Danazol therapy combined with intermittent application of chemotherapy induces lasting remission in myeloproliferative disorder (MPD): an alternative for the elderly with advanced MPD.
There is no good alternative therapy available for elderly patients with advanced myeloproliferative disorders (MPD) who failed on conventional therapies and are not candidates for bone marrow transplant. We report here an effective therapy that induced exceptionally long-lasting remissions and improved quality of life. Eighteen elderly patients (mean age: 70·6 years) (16 myelofibrosis and 2 thrombocythemia) who had failed on conventional therapies were treated. Danazol was administered daily at 200-800 mg throughout the study. Chemotherapy was applied intermittently as needed to reduce spleen size and blood counts. Busulfan (2-4 mg/day) was used most often and 6-mercaptopurine (6-MP) (50-100 mg/day) and/or cytarabine (100-200 mg/m(2)) if the white blood cell (WBC) count rose rapidly. When MPD stabilized, chemotherapy was discontinued and dosage of danazol was reduced. Therapy was well tolerated. Overall, 61% of patients responded with unexpectedly long-lasting remissions and improved quality of life. Three (17%) had excellent (E) response, defined by normalization of blood counts and non-palpable spleen, while eight (44%) had good (G) response, defined by rise of Hct by ≥7% and ≥50% reduction of spleen. Mean duration of remission was 45 months (10-78 months) in E responders and 11 months in G responders (2-22 months). This regimen offers a safe and effective alternative for advanced MPD in the elderly.


The anterior thalamic nuclei and cognition: A role beyond space?
The anterior thalamic nuclei are a vital node within hippocampal-diencephalic-cingulate circuits that support spatial learning and memory. Reflecting this interconnectivity, the overwhelming focus of research into the cognitive functions of the anterior thalamic nuclei has been spatial processing. However, there is increasing evidence that the functions of the anterior thalamic nuclei extend beyond the spatial realm. This work has highlighted how these nuclei are required for certain classes of temporal discrimination as well as their importance for processing other contextual information; revealing parallels with the non-spatial functions of the hippocampal formation. Yet further work has shown how the anterior thalamic nuclei may be important for other forms of non-spatial learning, including a critical role for these nuclei in attentional mechanisms. This evidence signals the need to reconsider the functions of the anterior thalamic within the framework of their wider connections with sites including the anterior cingulate cortex that subserve non-spatial functions.


[Relationship between redox state of whole arterial blood glutathione and left ventricular function after acute myocardial infarction].
To investigate the role of oxidative stress in left ventricular function after acute myocardial infarction. We studied 41 patients with acute myocardial infarction (30 men and 11 women, mean age 61.7 +/- 11.6 years) with Thrombolysis in Myocardial Infarction grade 3 recanalization of occluded coronary arteries within 12 hr after onset. Cardiac catheterization was performed at the time of admission and before discharge. Three markers for oxidative stress were measured: plasma lipid hydroperoxide, plasma creatol and whole arterial blood glutathione at the time of admission. Mean time from onset to recanalization was 5.2 +/- 0.6 hr. The patients were divided into two groups according to the changes in left ventricular wall motion (LVWM); patients who showed improvement in LVWM and those without improvement. There were no significant differences in age, sex, coronary risk factors, severity of coronary artery disease, time from onset to recanalization or ejection fraction between two groups. Maximum creatine kinase and C-reactive protein levels in patients without LVWM improvement were significantly higher than in patients with improvement. Plasma levels of lipid hydroperoxide and creatol did not differ significantly between two groups. On the other hand, reduced glutathione/oxidized glutathione ratio in arterial blood in patients without LVWM improvement was significantly lower than in patients with LVWM improvement (69.8 +/- 3.4 vs 85.5 +/- 2.9, p < 0.05). Our results suggest that whole arterial blood glutathione is more oxidized in acute myocardial infarction patients without LVWM improvement than in patients with improvement. Redox state of arterial blood can be a predicting factor for left ventricular function after acute myocardial infarction.


D-cycloserine facilitates socially reinforced learning in an animal model relevant to autism spectrum disorders.
There are no drugs that specifically target the social deficits of autism spectrum disorders (ASD). This may be due to a lack of behavioral paradigms in animal models relevant to ASD. Partner preference formation in the prairie vole represents a social cognitive process involving socially reinforced learning. D-cycloserine (DCS) is a cognitive enhancer that acts at the N-methyl-D-aspartate receptor to promote learning. If DCS enhances socially reinforced learning in the partner preference paradigm, it may be useful in combination with behavioral therapies for enhancing social functioning in ASD. Female prairie and meadow voles were given DCS either peripherally or directly into one of three brain regions: nucleus accumbens, amygdala, or caudate putamen. Subjects were then cohabited with a male vole under conditions that do not typically yield a partner preference. The development of a preference for that stimulus male vole over a novel male vole was assessed using a partner preference test. A low dose of DCS administered peripherally enhanced preference formation in prairie voles but not meadow voles under conditions in which it would not otherwise occur. These effects were replicated in prairie voles by microinfusions of DCS into the nucleus accumbens, which is involved in reinforcement learning, and the amygdala, which is involved in social information processing. Partner preference in the prairie vole may provide a behavioral paradigm with face, construct, and predictive validity for identifying prosocial pharmacotherapeutics. D-cycloserine may be a viable treatment strategy for social deficits of ASD when paired with social behavioral therapy.


Dehydration inhibits matrix synthesis and cell proliferation. An in vitro study of rabbit flexor tendons.
Segments of the deep flexor tendon of the rabbit were exposed to air; the effects of dehydration on in vitro synthesis of proteoglycan, collagen, noncollagenous protein, and cell proliferation were compared with tendon segments that were kept moist with physiologic saline. After 20 min of exposure to air, the tendons lost half and after 40 min all of their ability to synthesize matrix components and to proliferate, whereas irrigated tendons remained viable during the entire experiment.


Factors Associated with Inflammatory Bowel Disease Flare During Pregnancy Among Women with Preconception Remission.
The factors associated with inflammatory bowel diseases (IBD) relapse throughout gestation in those with preconception remission remain unknown. We aimed to investigate disease and pregnancy course among IBD women with quiescent disease at conception. Women with IBD attending a multidisciplinary clinic for preconception, antenatal and postnatal treatment were prospectively recruited during 2011-2018. Overall, 298 women with IBD with quiescent disease at the time of conception constituted the study cohort. Of these, 112 (37.6%) women experienced disease flare during pregnancy. The risk of disease relapse was higher in those with ulcerative colitis (UC) as compared to those with Crohn's disease (CD) (48.1% vs. 31.8%, P = 0.005). The proportion of women with prior IBD-related gastrointestinal surgery was lower in those who experienced disease flare up (13.4% vs. 26.3%, P = 0.009). The use of biologic therapy at the time of conception was associated with lower rates of disease relapse (25.0% vs. 43.9%, P = 0.001). In multivariate analysis, use of conventional medications or no treatment (aOR [95% CI]: 2.0 (1.12, 3.57), P = 0.02) and lack of prior history of IBD-related surgery (aOR [95% CI]: 3.13 (1.37, 7.14), P = 0.007) were independently positively associated with disease relapse. Rates of hospitalization during pregnancy (21.4% vs. 2.2%, P < 0.001) and preterm delivery (22.3% vs. 9.1%, P = 0.002) were higher, and birthweight was lower (median 2987 vs. 3153 grams, P = 0.05) in those with disease flare as compared to those who maintained remission. Prior IBD-related surgery and biologic therapy were found as independent protective factors against relapse during pregnancy among women with quiescent disease at conception.


Post-Surgical Adhesion Prevention with a Biodegradable Gel Compatible with Laparoscopic Use
A useful laparoscopic product for adhesion prevention must be easy to apply with minimal handling and manipulation of tissue and product. With this objective in mind, we have developed an injectable gel (HALTM) based on hyaluronic acid that is intended to limit adhesion formation after laparoscopic and open surgical procedures. We tested the effectiveness of HALTM gels in a rat sidewall defect model. In 50 adult female rats a 1 cm x 1 cm peritoneal defect was made along the abdominal wall. The defect was enclosed with #3-0 silk suture to induce ischemia. The animals were randomized to gel treatment (0.5 ml placed on defect) or non-treatment control groups. Seven days after surgery the extent (0-4 scale) and severity (0-3 scale) of adhesions were scored. HALTM gel significantly reduced the extent and severity of sidewall adhesions. Moreover, the number of animals with no adhesions was significantly increased compared with non-treatment. These results indicate that HALTM gel, which is easily applied to tissue and organs, may be a useful adjuvant for adhesion prevention in open and laparoscopic surgical procedures. The effectiveness and safety of HALTM gels will be tested in human clinical studies.


Kisspeptin and seasonal control of reproduction in male European sea bass (Dicentrarchus labrax).
In the present study, we developed and validated real-time quantitative RT-PCR assays for a suite of genes involved in the brain-pituitary gonadal axis in fish including kisspeptin genes and its receptor (Kiss1, kiss2, kissr4) and gonadotropin-releasing hormone genes (sbGnRH, sGnRH, cGnRHII) in the brain, and gonadotropin genes (fshβ and lhβ) in the pituitary. Sex steroid profiles (T and 11-KT) and gonadal development were also studied over a full annual reproductive cycle in adult male sea bass. The cDNA partial sequence of sea bass kissr4 encoding 185 amino acids showed a high degree of conservation with other fish kissr4 subtype. Results clearly showed a seasonal profile for Kiss1, kiss2 and kissr4 mRNAs. Kissr4, fshβ and lhβ levels increased gradually and peaked during spermatogenesis (January) while Kiss1, kiss2, cGnRH-II as well as steroids showed peaks during early spawning (March). No significant seasonal changes were observed for sbGnRH and sGnRH expression. These results support the possible involvement of the kiss genes and their receptor (kissr4) in the seasonal control sea bass reproduction. However, a lack of correlation between kiss genes and sbGnRH expression and the mismatch between kisspeptin and the onset of gonadotropin surge contrast with previous findings.


[A case report of chordoid glioma with unusual features: Immunohistochemical and molecular findings and differential diagnoses].
We report the case of a 63-year-old healthy patient who was admitted for surgery of a suprasellar tumor with extension to the optic chiasm responsible of visual disturbance. Histopathological examination revealed a tumoral proliferation composed of epithelioid cells without atypia arranged in cords in a mucinous matrix surrounded by some lymphocytic inflammatory infiltrates. On immunohistochemistry, the neoplastic cells strongly expressed GFAP and CD34, a weak expression of EMA, an expression of TTF1 without immunoreactivity for brachyury. Ki-67 labeling index was low around 1%. The diagnosis of chordoid glioma was made. Surprisingly, tumor cells expressed IDH1R132H but molecular analysis did not reveal any mutation of IDH1/2 genes. There was no expression of p53 but high overexpression of EGFR. Chordoid glioma is a rare and low-grade entity. The precise histogenesis remains debated. Our case is unusual because of the infiltration of the optic chiasm and because of the immunoexpression of IDH1R132H without underlying mutations of IDH1/2 genes.


The renal compression syndrome.
A clinical example of perirenal compression producing documented renin-mediated hypertension is presented. The pathophysiology of this disorder is discussed as it relates to renin release mechanisms. In the future, recognition of the renal compression syndrome may obviate needless nephrectomies since simple removal of the source of compression should result in the cure of hypertension.


Salmonella phages and prophages: genomics, taxonomy, and applied aspects.
Since this book was originally published in 2007 there has been a significant increase in the number of Salmonella bacteriophages, particularly lytic virus, and Salmonella strains which have been fully sequenced. In addition, new insights into phage taxonomy have resulted in new phage genera, some of which have been recognized by the International Committee of Taxonomy of Viruses (ICTV). The properties of each of these genera are discussed, along with the role of phage as agents of genetic exchange, as therapeutic agents, and their involvement in phage typing.


The nucleotide exchange factors Grp170 and Sil1 induce cholera toxin release from BiP to enable retrotranslocation.
Cholera toxin (CT) intoxicates cells by trafficking from the cell surface to the endoplasmic reticulum (ER), where the catalytic CTA1 subunit hijacks components of the ER-associated degradation (ERAD) machinery to retrotranslocate to the cytosol and induce toxicity. In the ER, CT targets to the ERAD machinery composed of the E3 ubiquitin ligase Hrd1-Sel1L complex, in part via the activity of the Sel1L-binding partner ERdj5. This J protein stimulates BiP's ATPase activity, allowing BiP to capture the toxin. Presumably, toxin release from BiP must occur before retrotranslocation. Here, using loss-and gain-of-function approaches coupled with binding studies, we demonstrate that the ER-resident nucleotide exchange factors (NEFs) Grp170 and Sil1 induce CT release from BiP in order to promote toxin retrotranslocation. In addition, we find that after NEF-dependent release from BiP, the toxin is transferred to protein disulfide isomerase; this ER redox chaperone is known to unfold CTA1, which allows the toxin to cross the Hrd1-Sel1L complex. Our data thus identify two NEFs that trigger toxin release from BiP to enable successful retrotranslocation and clarify the fate of the toxin after it disengages from BiP.


Associations Between Adherence to Evidence-Based, Stroke Quality Indicators and Outcomes of Acute Reperfusion Therapy.
Quality indicators (QIs) are an accepted tool for measuring a hospital's performance in routine care. We examined national trends in adherence to the QIs developed by the Close The Gap-Stroke program by combining data from the health insurance claims database and electronic medical records, and the association between adherence to these QIs and early outcomes in patients with acute ischemic stroke in Japan. In the present study, patients with acute ischemic stroke who received acute reperfusion therapy in 351 Close The Gap-Stroke-participating hospitals were analyzed retrospectively. The primary outcomes were changes in trends for adherence to the defined QIs by difference-in-difference analysis and the effects of adherence to distinct QIs on in-hospital outcomes at the individual level. A mixed logistic regression model was adjusted for patient and hospital characteristics (eg, age, sex, number of beds) and hospital units as random effects. Between 2013 and 2017, 21 651 patients (median age, 77 years; 43.0% female) were assessed. Of the 25 defined measures, marked and sustainable improvement in the adherence rates was observed for door-to-needle time, door-to-puncture time, proper use of endovascular thrombectomy, and successful revascularization. The in-hospital mortality rate was 11.6%. Adherence to 14 QIs lowered the odds of in-hospital mortality (odds ratio [95% CI], door-to-needle <60 min, 0.80 [0.69-0.93], door-to-puncture <90 min, 0.80 [0.67-0.96], successful revascularization, 0.40 [0.34-0.48]), and adherence to 11 QIs increased the odds of functional independence (modified Rankin Scale score 0-2) at discharge. We demonstrated national marked and sustainable improvement in adherence to door-to-needle time, door-to-puncture time, and successful reperfusion from 2013 to 2017 in Japan in patients with acute ischemic stroke. Adhering to the key QIs substantially affected in-hospital outcomes, underlining the importance of monitoring the quality of care using evidence-based QIs and the nationwide Close The Gap-Stroke program.


Comparison of coagulation profile and thromboembolic events among patients undergoing spinal surgery before and after COVID-19 pandemic.
Impairment of coagulation parameters and increased rate of thromboembolism are known complications of COVID-19 infection. In this study the coagulation profile and rate of thromboembolic events between two groups of patients who underwent spinal surgery before and after the COVID-19 pandemic was compared. Clinically and laboratory negative for COVID-19 elective patients before (n: 211) and during COVID- 19 pandemic (n: 294) with spinal surgeries were included in this retrospective study. Surgical characteristics, Physiologic parameters, coagulation parameters and thromboembolic events were compared between the two study groups. Preoperative coagulation parameters, including PT, PTT, and INR were significantly increased during the COVID-19 pandemic (P < 0.001. P = 0.001, and P < 0.001, respectively), while the platelet count was significantly reduced (P = 0.04). The same differences were observed between the two study groups after the spinal surgery. In addition, respiratory rate and postoperative bleeding of the first postoperative 24 h was significantly more in patients who were operated on during COVID-19 outbreak (P = 0.03 and P = 0.002, respectively). The rate of thromboembolic events was 3.1% during the COVID-19 pandemic (seven PE, one DVT, and one MI) and 0% before that. This difference was statistically significant (P = 0.043). The rate of thromboembolic events seems to be increased during the COVID-19 pandemic. These findings urge more stringent monitoring of the patients' coagulation parameters during the COVID-19 outbreak.


Risk factors for metabolic and cardiovascular disease in inpatients with severe mental illness.
Patients with severe mental illness (SMI) have increased burden of somatic illnesses, especially cardiovascular disease. Characterizing the cardiovascular risk profile of patients with SMI is therefore crucial to understanding how to decrease morbidity and mortality in these vulnerable populations. In this observational study, entropy balancing (a form of propensity score matching) was used to compare cardiometabolic health in a sample of the general population from the National Health and Nutrition Examination Survey (NHANES) datasets to inpatients hospitalized in a large, urban, academic psychiatric hospital in Harris County, Texas. Data were analyzed using independent linear regression models for blood pressure, blood glucose, TG:HDL ratio, total cholesterol, and body mass index as outcome variables. Systolic blood pressure (F=34•75, p<0•0001), diastolic blood pressure (F=90•53, p<0•0001), blood glucose (F=12•89, p<0•0001), and the TG:HDL ratio (F=3•16, p<0•0001) were all elevated in the psychiatric inpatient sample vs. the NHANES sample. Contrary to expectations, total cholesterol (F=32•18, p<0•0001) and BMI (F=15•05, p<0•0001) were lower in this sample vs. the NHANES sample. Patients hospitalized with SMI show a cardiometabolic profile which confers greater risk of diabetes- and hypertension-related mortality. Approaches should be developed to target indicators of cardiometabolic health in this population to reduce long-term mortality.


Epidemiology and Outcomes of Critically Ill Children at Risk for Pediatric Acute Respiratory Distress Syndrome: A Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology Study.
Interventional trials aimed at pediatric acute respiratory distress syndrome prevention require accurate identification of high-risk patients. In this study, we aimed to characterize the frequency and outcomes of children meeting "at risk for pediatric acute respiratory distress syndrome" criteria as defined by the Pediatric Acute Lung Injury Consensus Conference. Planned substudy of the prospective multicenter, international Pediatric Acute Respiratory Distress Syndrome Incidence and Epidemiology study conducted during 10 nonconsecutive weeks (May 2016-June 2017). Thirty-seven international PICUs. Three-hundred ten critically ill children meeting Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria. None. We evaluated the frequency of children at risk for pediatric acute respiratory distress syndrome and rate of subsequent pediatric acute respiratory distress syndrome diagnosis and used multivariable logistic regression to identify factors associated with subsequent pediatric acute respiratory distress syndrome. Frequency of at risk for pediatric acute respiratory distress syndrome was 3.8% (95% CI, 3.4-5.2%) among the 8,122 critically ill children who were screened and 5.8% (95% CI, 5.2-6.4%) among the 5,334 screened children on positive pressure ventilation or high-flow oxygen. Among the 310 at-risk children, median age was 2.1 years (interquartile range, 0.5-7.3 yr). Sixty-six children (21.3%) were subsequently diagnosed with pediatric acute respiratory distress syndrome, a median of 22.6 hours (interquartile range, 9.8-41.0 hr) later. Subsequent pediatric acute respiratory distress syndrome was associated with increased mortality (21.2% vs 3.3%; p < 0.001) and longer durations of invasive ventilation and PICU care. Subsequent pediatric acute respiratory distress syndrome rate did not differ by respiratory support modality at the time of meeting at risk criteria but was independently associated with lower initial saturation:Fio2 ratio, progressive tachycardia, and early diuretic administration. The Pediatric Acute Lung Injury Consensus Conference "at-risk for pediatric acute respiratory distress syndrome" criteria identify critically ill children at high risk of pediatric acute respiratory distress syndrome and poor outcomes. Interventional trials aimed at pediatric acute respiratory distress syndrome prevention should target patients early in their illness course and include patients on high-flow oxygen and positive pressure ventilation.


Child and adult disability in the 2000 Census: disability is a household affair.
Survey data indicate that individuals with disabilities in the United States often experience less advantageous economic and social resources than individuals without disabilities. Furthermore, they often reside with other individuals with disabilities in the same household. However, less is known about resource availability when multiple child and adult household members have a disability. We use child-level data from the 2000 Census to examine the relationship between aggregation of disability in households with children and education, labor force participation, poverty level, and inadequate housing. We utilize tabular analysis and Kruskal-Wallis tests to examine how resources in education, employment, income, and housing adequacy compare for children with disabilities who are the only member of their household with a disability, children with disabilities who live in a household with at least one other member with a disability, children without disabilities who live in a household where no other member has a disability, and children without disabilities who live in a household where at least one other member has a disability. Among children without a disability, 86% live in a household in which no other member has a disability. Among children with a disability, 53% live in a household in which no other adult or child has a disability. Poverty, inadequate housing, and low adult education were more than two times more likely - and adult unemployment over five times more likely - in households with multiple members with disability versus households without disability. There is a high prevalence of aggregation of adults and children with disability in households of children with disability. These households have substantially fewer resources than households who do not have children or adults with disabilities.


The usefulness of work-based assessments in higher surgical training: A systematic review.
Work-based assessments including procedure based assessments, case based discussions, clinical evaluation exercises and direct observation of procedural skills are used in Higher Surgical Training Program. This systematic review aims to investigate the trainer and trainee's perception of the usefulness of workplace based assessments in Higher Surgical Training Programme. Embase, MEDLINE and PubMed databases were searched for relevant studies published up to Jan 15, 2021. The following search terms were used: procedure based assessments, case based discussions, clinical evaluation exercises, direct observation of procedural skills, Higher Surgical Training Program (with and without their abbreviations), surgical training, formative assessment. Usefulness was analysed according to van der Vleuten's utility formula, which is the product of educational impact, validity, reliability, acceptability, cost-effectiveness and feasibility. 23 studies were included; Six on procedure based assessments, two on case based discussions, one on mini clinical evaluation exercises, three on direct observation of procedural skills and eleven on multiple methods. Overall, procedure based assessments had positive Kirkpatrick level 1 or 2 impact were valid, reliable and acceptable. Mini clinical evaluation exercises showed positive Kirkpatrick level 1 satisfaction in trainees and trainers and were feasible. Case based discussions were shown to have both positive and negative Kirkpatrick levels 1 and 2 impact and were rated valid and reliable. Direct observation of procedural skills were valid with favourable Kirkpatrick level 1 impact with more usage and modification of the forms. Multiple methods as used in the intercollegiate surgical curriculum programme portfolio was found to be less encouraging in achieving positive higher level of educational impact. The barriers included lack of time, lack of faculty development and lack of engagement. It is important that work-based assessments are used properly, so that trainees get the maximum benefit from them. None of the studies included in our systematic review demonstrated an impact on behaviour or society (Kirkpatrick level 3 and 4), towards which future research should be directed to.


Reconstitution of blood supply of the denuded bronchial stump.
Our aim was to study the process of microcirculatory reconstitution in the bronchial stump after pneumonectomy. Eighteen juvenile pigs (median weight 40.6 kg) were randomly assigned to three groups. In all animals left pneumonectomy was performed and the stapled bronchial stump (median length 3.8 cm) carefully denuded. Group I animals received coverage of the stump by intercostal flap. In group II, the stump was covered with TachoComb, an impermeable hemostatic fleece; and group III served as a control without any coverage of the stump. Animals were sacrificed at day 14 after surgery. Vascular density was evaluated in serial histologic sections at multiple levels stained with CD-31 antibody. One-way analysis of variance and the Wilcoxon test were used for data analysis. At autopsy, stumps of group III animals were totally covered by adjacent mediastinal structures. In group I, intercostal flaps were viable and completely healed to the bronchial stumps. There were no signs of infection or stump insufficiency in these groups. In all group II animals, empyema developed, and stumps were found necrotic at macroscopic and histologic evaluation. Statistical analysis revealed significantly lower vascular density of mature vessels in the area of the bronchial stump in group II compared with both other groups. Reconstitution of microcirculation of the denuded bronchial stump after pneumonectomy takes place in a centripetal way from adjacent viable tissue. Hence, the purpose of covering the bronchial stump is the improvement of blood supply rather than mechanical reinforcement.


A burned body with a shotgun head injury found on an "altar" made of banknotes: A case report from Greece and brief review of the literature.
We describe an unusual case of a burnt body with a shotgun head injury found on a "bed" made of wooden boards on a pile of banknotes, resembling an altar. The body belonged to a 64-year-old man, of Greek nationality, with cancer who set his house (including the room in which he was found) and vehicle on fire before shooting himself, planning this way his postmortem burning. The combination of fire with the use of an "altar" and the destruction of body and possessions creates a unique death scene that implies a suicide with a ritual character.


A cellular screening platform, stably expressing DENV2 NS5, defines a novel anti-DENV mechanism of action of Apigenin based on STAT2 activation.
Type I interferon (IFN-I) evasion by Dengue virus (DENV) is key in DENV pathogenesis. The non-structural protein 5 (NS5) antagonizes IFN-I response through the degradation of the signal transducer and activator of transcription 2 (STAT2). We developed a K562 cell-based platform, for high throughput screening of compounds potentially counteracting the NS5-mediated antagonism of IFN-I signaling. Upon a screening with a library of 1220 approved drugs, 3 compounds previously linked to DENV inhibition (Apigenin, Chrysin, and Luteolin) were identified. Luteolin and Apigenin determined a significant inhibition of DENV2 replication in Huh7 cells and the restoration of STAT2 phosphorylation in both cell systems. Apigenin and Luteolin were able to stimulate STAT2 even in the absence of infection. Despite the "promiscuous" and "pan-assay-interfering" nature of Luteolin, Apigenin promotes STAT2 Tyr 689 phosphorylation and activation, highlighting the importance of screening for compounds able to interact with host factors, to counteract viral proteins capable of dampening innate immune responses.


Promoting college and career readiness among underserved adolescents: A mixed methods pilot study.
Many underserved adolescents, defined as those with inequitable access to educational resources, face limited access to interventions that develop their college and career know-how. In our study, we implemented and evaluated a pilot college and career readiness curriculum intervention called Paths to the Future for All (P2F4A). P2F4A takes a developmental approach to college and career development, weaving together the procedural know-how of college and career planning with a broader focus on building social-emotional skills that support positive trajectories towards the future. We evaluated pre-post changes in adolescents' career-related and social-emotional outcomes alongside views of their personal growth. We used a purposeful sample of five schools in the Western region of the United States and recruited a sample of adolescents (N = 61; Mage = 16.3 years; 57.4% female) who experienced challenging academic and life circumstances to participate in P2F4A. We conducted pre-post surveys as well as focus groups and interviews with adolescents. We detected significant (p < .05) pre-post gains in adolescents' knowledge of P2F4A curricular content and selected coping skills, such as relaxing and solving family problems. Our focus groups and interviews revealed that P2F4A helped adolescents build stronger interpersonal relationships with peers and the content was directly applicable to real life. Our new findings suggest that college and career readiness curriculum interventions-if appropriately developed for and targeted to underserved adolescents-have strong potential to build underserved adolescents' foundational skills that they can apply towards realizing their future college and career aspirations.


Predictive factors for achieving independent walking in children with Guillain-Barre syndrome.
BackgroundTo determine the predictors of achieving independent walking at 2 and 6 months after onset of weakness in children with Guillain-Barre syndrome (GBS).MethodsChildren with GBS admitted to the Tabriz Children's Hospital were studied prospectively. All patients had frequent clinical evaluations until achieving independent walking. Unaided walking at 2 and 6 months and factors influencing these outcomes were determined using both univariate and multiple analyses.ResultsBetween 2003 and 2014, 324 children (mean age: 5.3±3.66 years) were admitted. The mean duration to independent walking was 2.97±3.02 months; 90.5% of patients could walk independently at 6 months. In the univariate analysis, disability score of >3 (P=0.03), autonomic nerve involvement (P=0.003), cranial nerve involvement (P=0.008), and absent compound muscle action potential (CMAP; P=0.048) were found to be significantly associated with poor walking outcome at 6 months. In the multivariate analysis, cranial nerve involvement (P=0.008) and absence of CMAP (P=0.022) were independently associated with poor functional outcome.ConclusionDisability score >3, cranial and autonomic nerve involvement, and absence of CMAP were predictors of independent walking in childhood GBS in this study; early rehabilitation program may prevent further impairments secondary to immobility in these patients.


Confounding and the dementia of schizophrenia.
Schizophrenia is often said to cause dementia, and previous studies have found cognitive impairment to be associated with schizophrenia. It is possible, however, that other causes of dementia and the study of patients not representative of all schizophrenics have contributed to these findings. The neuropsychological test scores of 26 schizophrenic outpatients were compared to those of 82 other patients with a history of psychosis. After other known causes of cognitive impairment were controlled for, the schizophrenics were not found to have cognitive impairment when compared to the other patients.


Different HLA antigen associations for the functionally active and inactive products of the complement C4F1 allele.
The genetic polymorphism of the fourth component of human complement, C4, was studied in 945 unrelated Caucasian individuals. A third allele of the C4F (Rodgers) locus, termed C4F1 was demonstrated. This allele is characterized using immunofixation electrophoresis, by the presence of an additional fast-moving anodal band of C4 which distinguishes it clearly from the common C4F variant. The allelic frequencies fit the Hardy-Weinberg equilibrium assuming three alleles at the C4F locus: C4F, C4Fo, and C4F1. The functional activity of the C4F variants was investigated using a specific hemolytic overlay technique for C4. It was found that in almost all individuals (75 out of 78), the C4F1 allele codes for a functionally inactive C4 product only when it occurs on an HLA-B17 positive haplotype but that the same allele codes for a functionally active fast variant of C4 when it occurs on an HLS-B37 positive haplotype (18 out of 18). Very strong genetic linkage disequilibrium was observed for the C4F1 allele with HLA-B17 and B37. The active and inactive C4F1 variant also has marked nonrandom gametic association to different alleles of the Bf locus and to HLA-C locus determinants. No further variants of the C4S (Chido) locus have been identified so far. Rodgers (Rg) typing by the plasma inhibition test of anti-Rg antiserum has shown that plasma from individuals homozygous for the C4F1 allele is only able to partially inhibit anti-Rg whereas all C4F positive individuals totally inhibited the reaction.


Thermodynamics of actin polymerization; influence of the tightly bound divalent cation and nucleotide.
Previous work by this laboratory has shown that the tightly bound divalent cation of actin affects the enthalpy of the polymerization reaction for ATP-actin (Selden et al. (1986) J. Muscle Res. Cell Motil. 7, 215-224). In the present study, we have measured the temperature dependence of polymerization for actin containing ATP or ADP as the bound nucleotide and Mg2+ or Ca2+ (Mg-actin or Ca-actin) as the tightly bound divalent cation. In contrast to the marked effect of the tightly bound divalent cation on enthalpy and entropy changes for the polymerization of ATP-actin, ADP-actin polymerization is affected very little by the tightly bound divalent cation. The Arrhenius and van't Hoff plots for polymerization of Ca-ATP-, Mg-ADP- and Ca-ADP-actin were found to be non-linear. The free energy data for actin polymerization have been analyzed as a second order function of absolute temperature (Osborne et al. (1976) Biochemistry 15, 317-320). The values of the enthalpy change and activation enthalpy change for Ca-ATP-, Mg-ADP- and Ca-ADP-actin polymerization were found to be temperature-dependent, in contrast to those for Mg-ATP-actin, which were nearly constant over the temperature range studied. These results suggest that (1) polymerization of actin which does not contain both Mg2+ and ATP may be a multi-step reaction including a rate-limiting step and (2) Mg-ATP-actin has a unique conformation which enhances its ability to polymerize.


Missing C, supplemental D and supplemental premolar all in one quadrant: a case report.
This case report describes a non-syndromic Caucasian patient who presented with a missing upper right primary canine and a supplemental upper right primary first molar. Later, a supplemental premolar developed in the upper right quadrant. The report highlights the importance of early diagnosis of dental anomalies and a multidisciplinary approach to treatment planning. A regular review and radiographic examination are essential.


Activating autophagy and ferroptosis of 3‑Chloropropane‑1,2‑diol induces injury of human umbilical vein endothelial cells via AMPK/mTOR/ULK1.
3‑Chloropropane‑1,2‑diol (3‑MCPD) is an internationally recognized food pollutant. 3‑MCPD has reproductive, renal and neurotoxic properties. However, whether 3‑MCPD induces human umbilical vein endothelial cell (HUVEC) injury has not been previously reported. In the present study, HUVECs were treated using 2 µg/ml 3‑MCPD for 24 h at 37˚C. The effects of 3‑MCPD on HUVEC proliferation and cell cycle arrest, death and senescence were then assessed using Cell Counting Kit‑8 (CCK‑8), flow cytometry and β‑galactosidase staining, respectively. Whether 3‑MCPD induced ferroptosis was evaluated using JC‑1 and FerroOrange staining and transmission electron microscopy. A small interfering RNA targeting AMPK was used to assess whether 3‑MCPD promoted ferroptosis via AMPK signaling. The results demonstrated that 3‑MCPD inhibited HUVEC proliferation in a dose‑dependent manner and induced cell cycle arrest. Furthermore, 3‑MCPD promoted senescence in HUVECs with elevated DNA damage and cell death. The CCK‑8 results demonstrated that ferroptosis and autophagy inhibitors significantly reversed cell death caused by 3‑MCPD. Moreover, 3‑MCPD increased mitochondrial membrane potential, which indicated that 3‑MCPD contributed to mitochondrial dysfunction. 3‑MCPD also markedly increased intracellular Fe2+ levels and lipid peroxidation in HUVECs. The present study assessed the underlying mechanism by which 3‑MCPD activated autophagy and ferroptosis in HUVECs. The data demonstrated that 3‑MCPD significantly increased phosphorylation levels of AMPK and unc‑51 like autophagy activating kinase (ULK1) but significantly decreased phosphorylation of mTOR in HUVECs. Furthermore, silencing of AMPK significantly reversed the increase in autophagy, lipid peroxidation and Fe2+ induced by 3‑MCPD. In conclusion, 3‑MCPD demonstrated a significant damaging effect on HUVECs via induction of autophagy and ferroptosis; such effects may be mediated by AMPK/mTOR/ULK1 signaling. To the best of our knowledge, the present study was the first to demonstrate the mechanism of 3‑MCPD‑induced vascular endothelial cell injury and lays a molecular foundation for the prevention of 3‑MCPD‑related vascular diseases.


Congenital Syphilis: A Case Report Demonstrating Missed Opportunities for Screening and Inadequate Treatment Despite Multiple Health Care Encounters During Pregnancy.
A case of congenital syphilis due to multiple missed opportunities, highlights the challenges of treating syphilis during pregnancy. Although cases are increasing in the United States, congenital syphilis, a disease with devastating consequences, is preventable.


Growth of Hybrid Perovskite Crystals from CH3NH3PbI3-xClx Solutions Subjected to Constant Solvent Evaporation Rates.
In this work, we subjected hybrid lead-mixed halide perovskite (CH3NH3PbI3-xClx) precursor inks to different solvent evaporation rates in order to facilitate the nucleation and growth of perovskite crystals. By controlling the temperature of perovskite solutions placed within open-air rings in precise volumes, we established control over the rate of solvent evaporation and, thus, over both the growth rate and the shape of perovskite crystals. Direct utilization of diluted lead-mixed halide perovskites solutions allowed us to control the nucleation and to favor the growth of only a low number of perovskite crystals. Such crystals exhibited a clear sixfold symmetry. While crystals formed at a lower range of temperatures (40-60 °C) exhibited a more compact dendritic shape, the crystals grown at a higher temperature range (80-110 °C) displayed a fractal dendritic morphology.


Elevation of guanosine 3',5'-monophosphate level by adenosine in cerebellar slices of guinea pig.
Effect of adenosine on the level of guanosine 3',5'-monophosphate in guinea pig cerebellar slices was investigated. Adenosine increased the concentration of guanosine 3',5'-monophosphate in the slices 3--4 fold. Upon removal of adenosine from the medium, the concentration of guanosine 3',5'-monophosphate returned to the initial level. AMP, ADP or ATP also increased the guanosine 3',5'-monophosphate level to the same extent as adenosine, while adenine or other nucleosides were not effective. In the absence of Ca2+ in the incubation medium, adenosine did not increase the concentration of guanosine 3',5'-monophosphate in cerebellar slices although level of adenosine 3',5'-monophosphate was elevated by adenosine. Anticholinergic agents, adrenergic blocking agents or antihistaminics did not prevent the increase of guanosine 3',5'-monophosphate by adenosine indicating that the effect of adenosine was not mediated by the release of neurotransmitters. The combination of adenosine with depolarizing agents showed an additive effect on the level of guanosine 3',5'-monophosphate indicating that adenosine increased the level of guanosine 3',5'-monophosphate by a different mechanism from the depolarization.


An adult education: learning and understanding what young service users and carers really, really want in terms of their mental well being.
For the past decade nurse education has incorporated service user and carer perspectives into their programme and research agendas. Moving from rhetoric to the reality of embedding adult service user and carer knowledge into nurse education this paper discusses how this good practice was extended to young people under the age of 18. Globally, the mental health of young people is coming under the spotlight and based on this two "World Café" events focusing on young people and their mental well being were organised. Targeting a multi-agency audience the aim was to develop a partnership consortium, bringing together local organisations involved in promoting the mental well being of young people. This paper reports on the first World Café, led by two local young people's groups, 'Florescent Adolescent' and 'Vocal'. Following the presentations four important areas were identified (1) Inclusive rather than exclusive (2) Crystal ball gazing--young people's futures (3) A hole in the net--catching young people at the right time (4) Exposing the hidden agenda. The day resulted in three collaborative research proposals and the realisation that young people need opportunity to participate through utilising more innovative ways of engaging with the professional adult world.


Molecular analysis of the argB gene of Aspergillus nidulans.
The transcriptional organization and sequence of the Aspergillus nidulans argB gene, encoding ornithine carbamoyl transferase (OCTase; E.C. 188.8.131.52.), was determined. Transcription of the gene begins within a methionine-initiated open translation reading frame, indicating that a second methionine codon of the open reading frame is used for translation initiation. The predicted length of the OCTase precursor peptide is 359 amino acids, and it contains a highly basic amino terminus that is probably involved in mitochondrial targeting. There is extensive homology between Aspergillus OCTase and mammalian and bacterial OCTases and weaker homology between the Aspergillus polypeptide and bacterial arginine carbamoyl transferase.


A rare case of oral epithelioid sarcoma of the gingiva.
Epithelioid sarcoma (ES) is a rare malignant soft tissue tumor. ES can be classified into proximal, distal, and fibroma-like subtypes. These tumors show both mesenchymal and epithelial immunophenotypes. Microscopically, the proximal type ES is usually characterized by nodules of spindle and epithelioid cells growing in granuloma-like pattern often presenting with central necrosis. Immunohistochemically these tumors are vimentin, pancytokeratin, and usually EMA (80%) positive. CD34 (50%) and CD99 (25%) may be positive, and occasionally SMA and S-100 immunopositivity has been reported. No specific genetic alterations have been found in ES. As far as we know, this is the first case in the literature to present ES in gingival mucosa.


Decreased ATP synthesis and lower pH may lead to abnormal muscle contraction and skin sensitivity in human skin.
Sensitive skin represents hyperactive sensory symptoms showing exaggerated reactions in response to internal stimulants or external irritants. Although sensitive skin is a very common condition affecting an estimated 50% of the population, its pathophysiology remains largely elusive, particularly with regard to its metabolic aspects. The objective of our study was to investigate the pathogenesis of sensitive skin. We recruited healthy participants with 'sensitive' or 'non-sensitive' skin based on standardized questionnaires and 10% lactic acid stinging test, and obtained skin samples for microarray analysis and subsequent experiments. Microarray transcriptome profiling revealed that genes involved in muscle contraction, carbohydrate and lipid metabolism, and ion transport and balance were significantly decreased in sensitive skin. These altered genes could account for the abnormal muscle contraction, decreased ATP amount in sensitive skin. In addition, pain-related transcripts such as TRPV1, ASIC3 and CGRP were significantly up-regulated in sensitive skin, compared with non-sensitive skin. Our findings suggest that sensitive skin is closely associated with the dysfunction of muscle contraction and metabolic homeostasis.


Interpersonal influences in college students' initial use of alcohol and drugs--the role of friends, self, parents, doctors, and dealers.
The use of alcohol and drugs by 1,711 college students was surveyed anonymously, with a special interest in determining the sources of influence that led them to the initial use of different substances. Depending on the chemical, friends, parents, the person himself or herself, and doctors were named as the initial introducers. Drug dealers, by contrast, were named rarely and only in connection with a few hard drugs. Factors influencing drug use are discussed, and suggestions for prevention and treatment are made.


Laparoendoscopic single-site retroperitoneal lymph node dissection in non-seminomatous germ cell malignancy.
Umbilical laparoendoscopic single-site (LESS) surgery represents an excellent alternative to laparoscopic or robotic multiport surgery. LESS surgery offers faster recovery, less postoperative pain and optimal cosmetic results. LESS is possible in virtually any urologic surgery. We present a 38-year-old male with BMI 31.2 and with history of stage I nonseminomatous mixed germ cell tumor showing interaortocaval lymph node recurrence without elevation of tumor markers. Patient was undergone to right laparoendoscopic single-site retroperitoneal lymph node dissection (LDRP-LESS) by umbilical approach using a single-site multichannel KeyPort (Richard Wolf GmbH, Knittlingen, Germany). After the placement of the device and triangulation of the clips, we proceeded to operate on posterior parietal peritoneum. The descending colon was mobilized to access the retroperitoneum. Complete retroperitoneal lymph node dissection on the right side from iliac vessels to renal vessels, including the paracaval and interaortocaval space, was performed. The specimen was inserted into a laparoscopic bag and was removed together with multichannel system. Abdominal drainage was not employed. Surgical time was 85 min and estimated bleeding 50 cc. The patient was very satisfied with the cosmetic results and was discharged the following day without needing analgesia. The pathology report revealed metastatic seminoma in 5 of 11 lymph nodes receiving systemic chemotherapy (VP16-CDDPs) for 4 cycles with good tolerance. A year later, the patient was disease-free and had no complications. Umbilical primary LDRP-LESS, with excellent oncologic and cosmetic results, is feasible in selected cases. This approach could be considered the least invasive surgical option economically advantageous due to the reusable nature of the instruments used.


Resuscitative endovascular balloon occlusion of the aorta (REBOA) is associated with improved survival in severely injured patients: A propensity score matching analysis.
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a technique for temporary control of arterial hemorrhage. However, its effectiveness and clinical outcomes are unclear. Using a nationwide database (2004-2016) in Japan, trauma patients with survival data were identified. Patients were divided between REBOA and non-REBOA groups, and a propensity score was developed using multivariate logistic regression. Survival to discharge was compared between the groups after propensity score matching. Among 82,371 patients included in this study, 385 were treated with REBOA. After propensity score matching, 117 pairs were selected. Survival to discharge was significantly higher among patients treated with REBOA than among those treated without REBOA (53 [45.3%] vs. 38 [32.5%]; odds ratio = 1.72; 95% CI = 1.01-2.93; p = 0.04). REBOA use was associated with improved survival to discharge and should therefore be considered during the management of severely injured trauma patients.


Preparation of Mesoporous Silica by Nonionic Surfactant Micelle-Templated Gelation of Na2SiO3 and H2SiF6 and Application as a Catalyst Carrier for the Partial Oxidation of CH4.
Mesoporous silica (MSPN12) was prepared by nonionic surfactant micelle-templated gelation of sodium silicate (Na2SiO3) and fluorosilicic acid (H2SiF6) in aqueous solution, characterized by a range of instrumental techniques, and tested as a support for Ni and Rh catalysts in the partial oxidation of methane (POM). Calcined and sintered MSPN12 exhibited well-defined d00l-spacings (3.5-4.39 nm), narrow pore distributions (2.4-3.1 nm), and large specific surface areas (552-1,246 m2 g-1), and was found to be highly thermally stable. Microscopic imaging revealed that MSPN12 comprised spherical particles with a uniform diameter of ~0.7 µm, with each particle featuring firm and regular honeycomb-type pores. MSPN12-loaded Ni and Rh maintained stable POM activity at 700 °C during almost 100 h on stream, which were comparable to those for the commercial Rh(5)/Al2O3 catalyst in terms of methane conversion and H2 formation selectivity. Thus, the combination of structural stability and favorable physicochemical properties resulted in good POM performance.


Epidemiological interpretation of antibiotic resistance studies - what are we missing?
Antimicrobial resistance is an emerging public-health threat. Studies of the relationship between antibiotic use and resistance, as well as surveillance programmes, examine changes in the proportion of isolates that are resistant. Although proportions are helpful to the clinician prescribing empirical therapy, proportion-based analyses can be misleading to the public-health professional as they can yield biased estimates. Proportions do not adequately reflect the burden of resistance, a measure often of interest in public health. A more appropriate measure of this burden is the rate of isolation of resistant organisms, that is, the absolute number of resistant isolates in a population over time.


Breast Disorders in Adolescence: A Review of the Literature.
Adolescence is accompanied by a variety of changes in young breast development, which greatly affects the adolescent's psychology and socialization. PubMed, EMBASE, and the Cochrane Library were searched for studies relative to epidemiology, clinical characteristics, diagnosis, and management of all breast disorders in adolescence and their consequences. Development disorders are breast asymmetry, breast atrophy, breast hypoplasia, hypomastia, juvenile breast hypertrophy, and tuberous breast. Breast congenital abnormalities include athelia, amastia, accessory breast tissue, polymastia, polythelia, and congenital disorders of nipples. Breast infections are commonly caused from Gram-positive coccus rather than Gram-negative bacteria. Breast abscess occurs when breast infections are not promptly treated. Nipple discharge is caused by a variety of conditions and should be managed carefully. Fibrocystic changes, cysts, and fibroadenomas are the most common benign masses in adolescence. Primary, secondary, or metastatic breast cancer is extremely rare in adolescence. However, clinicians should include breast cancer in the differential diagnosis of a breast mass in adolescence. Clinicians should be aware of all breast disorders that may occur in adolescence. Early diagnosis and treatment will result in the reassurance of adolescents and their families without any detrimental effect on their psychology, sexual behavior, and socialization. Adolescents with breast disorders may require a multidisciplinary approach by a pediatrician, a gynecologist specializing in pediatric-adolescent gynecology, a plastic surgeon, and a psychologist for the best management of breast disorders.


Application of DNA condensation for removal of mercury ions from aqueous solutions.
DNA has a unique character that allows it to combine with various chemical substrates at the molecular level, and the DNA binding with chemical pollutants can cause serious damage to the organism. The purpose of this research was to apply the strong bonding character of DNA for the removal of mercury ions. In this research, we used DNA condensation promoted by the action of DNA condensing agents, such as cetyltrimethylammonium bromide and a commercially available combination flocculant made of zeolite, to precipitate out the DNA bound with mercury ion in an aqueous solution. When solutions of mercury at 0.02-100 ppm (parts per million) concentrations at a pH range of 2-11 were treated with double-stranded DNA followed by the condensing agent, more than 95% of the mercury ions could be removed after simple filtration or sedimentation.


The effect of lower limb muscle fatigue on obstacle negotiation during walking in older adults.
Tripping over obstacles is a common cause of falls in older adults, and muscle fatigue, which can alter walking patterns, may add to this risk. To date, no study has examined the effect of lower limb muscle fatigue on obstacle negotiation in older adults. 30 older adults (13 women, aged 78.3 [6.2] years) negotiated a 12 m obstacle course, while completing a visual secondary task, under two randomized conditions: rested or fatigued. For the fatigue condition, participants performed a repeated sit-to-stand movement, as fast as possible, until they could no longer continue. Participants then immediately began walking trials. Kinematic and kinetic data were collected on approach to, during, and after crossing a height-adjustable target obstacle (10% and 20% of leg length). Repeated measures ANOVA showed a statistically significant increase in lead limb vertical loading rate after stepping over the 10% obstacle when fatigued, relative to rested (P=0.046). No other significant between-condition differences (>0.05) were observed for the other kinematic variables when negotiating the 10% obstacle. Furthermore, no significant between-condition differences (P>0.05) were observed for any kinetic or kinematic variables when negotiating the 20% obstacle. This study describes a feasible method for investigating the consequences of lower limb muscle fatigue on obstacle crossing. The current finding of increased vertical loading rate when fatigued supports the need for further investigation into the effect of muscle fatigue on gait under different environmental conditions, fatiguing a range of muscles, analyzing a more comprehensive array of kinetic and kinematic measures, and in healthy and clinical populations.


Reaction Kinetics of Green Leaf Volatiles with Sulfate, Hydroxyl, and Nitrate Radicals in Tropospheric Aqueous Phase.
Green plants exposed to abiotic or biotic stress release C-5 and C-6 unsaturated oxygenated hydrocarbons called Green Leaf Volatiles (GLVs). GLVs partition into tropospheric waters and react to form secondary organic aerosol (SOA). We explored the kinetics of aqueous-phase reactions of 1-penten-3-ol (PENTOL), (Z)-2-hexen-1-ol (HEXOL), and (E)-2-hexen-1-al (HEXAL) with SO4•-, •OH, and NO3•. At 298 K, the rate constants for reactions of PENTOL, HEXOL, and HEXAL with SO4•- were, respectively, (9.4 ± 1.0) × 108 L mol-1 s-1, (2.5 ± 0.3) × 109 L mol-1 s-1, and (4.8 ± 0.2) × 108 L mol-1 s-1; with •OH - (6.3 ± 0.1) × 109 L mol-1 s-1, (6.7 ± 0.3) × 109 L mol-1 s-1, and (4.8 ± 0.3) × 109 L mol-1 s-1; and with NO3• - (1.5 ± 0.15) × 108 L mol-1 s-1, (8.4 ± 2.3) × 108 L mol-1 s-1, and (3.0 ± 0.7) × 107 L mol-1 s-1. The rate constants increased weakly with temperatures ranging from 278 to 318 K. The diffusional limitations of the rate constants appeared significant only for the GLV-•OH reactions. The aqueous-phase reactions appeared negligible in deliquescent aerosol and haze water but not in clouds and rains. The atmospheric lifetimes of GLVs decreased from many days to hours with increasing liquid water content and radicals' concentration.


Production of 5-hydroxymethylfurfural from corn stalk catalyzed by corn stalk-derived carbonaceous solid acid catalyst.
A carbonaceous solid acid was prepared by hydrothermal carbonization of corn stalk followed by sulfonation and was characterized by FT-IR, XRD, SEM and elemental analysis techniques. The as-prepared corn stalk-derived carbonaceous solid acid catalyst contained SO3H, COOH, and phenolic OH groups, and was used for the one-step conversion of intact corn stalk to 5-hydroxymethylfurfural (5-HMF) in the ionic liquid 1-butyl-3-methyl imidazolium chloride ([BMIM][Cl]), where a 5-HMF yield of 44.1% was achieved at 150 °C in 30 min reaction time. The catalytic system was applicable to initial corn stalk concentration of up to ca. 10 wt.% for the production of 5-HMF. The synthesized catalyst and the developed process of using corn stalk-derived carbon catalyst for corn stalk conversion provide a green and efficient strategy for crude biomass utilization.


Alcohol abuse in elderly emergency department patients.
To determine the prevalence of alcohol abuse in elderly emergency department (ED) patients; to determine the prevalence of alcohol abuse for various categories of illness and injury among these patients; and to determine the frequency of detection of elderly alcohol abusers by ED physicians. Cross-sectional prevalence study. The emergency department of a 625-bed university hospital that serves a mixed urban and rural population. 205 patients aged 65 and over who came to the ED during an 8-week period. A structured interview, which included the CAGE questionnaire and other questions regarding alcohol use, was administered. Emergency department records and past medical records were reviewed. The prevalence of lifetime alcohol abuse (CAGE positive or self-reported drinking problem) was 24%. The prevalence of current alcohol abuse (CAGE positive or self-reported drinking problem and alcohol use within the last year) was 14%. There was a particularly high prevalence (22%) among those presenting with gastrointestinal problems and a surprisingly low prevalence (7%) among those who presented with falls or other trauma. Physicians detected only 21% of the current alcohol abusers. Alcohol abuse is a prevalent and important problem among elderly ED patients. It is not well detected by physicians in this setting. Alcohol abuse appears to be less common among elderly trauma patients than their younger counterparts, but is very common among patients with gastrointestinal problems.


How Prior Knowledge Affects Word Identification and Comprehension.
While prior knowledge of a passage topic is known to facilitate comprehension, little is known about how it affects word identification. We examined oral reading errors in good and poor readers when reading a passage where they either had prior knowledge of the passage topic or did not. Children who had prior knowledge of the topic were matched on decoding skill to children who did not know the topic so that the groups differed only on knowledge of the passage topic. Prior knowledge of the passage topic was found to significantly increase fluency and reduce reading errors, especially errors based on graphic information, in poor readers. Two possible mechanisms of how prior knowledge might operate to facilitate word identification were evaluated using the pattern of error types, as was the relationship of errors to comprehension. Implications of knowledge effects for assessment and educational policy are discussed.


The effect of hyperthyroidism on procoagulant, anticoagulant and fibrinolytic factors: a systematic review and meta-analysis.
Several coagulation and fibrinolytic parameters appear to be affected by thyroid hormone excess; however, the net effect on the haemostatic system remains unclear. We aimed to update our previous review and systematically summarise and meta-analyse the data by assessing the effects of thyrotoxicosis on the coagulation and fibrinolytic system in vivo . Data sources included MEDLINE (2006-2012), EMBASE (2006-2012), and reference lists. The sources were combined with our previous search containing studies from 1980-2006. Eligible studies were all observational or experimental studies. Two investigators independently extracted data and rated study quality. Weighted mean proportion and 95% confidence intervals were calculated and pooled using a fixed and a random-effects model. A total of 29 articles consisting of 51 studies were included, as in several articles more than one study was described. We included four intervention (before and after treatment in hyperthyroid patients), five cross-sectional (hyperthyroid subjects and euthyroid controls), and four experimental (before and after use of thyroid hormone in euthyroid subjects) medium/high quality studies for meta-analysis. We found that thyrotoxicosis shifts the haemostatic balance towards a hypercoagulable and hypofibrinolytic state with a rise in factors VIII and IX, fibrinogen, von Willebrand factor, and plasminogen activator inhibitor-1. This was observed in endogenous and exogenous thyrotoxicosis, and in subclinical as well as overt hyperthyroidism. We conclude that both subclinical and overt hyperthyroidism induce a prothrombotic state, which is therefore likely to be a risk factor for venous thrombosis.


Identification of a widespread monomolecular odor differentially attractive to several Delia radicum ground-dwelling predators in the field.
Dimethyl disulfide (DMDS) was identified as a major volatile constituent of Brassica napus roots heavily infested by Delia radicum, the cabbage root fly. Attractiveness of this widespread compound was tested in the field in a naturally complex odorous environment. By using an original setup especially designed for ground dwelling beetles, different concentrations of the pure molecule as well as attractiveness of the natural blend emitted by the rotten part of infested roots were tested simultaneously. The use of general linear model (GLM) statistics permitted us to finely discriminate the responses among the different treatments. The main predators of D. radicum (i.e., two staphylinids Aleochara bilineata and Aleochara bipustulata and carabid beetles of the genus Bembidion) were significantly attracted by DMDS, but responded in different ways to the natural blend and to the different concentrations tested. The dose-response curves were similar for the two staphylinids. However, whereas A. bilineata was more attracted by the natural volatile blend than by its preferred DMDS concentration, A. bipustulata was attracted as much by the natural blend as by its preferred DMDS concentration. Carabid beetles exhibited a different response. They were not attracted by the natural blend, but responded to a wider range of DMDS concentrations that included low concentrations that did not attract the staphylinid beetles. These results are discussed according to the potential resources searched by each taxon studied and their specificity for the resources. The possible use of DMDS for enhancing biological control of D. radicum is mentioned.


[Parietal dissemination of carcinoma of the gallbladder after celioscopic surgery].
A case of tumor seeding in an abdominal trocar hole after laparoscopic extraction of an incidental gallbladder carcinoma is reported. The high incidence of occult tumors of the gallbladder and appendix warrants caution when dissecting and extracting operative specimens.


Screening of compound library identifies novel inhibitors against the MurA enzyme of Escherichia coli.
Bacterial cell has always been an attractive target for anti-infective drug discovery. MurA (UDP-N-acetylglucosamine enolpyruvyl transferase) enzyme of Escherichia coli (E.coli) is crucial for peptidoglycan biosynthetic pathway, as it is involved in the early stages of bacterial cell wall biosynthesis. In the present study we aim to identify novel chemical structures targeting the MurA enzyme. For screening purpose, we used in silico approach (pharmacophore based strategy) for 52,026 library compounds (Chembridge, Chemdiv and in house synthetics) which resulted in identification of 50 compounds. These compounds were screened in vitro against MurA enzyme and release of inorganic phosphate (Pi) was estimated. Two compounds (IN00152 and IN00156) were found to inhibit MurA enzyme > 70% in primary screening and IC50 of 14.03 to 32.30 μM respectively. These two hits were further evaluated for their mode of inhibition studies and whole-cell activity where we observed 2-4 folds increase in activity in presence of Permeabilizer EDTA (Ethylenediaminetetraacetic acid). Combination studies were also performed with known antibiotics in presence of EDTA. Hits are reported for the first time against this target and our report also support the use of OM permeabilizer in combination with antibacterial compounds to address the permeability and efficacy issue. These lead hits can be further optimized for drug discovery. KEY POINTS: • Emerging Gram negative resistant strains is a matter of concern. • Need for new screening strategies to cope with drying up antibiotics pipeline. • Outer membrane permeabilizers could be useful to improve potency of molecules to reach its target.


Sociodemographic profile and description of the presenting symptom in women with breast cancer in a population-based study: Implications and role for nurses.
To describe the frequency and typology of the presenting symptom of women diagnosed of breast cancer in Spain and their socio-demographic profile. Descriptive study nested in a population epidemiological study (MCC-SPAIN) in 10 Spanish provinces. Between 2008 and 2012, 836 histologically confirmed incident cases of breast cancer were recruited who reported some symptom prior to diagnosis in a direct computerized interview. For the comparison of 2 discrete variables, the Pearson Chi square test was used. The most frequent presenting symptom among women who reported at least one symptom was noticing a "lump in the breast" (73%), followed far behind by noticing "changes in the breast" (11%). Geographic heterogeneity was observed in the frequency of the presenting symptom, as well as with menopausal status. No association was observed between the type of presenting symptom and the rest of the sociodemographic variables explored, except for the educational level in which women with a higher educational level tended to proportionally report other symptoms different from the "lump in the breast" more frequently than less educated. Postmenopausal women reported noticing changes in the breast (13%) more frequently than premenopausal women (8%), although without reaching statistical significance (P = .056). The most frequent presenting symptom is "breast lump", followed by "breast changes". There could be sociodemographic heterogeneity in the type of presenting symptom to be taken into account by nurses in their socio-sanitary interventions.


Atypical presentation of a locally advanced hepatocellular carcinoma: Extensive workup of an incidental finding on computed tomography performed for planning of transcatheter aortic valve implantation.
This case report presents the diagnostic workup of liver malignancy incidentally detected in a 72-year-old male patient on routine body computed tomography angiography (CTA) performed for planning transcatheter aortic valve implantation (TAVI). The patient initially presented to an outside hospital with chest discomfort, where routine diagnostic procedures in the emergency room revealed grade III aortic valve stenosis. Routine CTA for TAVI planning in our department then revealed tumor thrombosis of the portal vein suspicious for hepatic malignancy. In contrast-enhanced ultrasound (CEUS) only the left hepatic lobe was inhomogeneously transformed with early arterial contrast enhancement. Magnetic resonance imaging (MRI) confirmed a primary hepatic malignancy involving the left liver. Transcutaneous biopsy with ultrasound guidance established the diagnosis of hepatocellular carcinoma (HCC). Incidental findings may be of prognostic relevance for the patient and in a number of cases, TAVI can be a prerequisite for the appropriate therapy.


Serum fructosamine and risk of cardiovascular and all-cause mortality: a 24-year prospective population-based study.
The association between fructosamine and cardiovascular complications is not well established. We sought to evaluate whether serum fructosamine may be a risk factor for cardiovascular and all-cause mortality in nondiabetic subjects. Fructosamine and other cardiovascular risk factors were measured in a sample of 1909 nondiabetic middle-aged men without a known history of coronary heart disease (CHD) at baseline. Associations between baseline fructosamine levels and fatal CHD and cardiovascular disease (CVD) events, and all-cause mortality were estimated using a Cox regression analysis, progressively adjusted for potential confounders. Mean baseline age was 52 years and 30% were smokers. During a median follow-up of 24 years (interquartile range: 18-26 years), 177 (9%) fatal CHD, 289 (15%) fatal CVD, and 728 (38%) all-cause mortality events occurred. In analyses adjusted for several conventional risk factors (i.e., age, systolic blood pressure, smoking, LDL- and HDL-cholesterol), the hazard ratios (HRs) comparing top vs bottom quartile of serum fructosamine levels resulted: 1.33 (95% CI: 0.97, 1.82; p = 0.078) for CHD death and 0.93 (0.72, 1.19; p = 0.567) for CVD death, and 1.04 (0.89, 1.22; p = 0.617) for all-cause mortality. In similar comparisons, further adjustments for body mass index, alcohol consumption, C-reactive protein, and fasting plasma glucose did not materially change these estimates. The exclusion of participants with prevalent CVD at baseline yielded similar results. In our cohort of nondiabetic men without known CHD, baseline fructosamine levels were not independently associated with cardiovascular and all-cause mortality. Further studies are warranted to confirm these results in other populations.


Enantioselective phospha-Michael addition of diarylphosphines to β,γ-unsaturated α-ketoesters and amides.
An enantioselective hydrophosphination of β,γ-unsaturated α-ketoesters and amides has been developed using a chiral palladacycle catalyst. Adducts can be obtained in excellent yields and enantioselectivities, providing direct access to chiral tertiary phosphines which are synthetically useful intermediates in the preparation of bidentate ligands.


Release of arachidonic acid metabolites from isolated human alveolar type II cells.
Human alveolar type II cells are thought to play a role in the pathogenesis of lung injury. Patterns of mediator release of arachidonic acid metabolism by type II cells were therefore studied after challenge with calcium ionophore A23187, opsonized zymosan and hydrogen peroxide. A time- and concentration dependent release of cyclooxygenase products was observed, with release of PGE2 greater than 6-keto-PGF1 alpha greater than TxB2. Addition of glutathione or bicarbonate further increased the production of PGE2. N-ethylmaleimide, a sulfhydryl (SH) reactant, induced a dose-dependent increase in the release of TxB2 and 6-keto-PGF1 alpha, but not of PGE2. This relates most likely to the SH-dependency and glutathione requirement of the PGE2 isomerase and SH-independence of thromboxane and prostacyclin isomerase.


Epidemiology of hypertension in African American women.
To describe the epidemiology of hypertension in U.S. African American women and to highlight priority areas for future research, data from the nationwide surveys of the U.S. National Center for Health Statistics, from selected multicenter studies of the U.S. National Heart, Lung, and Blood Institute, as well as from selected other population-based studies, were reviewed. In 1988 through 1991, an estimated 3 million African American women aged 18 and older had hypertension. Compared with that in U.S. whites, hypertension in black women is characterized by higher incidence, earlier onset, longer duration, higher prevalence, and higher rates of hypertension-related mortality and morbidity. Risk factors for hypertension incidence in black women include obesity and weight gain. The effectiveness of drug therapy of hypertension has been established in black women, and important gains in rates of treatment and control have been accomplished. Nevertheless, rates of hypertension-related mortality for black women remain among the highest in the industrialized nations. Further research on causes and prevention of hypertension in black women is needed. Goals related to prevention and control of hypertension in African Americans for the year 2000 have been established and must be vigorously pursued.


5,6,7-Trichloro-2-meth-oxy-8-hy-droxy-quinoline.
In the title compound, C(10)H(6)Cl(3)NO(2), a mean plane fitted through all non-H atoms has an r.m.s. deviation of 0.035 Å. In the crystal, adjacent mol-ecules are connected by O-H⋯O hydrogen bonds and π-π stacking inter-actions [centroid-centroid distance = 3.650 (1) Å], resulting in an infinite chain which propagates in the b-axis direction.


RETRACTED: Oral dydrogesterone treatment during early pregnancy to prevent recurrent pregnancy loss and its role in modulation of cytokine production: a double-blind, randomized, parallel, placebo-controlled trial.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the ASRM Publications Committee. The Committee reviewed concerns related to the accuracy of data reported in Table 2 and the authors acknowledged significant errors that could not be corrected because they were unable to provide the original data. As the Committee cannot vouch for the accuracy of the data, we have issued a retraction of this article.


Disseminated lipogranulomas and sudden death from self-administered mineral oil injection.
The cosmetic injection of exogenous lipids and more recently of polydimethyl siloxane (injectable silicone) into the scrotum has been described since 1899. Sclerosing lipogranuloma and paraffinoma are terms applied to a complication of this practice in which the injected oils or silicone elicit a marked granulomatous reaction with prominent surrounding fibrosis. Although this complication has been described as a localized process occurring mainly in the scrotal area and regional lymph nodes, few studies have documented systemic manifestations. In this report we describe the autopsy findings of a 48-year-old man who had scrotal and systemic lipogranulomas from repeated self-administered injection of mineral oil. In addition, severe acute pulmonary edema resulted in sudden unexpected death. To our knowledge, this fatal complication of exogenous lipogranuloma has not been previously reported.


Glyburide-induced acute haemolysis in a G6PD-deficient patient with NIDDM.
In a 61-year-old man with glucose-6-phosphate dehydrogenase (G6PD) deficiency and poorly controlled non-insulin-dependent diabetes mellitus, an episode of acute haemolysis occurred after the administration of glyburide (glibenclamide). Erythrocyte fragmentation, with haemoglobin condensation zones next to clear zones, was observed on peripheral blood smears. Since autoimmune haemolysis was excluded on the basis of laboratory data, acute haemolysis was ascribed to G6PD deficiency.


Interruption of the aortic arch with complete transposition of the great arteries. Clinical and angiocardiographic diagnosis at the age of one day.
The association of complete transportation of the great arteries and complete interruption of the aortic arch is very rare. This combined lesion was diagnosed clinically in a 1-day-old infant in whom it caused cyanosis of the upper half of the body. The diagnosis was confirmed angiocardiographically. We believe this is the youngest patient in whom this diagnosis was made in vivo.


Rapid modulation of lipogenesis by clofibrate in rat and monkey hepatocytes.
Previous studies have proposed various possible mechanisms for the hypolipidemic actions of clofibrate. In the present study, isolated liver cells freshly prepared from rats and squirrel monkeys were used to investigate the acute effects of sodium clofibrate (sodium chlorophenoxyisobutyrate) on hepatic lipogenesis. Incubation of liver cells with levels of the drug (1 mM) known to lower plasma lipid level in vivo produced a rapid inhibition of [14C]acetate incorporation into cellular lipids. The degree of inhibition caused by the drug was not diminished by preincubation with an excess of unlabeled acetate. Conversion of [14C]acetate to 14CO2 was not significantly altered by sodium clofibrate at 1--3 mM levels, but was decreased at 5--10 mM levels. Incorporation of [14C]acetate into all lipid classes was suppressed by this agent, but inhibition of sterol synthesis was more pronounced than that of fatty acids. Sodium clofibrate (1 mM) reduced the synthesis of sterols from either labeled acetate or labeled mevalonate to a similar degree, but the decline was augmented in each case by a 30-min preincubation of the cells with sodium clofibrate. Addition of fatty acids to cell incubations stimulated sterol generation from [14C] acetate or from [3H] mevalonate, but did not reverse the inhibitory effects of the drug. These results suggest (a) the sodium clofibrate rapidly interferes with hepatic fatty acid and sterol synthesis by direct or indirect actions at diverse loci; (b) that these effects probably occur after acetyl-CoA formation and do not stem from precursor pool dilution; (c) that sodium clofibrate diminishes sterol production at post-mevalonic and perhaps also at pre-mevalonic sites; (d) that a similar pattern of inhibition occurs with sodium clofibrate in the presence of added fatty acids; and (e) that rat and primate livers demonstrate similar metabolic responses to the drug.


N-terminal pro B-type natriuretic peptide in the early evaluation of suspected acute myocardial infarction.
Myocardial ischemia is a strong trigger of N-terminal pro-B-type natriuretic peptide (NT-proBNP) release. As ischemia precedes necrosis in acute myocardial infarction, we hypothesized that NT-proBNP might be useful in the early diagnosis and risk stratification of patients with suspected acute myocardial infarction. In a prospective multicenter study, NT-proBNP was measured at presentation in 658 consecutive patients with acute chest pain. The final diagnosis was adjudicated by 2 independent cardiologists. Patients were followed long term regarding mortality. Acute myocardial infarction was the adjudicated final diagnosis in 117 patients (18%). NT-proBNP levels at presentation were significantly higher in acute myocardial infarction as compared with patients with other final diagnoses (median 886 pg/mL vs 135 pg/mL, P <.001). The diagnostic accuracy of NT-proBNP for acute myocardial infarction as quantified by the area under the receiver operating characteristic curve (AUC) was 0.79 (95% confidence interval [CI], 0.75-0.83). When added to cardiac troponin T, NT-proBNP significantly increased the AUC from 0.89 (95% CI, 0.84-0.93) to 0.91 (95% CI, 0.88-0.94; P=.033). Cumulative 24-month mortality rates were 0% in the first, 1.3% in the second, 8.3% in the third, and 23.3% in the fourth quartile of NT-proBNP (P <.001). NT-proBNP (AUC 0.85, 95% CI, 0.81-0.89) predicted all-cause mortality independently of and more accurately than both cardiac troponin T (AUC 0.66, 95% CI, 0.58-0.74; P <.001) and the Thrombolysis in Myocardial Infarction risk score (AUC 0.79, 95% CI, 0.74-0.84; P <.001). Net reclassification improvement (Thrombolysis in Myocardial Infarction vs additionally NT-proBNP) was 0.188 (P <.009), and integrated discrimination improvement was 0.100 (P <.001). Use of NT-proBNP improves the early diagnosis and risk stratification of patients with suspected acute myocardial infarction.


Detection of leukemic cell colonies in agar plates by immunostaining for human malignancy-associated nucleolar antigen.
We have developed an indirect immunofluorescence technique to stain individual colonies in situ in agar to detect the presence of a human malignancy-associated nucleolar antigen. Bone marrow and peripheral blood cells from leukemia patients who were untreated or suffering relapse were used as a source for colony formation. The agar layer containing the colonies was stabilized by overlaying it with an additional agar layer. Cells in the colonies were fixed with methanol, rehydrated, and incubated for prolonged periods in both the primary and the secondary antibodies. The agar was then transferred onto a glass slide, air dried, and examined using a fluorescence microscope. The method is widely applicable for staining colonies in situ in agar with both polyclonal and monoclonal antibodies.


Co-oxygenation of organic substrates by the prostaglandin synthetase of sheep vesicular gland.
The microsomal fraction of sheep vesicular glands has been found to oxygenate 1,3-diphenylisobenzofuran, luminol, and the carcinogenic hydrocarbon benzopyrene when incubated with arachidonic acid. The oxygenations demonstrate an absolute dependence on enzyme and fatty acid and can be completely inhibited by indomethacin and 2,3-dimercaproptopanol, inhibitors of prostaglandin synthetase. The oxygenations can also be stimulated by the hydroperoxy endoperoxide, prostaglandin G2, and 15-hydroperoxy-5,8,11,13-eicosatetraenoic acid. These latter reactions are not inhibited by indomethacin or dimercaptopropanol but do require the microsomal enzyme system. The involvement of superoxide anion in the transformations could not be demonstrated. The oxygenations occurring in the presence of arachidonic acid appear to arise via the interaction of a microsomal enzyme system with hydroperoxide intermediates of prostaglandin biosynthesis. The ability of various sulfur reagents (reduced glutathione, alpha-lipoic acid, methional) to inhibit co-oxygenation is probably related to their ability to stimulate the conversion of the intermediate to prostaglandins.


Micro-computed tomography of sandstone rocks: Raw, filtered and segmented datasets.
High-resolution computed micro-tomography is an important area of science, which correlates well with several experimental methodologies and serves as a basis for advanced computational physics studies, in which high-resolution images are used as input to different scientific simulation models. The dataset presented herein includes (raw) grayscale images obtained using the Bruker Skyscan 1272 X-Ray tomograph; filtered images acquired through contrast enhancement and noise reduction filters; and segmented images obtained by using the IsoData segmentation method. All images have a resolution of 2.25 µm (isometric voxels) and size of 10003 voxels.


Impact of the use of autologous stem cell transplantation at first relapse both in naive and previously rituximab exposed follicular lymphoma patients treated in the GELA/GOELAMS FL2000 study.
We analyzed detailed characteristics and salvage treatment in 175 follicular lymphoma patients from the FL2000 study who were in progression after first-line therapy with or without addition of rituximab to chemotherapy and interferon. The impact of using autologous stem cell transplantation and/or rituximab administration at first progression was investigated, taking into account initial therapy. With a median follow up of 31 months, 3-year event free and overall survival rates after progression were 50% (95%CI 42-58%) and 72% (95%CI 64-78%), respectively. The 3-year event free rate of rituximab re-treated patients (n=112) was 52% (95%CI 41-62%) versus 40% (95%CI 24-55%) for those not receiving rituximab second line (n=53) (P=0.075). There was a significant difference in 3-year overall survival between patients receiving autologous stem cell transplantation and those not: 92% (95%CI 78-97%) versus 63% (95%CI 51-72%) (P=0.0003), respectively. In multivariate analysis, both autologous stem cell transplantation and period of progression/relapse affected event free and overall survival. Regardless of front-line rituximab exposure, this study supports incorporating autologous stem cell transplantation in the therapeutic approach at first relapse for follicular lymphoma patients.


Incidence of magnet mode in patients with implantable cardioverter defibrillators.
To determine the current incidence of antitachycardia therapy suspension due to magnet reversion in patients with implantable cardioverter defibrillators (ICDs). From March 2012 to September 2018, all St. Jude Medical ICD interrogations performed at the Deutsches Herzzentrum München were screened for stored events of antitachycardia therapy suspension caused by static magnetic fields (flux densities ≥ 1 mT as defined in St. Jude Medical ICDs) affecting the giant magnetoresistance (GMR) sensor. Intentional ICD deactivation or inappropriate magnet application in the hospital was classified as non-environmental electromagnetic interference (EMI) whereas in the case of any other stored magnet reversion, the event was classified as presumably environmental EMI. Data from 201 St. Jude Medical ICD patients (mean age 62 ± 24 years, 165 males/36 females) were included in the analysis. ICD interrogations occurred at a mean follow-up of 25.1 months ± 15.6 months and summed up to a total of 464 patient-years of follow-up. A total number of 43 magnet reversion events were detected in 21 patients. Thirty-two events in 13 patients were presumably related to environmental EMI sources. Suspension of antitachycardia therapy only occurred in a temporary fashion. None of the patients experienced any ventricular tachyarrhythmia during ICD inhibition. The incidence of antitachycardia therapy suspension due to magnet reversion related to presumably environmental EMI sources was 6.9% per patient and year. Although none of the patients experienced any harmful event, antitachycardia therapy suspension due to magnet reversion is a common issue. Patients should be well-educated about potential EMI sources as well as trained in handling them.


Astragaloside IV ameliorates diet-induced hepatic steatosis in obese mice by inhibiting intestinal FXR via intestinal flora remodeling.
Nonalcoholic fatty liver disease (NAFLD) is a major clinical and public health burden worldwide with no established pharmacological therapy. Changes in the intestinal flora and associated metabolite bile acids (BAs) have been described in NAFLD. Astragaloside IV (AS-IV) is a low drug permeability saponin with protective effects against multiple diseases. However, the specific mechanism underlying the involvement of AS-IV in the regulation of NAFLD is yet to be clarified. This study aimed to investigate the effect of AS-IV on NAFLD and explore whether intestinal flora was involved. The effect of AS-IV was evaluated on high-fat diet-fed mice. Real-time PCR, immunohistochemistry, immunofluorescence, and biochemical analyses were performed. 16S rRNA gene sequencing and UPLC-TQMS were used to determine the alterations in the intestinal flora and concentration of BAs. Fecal microbiota transplantation (FMT) and intestine-specific farnesoid X receptor (FXR) knockout were also performed. AS-IV treatment alleviated diet-induced metabolic impairments, particularly hepatic steatosis. These changes occurred in the setting of decreased intestinal bile salt hydrolase (BSH)-expressing flora. Further analysis showed that the reduced BSH activity increased intestinal tauro-β-muricholic acid levels, an inhibitor of intestinal FXR. Inhibition of intestinal FXR signaling by AS-IV was accompanied by decreased expression of intestinal fibroblast growth factor 15 and subsequent hepatic FXR activation as well as increased glucagon-like peptide-1 and decreased ceramide production, all of which contribute to the inhibition of sterol regulatory element-binding protein-1c-mediated hepatic steatosis. Furthermore, intestine-specific Fxr knockout and FMT further demonstrated an FXR- and intestinal flora-dependent preventive effect of AS-IV on hepatic steatosis. These results show that the changes in intestinal flora and BAs serve an essential role in the remission of hepatic steatosis by AS-IV, thereby suggesting that AS-IV may be used as a prebiotic agent to provide viable treatment for NAFLD.


Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus.
Patients with primary hyperparathyroidism have impaired glucose tolerance more often than do controls, and parathyroid resection sometimes improves this derangement. However, it is unclear whether serum calcium (Ca) or parathyroid hormone (PTH) is more strongly related to impaired glucose metabolism in subjects without primary hyperparathyroidism. In this cross-sectional study, we examined patients with type 2 diabetes mellitus (DM) (271 men and 209 women) and analyzed the relationships between serum concentrations of Ca or intact PTH and DM-related variables. Simple regression analyses showed that the level of serum Ca was significantly and positively correlated with the levels of fasting plasma glucose, immunoreactive insulin, and homeostasis model assessment insulin resistance in men (P < .05), but not in women. In contrast, intact PTH was not significantly correlated with DM-related parameters in either sex. Multiple regression analyses showed that the significant and positive correlations between serum Ca vs fasting plasma glucose and homeostasis model assessment insulin resistance in men still remained after adjustment for intact PTH as well as age, body weight, height, creatinine, albumin, phosphate, bone metabolic markers, and estradiol (P < .05). Serum Ca level is positively associated with impaired glucose metabolism, independent of PTH or bone metabolism, in men with type 2 DM.


Influences of laryngeal afferent inputs on intralaryngeal muscle activity during vocalization in the cat.
The present study was undertaken to elucidate the possible role of the laryngeal afferent inputs in the regulation of intralaryngeal muscle activity during vocalization. We studied the influences of airflow and/or pressure applied to the larynx on intralaryngeal muscle activity during vocalization in ketamine-anesthetized cats. Vocalization was induced by airflow applied to the upper airway, which was isolated from the lower airway, during pontine call site stimulation. When the upper airway was open to the atmosphere through the nostrils and mouth, the airflow increased not only the vocal fold adductor and tensor activities but also the duration of these activities. The adductor and tensor activities were increased suddenly at a critical subglottic pressure level equivalent to the subglottic pressure threshold for vocalization. These effects were significantly reduced by sectioning of the internal branch of the superior laryngeal nerve or by lidocaine application to the laryngeal mucosa. Sustained pressure applied to the isolated upper airway, when the mouth and nostrils were occluded, did not affect adductor or tensor activities. These results indicate that the afferent inputs evoked by vocal fold stretching or vibration play an important role in the motor control of intralaryngeal and respiratory muscles during vocalization.


MicroRNA-30a functions as tumor suppressor and inhibits the proliferation and invasion of prostate cancer cells by down-regulation of SIX1.
Increasing reports have demonstrated that aberrant expression of microRNAs (miRNAs) is found in multiple human cancers. Many studies have shown that down-regulated level of miR-30a is in a variety of cancers including prostate cancer (PCa). However, the precise mechanisms of miR-30a in PCa have not been well explored. In this study, we investigated the biological functions and molecular mechanism of miR-30a in PCa cell lines, discussing whether it could be a therapeutic biomarker of PCa in the future. We found that miR-30a is down-regulated in PCa tissues and cell lines. Moreover, the low level of miR-30a was associated with increased expression of SIX1 in PCa tissues and cell lines. Up-regulation of miR-30a significantly inhibited proliferation of PCa cells. In addition, invasion of PCa cells was suppressed by overexpression of miR-30a. However, down-regulation of miR-30a promoted cell growth and invasion of PCa cells. Bioinformatics analysis predicted that the SIX1 was a potential target gene of miR-30a. Next, luciferase reporter assay confirmed that miR-30a could directly target SIX1. Consistent with the effect of miR-30a, down-regulation of SIX1 by siRNA inhibited proliferation and invasion of PCa cells. Overexpression of SIX1 in PCa cells partially reversed the effect of miR-30a mimic. In conclusion, introduction of miR-30a dramatically inhibited proliferation and invasion of PCa cells by down-regulating SIX1 expression, and that down-regulation of SIX1 was essential for inhibition of cell growth and invasion of PCa cells by overexpression of miR-30a.


Inhaled Nitric Oxide and Higher Necrotizing Enterocolitis Rates in Congenital Heart Disease Patients.
Certain congenital cardiac lesions are at increased risk for the development of necrotizing enterocolitis (NEC). These patients are often reliant on pulmonary and systemic vasomodulators to maintain adequate perfusion and oxygenation. This study sought to determine whether pulmonary or systemic vasodilator treatment is protective against the development of NEC in this population. We utilized International Classification of Diseases (ICD) codes to identify high risk congenital cardiac disease patients ≤6 mo of age, cared for at a tertiary children's hospital between January 2011 and January 2021. Cardiac anomalies were stratified into ductal dependent (pulmonary DD-P or systemic DD-S) or independent lesions. The rate of NEC development in those who received vasodilators (inhaled nitric oxide [iNO], pulmonary vasodilators, systemic vasodilators) was compared to controls in a multivariate analysis. Of the 352 patients, who met inclusion criteria, 77.6% had ductal dependent lesions (DD-S 41.9%, DD-P 35.7%), 19.5% received iNO, and 37.5% received other vasodilatory drugs. The overall NEC rate was 15.1%. On univariate analysis, DD-S, iNO use, and systemic vasodilators was associated with a significantly higher risk of NEC, while DD-P was associated with lower NEC risk. On multivariate analysis, only iNO (odds ratio 2.725, confidence interval [1.36-5.44]) and DD-S (odds ratio 2.279, confidence interval [1.02-5.11]) were independent risk factors for NEC. In patients with at-risk congenital cardiac disease lesions, a ductus dependent systemic circulation or iNO treatment is associated with an increased risk of developing NEC. The presence of iNO or DD-S should be utilized as markers of increased risk both in the prevention and workup of suspected NEC.