What do early bone scans tell about breast cancer patients?
In 1978, 1012 out of a total of 1888 Danish breast cancer patients registered for a nationwide therapeutical trial were bone-scanned to find osseous metastases. A re-reading group (N.R., O.M. and S.P.N.) interpreted 842 of the scans produced in the twelve participating hospitals. Specific criteria were used for grading the scintiscans. Of the 842 scans 682 were performed within 30 days of the operation and were defined as initial. The re-reading group found 50 (7%) of these scans to be equivocal and 46 (7%) to be indicative of bone metastases at the time of operation. The number of X-ray-verified bone metastases was only 5 (0.6%). The frequency of positive bone scans correlated with the age of the patients and tumor size, but not with clinical staging at the time of operation, number of positive axillary lymph nodes or degree of tumor anaplasia. Recurrences and death rates during a 2-yr follow-Up period correlated significantly with initial clinical staging. In the clinical low-risk group a positive initial bone scan worsened the prognosis, but this was not statistically significant for all patients grouped together. Although the prognostic value of the initial bone scan per se is dubious, it serves as a guidance for elective X-ray examination and as a basis for comparing subsequent scans.


Preclinical evaluation and molecular docking of 4-phenyl-1-Napthyl phenyl acetamide (4P1NPA) from Streptomyces sp. DPTB16 as a potent antifungal compound.
The incidence of fungal disease has increased dramatically over the past decades, mainly due to the emergence and transmission of antifungal resistance within the fungal pathogens. The present study investigates the use of novel antifungal compound 4-Phenyl-1-Napthyl Phenyl Acetamide (4P1NPA), isolated from marine Streptomyces sp. DPTB16 as a potent antifungal drug. The preclinical studies and molecular docking for 4P1NPA against Cytochrome P450 51 (CYP 51) were performed using in silico pharmacology and docking tools. The finding reveals the drug likeliness of 4P1NPA and satisfactory interaction of 4P1NPA with CYP 51. These results collectively evidence the use of 4P1NPA as a drug to treat fungal infections. On the whole, we highlight the findings of this research will be helpful to design 4P1NPA as novel antifungal drug to defend the emerging antifungal resistance.


Inositol monophosphatase activity in normal, Down syndrome and dementia of the Alzheimer type CSF.
Inositol monophosphatase (IMPase), a cytoplasmic enzyme that hydrolyses inositol monophosphates to produce inositol is also found in the cerebrospinal fluid (CSF). Since levels of inositol have been previously reported to be elevated in Down syndrome (DS) CSF, IMPase activity was measured in CSF of DS subjects to establish whether altered inositol levels may be related to changes in IMPase activity. In addition, and to better understand the regulation of IMPase expression in the CSF, enzyme activity was measured in normal aging, patients with Alzheimer-type or multi-infarct dementia (DAT and MID, respectively) and in CSF obtained by repeat lumbar puncture or from sequential aliquots of CSF from along the rostro-caudal axis. IMPase activity was relatively constant in CSF obtained from repeated lumbar puncture and there was no significant rostro-caudal gradient of activity in either normal or DS subjects, indicating that the enzyme originates from both brain and spinal cord. Compared to respective age-matched normal subjects, CSF IMPase activity was unaltered in DS, DAT and MID. However, in normal volunteers there was a significant positive correlation between age and CSF IMPase activity. Furthermore, there were significant correlations between CSF IMPase activity and acetylcholinesterase and butyrylcholinesterase activities and total protein, suggesting co-regulation of these parameters within the CSF.


Discordance between family report and clinical assessment of suicide attempts: a prospective study from the emergency department.
Developing accurate identification methods for individuals with suicide attempts and providing them with follow-up care and supports can be a vital component of all comprehensive suicide prevention strategies. However, because of the difficulties concerning one's intentions behind injurious behaviour, identifying suicide attempts is a challenge for families and clinicians. The aim of this study was to investigate the differences between family report and clinical assessment for suicide attempts in the emergency department (ED). A total of 148 patients with suspected suicide attempts (SSAs) and 148 family caregivers in the ED were enrolled. The suicide risk module of the Chinese version of the MINI International Neuropsychiatric Interview and the self-report measure were used to assess those with SSA's suicidal behaviours. The Family Adaptability and Cohesion Evaluation Scales and semi-structured interviews were used to investigate the characteristics of suicide risk and demographics of patients with SSA, as well as the rate and influencing factors of omitted suicide attempts reported by family caregivers. The underreporting rate for family reported suicide attempts in the ED was 69.0%. The suicide attempts group indicated lower mean scores on perceptions of family resources, adaptability and cohesion. Patients' suicide risk rating (OR =-1.81, 95% CI: -3.87 to -0.33, p=0.036), family satisfaction (OR =-1.11, 95% CI: -2.29 to -0.06, p=0.048), and caregiver's age (OR =-1.68, 95% CI: -3.10 to -0.48, p=0.010) might be associated with underreporting by families. If patients committed suicide attempts through a falling injury or medication overdose, their families may have misreported the suicide attempt. The discordance of suicide attempt records between family report and clinical assessment reveals the limitations of family self-reports when identifying suicide attempts. Interviews and observations, together with information from certain diagnoses, should be combined to accurately identify suicide attempters in the ED.


Exploring the dynamic nexus between renewable energy, poverty alleviation, and environmental pollution: fresh evidence from E-9 countries.
The present study aims to scrutinize the long- and short-run relationship along with the direction of causality among environmental pollution (CO2), renewable, non-renewable energy, income disparity, exchange rate, and poverty alleviation in E-9 countries of continent Asia, using a panel dataset from 1990 to 2018. The current study used pooled mean group autoregressive distributed lag (PMG ARDL) and Dumitrescu-Hurlin (D-H) causality test after affirming a stable long-run association among environmental pollution and all the explanatory variables. However, ECM (error correction mechanism) was specified to explore short-run dynamics. The study's outcomes confirmed strong co-integration among environmental pollution (CO2), renewable, non-renewable energy, income disparity, exchange rate, and poverty alleviation. Moreover, uni (bi) directional causality runs from non-renewable energy, exchange rate, and income disparity (poverty alleviation and renewable energy) to environmental pollution (CO2). Results also revealed that poverty alleviation, exchange rate, and renewable energy usage substantially negatively influence environmental pollution (CO2). Contrarily, income disparities and non-renewable energy usage positively influence long- and short-run environmental pollution. Therefore, from the policy perspective, the current study focused on twofold; first, there is a desire to alleviate poverty, the decline in non-renewable energy use and income disparity among upper and lower-income quintiles. Second, boost exchange rate and renewable energy use to control environmental pollution in the described least developed countries (LDCs).


[Impact of blood pressure control on the ankle-brachial index in hypertensive patients].
The guidelines for arterial hypertension recommend a systematic determination of ankle-brachial index (ABI) in the initial risk stratification in hypertensive patients, while not indicating whether controls should be evolutionary. Our aim was to analyze the evolution of the ABI value in hypertensive patients in terms of control of blood pressure (BP) after one year follow-up. We included 209 hypertensive patients, in whom ABI was determined at baseline and after one year of antihypertensive treatment. Patients were divided into 2 groups in terms of good/poor clinical control of BP (<140/90 mmHg). A total of 82.8% of the population showed a good control of the BP after one year of treatment and it was associated with significant increase in the ABI value (1.081 versus 1.046 at baseline, P=.002). By contrast, there was no difference of ABI value in patients with poor BP control (1.054 versus 1.093 at baseline). A good clinical control of BP is associated with an increase in the value of the ABI.


High expression of spliced X-Box Binding Protein 1 in lung tumors is associated with cancer aggressiveness and epithelial-to-mesenchymal transition.
Proteostasis imbalance is emerging as a major hallmark of cancer, driving tumor growth and aggressiveness. Endoplasmic Reticulum (ER) stress has been documented in most major cancers, and the ability to tolerate persistent ER stress through an effective unfolded protein response enhances cancer cell survival, angiogenesis, metastasis, drug resistance and immunosuppression. The ER stress sensor IRE1α contributes to tumor progression through XBP1 mRNA splicing and regulated IRE1α-dependent decay of mRNA and miRNA. The aim of this study was to perform a molecular characterization of series of tumor samples to explore the impact of intratumoral IRE1 signaling in non-small cell lung cancer characteristics. To monitor IRE1 splicing activity, we adopted a fragment length analysis to detect changes in the length of the XBP1 mRNA before and after splicing as a method for measuring sXBP1 mRNA levels in tumors because sXBP1 mRNA is not probed by standard transcriptomic analyses. We demonstrate for the first time that XBP1 splicing is a valuable marker of lung cancer aggressiveness, and our results support a model in which IRE1 downstream signaling could act as a regulator of Epithelial to Mesenchymal Transition (EMT). Our findings study highlights the role of IRE1α downstream signaling in non-small cell lung cancer and opens a conceptual framework to determine how IRE1α endoribonuclease activity shapes the EMT program.


Nicastrin overexpression in transgenic mice induces aberrant behavior and APP processing.
Nicastrin (NCT) is a component of the presenilin protein complex, which is involved in the cleavage of β-amyloid precursor protein (βAPP) and Notch. The aim of this study was to determine the manner in which overexpression of wild-type human nicastrin (hNCTw) or mutant human nicastrin (hNCTm, D336A/Y337A) regulates brain functions and amyloid precusor protein (APP) processing. For this, we created transgenic (Tg) mice expressing neuron-specific enolase (NSE)-controlled hNCTw or hNCTm and measured their phenotypes as time passed. The NSE/hNCTw and NSE/hNCTm Tg groups exhibited greater behavioral dysfunction from 10 months of age than the non-Tg group, although their severities differed. Further, activity and component levels of the γ-secretase complex were significantly elevated in NSE/hNCTw Tg mice, expect for PEN-2. These alterations induced stimulation of APP processing, resulting in overproduction of Aβ-42 peptide in the NSE/hNCTw Tg group, whereas the NSE/hNCTm Tg group showed a comparatively weaker effect. Furthermore, the highest expression levels of β-secretase and NICD were observed in the NSE/hNCTw Tg group, similar to other phenotypes. Especially, a significances interference on the interaction between NCT and γ-secretase substrates was detected in NSE/hNCTm Tg groups compare with NSE/hNCTw Tg group. These results indicate that hNCTw overexpression in Tg mice promoted active assembly of the γ-secretase complex through modulation of APP processing and behavior, whereas the lesser effect in NSE/hNCTm Tg mice was due to reduced expression of hNCTm. These Tg mice could be useful for the development and application of therapeutic drugs in an animal model of Alzheimer's disease.


Mechanical manipulation of the lids and tear break-up time measurements in Hong Kong Chinese.
We measured tear break-up time (TBUT) after lid-rubbing in a single masked experiment, and found that TBUT was unaltered. A further single masked experiment in which non-invasive tear break-up time (NITBUT) was measured after the lids were raised as if to apply fluorescein also showed no effect of this interference with the lids. An experiment in which fluorescein was applied either with the lid raised or not raised during fluorescein application, again with the experimenter masked with respect to treatment, also produced no significant difference in TBUT. When we measured TBUT with the lid raised so that it was not in contact with the cornea, there was no difference in TBUT for the group between the 'lifted' and 'non-lifted' eye; some subjects showed substantially shorter TBUT values, while others showed substantially longer TBUT values. These findings are surprising in view of the concerns expressed in the literature regarding the sensitivity of the tear film to mechanical interference, and suggest that the tear film is more resistant to disruption than has previously been thought.


Copper-induced Genotoxicity, Oxidative Stress, and Alteration in Transcriptional Level of Autophagy-associated Genes in Snakehead Fish Channa punctatus.
Copper (Cu) is an essential and important trace element for some significant life processes for most organisms. However, an excessive amount of Cu can be highly toxic. The present study was conducted to elucidate the oxidative stress-induced alteration in transcriptional level of autophagy-related genes in the liver and kidney tissue of fish Channa punctatus after treatment with three different sublethal concentrations of CuSO4 for 28 days. All the studied enzymatic and non-enzymatic oxidative stress markers viz. superoxide dismutase-SOD, catalase-CAT, glutathione peroxidase-GPx, glutathione reductase-GR, and glutathione-GSH showed an increase in their activity levels in the treated groups in a dose-dependent manner. Particularly SOD and CAT have shown a significant hike in activity levels. ROS levels in blood cells increased significantly (p < 0.05) in all the treated groups, i.e., Group II-1/20th of 96 h-LC50 (0.2 mg/L), Group III-1/10th of 96 h-LC50 (0.4 mg/L), and Group IV-1/5 h of 96 h-LC50 (0.8 mg/L) of Cu2+ in a dose-dependent manner as compared to control (Group I). The upregulation in mRNA levels of autophagy-related genes Microtubule-associated protein 1 light chain 3 (LC3), Gamma-aminobutyric acid receptor-associated protein precursor (Gabarap), and Golgi-associated ATPase enhancer of 16 kDa (GATE16), autophagy-related 5 (ATG5) was observed while mammalian target of rapamycin (mTOR) showed downregulation in the liver and kidney tissue of fish. The decrease in mTOR and increase in ATG5 gene expression projects autophagic vesicle formation due to oxidative stress. There was significant induction in micronuclei (MN) frequency in all the treated groups. The highest frequency of MN induced by Cu2+ was recorded in Group IV after 28 days of the exposure period. Thus, it can be concluded that the available information about Cu2+-induced oxidative stress-mediated autophagy in the liver and kidney of fish C. punctatus remains largely unclear to date, so to fill the aforesaid gap, the present study was undertaken, which gives an insight for the mechanisms of autophagy induced by Cu2+ in fish.


Promoter trapping identifies real genes in C. elegans.
Promoter trapping involved screening uncharacterized fragments of C. elegans genomic DNA for C. elegans promoter activity. By sequencing the ends of these DNA fragments and locating their genomic origin using the available genome sequence data, promoter trapping has now been shown to identify real promoters of real genes, exactly as anticipated. Developmental expression patterns have thereby been linked to gene sequence, allowing further inferences on gene function to be drawn. Some expression patterns generated by promoter trapping include subcellular details. Localization to the surface of particular cells or even particular aspects of the cell surface was found to be consistent with the genes, now associated with these patterns, encoding membrane-spanning proteins. Data on gene expression patterns are easier to generate and characterize than mutant phenotypes and may provide the best means of interpreting the large quantity of sequence data currently being generated in genome projects.


Self-reported cognitive problems in women receiving adjuvant therapy for breast cancer.
Self-reported cognitive problems are common among women receiving adjuvant therapy for breast cancer but are unrelated to actual cognitive impairment. To date, no studies have objectively measured impairment and asked patients to speak about the type and extent of problems they encounter. We report interview data from 142 breast cancer patients receiving adjuvant therapy. We aimed to identify the types of problems and the extent to which they interfered with everyday life. We investigated the relationship between self-reported and objective cognitive impairment, quality of life and psychological distress. The majority of participants reported problems with their memory (71% overall at 6 months, 60% at 18 months) and concentration (64% and 42%, respectively). This was unrelated to objective cognitive decline; rather, it was associated with psychological distress and quality of life. For the vast majority, the problems reported were everyday slips and lapses. The neuropsychological measures routinely used may lack the sensitivity to detect these subtle changes experienced by this group. In addition, the effects of mood on cognition may be more important in everyday life than in the highly structured neuropsychological test situation. Future research should focus on developing cognitive assessments that tap everyday functioning.


Influence of weight on aminoglycoside pharmacokinetics in normal weight and morbidly obese patients.
Aminoglycoside pharmacokinetics were determined in 30 normal weight patients and 30 morbidly obese patients (greater than 90% overweight). All had normal renal function and a gram-negative infection (documented by cultures, fever and elevated white blood cell counts) which was treated only with aminoglycoside antibiotics. The normal weight and morbidly obese patients were matched with respect to the following criterion: age, sex, ideal body weight (IBW), serum creatinine, site of infection, and type of aminoglycoside antibiotic (gentamicin, tobramycin, or amikacin). The results were similar for all 3 drugs. Average half-life was 2 h for both the morbidly obese and normal weight patients. The mean volumes of distribution and clearances were significantly larger in the morbidly obese (23.3 l and 135.8 ml/min for gentamicin, 29.9 l and 162.4 ml/min for tobramycin, and 26.8 l and 157.3 ml/min for amikacin) than in normal weight patients (17.0 l and 95.9 ml/min for gentamicin, 18.3 l and 101.3 ml/min for tobramycin, and 18.6 l and 99.2 ml/min for amikacin). As a result of altered aminoglycoside pharmacokinetics, morbidly obese patients required significantly larger mean doses (540 mg/d for gentamicin, 690 mg/d for tobramycin and 1970 mg/d for amikacin) when compared to the normal weight patients (380 mg/d, 420 mg/d and 1420 mg/d, respectively; p less than 0.005) in order to achieve comparable serum concentrations.


Expression of proliferating cell nuclear antigen in ameloblastomas and odontogenic cysts.
The identification of the proliferative activity in tumours may be useful to predict the biological behaviour of different lesions. Proliferating cell nuclear antigen (PCNA) has been used for the evaluation of the proliferative ability of many lesions. In this study 22 ameloblastomas (4 follicular, 5 plexiform, 4 acanthomatous, 5 unicystic, 4 recurrent), 12 odontogenic keratocysts (OKC), 8 dentigerous cysts (DC), and 12 radicular cysts (RC) were analysed. PCNA+ cells were present in all cyst types but the OKC contained the highest number of PCNA+ cells. In OKC the location of PCNA+ cells was mainly suprabasal. In ameloblastoma PCNA+ cells were located mainly in the peripheral portion of the tumour islands. Statistical analysis showed that ameloblastoma had higher PCNA+ cell counts than OKC (P < 0.0001); OKC had higher values than DC and RC (P < 0.0001). Recurrent ameloblastoma presented higher PCNA+ cell counts than other types of ameloblastoma, while unicystic ameloblastoma showed lower values than acanthomatous, plexiform and follicular ameloblastomas (in this latter case the difference was not statistically significant). These data could help to explain the different biological behaviour of these lesions.


Conformon-driven biopolymer shape changes in cell modeling.
Conceptual models of the atom preceded the mathematical model of the hydrogen atom in physics in the second decade of the 20th century. The computer modeling of the living cell in the 21st century may follow a similar course of development. A conceptual model of the cell called the Bhopalator was formulated in the mid-1980s, along with its twin theories known as the conformon theory of molecular machines and the cell language theory of biopolymer interactions [Ann. N.Y. Acad. Sci. 227 (1974) 211; BioSystems 44 (1997) 17; Ann. N.Y. Acad. Sci. 870 (1999a) 411; BioSystems 54 (2000) 107; Semiotica 138 (1-4) (2002a) 15; Fundamenta Informaticae 49 (2002b) 147]. The conformon theory accounts for the reversible actions of individual biopolymers coupled to irreversible chemical reactions, while the cell language theory provides a theoretical framework for understanding the complex networks of dynamic interactions among biopolymers in the cell. These two theories are reviewed and further elaborated for the benefit of both computational biologists and computer scientists who are interested in modeling the living cell and its functions. One of the critical components of the mechanisms of cell communication and cell computing has been postulated to be space- and time-organized teleonomic (i.e. goal-directed) shape changes of biopolymers that are driven by exergonic (free energy-releasing) chemical reactions. The generalized Franck-Condon principle is suggested to be essential in resolving the apparent paradox arising when one attempts to couple endergonic (free energy-requiring) biopolymer shape changes to the exergonic chemical reactions that are catalyzed by biopolymer shape changes themselves. Conformons, defined as sequence-specific mechanical strains of biopolymers first invoked three decades ago to account for energy coupling in mitochondria, have been identified as shape changers, the agents that cause shape changes in biopolymers. Given a set of space- and time-organized teleonomic shape changes of biopolymers driven by conformons, all of the functions of the cell can be accounted for in molecular terms-at least in principle. To convert a conceptual model of the cell into a computer model, it is necessary to represent the conceptual model in an algebraic language. To this end, we have begun to apply the process algebra of Milner [Communicating and Mobile Systems: The pi-calculus, Cambridge University Press, Cambridge, 1999] to develop what is here called the "shape algebra," capable of describing complex and mobile patterns of interactions among biomolecules leading to cell functions.


Histocompatibility antigens associated with motor neurone disease.
The distribution of histocompatibility antigens was studied in 44 patients with motor neurone disease (MND). An unusually high incidence of HLA antigens A2 and A28 was found, compared to a control population.


Injectable contraception: what should the longest interval be for reinjections?
Progestin-only injectable contraceptives continue to gain in popularity, but uncertainty remains about pregnancy risk among women late for reinjection. The World Health Organization (WHO) recommends a "grace period" of 2 weeks after the scheduled 13-week reinjection. Beyond 2 weeks, however, many providers send late clients home to await menses. A prospective cohort study in Uganda, Zimbabwe and Thailand followed users of depot-medroxyprogesterone acetate (DMPA) for up to 24 months. Users were tested for pregnancy at every reinjection, allowing analysis of pregnancy risk among late comers. The analysis consists of 2290 participants contributing 13,608 DMPA intervals. The pregnancy risks per 100 women-years for "on time" [0.6; 95% confidence interval (CI), 0.33-0.92], "2-week grace" (0.0; 95% CI, 0.0-1.88) and "4-week grace" (0.4; 95% CI, 0.01-2.29) injections were low and virtually identical. Extending the current WHO grace period for DMPA reinjection from 2 to 4 weeks does not increase pregnancy risk and could increase contraceptive continuation.


The Effects of Socioeconomic Status on Parent and Child Moderate-to-Vigorous Physical Activity and Body Mass Index.
Purpose: Physical inactivity and overweight status has been linked to low socioeconomic status (SES) in youth. Parents are known to influence both their child's weight and physical activity (PA). The relationship between parent and child PA is of interest to many researchers; however, previous research typically relies on self-reported measures. The purpose of this study was to examine the relationship between parent and child moderate-to-vigorous PA (MVPA) and body mass index (BMI) in a sample of children (4-11 years old) using wrist-worn accelerometers and to explore mediating processes by which SES influences child MVPA and BMI through their parents MVPA and BMI. Methods: Parent and child dyads (n = 174) wore an ActiGraph GT3X+ accelerometer on their non-dominant wrist for 7 days. Mediation analyses were conducted to understand the indirect relationships between SES and child MVPA and BMI. Results: Weekend parent and child MVPA was significantly related (p < .01). Parent and child BMIs were also significantly related (p < .001). There was a significant negative direct effect of SES on child BMI (p < .05). Additionally, we observed a significant negative indirect effect of SES on child BMI via their parents BMI (B = -.04, SE .02, 95% CI = -.07 to -.01). Conclusions: Whilst parent and child MVPA were significantly related during the weekend, there were no associations between SES and MVPA. Future interventions aiming to improve health outcomes in children should consider the influence SES can have as well as parental activity on children's weekend MVPA.


The effect of DMA level on morphology and fertilising ability of Japanese quail (Coturnix japonica) spermatozoa.
The effect of different levels (2, 4 or 6%) of DMA (dimethylacetamide) on the morphology and fertilising ability of unfrozen quail spermatozoa was evaluated. Semen was collected from 72 males kept individually in cages and randomly divided into four groups: Group I--control -- fresh undiluted semen (12 males) and three experimental groups (20 males each) - semen diluted 1:1 with Lake's extender and supplemented with 2% (Group II), 4% (Group III) or 6% (Group IV) of DMA (final concentration). Sperm morphology was evaluated at each step of semen preparation, i.e. in fresh and diluted semen, semen supplemented with DMA and semen that remained after insemination. For fertility tests, 36 females were divided into four groups (nine females each). Females in the control group were inseminated with 10 microl of fresh semen, in the experimental groups with 40 microl of diluted semen. Each stage of quail semen treatment had a deleterious effect on sperm morphology. The highest percentage of morphologically normal cells in semen evaluated after insemination, was observed in samples with 2% DMA, and the lowest--in samples with 6% DMA. Semen dilution and DMA addition significantly affected the fertilising potency of spermatozoa. Fertility of eggs collected from the control group (71.5% on average) was significantly higher (P<or=0.01) compared to experimental groups (Group II: 2.3%; Group III: 3.9%; Group IV: 2.8%). However, differences between the experimental groups were not significant (P<or=0.05).


Immunoprotective potential of BamA, the outer membrane protein assembly factor, against MDR Acinetobacter baumannii.
Acinetobacter baumannii infections are responsible for major health problems in immunocompromised patients particularly in intensive care units. Due to rapid acquisition of and also inherent drug resistance, a vaccine is an effective treatment option against this pathogen. BamA, an outer membrane β-barrel assembly protein, was identified in A. baumannii as potential vaccine candidate by in silico analysis. The immunoprotective efficacy of this highly conserved protein was investigated against a virulent multidrug resistant clinical isolate using murine pneumonia model. Recombinant BamA elicited a high IgG antibody titer (160000) in mice. Opsonophagocytic killing assay showed non-neutrilizing, opsonizing antibodies with combinatorial bactericidal activity of antibodies and complement components. Active and passive immunization protected 80 and 60% mice respectively against intranasal challenge with lethal dose (109 CFU) of virulent A. baumannii along with efficient clearance of bacteria in mice lungs and reduction in levels of pro-inflammatory cytokines viz. TNF-α, IL-6 and IL-1β in sera and lung tissue homogenate. Increase in levels of IL-10, an anti-inflammatory cytokine and reduction of neutrophils in lungs facilitated the control of infection. This study demonstrates the potential of BamA as effective vaccine candidate and a promising target for antibody-based therapy to protect against MDR A. baumannii infections.


Determinants of advanced stage presentation of breast cancer in 87,969 Brazilian women.
Breast cancer is commonly diagnosed at an advanced stage in Brazil. Analyze the determinants of advanced staging in Brazilian women with breast cancer. Crosssectional study, including women diagnosed with breast cancer in Brazil, between 2000 and 2009. A total of 59,317 women were included, 53.5% being classified as advanced stage (≥IIB). Younger age (18 to 49 years old) (OR=1.61 95% CI 1.51 to 1.72) or between 40 and 49 years old (OR=1.08 95% CI 1.03 to 1.14), having low educational level (OR=1.53 95% CI 1.48 to 1.58), living in less developed geographical regions (OR=1.27 95% CI 1.21 to 1.33), having invasive ductal carcinoma (OR=2.70 95% CI 2.56 to 2.84) and invasive lobular carcinoma (OR=2.63 95% CI 2.42 to 2.86) were associated with advanced breast cancer. We conclude that future interventions should focus on these high risk groups.


Postspinal anesthesia shivering in lower abdominal and lower limb surgeries: a randomized controlled comparison between paracetamol and dexamethasone.
Shivering is known to be a frequent complication in patients undergoing surgery under neuraxial anesthesia with incidence of 40-70%. Although many pharmacological agents have been used to treat or prevent postspinal anesthesia shivering (PSAS), the ideal treatment wasn't found. This study evaluated the efficacy of paracetamol and dexamethasone to prevent PSAS in patients undergoing lower abdominal and lower limb surgeries. Three hundred patients scheduled for surgeries under spinal anesthesia (SA) were allocated into three equal groups to receive a single preoperative dose of oral paracetamol 1 g (P group), dexamethasone 8 mg intravenous infusion (IVI) in 100 ml normal saline (D group) or placebo (C group), 2 h preoperatively, in a randomized, double-blind trial. The primary endpoint was the incidence of clinically significant PSAS. Secondary endpoints included shivering score, the change in hemodynamics, adverse events (e.g., nausea, vomiting and pruritis) and patients` satisfaction. Clinically significant PSAS was recorded as (15%) in P group, (40%) in D group and (77%) in C group (P < 0.001). The mean blood pressure values obtained over a 5-25 min observation period were significantly higher in the D group (P < 0.001). Core temperature 90 min after SA was significantly lower in the 3 groups compared to prespinal values (P < 0.001). Nausea, vomiting and pruritis were significantly higher in the C group (P < 0.001). P and D groups were superior to C group regarding the patients' satisfaction score (P < 0.001). Paracetamol and dexamethasone were effective in prevention of PSAS in patients undergoing lower abdominal and lower limb surgeries compared to placebo controls. ClinicalTrials.gov Identifier: NCT03679065 / Registered 20 September 2018 - Retrospectively registered, http://www.ClinicalTrial.gov .


On the possible role of reactive oxygen species in angiogenesis.
Human microvascular endothelial cells grown on a 3-D reconstituted extracellular matrix (Matrigel) spontaneously and rapidly form a capillary network of tubular structures, thus modeling part of the angiogenic cascade. Exposure of the cells at the time of plating onto Matrigel to a brief episode of hypoxia (40-60) min and subsequent reoxygenation, significantly accelerated (up to 3-fold) the rate of tubular morphogenesis, as determined by computer-aided morphometry. This effect was not dependent on activation of PKC or upregulation/release of angiogenic growth factors. Rather, hypoxia/reoxygenation (H/R), but not hypoxia alone, caused the formation of reactive oxygen species (ROS) and the activation of the nuclear transcription factor NF kappa B, both of which were inhibited by ROS-scavengers, such as pyrollidine dithiocarbamate. Tube formation was inhibited, also under normoxic conditions, by diverse ROS antagonists in a dose-dependent fashion. Our results indicate that angiogenesis is accompanied by and/or requires generation of ROS. We hypothesize that in the clinical setting of hypoxia/reoxygenation during ischemic pre-conditioning, enhanced activation of ROS-dependent intracellular signaling may accelerate the rate of neovascularization also in vivo, thus contributing to the alleviation of certain ischemic lesions.


Evaluation of comorbidity scores to predict all-cause mortality in patients with established coronary artery disease.
To assess the value of scores based on the presence of comorbid conditions for mortality risk-stratification in patients with coronary artery disease (CAD) METHODS: We prospectively followed 305 males with CAD undergoing coronary angiography for 58 months. We correlated the modified Charlson Index (MCI) and the recently proposed CAD-specific index (CSI) with the risk of all-cause mortality. The odds ratio (OR) for death increased by 31% per point increase in the MCI (95% CI=17-46%; p<0.0001). The OR for death increased by 16% per point increase in the CSI (95% CI=8.5-25%; p<0.0001). In logistic regression models that adjusted for age, left ventricular ejection fraction, and the number of vessels involved with CAD, both the MCI and the CSI were the strongest predictors of mortality according to the chi2 value for each term, with the MCI having the highest value. The adjusted OR per point increase in the MCI was 1.32 (95% CI=1.17-1.48; p<0.0001); the corresponding adjusted OR per point increase in the CSI was 1.17 (95% CI=1.09-1.26; p<0.0001). The model including the MCI had a slightly higher chi2 value (45.1 vs. 39.1) and area under the receiver operator characteristic curve (0.742 vs. 0.727) than the model including the CSI. The MCI and the newly proposed CSI are powerful tools to predict all-cause mortality in patients with established CAD. Although the CSI was not superior to the MCI, its simplicity might make it useful in populations with a low prevalence of comorbidities not included in this score.


Looking for Sunshine: Genetic Predisposition to Sun Seeking in 265,000 Individuals of European Ancestry.
Despite growing public awareness of the adverse consequences of excessive sun exposure, modifying sun-seeking behavior is challenging because it appears to be driven by addictive mechanisms. This can have effects on health because sun exposure, although beneficial, when prolonged and repeated shows a causal relationship with skin cancer risk. Using data from 2,500 United Kingdom twins, we observed sun seeking to be significantly heritable (h2 ≥ 58%). In a GWAS meta-analysis of sun-seeking behavior in 261,915 subjects of European ancestry, we identified five GWAS-significant loci previously associated with addiction, behavioral and personality traits, cognitive function, and educational attainment and enriched for CNS gene expression: MIR2113 (P = 2.08 × 10-11), FAM76B/MTMR2/CEP57 (P = 3.70 × 10-9), CADM2 (P = 9.36 × 10-9), TMEM182 (P = 1.64 × 10-8), and PLCL1/LINC01923/SATB2 (P = 3.93 × 10-8). These findings imply that the behavior concerning UV exposure is complicated by a genetic predisposition shared with neuropsychological traits. This should be taken into consideration when designing awareness campaigns and may help improve people's attitudes toward sun exposure.


Targeted gene transfer into head and neck squamous cell carcinoma by nanosecond pulsed laser-induced stress waves.
The search for new strategies to improve patient outcome and organ preservation is of great clinical interest in head and neck squamous cell carcinoma (HNSCC) treatment, and gene therapy is expected to play a promising role. In this study, we demonstrated the value of laser-induced stress waves (LISWs) as a novel method for nonviral gene transfer for gene therapy in HNSCC. The in vitro and in vivo transfection efficiency as well as in vitro cytotoxicity for HNSCC was investigated. Green fluorescent protein (GFP) expression and cell viability were analyzed in vitro after administration of a GFP-expressing plasmid or cationically modified GFP-expressing plasmid with LISW application. Luciferase expression in xenograft tumors was also quantitatively analyzed in vivo. The GFP gene was successfully transfected into HNSCC cells in vitro by LISW application. The cationically modified plasmid demonstrated enhanced transfection efficiency. LISWs are not associated with adverse effects after application to cells in vitro. The reporter genes were also successfully transfected into HNSCC tumors in vivo by LISW application. This technique is site specific, safe, and easily applicable for practical purposes. LISW gene therapy with therapeutic factors that inhibit tumor growth therefore has the potential as a future treatment for HNSCC.


Preventive effects of rutin on lysosomal enzymes in isoproterenol induced cardio toxic rats: biochemical, histological and in vitro evidences.
This study was aimed to evaluate the preventive effect of rutin on lysosomal enzymes in isoproterenol induced cardio toxic rats. Male albino Wistar rats were pretreated with rutin (80 mg/kg) daily for a period of 42 days. After the pretreatment period, isoproterenol (100 mg/kg) was subcutaneously injected to rats at an interval of 24 h for two days. The activity of serum creatine kinase-MB and the levels of serum troponins T and I and the activities of serum and heart lysosomal enzymes (β-glucuronidase, β-N-acetylglucosaminidase, β-galactosidase, cathepsin-B and D) were increased significantly (P<0.05) in isoproterenol induced cardio toxic rats. Isoproterenol induced cardio toxic rats also resulted in decreased stability of membranes, which was reflected by decreased activities of β-glucuronidase and cathepsin-D in mitochondrial, nuclear, lysosomal and microsomal fractions. Pretreatment with rutin daily for a period of 42 days to isoproterenol induced cardio toxic rats prevented the changes in the activities of these enzymes. Oral treatment with rutin (80 mg/kg) to normal rats did not show any significant effect in all the biochemical parameters studied. Histopathology of myocardium showed the preventive effects of rutin in isoproterenol induced cardio toxic rats. In vitro study also confirmed the mechanism of action of rutin. Thus, the results of our study show that rutin protects the lysosomal membrane against isoproterenol induced cardiac damage. The observed effects are due to the free radical scavenging, antioxidant and membrane stabilizing properties of rutin.


Parthenogenetic development of bovine oocytes matured in vitro for 24 hr and activated by ethanol and cycloheximide.
This research was undertaken to improve development of parthenogenetic embryos following various combined treatments of ethanol and cycloheximide. In Experiment 1 in vitro matured oocytes (IVM, 24 hr) were treated with 7% ethanol for 5 min followed by incubation in 10 micrograms/ml cycloheximide in Medium 199 for 0 (control), 5, 10, and 20 hr. Development to 2-8 cells following culture for 3 days was similar among treated groups (32-41%; P > 0.05), which was higher than that of controls (6%; P < 0.05). Experiment 2 compared pre-ethanol exposures for 0, 1, 2.5, and 5 min, followed by 5 hr cycloheximide treatment on activation development. One- to 5-min groups resulted in 42-44% cleavage contrasted to 1-12% for controls (P < 0.05). Experiment 3 examined the effect on oocyte development of ethanol and different concentrations of cycloheximide (0, 1, 5, and 10 micrograms/ml). Cleavage to 2-8 cells was similar among the 5 and 10 micrograms/ml cycloheximide groups (36% and 42%, P > 0.05) but lower (P < 0.05) for the 1 micrograms/ml group (24%) and the controls (2-13%). When 5 micrograms/ml cycloheximide was used (Experiment 4), pre-exposure to ethanol (1, 2.5, and 5 min) resulted in more oocytes cleaved (38-41%) than in the cycloheximide alone group (0%) or the control (0%, P < 0.05). Experiment 5 tested blastocyst development of the activated oocytes with or without cytochalasin B treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of elapsed time after standing up on orthostatic blood pressure change in the elderly].
The effect of time elapsed after standing on the orthostatic change in blood pressure was investigated. The study subjects were recruited from 237 community-dwelling elderly residents free from any history of cardiovascular disease and not on medication. Basal blood pressure was determined by averaging two determinations of supine blood pressure measured with an automatic oscillometric blood pressure recorder after resting for more than 10 minutes. Orthostatic change in systolic blood pressure (SBP) was determined as more than a 10% increase or decrease in SBP after standing. In the total population, maximum change in SBP was observed at 1 minute after standing-up. However, 8.4% and 7.2% of subjects showed abnormal increase or decrease in SBP only after 3 minutes. These results suggests that orthostatic dysregulation of blood pressure could be evaluated by measuring at 1 minute after standing up. However, if abnormal variation of blood pressure was not observed at 1 minute after standing up, repeated measurement at 3 minutes would be necessary.


Telomeric DNA sequences differentially activated by heat shock in two Chironomus subspecies.
The patterns of puffing, transcription and protein synthesis under heat shock were analysed in polytene nuclei of Chironomus thummi piger, in comparison with those obtained in the closely related subspecies C. th. thummi. Most chromosomal heat shock puffs, as well as heat shock induced polypeptides, in C. th. piger paralleled those previously reported for C. th. thummi. Nevertheless, we found a striking difference in behaviour in the induction of telomeric Balbiani rings by heat shock in the two subspecies. Although homologous sequences were present at all the telomeres in both subspecies, they were not always transcriptionally activated by heat shock. The most frequently puffed telomeres were that of chromosome III R in C. th. thummi and that of chromosome IV R in piger. Transcription of the same sequences from both telomeric Balbiani rings (T-BR-III and T-BR-IV) occurred under heat shock. The enigmatic behaviour of telomeres and the functional significance of T-BRs are discussed in relation to possible equivalents in other Diptera.


Vaginal hysterectomy and relative merits over abdominal and laparoscopically assisted hysterectomy.
Hysterectomy is the most common operative procedure for benign gynaecological disease. The choice of hysterectomy will highlight the surgeon's mental attitude and surgical dexterity in offering the patient the safest cost-effective and reliable procedure. At present, abdominal hysterectomy is the most common method of hysterectomy, but evidence shows that patients prefer vaginal hysterectomy. With the advent of laparoscopic hysterectomy and improved surgical equipment and laparoscopic training programmes, laparoscopic hysterectomy provides equally effective hysterectomy; the patient should, therefore, have the benefit of either vaginal hysterectomy or laparoscopically assisted vaginal hysterectomy in preference to abdominal hysterectomy.


Domestic violence survivors and their experiences during legal process.
Many victims of domestic violence do not seek recourse to the needed medical and legal services. The aim of this study was to determine the difficulties faced by and experiences of female survivors of domestic violence during their medical and legal proceedings. We designed our study using a qualitative approach to understand the experiences of survivors during the legal process as well as their feelings and attitudes towards domestic violence through in-depth interviews. The data obtained from the participants were analyzed and synthesized using a thematic analysis procedure. Most of our participants reported different types of domestic violence, citing feelings of fear and loneliness during these experiences. They reported feeling dissatisfied with their complaints being ignored by the police and the perpetrators remaining unpunished. They complained of the complex procedures and negligence of staff in health-care centers such as hospitals, and they reported being shifted to several different places. We believe that an assessment of such female survivors in terms of specific standards set by specialists will help make improvements to the legal process. Education programs should be organized for professionals dealing with survivors of domestic violence. Special health-care services with fast proceedings must be established in health-care centers.


In vivo radiation dosimetry and image quality of turbo-flash and retrospective dual-source CT coronary angiography.
To compare measured radiation dose (MD), estimated radiation dose (ED) and image quality in coronary computed tomography between turbo-flash (TFP) and retrospective protocol (RP) and correlate MD with size-specific dose estimates (SSDE). In this prospective study, we selected 68 patients (mean age, 59.2 ± 9.7 years) undergoing 192 × 2 dual-source CT (SOMATOM Force, Siemens) to rule out coronary artery disease. Thirty-one underwent TFP and 37 RP. To evaluate in vivo MD, thermoluminescent dosimeters were placed, superficially, at thyroid and heart level, left breast areola and left hemi-thorax. MD in each site, and ED parameters, such as volume CT dose index (CTDIvol), SSDE, dose length product (DLP), effective dose (E), were compared between two protocols with a t test. Image quality was compared between two protocols. Inter-observer agreement was evaluated with a kappa coefficient (k). In each protocol, MD was correlated with SSDE using a Pearson coefficient (r). Comparing TFP and RP, MD at thyroid (1.43 vs. 2.58 mGy; p = 0.0408), heart (3.58 vs. 28.72 mGy; p < 0.0001), left breast areola (3.00 vs. 24.21 mGy; p < 0.0001) and left hemi-thorax (2.68 vs. 24.03 mGy; p < 0.0001), CTDIvol, SSDE, DLP and E were significantly lower. Differences in image quality were not statistically significant. Inter-observer agreement was good (k = 0.796) in TFP and very good (k = 0.817) in RP. MD and SSDE excellently correlated with TFP (r = 0.9298, p < 0.0001) and RP (r = 0.9753, p < 0.0001). With TFP, MD, CTDIvol, SSDE, DLP and E were significantly lower, than with RP. Image quality was similar between two protocols. MD correlated excellently with SSDE in each protocol.


The development of the error-related negativity in large sample of adolescent females: Associations with anxiety symptoms.
Anxiety is the most common form of psychopathology and tends to begin early in the course of development. Given this, there is great interest in identifying developmental changes in neural systems that may delineate healthy versus anxious trajectories. A substantial amount of work has focused on the error-related negativity as a neural marker of anxiety. The ERN is a negative deflection in the event-related potential that occurs when individuals make mistakes and is increased in anxious individuals. A separate body of work has focused on normative developmental changes in the ERN - demonstrating an age-related increase in the ERN that occurs across childhood and adolescence. In the current study, we examine the ERN in relation to specific phenotypic expressions of anxiety during a core risk period in a sample of females (N = 220) ranging from 8 to 14 years old. Results from the current study suggest that error-related brain activity is related to both parent and child report of social anxiety symptoms, even when controlling for all other symptom scales. Additionally, mediation models suggest that the normative developmental increase observed in the ERN is partially mediated by increases in social anxiety symptoms. The current results are novel insofar as they identify a specific phenotypic expression of anxiety that underlies developmental increases in this neural biomarker.


Seasonal variations of cadmium and zinc in Arrhenatherum elatius, a perennial grass species from highly contaminated soils.
There is interest in studying bioaccumulation in plants because they form the base of the food chain as well as their potential use in phytoextraction. From this viewpoint, our study deals with the seasonal variation, from January to July, of Cd and Zn bioaccumulation in three metallicolous populations of Arrhenatherum elatius, a perennial grass with a high biomass production. In heavily polluted soils, while Zn bioaccumulation is weak, A. elatius accumulates more Cd than reported gramineous plants, with concentration of up to 100 microg g(-1). Our results also showed seasonal variations of bioaccumulation, underlying the necessity for in situ studies to specify the date of sampling and also the phenology of the collected plant sample. In our experimental conditions, accumulation is lower in June, leading us to the hypothesis of restriction in heavy metals translocation from roots to aerial parts during seed production.


The role of voltage-gated Ca2+ channels in anoxic injury of spinal cord white matter.
Dorsal column axons of the rat spinal cord are partially protected from anoxic injury following blockade of voltage-sensitive Na+ channels and the Na+/--Ca2+ exchanger. To examine the potential contribution of voltage-gated Ca2+ channels to anoxic injury of spinal cord axons, we studied axonal conduction in rat dorsal columns in vitro following a 60-min period of anoxia. Glass microelectrodes were used to record field potentials from the dorsal columns following distal local surface stimulation. Perfusion solutions containing blockers of voltage-gated Ca2+ channels were introduced 60 min prior to onset of anoxia and continued until 10 min after reoxygenation. Pharmacological blocking agents which are relatively selective for L- (verapamil, diltiazem, nifedipine) and N- (omega-conotoxin GVIA) type calcium channels were significantly protective against anoxia-induced loss of conduction, as was non-specific block using divalent cations. Other Ca2+ channel blockers (neomycin and omega-conotoxin MVIIC) that affect multiple Ca2+ channel types were also neuroprotective. Ni2+, which preferentially blocks R-type Ca2+ channels more than T-type channels, was also protective in a dose-dependent manner. These data suggest that the influx of Ca2+, through L-, N- and possibly R-type voltage-gated Ca2+ channels, participates in the pathophysiology of the Ca2+-mediated injury of spinal cord axons that is triggered by anoxia.


Comprehension and recall from the informed consent process by phase I healthy volunteers before dose administration.
A fundamental part of all clinical trials is informed consent, reflecting the respect for the volunteer's autonomy. Research participation is voluntary; therefore, certain aspects of the proposed study must be disclosed so that volunteers can make an informed decision. In this study, we aimed to examine the level of comprehension and recall of healthy volunteers from the informed consent process. The study was carried out at a single phase I clinical trials unit. A questionnaire was administered to each volunteer to assess recall of important aspects of the study at the day-1 visit following the informed consent process. The questionnaire contained seven questions regarding study objectives, route, frequency and type of drug administration, adverse effects, number of subjects previously exposed and remuneration. One point was awarded for each correct answer. A total of 266 volunteers were administered the questionnaire. The mean total score (±standard deviation) for all volunteers was 4.5 ± 1.1 points out of 7, with a range of 0.8-6.7. For all 10 studies, 91% of volunteers responded correctly when answering about the route of administration, and 90% were able to accurately state the correct payment amount. Only 7% were able to repeat the aims of the study correctly. The poor performance of our study volunteers raises concerns about recall of information prior to study drug administration. This has implications for the volunteer's safety and ability to provide true informed consent. Interventions to improve recall prior to dosing should be undertaken.


Relationship between Epicardial Fat Tissue Thickness and CRP and Neutrophil-Lymphocyte Ratio in Metabolic Syndrome Patients Over 65 Years.
There are no data evaluating the association of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) with epicardial fat tissue thickness (EFTT) in elderly metabolic syndrome (MS) patients. In this study, we aimed to investigate the relationship of EFTT with CRP and NLR in patients with MS over 65 years. A cross-sectional study was performed. Fifty patients (patient group) with MS and 25 subjects (control group) without MS were allocated in the study. All parameters were compared in patient and control groups. The correlations between NLR, CRP, and EFTT were evaluated. White blood cell and neutrophil levels were higher in MS group (p=0.020 and p=0.019, respectively). Both transverse and longitudinal EFTT were increased in MS patients (p<0.001). There was a significant correlation between the EFTT and NLR but not with CRP in the MS group (r=0.4, p=0.003). Our study showed that both longitudinal and transverse EFTT are associated with NLR in patients older than 65 years with MS. In geriatric MS patients, higher NLR level may be an indicator of increased visceral fat around the myocardium.


Complexes with biologically active ligands. Part 4. Coordination compounds of chlorothiazide with transition metal ions behave as strong carbonic anhydrase inhibitors.
Complexes of the diuretic benzothiadiazine derivative chlorothiazide (6-chloro-7-sulfamoyl- 1,2,4-benzothiadiazine-1,1-dioxide) with V(IV); Fe(II); Co(II); Ni(II); Cu(II), Ag(I) and U(VI) were prepared and characterized by elemental analysis, spectroscopic, thermogravimetric, magnetic and conductimetric measurements. The complexes behave as effective inhibitors for two isozymes (I and II) of carbonic anhydrase (CA).


A simple approach to studying cerebral blood flow during psychological stress.
The purpose of this work was to determine, in the Wistar male rats, the role of the stress system in the control of cerebral hemodynamics induced by emotional stress (air jet). Blood flow rates in the internal carotid arteries have been obtained using chronically implanted Doppler probes. In this investigation, air-jet stress provokes a rapid and substantial elevation of blood pressure combined with hyperemia and vasodilation. Spectral analysis reveals an increase in the variability of carotid blood flow and carotid vascular conductance during stress compared to the baseline state. The coherence between the two carotid blood flow, which provides a linear correlation index in the frequency domain, was calculated before (ordinary coherence) and after mathematical elimination of the influence of blood pressure (partial coherence). The main advantages of the technique are as follows:• It allows the measurement of cerebral blood flow while comparing them with the physiological parameters of the animal such as blood pressure.• Air-jet stress is a psychological rather than physical stress that generates hyperemia in a non-pharmacological way (no side effects) without injuring the animal or damaging the experimental installation during the recording sessions.• A simple method for tracing a kinetic path before and at the moment of stress initiation.• The presence of a catheter facilitates the administration of drug substances if required.• Laboratory-developed software, based on the Lab VIEW 5.1, allows real-time monitoring of blood pressure and carotid flow rates signals using fast Fourier transform.


Correlation of low and high affinity thiol methyltransferase and phenol methyltransferase activities in human erythrocyte membranes.
Human red blood cell (RBC) membranes have been reported to contain both high and low affinity 'forms' of the drug metabolizing enzyme thiol methyltransferase (TMT). The biochemical characteristics of the two 'forms' of human RBC TMT were compared. Apparent Km constants of the high affinity activity for 2-mercaptoethanol and S-adenosyl-L-methionine, cosubstrates for the TMT reaction, were 0.38 mumol/l and 2.6 mumol/l, respectively. These constants may be compared with values of 20 mmol/l and 43 mumol/l, respectively, previously reported for the low affinity form of RBC TMT activity. The properties and regulation of the two forms of TMT were then compared with each other and also with those of two 'control' enzymes, phenol methyltransferase (PMT) and beta-glucuronidase. When high and low affinity TMT, PMT and beta-glucuronidase activities were measured in RBC membranes from 22 individual subjects, there were highly significant correlations among all three methyltransferase activities (all r values greater than 0.95), but beta-glucuronidase activity did not correlate significantly with any of the methyltransferase activities (all r values less than 0.40). The thermal stabilities of the three methyltransferases were very similar. They were all inactivated approximately 50% by incubation at 48 degrees C for 15 min. beta-Glucuronidase activity was approximately 50% inactivated by incubation at 76 degrees C for 15 min. PMT and both TMT activities had similar subcellular distributions and similar responses to ions and to enzyme inhibitors. These results suggested that high and low affinity TMT and PMT activities might be catalyzed by the same enzyme. Alternatively, these three RBC membrane methyltransferase activities might be regulated in a parallel fashion.


Horse versus rabbit antithymocyte globulin in immunosuppressive therapy of treatment-naïve aplastic anemia: a systematic review and meta-analysis.
The first-line formulation of antithymocyte globulin (ATG) remains unknown. We aimed to systematically review evidence to compare the efficacy and safety profiles of different ATGs. We did a systematic review and meta-analysis of randomized controlled trials (RCTs) and cohort controlled studies comparing horse and rabbit ATG in immunosuppressive therapy of treatment-naïve aplastic anemia. We searched The Cochrane Library, PubMed, EMBASE, ClinicalTrials.gov , and conference proceedings of American Society of Hematology and European Society for Blood and Marrow Transplantation annual meetings. The outcomes were 3-, 6-, and 12-month response; early mortality; relapse; and evolution. We pooled hazard ratios for relapse and odds ratios (ORs) for other outcomes using fixed-effect or random-effect models based on the heterogeneity. This study was registered with PROSPERO, number CRD42016036945. We included 1636 participants from three RCTs and 11 cohort controlled studies. Allocation to horse ATG increased 6-month response events by 86% compared with rabbit ATG. The benefit of horse ATG was mainly driven by increase in studies with non-Asian (OR 95% CI = 2.39 (1.54-3.69), p < 0.0001) and good partial response criterion (OR 95% CI = 2.73 (1.53-4.89), p = 0.0007). The early mortality and evolution were similar between groups. Compared with rabbit ATG, horse ATG had superior remission by 6 months and equivalent safety profiles in patients with treatment-naïve AA. Evidence for further responses beyond 6 to 12 months was limited.


Slope of change in HbA1c from baseline with empagliflozin compared with sitagliptin or glimepiride in patients with type 2 diabetes.
To analyse the effect of baseline glycated haemoglobin (HbA1c) on the reduction in HbA1c with empagliflozin compared with sitagliptin or glimepiride in patients with type 2 diabetes. Using regression analyses of individual patient data from two Phase III studies, we compared the change in HbA1c according to a unit change in baseline HbA1c (the slope) with empagliflozin 10 mg or 25 mg vs sitagliptin (monotherapy) after 24 weeks, and with empagliflozin 25 mg vs glimepiride (as add-on to metformin) after 52 weeks. Steeper slopes of HbA1c decline were observed with empagliflozin 10 or 25 mg vs sitagliptin monotherapy at week 24. Regression analysis showed slopes of -0.59 (95% CI -0.70, -0.47), -0.49 (95% CI -0.62, -0.37) and -0.29 (95% CI -0.42, -0.15) for empagliflozin 10 mg, empagliflozin 25 mg and sitagliptin, respectively (P < .001 and P < .05 for empagliflozin 10 mg and empagliflozin 25 mg, respectively, vs sitagliptin). Similarly, a steeper slope of HbA1c decline was observed with empagliflozin 25 mg vs glimepiride as add-on to metformin at week 52. Regression analysis showed slopes of - 0.52 (95% CI -0.59, -0.44) and -0.32 (95% CI -0.39, -0.25) for empagliflozin 25 mg and glimepiride, respectively (P < .001 for empagliflozin 25 mg vs glimepiride). Incremental reductions in HbA1c with increasing baseline HbA1c are greater with empagliflozin compared with sitagliptin or glimepiride in patients with type 2 diabetes.


[The pelvicaliceal system in the sonogram--distinction between physiological and pathological dilatation].
Dilatation of the pelvicalyceal system was documented in volunteers with healthy kidneys in whom renal excretation was increased by means of a variety of methods. As a rule, the proximal ureter is not visualised. In mild or moderate urinary obstruction, however, the ureter is almost always visible, and stasis is mostly unilateral. Although sonography is a method of good sensitivity, the excretory urogram remains an essential diagnostic tool in the examination of the pelvicalyceal and ureteral systems.


Changes in transcriptional factor binding capacity resulting from promoter region methylation induce aberrantly high GDNF expression in human glioma.
Glial cell line-derived neurotrophic factor (GDNF), which belongs to transforming growth factor β superfamily, plays important roles in glioma pathogenesis. Gdnf mRNA is aberrantly increased in glioma cells, but the underlying transcription mechanism is unclear. Here, we found that although the base sequence in the promoter region of the gdnf gene was unchanged in glioma cells, there were significant changes in the methylation level of promoter region I (P < 0.05) in both high- and low-grade glioma tissues. However, the methylation degree in promoter region II was notably decreased in low-grade glioma tissue compared to normal brain tissue (P < 0.05), and the demethylation sites were mainly located in the enhancer region. Conversely, methylation was markedly increased in high-grade glioma tissue (P < 0.05), and the sites with decreased methylation level were mainly located in the silencer region. The binding capacities of several transcriptional factors, such as activating protein 2, specificity protein 1, ETS-related gene 2, and cAMP response element binding protein, which specifically bind to regions with altered methylation status decreased along with the pathological grade of glioma, and the differences between high-grade glioma and normal brain tissue were significant (P < 0.05). The results suggest that changes in transcriptional factor binding capacity are due to changes in promoter region methylation and might be the underlying mechanism for aberrantly high gdnf expression in glioma.


Vascular endothelial growth factor A gene (VEGFA) polymorphisms and expression of VEGFA gene in lung cancer patients of Kashmir Valley (India).
The vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. Polymorphisms in the VEGF gene may regulate VEGF production. In this case-control study, we investigated whether functional polymorphisms (+405 C > G and +936 C > T) in the VEGF gene are associated with the risk of lung cancer. Genomic DNA was isolated from the blood of 100 lung cancer patients and 150 healthy controls, and total RNA was isolated from 48 tumor tissues and adjacent normal lung tissues. Two DNA polymorphisms (+405 C > G and +936 C > T) in the 3'-untranslated regions (3'-UTR) and 5'-untranslated regions (5'-UTR) of vascular endothelial growth factor A (VEGFA) were studied using PCR-RFLP method, and mRNA expression of VEGFA was studied by quantitative real-time PCR. Polymorphisms in the 5'-UTR (+405 C > G) and 3'-UTR (+936 C > T) did not show significant difference between lung cancer cases and control samples (P = 0.11 and P = 0.09, respectively). VEGF +405 CG and GG are significantly more in age group >50 years old, in all grades, and in early pathological stages (P = 0.04, P = 0.03, and P = 0.006, respectively). Also, increased expression of VEGFA mRNA was noted in tumorous compared to non-tumorous tissue (P < 0.0001). Overexpression of the gene was considered at ΔC (T) > 6.0. Within the group of patients with conventional tumor, those with histology other than squamous cell carcinoma (SCC) had a higher level of VEGFA mRNA expression than SCC patients (P = 0.04). Overexpression of VEGFA mRNA was noted in lung cancer and more so in lung cancer with adenocarcinoma and large cell carcinoma histology and in pathological stages III and IV. VEGFA +405 C > G SNP showed an association with age, pathological grade, and stage.


[Prevalence of reactions secundary to mosquito bites Aedes aegypti at en el Regional Center of Allergy and Clinical Immunology, University Hospital, de Monterrey, Nuevo Leon].
although systemic reactions resulting from hymenoptera stings have been studied extensively, the prevalence of allergic reactions to mosquitoes is unknown. to investigate the prevalence of allergic reactions to Aedes aegypti bites in patients seeking treatment at the Allergy and Clinical Immunology Regional Center of Jose E Gonzalez University Hospital in Monterrey, Mexico. we carried out a cross-sectional, descriptive study that included patients receiving skin tests for aeroallergens; skin sensitivity to mosquito bites was also tested. A questionnaire was used to obtain information about previous allergic reactions to mosquito bites. a total of 482 patients between 2 and 60 years of age were included; 53% were female, 407 (84.4%) had a history of local reactions to mosquito bites. Twelve patients (2.4%) stated a history of large local reaction; three (0.6%) of them with a positive skin prick test, one (0.2%) of those had systemic reaction history to mosquito. Eighty five (17.6%) patients had a positive mosquito skin test and 307 (63.6%) had a positive skin test for at least one aeroallergen. Seventy-eight (91.7%) of the 85 patients with a positive mosquito skin test had a history of local skin reactions to mosquito bite (odds ratio: 2.303 [confidence interval (CI) 1.037-5.10]. There was no statistically significance association between allergic diseases and mosquito allergy. adverse reactions and allergic reactions to mosquito bites occur frequently. However mosquito allergy is low. Further studies are required to determine the prevalence of mosquito allergy in the general population.


Hormetic modulation of angiogenic factors by exercise-induced mechanical and metabolic stress in human skeletal muscle.
This study used an integrative experimental model in humans to investigate whether muscle angiogenic factors are differentially modulated by exercise stimuli eliciting different degrees of mechanical and metabolic stress. In a randomized crossover design, 12 men performed two low-volume high-intensity exercise regimens, including short sprint intervals (SSI) or long sprint intervals (LSI) inducing pronounced mechanical/metabolic stress, and a high-volume moderate-intensity continuous exercise protocol (MIC) inducing mild but prolonged mechanical/metabolic stress. Gene and protein expression of angiogenic factors was determined in vastus lateralis muscle samples obtained before and after exercise. Exercise upregulated muscle VEGF mRNA to a greater extent in LSI and MIC compared with SSI. Analysis of angiogenic factors sensitive to shear stress revealed more marked exercise-induced VEGF receptor 2 (VEGF-R2) mRNA responses in MIC than SSI, as well as greater platelet endothelial cell adhesion molecule (PECAM-1) and endothelial nitric oxide synthase (eNOS) mRNA responses in LSI than SSI. No apparent exercise-induced phosphorylation of shear stress-sensory proteins VEGF-R2Tyr1175, PECAM-1Tyr713, and eNOSSer1177 was observed despite robust elevations in femoral artery shear stress. Exercise evoked greater mRNA responses of the mechanical stretch sensor matrix metalloproteinase-9 (MMP9) in SSI than MIC. Exercise-induced mRNA responses of the metabolic stress sensor hypoxia-inducible factor-1α (HIF-1α) were more profound in LSI than SSI. These results suggest that low-volume high-intensity exercise transcriptionally activates angiogenic factors in a mechanical/metabolic stress-dependent manner. Furthermore, the angiogenic potency of low-volume high-intensity exercise appears similar to that of high-volume moderate-intensity exercise, but only on condition of eliciting severe mechanical/metabolic stress. We conclude that the angiogenic stimulus produced by exercise depends on both magnitude and protraction of myocellular homeostatic perturbations.NEW & NOTEWORTHY Skeletal muscle capillary growth is orchestrated by angiogenic factors sensitive to mechanical and metabolic signals. In this study, we employed an integrative exercise model to synergistically target, yet to different extents and for different durations, the mechanical and metabolic components of muscle activity that promote angiogenesis. Our results suggest that the magnitude of the myocellular perturbations incurred during exercise determines the amplitude of the angiogenic molecular signals, implying hormetic modulation of skeletal muscle angiogenesis by exercise-induced mechanical and metabolic stress.


Tackling the Challenges of 21st-Century Open Science and Beyond: A Data Science Lab Approach.
In recent years, there has been a drive toward more open, cross-disciplinary science taking center stage. This has presented a number of challenges, including providing research platforms for collaborating scientists to explore big data, develop methods, and disseminate their results to stakeholders and decision makers. We present our vision of a "data science lab" as a collaborative space where scientists (from different disciplines), stakeholders, and policy makers can create data-driven solutions to environmental science's grand challenges. We set out a clear and defined research roadmap to serve as a focal point for an international research community progressing toward a more data-driven and transparent approach to environmental data science, centered on data science labs. This includes ongoing case studies of good practice, with the infrastructural and methodological developments required to enable data science labs to support significant increase in our cross- and trans-disciplinary science capabilities.


When simple hernia is not that simple: Treatment of concomitant pathology in acute care surgery, a case report.
Obstructed colon cancer is not an uncommon surgical emergency. Many other surgical diseases may overlap their presenting symptoms. This paper aims to report a colon cancer case with delayed diagnosis due to a long-standing para-umbilical hernia (PUH). 60-year-old female patient presented to our emergency department (ED) with an obstructed PUH. The patient underwent watchful conservative management many times before due to associated comorbidities. This history of recurrent intestinal obstruction and incomplete regain of regular bowel habits after every hospital admission raises the possibility for concealed pathology. Further investigations, including computed tomography (CT), revealed a suspicion of an obstructed malignant mass at the colon's splenic flexure accompanied with complete bowel obstruction. The patient and their family consulted for exploratory laparotomy and the possibility of stoma formation. The intra-operative finding was constant with a small ventral defect, and a dilated bowel loops up to a left colon transition zone. We achieved left hemicolectomy with a primary anastomosis after intra-operative bowel lavage. The postoperative period was uneventfully, and the patient was discharged home after seven days of admission. Follow up in the outpatient surgical clinic for three months revealed no recordable complications. The patient had transferred to the oncology center for the completion of adjuvant therapy. This case had a small PUH with recurrent obstruction. The delay in its management was due to the patient's comorbidities. However, the incomplete resolution of patient symptoms during watchful oversight increases the likelihood of another hidden pathology that required further investigation. We expanded CT indication in such patients to find the exact cause of patient symptoms, especially chronic constipation and incomplete recovery after every admission. While concurrent pathology is the norm in elective surgery and can be dealt with safely, in non-elective surgery, a thorough search about the patient's exact complaints is mandatory to decrease morbidity and mortality rates. In the same patient, both colon cancer and abdominal wall hernias can produce conflicting symptoms and delay diagnosis. However, with a high index of suspicion and correlation of patient symptoms, can be safely managed without morbidity.


Substitution of porphyropsin for rhodopsin in mouse retina.
Weanling, male albino mice were placed on a vitamin A-free diet for three months to deplete their vitamin A stores. The vitamin A-deficient mice were injected intraperitoneally with all-trans 3-dehydroretinol. 3-dehydroretinol was rapidly incorporated into the liver as a fatty acid ester. The chromophore of visual pigment increased gradually and reached a normal level 13 days after the injection. 3-Dehydroretinal accounted for 95% of the total chromophore in the retina. The high proportion of 3-dehydroretinal was observed also in the long-term experiment which was continued for six weeks with the injection of 3-dehydroretinol once a week. When the animal was injected with a mixture of 3-dehydroretinol and retinol, the ratio of dehydroretinal/retinal in the retina was far lower than the ratio of dehydroretinol/retinol in the liver. These results indicate that 3-dehydroretinol is not converted to retinol in mouse and is used less efficiently than retinol for the chromophore of visual pigment. The synthesis of visual pigment was observed even when the animal was kept in complete darkness after the injection of all-trans 3-dehydroretinol. This fact indicates that light is not required for the production of 11-cis chromophore of visual pigment.


Trihexyphenidyl dependence-report of two cases.
Two cases of normal dose dependence on Trihexyphenidyl are reported. The literature on anti parkinsonian drug abuse and dependence is briefly reviewed.


G2-phase radiation response in lymphoblastoid cell lines from Nijmegen breakage syndrome.
The relationship between G2-phase checkpoint activation, cytoplasmic cyclin-B1 accumulation and nuclear phosphorylation of p34CDC2 was studied in Nijmegen breakage syndrome cells treated with DNA damaging agents. Experiments were performed on lymphoblastoid cell lines from four Nijmegen breakage syndrome patients with different mutations, as well as on cells from an ataxia telangiectasia patient. Lymphoblastoid cell lines were irradiated with 0.50-2 Gy X-rays and the percentage of G2-phase accumulated cells was evaluated by means of flow cytometry in samples that were harvested 24 h later. The G2-checkpoint activation was analysed by scoring the mitotic index at 2 and 4 h after treatment with 0.5 and 1 Gy X-rays and treatment with the DNA double-strand break inducer calicheamicin-gamma1. Cytoplasmic accumulation of cyclin-B1 was evaluated by means of fluorescence immunostaining or Western blotting, in cells harvested shortly after irradiation with 1 and 2 Gy. The extent of tyrosine 15-phosphorylated p34CDC2 was assessed in the nuclear fractions. Nijmegen breakage syndrome cells showed suboptimal G2-phase checkpoint activation respect to normal cells and were greatly different from ataxia telangiectasia cells. Increased cytoplasmic cyclin-B1 accumulation was detected by both immunofluorescence and immunoblot in normal as well as in Nijmegen breakage syndrome cells. Furthermore, nuclear p34CDC2. phosphorylation was detected at a higher level in Nijmegen breakage syndrome than in ataxia telangiectasia cells. In conclusion, our data do not suggest that failure to activate checkpoints plays a major role in the radiosensitivity of Nijmegen breakage syndrome cells.


Impaired delta NP63 expression is associated with poor tumor development in transitional cell carcinoma of the bladder.
The oncogenic isoform of the p63 protein, delta Np63 (delta Np63), plays an important role in the pathogenesis of many epithelial carcinomas, and emerging evidences suggest that delta Np63 is a promising drug target. However, the functions of delta Np63 in transitional cell carcinoma of bladder (TCCB) are poorly defined. In this study, a delta Np63 shRNA expression vector was transfected into TCCB cell line 5637 and cell cycling, cell proliferation and protein expression were assessed by flow cytometry and 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-dimethyl tetrazolium bromide (MTT) assay, and immunohistochemistry, respectively. The delta Np63 shRNA expression vector was also injected into 5637 cell xenograft tumors in nude mice, and tumor size was measured, tumor tissue morphology was assessed by immunohistopathology and transmission electron microscopy. In the in vitro study, delta Np63 shRNA transfection caused successful delta Np63 gene silencing and resulted in significant arrest of cell cycling and cellular proliferation (p<0.05) as well as cyclin D1 expression. In the nude mouse xenograft model, delta Np63 shRNA greatly inhibited tumor growth, induced tumor cell apoptosis (p<0.05) and resulted in cyclin D1 downregulation. Our data suggest that delta Np63 may play an oncogenic role in TCCB progression through promoting cell survival and proliferation. Intratumoral administration of delta Np63-specific shRNA suppressed tumor delta Np63 expression and cellular proliferation while promoted tumor cellular apoptosis, and therefore inhibited tumor growth and improved survival of xenograft-bearing mice, which was not accompanied by significant signs of systemic toxicity.


Midterm effects and clinical benefits of left ventricular vs biventricular pacing in heart failure.
Although left ventricular pacing (LVP) leads to a greater acute hemodynamic response than does biventricular pacing (BVP), the long-term effects are diverse. We aimed to assess the efficacy of LVP and BVP in patients undergoing cardiac resynchronization therapy and determine which patients would benefit more from LVP or BVP. Randomized controlled trials that compared left and biventricular pacing were retrieved from MEDLINE and analyzed for changes in cardiac function and dimensions, cardiac resynchronization therapy response, and electromechanical effects. A total of 811 patients were included from 9 trials. After a mean follow-up, a shorter QRS duration (-40.92 milliseconds; 95% confidence interval [CI], -64.50 to -17.34; P = 0.0007), and improved left ventricular dimensions were observed in the BVP group compared with the LVP group. Moreover, the BVP group had a longer 6-minute hall walk (6MHW) test (37.19 m; 95% CI, 4.72 to 69.67; P = 0.02). Our results indicate that BVP results in a better electromechanical effect and leads to a better 6MHW test. For all other test criteria, LVP showed a benefit equal to that of BVP. Thus, there is currently insufficient evidence to advocate for LV-only pacing.


Suture configuration techniques have no effect on mid-term clinical outcomes of arthroscopic meniscus root repairs.
The aim of this study was to evaluate the clinical and radiological outcomes of arthroscopic transtibial pullout repair (ATPR) for the medial meniscus with both two modified loop stitches (TLS) and two simple stitches (TSS) techniques. Between January 2013 and January 2016, 41 patients who had undergone ATPR for medial root tears with TLS and TSS techniques were retrospectively evaluated. The mean age at operation was 53 years (range 45-58). The mean follow-up period was 44.6 months (range 26-64). Lysholm knee score was used for clinical evaluation before and after surgery. For all patients, meniscal extrusion distances in the coronal plane were measured using magnetic resonance imaging and were recorded both preoperatively and at final follow-up. There was no difference in terms of meniscus extrusion measurements between groups preoperatively (P > .05). Postoperative meniscus extrusion measurements were 2.1 ± 0.3 and 2.9 ± 0.6 in TLS and TSS groups, respectively. The difference between groups was statistically significant (P < .01). The increase in postoperative Lysholm score was found to be statistically significant in both groups (P < .01). Postoperative Lysholm scores were 88.8 ± 3.7 and 87.6 ± 4.8 in TLS and TSS groups, respectively. The difference between groups was statistically insignificant (P > .05). There was a significant improvement in Lysholm knee scores postoperatively in patients that underwent transtibial pullout medial meniscus posterior root repair regardless of meniscus reduction level and suture configuration types. Although TLS technique was superior to TSS technique in terms of meniscus reduction, this meniscus reduction did not create any clinical difference at clinical outcome.


Detection of RNA-DNA association by a proximity ligation-based method.
We describe a proximity ligation assay (PLA)-based method of assessing association of DNA and RNA in single cells during the cell cycle. Pulse-labeling of DNA with EdU and RNA with BrU and testing their close proximity by PLA demonstrates that RNA synthesis in individual cells resumes about 30-45 min after DNA replication. Consistent with this conclusion, RNA Pol II phosphorylated at Ser2 of its CTD is detected at the same time as RNA transcripts on nascent DNA. Our results also show that RNA is associated with DNA foci during all stages of mitosis.


A reflection on economic uncertainty and fertility in Europe: The Narrative Framework.
The generalized and relatively homogeneous fertility decline across European countries in the aftermath of the Great Recession poses serious challenges to our knowledge of contemporary low fertility patterns. In this paper, we argue that fertility decisions are not a mere "statistical shadow of the past", and advance the Narrative Framework, a new approach to the relationship between economic uncertainty and fertility. This framework proffers that individuals act according to or despite uncertainty based on their "narrative of the future" - imagined futures embedded in social elements and their interactions. We also posit that personal narratives of the future are shaped by the "shared narratives" produced by socialization agents, including parents and peers, as well as by the narratives produced by the media and other powerful opinion formers. Finally, within this framework, we propose several empirical strategies, from both a qualitative and a quantitative perspective, including an experimental approach, for assessing the role of narratives of the future in fertility decisions.


Association of TMPRSS2 Gene Polymorphisms with COVID-19 Severity and Mortality: a Case-Control Study with Computational Analyses.
Coronavirus disease 2019 (COVID-19) is a severe disease caused by a new variant of beta-coronavirus that first appeared in China. Human genetic factors, including polymorphisms, serve pivotal roles in the high transmission of SARS-CoV-2 and the stubbornly progressing sickness seen in a small but significant percentage of infected people; however, but these factors remain ill-defined. A total of 288 COVID-19 patients and 288 controls were genotyped for TMPRSS2 polymorphisms using both restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and amplification refractory mutation system (ARMS)-PCR techniques. Different genotypes of TMPRSS2 polymorphisms were compared in terms of disease susceptibility and mortality. The statistical analysis showed that minor alleles of all studied variants statistically increased the risk of COVID-19, except for the rs75603675 C > A variant. The T allele of rs12329760 conferred an increased risk of COVID-19. Moreover, the AG/AC/TT/AG combination of genotypes significantly enhanced the risk of COVID-19 in our population. Different haplotypes of rs17854725/rs75603675/rs12329760/rs4303795 polymorphisms, including GACA, GACG, GATG, GATA, AATA, ACCG, ACTG, ACTA, GCCA, and GCTG, were found to be associated with increased risk of the disease (odds ratio > 1). Regarding the clinical and paraclinical characteristics, a statistically significant difference was found between non-severe and severe forms except for gender, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and underlying diseases. In addition, case genotypes of TMPRSS2 rs17854725 A > G, rs12329760 C > T, and rs4303795 A > G were significantly different regarding severe and non-severe forms of the disease (P-value < 0.001). Specifically, death was more frequent in carriers of the AG genotype of rs17854725 A > G (P-value = 0.022). Patients who carry the minor alleles of the four studied TMPRSS2 variants were rather vulnerable to COVID-19 infection. Our findings indicated that rs17854725 A > G (AA vs. AG and AA vs. GG), rs12329760 C > T (CC vs. CT and CC vs. TT), and rs4303795 A > G (AA vs. AG) genotypes of TMPRSS2 variations are associated with a more invasive disorder pattern. More studies on larger populations are needed to confirm our results.


Adrenoceptors involved in the contractile activity of islated pregnant rat uterus.
Cumulative log dose-response curves of soterenol, isoproterenol, phenylephrine and norepinephrine on isolated pregnant rat uterus at different days of gestation, were investigated. Soterenol produced a sustained inhibition of spontaneous motility during the whole pregnancy and this effect was blocked by butoxamine. The affinity of myometrium for the beta 2-adrenoceptor agonist was parallel to the concentration of progesterone in plasma during pregnancy. Isoproterenol, norepinephrine and phenylephrine caused dual, alpha- and beta-mediated responses, their relative dominance varied with the concentration and the days of pregnancy, alpha-Adrenoceptor effects of the amines coincided with increased plasma concentrations of estrogens, whereas beta ones were in parallel with the increment of plasma progesterone. It is concluded that: (a) there exist in the pregnant rat uterus beta 2-receptor-mediated responses influenced by the length of gestation; and (b) the concentration-pregnancy-dependent biphasic actions of isoproterenol, norepinephrine or phenylephrine suggest that their variable hormone-modulated ability interacts with both alpha- and beta-adrenoceptive uterine sites.


Augmented Oscillations in QT Interval Duration Predict Mortality Post Myocardial Infarction Independent of Heart Rate.
This study seeks to decompose QT variability (QTV) into physiological sources and assess their role for risk stratification in patients post myocardial infarction (MI). We hypothesize that the magnitude of QTV that cannot be explained by heart rate or respiration carries important prognostic information. Elevated beat-to-beat QTV is predictive of cardiac mortality, but the underlying mechanisms, and hence its interpretation, remain opaque. We decomposed the QTV of 895 patients post MI into contributions by heart rate, respiration, and unexplained sources. Cox proportional hazard analysis demonstrates that augmented oscillations in QTV and their level of dissociation from heart rate are associated with a higher 5-year mortality rate (18.4% vs. 4.7%, p < 0.0001). In patients with left ventricular ejection fraction (LVEF) > 35%, a higher QTV risk score was associated with a significantly higher 5-year mortality rate (16% vs. 4%, p < 0.0001). In patients with a GRACE score ≥ 120, a higher QTV risk score was associated with a significantly higher 5-year mortality (25% vs. 11%, p < 0.001). Augmented oscillations in QTV and discordance from heart rate, possibly indicative of excessive sympathetic outflow to the ventricular myocardium, predict high risk in patients post MI independent from established risk markers. www.ClinicalTrials.gov, identifier NCT00196274.


The role of the limbus in corneal allograft rejection.
The state of the recipient peripheral cornea and limbus exerts a strong influence on subsequent corneal graft survival. In particular, graft outcome is influenced by the number of dendritic cells (Langerhans cells) that have infiltrated the graft bed from the limbus. The number of dendritic cells present in the donor button also affects subsequent graft survival.


Effect of nitrogen supply and Azospirillum brasilense Sp-248 on the response of wheat to seawater irrigation.
Response of wheat to Azospirillum brasilense Sp-248 inoculation with different N-fertilizer levels using seawater irrigation was investigated. All inoculated treatments increased plant height, shoot and root dry weight, and tiller number in compared with uninoculated treatments. Yield parameters measured were also increased due to the inoculation. In terms of the effect of saline irrigation, there were no significant differences in growth and yield parameters in plants treated with tap water and others irrigated with 8.0% seawater concentration. This would indicate a relatively high tolerance of A. brasilense to saline irrigation and its ability to reduce the deleterious effects of saline on growth by increasing the plant's adaptation. However, increasing the seawater concentration in the irrigation water to 16.0% significantly decreased all tested parameters. Inoculation treatments generally increased NPKCa contents and decreased sodium ratio of the grains in compared with the uninoculated treatments. Overall results clearly revealed that the Azospirillum inoculation saved about 20 units of N-fertilizer and that saving was made economically feasible by decreasing the chemical fertilizers needed, improving the nitrogen content and counteracting the effects of salinity.


[The wife of the impotent person. Key element in the prognosis].
The authors develop the key position of the wife in male impotence, even if organic. This influence may be positive or negative and plays an important role in the prognosis.


Anatomical relationship of coronary sinus/great cardiac vein and left circumflex coronary artery along mitral annulus in atrial fibrillation before radiofrequency catheter ablation using 320-slice CT.
We evaluated anatomical relationships between the coronary sinus and great cardiac vein (CS/GCV) and left circumflex coronary artery (LCX) along the mitral annulus (MA) in patients with atrial fibrillation (AF) using 320-slice CT. Fifty-three patients with AF (44 males; mean 63 ± 11 years; 28 paroxysmal, 10 persistent, and 15 permanent AF) underwent 320-slice CT. Double-oblique CT images perpendicular to the MA short axis were created every 10° for 36 circumferential sections. The angle of 0° corresponded to the 12 o'clock position. CS/GCV-MA distance was greatest in the posterolateral MA. CS/GCV diverged from the LCX more widely in the lateral through posterolateral MA than the anterior through anterolateral MA. CS/GCV crossed the LCX in 51 patients (96.2%) and left main coronary artery in 2 patients (3.8%). Median angle of the CS/GCV-LCX crossing point was at 40° but ranged widely (0° to 150°) and was more frequent in the anterior and anterolateral MA than in the lateral, posterolateral, and posterior MA (31.4%, 45.1%, 11.8%, 11.8%, and 0%, respectively; P<0.01). CS/GCV crossed over the LCX in 39 patients and under the LCX in 12 patients. Range of the CS/GCV-LCX overlapping course increased significantly as the CS/GCV-LCX crossing point neared the CS ostium. Correlation coefficient between the range of the overlapping course and crossing point angle was 0.78. Anatomical relationships between CS/GCV and LCX greatly varied in location and proximity among AF patients. Interventional electrophysiologists should know the potential risk for LCX injury when radiofrequency energy is delivered within the CS/GCV.


Mutational studies with the trp repressor of Escherichia coli support the helix-turn-helix model of repressor recognition of operator DNA.
Several classes of trp repressor mutants were selected and analyzed in vivo. Mutants that produced repressors with either enhanced or reduced activity were obtained. One class of mutants produced inactive or slightly active repressors that were trans-dominant to the wild-type repressor. The amino acid substitutions in many of these repressors were clustered in a segment of the polypeptide that is homologous to the DNA recognition domain of the lambda cro repressor. A second functionally important region of the trp repressor was identified; this region could participate in L-tryptophan binding. Observations with trpR nonsense mutants suggest that the first 67 residues of the repressor polypeptide are sufficient for subunit association.


Biopharmaceutics classification evaluation for paris saponin VII.
To study the biopharmaceutics characteristics of paris saponin VII (PSVII). The solubility of PSVII was evaluated by measurement of the equilibrium solubility in different solvents and media. The permeability of PSVII was evaluated by measuring the oil/water partition coefficient (lgPapp) and determining the apparent permeability coefficient (PCapp) on a mono-layer Caco-2 cell model. The effects of p-glycoprotein and multidrug resistance related protein 2 on PSVII transport in mono-layer Caco-2 cell model were further investigated. Finally, the small intestinal absorption of PSVII was investigated in rat. In solvents of different pH, the equilibrium solubility of PSVII was quite low, and the dose number of PSVII was larger than 1. The lgPapp of PSVII was less than 0. The apparent permeability coefficient [PCapp(AP-BL)] of PSVII in mono-layer Caco-2 cell model was less than 14.96 × 10-6 cm·s-1, and the efflux ratio of PSVII in mono-layer Caco-2 cell model was less than 1. The transport rate of PSVII in mono-layer Caco-2 cell model was not affected by the inhibitors of p-glycoprotein and multidrug resistance related protein 2. After oral administration, PSVII could be detected in rat intestinal contents, but could not be detected in the small intestinal mucosa. PSVII showed low solubility and permeability, which would result in low oral bioavailability in clinic. PSVII belonged to Class IV compound in biopharmaceutics classification system.


HLA-A, -B and -DRB1 polymorphism in Koreans defined by sequence-based typing of 4128 cord blood units.
Human leucocyte antigen (HLA) alleles and haplotypes differ significantly among different ethnic groups, and high-resolution typing methods allow for the detection of a wider spectrum of HLA variations. In this study, HLA-A, -B and -DRB1 genotypes were analysed in 4128 cord blood units obtained from Korean women using the sequence-based typing method. A total of 44 HLA-A, 67 HLA-B and 48 HLA-DRB1 most probable alleles were identified. Of these, high-frequency alleles found at a frequency of ≥5% were 6 HLA-A (A*02:01, A*02:06, A*11:01, A*24:02, A*31:01, A*33:03), 5 HLA-B (B*15:01, B*44:03, B*51:01, B*54:01, B*58:01) and 7 HLA-DRB1 (DRB1*01:01, DRB1*04:05, DRB1*07:01, DRB1*08:03, DRB1*09:01, DRB1*13:02, DRB1*15:01) alleles. At each locus, A*02, B*15 and DRB1*04 generic groups were most diverse at allelic level, consisting of 8, 11 and 10 different alleles, respectively. Two- and three-locus haplotypes estimated by the maximum likelihood method revealed 73 A-B, 74 B-DRB1 and 42 A-B-DRB1 haplotypes with frequencies of ≥0.3%. A total of 193 A-B-DRB1 haplotypes found at a frequency of ≥0.1% were presented, and the six most common haplotypes were A*33:03-B*44:03-DRB1*13:02 (4.6%), A*33:03-B*58:01-DRB1*13:02 (3.0%), A*24:02-B*07:02-DRB1*01:01 (2.7%), A*33:03-B*44:03-DRB1*07:01 (2.5%), A*30:01-B*13:02-DRB1*07:01 (2.2%) and A*24:02-B*52:01-DRB1*15:02 (2.1%). Compared with previous smaller scale studies, this study further delineated the allelic and haplotypic diversity in Koreans including low-frequency alleles and haplotypes. Information obtained in this study will be useful for the search for unrelated bone marrow donors and for anthropologic and disease association studies.