Stressful life events and resilience in individuals with and without a history of eating disorders: a latent class analysis.
Eating disorders (EDs) are associated with a range of stressful life events, but few have investigated protective factors that may affect these associations. The current study used mixture modelling to describe typologies in life stress exposure and availability of protective resources in individuals with and without eating disorders (EDs). A case - control sample (n = 916) completed measures of stressful life events, resilience protective factors, emotion regulation, and symptoms of EDs, depression and anxiety. We conducted latent class analyses to identify subgroups of stress exposure and profile analyses of emotional regulation and resilience. The resulting two latent variables were combined to explore effects on ED status and symptomatology, depression, and anxiety as distal outcome variables. We identified four classes of stressful life events (generally low, some abuse/bullying, sexual/emotional assaults, and high adversity). For protective resources, we identified six profiles that ranged from low to higher levels of protection with variations in social/family resources. The latent protection variable contributed more strongly to the distal outcomes than the latent stress variable, but did not moderate the latent stress and distal outcome variable relationships. Profiles characterized by lower protective resources included higher proportions of individuals with a lifetime ED, and were associated with higher scores on all symptom measures. Intra- and interpersonal protective resources were strongly associated with lifetime EDs and current mental health symptom burden after accounting for stressful event exposure, suggesting protective factors may be useful to target in the clinical treatment of patients with ED.


Evaluation of classical and novel autoantibodies for the diagnosis of Primary Biliary Cholangitis-Autoimmune Hepatitis Overlap Syndrome (PBC-AIH OS).
Up to 20% of Primary Biliary Cholangitis (PBC) patients are estimated to have features that overlap with Autoimmune Hepatitis (AIH). Patients with PBC-AIH overlap syndrome (PBC-AIH OS) have been reported to exhibit suboptimal responses to ursodeoxycholic acid therapy, and are more likely to progress to cirrhosis. Anti-double stranded DNA (anti-dsDNA) and anti-p53 have been previously suggested to be potential autoantibodies for identifying patients with PBC-AIH OS. In our well defined PBC patient cohorts, a comprehensive assessment of various classical and novel autoantibodies was evaluated for their utility in identifying PBC-AIH OS patients. PBC-AIH OS was classified according to the Paris criteria and PBC as per the European Association for the Study of the Liver guidelines. Biobanked serum samples from 197 patients at the University of Calgary Liver Unit and the University of Alberta were analyzed for classical and novel autoantibodies. Anti-dsDNA was measured by the Crithidia luciliae immunofluorescence (CLIFT) assay (1:20 dilution) and chemiluminescence (CIA: QUANTA Flash®, Inova Diagnostics, San Diego). Anti-p53, anti-Ro52/TRIM21, anti-YB 1, anti-GW182, anti-Ge-1, and anti-Ago 2 were measured by either an addressable laser bead immunoassay (ALBIA) or line immunoassay (LIA). Autoantibodies against MIT3, gp210, sp100, LKM1, SLA, and the novel autoantibodies Hexokinase-1 (HK-1), and Kelch like protein 12 (KLHL-12) were measured using QUANTA Lite® ELISA assays. We applied non-parametric methods to compare the biomarkers frequencies between study groups. We used multivariate adjusted models and AUROC to compare the diagnostic accuracy of the different autoantibodies alone or in combination with serum biochemistry. 16 out of 197 PBC patients (8.1%) were classified as PBC-AIH OS. Compared to PBC patients, PBC-AIH OS patients were similar in age (median: 59 vs. 63, P = 0.21) and female predominance (94% vs. 89%, P = 1.00). Anti-dsDNA-by CLIFT (37.5% in PBC-AIH OS vs 9.9% in PBC alone, P <0.01) was the only autoantibody associated with PBC-AIH OS; a finding consistent with previous reports. Significant elevation in serum ALT (62 IU/L in PBC-AIH OS vs 37 IU/L in PBC alone, P < 0.01), and serum IgG (17.6 g/L in OS vs 12.1 g/L in PBC alone, P <0.01) were observed in patients with PBC-AIH OS receiving medical/immunosuppressive therapy. In a multivariate model, positive anti-dsDNA by CLIFT, ALT and IgG were significant predictors of PBC-AIH OS with an area under the receiver operator curve (AUROC) value of 0.84. Consistent with previous findings, the presence of anti-dsDNA by CLIFT is associated with PBC-AIH OS. Contrary to previous reports, anti-p53 was not associated with PBC-AIH OS. Our comprehensive evaluation of various classical and novel autoantibody biomarkers including Ro52/TRIM21, anti-p53, anti-KLHL-12 and anti-HK-1 were not significantly associated with PBC-AIH OS. Our findings highlight the ongoing need for the research and development of new autoantibody biomarkers to aid in the diagnosis of PBC-AIH OS.


Interaction of quercetin with DNA.
In vitro experiments to study interaction of the mutagenic flavonoid quercetin with DNA are described. Calf thymus DNA treated with quercetin for various time periods was subjected to S1 nuclease hydrolysis. Thermal melting profiles of treated DNA were also determined using S1 nuclease. The rate of DNA hydrolyzed after 1 hr of pretreatment with quercetin was found to be only about 50% of that in its absence. However, after 10 and 24 hrs of treatment with the drug, the rate of S1 nuclease hydrolysis was observed to be greater than that of native DNA. Thermal melting profiles of DNA, treated with quercetin for 10 and 24 hrs, indicated a slight decrease in melting temperatures. Gel filtration of native DNA, which had been digested with S1 nuclease after preincubation with quercetin for 24 hrs, indicated the production of various sized degraded molecules. The results suggest that the initial interaction of quercetin with DNA may have a stabilizing effect on its secondary structure, but prolonged treatment leads to an extensive disruption of the double helix.


Trends in corneal transplantation from 2001 to 2016 in Brazil.
A retrospective and analytical study was conducted by using data from the National Transplantation System on 184,575 corneal transplantations performed between January 2001 and December 2016 in order to analyze thetrends in corneal transplantation from 2001 to 2016 in Brazil. The Cochran-Armitage test, analysis of variance, and Duncan's multiple comparisons were used to verify the existence of trends, compare the mean values between regions, and verify the mean differences, respectively. A significance level of 5% was used for all tests. The analysis showed that there was a 2.4-fold increase in the number of corneal transplantations (from 6,193 [35.2 per million people (pmp)] to 14,641 [71 pmp]; p<0.001), a 50.7% increase in the efficacy of meeting the population's demand for corneal transplantation (from 35.3% to 53.2%; p<0.001), an 11-fold increase in the number of corneal transplantation centers (from 32 to 356), and a 2.5-fold increase in the number of corneal transplantation teams (from 276 to 688) in Brazil during the period studied. The waiting list for corneal transplantation decreased by 45.4% (from 23,549 [123 pmp] to 12,865 [62.4 pmp]; p<0.001), and the corneal transplantation teams performed about 19 corneal transplantations per year. The best indices were observed in the southern, midwestern, and southeastern regions, and the worst indices were in the northern and northeastern regions. Brazil has been improving its capacity to perform corneal transplantation in the past 16 years, although this improvement varies across regions. However, the population's demand for corneal transplantation is yet to be satisfactorily met, primarily due to the low number of corneal donations.


Evaluation of the usefulness of EQ-5D as a patient-reported outcome measure using the Paretian classification of health change among patients with chronic heart failure.
The aim of this study was to evaluate the usefulness of EQ-5D as a patient-reported outcome measure using different analytical methods. Especially we used the Paretian Classification of Health Change, to see if this gave better information compared to measures that are more traditional. For the evaluation we used data from patients with chronic heart failure (HF). We compared results of EQ-5D at baseline and at 1 year's follow up for HF patients with preserved or reduced ejection fraction (EF), HFpEF (EF > 50%, n = 930) and HFrEF (EF < 40%, n = 3831) using individual patient data from the Swedish Heart Failure Registry. Statistical analysis included EQ-5D index and proportions for all five dimensions of the EQ-5D. In addition, we also used the Paretian classification of Health Change to judge overall improvements (improved in at least one dimension and not worsened in any other dimension) or worsening (vice versa) in EQ-5D profiles. Mean EQ-5D index showed minor changes at the one-year follow-up, likewise in both groups. The proportions reporting moderate, or severe, problems increased for all five dimensions of the EQ-5D in the HFpEF group. In the HFrEF group this was seen only for three dimensions, with no change for "anxiety/depression" and reduction of problems for "usual activities ". The Paretian classification showed that 24% (n = 200) of the HFpEF group and 34% (n = 1059) of the HFrEF group reported overall improvement while 43% (n = 355) and 39% (n = 1212) respectively reported overall worsening. Multiple logistic regressions showed different patterns of determinants e.g. that treatment in a cardiology clinic only affected overall health outcome in the HFrEF group. The usefulness of EQ-5D is dependent on the analytical method used. While the index showed minor differences between groups, analyses of specific dimensions showed different patterns of change in the two groups with better prognosis for the HFrEF group. The Paretian classification of Health Change could further identify subgroups that showed overall improvements or overall worsening. This method can therefore help to identify needs for more tailored interventions in health services.


Anti-inflammatory activity of Echium amoenum extract on macrophages mediated by inhibition of inflammatory mediators and cytokines expression.
Echium amoenum (Boraginaceae) is an important remedy used for various illnesses. In this study, we investigated the anti-inflammatory effects of E. amoenum in the J774.1A macrophage cell line. We prepared ethyl acetate, dichloromethane and hexane extracts from E. amoenum flowers and examined their possible cytotoxic effects using MTT assay. Lipopolysaccharide (LPS)-stimulated macrophages were treated with the extracts after which we measured nitric oxide (NO) production by Griess method. Inducible NO synthase (iNOS), cyclooxygenase-2 (COX2), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 gene expressions were examined by real time-PCR. IL-1β and IL-6 cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA). The hexane extract with a half maximal inhibitory concentration (IC50) of 39.8 μg/mL most effectively reduced NO production. Real time-PCR analysis indicated reduced levels of iNOS ((0.05 ± 0.006 relative fold change (RFC)) and COX2 (0.06 ± 0.002 RFC) gene expressions with the 100 μg/mL hexane extract (P < 0.001). IL1-β, TNF-α, and IL-6 gene expression levels decreased at all concentrations of the extract (less than ≈ 0.28 RFC). Treatment of LPS-stimulated cells with 100 μg/mL of the extract reduced IL-1β secretion to 27.9 ± 0.21 pg/mL and IL-6 to 555 ± 166 pg/mL. In conclusion, E. amoenum hexane extract showed the greatest reduction in macrophage NO secretion compared to other extracts. This extract could modulate the inflammatory mode of the macrophages by causing reductions in iNOS and COX2 enzymes as well as IL-1β, IL-6, and TNF-α cytokine levels. The results of this study have shown the anti-inflammatory effects of this plant. Further studies regarding its therapeutic potential in inflammatory disorders are recommended.


Illiteracy, low educational status, and cardiovascular mortality in India.
Influence of education, a marker of SES, on cardiovascular disease (CVD) mortality has not been evaluated in low-income countries. To determine influence of education on CVD mortality a cohort study was performed in India. 148,173 individuals aged ≥ 35 years were recruited in Mumbai during 1991-1997 and followed to ascertain vital status during 1997-2003. Subjects were divided according to educational status into one of the five groups: illiterate, primary school (≦ 5 years of formal education), middle school (6-8 years), secondary school (9-10 years) and college (> 10 years). Multivariate analyses using Cox proportional hazard model was performed and hazard ratios (HRs) and 95% confidence intervals (CIs) determined. At average follow-up of 5.5 years (774,129 person-years) 13,261 deaths were observed. CVD was the major cause of death in all the five educational groups. Age adjusted all-cause mortality per 100,000 in illiterate to college going men respectively was 2154, 2149, 1793, 1543 and 1187 and CVD mortality was 471, 654, 618, 518 and 450; and in women all-cause mortality was 1444, 949, 896, 981 and 962 and CVD mortality was 429, 301, 267, 426 and 317 (ptrend < 0.01). Compared with illiterate, age-adjusted HRs for CVD mortality in primary school to college going men were 1.36, 1.27, 1.01 and 0.88 (ptrend < 0.05) and in women 0.69, 0.55, 1.04 and 0.74, respectively (ptrend > 0.05). Inverse association of literacy status with all-cause mortality was observed in Indian men and women, while, for CVD mortality it was observed only in men.


The Effects of Trauma, Violence, and Stress on Sexual Health Outcomes Among Female Clinic Clients in a Small Northeastern U.S. Urban Center.
Background: Threats to sexual health can emerge across one's life span and are influenced by individual and interpersonal experiences, as well as certain environmental exposures. Although previous research has recognized the importance of ecological frameworks to understand the complexity of health and behaviors in marginalized communities, there continues to be a dearth of research that truly utilizes this perspective to gain insight into the multifaceted factors that can concurrently influence threats to sexual health among women. Methods: A sample of 279 ethnoracially diverse women were recruited from a U.S. northeastern small urban center health clinic to participate in a parent study on trauma and immunity. A hierarchical block analysis was conducted to investigate associations between women's experiences of trauma, stress and violence (i.e., childhood trauma (CHT), intimate partner violence (IPV), neighborhood stressors), and sexual health outcomes and behaviors (i.e., lifetime sexually transmitted infection [STI] diagnosis, concurrent partnerships, and lifetime sex trading). Results: In the full hierarchical model, IPV and life stress trauma were associated with lifetime sex trading and partner concurrency. Also in the full model, sexual CHT was associated with lifetime STI acquisition and partner concurrency, while emotional CHT was associated with lifetime sex trading. Lastly, as neighborhood disorder increased, so did the number of lifetime sex trading partners. Conclusion: Sexual health assessments in clinical and community settings require a holistic, comprehensive, and meaningful approach to inform person-centered health promotion intervention. Prevention and treatment interventions require a focus on parents and families, and should assist adolescents and young adults to adopt therapies for healing from these experiences of trauma, violence, and stress. Interventions to enhance sexual health promotion must also include the following: advocacy for safe environments, social policy that addresses lifelong impacts of CHT, and fiscal policy that addresses economic vulnerability among women and threatens sexual health. Further recommendations are discussed.


Damage and healing in the conducting tissue of the heart (an experimental study in dogs infected with Trypanosoma cruzi).
The consequences of acute inflammatory damage and chronic repair in the conducting system of the canine heart were observed after experimental Trypanosoma cruzi infection of young dogs. Acute infection lasted for 18-25 days and caused hyaline and lytic necrosis of the atrio-ventricular conducting fibres, the sinus node and the neurons in the cardiac para-sympathetic ganglia. Dogs that survived acute disease were examined after periods from 8 months to 3 years. Three main types of healing were found in the conducting system: fibrosis (diffuse and/or focal), sclero-atrophy and fatty infiltration. No signs of active chronic inflammation were present, although small focal residual accumulations of mononuclear cells were present in some animals. No evident electrocardiographic alterations were elicited by the presence of such cicatricial lesions. The animal model appears worthwhile for the study of the healing process in conducting tissue of the heart and for the better understanding of the asymptomatic phase of T. cruzi infection in man.


The Impact of Tobacco Use on COVID-19 Outcomes: A Systematic Review.
Tobacco use increases risks for numerous diseases, including respiratory illnesses. We examined the literature to determine whether a history of tobacco use increases risks for adverse outcomes among COVID-19 patients. We conducted a systematic search of PubMed, LitCovid, Scopus, and Europe PMC (for preprints) using COVID-19 and tobacco-related terms. We included studies of human subjects with lab-confirmed COVID-19 infections that examined tobacco use history as an exposure and used multivariable analyses. The data was collected between March 31st, 2020, and February 20th, 2021. Outcomes included mortality, hospitalization, ICU admission, mechanical ventilation, and illness severity. Among the 39 studies (33 peer-reviewed, 6 preprints) included, the most common outcome assessed was mortality (n = 32). The majority of these studies (17/32) found that tobacco use increased risk, one found decreased risk, and 14 found no association. Tobacco use was associated with increased risk of hospitalization in 7 of 10 studies, ICU admission in 6 of 9 studies, mechanical ventilation in 2 of 6 studies, and illness severity in 3 of 9 studies. One study found that tobacco use history increased risk of pulmonary embolism in COVID-19 patients. Tobacco use was found to compound risks associated with diabetes (n = 1), cancer (n = 2), and chronic liver disease (n = 1). There is strong evidence that tobacco use increases risks of mortality and disease severity/progression among COVID-19 patients. Public health efforts during the pandemic should encourage tobacco users to quit use and seek care early and promote vaccination and other preventive behaviors among those with a history of tobacco use.


Developing a coding scheme for detecting usability and fun problems in computer games for young children.
This article describes the development and assessment of a coding scheme for finding both usability and fun problems through observations of young children playing computer games during user tests. The proposed coding scheme is based on an existing list of breakdown indication types of the detailed video analysis method (DEVAN). This method was developed to detect usability problems in task-based products for adults. However, the new coding scheme for children's computer games takes into account that in games, fun, in addition to usability, is an important factor and that children behave differently from adults. Therefore, the proposed coding scheme uses 8 of the 14 original breakdown indications and has 7 new indications. The article first discusses the development of the new coding scheme. Subsequently, the article describes the reliability assessment of the coding scheme. The any-two agreement measure of 38.5% shows that thresholds for when certain user behavior is worth coding will be different for different evaluators. However, the any-two agreement of .92 for a fixed list of observation points shows that the distinction between the available codes is clear to most evaluators. Finally, a pilot study shows that training can increase any-two agreement considerably by decreasing the number of unique observations, in comparison with the number of agreed upon observations.


A community pharmacist-led smoking cessation intervention using a smartphone app (PharmQuit): A randomized controlled trial.
WHO supports the harnessing of mobile technologies to improve access to smoking cessation services. As such, this study evaluated the effectiveness of smoking cessation services provided by community pharmacists using PharmQuit compared with standard care. The study was a prospective, multicenter, randomized controlled trial that included 156 participants who were 18 years or older and smoked at least one cigarette daily for a month, were ready to quit, willing to participate, and had a smartphone. The study was performed at seven community pharmacies in three provinces in Thailand. Participants were allocated to the intervention (n = 78) and control groups (n = 78). Both groups received the usual smoking cessation services with pharmacotherapy and counseling from community pharmacists for 6 months. The intervention group received PharmQuit as an additional service. Both groups were scheduled for follow-up visits on days 7, 14, 30, 60, 120, and 180. The primary outcome was continuous abstinence rate on day 180. The secondary outcomes included 7-day point abstinence rate, number of cigarettes smoked per day, exhaled carbon monoxide levels, adherence rate to the program, and satisfaction with PharmQuit. An analysis using the intent-to-treat principle was performed. Smoking cessation rates and the number of cigarettes smoked per day were significantly higher during the follow-up visits in both groups (p < 0.05). However, there were no statistically significant differences between the two groups. The adherence rate to the smoking cessation program was higher in the intervention group than in the control group (74 days vs. 60 days, p > 0.05). The results showed the benefits of the contribution of community pharmacists. Although the inclusion of PharmQuit did not yield better results than pharmacists' counselling alone, it may help obtain better adherence to smoking cessation programs. Trial registration: Thai Clinical Trials Registry: TCTR20200925004 on September 25, 2020 -retrospectively registered, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=6841.


[Myocardial infarction in infective endocarditis].
Two patients with chronic valvular heart disease and myocardial infarction were assisted at our hospital. Both of them were febrile and only one had petechiae associated with signs of valvular involvement led to suspicion of infective endocarditis. Although blood cultures were negative, echocardiographic, surgical and anatomopathologic findings were compatible with infective endocarditis. They required cardiac surgery during the acute phase of the infection because they presented progressive hemodynamic deterioration and no satisfactory response to antimicrobial regimen too. One patient died at late follow-up (two weeks after the hospital discharge) and the other survived, but with signs of cardiac failure (class II of NYHA) one year after the procedure.


The Vacuolar ATPase a2-subunit regulates Notch signaling in triple-negative breast cancer cells.
Triple Negative Breast Cancer (TNBC) is a subtype of breast cancer with poor prognosis for which no targeted therapies are currently available. Notch signaling has been implicated in breast cancer but the factors that control Notch in TNBC are unknown. Because the Vacuolar ATPase has been shown to be important in breast cancer invasiveness, we investigated the role of a2-subunit isoform of Vacuolar ATPase (a2V) in regulating Notch signaling in TNBC. Confocal microscopy revealed that among all the 'a' subunit isoforms, a2V was uniquely expressed on the plasma membrane of breast cancer cells. Both a2V and NOTCH1 were elevated in TNBC tumors tissues and cell lines. a2V knockdown by siRNA as well as V-ATPase inhibition by Bafilomycin A1 (Baf A1) in TNBC cell lines enhanced Notch signaling by increasing the expression of Notch1 intracellular Domain (N1ICD). V-ATPase inhibition blocked NICD degradation by disrupting autophagy and lysosomal acidification as demonstrated by accumulation of LC3B and diminished expression of LAMP1 respectively. Importantly, treatment with Baf A1 or anti-a2V, a novel-neutralizing antibody against a2V hindered cell migration of TNBC cells. Our findings indicate that a2V regulates Notch signaling through its role in endolysosomal acidification and emerges as a potential target for TNBC.


Vanadate elevates lipogenicity of starved rat adipose tissue: mechanism of action.
We have established an experimental system in rats in which the lipogenic capacity of adipose tissue was decreased in vivo by prolonged fasting, and restored in vitro by glucose together with insulin or vanadate. Incubation of fasted adipose explants for 5 h at 37 C with 2 mM glucose alone did not elevate lipogenic capacity. However, glucose with insulin (17 nM) or vanadate (100 microM), led, respectively, to 2.2- and 8- to 10-fold elevation. Actinomycin D (50 microM) completely blocked this increase, while low concentrations (ED50 = 4.0 +/- 0.4 microM) of vanadate potentiated it. Neither insulin nor vanadate elevated fasted adipose explants' lipogenic capacity in the absence of glucose, or in the presence of the nonmetabolizable glucose analog 3-O-methylglucose. Upon replacing glucose with 2-deoxyglucose (1 mM), a glucose analog that undergoes phosphorylation to 2-deoxyglucose-6-phosphate with no further metabolism, vanadate was nearly as potent as with glucose in elevating lipogenic capacity. Vanadate was superior to insulin in increasing glucose-6-phosphate level in fasted-adipose explants. Adipose glucose-6-phosphatase activity was inhibited by vanadate (IC50 = 7.0 +/- 0.4 microM). We have concluded that glucose-6-phosphate is the key metabolite of glucose involved in the transcriptionally regulated elevation of lipogenic capacity of fasted adipose explants. Vanadate has a more profound effect than insulin, as it elevates glucose-6-phosphate to higher levels and the subsequent increase in lipogenic capacity is four to five times greater than that induced by insulin. The mechanism involved is the combined action of vanadate in enhancing glucose entry and in inhibiting dephosphorylation of endogenously formed glucose-6-phosphate. The latter effect is not exerted by insulin.


Value-based chronic care model approach for vulnerable older patients with multiple chronic conditions.
"Old age, itself, is not a disease" (Suborne 2007). The rising rate of the global aging population is predicted to create a health care crisis within the next three decades. Vulnerable older adults suffer from multiple chronic conditions (MCCs) in addition to cognitive and physical decline during the process of aging resulting in an inability to optimally achieve self-management. In terms of resource utilization, complex inpatient, and outpatient care results in higher physician visits, polypharmacy, and higher prescription costs. Health literacy has become known as an important social determinant of health affecting the older population. Both reductions in health literacy and self-management are associated with poorer health outcomes. The patient activation measure (PAM) has been coined "a vital sign" to ascertain a patient activation level throughout the continuum of care with the introduction of an intervention's progress. In this review, we conceptualize a systematic approach of the development of a "tailored" integrated community and care team to develop a partnership in assisting senior adults with MCCs. Through this intervention the value-based chronic care model (CCM) and PAM allows for an adaptable integration between the activated patient, their caregivers, and the community. The Model for Improvement (MFI) serves as a well-recognized technique for developing and executing quality improvement strategies in this "tailored" engaged and activated individual and community care team approach in achieving health outcomes and quality of life among the vulnerable older adult population worldwide.


Genetic Characterization of Circulating African Swine Fever Viruses in Nigeria (2007-2015).
Sequencing and analysis of three discrete genome regions of African swine fever viruses (ASFV) from archival samples collected in 2007-2011 and active and passive surveillance between 2012 and 2015 in Nigeria were carried out. Analysis was conducted by genotyping of three single-copy African swine fever (ASF) genes. The E183L and B646L genes that encode structural proteins p54 and p72, respectively, were utilized to delineate genotypes before intragenotypic resolution by characterization of the tetrameric amino acid repeat region within the hypervariable central variable region of the B602L gene. The results showed no variation in the p72 and p54 gene regions sequenced. Phylogeny of p72 sequences revealed that all the Nigerian isolates belonged to genotype I, while that of the p54 recovered the Ia genotype. Analysis of B602L gene revealed the differences in the number of tetrameric repeats. Four new variants (Tet-15, Tet-17a, Tet-17b and Tet-48) were recovered, while a fifth variant (Tet-20) was the most widely distributed in the country displacing Tet-36 reported previously in 2003-2006. The viruses responsible for ASF outbreaks in Nigeria are from very closely related but mutated variants of the virus that have been circulating since 1997. A practical implication of the genetic variability of the Nigerian viral isolates in this study is the need for continuous sampling and analysis of circulating viruses, which will provide epidemiological information on the evolution of ASFV in the field versus new incursion for informed strategic control of the disease in the country.


Analysis of adaptive mutations selected during the consecutive passages of hepatitis E virus produced from an infectious cDNA clone.
To characterize the genomic mutations of hepatitis E virus (HEV) during consecutive passages associated with adaptation to growth in cell culture, a cloned genotype 3 HEV [pJE03-1760F/wt, starting virus (SV)] was passaged 10 times in A549 cells, and the entire genomic sequence of the passage 10 (P10) progeny was determined. Compared to SV, P10 virus possessed two non-synonymous (T2808C and A5054G) and four synonymous mutations (C1213T, T2557C, C3118T and C4435T) in the ORF1. Full-length infectious cDNA clones with a single, double (T2808C and A5054G), or all six mutations, identical to P10, were constructed, and their replication capacity was compared. Four (C1213T, T2557C, T2808C and A5054G) of the six viruses with a single mutation grew more efficiently than SV. The P10 virus propagated more rapidly and grew more efficiently than SV and T2808C+A5054G and reached a higher viral load (95.1- and 8.5-fold, respectively) at 20days post-inoculation. An immunofluorescence analysis revealed that a high percentage (>80%) of cells inoculated with the P10 virus expressed ORF2 proteins, while relatively low percentages (nearly 30% or 5%) inoculated with T2808C+A5054G or SV, respectively, expressed ORF2 proteins. We found that not only non-synonymous but also synonymous HEV mutations are independently associated with increased virus production.


The DEAD-box RNA helicase RhlB is required for efficient RNA processing at low temperature in Caulobacter.
The RNA helicases from the DEAD-box family participate in several biochemical processes, with special relevance in the assembly of ribosome ribonucleoparticles and in RNA turnover as part of the multi-enzymatic RNA degradosome complex. Caulobacter crescentus has three DEAD-box RNA helicases, including RhlB, the main RNA helicase associated with the RNA degradosome. In this work, we evaluated the impact of RhlB on C. crescentus gene expression both at normal and low temperatures and its role in global RNA decay. The rhlB null mutant showed a freezing-sensitive phenotype after pre-incubation at low temperature, indicating a failure in assembling a proper cryotolerance response. A global transcriptomic profile of the wild-type and rhlB mutants was carried out at 30°C and 10°C and showed 73 and 477 differentially expressed genes, with the most affected gene categories being translation and posttranslational modifications. The rhlB mutant is more sensitive to streptonigrin, suggesting that the downregulation of iron-regulated genes may be due to a higher intracellular iron concentration. A high throughput screening for RhlB-binding RNAs identified 220 transcripts at 30°C, and global RNA decay analyses identified several mRNAs and sRNAs that displayed altered profiles of RNA decay rates. Analyses of the transcripts' 5'-ends from the C. crescentus rhlB mutant and from Pseudomonas aeruginosa PAO1 rhlE1 and rhlE2 mutants confirm that in the absence of the DEAD-box RNA helicase associated with RNase E, there is an accumulation of RNA degradation intermediates.IMPORTANCEOne of the most important control points in gene regulation is RNA stability, which determines the half-life of a transcript from its transcription until its degradation. Bacteria have evolved a sophisticated multi-enzymatic complex, the RNA degradosome, which is dedicated mostly to RNA turnover. The combined activity of RNase E and the other RNA degradosome enzymes provides an efficient pipeline for the complete degradation of RNAs. The DEAD-box RNA helicases are very often found in RNA degradosomes from phylogenetically distant bacteria, confirming their importance in unwinding structured RNA for subsequent degradation. This work showed that the absence of the RNA helicase RhlB in the free-living Alphaproteobacterium Caulobacter crescentus causes important changes in gene expression and cell physiology. These are probably due, at least in part, to inefficient RNA processing by the RNA degradosome, particularly at low-temperature conditions.


Antimicrobial effect of thymol and carvacrol added to a vinegar-based marinade for controlling spoilage of marinated beef (Shawarma) stored in air or vacuum packaging.
Controlling spoilage of the popular ethnic marinated beef "Shawarma" is crucial to achieve high quality, extend shelf-life, reduce food waste and meet the need of the globalized supply chain. Active essential oil (EO) components (thymol and carvacrol) were added at 0.4% and 0.8% (w/w) to preserve marinated beef, stored under aerobic or vacuum packaging. Microbiological and sensory (odor) parameters were assessed during 21 days at 4 °C. The treatments with higher EO concentration achieved higher antimicrobial activity than the lower ones and significantly reduced the mesophilic total viable count (TVC), lactic acid bacteria (LAB), Brochothrix thermosphacta, Pseudomonas spp., total coliforms, Escherichia coli, yeasts and molds. The higher EO concentration extended the microbiological shelf-life by 6 days, as judged by TVC and compared to the controls (aerobic and vacuum packaging) but was unacceptable sensorially. The lower EO concentration increased the microbiological shelf-life by 3 days and the sensorial shelf-life by 9 and > 12 days, under aerobic and vacuum conditions, respectively.


The microvasculature of the lateral choroid plexus in the rat: a scanning electron microscopy study of vascular corrosion casts.
The three-dimensional microvascular structure of many organs can be adequately investigated only using the corrosion casting technique. We applied this method, consisting of an injection of low viscosity acrylic resin through the major vessels and the subsequent digestion of the organic component with strong alkali or acids, to the choroid plexus of the lateral ventricles in the rat, focusing on its structural vascular features. This approach allowed a qualitative morphological description of the choroid plexus of the lateral ventricles, revealing several aspects of their capillary architecture as well as the morphological details underlying its main functional activity, essential to cerebrospinal fluid turnover. Observation of the casts with scanning electron microscopy gave a detailed picture of the choroid plexus of the lateral ventricles of the rat and enabled us to distinguish four different regions, depending on the site that the lateral ventricles occupied: the anterior olfactory region, the main central region, the longer branch and the inferior horn. Each region mostly consisted of spiral capillaries and had specific characteristics. At high magnification, the casts revealed distinctive vascular specializations, such as numerous bulges regularly placed on the capillaries. This morphological investigation underpins a better comprehension of the pathological mechanisms involving the choroid plexus in the lateral ventricles.


Raising research awareness: a strategy for nurses.
Strategies for promoting research awareness should be tailored to individual nursing needs. A survey was used to help develop a strategy for the promotion of nursing research in the gynaecology unit at Queen's Medical Centre, Nottingham. After a brief description of the background associated with research awareness among nurses, the survey design, implementation and results are discussed. The survey led to the development of a strategy to raise research awareness, which is also described.


Overexpression of E3 Ubiquitin Ligase Gene AdBiL Contributes to Resistance against Chilling Stress and Leaf Mold Disease in Tomato.
Ubiquitination is a common regulatory mechanism, playing a critical role in diverse cellular and developmental processes in eukaryotes. However, a few reports on the functional correlation between E3 ubiquitin ligases and reactive oxygen species (ROS) or reactive nitrogen species (RNS) metabolism in response to stress are currently available in plants. In the present study, the E3 ubiquitin ligase gene AdBiL (Adi3 Binding E3 Ligase) was introduced into tomato line Ailsa Craig via Agrobacterium-mediated method. Transgenic lines were confirmed for integration into the tomato genome using PCR. Transcription of AdBiL in various transgenic lines was determined using real-time PCR. Evaluation of stress tolerance showed that T1 generation of transgenic tomato lines showed only mild symptoms of chilling injury as evident by higher biomass accumulation and chlorophyll content than those of non-transformed plants. Compared with wild-type plants, the contents of AsA, AsA/DHA, GSH and the activity of GaILDH, γ-GCS and GSNOR were increased, while H2O2, [Formula: see text], MDA, NO, SNOs, and GSNO accumulations were significantly decreased in AdBiL overexpressing plants in response to chilling stress. Furthermore, transgenic tomato plants overexpressing AdBiL showed higher activities of enzymes such as G6PDH, 6PGDH, NADP-ICDH, and NADP-ME involved in pentose phosphate pathway (PPP). The transgenic tomato plants also exhibited an enhanced tolerance against the necrotrophic fungus Cladosporium fulvum. Tyrosine nitration protein was activated in the plants infected with leaf mold disease, while the inhibition could be recovered in AdBiL gene overexpressing lines. Taken together, our results revealed a possible physiological role of AdBiL in the activation of the key enzymes of AsA-GSH cycle, PPP and down-regulation of GSNO reductase, thereby reducing oxidative and nitrosative stress in plants. This study demonstrates an optimized transgenic strategy using AdBiL gene for crop improvement against biotic and abiotic stress factors.


Distribution of COX-1 and COX-2 in normal and inflamed tissues.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of a number of inflammatory diseases and are believed to act via inhibition of the enzyme cyclooxygenase (COX). This enzyme catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDs are efficacious anti-inflammatory agents, significant side effects limit their use. Recently two forms of COX were identified-a constitutively expressed COX-1 and a cytokine-inducible COX-2. Potent anti-inflammatory agents like the glucocorticoids are known to inhibit specifically the expression of COX-2 while commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2. These findings have led to the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1), whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2. We have examined the relative distribution of COX-1 and COX-2 in both normal and inflamed tissues and report that COX-1 expression dominates normal tissues while COX-2 mRNA is induced at the inflammatory site. Furthermore, compounds that selectively inhibit COX-2 are anti-inflammatory without gastric toxicity.


Synthesis, Profiling, and in Vivo Evaluation of Cyclopeptides Containing N-Methyl Amino Acids as Antiplasmodial Agents.
Malaria is a major tropical disease where important needs are to mitigate symptoms and to prevent the establishment of infection. Cyclopeptides containing N-methyl amino acids with in vitro activity against erythrocytic forms as well as liver stage are presented. The synthesis, parasitological characterization, physicochemical properties, in vivo evaluation, and mice pharmacokinetics are described.


Effects of dibutylphthalate and ethynylestradiol on liver peroxisomes, reproduction, and development of zebrafish (Danio rerio).
The aim of the present work was to study the effects of the peroxisome proliferator dibutylphthalate (DBP) and the xenoestrogen 17alpha-ethynylestradiol (EE2) on liver peroxisomes, reproduction, and development of zebrafish (Danio rerio). In experiment 1, newly fertilized zebrafish eggs were exposed for five weeks, covering the entire period of sexual determination, to nominal concentrations of 25 and 100 microg/L of DBP and 5 microg/L of EE2. In experiment 2, adult female zebrafish were exposed for 15 d to 100 and 500 microg/L of DBP and 5 microg/L of EE2, and afterward, they were paired with untreated males to study the effects in the resultant offspring. Ethynylestradiol provoked marked mortality (approximately 50%) and delayed development of larvae as well as sterility of adult females, possibly related to alterations in aromatase gene expression. Ethynylestradiol up-regulated vitellogenin expression in the early life stages and increased vitellogenin synthesis and accumulation in adult females. Ethynylestradiol caused liver peroxisome proliferation in early life stages but not in adult females. Dibutylphthalate caused teratogenic effects in early life stages and mortality of the larvae obtained from exposed females. Dibutylphthalate provoked liver peroxisome proliferation and up-regulation of cytochrome P450A1 in early life stages at the end of the exposure and in adult females. Dibutylphthalate also up-regulated the expression of aromatase genes. In conclusion, the xenoestrogen EE2 caused liver peroxisome proliferation in early life stages of zebrafish, but the peroxisome proliferator DBP did not behave as a typical xenoestrogen. Overall, changes in gene expression were more marked during early life stages than in adult female zebrafish.


Ceriporic acid B, an extracellular metabolite of Ceriporiopsis subvermispora, suppresses the depolymerization of cellulose by the Fenton reaction.
The white rot fungus, Ceriporiopsis subvermispora, is able to degrade lignin in wood without intensive damage to cellulose. Since lignin biodegradation by white rot fungi proceeds by radical reactions, accompanied by the production of a large amount of Fe3+-reductant phenols and reductive radical species in the presence of iron ions, molecular oxygen, and H2O2, C. subvermispora has been proposed to possess a biological system which suppresses the production of a cellulolytic active oxygen species, *OH, by the Fenton reaction. In the present paper, we demonstrate that 1-nonadecene-2,3-dicarboxylic acid (ceriporic acid B), an extracellular metabolite of C. subvermispora, strongly inhibited *OH production and the depolymerization of cellulose by the Fenton reaction in the presence of iron ions, cellulose, H2O2, and a reductant for Fe3+, hydroquinone (HQ), at the physiological pH of the fungus.


Long noncoding RNA UCA1 promotes multiple myeloma cell growth by targeting TGF-β.
To investigate the role of long noncoding RNA (lncRNA) UCA1 in the multiple myeloma (MM) development. In samples of MM, the expression of UCA1 and TGF-β was investigated using real-time PCR. UCA1 lentiviral small hairpin RNA (shRNA) was transfected in MM cell lines. CCK-8 and colony formation assay were used to detect cell lines proliferation. The cell apoptosis assay was conducted to detect cell apoptosis. Western blot was utilized to detect the protein level of TGF-β. The expression level of UCA1 increased in MM samples and cell lines, and its high expression was associated with poor MM prognosis. Downregulation of UCA1 significantly inhibited cell lines proliferation and promoted cell apoptosis. UCA1 could positively regulate TGF-β in MM. Overexpression of TGF-β partially reversed the effect of UCA1 knockdown. UCA1 promotes MM cell lines proliferation by targeting TGF-β.


[Psychosocial predictors for initiating a pension procedure after bypass operation].
From the psychologist's point of view, a routine coronary artery bypass operation is often looked upon by patients as a negative situation. The patient develops the feeling that his or her life has been dramatically altered, thus the patient feels he must somehow make a change in the upcoming pattern of the future. The patient, as well as his employer, is convinced of subjective models of etiology, which cause the attitude that circumstances of living must change rapidly. In this context continued employment is viewed as a significant burden and hindrance, despite an excellent post-operative discharge diagnosis. According to the hypothesis, emotions and attitudes directly concerning the working environment, that lead to an application for early retirement should be identified. Medical and psychological counseling before surgery and post-op rehabilitation, should be carried out to ease the obsession with early retirement and prevent possibly following psychopathological disturbances.


Inhibition of the cardiovascular effects of acupuncture (moxibustion) by phentolamine in dogs during halothane anesthesia.
The cardiovascular effects of acupuncture, moxibustion by electrocautery, at Jen Chung (Go-26) and phentolamine (0.1 mg/kg-i.v.) alone were compared to phentolamine (0.1 mg/kg-i.v.) prior to moxibustion at Go-26 in groups of ten dogs under 0.75 percent halothane anesthesia. Cardiac output, stroke volume, heart rate, mean arterial pressure, central venous pressure, total peripheral resistance, pH, PaCO2, PaO2 and base deficit were measured over a two hour period. A significant increase (5% level) in cardiac output, stroke volume, heart rate, mean arterial pressure, pulse pressure and a significant decrease in total peripheral resistance were observed following acupuncture, moxibustion with electrocautery, at Jen Chung (Go-26) in dogs under halothane anesthesia. These effects were inhibited by pretreatment with the alpha blocking agent, phentolamine (0.1 mg/kg-i.v.). The cardiovascular effects of phentolamine (0.1 mg/kg-i.v.) alone were similar to those of dogs in which phentolamine was administered prior to moxibustion.


Leukotriene release by endometrium and myometrium throughout the menstrual cycle in dysmenorrhoea and menorrhagia.
Endometrium and myometrium were collected at hysterectomy from 21 women with measured menstrual blood loss. Eight women complained of dysmenorrhea and the remaining 13 had pain-free periods. Specimens were obtained throughout the menstrual cycle (menstrual, n = 5; follicular, n = 4; early luteal, n = 3; mid-luteal, n = 5; late luteal, n = 4). Leukotriene C4, leukotriene D4 and leukotriene E4 release were examined using a short-term incubation technique. Endometrial leukotriene release, which was always significantly greater than myometrial release, changed throughout the menstrual cycle and the highest concentrations were found during menstruation. Endometrial, but not myometrial, leukotriene concentrations were significantly higher in tissues obtained from women with a complaint of dysmenorrhoea compared with those in tissue from pain-free women. No correlation was found between leukotriene release in either endometrium or myometrium and menstrual blood loss (range 15-457 ml).


Recreational pools filled with mineralized thermal water are potential reservoirs of pathogenic Vibrio spp.
Vibrio spp. are Gram-negative rod-shaped bacteria commonly present in marine, estuarine and natural freshwater environments. A few members of this genus are associated with human diseases. Here we present the study of Vibrio spp. isolations from 20 artificial recreational pools in Slovakia. Water samples were collected from artificial pools filled with mineralized thermal water in eight recreational areas in Slovakia in 2019 and 2020. Ninety six out of 176 samples were positive for Vibrio spp. Totally 118 different strains of Vibrio spp. were isolated, from which 77 belonged to potentially pathogenic species - V. cholerae (34 isolates), V. vulnificus (4 isolates), V. furnissii (3 isolates), V. fluvialis (25 isolates), V. alginolyticus (10 isolates) and V. mimicus (1 isolate). To our knowledge this is the first study demonstrating the presence of pathogenic or potentially pathogenic Vibrio spp. in artificial pools filled with thermal mineralized waters even disinfected with chlorine compounds.


Understanding lupus nephritis: diagnosis, management, and treatment options.
Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years. Renal disease (glomerulonephritis) is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF) has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.


[Pathological features at autopsy in elderly patients with acute myocardial infarction].
Objective: To analyze the cardiac pathological features of elderly coronary artery disease (CAD) patients (60 years and over) and evaluate the pathological features at autopsy and risk factors of patients with acute myocardial infarction (AMI). Methods: Data from 471 elderly patients (aged from 60 to 100 years old) with CAD confirmed by autopsy hospitalized in our hospital from April 1969 to October 2013 were retrospectively reviewed. Patients were divided into 2 groups: AMI group(n=128) with AMI as the primary cause of death and the rest served as control group(n=343). The pathological features of coronary lesion and related risk factors of AMI were analyzed. Results: In patients aged 60 and over with CAD, 48.8%(230/471) had severe coronary stenosis, 18.7%(88/471) had three-vessel disease, 71.8% cases (338/471) had left anterior descending artery(LAD)grade Ⅲ and over stenosis, 29.9% (141/471) had LAD grade Ⅳ stenosis, 25.9%(122/471) had left main coronary artery(LM) grade Ⅲ and over stenosis, 9.6%(45/471) had LM grade Ⅳ stenosis, 27.1%(128/471) had AMI. The first AMI accounts for 39.1%(50/128), and 60.9%(78/128) had both AMI and old MI. Compared with the control group, AMI group were younger ((77.1±11.6) years vs. (83.2±9.1) years, P<0.01), had more severe coronary artery stenosis lesion (77.3%(99/128) vs. 38.2%(131/343), P<0.01), higher coronary index which reflects the overall arteriosclerosis (9.9±2.8 vs. 8.0±2.5, P<0.01), more three-vessel disease (30.3%(43/128) vs. 13.7%(45/343), P<0.01), heavier heart weight ((447.8±90.6)g vs. (426.6±99.1)g, P<0.05), higher prevlence of pulmonary congestion or edema (57.8%(74/128) vs. 39.9%(137/343), P<0.01). Twenty-three cardiac ruptures (23/128, 18.0%) were observed in AMI group. Logistic regression analysis showed that grade Ⅳ LAD stenosis (OR=3.55, 95%CI 2.05-6.17, P<0.01), three-vessel disease(OR=2.47, 95%CI 1.30-4.67, P<0.01) were the independent risk factors of AMI in elderly patients with CAD. Conclusions: Severe coronary stenosis is common in CAD patients aged 60 and over. Patients aged 60 and over with AMI have more severe coronary artery stenosis lesion and heavier heart weight. Cardiac rupture is not uncommon in elderly patients with AMI. Severe LAD stenosis and three-vessel disease are the independent risk factors of AMI in the elderly.


Ultrafast Elemental and Oxidation-State Mapping of Hematite by 4D Electron Microscopy.
We describe a new methodology that sheds light on the fundamental electronic processes that occur at the subsurface regions of inorganic solid photocatalysts. Three distinct kinds of microscopic imaging are used that yield spatial, temporal, and energy-resolved information. We also carefully consider the effect of photon-induced near-field electron microscopy (PINEM), first reported by Zewail et al. in 2009. The value of this methodology is illustrated by studying afresh a popular and viable photocatalyst, hematite, α-Fe2O3 that exhibits most of the properties required in a practical application. By employing high-energy electron-loss signals (of several hundred eV), coupled to femtosecond temporal resolution as well as ultrafast energy-filtered transmission electron microscopy in 4D, we have, inter alia, identified Fe4+ ions that have a lifetime of a few picoseconds, as well as associated photoinduced electronic transitions and charge transfer processes.


The Comparative Study of Ondansetron and Metoclopramide Effects in Reducing Nausea and Vomiting After Laparoscopic Cholecystectomy.
Postoperative nausea and vomiting (PONV) are one of the most common complications of anesthesia and without prophylactic intervention occurs by about one-third of patients under general anesthesia. The aim of this study was to compare the efficacy of ondansetron and metoclopramide in reducing PONV after laparoscopic cholecystectomy. In this study, 60 patients undergoing laparoscopic cholecystectomy were randomly allocated into two equal groups (n=30), and in the first group 10 mg metoclopramide and in the second group 4 mg ondansetron preoperatively were injected. Nausea and vomiting and the need for rescue antiemetic treatment in recovery and 6 hr. and 6-24 hrs. After surgery were evaluated. Data were analyzed by SPSS software with chi-square test and analysis of variance (ANOVA). The incidence of nausea in metoclopramide was 43.3 % and in ondansetron was 33.3 %. The difference between two groups was not significant (P=0.6). The incidence of vomiting in metoclopramide was 20% and in ondansetron was 26.7%, and there was not any significant difference between intervention groups (P=0.12). For prevention of PONV after laparoscopic cholecystectomy, both metoclopramide and ondansetron are effective, and in preventing of nausea, ondansetron is more effective than metoclopramide, whereas there was not any significant difference between two drugs in preventing of vomiting.


Alpha-Particle Exposure Induces Mainly Unstable Complex Chromosome Aberrations which do not Contribute to Radiation-Associated Cytogenetic Risk.
The mechanism underlying the carcinogenic potential of α radiation is not fully understood, considering that cell inactivation (e.g., mitotic cell death) as a main consequence of exposure efficiently counteracts the spreading of heritable DNA damage. The aim of this study is to improve our understanding of the effectiveness of α particles in inducing different types of chromosomal aberrations, to determine the respective values of the relative biological effectiveness (RBE) and to interpret the results with respect to exposure risk. Human peripheral blood lymphocytes (PBLs) from a single donor were exposed ex vivo to doses of 0-6 Gy X rays or 0-2 Gy α particles. Cells were harvested at two different times after irradiation to account for the mitotic delay of heavily damaged cells, which is known to occur after exposure to high-LET radiation (including α particles). Analysis of the kinetics of cells reaching first or second (and higher) mitosis after irradiation and aberration data obtained by the multiplex fluorescence in situ hybridization (mFISH) technique are used to determine of the cytogenetic risk, i.e., the probability for transmissible aberrations in surviving lymphocytes. The analysis shows that the cytogenetic risk after α exposure is lower than after X rays. This indicates that the actually observed higher carcinogenic effect of α radiation is likely to stem from small scale mutations that are induced effectively by high-LET radiation but cannot be resolved by mFISH analysis.


Prolactin induces ERK phosphorylation in epithelial and CD56(+) natural killer cells of the human endometrium.
Functional PRL receptors are expressed in the human endometrium during the secretory phase of the menstrual cycle in which PRL stimulates tyrosine phosphorylation of Janus kinase 2 and STAT (signal transducer and activator of transcription) 1 and 5. In this study, we investigated the effect of PRL on the MAPK/ERK pathway in the human endometrium. Human endometrial tissue was collected during the mid to late secretory phase of the menstrual cycle. Western blot analysis performed on proteins, extracted after up to 30 min culture with PRL, demonstrated rapid tyrosine and threonine phosphorylation of ERK 1 and 2 MAPKs. The phosphorylation of ERK, in response to PRL, was localized by immunohistochemistry to glandular epithelial cells and a subset of stromal cells. Using immunofluorescence histochemistry, PRL-induced phosphorylation of ERK in the stromal compartment was localized to the uterine-specific CD56(+) natural killer (NK) cells. We have demonstrated that the PRL receptor is expressed in uterine CD56(+) NK cells in situ by immunofluorescence and in purified decidual CD56(+) NK cells by RT-PCR and Western blotting analysis. We have further demonstrated phosphorylation of ERK 1 and 2 in cultures of purified uterine CD56(+) NK cells, in response to PRL. Our data demonstrate that PRL stimulates the ERK pathway in multiple cellular compartments of the human endometrium and identify uterine CD56(+) NK cells as novel PRL target cells.


Albendazole, levamisole and ivermectin are effective against monogeneans of Colossoma macropomum (Pisces: Serrasalmidae).
This study evaluated the efficacy of albendazole, ivermectin, levamisole, mebendazole and praziquantel on monogeneans of Colossoma macropomum, based on in vitro and in vivo assays. In vitro assays indicated that albendazole (500, 100, 1,500 and 2,000 mg/L), ivermectin (200, 250, 300 and 350 mg/L) and levamisole (50, 75, 100 and 125 mg/L) were 100% effective against Anacanthorus spatulatus, Notozothecium janauachensis, Mymarothecium boegeri and Linguadactyloides brinkmanni, while mebendazole (125, 150, 175 and 200 mg/L) and praziquantel (5, 10, 15 and 20 mg/L) were ineffective. Fish mortality in 24 hr therapeutic baths with 500 mg/L of albendazole was 6.6%, but the behaviour of the animals remained unchanged, while 200 mg/L of ivermectin caused lethargy, signs of hypoxia and 100% mortality within 2 hr, and 125 mg/L of levamisole caused no mortality. The efficacy of 500 mg/L of albendazole was 48.6% in the 24 hr baths, while that of 125 mg/L levamisole was 88.2%. Although ivermectin showed in vitro efficacy, the lowest concentration used in baths was highly toxic to fish. Therefore, we recommend the use of 125 mg/L of levamisole to control and treat monogenean infestations on C. macropomum in fish farming.


Bone density in children with single ventricle physiology.
Children with chronic diseases are at risk for low bone mineral density (BMD). There are no studies of BMD in children with congenital heart disease and particularly single ventricle (SV). Children with this defect are often treated with warfarin, suspected to negatively impact BMD in adults. We assessed BMD in patients with SV physiology and compared the BMD of subjects taking warfarin to those who were not. Subjects 5-12 years with SV were included. BMD z scores by dual-energy X-ray absorptiometry of the spine and total body less head (TBLH) were obtained. Calcium intake, activity level, height, and Tanner stage were assessed. Linear regression models and t tests were used to investigate differences between participants and normative data as well as between subjects' subgroups. Twenty-six subjects were included and 16 took warfarin. Mean BMD z score at the spine was significantly lower than expected at -1.0 ± 0.2 (p < 0.0001), as was the BMD z score for TBLH at -0.8 ± 0.2 (p < 0.0001). Those results remained significant after adjusting for height. Subjects who were on warfarin tended to have lower BMD at both the spine and TBLH than those who were not, with a z score difference of 0.6 ± 0.46 at the spine (p = 0.106) and a difference of 0.4 ± 0.34 at TBLH (p = 0.132). BMD is significantly reduced in children with SV. Warfarin appears to lower BMD but the effect is less conclusive. Continued evaluation is recommended for these patients at risk for reduced bone density. Evaluation of other cardiac patients on warfarin therapy should also be considered.


Diurnal variation of tight junction integrity associates inversely with matrix metalloproteinase expression in Xenopus laevis corneal epithelium: implications for circadian regulation of homeostatic surface cell desquamation.
The corneal epithelium provides a protective barrier against pathogen entrance and abrasive forces, largely due to the intercellular junctional complexes between neighboring cells. After a prescribed duration at the corneal surface, tight junctions between squamous surface cells must be disrupted to enable them to desquamate as a component of the tissue homeostatic renewal. We hypothesize that matrix metalloproteinase (MMPs) are secreted by corneal epithelial cells and cleave intercellular junctional proteins extracellularly at the epithelial surface. The purpose of this study was to examine the expression of specific MMPs and tight junction proteins during both the light and dark phases of the circadian cycle, and to assess their temporal and spatial relationships in the Xenopus laevis corneal epithelium. Expression of MMP-2, tissue inhibitor of MMP-2 (TIMP-2), membrane type 1-MMP (MT1-MMP) and the tight junction proteins occludin and claudin-4 were examined by confocal double-label immunohistochemistry on corneas obtained from Xenopus frogs at different circadian times. Occludin and claudin-4 expression was generally uniformly intact on the surface corneal epithelial cell lateral membranes during the daytime, but was frequently disrupted in small clusters of cells at night. Concomitantly, MMP-2 expression was often elevated in a mosaic pattern at nighttime and associated with clusters of desquamating surface cells. The MMP-2 binding partners, TIMP-2 and MT1-MMP were also localized to surface corneal epithelial cells during both the light and dark phases, with TIMP-2 tending to be elevated during the daytime. MMP-2 protein expression is elevated in a mosaic pattern in surface corneal epithelial cells during the nighttime in Xenopus laevis, and may play a role in homeostatic surface cell desquamation by disrupting intercellular junctional proteins. The sequence of MMP secretion and activation, tight junction protein cleavage, and subsequent surface cell desquamation and renewal may be orchestrated by nocturnal circadian signals.


Functional Characterization of Two Cell Wall Integrity Pathway Components of the MAPK Cascade in Phomopsis longicolla.
The pathogenic fungus Phomopsis longicolla causes numerous plant diseases, such as Phomopsis seed decay, pod and stem blight, and stem canker, which seriously affect the yield and quality of soybean production worldwide. Because of a lack of technology for efficient manipulation of genes for functional genomics, understanding of P. longicolla pathogenesis is limited. Here, we developed an efficient polyethylene glycol-mediated protoplast transformation system in P. longicolla that we used to characterize the functions of two genes involved in the cell wall integrity (CWI) pathway of the mitogen-activated protein kinase (MAPK) cascade, including PlMkk1, which encodes MAPK kinase, and its downstream gene PlSlt2, which encodes MAPK. Both gene knockout mutants ΔPlMkk1 and ΔPlSlt2 displayed a reduced growth rate, fragile aerial hyphae, abnormal polarized growth and pigmentation, defects in sporulation, inadequate CWI, enhanced sensitivity to abiotic stress agents, and significant deficiencies in virulence, although there were some differences in degree. The results suggest that PlMkk1 and PlSlt2 are crucial for a series of growth and development processes as well as pathogenicity. The developed transformation system will be a useful tool for additional gene function research and will aid in the elucidation of the pathogenic mechanisms of P. longicolla. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


SH3 domains come of age.
With the sequencing of an eukaryotic genome, it is possible to inventory the predicted proteome for proteins that carry one or more Src Homology 3 (SH3) domains. Due to the current ease of cloning and gene synthesis, these short domains can be readily overexpressed and manipulated for the purpose of characterizing their specificity and affinity for peptide ligands, as well as solving the three-dimensional structures of the domains. This information can be used to predict and confirm their cellular interacting partners, in the effort to understand the function of a eukaryotic protein by focusing on its SH3 domain. Finally, capitalizing on our mature understanding about protein-protein interacting modules, like the SH3 domain, it is possible to use directed evolution to enhance or change the specificity and affinity of an SH3 domain for the purpose of creating reagents to be used in biochemical purification or cell perturbation studies.


The permeability of fractured rocks in pressurised volcanic and geothermal systems.
The connectivity of rocks' porous structure and the presence of fractures influence the transfer of fluids in the Earth's crust. Here, we employed laboratory experiments to measure the influence of macro-fractures and effective pressure on the permeability of volcanic rocks with a wide range of initial porosities (1-41 vol. %) comprised of both vesicles and micro-cracks. We used a hand-held permeameter and hydrostatic cell to measure the permeability of intact rock cores at effective pressures up to 30 MPa; we then induced a macro-fracture to each sample using Brazilian tensile tests and measured the permeability of these macro-fractured rocks again. We show that intact rock permeability increases non-linearly with increasing porosity and decreases with increasing effective pressure due to compactional closure of micro-fractures. Imparting a macro-fracture both increases the permeability of rocks and their sensitivity to effective pressure. The magnitude of permeability increase induced by the macro-fracture is more significant for dense rocks. We finally provide a general equation to estimate the permeability of intact and fractured rocks, forming a basis to constrain fluid flow in volcanic and geothermal systems.


Ocular wavefront aberrations in patients after diffuse lamellar keratitis.
To study ocular wavefront aberrations after laser in situ keratomileusis (LASIK) in patients who developed diffuse lamellar keratitis (DLK). A case-control evaluation of 47 patients with DLK and 30 uneventful LASIK-operated controls. Measurements of visual acuities, cycloplegic refraction, eye's wave aberrations using a LADARWAVE aberrometer (up to eighth order), and corneal topography were obtained after LASIK treatment. All of the surgeries were performed using the Hansatome or the Moria microkeratome and the LadarVision excimer laser system. Mean follow-up interval from the day of the operative procedure to the examination day was 6.26 (DLK group; range, 2-13 months) and 6.23 months (control group; range, 3-9 months). Mean preoperative spherical equivalent was -3.7 D in patients with DLK and -3.7 D in controls. High-order aberration S7+7 (P = 0.015) was statistically different in the DLK group from that in controls. High-order aberrations S3+3 (P = 0.091) and S8+4 (chi = 8.014, P = 0.046) showed a tendency to be different from controls. Loss of best-corrected visual acuity was greater in patients with DLK. The occurrence of DLK after LASIK surgery may not significantly affect the visual outcome.


Evaluation of resource burden for bladder adaptive strategies: A timing study.
Interfraction bladder motion is substantial and therefore many different adaptive radiotherapy approaches have been developed to accommodate that motion. Previous studies comparing the efficacy of those adaptive strategies have demonstrated that reoptimization (ReOpt) was dosimetrically superior when compared to Plan of the Day (POD) and Patient-specific PTV (PS-PTV). However, the feasibility of clinical implementation is dependent upon assessment of the resource burden. This study assessed and compared the resource burden of three adaptive strategies. Using the planning CT and all daily CBCTs of 10 bladder patients, the following adaptive strategies were simulated offline to deliver 46 Gy in 23 fractions: POD, PS-PTV and ReOpt. Additional activities required to execute these strategies compared to a nonadaptive approach were identified and categorized. Time consumed for the execution of each strategy was measured for a single, experienced observer. The time (minutes) consumed to execute the additional activities for PS-PTV, POD and ReOpt was 14.4, 49.1 and 248.5, respectively. In addition to a significantly shorter time spent, all activities associated with PS-PTV were categorized as those that could be performed without the presence of the patient or a treatment room. On the other hand, ReOpt was the most time intensive and all activities were categorized as those that could lead to increasing patient's time in the treatment room and decreasing capacity. Although ReOpt was preferred with respect to improving dosimetry, the heavy resource burden it incurred could be a deterrent for clinical implementation. PS-PTV was the least resource-intensive strategy.


Telithromycin inhibits the number of viable bacteria but not lymphocyte accumulation in a murine model of chronic respiratory infection.
The 14-membered macrolides, such as clarithromycin (CAM) and erythromycin (EM), are effective against diffuse panbronchiolitis. However, there have been no studies on the effects of telithromycin (TEL) on chronic respiratory infection in vivo. In this study, we determined the effect of TEL on an experimental murine model of chronic respiratory infection caused by Pseudomonas aeruginosa with biofilm formation. TEL significantly reduced the number of viable bacteria but had no effect on the proliferation of lymphocytes. In contrast, CAM decreased the number of lymphocytes but had no effect on the number of viable bacteria in the lung. These results suggest that TEL and CAM have different effects on chronic respiratory infection caused by P. aeruginosa.


Facile preparation of fibrin coated open tubular column for characterization of monoclonal antibody variants by capillary electrochromatography.
Monoclonal antibodies (mAbs) are one of the most promising classes of therapeutic protein biopharmaceuticals. However, the complexity of mAbs poses a daunting analytical challenge for heterogeneity characterization of mAbs. In this study, inspired by blood coagulation, we adopted a fibrin coating as a novel stationary phase in open tubular (OT) column for the separation of the mAbs variants by capillary electrochromatography. The fibrin coating was prepared by in situ polymerization of fibrin in the presence of thrombin as a catalyst inside a fused-silica capillary. Scanning electron microscopy and electroosmotic flow measurement were carried out to characterize the fibrin coated OT columns. The average thickness of the fibrin coating was about 1.13μm. And the EOF of the column was pH-dependent. The electrochromatographic performance of the prepared columns was evaluated by characterization of the variants of three mAbs (cetuximab, trastuzumab and rituximab). The columns demonstrated good repeatability with the run-to-run, day-to-day and column-to-column relative standard deviations of migration times less than 2.42%. The study highlighted the potential of adsorbed proteins as stationary phases for the separation of mAbs variants. Furthermore, the study provided a new platform for characterization of heterogeneity of mAbs in pharmaceutical industry.


Intramedullary spinal melanocytoma.
Meningeal melanocytoma is a benign lesion arising from leptomeningeal melanocytes that at times can mimic its malignant counterpart, melanoma. Lesions of the spine usually occur in extramedullary locations and present with spinal cord compression symptoms. Because most reported spinal cases occur in the thoracic region, these symptoms usually include lower extremity weakness or numbness. The authors present a case of primary intramedullary spinal meningeal melanocytoma presenting with bilateral lower extremity symptoms in which the patient had no known supratentorial primary lesions. Gross total surgical resection allowed for full recovery, but early recurrence of tumor was detected on close follow-up monitoring, allowing for elective local radiation without loss of neurological function. Case reports of such tumors discuss different treatment strategies, but just as important is the close follow-up monitoring in these patients even after gross total surgical resection, since these tumors can recur.


Radiation damping effects on the interaction of ultraintense laser pulses with an overdense plasma.
A strong effect of radiation damping on the interaction of an ultraintense laser pulse with an overdense plasma slab is found and studied via a relativistic particle-in-cell simulation including ionization. Hot electrons generated by the irradiation of a laser pulse with a radiance of I lambda(2)>10(22) W microm(2)/cm(2) and duration of 20 fs can convert more than 35% of the laser energy to radiation. This incoherent x-ray emission lasts for only the pulse duration and can be intense. The radiation efficiency is shown to increase nonlinearly with laser intensity. Similar to cyclotron radiation, the radiation damping may restrain the maximal energy of relativistic electrons in ultraintense-laser-produced plasmas.


Uranium gastrointestinal absorption: the f1 factor in humans.
The present investigation was undertaken by the Department of Health, Canada, to determine the most appropriate value to use for uranium gastrointestinal absorption (f1) in setting the guideline for drinking water. Fifty participants, free from medical problems, were recruited from two communities: a rural area where drinking water, supplied from drilled wells, contained elevated levels of uranium and an urban area where the water supplied by the municipal water system contained < 1 microg l(-1). Uranium intake through food, drinking water and other beverages was monitored using the duplicate diet approach. Intake and excretion were measured by inductively coupled plasma-mass spectrometry (ICP-MS) in samples collected concurrently from the same individuals over a 3 d period. The range of f1 values was between 0.001 and 0.06, with a median of 0.009. These values were independent of gender, age, duration of exposure, daily total uranium intake and allocation of intake between food and water. Consistent with the recommendation of ICRP Publication 69, 78% were below 0.02.


The natural anticancer agent cantharidin alters GPI-anchored protein sorting by targeting Cdc1-mediated remodeling in endoplasmic reticulum.
Cantharidin (CTD) is a potent anticancer small molecule produced by several species of blister beetle. It has been a traditional medicine for the management of warts and tumors for many decades. CTD suppresses tumor growth by inducing apoptosis, cell cycle arrest, and DNA damage and inhibits protein phosphatase 2 phosphatase activator (PP2A) and protein phosphatase 1 (PP1). CTD also alters lipid homeostasis, cell wall integrity, endocytosis, adhesion, and invasion in yeast cells. In this study, we identified additional molecular targets of CTD using a Saccharomyces cerevisiae strain that expresses a cantharidin resistance gene (CRG1), encoding a SAM-dependent methyltransferase that methylates and inactivates CTD. We found that CTD specifically affects phosphatidylethanolamine (PE)-associated functions that can be rescued by supplementing the growth media with ethanolamine (ETA). CTD also perturbed endoplasmic reticulum (ER) homeostasis and cell wall integrity by altering the sorting of glycosylphosphatidylinositol (GPI)-anchored proteins. A CTD-dependent genetic interaction profile of CRG1 revealed that the activity of the lipid phosphatase cell division control protein 1 (Cdc1) in GPI-anchor remodeling is the key target of CTD, independently of PP2A and PP1 activities. Moreover, experiments with human cells further suggested that CTD functions through a conserved mechanism in higher eukaryotes. Altogether, we conclude that CTD induces cytotoxicity by targeting Cdc1 activity in GPI-anchor remodeling in the ER.


State-Specific Prevalence of Tobacco Product Use Among Adults - United States, 2014-2015.
Despite recent declines in cigarette smoking prevalence, the tobacco product landscape has shifted to include emerging tobacco products* (1,2). Previous research has documented adult use of smokeless tobacco and cigarettes by state (3); however, state-specific data on other tobacco products are limited. To assess tobacco product use in the 50 U.S. states and the District of Columbia (DC), CDC and the National Cancer Institute analyzed self-reported use of six tobacco product types: cigarettes, cigars, regular pipes, water pipes, electronic cigarettes (e-cigarettes), and smokeless tobacco products among adults aged ≥18 years using data from the 2014-2015 Tobacco Use Supplement to the Current Population Survey (TUS-CPS). Prevalence of ever-use of any tobacco product ranged from 27.0% (Utah) to 55.4% (Wyoming). Current (every day or some days) use of any tobacco product ranged from 10.2% (California) to 27.7% (Wyoming). Cigarettes were the most common currently used tobacco product in all states and DC. Among current cigarette smokers, the proportion who currently used one or more other tobacco products ranged from 11.5% (Delaware) to 32.3% (Oregon). Differences in tobacco product use across states underscore the importance of implementing proven population-level strategies to reduce tobacco use and expanding these strategies to cover all forms of tobacco marketed in the United States. Such strategies could include comprehensive smoke-free policies, tobacco product price increases, anti-tobacco mass media campaigns, and barrier-free access to clinical smoking cessation resources (1,4).


A comparison of inbreeding depression in tropical and widespread Drosophila species.
The evolutionary history of widespread and specialized species is likely to cause a different genetic architecture of key ecological traits in the two species groups. This may affect how these two groups respond to inbreeding. Here we investigate inbreeding effects in traits related to performance in 5 widespread and 5 tropical restricted species of Drosophila with the aim of testing whether the two species groups suffered differently from inbreeding depression. The traits investigated were egg-to-adult viability, developmental time and resistance to heat, cold and desiccation. Our results showed that levels of inbreeding depression were species and trait specific and did not differ between the species groups for stress resistance traits. However, for the life history traits developmental time and egg-to adult viability, more inbreeding depression was observed in the tropical species. The results reported suggest that for life history traits tropical species of Drosophila will suffer more from inbreeding depression than widespread species in case of increases in the rate of inbreeding e.g. due to declines in population sizes.


Nerve growth factor from Indian Russell's viper venom (RVV-NGFa) shows high affinity binding to TrkA receptor expressed in breast cancer cells: Application of fluorescence labeled RVV-NGFa in the clinical diagnosis of breast cancer.
Nerve growth factor (NGF) is a minor and neglected component of snake venom. Present study describes the purification and characterization of a NGF isoform (RVV-NGFa) from Indian Russell's viper venom (RVV). RVV-NGFa showed a protonated molecular ion [MH+] at m/z 17388.725 Da. The RVV-NGFa induced neuritogenesis in PC-12 cells but did not show cytotoxicity in mammalian cells, hemolytic activity, platelet modulation, and interference in blood coagulation system which are the characteristic pharmacological properties of RVV. By ELISA and immunofluorescence microplate reader assay, the RVV-NGFa showed appreciable binding to TrkA receptor expressed in breast cancer MDA-MB-231 and MCF-7 cells; nevertheless, pre-incubation of cells with anti-TrkA (and not TrkB or TrkC) or anti-p75NTR antibody significantly decreased (p < 0.05) this binding. The RVV-NGFa demonstrated insignificant binding with non-cancerous cells (HEK-293, L6) lacking TrkA receptor. The binding of RVV-NGFa to TrkA receptor of breast cancer cells resulted in internalization of ligand (RVV-NGFa)-receptor (TrkA) complex to cell cytoplasm in a time-dependent manner. The spectrofluorometric study demonstrated an interaction between RVV-NGFa and cytosolic domain of the purified TrkA receptor. The fluorescence (FITC)-tagged RVV-NGFa depicted a strong fluorescence signal that was observed under a fluorescence microscope and determined by fluorescence microplate reader assay post binding to breast cancer cells; but no fluorescence signal was detected after incubating FITC-RVV-NGFa with non-cancerous L6 and HEK-293 cells. The clinical application of FITC/fluorescence nanoparticle tagged RVV-NGFa for the ex vivo and in vivo diagnosis of breast cancer is highly promising.


Crystallization-driven one-dimensional self-assembly of polyethylene-b-poly(tert-butylacrylate) diblock copolymers in DMF: effects of crystallization temperature and the corona-forming block.
Crystallization-driven self-assembly of polyethylene-b-poly(tert-butylacrylate) (PE-b-PtBA) block copolymers (BCPs) in N,N-dimethyl formamide (DMF) was studied. It is found that all three PE-b-PtBA BCPs used in this work can self-assemble into one-dimensional crystalline cylindrical micelles. When the BCP solution is cooled to crystallization temperature (Tc) from 130 °C, the seed micelles may be produced via two competitive processes in the initial period: stepwise micellization/crystallization and simultaneous crystallization/micellization. Subsequently, the seed micelles can undergo growth driven by the epitaxial crystallization of the unimers. The lengths of both the seed micelles and the grown micelles are longer for the BCP with a longer PtBA block at a higher Tc. Quasi-living growth of the PE-b-PtBA crystalline cylindrical micelles is achieved at a higher Tc. A longer PtBA block evidently retards the attachment of unimers to the crystalline micelles, leading to a slower growth rate.


What Can Rats Tell Us about Adolescent Cannabis Exposure? Insights from Preclinical Research.
Marijuana is the most widely used drug of abuse among adolescents. Adolescence is a vulnerable period for brain development, during which time various neurotransmitter systems such as the glutamatergic, GABAergic, dopaminergic, and endocannabinoid systems undergo extensive reorganization to support the maturation of the central nervous system (CNS). ▵-9-tetrahydrocannabinol (THC), the psychoactive component of marijuana, acts as a partial agonist of CB1 cannabinoid receptors (CB1Rs). CB1Rs are abundant in the CNS and are central components of the neurodevelopmental changes that occur during adolescence. Thus, overactivation of CB1Rs by cannabinoid exposure during adolescence has the ability to dramatically alter brain maturation, leading to persistent and enduring changes in adult cerebral function. Increasing preclinical evidence lends support to clinical evidence suggesting that chronic adolescent marijuana exposure may be associated with a higher risk for neuropsychiatric diseases, including schizophrenia. In this review, we present a broad overview of current neurobiological evidence regarding the long-term consequences of adolescent cannabinoid exposure on adult neuropsychiatric-like disorders.


[Application of slightly acidic hypochlorous acid water to the dental field--setting expansion and compressive strength of dental gypsum mixed with slightly acidic hypochlorous acid water].
This study investigated both the setting expansion and compressive strength of dental gypsum mixed with slightly acidic hypochlorous acid water for the prevention of hospital infection. Slightly acidic hypochlorous acid water (PURESTER Mp-240B, Morinaga Milk Industry) was used to mix each of three types of gypsum (model plaster, dental stone and high strength dental stone), and both the setting expansion and compressive strength of these gypsum products were analyzed in comparison with those mixed with tap water. 1. With regard to the setting expansion, a significant difference was not observed between gypsum products mixed with the two types of water, except for both the model plaster and dental stone 30 minutes after the start of mixing. 2. Regarding the compressive strength, a significant difference was not observed between gypsum products mixed with the two types of water, except for the model plaster 90 minutes after the start of mixing. From the results of the study, it was revealed that both the setting expansion and compressive strength of gypsum products using the slightly acidic hypochlorous acid water showed almost the same characteristics as those using tap water.


Occurrence of a new generation of disinfection byproducts.
A survey of disinfection byproduct (DBP) occurrence in the United States was conducted at 12 drinking water treatment plants. In addition to currently regulated DBPs, more than 50 DBPs that rated a high priority for potential toxicity were studied. These priority DBPs included iodinated trihalomethanes (THMs), other halomethanes, a nonregulated haloacid, haloacetonitriles, haloketones, halonitromethanes, haloaldehydes, halogenated furanones, haloamides, and nonhalogenated carbonyls. The purpose of this study was to obtain quantitative occurrence information for new DBPs (beyond those currently regulated and/or studied) for prioritizing future health effects studies. An effort was made to select plants treating water that was high in total organic carbon and/or bromide to enable the detection of priority DBPs that contained bromine and/or iodine. THMs and haloacetic acids (HAAs) represented the two major classes of halogenated DBPs formed on a weight basis. Haloacetaldehydes represented the third major class formed in many of the waters. In addition to obtaining quantitative occurrence data, important new information was discovered or confirmed at full-scale plants on the formation and control of DBPs with alternative disinfectants to chlorine. Although the use of alternative disinfectants (ozone, chlorine dioxide, and chloramines) minimized the formation of the four regulated THMs, trihalogenated HAAs, and total organic halogen (TOX), several priority DBPs were formed at higher levels with the alternative disinfectants as compared with chlorine. For example, the highest levels of iodinated THMs-which are not part of the four regulated THMs-were found at a plant that used chloramination with no prechlorination. The highest concentration of dichloroacetaldehyde was at a plant that used chloramines and ozone; however, this disinfection scheme reduced the formation of trichloroacetaldehyde. Preozonation was found to increase the formation of trihalonitromethanes. In addition to the chlorinated furanones that have been measured previously, brominated furanones-which have seldom been analyzed-were detected, especially in high-bromide waters. The presence of bromide resulted in a shift to the formation of other bromine-containing DBPs not normally measured (e.g., brominated ketones, acetaldehydes, nitromethanes, acetamides). Collectively, -30 and 39% of the TOX and total organic bromine, respectively, were accounted for (on a median basis) bythe sum of the measured halogenated DBPs. In addition, 28 new, previously unidentified DBPs were detected. These included brominated and iodinated haloacids, a brominated ketone, and chlorinated and iodinated aldehydes.


Social and behavioural predictors of women's cancer screening practices in Northern Ireland.
The aim of this study was to describe the extent of cancer screening practices among women resident in Northern Ireland and to identify the social and behavioural characteristics associated with these practices. The study involved a survey of adults resident in the community in Northern Ireland. Contact was made with a sample of 1162 residents who were asked to complete a questionnaire about preventive health practices and attitudes. This produced a response rate of 65.1 per cent. Of these, 391 were women who were asked questions about breast self-examination (BSE), attendance for cervical screening, and certain social and behavioural factors. Approximately 28 per cent of the women performed BSE regularly, a further 28 per cent performed it occasionally, and the remainder rarely or not at all. Almost 20 per cent of the women had had a smear test once, 48 per cent several times, and the rest never. Performance of BSE and attendance for smear tests and BSE was more common among those women aged 35-54 years, who were married, worked outside the home, and whose religion was Church of Ireland (Anglican). The most frequent reason given for not performing BSE was fear of finding a lump and ignorance of the procedure. The most frequent reason given for non-attendance for a smear test was that it was not thought necessary at their age. Public health strategies designed to promote cancer screening need to consider the value of directing their campaigns at those who are most reluctant to perform these practices.


Non-human primate malaria in travelers.
Emerging zoonotic malaria caused by Plasmodium knowlesi, P. cynomolgi and P. inui occurred in humans amid a decline of malaria prevalence in Thailand during the past decade. Diagnosis of non-human primate malaria in ecotourists is challenging. Molecular diagnosis seems to be mandatory such as species-specific PCR and targeted amplicon deep sequencing.


Natural killer cell as the effector which mediates in vivo apoptosis in AK-5 tumor cells.
AK-5 tumor cell death is mediated by natural killer cells through necrosis (perforin mediated) and apoptosis. Apoptosis is the mechanism which operates in immune animals in vivo. We have identified natural killer (NK) cell as the effector cell which induces apoptosis leading to tumor cell death in vivo. Naive NK cell which is unable to kill the AK-5 tumor cell can be activated with IL-2/IL-12 to make it capable of inducing apoptosis in tumor cells. NK cells from tumor-rejected animals show higher expression of Fas ligand and serine esterase granzyme B. In addition, NK cell-mediated apoptosis in AK-5 cells is totally abolished when effector cells are treated with anti-NKR-P1 mAb 3.2.3 and complement. NK cell-mediated apoptotic activity is inhibited in bcl-2 transfected tumor cells; however, the cytotoxic activity (perforin-mediated) remains unaffected. These observations suggest an important role for activated NK cells in inducing tumor cell death through necrosis (ADCC) and apoptosis leading to spontaneous regression of the AK-5 tumor in syngeneic animals.


Effect of growth hormone treatment on children with idiopathic short stature and idiopathic growth hormone deficiency.
There are inconsistencies in the results reported in a small number of previous studies into growth hormone (GH) treatment in Korean children with idiopathic short stature (ISS) and idiopathic growth hormone deficiency (IGHD). Thus, the authors retrospectively compared the effects of GH in ISS and IGHD. From the medical records of 26 ISS and 30 IGHD children, auxological and biochemical changes including chronologic age (CA), bone age (BA), height standard deviation score (HT-SDS), predicted adult height (PAH), midparental height (MPH), insulin-like growth factor-1 (IGF-1), and insulin-like growth factor binding protein-3 (IGFBP-3) were compared. Before treatment, IGHD group had younger BA, lower BA/CA ratio, and lower IGF-1 level than those in the ISS group. During GH treatment, the levels of IGF-1 and IGFBP-3 were not different. Although annual BA increment was higher in IGHD group, and annual PAH-SDS increment was higher in ISS group, annual HT-SDS increments were not different. Both HT-SDS and PAH-SDS in the ISS group increased significantly until the end of the second year, and then those were not significantly different from MPH-SDS. In the IGHD group, the HT-SDS showed a significant increase till the end of the second year, and the PAH-SDS was not significantly changed at each year, but both HT-SDS and PAH-SDS were not significantly different from MPH-SDS at the end of the third year. During GH treatment, both HT-SDS and PAH-SDS approached the genetic target range of MPH-SDS after 2 years in ISS children and 3 years in IGHD children.


Cell cycle stage-specific differential expression of topoisomerase I in tobacco BY-2 cells and its ectopic overexpression and knockdown unravels its crucial role in plant morphogenesis and development.
DNA topoisomerases catalyze the inter-conversion of different topological forms of DNA. Cell cycle coupled differential accumulation of topoisomerase I (Topo I) revealed biphasic expression maximum at S-phase and M/G1-phase of cultured synchronized tobacco BY-2 cells. This suggested its active role in resolving topological constrains during DNA replication (S-phase) and chromosome decondensation (M/G1 phase). Immuno-localization revealed high concentrations of Topo I in nucleolus. Propidium iodide staining and Br-UTP incorporation patterns revealed direct correlation between immunofluorescence intensity and rRNA transcription activity within nucleolus. Immuno-stained chromosomes during metaphase and anaphase suggested possible role of Topo I in resolving topological constrains during mitotic chromosome condensation. Inhibitor studies showed that in comparison to Topo I, Topo II was essential in resolving topological constrains during chromosome condensation. Probably, Topo II substituted Topo I functioning to certain extent during chromosome condensation, but not vice-versa. Transgenic Topo I tobacco lines revealed morphological abnormalities and highlighted its crucial role in plant morphogenesis and development.


Impact of severe hypoglycemia on the heat shock and related protein response.
Heat shock proteins contribute to diabetes-induced complications and are affected by glycemic control. Our hypothesis was that hypoglycemia-induced heat shock and related protein changes would be amplified in type 2 diabetes (T2D). This prospective, case-control study enrolled 23 T2D patients and 23 control subjects who underwent hyperinsulinemic-induced hypoglycemia (≤ 2.0 mmol/L (36 mg/dl)) with blood sampling at baseline, at hypoglycemia and after a 24-h post-hypoglycemia follow-up period. Proteomic analysis of heat shock-related and pro-inflammatory proteins was performed. At baseline, MAPKAPK5 (p = 0.02) and UBE2G2 (p = 0.003) were elevated and STUB1 decreased (p = 0.007) in T2D. At hypoglycemia: PPP3CA (p < 0.03) was increased and EPHA2 (p = 0.01) reduced in T2D; by contrast, three proteins were reduced in controls [HSPA1A (p = 0.007), HSPB1 (p < 0.02), SMAD3 (p = 0.005)] while only MAPKAPK5 was elevated (p = 0.02). In the post-hypoglycemia follow-up period, most proteins normalized to baseline by 24-h; however, STIP1 (p = 0.003), UBE2N (p = 0.004) and UBE2L3 (p < 0.04) were decreased in controls at 24-h. No protein differed from baseline at 24-h in T2D. Pro-inflammatory interleukin-6 increased at 4-h post-hypoglycemia in controls and T2D (p < 0.05 and p < 0.003, respectively) and correlated with HSPA1A; anti-inflammatory IL-10 decreased 2-h post-hypoglycemia in T2D only. Other pro-inflammatory proteins, IL-1α, IFN-γ and TNF-α, were unchanged. Heat shock and related proteins differed at baseline between T2D and controls, with an exaggerated response of heat shock and related proteins to hypoglycemia that returned to baseline, though with changes at 24-h in controls alone. An increase in pro-inflammatory IL-6, with a decrease in anti-inflammatory IL-10, suggests that the HSP system is overactivated due to underlying inflammation in T2D.Trial registration: ClinicalTrials.gov NCT03102801.