polymerase, with the highlight on its C-terminal folding, determined by X-ray crystallography at 2.1-A resolution. Structural analysis revealed that a stretch of C-terminal residues of HCV NS5B inserted into the putative RNA binding cleft, where they formed a hydrophobic pocket and interacted with several important structural elements. This region was found to be conserved and unique to the RNA polymerases encoded by HCV and related viruses. Through biochemical analyses, we confirmed that this region interfered with the binding of HCV NS5B to RNA. Deletion of this fragment from HCV NS5B enhanced the RNA synthesis rate up to approximately 50-fold. These results provide not only direct experimental insights into the role of the C-terminal tail of HCV NS5B polymerase but also a working model for the RNA synthesis mechanism employed by HCV and related viruses.


Seasonal patterns of ascorbate in the needles of Scots Pine (Pinus sylvestris L.) trees: correlation analyses with atmospheric O3 and NO2 gas mixing ratios and meteorological parameters.
In the present field study the role of ascorbate in scavenging the harmful atmospheric trace gases O3 and NO2 was examined. For this purpose ascorbate contents were determined in needles of adult Scots pine trees (Pinus sylvestris L.) during three consecutive years. Ascorbate contents were correlated with ambient tropospheric O3 and NO2 concentrations and with meteorological parameters. The results showed a strong correlation of atmospheric O3 but not of atmospheric NO2 concentrations with the apoplastic content of ascorbate during the seasonal course. Ascorbate contents in needle extracts did not correlate with ambient trace gas concentrations. In the apoplastic space, but not in needle extracts ascorbate contents correlate highly significantly with global radiation. From these results it is assumed that apoplastic ascorbate in Scots pine needles is adapted to the actual atmospheric O3 concentration to mediate immediate detoxification of O3, while the atmospheric O3 concentration itself is largely dependent on light intensity.


Comparative filter binding study of H5 to nucleosome core particles, H1, H5 depleted chromatosomes and DNA fragments.
The filter-binding technique with PEI treated glass fiber is used to study the interaction of histone H5 to core particles, chromatosomes and DNA derived from it. By working at very low concentrations of interacting particles we are able to study the effective binding process independent of interfering insoluble complexes. The interactions are characterized by a very high affinity. An intrinsically higher affinity of H5 for cores and chromatosomes versus chromatosome derived DNA is demonstrated. Both chromatosomes and DNA derived from these bind about twice the amount as compared to core particles, which saturate at about one H5 per core particle.


Inhibition of the renin-angiotensin system ameliorates genetically determined hyperinsulinemia.
This study was performed in order to assess the potentially different effects of the angiotensin-converting enzyme inhibitor captopril and of the angiotensin II receptor antagonist irbesartan on the metabolic syndrome in an animal model. Male NZO/BL6 F1 mice were treated with captopril, irbesartan, or placebo for 10 months: Control animals treated with placebo developed a metabolic syndrome with obesity (55.5+/-6.3 g), hypertension (146+/-10 mm Hg), hyperinsulinemia (7.2+/-5.7 ng/ml), hypercholesterolemia (5.1+/-0.7 mmol/l), cardiac hypertrophy (269+/-44 mg) and atherosclerotic plaques in the ascending aorta (3.6+/-1.5 microm(2)). Treatment with angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist significantly (p<0.001) reduces hypertension (73+/-5 and 78+/-11 mm Hg), cardiac hypertrophy (203+/-26 and 202+/-18 mg) and atherosclerosis (2.2+/-0.9 and 1.8+/-0.8 microm(2)). In addition, they prevented the development of obesity (42.2+/-3.5 and 38.3+/-2.8 g) and hyperinsulinemia (3.6+/-1.5 and 1.8+/-0.4 ng/ml). In conclusion, long-term treatment with an angiotensin-converting enzyme inhibitor or an angiotensin II receptor antagonist can ameliorate obesity and hyperinsulinemia in a genetically determined mouse model.


Photic driving in the early premature infant.
Thirty-two infants born at gestational ages of 27-32 weeks were subjected to isolated flashes and intermittent photic stimulation. Their gestational age (GA) was assessed by maternal dates, physical examination and, when possible, examination of lens vasculature. The babies were selected for being of less than 33 weeks GA and being normal for GA on examination. Responses to isolated flashes were present in 63% and photic driving at 2-10 f/sec was present in 66% of the babies. Apparent discrepancies of these findings with previous reports about photic driving in prematures are discussed.


Dermal application of nitric oxide in vivo: kinetics, biological responses, and therapeutic potential in humans.
Many local hemodynamic and vascular disorders may be the result of impaired bioavailability of nitric oxide (NO). Previous findings point to a therapeutic potential of dermal NO application in the treatment of hemodynamic disorders, but no reliable data are available on the mechanisms, kinetics, or biological responses relating to cutaneous exposure to NO in humans in vivo. Here we show that, owing to its excellent diffusion capacity, cutaneously applied NO rapidly penetrates the epidermal barrier in significant amounts, strongly enriching skin tissue and blood plasma with its vasoactive derivates. In parallel, it significantly increased vasodilatation and blood flow and reduced thrombocyte aggregation capacity. Data presented here for the first time show that, in humans, dermal application of NO has strong potential for use in the therapy of local hemodynamic disorders arising from insufficient availability of NO or its bioactive derivates.


Integrative analysis of the circRNA-miRNA regulatory network in atrial fibrillation.
We aimed to investigate the circRNA-miRNA regulatory network in atrial fibrillation (AF) by using Cytoscape and HMDD v3.0. Finally, 120 differentially expressed circRNAs in peripheral blood monocytes of 4 AF patients were preliminarily screened by circRNA microarray. circRNA_4648, circRNA_4631, and circRNA_2875 were the first four circRNAs with the most binding nodes in the circRNA-miRNA network. The top three most frequent miRNAs for up-regulated circRNAs were hsa-miR-328 that interacted with 5 up-regulated circRNAs, hsa-miR-4685-5p with 4 up-regulated circRNAs, hsa-miR-3150a-3p, hsa-miR-4649-5p, hsa-miR-4783-3p, and hsa-miR-8073 with 3 up-regulated circRNAs,, while the top three most frequent miRNAs for down-regulated circRNAs were hsa-miR-328 that interacted with 14 down-regulated circRNAs, hsa-miR-4685-5p with 11 down-regulated circRNAs and hsa-miR-661 with 9 down-regulated circRNAs. According to HMDD v3.0, five up-regulated and eleven down-regulated circRNAs were found to interact with AF related miRNAs. These results indicated the possible regulatory network between circRNAs and miRNAs in the pathogenesis of AF.


Exploring the intersection of neighborhood racial and economic composition and individual race on substance use among male adolescents.
This article examines how Blacks and Whites living in neighborhoods with divergent racial and income profiles differed in early onset (by age 14 years) and adolescent lifetime prevalence (by age 18 years) of substance use, with longitudinal data from 473 high-risk boys (58% Black). A latent profile analysis identified four neighborhood classes: Black, lower-income; racially mixed, middle-income; White, middle-income; and White, upper-income. Bivariate analyses showed that Blacks living in racially mixed, middle-income neighborhoods reported the lowest rates of tobacco and marijuana use. Whites living in White, upper-income neighborhoods reported higher substance use prevalence, particularly marijuana. Findings suggest that substance use prevention efforts are critical for Whites in upper-income communities.


Enhanced roles of biochar and organic fertilizer in microalgae for soil carbon sink.
Improved soil carbon sink capability is important for the mitigation of carbon dioxide emissions and the enhancement of soil productivity. Biochar and organic fertilizer (OF) showed a significant improving effect on microalgae in soil carbon sink capacity, and the ultimate soil total organic carbons with microalgae-OF, microalgae-biochar, microalgae-OF-biochar were about 16, 67 and 58% higher than that with microalgae alone, respectively, indicating that carbon fixation efficiency of microalgae applied in soil was improved with biochar and OF whilst the soil carbon capacity was promoted, the mechanism of which is illustrated through simulative experiments. Organic fertilizer could spur algal conversion of carbon into cell molecules by increasing intracellular polysaccharide production of microalgae. Biochar could change carbon metabolism pathway of microalgae through altering the yield of intracellular saccharides, and yield and type of extracellular saccharides. There was a superimposition effect on the soil carbon sink when biochar and OF were both present with microalgae.


MOG antibody associated disease (MOGAD) presenting with extensive brain stem encephalitis: A case report.
Myelin oligodendrocyte glycoprotein antibody disease (MOGAD) is a relatively new entity of demyelinating diseases, clinically presenting with optic neuritis, transverse myelitis, or encephalic symptoms. Typical radiological features include demyelinating cerebral and spinal lesions, cortical involvement, leptomeningeal enhancement, or tumefactive lesions. Here we present a rare case of a young patient with extensive brain stem lesion on the MRI while exhibiting nystagmus, singultus and somnolence. A 30-year-old male patient presented initially with fever and impaired consciousness, but furthermore developed nystagmus, singultus and tetraparesis during the following week. Repeated MRI examinations revealed extensive brain stem edema with notable bilateral affection of the cerebellar peduncles and the pons. Antiviral and antibiotic treatment was changed to intravenous corticosteroids and immunoglobulins as soon as the diagnosis of MOGAD was established by testing serum and cerebrospinal fluid positive for MOG specific antibodies. MRI alterations vanished completely over time with a delayed, nearly complete clinical recovery of our patient. Brain stem affection in MOGAD is rare. However, in patients presenting with an unclear brain stem encephalitis the possibility of MOGAD should be considered and tested using MOG antibodies. In case of a positive testing treatment with steroids and immunoglobulins seems recommendable.


Effect of PM2.5 air pollution on the global burden of lower respiratory infections, 1990-2019: A systematic analysis from the Global Burden of Disease Study 2019.
Particulate matter (PM) air pollution is closely related to lower respiratory infections (LRIs). However, the global LRI burden attributable to PM remains unclear. Here, we provide a comprehensive assessment of the PM2.5-attributable LRI burden using data from the Global Burden and Disease Study (GBD) 2019. We found that PM2.5 air pollution contributed to approximately 0.7 million deaths and 37.6 million disability-adjusted life years (DALYs) of LRIs in 2019. The LRI burden attributable to PM2.5 has decreased from 1990 to 2019, with a more pronounced decrease in household PM2.5 than in ambient PM2.5. Unlike the decreasing trend in LRI burden due to household PM2.5 worldwide, nearly one fifth of countries experienced an increase of LRI burden due to ambient PM2.5. The burden was unevenly distributed to less developed countries, mainly in Sub-Saharan Africa. All age groups experienced a decrease in the PM2.5-attributable burden, with the most significant decrease in children younger than 10 years. Notably, individuals aged 20-84 years experienced an increase in the LRI burden attributable to ambient PM2.5. Males had higher burden than females in the elder age and higher SDI regions. This study provided an evidence-based guidance for the prevention of LRIs and control of PM2.5 air pollution.


Metal-free deprotonative functionalization of heteroaromatics using organic superbase catalyst.
Metal-free deprotonative functionalization of heteroaromatic compounds was achieved using an organic superbase catalyst; an organosilicon additive such as trimethylsilylpropyne was employed for activating the catalytic cycle of 1,2-addition to carbonyl compounds.