Paranormal belief, cognitive-perceptual factors, and well-being: A network analysis.
By assessing interrelationships among variables within a specified theoretical framework, network analysis (NA) provides nuanced insights into how associations between psychological constructs are related to outcome measures. Noting this, the authors used NA to examine connections between Paranormal Belief, cognitive-perceptual factors (Schizotypy, Transliminality, and Manic-Depressive Experience), and well-being (Life Satisfaction, Meaning in Life, Somatic Complaints, Perceived Stress, Depressive Symptoms). Data derived from a sample of 3,090 participants (mean age = 50.30, standard deviation = 15.20; 46.5% male, 53.1% female) who completed standardised self-report measures capturing the study constructs online. Transliminality, Unusual Experiences (positive schizotypy), and Depressive Experience demonstrated high expected influence centrality. This indicated that these factors were the most strongly connected and influential in the network. Moreover, Transliminality was a connecting variable between Paranormal Belief, positive schizotypy, and psychopathology. Depressive Experience bridged the relationship between Transliminality and well-being. The conceptual implications of these outcomes are discussed with regards to better understanding relationships between Paranormal Belief, cognitive-perceptual factors, and well-being.


Landscape of Immune-Related Pneumonitis in Cancer Patients with Asthma Being Treated with Immune Checkpoint Blockade.
Predicting the factors that increase the risk of immune-related pneumonitis, a potentially life-threatening complication of treatment with immune checkpoint inhibitors for cancer, is a clinical challenge. Baseline clinical factors such as asthma may portend the development of pneumonitis due to pre-existing airway inflammation prior to immunotherapy. The purpose of the study was to investigate whether a prior diagnosis of asthma is associated with an increased risk of immune-related pneumonitis in patients undergoing cancer immunotherapy. Patients at the Moores Cancer Center at UC San Diego Health undergoing immunotherapy were identified on an IRB-approved protocol. Clinical charts were reviewed for asthma documented in the medical records and CT scans were reviewed during and after treatment. Pneumonitis was defined as the onset of new pulmonary symptoms with characteristic imaging findings during or after a patient's first course of immunotherapy that could not be readily explained as infection or a progression of malignancy. It was graded according to the Common Terminology Criteria for Adverse Events. A total of 187 patients were included. A diagnosis of asthma was found in the records of 26 cases (13.9%). Pneumonitis was found in 10 cases (5.35%); 50% were grade 2 and 50% were grade 3-4. Two of the grade 3-4 cases (40%) occurred in patients with non-small-cell lung cancer. Three patients with asthma developed pneumonitis (11.5% of patients with asthma), all grade 3-4. Only 28.6% of the non-asthma-pneumonitis cases were grade 3-4. All (100%) of the asthma-pneumonitis patients were former smokers, while 71.4% of the non-asthma-pneumonitis patients were former smokers. A history of asthma may be associated with a higher grade of pneumonitis if it develops, and a history of smoking may augment this relationship.


Predictors of burnout, compassion fatigue, and compassion satisfaction experienced by community health workers offering maternal and infant services in New York State.
Although burnout has been increasingly well studied among medical (nurses, physicians, residents) and mental health providers (psychologists, psychiatrists, social workers), there continues to be a lack of attention on the well-being of community-based providers, such as Community Health Workers (CHWs), within the United States. Using cross-sectional data from 75 CHWs employed in 14 agencies funded through the Maternal and Infant Community Health Collaboratives Initiative (MICHC) in New York, our study examined predictors (anxiety, physical health, adverse childhood experiences, job satisfaction, role certainty, demographic and work characteristics) of burnout, compassion fatigue (CF) and compassion satisfaction (CS). Descriptive statistics were used to characterize our sample and linear regression was employed to investigate the correlates of burnout, CF and CS. Results indicated that CHWs with higher levels of anxiety and lower job satisfaction were more likely to have higher burnout scores. CHWs with higher levels of anxiety, lower job satisfaction and fewer days of poorer health were more likely to report higher CF. Those who worked more than 35 h per week were less likely to report higher CS. The study provides recommendations for organizational-level interventions to address risk factors of burnout and CF and promote CS among CHWs, such as bolstering supervision, encouraging greater communication, offering recognition/appreciation of CHWs and creating opportunities for self-care. Findings should be considered when designing organizational-level preventive measures that mitigate burnout and CF and promote CS.


Absence of patient-to-patient intrahospital transmission of Staphylococcus aureus as determined by whole-genome sequencing.
Nosocomial transmission of pathogens is a major health care challenge. The increasing spread of antibiotic-resistant strains represents an ongoing threat to public health. Previous Staphylococcus aureus transmission studies have focused on transmission of S. aureus between asymptomatic carriers or used low-resolution typing methods such as multilocus sequence typing (MLST) or spa typing. To identify patient-to-patient intrahospital transmission using high-resolution genetic analysis, we sequenced the genomes of a consecutive set of 398 S. aureus isolates from sterile-site infections. The S. aureus strains were collected from four hospitals in the Houston Methodist Hospital System over a 6-month period. Importantly, we discovered no evidence of transmission of S. aureus between patients with sterile-site infections. The lack of intrahospital transmission may reflect a fundamental difference between day-to-day transmission events in the hospital setting and the more frequently studied outbreak scenarios. Importance: Previous studies have suggested that nosocomial transmission of S. aureus is common. Our data revealed an unexpected lack of evidence for intrahospital transmission of S. aureus between patients with invasive infections. This finding has important implications for hospital infection control and public health efforts. In addition, our data demonstrate that highly related pools of S. aureus strains exist in the community which may complicate outbreak investigations.


Preliminary results indicate resveratrol affects proliferation and apoptosis of leukemia cells by regulating PTEN/PI3K/AKT pathway.
PTEN-PI3K/AKT signaling pathway is widely involved in the regulation of cell proliferation, cell cycle, apoptosis, and invasion. Resveratrol (Resv) is a natural botanical ingredient involved in several biological activities. It is still unclear in terms of whether Resv may exert anti-leukemia effects by regulating the PTEN-PI3K/AKT pathway. This study investigated the effect of Resv on leukemia cell proliferation and apoptosis by regulating PTEN-PI3K/AKT pathway. Human normal peripheral blood PBMC cells, and human acute promyelocytic leukemia (APL) cell line NB-4 and HL-60 cells were cultured in vitro. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect Phosphatase and tensin homolog (PTEN) mRNA expression. Western blot was adopted to test PTEN protein expression. HL-60 and NB-4 cells were treated with 0, 5, 10, and 20 μM Resv, respectively. Cell proliferation was analyzed by cell counting kit8 (CCK-8) assay. The level of caspase-3 was measured by Western blot. HL-60 cells were divided into control group, 20 μM Resv treatment group, and Resv+PTEN inhibitor SF1670 group. Cell apoptosis was determined by flow cytometry. Cell proliferation was assessed by EdU staining. Compared with peripheral blood mononuclear cell (PBMC), PTEN mRNA and protein levels were significantly decreased in NB-4 and HL-60 cells. Resv significantly inhibited the proliferation activity in HL-60 and NB-4 cells, and increased the activity of caspase-3. Resv treatment up-regulated the expression of PTEN and reduced the expression of p-AKT protein in HL-60 cells. However, Resv treatment markedly suppressed the proliferation of HL-60 and induced apoptosis. SF1670 treatment in the presence of Resv significantly antagonized the down-regulation of p-AKT protein expression induced by Resv, resulting in decreased apoptosis and enhanced cell proliferation. Resv can up-regulate PTEN expression and inhibit the activity of PI3K/AKT pathway to play an anti-leukemia effect through suppressing cell proliferation and inducing apoptosis.


Age and Training-Related Changes on Body Composition and Fitness in Male Amateur Cyclists.
Master athletes are considered as a model of healthy aging because they can limit the age-related decline of physiological abilities compared to sedentary individuals. The main objective of this study is to analyze age-related changes and annual training on body composition (BC) and cardiorespiratory fitness (CRF) parameters. The participants in this retrospective cross-sectional study were 176 male cyclists, aged 40-60 years. BC was evaluated through anthropometric measurements and CRF was determined by an incremental cycle ergometer test to exhaustion. A comparative study between age groups was carried out through a one-way ANOVA test and the associations between the variables were assessed by Spearman's correlation coefficients and multiple regression analysis to estimate the performance. Training was generally associated with a decrease in both body weight and body fat (p < 0.05). A decrease in resting heart rate was observed as a vagal effect of kilometers cycled per year (p < 0.05). Kilometers cycled per year were associated with an increase in peak power output, which was larger in the master 40 group (p < 0.05) with a non-significant upward in VO2max (p > 0.05). In the performance prediction model, the included variables explained 52% of the variance. In summary, the changes induced by age were minimal in BC and negligible in CRF, whereas HR decreased with age. Training load was generally associated with a decrease in body weight, BMI and body fat percentage that was particularly notable in the abdominal skin folds. A decrease in HRrest was observed as a vagal effect due to kilometers cycled per year, and age did not seem to have a significant effect. The annual cycling kilometers were associated with to high PPO that is greater in the M40 group and a non-significant upward trend in VO2max.


Responses to methylphenidate in adolescent AD/HD: evidence from concurrently recorded autonomic (EDA) and central (EEG and ERP) measures.
This paper aims to examine the effects of methylphenidate (MPH) on integrated baseline and event-related psychophysiological measures in AD/HD. Thirty-four unmedicated AD/HD adolescents (11-17 years; 6 females) were first compared to 34 age- and sex-matched controls, and then re-tested at least 4 weeks after methylphenidate (MPH) medication. In each testing session, EDA was recorded simultaneously with EEG during a resting eyes open condition, and with ERPs during an auditory oddball task. Unmedicated AD/HD subjects were compared to controls and then AD/HD subjects were compared pre- and post-medication. Correlations between the change in EEG theta and the remaining psychophysiological variables were undertaken to provide information about post MPH treatment changes. In the unmedicated state, AD/HD was characterized by abnormally enhanced theta, across fronto-central sites, generally reduced P2 responses, with larger non-specific and oddball-elicited SCRs and poor behavioural performance on the oddball task. Following treatment, AD/HD showed a 'normalization' of theta activity (particularly in the right hemisphere), a reduction in the rate of decrement of EDA and a general increase in P3 amplitude. These findings suggest that methylphenidate is associated with a robust 'normalization' of low frequency EEG activity during the resting brain state, but has less impact on task-related brain activity or phasic changes in autonomic function. This dissociation of resting and task-related activity may prove to be useful in elucidating the effects of stimulant versus new non-stimulant medications in AD/HD.


Effects of a high-density intramammary device on mammary glands, production, and reproductive performance in dairy cows.
A clinical field trial was undertaken to determine the influence of an intramammary device (IMD) on environmental mastitis and production. On 4 central California dairies, 200 Holstein first-lactation cows were randomly assigned to 2 groups. Cows in the treatment group were fitted with an IMD, and cows in the control group were not. The incidence of clinical mastitis for the 2 groups was determined during the study period. Bacteriologic monitoring at intervals over 2 lactations (lactation 2 and through 60 days of lactation 3) was used to determine the incidence of subclinical infection. In addition, data were collected to determine whether the groups differed in milk production, butterfat production, post-milking and test-day somatic cell counts, and reproductive efficiency. Total milk production and butterfat production over the 2 lactation periods did not vary significantly between the groups. Also, the groups did not differ in calving-to-conception interval, duration of lactation, calving interval, and calving-to-first service interval. Cows with IMD were significantly less likely to develop clinical mastitis (5% vs 13%) than control cows. The IMD did not appear to affect subclinical infection rates (minor pathogens only) except at day 300 of lactation 2 and at day 10 of lactation 3, when prevalence was greater in the cows with IMD. The minor pathogens were predominately (80%) coagulase-negative staphylococci. It was unusual to have coagulase-negative staphylococci in the same quarter at 2 consecutive samplings, prompting the speculation that during lactation, the duration of coagulase-negative staphylococci infection is short (resolves without intervention).(ABSTRACT TRUNCATED AT 250 WORDS)


Interaction between 5-HTTLPR polymorphism and abuse history on adolescent African-American females' condom use behavior following participation in an HIV prevention intervention.
Not everyone exposed to an efficacious human immunodeficiency virus (HIV) intervention will reduce sexual risk behaviors, yet little is known about factors associated with "failure to change" high-risk sexual behaviors post-intervention. History of abuse and polymorphisms in the serotonin transporter gene (5-HTT) may be associated with non-change. The current study sought to identify genetic, life history, and psychosocial factors associated with adolescents' failure to change condom use behaviors post-participation in an HIV prevention intervention. A sub-set of participants from a clinic-based sample of adolescent African-American females (N = 254) enrolled in a randomized trial of an HIV-prevention was utilized for the current study. Forty-four percent did not increase their condom use from baseline levels 6 months after participating in the sexually transmitted infection (STI)/HIV prevention intervention. In multivariable logistic regression analysis, an interaction between abuse and 5-HTTLPR group was significantly associated with non-change status, along with partner communication frequency scores at follow-up. Follow-up tests found that having a history of abuse was significantly associated with greater odds of non-change in condom use post-intervention for only those with the s allele. For those with ll allele, participants with higher partner communication frequency scores were at decreased odds of non-change in condom use post-intervention. Thus, STI/HIV interventions for adolescent females may consider providing a more in-depth discussion and instruction on how to manage and overcome fear or anxiety related to being assertive in sexual decisions or sexual situations. Doing so may improve the efficacy of STI/HIV prevention programs for adolescent women who have experienced abuse in their lifetime.


Classical conditioning of heart rate and blood pressure in Macaca mulatta.
Classical delay conditioning of heart rate, and of systolic and diastolic blood pressures, was carried out in 16 rhesus monkeys. Blood pressure and inter-systolic interval were measured from an in-dwelling arterial catheter; recordings were taken prior to conditioned stimulus (CS) on each trial, during a 20 sec visual stimulus that filled the conditioned-unconditioned stimulus (CS-UCS) interval, and following UCS (a brief electric tail-shock). The heart rate response both to CS and to UCS was biphasic (acceleration followed by deceleration); the blood pressure response functions were more complex, and were different for the CS and post-UCS periods. Comparison of the patterns of cardiac and blood pressure responses on any trial indicates a possible sequence of baroreceptor reflex activity.


Do Resveratrol and Dehydroepiandrosterone Increase Diminished Ovarian Reserve?
In this study, the aim is to observe changes induced by dehydroepiandrosterone (DHEA) and resveratrol (RES) in diminished ovarian follicles that was induced by 4-vinylcyclohexenediepoxide (VCD). Twenty four Wistar albino female rats were divided into 3 groups: control, DHEA and RES. Unilateral oophorectomy was performed in control group to remove the right ovary of 4 rats and the left ovary of 4 rats. After administration of 160 mg/kg VCD, remaining ovaries were removed. Following the same VCD treatment, in DHEA and RES groups, 60 mg/kg DHEA and 20 mg/kg RES were given for 45 days respectively and residual ovaries were removed. Hematoxylin-eosin and TUNEL staining were performed. Follicle stimulating hormone (FSH), estradiol (E2) and anti-mullerian hormone (AMH) values were measured. In control group, VCD-induced apoptosis in follicles increased the TUNEL-positive cell counts (p<0.001) with decreased number of follicles. On the other hand, DHEA significantly increased all three follicle types in the ovaries and decreased apoptosis (p<0.001). The decreased follicle number in all three follicle types after VCD treatment were found to be significantly increased after RES treatment (p<0.001). Apoptosis in the follicles was significantly decreased by RES administration (p<0.001). FSH values were found to be increased with VCD and to reach control values with DHEA and RES. E2 values significantly decreased with VCD, but significantly increased with RES and DHEA. Both DHEA and RES may improve VCD-induced diminished ovarian reserve. DHEA and RES increased the number of primary, primordial and growing follicles, with no significant difference between them.


Six months of desipramine for dysthymia: can dysthymic patients achieve normal social functioning?
There is evidence that antidepressant medication improves social dysfunction during acute treatment in dysthymic patients but it is unknown if the gain in social functioning persists or progresses with longer-term antidepressant treatment. We examine the effect of 6 months of desipramine treatment on social functioning in dysthymic patients. Forty-six subjects with DSM-III-R dysthymia (70% with superimposed major depression) who had responded to 10 weeks of open-label desipramine (DMI) treatment received 16 additional weeks of continuation DMI. Social functioning was measured at weeks 0, 10 and 26 with the Social Adjustment Scale-Self Report. Euthymia was maintained and a marginally significant trend for further improvement in overall social functioning appeared during continuation treatment. Only 24% of subjects achieved normative level of social adjustment after 6 months of DMI treatment. The main limitation was the lack of a placebo control group. Acute improvement in social functioning persists during continuation treatment. However, most dysthymic patients did not achieve a community level of social adjustment. Significant social dysfunction persists in dysthymic patients with low levels of depressive symptomatology after 6 months of intense DMI treatment.


Primary amelanotic malignant melanoma masquerading as adenocarcinoma prostate - A pathological dilemma.
A rare disease at an aberrant location can mimic a usual presentation of another disease. We report a case of primary amelanotic malignant melanoma of the prostate with clinical and histological characteristics that closely mimic poorly differentiated adenocarcinoma prostate.


Implementation options for DNA-based identification into ecological status assessment under the European Water Framework Directive.
Assessment of ecological status for the European Water Framework Directive (WFD) is based on "Biological Quality Elements" (BQEs), namely phytoplankton, benthic flora, benthic invertebrates and fish. Morphological identification of these organisms is a time-consuming and expensive procedure. Here, we assess the options for complementing and, perhaps, replacing morphological identification with procedures using eDNA, metabarcoding or similar approaches. We rate the applicability of DNA-based identification for the individual BQEs and water categories (rivers, lakes, transitional and coastal waters) against eleven criteria, summarised under the headlines representativeness (for example suitability of current sampling methods for DNA-based identification, errors from DNA-based species detection), sensitivity (for example capability to detect sensitive taxa, unassigned reads), precision of DNA-based identification (knowledge about uncertainty), comparability with conventional approaches (for example sensitivity of metrics to differences in DNA-based identification), cost effectiveness and environmental impact. Overall, suitability of DNA-based identification is particularly high for fish, as eDNA is a well-suited sampling approach which can replace expensive and potentially harmful methods such as gill-netting, trawling or electrofishing. Furthermore, there are attempts to replace absolute by relative abundance in metric calculations. For invertebrates and phytobenthos, the main challenges include the modification of indices and completing barcode libraries. For phytoplankton, the barcode libraries are even more problematic, due to the high taxonomic diversity in plankton samples. If current assessment concepts are kept, DNA-based identification is least appropriate for macrophytes (rivers, lakes) and angiosperms/macroalgae (transitional and coastal waters), which are surveyed rather than sampled. We discuss general implications of implementing DNA-based identification into standard ecological assessment, in particular considering any adaptations to the WFD that may be required to facilitate the transition to molecular data.


Update on Novel Taxa and Revised Taxonomic Status of Bacteria Isolated from Nondomestic Animals Described in 2018 to 2021.
Revisions and new additions to bacterial taxonomy can have a significant widespread impact on clinical practice, infectious disease epidemiology, veterinary microbiology laboratory operations, and wildlife conservation efforts. The expansion of genome sequencing technologies has revolutionized our knowledge of the microbiota of humans, animals, and insects. Here, we address novel taxonomy and nomenclature revisions of veterinary significance that impact bacteria isolated from nondomestic wildlife, with emphasis being placed on bacteria that are associated with disease in their hosts or were isolated from host animal species that are culturally significant, are a target of conservation efforts, or serve as reservoirs for human pathogens.


Are video sharing web sites a useful source of information on hypertension?
Hypertension (HTN) is a prevalent and growing public health problem in the United States and worldwide. Video sharing Web sites such as YouTube could potentially influence patient behaviors via properties of interpersonal and mass media communication. We conducted this cross-sectional study to assess the accuracy and content of YouTube videos on HTN and understand how viewers interact with this online information. We analyzed 209 videos (31.57 hours) of which 63% were classified as useful, 33% as misleading, and 4% represented patient's personal experiences. Number of views per day and "likes" were significantly lower for useful videos. Approximately half the misleading videos contained product advertisements, 70% advocated unproven alternative treatments, and 91% targeted patients. Viewer engagement (number of views) was a poor predictor of usefulness and/or content whereas source of upload, and target audiences were good predictors of usefulness and/or content. Videos uploaded by university channels and/or professional organizations that targeted physicians had a 99.4% (P < .001) probability of being useful whereas videos uploaded by individuals with unknown credentials that targeted patients had a 21.2% (P < .001) probability of being useful. A majority of HTN-related videos on YouTube are useful. Viewer engagement is significantly higher with videos that contain misleading and/or erroneous information in comparison to videos that contain useful information.


Selective attention gates visual processing in the extrastriate cortex.
Single cells were recorded in the visual cortex of monkeys trained to attend to stimuli at one location in the visual field and ignore stimuli at another. When both locations were within the receptive field of a cell in prestriate area V4 or the inferior temporal cortex, the response to the unattended stimulus was dramatically reduced. Cells in the striate cortex were unaffected by attention. The filtering of irrelevant information from the receptive fields of extrastriate neurons may underlie the ability to identify and remember the properties of a particular object out of the many that may be represented on the retina.


Potentiation of imipenem by relebactam for Pseudomonas aeruginosa from bacteraemia and respiratory infections.
Imipenem resistance in Pseudomonas aeruginosa most often entails loss of the 'carbapenem-specific' porin OprD; more rarely it reflects acquired carbapenemases. Loss of OprD only confers resistance to imipenem if AmpC β-lactamase is expressed, and we investigated whether this mechanism was overcome by relebactam, a developmental diazabicyclooctane β-lactamase inhibitor. Consecutive P. aeruginosa isolates causing bacteraemia or hospital-onset lower respiratory tract infections were collected between 2014 and 2016 under the aegis of the BSAC Resistance Surveillance Programme. Imipenem MICs were determined centrally by BSAC agar dilution, with relebactam at a fixed concentration (4 mg/L). For most imipenem-susceptible P. aeruginosa (726/759, 95.7%), the MICs of imipenem alone were 0.5-2 mg/L and were decreased 3- to 4-fold by addition of relebactam, as based on geometric means or modes. For most imipenem-resistant P. aeruginosa (82/92, 89%), imipenem MICs were 8-16 mg/L, and were reduced to 1-2 mg/L by relebactam. These patterns applied regardless of whether the isolates were susceptible to penicillins and cephalosporins or had phenotypes suggesting derepressed AmpC or up-regulated efflux. Imipenem MICs for five P. aeruginosa with MBLs remained high (≥16 mg/L) regardless of relebactam. Potentiation of imipenem by relebactam was almost universal, in accordance with the view that endogenous pseudomonal AmpC ordinarily protects against this carbapenem to a small degree. Imipenem MICs were reduced to the current breakpoint, or lower, except for MBL producers. Potentiation was not compromised by derepression of AmpC or up-regulation of efflux.


Expression of the CD11/CD18, leukocyte adhesion molecule 1, and CD44 adhesion molecules during normal myeloid and erythroid differentiation in humans.
We have used three-color flow cytometry to investigate the pattern of expression of the CD11/CD18, CD44, and leukocyte adhesion molecule 1 (LAM-1) adhesion molecules during myeloid and erythroid differentiation in humans. The earliest myeloid cells, identified as CD33loCD15-, were exclusively CD44hi but contained both leukocyte function-associated antigen 1 (LFA-1hi) and LFA-1lo cells, as well as LAM-1+ and LAM-1- cells. This CD33loCD15- myeloid subpopulation expressed only low levels of CD11c and failed to express CD11b, CD14, or any lymphoid (CD3, CD16, CD19) antigens or glycophorin. Commitment to monocyte differentiation, suggested by the presence of an LFA-1hi CD11c+ subset within the CD33loCD15- subpopulation, was clearly signaled by upregulation of CD33; these monocyte-lineage committed cells were exclusively CD33hi, CD44hi, CD11ahi, CD11c+, and exhibited a broad range of intensity of CD15 expression. Later stages of monopoiesis were identified by acquisition of CD11b, and subsequently of CD14. Myeloid cells committed to granulopoiesis remained LFA-1lo, and underwent a sharp upregulation of CD15 along with downregulation of both CD33 and CD44. Successive stages of granulocyte development were marked by expression of CD11b and, subsequently, of CD16. The earliest cells capable of erythroid differentiation were CD44hi, LFA-1lo, and LAM-1+. Both LFA-1 and LAM-1 were lost before the onset of glycophorin (glyco) expression, whereas CD44 expression remained high on glyco+ cells, which also expressed CD45. CD44 expression was intermediate on glyco+ CD71+ cells, and low on glyco+ CD45- CD71- cells, similar to normal, circulating erythrocytes. Our results allow us to phenotypically define discrete stages in the normal development of monocytes, neutrophils, and erythrocytes. The expression of LFA-1, LAM-1, and high levels of CD44 on the most primitive hematopoietic cells detectable by flow cytometry suggests that at least some of these molecules are critically involved in leukocyte adhesion during development.


Knowledge and attitudes towards COVID-19 among emergency medical service workers.
Good knowledge of the coronavirus disease 2019 (COVID-19) among healthcare workers is essential for keeping health systems active and controlling the outbreak. We aimed to investigate the knowledge and attitudes of Emergency Medical Service (EMS) employees who fight COVID-19 at the forefront. A total of 400 EMS workers (doctors, nurses, emergency medical technicians, paramedics, and ambulance drivers) were included in this study. Knowledge, attitude, and preventive behaviors for COVID-19 were evaluated using an online questionnaire. A total of 275 EMS workers participated in the study with a response rate of 68.8%. The respondents reported that their highest common sources of knowledge about COVID-19 were social media and television (n=240, 88%). Overall, > 96% of the participants had adequate knowledge about the transmission routes of COVID-19. Among the respondents, 36% of them were unaware of the correct hand washing or scrubbing technique. In addition, 78% of the participants had poor knowledge about floor and surface disinfection. The majority of the participants exhibited inaccurate attitudes toward the use of personal preventive equipment. More than half of EMS workers (52%) agreed that a surgical mask is not enough during the procedures that do not generate aerosol. Moreover, a significant proportion of the participants (66%) perceived that a N95 mask is required. As a consequence, although emergency workers have sufficient basic knowledge about COVID-19, there is a need for postgraduate training in many subjects.


Peripheral neuropathy of dietary riboflavin deficiency in chickens.
A strain of rapidly growing meat-type chickens was fed a diet deficient in riboflavin from 1-40 days of age. Diminished growth rate, progressive gait abnormality and reluctance to move were noted beginning on day 8. Neurologic abnormalities were related to peripheral neuropathy characterized by Schwann cell hypertrophy and degeneration with cytoplasmic lipid droplets' and segmental demyelination. Lesions were initially detected on day 10, and in concert with clinical signs became more profound between days 14 and 21. Sequestration of myelin debris within Schwann cells was common. Other features of the neuropathy included the presence of endoneurial edema and axonal degeneration involving small numbers of fibers. Remyelination of peripheral nerve fibers in birds on the deficient diet was occasionally seen on day 10, became progressively more prominent, and was marked by day 37. There was an associated, variable but incomplete, clinical improvement evident in later stages of the study. Liver concentrations of riboflavin in deficient birds were significantly reduced on day 13 but not on day 26. This neuropathy may be related to diminished tissue levels of the riboflavin-based coenzymes flavin-adenine dinucleotide (FAD) and flavin mononucleotide (FMN) leading to reduced cellular energy levels and profoundly affecting Schwann cells at some critical point in growth.


Global Trends in Bumble Bee Health.
Bumble bees (Bombus) are unusually important pollinators, with approximately 260 wild species native to all biogeographic regions except sub-Saharan Africa, Australia, and New Zealand. As they are vitally important in natural ecosystems and to agricultural food production globally, the increase in reports of declining distribution and abundance over the past decade has led to an explosion of interest in bumble bee population decline. We summarize data on the threat status of wild bumble bee species across biogeographic regions, underscoring regions lacking assessment data. Focusing on data-rich studies, we also synthesize recent research on potential causes of population declines. There is evidence that habitat loss, changing climate, pathogen transmission, invasion of nonnative species, and pesticides, operating individually and in combination, negatively impact bumble bee health, and that effects may depend on species and locality. We distinguish between correlational and causal results, underscoring the importance of expanding experimental research beyond the study of two commercially available species to identify causal factors affecting the diversity of wild species.


The fate of hydrogen peroxide as an oxygen source for bioremediation activities within saturated aquifer systems.
In situ bioremediation is an innovative technique for the remediation of contaminated aquifers that involves the use of microorganisms to remediate soils and groundwaters polluted by hazardous substances. During its application, this process may require the addition of nutrients and/or electron acceptors to stimulate appropriate biological activity. Hydrogen peroxide has been commonly used as an oxygen source because of the limited concentrations of oxygen that can be transferred into the groundwater using above-ground aeration followed by reinjection of the oxygenated groundwater into the aquifer or subsurface air sparging of the aquifer. Because of several potential interactions of H2O2 with various aquifer material constituents, its decomposition may be too rapid, making effective introduction of the H2O2 into targeted treatment zones extremely difficult and costly. Therefore, a bench-scale study was conducted to determine the fate of H2O2 within subsurface aquifer environments. The purpose of this investigation was to identify those aquifer constituents, both biotic and abiotic, that are most active in controlling the fate of H2O2. The decomposition rates of H2O2 were determined using both equilibrated water samples and soil slurries. Results showed H2O2 decomposition to be effected by several commonly found inorganic soil components; however, biologically mediated catalytic reactions were determined to be the most substantial.


Characterization and molecular identification of lactic acid bacteria isolated from kefir and evaluation of their antibacterial activity against food-borne pathogens in Saudi Arabia.
Pathogenic bacteria are usually present in raw milk. In order to prevent pathogens from growing, milk should be fermented. The present research work aimed to isolate lactic acid bacteria (LAB) from kefir, a fermented milk beverage, and assess their antibacterial activity against chosen pathogenic strains of bacteria. An experimental investigation was carried out in the laboratory. Samples of kefir were collected from a local organic food store in Jeddah City, Saudi Arabia. LAB isolates were identified phenotypically and biochemically. The agar well diffusion technique evaluated the antimicrobial activities (AMAs) of LAB isolates against Escherichia coli, Listeria monocytogenes, and Salmonella Typhimurium. The isolates were molecularly identified through polymerase chain reaction PCR amplification of the 16S rRNA gene. Six LAB isolates were identified and given the following numbers: SK9, SK17, SK23, SK24, SK28, and SK33. The isolates belong to Enterococcus durans and Leuconostoc mesenteroides. After screening for antibacterial activity against food-borne bacteria, SK28 showed the strongest AMA against E. coli and S. Typhimurium. SK23 showed the highest AMA against L. monocytogenes, while SK33 showed no AMA against L. monocytogenes. LAB isolates exhibited AMA against the selected strains of bacteria. Enterococcus isolates showed the highest antibacterial activities against the tested bacterial strains. Therefore, in the era of antimicrobial resistance, they might serve as antibiotic alternatives. L. monocytogenes was the least sensitive to the antimicrobial activities of LAB isolates. Further experiments are required to isolate and identify the molecules responsible for the antimicrobial activities.


What are the veterinary schools and colleges doing to improve the nontechnical skills, knowledge, aptitudes, and attitudes of veterinary students?
The KPMG study signaled the need for change in the veterinary profession, and the NCVEI was formed to follow up on the study's findings. As founding organizations, the AVMA, American Animal Hospital Association, and the Association of American Veterinary Medical Colleges remain committed to the cause, as do the NCVEI's corporate sponsors. In addition, it is clear that substantial change is also underway within the individual veterinary schools and colleges. The programs compiled should not be considered exhaustive because of the possibility that not all schools replied to the survey and because of ongoing changes. Widespread programmatic changes are being implemented in the veterinary schools and colleges, with short- and long-term implications for the veterinary profession. Such changes are not taken lightly in academia, and the schools and colleges are to be commended for their leadership and initiative. The momentum that is apparent can be expected to yield benefits for the veterinary profession well into the future.


Osteoclast differentiation is impaired in the absence of inhibitor of kappa B kinase alpha.
Signaling through the receptor activator of nuclear factor kappa B (RANK) is required for both osteoclast differentiation and mammary gland development, yet the extent to which RANK utilizes similar signaling pathways in these tissues remains unclear. Mice expressing a kinase-inactive form of the inhibitor of kappa B kinase alpha (IKK alpha) have mammary gland defects similar to those of RANK-null mice yet have apparently normal osteoclast function. Because mice that completely lack IKK alpha have severe skin and skeletal defects that are not associated with IKK alpha-kinase activity, we wished to directly examine osteoclastogenesis in IKK alpha(-/-) mice. We found that unlike RANK-null mice, which completely lack osteoclasts, IKK alpha(-/-) mice did possess normal numbers of TRAP(+) osteoclasts. However, only 32% of these cells were multinucleated compared with 57% in wild-type littermates. A more profound defect in osteoclastogenesis was observed in vitro using IKK alpha(-/-) hematopoietic cells treated with colony-stimulating factor 1 and RANK ligand (RANKL), as the cells failed to form large, multinucleated osteoclasts. Additionally, overall RANKL-induced global gene expression was significantly blunted in IKK alpha(-/-) cells, including osteoclast-specific genes such as TRAP, MMP-9, and c-Src. IKK alpha was not required for RANKL-mediated I kappa B alpha degradation or phosphorylation of mitogen-activated protein kinases but was required for RANKL-induced p100 processing. Treatment of IKK alpha(-/-) cells with tumor necrosis factor alpha (TNF alpha) in combination with RANKL led to partial rescue of osteoclastogenesis despite a lack of p100 processing. However, the ability of TNF alpha alone or in combination with transforming growth factor beta to induce osteoclast differentiation was dependent on IKK alpha, suggesting that synergy between RANKL and TNFalpha can overcome p100 processing defects in IKK alpha(-/-) cells.


Associations of self-report measures with gait, range of motion and proprioception in patients with lumbar spinal stenosis.
Spinal stenosis is defined as neurogenic claudication due to narrowing of the spinal canal lumen diameter. As the disease progresses, ambulation and gait may be impaired. Self-report measures are routinely used in the clinical setting to capture data related to lumbar pain symptoms, function and perceived disability. The associations between self-report measures and objective measures of physical function in patients with lumbar spinal stenosis are not well characterized. The purpose of this study was to determine the correlation between self-reported assessments of function with objective biomechanical measures of function. 25 subjects were enrolled in this study. Subjects completed self-report questionnaires and biomechanical assessments of gait analysis, lumbar 3D ROM and lumbar proprioception. Correlations were determined between self-report measures and biomechanical data. The Oswestry Disability Index (ODI) was strongly correlated with stride length and gait velocity and weakly correlated with base of support. ODI was also weakly correlated with left lateral bending proprioception but not right lateral bending. The SF12 was not significantly correlated with any of the biomechanical measurements. Pain scores were weakly correlated with velocity, and base of support, and had no correlation any of the other biomechanical measures. There is a strong correlation between gait parameters and functional disability as measured with the ODI. Quantified gait analysis can be a useful tool to evaluate patients with lumbar spinal stenosis and to assess the outcomes of treatments on this group of patients.


The DosR Regulon Modulates Adaptive Immunity and Is Essential for Mycobacterium tuberculosis Persistence.
Hypoxia promotes dormancy by causing physiologic changes to actively replicating Mycobacterium tuberculosis. DosR controls the response of M. tuberculosis to hypoxia. To understand DosR's contribution in the persistence of M. tuberculosis, we compared the phenotype of various DosR regulon mutants and a complemented strain to M. tuberculosis in macaques, which faithfully model M. tuberculosis infection. We measured clinical and microbiologic correlates of infection with M. tuberculosis relative to mutant/complemented strains in the DosR regulon, studied lung pathology and hypoxia, and compared immune responses in lung using transcriptomics and flow cytometry. Despite being able to replicate initially, mutants in DosR regulon failed to persist or cause disease. On the contrary, M. tuberculosis and a complemented strain were able to establish infection and tuberculosis. The attenuation of pathogenesis in animals infected with the mutants coincided with the appearance of a Th1 response and organization of hypoxic lesions wherein M. tuberculosis expressed dosR. The lungs of animals infected with the mutants (but not the complemented strain) exhibited early transcriptional signatures of T-cell recruitment, activation, and proliferation associated with an increase of T cells expressing homing and proliferation markers. Delayed adaptive responses, a hallmark of M. tuberculosis infection, not only lead to persistence but also interfere with the development of effective antituberculosis vaccines. The DosR regulon therefore modulates both the magnitude and the timing of adaptive immune responses in response to hypoxia in vivo, resulting in persistent infection. Hence, DosR regulates key aspects of the M. tuberculosis life cycle and limits lung pathology.


Upregulation of TRPC6 Mediated by PAX6 Hypomethylation Is Involved in the Mechanical Allodynia Induced by Chemotherapeutics in Dorsal Root Ganglion.
Although the action mechanism of antineoplastic agents is different, oxaliplatin, paclitaxel, or bortezomib as first-line antineoplastic drugs can induce painful neuropathy. In rodents, mechanical allodynia is a common phenotype of painful neuropathy for 3 chemotherapeutics. However, whether there is a common molecular involved in the different chemotherapeutics-induced painful peripheral neuropathy remains unclear. Mechanical allodynia was tested by von Frey hairs following i.p. injection of vehicle, oxaliplatin, paclitaxel, or bortezomib in Sprague-Dawley rats. Reduced representation bisulfite sequencing and methylated DNA immunoprecipitation were used to detect the change of DNA methylation. Western blot, quantitative polymerase chain reaction, chromatin immunoprecipitation, and immunohistochemistry were employed to explore the molecular mechanisms. In 3 chemotherapeutic models, oxaliplatin, paclitaxel, or bortezomib accordantly upregulated the expression of transient receptor potential cation channel, subfamily C6 (TRPC6) mRNA and protein without affecting the DNA methylation level of TRPC6 gene in DRG. Inhibition of TRPC6 by using TRPC6 siRNA (i.t., 10 consecutive days) relieved mechanical allodynia significantly following application of chemotherapeutics. Furthermore, the downregulated recruitment of DNA methyltransferase 3 beta (DNMT3b) at paired box protein 6 (PAX6) gene led to the hypomethylation of PAX6 gene and increased PAX6 expression. Finally, the increased PAX6 via binding to the TPRC6 promoter contributes to the TRPC6 increase and mechanical allodynia following chemotherapeutics treatment. The TRPC6 upregulation through DNMT3b-mediated PAX6 gene hypomethylation participated in mechanical allodynia following application of different chemotherapeutic drugs.


Supercritical hydrothermal synthesis of MoS2 nanosheets with controllable layer number and phase structure.
Molybdenum disulfide (MoS2), an attractive material for energy conversion devices, is known to exhibit varying properties depending on the number of layers and the phase structure. In this study, we developed a supercritical hydrothermal process that allows the controllable synthesis of MoS2 nanosheets with various structural and morphological characteristics. Detailed characterization of the synthesized materials confirmed that the number of layers in the MoS2 nanosheets could be controlled by varying the organic reducing agent under supercritical hydrothermal conditions. In addition, the MoS2 phase could be controlled kinetically by varying the reaction time with ascorbic acid as the reducing agent. Because water and elemental sulfur were respectively used as the solvent and sulfur source and as the reaction time was minimal, the developed hydrothermal process represents a facile processing method for different types of MoS2 nanosheets.


Dynamics of the vocal imitation process: how a zebra finch learns its song.
Song imitation in birds provides good material for studying the basic biology of vocal learning. Techniques were developed for inducing the rapid onset of song imitation in young zebra finches and for tracking trajectories of vocal change over a 7-week period until a match to a model song was achieved. Exposure to a model song induced the prompt generation of repeated structured sounds (prototypes) followed by a slow transition from repetitive to serial delivery of syllables. Tracking this transition revealed two phenomena: (i) Imitations of dissimilar sounds can emerge from successive renditions of the same prototype, and (ii) developmental trajectories for some sounds followed paths of increasing acoustic mismatch until an abrupt correction occurred by period doubling. These dynamics are likely to reflect underlying neural and articulatory constraints on the production and imitation of sounds.


Intramedullary tuberculoma mimicking primary CNS lymphoma.
The incidence of primary central nervous system lymphoma (PCNSL) has been on the rise in the setting of immunodeficiency syndromes such as acquired immune deficiency syndrome (AIDS). Its diagnosis has been facilitated by the advent of a cerebrospinal fluid (CSF) Epstein-Barr virus (EBV) PCR assay. The reported high sensitivity and specificity of this assay has made it the cornerstone of diagnosis of PCNSL, replacing more traditional methods such as an open CNS biopsy. Here, we have described a patient with a known history of C3 AIDS presenting with lower extremity weakness and eventual myelopathy who was later diagnosed as having intramedullary PCNSL after detection of EBV DNA in his CSF. After failing to respond to radiotherapy, he underwent a spinal cord biopsy revealing intramedullary tuberculoma. This case illustrates the risk of misdiagnosis with this assay and the importance of histological confirmation of a pathological lesion prior to implementation of therapy.


Steady-state tyrosine fluorescence to study the lipid-binding properties of a wheat non-specific lipid-transfer protein (nsLTP1).
The binding properties of a wheat non-specific lipid-transfer protein (nsLTP1) for different mono- and diacylated lipids was investigated. Lipids varied by their chain length, unsaturation and/or polar head group. In the case of fatty acid or lysophospholipid with a C10 chain length, no interaction can be measured, while poor affinity is reported for a C12 chain length. The dissociation constant (K(d)) is about 0.5 µM independent of chain length from C14 to C18. The same affinity is obtained for C18 fatty acids with one or two unsaturations, whatever the cis-trans double bond isomery. In all cases, the number of binding sites, n, by protein ranges between 1.6 and 1.9, suggesting that two lipids can fit within the protein. omega-Hydroxy-palmitic acid, a natural monomer of cutin polymer, is found to interact with nsLTP1 with a K(d) of 1 µM and n=2. In contrast with previous data that reported the binding of the anionic diacylated phospholipid, DMPG (Sodano et al., FEBS Lett. 416 (1997) 130-134), nsLTP1 is not able to bind dimyristoylphosphatidylcholine, dimyristoylphosphatidic acid, palmitoyl-oleoylphosphatidylcholine or palmitoyl-oleoylphosphatidylglycerol added as liposomes or solubilized in ethanol. However, when both nsLTP1 and lipids are first solubilized in methanol, and then in the buffer, it was evidenced that the protein can bind these lipids. These results suggest that lipid-lipid interactions play an essential role in the binding process of plant nsLTP1 as previously mentioned for other lipid-transfer proteins.


Occurence of Cutaneous Marginal Zone B-Cell Lymphoma Post Breast Cancer Chemotherapy: A Case Report.
Primary cutaneous marginal zone B-cell lymphomas (PCMZLs) are classified as low-grade as they run an indolent course. They are histologically characterized through non-epidermotropic nodular or diffuse infiltrates consisting of small or medium heterogeneous atypical lymphoid cells. In the past few years, chemotherapy has increased the survival rate of breast cancer patients. However, the adverse effects of treatment, such as leukemia, have also been shown to emerge gradually. Additionally, cases of occurrence of non-Hodgkin lymphoma (NHL) post chemotherapy have also been reported. A 48-year-old female patient was presented with a violaceous nodule on her left thigh. Around 15 months ago, she completed breast cancer chemotherapy. Eight months later, a skin lesion appeared. Histological findings revealed dense and nodular lymphocyte infiltration. Immunohistochemical staining was positive for CD20 and BCL2. Clinical and histological examination of the lesions confirmed PCMZL. After systemic evaluation, lymphoma was found to be limited to the skin, and thus, she underwent complete excision of the lesion. At the first month follow-up, there was a recurrent lesion on the right wrist, which was excised successfully. However, recurrences occurred again in the calf and forearm in the following five and two months, respectively. These lesions were also confirmed with PCMZL using biopsy. We assume that this case is related to chemotherapy as it was presented and recurred abruptly post chemotherapy. Additionally, there are several reported cases of NHL post breast cancer chemotherapy. However, this is the first case report of PCMZL associated with chemotherapy.


Cathepsin L-mediated EGFR cleavage affects intracellular signalling pathways in cancer.
Proteolytic activity in the tumour microenvironment is an important factor in cancer development since it can also affect intracellular signalling pathways via positive feedback loops that result in either increased tumour growth or resistance to anticancer mechanisms. In this study, we demonstrated extracellular cathepsin L-mediated cleavage of epidermal growth factor receptor (EGFR) and identified the cleavage site in the extracellular domain after R224. To further evaluate the relevance of this cleavage, we cloned and expressed a truncated version of EGFR, starting at G225, in HeLa cells. We confirmed the constitutive activation of the truncated protein in the absence of ligand binding and determined possible changes in intracellular signalling. Furthermore, we determined the effect of truncated EGFR protein expression on HeLa cell viability and response to the EGFR inhibitors, tyrosine kinase inhibitor (TKI) erlotinib and monoclonal antibody (mAb) cetuximab. Our data reveal the nuclear localization and phosphorylation of EGFR and signal trancducer and activator of transcription 3 (STAT3) in cells that express the truncated EGFR protein and suggest that these phenomena cause resistance to EGFR inhibitors.


Lessons Learned From Past Gene-Environment Interaction Successes.
Genetic and environmental factors are both known to contribute to susceptibility to complex diseases. Therefore, the study of gene-environment interaction (G×E) has been a focus of research for several years. In this article, select examples of G×E from the literature are described to highlight different approaches and underlying principles related to the success of these studies. These examples can be broadly categorized as studies of single metabolism genes, genes in complex metabolism pathways, ranges of exposure levels, functional approaches and model systems, and pharmacogenomics. Some studies illustrated the success of studying exposure metabolism for which candidate genes can be identified. Moreover, some G×E successes depended on the availability of high-quality exposure assessment and longitudinal measures, study populations with a wide range of exposure levels, and the inclusion of ethnically and geographically diverse populations. In several examples, large population sizes were required to detect G×Es. Other examples illustrated the impact of accurately defining scale of the interactions (i.e., additive or multiplicative). Last, model systems and functional approaches provided insights into G×E in several examples. Future studies may benefit from these lessons learned.


De Novo Genome Assembly and Comparative Genomics of the Barley Leaf Rust Pathogen Puccinia hordei Identifies Candidates for Three Avirulence Genes.
Puccinia hordei (Ph) is a damaging pathogen of barley throughout the world. Despite its importance, almost nothing is known about the genomics of this pathogen, and a reference genome is lacking. In this study, the first reference genome was assembled for an Australian isolate of Ph ("Ph560") using long-read SMRT sequencing. A total of 838 contigs were assembled, with a total size of 207 Mbp. This included both haplotype collapsed and separated regions, consistent with an estimated haploid genome size of about 150Mbp. An annotation pipeline that combined RNA-Seq of Ph-infected host tissues and homology to proteins from four other Puccinia species predicted 25,543 gene models of which 1,450 genes were classified as encoding secreted proteins based on the prediction of a signal peptide and no transmembrane domain. Genome resequencing using short-read technology was conducted for four additional Australian strains, Ph612, Ph626, Ph608 and Ph584, which are considered to be simple mutational derivatives of Ph560 with added virulence to one or two of three barley leaf rust resistance genes (viz. Rph3, Rph13 and Rph19). To identify candidate genes for the corresponding avirulence genes AvrRph3, AvrRph13 and AvrRph19, genetic variation in predicted secreted protein genes between the strains was correlated to the virulence profiles of each, identifying 35, 29 and 46 candidates for AvrRph13, AvrRph3 and AvrRph19, respectively. The identification of these candidate genes provides a strong foundation for future efforts to isolate these three avirulence genes, investigate their biological properties, and develop new diagnostic tests for monitoring pathogen virulence.


Preparation and characterizations of silver incorporated polyurethane composite nanofibers via electrospinning for biomedical applications.
We report on the preparation and characterization of polyurethane (PU) nanofibers containing silver (Ag) nanoparticles were synthesized by using electrospinning. Two different approaches were adopted to incorporate the Ag nanoparticles in to PU nanofibers. In the first approach, a homogeneous solution of 10 wt% PU containing silver nitrate was electrospun to obtain PU-Ag composite nanofibers. And in the second approach, the pristine PU nanofibers were initially electrospun and then Ag nanoparticles were coated via wet casting method. The surface morphology, structure, bonding configuration, optical and thermal properties of the resultant products were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, UV-vis spectroscopy and thermogravimetric analysis. The antibacterial activity was tested against four common food borne pathogenic bacteria, namely, Staphylococcus aureus, Escherichia coli, Salmonella typhimurium and Klebsiella pneumoniae by minimum inhibitory concentration (MIC) method. Our results demonstrated that no bactericidal activity was detected for the pristine PU nanofibers. Further on, antibacterial activity was observed to be more pronounced for the composite nanofibers which were attributed to the presence of Ag nanoparticles in the composite nanofibers. Overall, this study demonstrates the fabrication of cheap, stable and effective nanofiber mats with excellent antimicrobial activity that can be utilized to inhibit the microbial growth associated with food stuff.


Growth factor induced activation of Rho and Rac GTPases and actin cytoskeletal reorganization in human lens epithelial cells.
To determine the involvement of the Rho GTPases-mediated signaling pathway in growth factor-stimulated actomyosin cytoskeletal organization and focal adhesion formation in lens epithelial cells. Serum starved human lens epithelial cells (SRA01/04) were treated with different growth factors including epidermal growth factor (EGF), basic-fibroblast growth factor (b-FGF), platelet derived growth factor (PDGF), transforming growth factor beta (TGF-beta), insulin-like growth factor 1 (IGF-1), lysophosphatidic acid (LPA), and thrombin. Growth factor stimulated activation of Rho and Rac GTPases were evaluated by GTP-loading pull-down assays. Changes in actin cytoskeletal organization and focal adhesions were determined by fluorescence staining using FITC-phalloidin and anti-vinculin antibody/rhodamine-conjugated secondary antibody, respectively. Fluorescence images were recorded using either confocal or fluorescence microscopy. Rho GTPase activity was significantly augmented in human lens epithelial cells treated with EGF, b-FGF, TGF-beta, IGF-1, and LPA. Rac GTPase activation, in contrast, was significantly enhanced in response to only EGF or b-FGF. Serum starved human lens epithelial cells exhibited a strong increase in cortical actin stress fibers and integrin-mediated focal adhesions in response to b-FGF, PDGF, TGF-beta, thrombin, and LPA. While EGF induced a striking increase in membrane ruffling and a marginal increase on focal adhesion formation, IGF-1 had no effect on either. Pretreatment of lens epithelial cells with C3-exoenzyme (an irreversible inhibitor of Rho-GTPase), lovastatin (an isoprenylation inhibitor), or the Rho kinase inhibitor Y-27632 abolished the ability of the different growth factors to elicit actin stress fiber and focal adhesion formation. EGF induced membrane ruffling, however, was not suppressed by Y-27632 and C3-exoenzyme. These results demonstrate that different growth factors induce actin cytoskeleton reorganization and formation of cell-ECM interactions in lens epithelial cells and this response of growth factors appears to be mediated, at least in part, through the Rho/Rho kinase-mediated signaling pathway. The ability of growth factors to trigger activation of Rho and Rac GTPases along with actomyosin cytoskeletal reorganization and formation of focal adhesions might well play a crucial role in lens epithelial cell proliferation, migration, elongation and survival.


Micro-fractional Epidermal Powder Delivery for Skin Vaccination.
Skin is a highly immunogenic site for vaccine delivery due to its richness of antigen-presenting cells. Several vaccines have been approved for skin delivery and in particular intradermal delivery in the last two decades. Yet intradermal delivery often causes frequent and severe local reactions, preventing the incorporation of adjuvants to further boost skin vaccination. Here we describe a novel skin delivery technology, called micro-fractional epidermal powder delivery or EPD, with minimized local reactions for improved skin vaccination. EPD is based on laser or microneedle treatment to generate microchannel arrays in the epidermis followed by topical application of powder vaccine-coated array patches to deliver vaccines into the skin via microchannels. Due to the fractional delivery, EPD significantly reduces vaccine/adjuvant-induced local reactions without compromising vaccine immunogenicity and adjuvant potency. EPD also eliminates needle injection-associated pain and is promising to improve vaccine stability due to the direct powder delivery. This chapter describes detailed methods for the advantageous EPD in preclinical animal models.


Performance Indicators of the Top Basketball Players: Relations with Several Variables.
The aim of this study was to determine the differences in performance indicators for top senior male basketball players, with respect to several independent variables: position in the team, total situation-related efficiency, age, playing experience and the time spent on the court within the game and during championship season. The final sample of participants was selected from all teams in A-1 Croatian men's basketball league. Significant differences have been found according to the players': position in the team, total situation-related efficiency, and in interactions of the position in the team / total situation-related efficiency and minutes spent on the court in a game / playing experience. The differences in the situation-related efficiency between players have not been found according to the players' age and the number of games played. Further research can be directed towards deeper analysis of the influence of more complex differentiated variables playing experience and time spent on the court in a game on situation-related efficiency in basketball.


Five cases of Creutzfeldt-Jakob disease: a clinical-pathological contribution.
Clinico-pathological features are reported in five cases of Creutzfeldt-Jakob disease. In three cases only the brain was examined while in the other two a complete autopsy was performed. In one case a brain biopsy was performed and in other two a piece of cerebral cortex was taken within three hours after death; the brain material was frozen and sent for inoculation in monkeys to Dr. Gajdusek of NINDS-Bethesda, with positive results in two. From the clinical point of view our cases may be classified as follows: two as "classic" type; one as "amaurotic" type; and the last two as "ataxic-amyotrophic" forms according to Alemà and Brion (see text). All five patients were females from 56 to 73 years of age. The duration of the disease ranged from 3 to 7 months. From the histological point of view, in the two "classic" cases the outstanding features was the neuronal loss in all cortical mantle, mainly in the fronto-parietal cortex; furthermore in one there was severe and diffuse spongiform state. In the "amaurotic" case the three types of lesion were mainly localized in the occipital cortex. In the two "ataxic-amyotrophic" forms the neuronal loss was particularly evident in the cerebellar cortex and especially in the granular layer. The Kuru plaques were seen especially in the cerebellum in four of the five cases examined. The aim of our study is to contribute to the epidemiology of this disease.


Rationale and design of the ADDITION-Leicester study, a systematic screening programme and randomised controlled trial of multi-factorial cardiovascular risk intervention in people with type 2 diabetes mellitus detected by screening.
Earlier diagnosis followed by multi-factorial cardiovascular risk intervention may improve outcomes in type 2 diabetes mellitus (T2DM). Latent phase identification through screening requires structured, appropriately targeted population-based approaches. Providers responsible for implementing screening policy await evidence of clinical and cost effectiveness from randomised intervention trials in screen-detected T2DM cases. UK South Asians are at particularly high risk of abnormal glucose tolerance and T2DM. To be effective national screening programmes must achieve good coverage across the population by identifying barriers to the detection of disease and adapting to the delivery of earlier care. Here we describe the rationale and methods of a systematic community screening programme and randomised controlled trial of cardiovascular risk management within a UK multiethnic setting (ADDITION-Leicester). A single-blind cluster randomised, parallel group trial among people with screen-detected T2DM comparing a protocol driven intensive multi-factorial treatment with conventional care. ADDITION-Leicester consists of community-based screening and intervention phases within 20 general practices coordinated from a single academic research centre. Screening adopts a universal diagnostic approach via repeated 75g-oral glucose tolerance tests within an eligible non-diabetic population of 66,320 individuals aged 40-75 years (25-75 years South Asian). Volunteers also provide detailed medical and family histories; complete health questionnaires, undergo anthropometric measures, lipid profiling and a proteinuria assessment. Primary outcome is reduction in modelled Coronary Heart Disease (UKPDS CHD) risk at five years. Seven thousand (30% of South Asian ethnic origin) volunteers over three years will be recruited to identify a screen-detected T2DM cohort (n = 285) powered to detected a 6% relative difference (80% power, alpha 0.05) between treatment groups at one year. Randomisation will occur at practice-level with newly diagnosed T2DM cases receiving either conventional (according to current national guidelines) or intensive (algorithmic target-driven multi-factorial cardiovascular risk intervention) treatments. ADDITION-Leicester is the largest multiethnic (targeting >30% South Asian recruitment) community T2DM and vascular risk screening programme in the UK. By assessing feasibility and efficacy of T2DM screening, it will inform national disease prevention policy and contribute significantly to our understanding of the health care needs of UK South Asians. Clinicaltrial.gov (NCT00318032).


PCuAC domains from methane-oxidizing bacteria use a histidine brace to bind copper.
Copper is critically important for methanotrophic bacteria because their primary metabolic enzyme, particulate methane monooxygenase (pMMO), is copper-dependent. In addition to pMMO, many other copper proteins are encoded in the genomes of methanotrophs, including proteins that contain periplasmic copper-Achaperone (PCuAC) domains. Using bioinformatics analyses, we identified three distinct classes of PCuAC domain-containing proteins in methanotrophs, termed PmoF1, PmoF2, and PmoF3. PCuAC domains from other types of bacteria bind a single Cu(I) ion via an HXnMX21/22HXM motif, which is also present in PmoF3, but PmoF1 and PmoF2 lack this motif entirely. Instead, the PCuAC domains of PmoF1 and PmoF2 bind only Cu(II), and PmoF1 binds additional Cu(II) ions in a His-rich extension to its PCuAC domain. Crystal structures of the PmoF1 and PmoF2 PCuAC domains reveal that Cu(II) is coordinated by an N-terminal histidine brace HX10H motif. This binding site is distinct from those of previously characterized PCuAC domains but resembles copper centers in CopC proteins and lytic polysaccharide monooxygenase (LPMO) enzymes. Bioinformatics analysis of the entire PCuAC family reveals previously unappreciated diversity, including sequences that contain both the HXnMX21/22HXM and HX10H motifs, and sequences that lack either set of copper-binding ligands. These findings provide the first characterization of an additional class of copper proteins from methanotrophs, further expand the PCuAC family, and afford new insight into the biological significance of histidine brace-mediated copper coordination.


Mechanical response of brain tissue under blast loading.
In this study, a framework for understanding the propagation of stress waves in brain tissue under blast loading has been developed. It was shown that tissue nonlinearity and rate dependence are the key parameters in predicting the mechanical behavior under such loadings, as they determine whether traveling waves could become steeper and eventually evolve into shock discontinuities. To investigate this phenomenon, in the present study, brain tissue has been characterized as a quasi-linear viscoelastic (QLV) material and a nonlinear constitutive model has been developed for the tissue that spans from medium loading rates up to blast rates. It was shown that development of shock waves is possible inside the head in response to high rate compressive pressure waves. Finally, it was argued that injury to the nervous tissue at the microstructural level could be partly attributed to the high stress gradients with high rates generated at the shock front and this was proposed as a mechanism of injury in brain tissue.


Myocardial effects of ventricular fibrillation in the isolated rat heart.
Ventricular fibrillation (VF) is known to increase myocardial oxygen requirements and to alter coronary vascular physiology. However, the significance of these effects during cardiac arrest and resuscitation is not well understood. A model was developed in the isolated rat heart to investigate the myocardial effects of VF during a simulated episode of cardiac arrest and resuscitation. We hypothesized that VF would intensify the severity of myocardial ischemia and consequently accentuate postischemic myocardial dysfunction. Prospective and randomized. Research laboratory. Twenty Sprague-Dawley rats. Hearts were harvested and perfused at a constant flow rate of 10 mL/min using a modified Krebs-Henseleit solution equilibrated with 95% oxygen and 5% CO2. In five hearts, VF was induced by a 0.05-mA current delivered to the right ventricular endocardium. The perfusate flow was then stopped for a 10-min interval and resumed at 20% of baseline flow for another 10 mins. After 20 mins of VF, the perfusate flow was returned to baseline and a sinus rhythm reestablished by epicardial electrical shocks. The studies were randomized and included three additional groups to control for the effects of ischemia without VF (n = 5), the effects of VF without ischemia (n = 5), and the stability of the preparation (n = 5). Isovolumic indices of left ventricular function were obtained using a latex balloon advanced through the mitral valve and distended to an end-diastolic pressure of 10 mm Hg. The coronary effluent was collected from the right ventricular cavity. VF during myocardial ischemia was associated with a higher coronary effluent PCO2, increased coronary vascular resistance, and development of ischemic contracture as indicated by increases in left ventricular pressure from 9+/-3 to 33+/-6 mm Hg (p < .05). After defibrillation, contractility and relaxation rapidly returned to baseline values, whereas the isovolumic end-diastolic pressure remained elevated for 20 mins. These changes were much less prominent when ischemia was not accompanied by VF. These findings indicate that VF may adversely affect myocardial ischemia by hastening the development of ischemic contracture, increasing coronary vascular resistance, and favoring the development of diastolic pump failure early after resuscitation from cardiac arrest.


Serum sTWEAK concentrations and risk of developing type 2 diabetes in a high cardiovascular risk population: a nested case-control study.
Because serum concentrations of soluble forms of TNF-like weak inducer of apoptosis (sTWEAK) and scavenger receptor CD163 (sCD163) have been associated with insulin resistance and type 2 diabetes mellitus (T2D), we tested the associations of sTWEAK and sCD163 with the future development of T2D in elderly subjects at high cardiovascular risk. A prospective, matched case-control study of 153 cases of newly diagnosed diabetic subjects and 306 individually matched controls who did not develop diabetes during a mean 5-year follow-up was conducted using data from the PREDIMED study. Conditional logistic regression was used to estimate the matched odds ratio (OR) for incident T2D according to categories of baseline sTWEAK and sCD163 concentrations measured by ELISA. Baseline sTWEAK concentrations were lower in cases than controls. There were no case-control differences in sCD163 concentrations. In the conditional logistic model that took into account the matching factors, the ORs for T2D incidence in the highest vs the lowest quartile of sTWEAK and the sCD163/sTWEAK ratio were 0.49 (95% confidence interval [CI], 0.31-0.76; P for trend <.01) and 1.67 (95% CI, 1.06-2.63; P for trend = .05), respectively. Further adjustment for potential lifestyle confounding factors had little impact on these estimates, whereas adjustment for metabolic syndrome components and fasting insulin levels attenuated the magnitude of associations and only the sTWEAK remained statistically significant (OR = 0.63; 95% CI, 0.40-0.98; P for trend = .05). These findings indicate that in a population at high cardiovascular risk, reduced circulating levels of sTWEAK are associated with an increased risk of diabetes incidence.


Application of Texture Analysis Technique in Formulation Development of Lyophilized Orally Disintegrating Tablets Containing Mannitol, Polyvinylpyrrolidone and Amino Acids.
Orally disintegrating tablets (ODTs) attract a great attention as this easy swallowing dosage form often improves patient compliance. In the current work, orally disintegrating tablets comprising mannitol, polyvinylpyrrolidone (PVP) and an amino acid (alanine, glycine or serine) with various PVP-to-amino acid ratios were formulated. The combination of mannitol and an amino acid was aimed to use the advantages of mannitol, the matrix-supporting and disintegration agent, and to reduce the total amount of sugar/polyol in tablets. Tablets were manufactured by freeze-drying and their properties (appearance, internal structure, disintegration, mechanical and texture properties, moisture uptake, shrinkage, thermal properties) were assessed. In the work, great emphasis was placed on illustrating the applicability of the Texture Analysis of the freeze-dried cakes directly in vials in formulation development. The results show that the appearance, mechanical properties, disintegration and shrinkage of the freeze-dried ODTs depend significantly on the excipient composition with PVP playing the leading role. Partial mannitol replacement with an amino acid has a limited impact on the tablet properties. The presence of an amino acid also has no impact on the PVP-mannitol interaction. The mechanical and texture properties of freeze-dried ODTs depend non-linearly on the PVP content. The transition between the different types of textures occurs in a narrow range of PVP concentrations regardless of the type of amino acid in a formulation. The non-linear effect of PVP on various tablet properties should be taken into account when designing ODT formulations as it can compromise the robustness of the manufacturing process.


Healthy and diseased corticospinal motor neurons are selectively transduced upon direct AAV2-2 injection into the motor cortex.
Direct gene delivery to the neurons of interest, without affecting other neuron populations in the cerebral cortex, represent a challenge owing to the heterogeneity and cellular complexity of the brain. Genetic modulation of corticospinal motor neurons (CSMN) is required for developing effective and long-term treatment strategies for motor neuron diseases, in which voluntary movement is impaired. Adeno-associated viruses (AAV) have been widely used for neuronal transduction studies owing to long-term and stable gene expression as well as low immunoreactivity in humans. Here we report that AAV2-2 transduces CSMN with high efficiency upon direct cortex injection and that transduction efficiencies are similar during presymptomatic and symptomatic stages in hSOD1(G93A) transgenic amyotrophic lateral sclerosis (ALS) mice. Our findings reveal that choice of promoter improves selectivity as AAV2-2 chicken β-actin promoter injection results in about 70% CSMN transduction, the highest percentage reported to date. CSMN transduction in both wild-type and transgenic ALS mice allows detailed analysis of single axon fibers within the corticospinal tract in both cervical and lumbar spinal cord and reveals circuitry defects, which mainly occur between CSMN and spinal motor neurons in hSOD1(G93A) transgenic ALS mice. Our findings set the stage for CSMN gene therapy in ALS and related motor neuron diseases.


Entry of simian virus 40 is restricted to apical surfaces of polarized epithelial cells.
The uptake of simian virus 40 (SV40) by polarized epithelial cells was investigated by growth of cells on permeable supports and inoculation on either the apical or the basolateral surface. Binding of radiolabeled SV40 occurred on the apical but not the basolateral surfaces of permissive polarized Vero C1008 cells and nonpermissive polarized MDCK cells. When similar experiments were performed on nonpolarized Vero or CV-1 cells, virus binding occurred regardless of the direction of virus input. Electron micrographs of Vero C1008 cells infected at high multiplicities revealed virions lining the surfaces of apically infected cells, while the surfaces of basolaterally infected cells were devoid of virus particles. Analysis of the binding data revealed a single class of virus receptors (9 x 10(4) per cell) with a high affinity for SV40 (Kd = 3.76 pM) on the apical surfaces of Vero C 1008 cells. Indirect immunofluorescence studies revealed that synthesis of viral capsid proteins in Vero C1008 cells occurred only when input virions had access to the apical surface. Virus yields from apically infected Vero C1008 cells were 10(5) PFU per cell, while yields obtained from basolaterally infected cells were less than one PFU per cell. These results indicate that a specific receptor for SV40 is expressed exclusively on the apical surfaces of polarized Vero C1008 cells.


[Comparative analysis of the informative value of 18F-fluorodeoxyglucose and 11C-methionine positron emission tomography in the differential diagnosis of solitary lung masses].
To study the possibilities of enhancing the efficiency of differential diagnosis of solitary lung masses by optimizing the quantitative analysis of positron emission tomography (PET) data when two radiopharmaceuticals (RP) (18F-fluorodeoxyglucose (18F-FDG) and 11C-methionine) are used alone and in combination. A comprehensive examination involving 18F-FDG and 11C-methionine PET was made in 116 patients with solitary lung masses of various genesis. A final diagnosis in the examinees was established from the results of postoperative material morphological analysis and/or laboratory tests and those of X-ray follow-up. No 18F-FDG and 11C-methionine hyperfixation was found in patients with benign tumors and in the majority of patients with focal pneumofibrosis. At 18F-FDG and 11C-methionine PET, RP accumulation was recorded in all patients with lung cancer (LC) and in patients with inflammatory diseases. Three patients with 18F-FDG PET-negative typical carcinoid tumors were noted to have increased 11C-methionine uptake. At 11C-methionine PET, RP accumulation was recorded in the projection of formation in all the patients with LC and in 38 of the 42 patients with inflammatory diseases. Regardless of the used RP, the Standardized Uptake Value (SUV) was significantly lower in the patients with inflammatory diseases than in those with LC (p ≤ 0.05). When RP is used alone, the diagnostic efficiency of C-methionine PET in the differential diagnosis of lung tumors and inflammations is higher than that of 18F-FDG PET. At the same time, the highest PET is seen when 18F-FDG and 11C-methionine are used in combination.


Preferential cholesteryl ester acceptors among triglyceride-rich lipoproteins during alimentary lipemia in normolipidemic subjects.
Triglyceride-rich lipoproteins (TRLs), namely chylomicrons (CMs), VLDL, and their remnants, are implicated in the atherogenic features of postprandial lipemia. In human plasma, cholesteryl ester transfer protein (CETP) mediates the heteroexchange of neutral lipids, ie, triglycerides (TG) and cholesteryl esters (CE), between distinct subpopulations of apoB- and of apoAI-containing lipoproteins. In fasting normolipidemic plasma, CETP plays an antiatherogenic role by promoting preferential CE redistribution from HDL to LDL particles of intermediate subclass with optimal binding affinity for the cellular LDL receptor. While the relative proportions and chemical compositions of donor and acceptor lipoproteins are known to influence CETP activity, elevated levels of TRL present during alimentary lipemia have been proposed to be associated with enhanced CETP activity. To identify the preferential CE acceptor particles among postprandial TRL subfractions, we investigated the effects of a typical Western meal (1200 kcal, 14% protein; 38% carbohydrate; and 48% fat, monounsaturated/polyunsaturated ratio 4:1) on the rates of postprandial CE transfer from HDL to apoB-containing lipoproteins in normolipidemic subjects (n=13). Two hours postprandially, plasma levels of TRL were significantly elevated (140 versus 51 mg/dL at baseline, P=.0001). Total rates of CE transferred (88 +/- 7 microg x h[-1] x mL[-1]) from HDL to apoB-containing lipoproteins were not significantly modified by alimentary lipemia over a period of 8 hours. Quantitatively, LDL accepted 64+/-5 microg CE per hour per milliliter plasma from HDL, whereas CM (Sf>400), VLDL1 (Sf 60 to 400), VLDL2 (Sf 20 to 60), and IDL (Sf 12 to 20) accepted 5+/-3, 16+/-3, 1.4+/-0.3, and 1.5+/-0.2, respectively. Quantitatively, VLDL1 was the major CE acceptor among TRLs (P=.0001); thus, VLDL1, but not CMs, represented the major CE acceptor among TRLs. Qualitatively however, VLDL2 and IDL displayed a higher capacity to accept CE from HDL (51.6+/-4.1 and 46.3+/-2.8 microg CE transferred per hour per milligram lipoprotein, respectively; P<.005) compared with CM, VLDL1, and LDL (12.6+/-2.8, 34.7+/-4.2, and 22.7+/-2.0 microg CE transferred per hour per milligram lipoprotein, respectively). In conclusion, elevated postprandial TRL levels are not associated with enhanced total CE transfer to these particles. Furthermore, the qualitative features of postprandial CE transfer from HDL to CM and VLDL1 were not related to the relative TG content of these particles. The CETP-facilitated enrichment of VLDL1 in CE therefore identifies them as potentially atherogenic particles during the postprandial phase.


[Percutaneous or intradermal BCG vaccine?].
To compare the intradermal and percutaneous routes of BCG administration. A review of the literature published between 1987 and 2002 was carried out in the MEDLINE and Lilacs databases. The following key words were used: BCG vaccine/administration, adverse effects, efficacy, tuberculosis/prevention and control. Some articles published before 1987 were included because of their relevance to the topic. There are no clinical studies comparing the efficacy of intradermal and percutaneous BCG. Percutaneous BCG causes a weaker reaction, however it is also less efficient in stimulating gamma-interferon production by Th1-lymphocytes, which is considered as the best marker of the anti-tuberculin immune response. In vivo and in vitro studies suggest a better immune response with intradermal BCG. The intradermal method should be recommended for BCG administration.


Chromosome damage induced by artificial seed aging in barley : 3. Behavior of chromosomal aberrations during plant growth.
Barley (Hordeum vulgare L. 'Himalaya') seeds were artificially aged under two storage conditions (32 °C/12% moisture content (m.c.) and 38 °C/18% m.c.) to study the behavior of induced chromosomal aberrations during plant growth. The frequencies of aberrant anaphases at first mitosis in root tips were correlated with loss of germinability. However, after 3 and 5 weeks' growth, aberration frequency declined. In plants grown from artificially aged seeds, the frequency of aberrant anaphases appeared to be stabilized at about 1% after 5 weeks' growth, in spite of the large differences in the frequencies at first mitosis. This suggests that because of their genetic imbalance, cells with chromosomal aberrations induced by seed aging were being excluded during plant growth. Meiotic chromosome configurations at MI were normal (7 II) in all plants studied, although a few precocious separations were found. Meiotic aberrations were found at AI-TI, AII-TII and the tetrad stages in the pollen mother cells of plants grown from the control and artificially aged seeds. However, there were no clear differences among the control and the two aging treatments. It was obvious that some cells with meiotic chromosomal aberrations were lost between the AI-TI and AII-TII stages, and still more between the AII-TII and tetrad stages. The frequency of tetrads with micronuclei in plants produced from artificially aged seeds was the same as in the control. The plants grown from artificially aged seeds showed high pollen fertility (95.2 to 97.0%) and seed fertility (90.1 to 97.2%) which was comparable to the control values (97.4 and 97.9%) respectively, indicating no special effects of seed aging. Anaphase cells of the first mitosis in the next (A2) generation were analyzed to study the transmission of chromosomal aberrations through mitotic and meiotic cell divisions in the A1 generation. Aberrant anaphases in the progeny from the artificially aged seeds were not higher than those of the control progeny. This indicates that the chromosomal aberrations induced by seed aging are not transmitted to the next generation.


[Peptic ulcer with hemorrhage. An analysis of hospital discharges].
The gastric and duodenal ulcer is the most common cause of gastrointestinal bleeding in 25% of patients, and accounting annually for approximately 50-100 admissions per 100,000 population. To determine prevalence of gastrointestinal bleeding in hospital admission, according to age and sex and identifying the risk factors. Determined the prevalence rates of number of hospital discharges of patients with gastrointestinal bleeding for GU and DU during period 1991 to 1997. Determined the prevalence rates of peptic ulcer occurrence for age-adjusted rates, sex and seasonal variation for 1000 hospital discharges. We investigated the features of hemorrhage of the upper gastrointestinal tract, and identification of risk factors as NSAID, alcohol and tobacco. Chi square and t Student. The annual prevalence rates were 46.6/1000 hospital discharges. There were more frequent between 6th to 8th decades, female sex and during May, June and November. The average stay of patients were 4.2 days (range 1 to 18). A total of 275 patients were found to have GU or DU with gastrointestinal bleeding, 66% were male and mean age was 57 years. The risk factors found were tobacco 52%, alcohol 40% and NSAID 44% (P < 0.05). Melena and hematemesis was found in 64% y 36% respectively. The GU (41%) was more frequent than DU (40%) (P NS). The annual prevalence rates were 46.6/1000 hospital discharges more frequent in males (66%) and gastric ulcer was found more frequent (41%) than DU (P NS).


[Evaluation of the E-learning training, early prevention and intervention in child protection"].
Prevention, intervention, and child protection in early childhood essentially need well-established interdisciplinary systematic networking. Currently there is a lack of education, training and qualification programs which take the specific demands for interdisciplinary knowledge about the early childhood as well as practical experience about early prevention and intervention in child protection into account. The Internet-based E-Learning training "Early Intervention and Child Protection" was developed to fill this gap. A pilot-study with 45 test-users showed, that they learned significantly while using the platform and changed aspects of their everyday routine. Thereupon the platform was opened in June 2011 to all professionals. At the moment 2,300 people are registered and participate at the training. The aim of this study, namely to make a systematic training on early prevention and intervention in child protection wide-ranging available, was achieved


Chemical composition and antibacterial activity of the essential oils of Callistemon citrinus and Callistemon viminalis from South Africa.
The chemical composition and the antibacterial activity of the essential oils obtained by hydrodistillation from the leaves of Callistemon citrinus and Callistemon viminalis were analyzed by GC and GC/MS. Twenty-four and twelve components were identified for C. citrinus and C. viminalis, representing 92.0% and 98.3% of the total oils. The major components of C. citrinus and C. viminalis were 1,8-cineole (61.2% and 83.2%) and alpha-pinene (13.4% and 6.4%), respectively. The in vitro antibacterial activity of the essential oils was studied against 12 bacteria strains using disc diffusion and broth microdilution methods. The oils exhibited strong zone of inhibitions against some bacteria such as S. faecalis (20.3-24.0 mm), both strains of S. aureus (23.0-26.3 mm), B. cereus (17.3-19.0 mm) and S. macrcesens (11.3-23.7 mm) when compared to standard antibiotics gentamycin and tetracycline used as controls. Expect for P. aeruginosa and S. macrcescens, the MIC values of both essential oils ranged from 0.31-2.50 mg/mL.


Unusual small choroid plexus cyst obstructing the foramen of monroe: case report.
This is a case report of unusual case of choroid plexus cyst at the right foramen of Monro in the anterior third ventricle that caused unilateral obstructive hydrocephalus. The value of small-FOV thin-section MR imaging in the diagnosis of small lesions of the foramen of Monroe is demonstrated. The immunohistochemical findings in choroid epithelial cysts in comparison with those of other types of cysts at this location are discussed.


Targeted dianthin is a powerful toxin to treat pancreatic carcinoma when applied in combination with the glycosylated triterpene SO1861.
Targeted cancer therapy provides the basis for the arrest of tumor growth in aggressive pancreatic carcinoma; however, a number of protein-based targeted toxins lack efficacy due to insufficient endosomal escape after being endocytosed. Therefore, we tested a fusion protein of the ribosome-inactivating protein dianthin and human epidermal growth factor in combination with a glycosylated triterpene (SO1861) that serves as an endosomal escape enhancer. In vitro investigations with the pancreatic carcinoma cell lines BxPC-3 and MIA PaCa-2 revealed no significant differences to off-target cells in the half maximal inhibitory concentration (IC50 ) for the fusion protein. In contrast, combination with SO1861 decreased the IC50 for BxPC-3 cells from 100 to 0.17 nm, whereas control cells remained unaffected. Monotherapy of BxPC-3 xenografts in CD-1 nude mice led to a 51.7% average reduction in tumor size (40.8 mm3 ) when compared to placebo; however, combined treatment with SO1861 resulted in a more than 13-fold better efficacy (3.0 mm3 average tumor size) with complete regression in 80% of cases. Immunohistochemical analyses showed that tumor cells with lower target receptor expression are, in contrast to the combination therapy, able to escape from the monotherapy, which finally results in tumor growth. At the effective concentration, we did not observe liver toxicity and saw no other side effects with the exception of a reversible skin hardening at the SO1861 injection site, alongside an increase in platelet counts, plateletcrit, and platelet distribution width. In conclusion, combining a targeted toxin with SO1861 is proven to be a very promising approach for pancreatic cancer treatment.


The influence of maternal age on pregnancy outcome in nulliparous women with twin gestation.
We sought to determine if outcomes of nulliparous twin pregnancies differ based on maternal age. Nulliparous women with current twin pregnancies were identified from a database of women enrolled for outpatient nursing surveillance. Data were stratified into four groups by maternal age: less than 20, 20 to 34, 35 to 39, and greater than or equal to 40 years. Maternal and neonatal outcomes for women less than 20, 35 to 39, and 40 or more were compared with 20- to 34-year-old controls using Kruskal-Wallis, Mann-Whitney, and Pearson chi-square analyses. We analyzed 2144 nulliparous twin pregnancies. Patients ≥35 years (34 to 39, 78.5% or ≥40, 85.9%) were more likely to have cesarean deliveries compared with controls 20 to 34 years old (71.2%). Women aged 35 to 39 were less likely to deliver at <37 weeks, and women in the ≥40 group were less likely to deliver at <35 weeks due to spontaneous preterm labor compared with the controls. Neonates born to women aged 35 to 39 had a greater gestational age at delivery and larger average birth weight than controls. Maternal and neonatal outcomes were not adversely influenced by advanced maternal age in nulliparous women carrying twin gestations.


Association of clonal hematopoiesis mutations with clinical outcomes: A systematic review and meta-analysis.
Clonal hematopoiesis (CH) mutations are common among individuals without known hematologic disease. CH mutations have been associated with numerous adverse clinical outcomes across many different studies. We systematically reviewed the available literature for clinical outcomes associated with CH mutations in patients without hematologic disease. We searched PubMed, EMBASE, and Scopus for eligible studies. Three investigators independently extracted the data, and each study was verified by a second author. Risk of bias was assessed using the Newcastle-Ottawa Scale. We identified 32 studies with 56 cohorts that examine the association between CH mutations and clinical outcomes. We conducted meta-analyses comparing outcomes among individuals with and without detectable CH mutations. We conducted meta-analyses for cardiovascular diseases (nine studies; HR = 1.61, 95% CI = 1.26-2.07, p = .0002), hematologic malignancies (seven studies; HR = 5.59, 95% CI = 3.31-9.45, p < .0001), therapy-related myeloid neoplasms (four studies; HR = 7.55, 95% CI = 4.3-13.57, p < .001), and death (nine studies; HR = 1.34, 95% CI = 1.2-1.5, p < .0001). The cardiovascular disease analysis was further stratified by variant allele fraction (VAF) and gene, which showed a statistically significant association only with a VAF of ≥ 10% (HR = 1.42, 95% CI = 1.24-1.62, p < .0001), as well as statistically significant associations for each gene examined with the largest magnitude of effect found for CH mutations in JAK2 (HR = 3.5, 95% CI = 1.84-6.68, p < .0001). Analysis of the association of CH mutations with hematologic malignancy demonstrated a numeric stepwise increase in risk with increasing VAF thresholds. This analysis strongly supports the association of CH mutations with a clinically meaningful increased risk of adverse clinical outcomes among individuals without hematologic disease, particularly with increasing VAF thresholds.