Cobalamin dependent methionine synthesis and methyl-folate-trap in human vitamin B12 deficiency.
The activity of methionine synthetase (MS) is important for the rapid growth of human haematopoietic cells and cultured lymphoblastoid cells. The MS reaction is the only known metabolic step in which both vitamin B12 and folate are essential in a single enzyme reaction. In vitamin B12 deficiency the MS activity in bone marrow cells is significantly lower than that in normal bone marrow. Free tetrahydrofolic acid (H4PteGlu) is normally liberated from its metabolically inactive storage form, 5-methyl-H4PteGlu (CH3H4PteGlu), in the cobalamin-dependent MS reaction. Thus, in vitamin B12 deficiency H4PteGlu is not available in sufficient concentration to maintain the de novo synthesis of thymidylate and purines, and accords with the methyl-folate-trap hypothesis. After treatment with amethopterin (Methotrexate), the incorporation of 3H-deoxyuridine into cellular DNA is reduced. In proliferating normal cells this effect of methotrexate can be prevented (and the cells rescued) with CH3-H4PteGlu or with CHO-H4PteGlu (5-formyl-H4PteGlu; Leucovorin). On the other hand, in vitamin B12 deficient bone marrow cells this so-called rescue-effect could only be achieved with CHO-H4PteGlu and not with CH3-H4PteGlu. These observations also support the hypothesis of the methyl-folate-trap in vitamin B12 deficiency. Decreased MS activity in vitamin B12 deficiency seems to be the essential metabolic fault, which is responsible for secondary alterations of folate metabolims. Thus, measurement of MS activity may allow direct functional assessment of vitamin B12 deficiency, at least with regard to DNA metabolism.


Healthcare workers' experiences of caring for patients colonized with carbapenemase-producing Enterobacterales (CPE) in an acute hospital setting - a scoping review.
Carbapenemase-producing Enterobacterales (CPE) is an increasing public health concern; these bacteria are highly transmissible in hospital environments and the number of patients with these multidrug-resistant bacteria is rising. Healthcare workers caring for patients colonized with CPE offer insight into care delivery and processes in the hospital setting. The aim of this review was to explore healthcare workers' experiences of caring for patients colonized with CPE. A scoping review method was employed and seven electronic databases (CINAHL, Academic Search Complete, Cochrane, Embase, Medline, Web of Science and Scopus) and four grey literature databases (Open Grey, Grey Literature Report, Clinical trials. gov and WHO International Clinical Trials Registry Platform) were searched using specific search terms and inclusion/exclusion criteria. A PRISMA flow diagram was used to illustrate the process of article selection and thematic analysis used to form themes. Three studies met the criteria to be included in this review. Two main themes were identified from analysing the articles: 'Safeguarding' and 'Power of Knowledge'. The desire to protect themselves, their families and patients was evident from the studies. Healthcare workers were aware of the importance on infection prevention and control measures such as hand hygiene, in preventing the transmission of CPE, however barriers to these were identified, such as time constraints. In conclusion, healthcare workers have negative associations when it comes to caring for patients with CPE. Very little research has been conducted in the area and there is an opportunity to further explore the experience of healthcare workers caring for patients with CPE to identify opportunities for improvement and support of staff.


The cost effectiveness of empiric intravenous immunoglobulin for the antepartum treatment of fetal and neonatal alloimmune thrombocytopenia.
The purpose of this study was to compare the cost effectiveness of empiric intravenous immunoglobulin (IVIG) with that of fetal blood sampling-indicated treatment for the antepartum care of fetal and neonatal alloimmune thrombocytopenia. We developed a decision analysis model to compare the cost effectiveness of 2 strategies for treatment of pregnancies in women with a history of fetal and neonatal alloimmune thrombocytopenia and an at-risk fetus: 1) IVIG and corticosteroids as indicated by fetal platelet levels determined by fetal blood sampling (FBS); and 2) empiric IVIG. In the first strategy, FBS is used to measure fetal platelets at 24 weeks of gestation and repeated 6 weeks later to guide pharmacotherapy. In the second strategy, weekly IVIG is empirically administered from 24 weeks' to 37 weeks' gestation. The main outcome measure was the marginal cost per quality-adjusted life years (QALY) gained. For every 1000 women with a fetus at risk for recurrent alloimmune thrombocytopenia, empiric therapy, compared with FBS-indicated treatment, decreases perinatal deaths from 31.7 to 11.8 while increasing the number of infants with long-term neurologic deficits from 6.1 to 9.6. These health outcomes translate to 382 QALYs gained with empiric therapy and a cost effectiveness ratio of dollar 32,747 per QALY favoring empiric therapy. In the sensitivity analysis, empiric therapy was not cost effective when the rate of perinatal ICH exceeded 28%. Empiric IVIG therapy is a cost-effective strategy for the treatment of women at risk for fetal and neonatal alloimmune thrombocytopenia when the rate of perinatal ICH is less than 28%.


Differences between immigrant and national students in motivational variables and classroom-motivational-climate perception.
The objective of this study is to see whether Immigrant (IM) and Spanish (National) students (SP) need different kinds of help from teachers due to differences in motivation, family expectancies and interests and classroom-motivational-climate perception. A sample of Secondary Students -242 Spanish and 243 Immigrants- completed questionnaires assessing goal orientations and expectancies, family attitudes towards academic work, perception of classroom motivational climate and of its effects, satisfaction, disruptive behavior and achievement. ANOVAs showed differences in many of the motivational variables assessed as well as in family attitudes. In most cases, Immigrant students scored lower than Spanish students in the relevant variables. Regression analyses showed that personal and family differences were related to student's satisfaction, achievement and disruptive behavior. Finally, multi-group analysis of classroom-motivational-climate (CMC) showed similarities and differences in the motivational value attributed by IM and SP to each specific teaching pattern that configure the CMC. IM lower self-esteem could explain these results, whose implications for teaching and research are discussed.


SlWRKY70 is required for Mi-1-mediated resistance to aphids and nematodes in tomato.
Plant resistance (R) gene-mediated defense responses against biotic stresses include vast transcriptional reprogramming. In several plant-pathogen systems, members of the WRKY family of transcription factors have been demonstrated to act as both positive and negative regulators of plant defense transcriptional networks. To identify the possible roles of tomato (Solanum lycopersicum) WRKY transcription factors in defense mediated by the R gene Mi-1 against potato aphid, Macrosiphum euphorbiae, and root-knot nematode (RKN), Meloidogyne javanica, we used tobacco rattle virus (TRV)-based virus-induced gene silencing and transcriptionally suppressed SlWRKY70, a tomato ortholog of the Arabidopsis thaliana WRKY70 gene. Silencing SlWRKY70 attenuated Mi-1-mediated resistance against both potato aphid and RKN showing that SlWRKY70 is required for Mi-1 function. Furthermore, we found SlWRKY70 transcripts to be inducible in response to aphid infestation and RKN inoculation. Mi-1-mediated recognition of these pests modulates this transcriptional response. As previously described for AtWRKY70, we found SlWRKY70 transcript levels to be up-regulated by salicylic acid and suppressed by methyl jasmonate. This indicates that some aspects of WRKY70 regulation are conserved among distantly related eudicots.


Antimüllerian hormone serum levels: a putative marker for ovarian aging.
To investigate whether serum concentrations of antimüllerian hormone may be used as a marker for ovarian aging. Longitudinal observational study. Academic research center. Forty-one normo-ovulatory premenopausal women and 13 healthy postmenopausal women. Concentrations of serum antimüllerian hormone (assessed on two occasions 2.6 +/- 1.7 years apart), FSH, inhibin B, and estradiol and number of ovarian follicles on ultrasonography. Concentrations of antimüllerian hormone decreased significantly over time (median value, 2.1 microg/L [range, 0.1-7.4 microg/L] at visit 1 vs. 1.3 microg/L [range, 0.0-5.0 microg/L] at visit 2), whereas the number of antral follicles and levels of FSH and inhibin B did not change. During visits 1 and 2, concentrations of antimüllerian hormone correlated with age (r = -.40, P=.01 and r = -.57, P<.001, respectively); number of antral follicles (r =.66, P<.001 and r =.71, P<.001); and, to a lesser extent, with FSH level (r = -.29, P=.07 and r = -.37, P<.05) but not with inhibin B levels. Serum concentrations of antimüllerian hormone decreased over time in young normo-ovulatory women, whereas other markers associated with ovarian aging did not change. Concentrations of antimüllerian hormone correlate with the number of antral follicles and age and less strongly with FSH level. Concentrations of antimüllerian hormone may be a novel marker for ovarian aging.


Patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement. Experimental study.
The experimental results of patch enlargement of the aortic and mitral valve rings with aortic and mitral double valve replacement are reported. The operative technique of this new surgical method is described and the indications are discussed.


Quantifying the relationship between disability progression and quality of life in patients treated for NMOSD: Insights from the SAkura studies.
To date, no specific scales have been developed to explore the impact of neuromyelitis optica spectrum disorder (NMOSD)-related disability on quality of life (QoL). The Expanded Disability Status Scale (EDSS) and the EuroQol 5-dimensions (EQ-5D) have been used to assess disability and QoL, respectively, in patients with NMOSD. However, there is limited evidence surrounding their use in this condition. We compared EDSS and EQ-5D data across two clinical trials to quantify the relationship between disability and QoL in patients with NMOSD. SAkuraSky (NCT02028884) and SAkuraStar (NCT02073279) were Phase 3, multicenter, randomized, international, double-blind, placebo-controlled, parallel-assignment studies of satralizumab, administered in combination with baseline immunosuppressants (SAkuraSky) or as monotherapy (SAkuraStar). EDSS and EQ-5D were assessed at baseline and at 24-week intervals thereafter. The relationship between disability and QoL was assessed by estimating EQ-5D utilities (UK tariff) for each incremental EDSS category. A repeated-measures linear model was used to regress health utilities on EDSS score-derived health states. Overall, 176 patients underwent at least one EDSS assessment and completed an EQ-5D survey and were included in this analysis. There was a clear association between mean EQ-5D score and EDSS score, with decreases in QoL being observed at each incremental increase in disability. The relationship between EDSS and EQ-5D score remained consistent across the different treatment groups. These results, generated from high-quality clinical trial data, demonstrated a strong and consistent relationship between disability and QoL in patients with NMOSD.


Anti-angiogenic properties of microRNA-29a in preclinical ocular models.
Abnormal neovascularization is an important cause of blindness in many ocular diseases, for which the etiology and pathogenic mechanisms remain incompletely understood. Recent studies have revealed the diverse roles of noncoding RNAs in various biological processes and facilitated the research and development of the clinical application of numerous RNA drugs, including microRNAs. Here, we report the antiangiogenic activity of microRNA-29a (miR-29a) in three animal models of ocular neovascularization. The miR-29a knockout (KO) mice displayed enhanced vessel pruning, resulting in a decreased vascularized area during retinal development. In contrast, miR-29a deletion in adult mice accelerated angiogenesis in preclinical disease models, including corneal neovascularization, oxygen-induced retinopathy, and choroidal neovascularization, while the administration of agomir-29a ameliorated pathological neovascularization. Furthermore, miR-29a exerted inhibitory effects on endothelial cell proliferation, migration, and tube formation capacities. RNA sequencing analysis of retinas from miR-29a KO mice and RNA interference experiments identified platelet-derived growth factor C and several extracellular matrix genes as downstream targets of miR-29a involved in regulating ocular angiogenesis. Our data suggest that miR-29a may be a promising clinical candidate for the treatment of neovascular diseases.


[Malignant intracerebral nerve sheath tumours: Two case reports and complete review of the literature cases].
Malignant peripheral nerve sheath tumours are extremely rare and can be associated with neurofibramatosis type 1. Their prognosis is poor and surgery remains the mainstay of therapy and should be the first line of treatment. Radiotherapy and chemotherapy are second line treatment and their effectiveness remains to demonstrate. The diagnosis is clinical, radiological, histological and immunohistochemical. Malignant peripheral nerve sheath tumours have a potential of local tumour recurrence very high and can metastasize. They often occur in extremity of the members but also rarely into brain. We report two cases of intracerebral nerve sheath tumour. The first was a 68-year-old woman who was admitted with progressive symptoms of headache and diplopia. A left frontotemporal malignant peripheral nerve sheath tumours was diagnosed and was treated by surgery and irradiation. Ten months later, she presented a local recurrence and spine bone's metastases were treated by vertebroplasty and irradiation. The patient died 15 months after the diagnosis. The second case was a 47-year-old woman who was referred because headache and vomiting symptoms. A right frontal malignant peripheral nerve sheath tumours was diagnosed and treated by surgery and irradiation. After that, the patient had three local recurrence operated and pulmonary and cranial bone's metastases. She was still alive after 20 months. We propose a literature review with 25 cases of intracerebral nerve sheath tumour identified, including the two current cases.


An index of past asbestos exposure as applied to car and bus mechanics.
Different ways to describe historic fibre exposure from asbestos-containing friction materials were studied and compared for a group of 103 car and bus mechanics with more than 20 years employment and 15 years of asbestos exposure. A model was constructed to calculate cumulative asbestos exposure from friction materials including duration, intensity and exposure last year. The model is a combination of an additive and a multiplicative model, where an asbestos index was constructed that takes both near field and far field exposure into consideration. The model was based upon data from the international literature and quantitative asbestos measurements performed 1976-1988 in Swedish car repair workshops. The fibres were counted by phase-contrast microscopy with fibre criteria of length > 5 microns and aspect ratio > or = 3:1. The mechanics' fibre exposure at 398 repair workshops during a period of 48 years were calculated using the model. The mean cumulative exposure was estimated to be 2.6 f ml-1 * year. The annual cumulative exposure was highest for truck mechanics in the early 1960s. The car mechanics had a time-weighted average fibre exposure range of 0.11-0.41 f ml-1 (mean 0.21 f ml-1) in 1965 compared to 0.003-0.08 f ml-1 (mean 0.021 f ml-1) in 1985. In order to validate the model, the mechanic's fibre exposure estimated using the model were compared with representative asbestos exposure measurements for car mechanics during the 1960s and the 1970s (correlation coefficient = 0.69). Five lung physiological variables (FVC, TLC, FEV1, TLco and CV%) were used to study exposure-response relationships. None of the exposure parameters suggested any significant relationship between exposure and decrease in lung function.


Impact of an integrated classifier using biomarkers, clinical and imaging factors on clinical decisions making for lung nodules.
An integrated classifier that utilizes plasma proteomic biomarker along with five clinical and imaging factors was previously shown to be potentially useful in lung nodule evaluation. This study evaluated the impact of the integrated proteomic classifier on management decisions in patients with a pretest probability of cancer (pCA) ≤50% in "real-world" clinical setting. Retrospective study examining patients with lung nodules who were evaluated using the integrated classifier as compared to standard clinical care during the same period, with at least 1-year follow-up. A total of 995 patients were evaluated for lung nodules over 1 year following the implementation of the integrated classifier with 17.3% prevalence of lung cancer. 231 patients met the study eligibility criteria; 102 (44.2%) were tested with the integrated classifier, while 129 (55.8%) did not. The median number of chest imaging studies was 2 [interquartile range (IQR), 1-2] in the integrated classifier arm and 2 [IQR, 1-3] in the non-integrated classifier arm (P=0.09). The median outpatient clinic visit was 2.00 (IQR, 1.00-3.00) in the integrated classifier arm and 2.00 (IQR, 2.00-3.00) in the non-integrated classifier (P=0.004). Fewer invasive procedures were pursued in the integrated classifier arm as compared to non-integrated classifier respectively (26.5% vs. 79.1%, P<0.001). All patients in the integrated classifier arm with post-pCA (likely benign n=39) had designated benign diagnosis at 1-year follow-up. In patients with lung nodules with a pCA ≤50%, use of the integrated classifier was associated with fewer invasive procedures and clinic visits without misclassifying patients with likely benign lung nodules results at 1-year follow-up.


Altered functional connectivity in common resting-state networks in patients with major depressive disorder: A resting-state functional connectivity study.
The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.


Atypical Facial Pain.
Atypical facial pain (AFP), or persistent idiopathic facial pain, is a chronic and diffuse distribution of facial pain along the territory of the trigeminal nerve. This condition occurs in the absence of any neurologic deficit or any other obvious etiology. AFP is one of the most challenging conditions to diagnose due to lack of clear diagnostic criteria. Diagnosis of this condition is made by exclusion of other known etiologies. Specific disease modalities cannot be targeted, resulting in a deficiency of clear treatment protocol. Despite the limitations of evidence-based literature, tricyclic antidepressants have proved effective and are considered the treatment choice for AFP.


Quality of Care and Outcomes for Patients with Acute Ischemic Stroke and Transient Ischemic Attack During the COVID-19 Pandemic.
Hospitalizations for acute ischemic stroke (AIS) and transient ischemic attack (TIA) decreased during the COVID-19 pandemic. We compared the quality of care and outcomes for patients with AIS/TIA before vs. during the COVID-19 pandemic across the United States Department of Veterans Affairs healthcare system. This retrospective cohort study compared AIS/TIA care quality before (March-September 2019) vs. during (March-September 2020) the pandemic. Electronic health record data were used to identify patient characteristics, quality of care and outcomes. The without-fail rate was a composite measure summarizing whether an individual patient received all of the seven processes for which they were eligible. Mixed effects logistic regression modeling was used to assess differences between the two periods. A decrease in presentations occurred during the pandemic (N = 4360 vs. N = 5636 patients; p = 0.003) and was greater for patients with TIA (-30.4%) than for AIS (-18.7%). The without-fail rate improved during the pandemic (56.2 vs. before 50.1%). The use of high/moderate potency statins increased among AIS patients (OR 1.26 [1.06-1.48]) and remained unchanged among those with TIA (OR 1.04 [0.83,1.29]). Blood pressure measurement within 90-days of discharge was less frequent during the pandemic (57.8 vs. 89.2%, p < 0.001). Hypertension control decreased among patients with AIS (OR 0.73 [0.60-0.90]) and TIA (OR 0.72 [0.54-0.96]). The average systolic and diastolic blood pressure was 1.9/1.4 mmHg higher during the pandemic than before (p < 0.001). Compared to before, during the pandemic fewer AIS patients had a primary care visit (52.5% vs. 79.8%; p = 0.0001) or a neurology visit (27.9 vs. 41.1%; p = 0.085). Both 30- and 90-day unadjusted all-cause mortality rates were higher in 2020 (3.6% and 6.7%) vs. 2019 (2.9, 5.4%; p = 0.041 and p = 0.006); but these differences were not statistically significant after risk adjustment. Overall quality of care for patients with AIS/TIA did not decline during the COVID-19 pandemic.


How to select epochs of the EEG at rest for quantitative analysis.
Before performing a quantitative analysis of the EEG at rest, it has to be specified how many seconds are to be used later on, and a criterion has to be set down according to which data are selected for further analysis. In this paper it is investigated which duration is appropriate for an analysis of background, non-transient activity. Furthermore, different criteria for automatically selecting such epochs for quantitative analysis are compared with respect to broad-band parameters of a sample of 42 children. A length of 20 sec turned out to be sufficient, since using 40 sec or 60 sec did not improve the statistical variability. Moreover, a criterion based on minimizing EOG power from 1.5 to 7.5 Hz was mildly superior to other criteria considered. The particular choice of epoch was, however, less crucial than anticipated.


Psychiatric home care. An evolving legal standard.
The treatment of mentally ill individuals in the home setting increases a psychiatrist's therapeutic responsibilities to the patient with commensurate greater legal exposure. Because psychiatric home care is in its infancy, the standard of care to be followed in implementing this therapy is still evolving. This article examines a psychiatrist's legal duties in providing home care as well as methods of practice to minimize allegations of inappropriate care.


Dorsolateral Nigral Hyperintensity on 1.5 T Versus 3 T Susceptibility-Weighted Magnetic Resonance Imaging in Neurodegenerative Parkinsonism.
An absent dorsolateral nigral hyperintensity (DNH) is a common finding in patients with neurodegenerative parkinsonism at high or ultra-high field susceptibility-weighted magnetic resonance imaging (SWI). Despite increasing use of high field magnetic resonance imaging (MRI) in specialized centers, these scanners are still frequently unavailable in primary care or outpatient facilities and underdeveloped or emerging countries. Therefore, the aim of the present study was to evaluate the diagnostic utility of DNH assessment at 1.5 versus 3 T MRI to distinguish patients with neurodegenerative parkinsonism, including Parkinson's disease (PD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), from healthy controls (HC). Absence of DNH was assessed on visual inspection of anonymized 1.5 T and 3.0 T SWI scans in a case-control study including 86 patients with neurodegenerative parkinsonism and 33 healthy controls (HC). All study participants were consecutively recruited to undergo 1.5 and 3 T MRI. Overall correct classification was 81.7% (95% CI, 72.6-88.4%) for 1.5 T and 95.7% (95% CI, 89.1-98.7%) for 3 T MRI in discriminating neurodegenerative parkinsonism from controls. However, while DNH was bilaterally present in all but one of the HC at 3 T MRI, it was rated as abnormal (at least unilateral absence) in 15 of 22 HC at 1.5 T MRI, resulting in a specificity of 31.8%. The results of the present study demonstrate an insufficient specificity of visual assessment of DNH at 1.5 T MRI for the diagnosis of neurodegenerative parkinsonism.


An epidemiologic study of osteoporosis in Taiwan.
In 1989, a cross-sectional study was carried out in Taiwan to understand the distribution of bone mineral density (BMD) in the lumbar spine of Chinese people and to identify the risk factors associated with osteoporosis. BMD of the lumbar spine was measured by dual-photon absorptiometry in 404 healthy volunteers (266 women and 138 men, aged 15 to 83 years) living in Lin-Kou Township. The age-specific mean values of lumbar spine BMD were higher for men than for women after age 60. Furthermore, the BMD of women declined significantly after age 40. However, the BMD of men did not show a downward trend with age. In a multiple logistic regression analysis of fracture risk expressed as a categorical level of BMD, age, diabetes, and years since menopause were associated with lower BMD, while body mass index was associated with higher BMD. In a multiple linear regression analysis of BMD, significant variables were years since menopause, age, body mass index, and seaweed diet. Variables that were significant in bivariate analysis, but not multiple variable analysis were education, milk consumption, breast-feeding, frequency of pregnancy, and age at first menstruation. However, cigarette habits, alcohol consumption, and physical activity were not associated with the BMD level in any of these analyses.


Precision Chain-Walking Polymerization of trans-4-Octene Catalyzed by α-Diimine Nickel(II) Catalysts Bearing ortho-sec-Phenethyl Groups.
α-Diimine nickel complexes bearing bulky ortho-sec-phenethyl groups (bis{[N,N'-(4-methyl-2,6-di-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel (1), bis{[N,N'-(4,6-dimethyl-2-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel (2), bis{[N,N'-(4-methyl-2-sec-phenethylphenyl)imino]-1,2-dimethylethane}dibromonickel (3)) and {bis[N,N'-(2,4,6-trimethylphenyl)imino]-1,2-dimethylethane}dibromidonickel (4) are used as a precatalyst for the polymerization of trans-4-octene upon activation with modified methylaluminoxane. These catalysts conduct chain-walking polymerization of trans-4-octene to give polymers possessing propyl and butyl branches with high molecular weight and narrow molecular weight distribution. The branching structure depends on the nickel complex as well as the polymerization temperature, and the ratio of propyl branch was increased with increasing the bulkiness of the ligand and decreasing the polymerization temperature. Consequently, the most bulky 1 among the complexes used is found to polymerize trans-4-octene with high 1,5-regioselectivity at -20 °C to give poly(1-propylpentan-1,5-diyl).


Active commuting is associated with a lower risk of obesity, diabetes and metabolic syndrome in Chilean adults.
There is limited evidence on how active commuting is associated with health benefits in developing countries. The aim of this study therefore was to investigate the associations between active commuting and markers of adiposity and cardiometabolic risk in the Chilean adult population. In total, 5157 participants from the Chilean National Health Survey 2009-10 were included in this cross-sectional study. Active commuting was measured using the Global Physical Activity Questionnaire (GPAQ v2). Body mass index (BMI) and waist circumference (WC) were measured and used to define obesity and central obesity. Type 2 diabetes (T2D) and metabolic syndrome were determined using WHO and updated ATPIII-NCEP criteria, respectively. The main finding of this study is that a 30 min increase in active commuting is associated with lower odds for BMI > 25.0 kg m-2 (0.93 [95% CI: 0.88-0.98, P = 0.010]). Similarly, the odds for central obesity was 0.87 [0.82-0.92, P < 0.0001]. Similar associations were found for T2D (0.81 [0.75-0.88], P < 0.0001) and metabolic syndrome (OR: 0.86 [0.80-0.92], P < 0.0001). Our findings show that active commuting is associated with lower adiposity and a healthier metabolic profile including lower risk for obesity, diabetes and metabolic syndrome.


Nods: a family of cytosolic proteins that regulate the host response to pathogens.
Genetic variation in Nod2 is associated with susceptibility to Crohn's disease. Nod2 and its homologue, Nod1, are members of a growing family of cytosolic factors related to the apoptosis regulator Apaf-1 and a class of plant disease resistance proteins. Nod1 and Nod2 confer responsiveness to lipopolysaccharides and interact with RICK, a mediator of NF-kappaB activation. Nod1 and Nod2 and related Nods appear to regulate the host response to pathogens, a process that may be faulty in certain inflammatory diseases. Recent studies that suggest that Nods may be involved in the recognition of pathogen components in the cytosol of mammalian cells are reviewed.


Enterotoxigenicity of Staphylococcus intermedius of canine origin.
Seventy-three staphylococcal strains isolated from pyrodermatitis in dogs were classified as Staphylococcus intermedius (52 strains) or Staphylococcus aureus (21 strains) on the basis of acetoin formation, anaerobic mannitol fermentation, aerobic maltose fermentation, pigmentation, coagulation of human plasma, and reaction on crystal violet agar. Enterotoxin was produced by 13 of the 52 S. intermedius strains and 6 of the S. aureus strains. The highest percentage of enterotoxigenic strains produced enterotoxins C (6 strains), D (7 strains), and E (6 strains). Four strains produced the toxic shock syndrome toxin-1. There was little difference in the antibiotic susceptibility between the enterotoxigenic and non-enterotoxigenic strains.


Paradoxical EU agricultural policies on genetically engineered crops.
European Union (EU) agricultural policy has been developed in the pursuit of laudable goals such as a competitive economy and regulatory harmony across the union. However, what has emerged is a fragmented, contradictory, and unworkable legislative framework that threatens economic disaster. In this review, we present case studies highlighting differences in the regulations applied to foods grown in EU countries and identical imported products, which show that the EU is undermining its own competitiveness in the agricultural sector, damaging both the EU and its humanitarian activities in the developing world. We recommend the adoption of rational, science-based principles for the harmonization of agricultural policies to prevent economic decline and lower standards of living across the continent.


Characterization of heat emission of light-curing units.
This study was designed to analyze the heat emissions produced by light-curing units (LCUs) of different intensities during their operation. The null hypothesis was that the tested LCUs would show no differences in their temperature rises. FIVE COMMERCIALLY AVAILABLE LCUS WERE TESTED: a "Flipo" plasma arc, "Cromalux 100" quartz-tungsten-halogen, "L.E. Demetron 1" second-generation light-emitting diode (LED), and "Blue Phase C5" and "UltraLume 5" third-generation LED LCUs. The intensity of each LCU was measured with two radiometers. The temperature rise due to illumination was registered with a type-K thermocouple, which was connected to a computer-based data acquisition system. Temperature changes were recorded in continues 10 and 20 s intervals up to 300 s. The Flipo (ARC) light source revealed the highest mean heat emission while the L.E. Demetron 1 LED showing the lowest mean value at 10 and 20 s exposure times. Moreover, Cromalux (QTH) recorded the second highest value for all intervals (12.71, 14.63, 14.60) of heat emission than Blue Phase C5 (LED) (12.25, 13.87, 13.69), interestingly at 20 s illumination for all intervals the highest results (18.15, 19.27, 20.31) were also recorded with Flipo (PAC) LCU, and the lowest (6.71, 5.97, 5.55) with L.E. Demetron 1 LED, while Blue Phase C5 (LED) recorded the second highest value at the 1st and 2nd 20 s intervals (14.12, 11.84, 10.18) of heat emission than Cromalux (QTH) (12.26, 11.43, 10.26). The speed of temperature or heat rise during the 10 and 20 s depends on light intensity of emitted light. However, the QTH LCU was investigated resulted in a higher temperature rise than LED curing units of the same power density. The PAC curing unit induced a significantly higher heat emission and temperature increase in all periods, and data were statistically different than the other tested groups (p < .05). LED (Blue Phase C5) was not statistically significant (p < .05) (at 10 s) than QTH units, also LED (Blue Phase C5, UltraLume 5) generates obvious heat emission and temperature rises than QTH units (at 20 s) except for those which have lower power density of LED curing units (first generation). Thus, the null hypothesis was rejected.


Candida species lens abscesses in infants with a history of neonatal Candida sepsis.
We report 3 patients who were delivered prematurely and who developed a lens opacity with signs of ocular inflammation at a postgestational age of 10-52 weeks. All patients had been treated for Candida sepsis as neonates. Each patient underwent lensectomy and anterior vitrectomy. In 2 infants Candida albicans was cultured from the lens/anterior chamber membrane; in 1 Candida parapsilosis was cultured from a lens aspirate. Despite eradication of the fungal infection, outcomes were poor: 2 eyes developed glaucoma, and 1 developed a retinal detachment with subsequent phthisis.


Life with chronic pain during COVID-19 lockdown: the case of patients with small fibre neuropathy and chronic migraine.
We aimed at investigating the impact of COVID-19-related distress on patients with chronic pain, highlighting the effects of changes in individual habits and public health care reconfiguration on physical and psychological health. During the pandemic, 80 participants (25 patients with small fibre neuropathy (SFN), 42 patients with chronic migraine (CM) and 13 patients' healthy family members (HFM)) were asked to evaluate their COVID-19 complains, changes in habits and clinical management, behaviour, mood, loneliness, quality of life (QoL), physical and mental health and coping strategies. Data were analysed by Spearman rho correlations and Mann-Whitney U tests. Patients had lower QoL, lower physical health and higher catastrophizing attitude towards pain than HFM. During the pandemic, SFN patients referred greater decline in clinical symptoms, worries about contagion and discomfort for disease management changes than CM patients. In the SFN group, the higher levels of disability were associated with suffering from changes in neurologist-patient relationship. CM patients complained of agitation/anxiety that was related to feelings of loneliness, depressive mood and catastrophism. Despite similar complains of change in habits and worries about COVID-19 pandemic, SFN and CM patients had distinct reactions. In SFN patients, pandemic distress impacted on physical health with worsening of clinical conditions, especially suffering from changes in their care. In CM patients, pandemic distress affected behaviour, mainly with psychological frailty. This suggests the need to customize public health care for patients with distinct chronic pain conditions.


Depression by ethionine of phosphorylating oxidation in hepatic mitochondria.
Induction of hepatic steatosis and suppression of hepatic ATP levels, protein synthesis and gluconeogenesis subsequent to administration of ethionine may be consequences of interference by this compound with mitochondrial phosphorylation of ADP. The mitochondrial dysfunction is not a direct action of ethionine on the organelle.


In vivo pH imaging with (99m)Tc-pHLIP.
A novel molecular imaging agent has been developed recently, which stains tissues of low extracellular pH [pH (low) insertion peptide, pHLIP(®)]. A pH-dependent process of peptide folding and insertion into cell membranes has been found in vitro. Targeting of acidic solid tumours has been demonstrated in vivo using fluorescence and PET labels. Here, we present proof of feasibility studies of pHLIP with a single-photon emission computed tomography (SPECT) label, (99m)Tc-AH114567, with focus on preclinical efficacy and imageability. Lewis lung carcinoma, lymph node carcinoma of the prostate and prostate adenocarcinoma tumour xenografts were grown in mice and characterised by the angiogenesis marker (99m)Tc-NC100692 and by extracellular pH measurements with (31)P-MRS of 3-aminopropyl phosphonate. Biodistribution was assessed and CT/SPECT imaging performed. Oral administration of bicarbonate served as control. Tc-AH114567 can be obtained via a robust synthesis with good radiolabelling profile and improved formulation. The tracer retains the pH-dependent ability to insert into membranes and to target tumours with similar pharmacokinetics and efficacy that had been demonstrated earlier for pHLIP with optical or (64)Cu PET labels. Despite the inherent challenges of SPECT compared to optical and PET imaging, e.g., in terms of lower sensitivity, (99m)Tc-AH114567 shows adequate image quality and contrast. The main development need for transitioning SPECT labelled pHLIP into the clinic is more rapid background signal reduction, which will be the focus of a subsequent optimisation study.


White-light directional false color coding in discrete imagery.
A white-light optical signal-processing technique is presented to color encode directional edges present in discrete-tone black and white imagery in real time with colors that are available in the white-light source.


Human cathepsin X/Z is a biologically active homodimer.
Human cathepsin X belongs to the cathepsin family of 11 lysosomal cysteine proteases. We expressed recombinant procathepsin X in Pichia pastoris in vitro and cleaved it into its active mature form using aspartic cathepsin E. We found, using size exclusion chromatography, X-ray crystallography, and small-angle X-ray scattering, that cathepsin X is a biologically active homodimer with a molecular weight of ~53 kDa. The novel finding that cathepsin X is a dimeric protein opens new horizons in the understanding of its function and the underlying pathophysiological mechanisms of various diseases including neurodegenerative disorders in humans.


The semantic deficit in aphasia: the relationship between semantic errors in auditory comprehension and picture naming.
Thirty aphasic subjects were asked to point to pictures on auditory command both when the distractors came from the same semantic category as the target and when the distractors were unrelated to the target picture. The aphasics made significantly more semantic errors than non-aphasic brain-damaged controls; the incidence of semantic comprehension errors was unrelated to aphasic diagnostic groups but was related to the overall severity of aphasia. The subjects were subsequently asked to name the pictures from the comprehension task; pictures that had elicited semantic errors in comprehension were no less likely to be named than those that had not, but the incidence of semantic errors in comprehension correlated significantly with their incidence in naming. The implications of a semantic deficit common to both auditory comprehension and naming that is not specific to particular lexical items is discussed in relation to a number of information processing models of the lexicon.


The use of multimedia to teach new cardiac anesthesia procedures.
Cardiac anesthesia is a complex field requiring extensive training and experience. Multimedia can be used effectively to teach new, complex, and rapidly developing anesthetic and surgical techniques. Minimally invasive Port-Access cardiac surgery is an area in which the computer can be used for educational purposes. As cardiac anesthesiologists become more adept at developing computerized instructional methods, and as new techniques in medicine emerge, greater use can be made of the computer as a valuable teaching tool.


[Chest magnetic resonance lymphography].
Lymphangio-MRI is a non-invasive technique that allows the precise imaging of thoracic lymphatic vessels without contrast-enhancing agents. This technique is still in progress, and will benefit from better knowledge of thoracic lymphatic diseases and further improvement of MRI spatial resolution.


EPR and redox characterization of iron-sulfur centers in nitrate reductases A and Z from Escherichia coli. Evidence for a high-potential and a low-potential class and their relevance in the electron-transfer mechanism.
The redox properties of the iron-sulfur centers of the two nitrate reductases from Escherichia coli have been investigated by EPR spectroscopy. A detailed study of nitrate reductase A performed in the range +200 mV to -500 mV shows that the four iron-sulfur centers of the enzyme belong to two classes with markedly different redox potentials. The high-potential group comprises a [3Fe-4S] and a [4Fe-4S] cluster whose midpoint potentials are +60 mV and +80 mV, respectively. Although these centers are magnetically isolated, they are coupled by a significant anticooperative redox interaction of about 50 mV. The [4Fe-4S]1+ center occurs in two different conformations as shown by its composite EPR spectrum. The low-potential group contains two [4Fe-4S] clusters with more typical redox potentials (-200 mV and -400 mV). In the fully reduced state, the three [4Fe-4S]1+ centers are magnetically coupled, leading to a broad featureless spectrum. The redox behaviour of the high-pH EPR signal given by the molybdenum cofactor was also studied. The iron-sulfur centers of the second nitrate reductase of E. coli, nitrate reductase Z, exhibit essentially the same characteristics than those of nitrate reductase A, except that the midpoint potentials of the high-potential centers appear negatively shifted by about 100 mV. From the comparison between the redox centers of nitrate reductase and of dimethylsulfoxide reductase, a correspondence between the high-potential iron-sulfur clusters of the two enzymes can be proposed.


Suxamethonium block in the myasthenic patient. Correlation with plasma cholinesterase.
The neuromuscular block of suxamethonium 1.5 mg.kg-1 was investigated in three myasthenic patients (Class IIA), undergoing thymectomy. Two of the patients were receiving pre-operative pyridostigmine therapy. In the three patients, plasma cholinesterase activity was determined on the morning of surgery and was correlated with the neuromuscular response to suxamethonium as monitored by electromyography. The results suggest that the response to suxamethonium in the myasthenic patients can show wide variations according to the level of their plasma cholinesterase activity. The degree and duration of suxamethonium block is inversely related to the plasma cholinesterase activity.


Water management in Angkor: human impacts on hydrology and sediment transportation.
The city of Angkor, capital of the Khmer empire from the 9th to 15th century CE, is well known for its impressive temples, but recent research has uncovered an extensive channel network stretching across over 1000 km2. The channel network with large reservoirs (termed baray) formed the structure of the city and was the basis for its water management. The annual long dry season associated with the monsoon climate has challenged water management for centuries, and the extensive water management system must have played an important role in the mitigation of such marked seasonality. However, by changing the natural water courses with off-take channels the original catchments were also reshaped. Moreover, severe problems of erosion and sedimentation in human built channels evolved and impacted on the whole water management system. This paper describes the present hydrology of the area and discusses the impacts of water management on hydrology during the Angkor era. The paper, moreover, attempts to summarise lessons that could be learnt from Angkorian water management that might apply to present challenges within the field.


The effect of digestion with keratanase (Pseudomonas sp.) on certain histochemical reactions for glycosaminoglycans in cartilaginous and corneal tissues.
The effect of digestion with keratanase (Pseudomonas sp.) on the Alcian Blue (AB) pH 1.0, pH 2.5, Aldehyde Fuchsin, high iron diamine, low iron diamine and dialysed iron-ferrocyanide reactions has been tested in the costal and ear cartilage tissues of the rabbit and corneal tissues of the rat and rabbit. The effect of digestion with chondroitinases ABC and AC on the same reactions was examined in the same tissues for comparison. Digestion with keratanase diminished the intensity of all the reactions in the cartilage tissues to a variable extent; however, the diminutions in intensity of the reactions appeared to be less marked as compared with those following digestion with two chondroitinases. In the corneal stroma, all the reactions were markedly reduced in intensity following digestion with keratanase. In contrast, these reactions were only slightly or moderately diminished in intensity by digestion with the two chondroitinases. As glycosamino-glycans are known to be present in cartilage and corneal tissues and the substrate specificities of the three enzymes used are now well established, the present results are consistent with the concept that keratanase specifically degrades and releases keratan sulphates involved in the tissues.


Strongly enhanced oxygen ion transport through samarium-doped CeO2 nanopillars in nanocomposite films.
Enhancement of oxygen ion conductivity in oxides is important for low-temperature (<500 °C) operation of solid oxide fuel cells, sensors and other ionotronic devices. While huge ion conductivity has been demonstrated in planar heterostructure films, there has been considerable debate over the origin of the conductivity enhancement, in part because of the difficulties of probing buried ion transport channels. Here we create a practical geometry for device miniaturization, consisting of highly crystalline micrometre-thick vertical nanocolumns of Sm-doped CeO2 embedded in supporting matrices of SrTiO3. The ionic conductivity is higher by one order of magnitude than plain Sm-doped CeO2 films. By using scanning probe microscopy, we show that the fast ion-conducting channels are not exclusively restricted to the interface but also are localized at the Sm-doped CeO2 nanopillars. This work offers a pathway to realize spatially localized fast ion transport in oxides of micrometre thickness.


Weekly oral vitamin K prophylaxis in Denmark.
To evaluate oral vitamin K prophylaxis at birth by giving 2 mg phytomenadione, followed by weekly oral vitamin K prophylaxis; 1 mg was administered by the parents until 3 mo of age. A total of 507850 live babies were born in Denmark during the study period, November 1992 to June 2000. Of these infants, 78% and 22% received oral and intra-muscular prophylaxis, respectively; i.e. about 396000 neonates received oral prophylaxis at birth. Weekly oral prophylaxis was recommended for all infants as long as they were mainly breastfed. A survey of possible cases of vitamin K deficiency bleeding (VKDB) was carried out by repeated questionnaires to all Danish paediatric departments and by checking the National Patient Register. No cases of VKDB were revealed, i.e. the incidence was 0-0.9:100000 (95% CI). The questionnaires were used to evaluate compliance with the regimen. Parents of 274 infants participated. A dose of vitamin K was regarded as having been given if the infant received a drop of vitamin K or was mostly formula-fed that week, and the prophylaxis was regarded as completed if the infant had received at least 9 doses. Compliance was good, with 94% of the infants completing the course of prophylaxis. Weekly oral vitamin K supplementation during the first 3 mo of life was an efficient prophylaxis against VKBD. Parental compliance with the regimen was good.


Fasciola hepatica: liver enzymes in rats and interaction with chemical inducers.
Adult male rats were sorted into control and infected groups, the latter receiving an oral dose of 20 metacercariae of Fasciola hepatica. In Weeks 3 and 6 after infection, some rats received phenobarbital or 3-methylcholanthrene which induced drug metabolizing enzymes. The parasitic pathology was ascertained by clinical observation of the rats and at autopsy. Hepatic microsomal cytochrome P-450 content was significantly decreased in infected rats compared to untreated phenobarbital treated groups. In all infected rats, the simultaneous increase in cytosolic calcium and decrease in cytosolic glutathione corresponded to oxidative cell injury occurring in the course of fascioliasis. Both arylamine acetyltransferase (EC 126.96.36.199.) and glutathione transferase (EC 18.104.22.168) activities were decreased in all newly infected and 6 week infected groups. Fascioliasis did not alter the substrate related uridine diphosphate glucuronosyltransferase activities (EC 184.108.40.206) of any rat group.


Adamts10 inactivation in mice leads to persistence of ocular microfibrils subsequent to reduced fibrillin-2 cleavage.
Mutations in the secreted metalloproteinase ADAMTS10 cause recessive Weill-Marchesani syndrome (WMS), comprising ectopia lentis, short stature, brachydactyly, thick skin and cardiac valve anomalies. Dominant WMS caused by FBN1 mutations is clinically similar and affects fibrillin-1 microfibrils, which are a major component of the ocular zonule. ADAMTS10 was previously shown to enhance fibrillin-1 assembly in vitro. Here, Adamts10 null mice were analyzed to determine the impact of ADAMTS10 deficiency on fibrillin microfibrils in vivo. An intragenic lacZ reporter identified widespread Adamts10 expression in the eye, musculoskeletal tissues, vasculature, skin and lung. Adamts10-/- mice had reduced viability on the C57BL/6 background, and although surviving mice were slightly smaller and had stiff skin, they lacked brachydactyly and cardiovascular defects. Ectopia lentis was not observed in Adamts10-/- mice, similar to Fbn1-/- mice, most likely because the mouse zonule contains fibrillin-2 in addition to fibrillin-1. Unexpectedly, in contrast to wild-type eyes, Adamts10-/- zonule fibers were thicker and immunostained strongly with fibrillin-2 antibodies into adulthood, whereas fibrillin-1 staining was reduced. Furthermore, fibrillin-2 staining of hyaloid vasculature remnants persisted post-natally in Adamts10-/- eyes. ADAMTS10 was found to cleave fibrillin-2, providing an explanation for persistence of fibrillin-2 at these sites. Thus, analysis of Adamts10-/- mice led to identification of fibrillin-2 as a novel ADAMTS10 substrate and defined a proteolytic mechanism for clearance of ocular fibrillin-2 at the end of the juvenile period.


Perioperative intravenous low-dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo-controlled study.
Chronic pain after major lower back surgery is frequent. We investigated in adults the effect of perioperative low-dose ketamine on neuropathic lower back pain, assessed by the DN4 questionnaire, 6 and 12 months after major lower back surgery. In this single-centre randomized trial, 80 patients received intravenous ketamine 0.25 mg/kg preoperatively, followed by 0.25 mg kg-1 hr-1 intraoperatively, and 0.1 mg kg-1 hr-1 from 1 hr before the end of surgery until the end of recovery room stay; 80 controls received placebo. Preoperatively, 47.4% of patients in the ketamine group and 46.3% in the placebo group had neuropathic pain; 10% and 3.8%, respectively, were using strong opioids. At the end of the infusion, the median cumulative dose of ketamine was 84.8 mg (IQR 67.4-106.7) and the median plasma level was 97 ng/ml (IQR 77.9-128.0). At 6 months, 28.8% of patients in the ketamine group and 23.5% in the placebo group had neuropathic pain (absolute difference, 5.2%; 95% CI -10.7 to 21.1; p = .607). At 12 months, 26.4% of patients in the ketamine group and 17.9% in the placebo group had neuropathic pain (absolute difference 8.5%; 95% CI -6.7 to 23.6; p = .319). In this patient population with a high prevalence of neuropathic lower back pain undergoing major lower back surgery, a perioperative intravenous low-dose ketamine infusion did not have an effect on the prevalence of neuropathic lower back pain at 6 or 12 months postoperatively. We were unable to show any analgesic benefit of a short-term perioperative ketamine infusion as an adjuvant to multimodal analgesia in patients with a high prevalence of neuropathic lower back pain undergoing major back surgery. Based on these data, the widespread opinion that ketamine is universally analgesic across different pain conditions must be challenged. Abstract presentation at the annual congress of the Swiss Society of Anaesthesiology, 2016, Basel, Switzerland. Registered by Dr Christoph Czarnetzki as principal investigator on February 20, 2008 at clinicaltrials.gov (NCT00618423).


Predictors of leaving nursing care: a longitudinal study among Swedish nursing personnel.
Despite extensive research on turnover among nursing personnel very little is known about the impact of physical workload and health on leaving. The aim of this study was to find predictors for leaving nursing care with special reference to physical working conditions and musculoskeletal problems. This study is based on longitudinal data from a survey of nursing personnel who were employed at various county hospitals in Sweden from 1992-95. A self administrated follow up questionnaire was used to identify their present position in the labour market. The response rate was 73% (n = 1095). The results showed that nursing personnel reporting musculoskeletal problems of the neck/shoulder or knees and those who had limited use of transfer devices were more likely to leave nursing care. The study highlights the importance of taking musculoskeletal problems and use of transfer devices into consideration in order to retain nursing personnel.


Tomorou attenuates progression of rheumatoid arthritis through alteration in ULK-1 independent autophagy pathway in collagen induced arthritis mice model.
Rheumatoid arthritis (RA) is a multifactorial disease which is complicated by apoptosis resistance. Autophagy is one of the key mechanisms which are involved in the development of resistance to apoptosis as well as to the standard therapies against RA. Aberration in autophagy and apoptosis homeostasis results in the development of oxidative stress thus complicates the pathogenesis of RA. In the given study, tomorou, an indigenous herb of Hunza-Nagar Valley, has been evaluated for its pro-apoptotic, anti-inflammatory, and anti-rheumatic activity. Several major classes of bioactive phytochemicals including steroids, terpenoids, phenols, flavonoids, and essential oils have been detected in the aqueous and ethyl acetate extracts of tomorou through phytochemical analysis. Plant extracts depicted enhanced free radical scavenging activity through di-phenyl-2-picryl hydrazyl hydrate (DPPH) assay and ameliorated the symptoms of arthritis in collagen induced arthritic (CIA) mice model. Moreover, the 6 week extract treatment resulted in the reduction of IL-6 serum levels thus making it an effective anti-inflammatory agent. Upregulation of microtubule-associated proteins light chain 3b (LC3b) and downregulation of UNC51-like kinase 1 (ULK-1) in arthritic mice proposed a ULK-1 independent non-canonical autophagy pathway. Treatment with extracts upregulated the expression of caspase 3 which in turn inhibited the activity of LC3b thus altering the autophagy pathway. However, ULK-1 expression was restored to normal in aqueous extract treated group whereas it was upregulated in ethyl acetate extract treated group. On the other hand, a novel LC3b-independent autophagy pathway was observed in mice treated with ethyl acetate extract due to ULK-1 upregulation. Despite of significantly high IL-6 levels, the arthritic symptoms waned off which suggested the participation of IL-6 in LC3b-independent autophagy pathway in the extract prepared in ethyl acetate. Conclusively, the study established pro-apoptotic, antioxidant, anti-inflammatory and anti-rheumatic activity of tomorou and suggested an intricate autophagy pathway shift.


Effect of epinephrine upon irreversible disposal and recycling of glucose in dogs.
Irreversible utilization and recycling of glucose during epinephrine-induced hyperglycemia were studied in adrenal-demedullated dogs exposed to neutral or cold ambient temperature. Whatever the ambient temperature, most of the extra glucose mobilized by epinephrine is recycled rather than irreversibly utilized by the peripheral tissue.


Modifications of the activities of key enzymes and intracellular levels of cyclic nucleotides, in correlation with the glyogen deposition in a cultured hepatoma cell line.
Glycogen accumulation in growing cultures of ZHC cells (originally derived from the Zajdela ascitic hepatoma) is accompanied by an increase in glycogen synthetase (E.C. 188.8.131.52) and phosphorylase (E.C. 188.8.131.52) activities. Essentially the synthetase b and the phosphorylase a are involved in this process. The glycogen accumulation in ZHC cells us preceeded by a noticeable peak of cAMP, whereas cGMP rises early after replating and then decreases simultaneously with the growth rate. The present results suggest that these cultured hepatoma cells undergo throughout every passage an induction process involved in glycogen synthesis storage. Since the original ascites cells growing in vivo (which lack glycogen) and the cultured ZHC cells exhibit similar glycogen synthetase and phosphorylase activities, the resurgence of the glycogenic function (Staedel and Beck, 1978) in the in vitro cultureed cells does not seem related to a change in these two enzymes. By contrast, the high cyclic nucleotide levels in the cultured cells, as compared to those in the ascites cells, offer a possible explanation.


An overview on surfactants as pollutants of concern: Occurrence, impacts and persulfate-based remediation technologies.
Surfactants are molecules that reduce interfacial energy and increase solubility of other pollutants in water. These properties make them suitable for various domestic and industrial applications, soil remediation, pesticide formulation, among others. The increase in their use and the lack of strict regulations regarding their disposal and management is a matter of concern and requires more attention since the release and distribution of these compounds into the environment can modify important water quality parameters. As a result of these changes, different toxicological effects to aquatic organisms are discussed and exposed herein. On this basis, we provide an overview of the classes of surfactants, as well as their occurrence in different aqueous matrices. In addition, existing regulations around the world regarding their concentration limit for different environments are discussed. Current research focuses on the application of conventional treatments, such as biological treatments; notwithstanding, more toxic and bioaccumulative products can be generated. Advanced Oxidation Processes are promising alternatives and have also been widely applied for the removal of surfactants. This study provides, for the first time, an overview of the application of persulfate-based processes for surfactants degradation based on recent literature findings, as well as the various factors related to the activation of the persulfate anions. This review also highlights the challenges and opportunities for future research to overcome the obstacles to the practical application of this process.


Inhibitory control task is decreased in vascular incontinence patients.
'Vascular incontinence' is a part of elderly incontinence due to cerebral white matter change (WMC). We studied the relationship between performance on several cognitive tasks and urodynamic detrusor overactivity (DO) in patients with vascular incontinence. We recruited 40 patients with lower urinary tract symptoms due to WMC [20 male, 20 female; mean age 77 years (60-89 years)]. Other neurologic, urologic, and systemic causes of LUT dysfunction were excluded. All patients underwent urodynamics tests and two sets of cognitive tasks, i.e., the Mini-Mental State Examination (MMSE) (general cognitive tasks), and the Frontal Assessment Battery (FAB) (frontal lobe tasks). The most common urinary symptom was urinary urgency (27 patients), followed by urinary incontinence (26) and nocturnal urinary frequency (25). The urodynamic testing revealed DO in 22 patients. The cognitive testing revealed that the patients' mean MMSE score was 25.8 (range 15-30), and their mean FAB score was 13.6 (4-18). There was no relationship between DO and the total MMSE or FAB score, but our analysis of the relationship between DO and the six subdomains of the FAB (conceptualization, mental flexibility, programming, sensitivity to interference, inhibitory control, and environmental autonomy) revealed a significant relationship between DO and the inhibitory control task (p < 0.005). The results of the present study showed that performance on an inhibitory control task is decreased in vascular incontinence patients with DO.


Beyond one-way determinism: San Frediano's miracle and climate change in Central and Northern Italy in late antiquity.
Integrating palaeoclimatological proxies and historical records, which is necessary to achieve a more complete understanding of climate impacts on past societies, is a challenging task, often leading to unsatisfactory and even contradictory conclusions. This has until recently been the case for Italy, the heart of the Roman Empire, during the transition between Antiquity and the Middle Ages. In this paper, we present new high-resolution speleothem data from the Apuan Alps (Central Italy). The data document a period of very wet conditions in the sixth c. AD, probably related to synoptic atmospheric conditions similar to a negative phase of the North Atlantic Oscillation. For this century, there also exist a significant number of historical records of extreme hydroclimatic events, previously discarded as anecdotal. We show that this varied evidence reflects the increased frequency of floods and extreme rainfall events in Central and Northern Italy at the time. Moreover, we also show that these unusual hydroclimatic conditions overlapped with the increased presence of "water miracles" in Italian hagiographical accounts and social imagination. The miracles, performed by local Church leaders, strengthened the already growing authority of holy bishops and monks in Italian society during the crucial centuries that followed the "Fall of the Roman Empire". Thus, the combination of natural and historical data allows us to show the degree to which the impact of climate variability on historical societies is determined not by the nature of the climatic phenomena per se, but by the culture and the structure of the society that experienced it. The online version contains supplementary material available at 10.1007/s10584-021-03043-x.


The clinical significance of renal resistance index (RRI) and renal oxygen saturation (RrSO2) in critically ill children with AKI: a prospective cohort study.
The purpose of this study was to look into the clinical significance of the renal resistance index (RRI) and renal oxygen saturation (RrSO2) in predicting the development of acute kidney injury (AKI) in critically ill children. A new non-invasive method for the early detection and prediction of AKI needs to develop. Patients admitted to the pediatric intensive care unit (PICU) affiliated with the capital institute of pediatrics from December 2020 to March 2021 were enrolled consecutively. Data of clinical information, renal Doppler ultrasound, RrSO2, and hemodynamic index within 24 h of admission were prospectively collected. Patients were divided into two groups: the study group was AKI occurred within 72 h, while the control group did not. SPSS (version 25.0) was used to analyze the data, and P < 0.05 was considered a statistical difference. 1) A total of 66 patients were included in this study, and the incidence of AKI was 19.70% (13/66). The presence of risk factors (shock, tumor, severe infection) increased the incidence of AKI by three times. 2) Univariate analysis showed significant differences in length of hospitalization, white blood cells (WBC), C-reactive protein (CRP), renal resistance index (RRI), and ejection fraction (EF) between the study and control groups (P < 0.05). There were no significant differences in renal perfusion semi-quantitative score (P = 0.053), pulsatility index (P = 0.051), pediatric critical illness score (PCIS), and peripheral vascular resistance index (P > 0.05). 3) Receiver operating characteristic (ROC) curve showed that if RRI > 0.635, the sensitivity, specificity, and AUC for predicting AKI were 0.889, 0.552, and 0.751, respectively; if RrSO2 < 43.95%, the values were 0.615, 0.719 and 0.609, respectively; if RRI and RrSO2 were united, they were 0.889, 0.552, and 0.766, respectively. The incidence of AKI is high in PICU patients. And infection, RRI, and EF are risk factors for AKI in PICU patients. RRI and RrSO2 have certain clinical significance in the early prediction of AKI and may provide a new non-invasive method for early diagnosis and prediction of AKI.


Automatic classification of electromyographic signals.
The results of the application of classification methods to electromyograph signals of weak contractions in normal and myopathic subjects are described. Methods of pattern recognition, previously presented, allow the selection of representative motor unit action potentials. The analysis is done with ordinal qualitative variables obtained by identification of shape descriptive parameters (amplitude, duration, number of phases, number of extrema). From this analysis, characteristic classes for normality and myopathy appear, from which a diagnostic aid by assignment can be made.


Integrated structure-guided computational design of novel substituted quinolizin-4-ones as Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) inhibitors.
Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is a known drug target for the development of antimalarial agents. Herein, we presented integrated structure-guided computational strategies for the design of novel quinolizin-4-ones as PfDHODH inhibitors. PROCHECK and ERRAT analysis were performed for the validation of co-crystal structures of PfDHODH enzyme bound to the inhibitors available on PDB. Based on the results, PDB ID: 6i55 was selected for further structure-guided in silico studies. Five featured-based pharmacophore model (AADRR) was generated, and validated using GH scoring (0.74) and ROC analysis (0.94). Validated structure-based model was further used as a 3D search query to screen the ZINC database. Retrieved database compounds ZINC00386658, ZINC08439293, and ZINC09089086 were found in agreement with query features based on their highest fitness scores. HTVS, SP and XP docking studies with these retrieved hits demonstrated important interactions (His185. Arg265) with PfDHODH. Mapping of features of the pharmacophore model on these retrieved hits along with the role played by scaffolds and functional groups in docking study helped in the selection of quinolizin-4-one as a main scaffold and different functional groups for the design of novel compounds as PfDHODH inhibitors. In silico ADMET prediction study suggested that designed quinolizin-4-ones are "drug-like" candidates and can be synthesised without too many difficulties. In docking study of newly designed compounds, 8d exhibited the highest docking score of - 12.78 kcal/mol and formed important polar interactions (His185. Arg265) with the PfDHODH. PfDHODH-8d complex showed stable RMSD between 2.5 Å and 3 Å during 100 ns MD simulation study. The RMSD, RMSF and RoG analysis of the PfDHODH-8d complex indicated the absolute stability of the complex. Overall, combined in silico study identified quinolizin-4-ones as selective PfDHODH inhibitors.


Use of medication reviews among older women with dementia, 2003-2015: A longitudinal cohort study.
To identify factors associated with incidence of medication reviews (MRs), particularly in women with dementia and in residential aged care (RAC). Data from 10 359 women in the 1921-1926 cohort of the Australian Longitudinal Study on Women's Health were linked to Medicare Benefits Schedule data to identify MRs for each year from 2003 to 2015. Incidence of MR increased from 2003 to 2013 (age 87-92 years) when 37.1% of women with dementia had a MR compared to 19.8% of women without dementia. Adjusting for time and other factors, the odds of having a MR were higher for women with dementia (AOR = 1.18, 95% CI: 1.06-1.32) and women in RAC (AOR = 3.61, 95% CI: 3.28-3.98). Although higher in women with dementia and those in RAC, utilisation of MR was modest. System-level interventions may be required to ensure the use and benefits of MRs.


Mapping of the podocin proximity-dependent proteome reveals novel components of the kidney podocyte foot process.
Introduction: The unique architecture of glomerular podocytes is integral to kidney filtration. Interdigitating foot processes extend from the podocyte cell body, wrap around fenestrated capillaries, and form specialized junctional complexes termed slit diaphragms to create a molecular sieve. However, the full complement of proteins which maintain foot process integrity, and how this localized proteome changes with disease, remain to be elucidated. Methods: Proximity-dependent biotin identification (BioID) enables the identification of spatially localized proteomes. To this end, we developed a novel in vivo BioID knock-in mouse model. We utilized the slit diaphragm protein podocin (Nphs2) to create a podocin-BioID fusion. Podocin-BioID localizes to the slit diaphragm, and biotin injection leads to podocyte-specific protein biotinylation. We isolated the biotinylated proteins and performed mass spectrometry to identify proximal interactors. Results and Discussion: Gene ontology analysis of 54 proteins specifically enriched in our podocin-BioID sample revealed 'cell junctions,' 'actin binding,' and 'cytoskeleton organization' as top terms. Known foot process components were identified, and we further uncovered two novel proteins: the tricellular junctional protein Ildr2 and the CDC42 and N-WASP interactor Fnbp1l. We confirmed that Ildr2 and Fnbp1l are expressed by podocytes and partially colocalize with podocin. Finally, we investigated how this proteome changes with age and uncovered a significant increase in Ildr2. This was confirmed by immunofluorescence on human kidney samples and suggests altered junctional composition may preserve podocyte integrity. Together, these assays have led to new insights into podocyte biology and support the efficacy of utilizing BioID in vivo to interrogate spatially localized proteomes in health, aging, and disease.


Prolonged postictal stupor: nonconvulsive status epilepticus, medication effect, or postictal state?
We describe a patient who entered a stuporous state after receiving benzodiazepine treatment for generalized tonic-clonic status epilepticus. A diagnosis of generalized NCSE with tonic seizures was made on the basis of the clinical picture and response to barbiturate anaesthetic, although the EEG pattern was not typical of the changes previously described in tonic seizures-tonic status epilepticus. This report discusses the differential diagnosis of postictal stupor, nonconvulsive status epilepticus with tonic seizures and sedation caused by the emergency treatment of status epilepticus, and summarizes the literature on tonic seizures and tonic status epilepticus.


Different protocols in treatment of placental retention in dairy cows and their influences on reproductive performance.
The study aimed to evaluate the effect of α-chymotrypsin on placental separation as a treatment protocol for retained placenta (RP) in dairy cows and its effect on reproductive performance after placental shedding. The study was conducted on 64 crossbred cows that suffered from retained placenta. Cows were divided into four equal groups: group I (n = 16) treated with prostaglandin F2α (PGF2α); group II (n = 16) treated with PGF2α in combination with α-chemotrypsin; group III (n = 16) treated with α-chemotrypsin only and group IV (n = 16) treated by manual removal of the RP. Cows were under observation after treatment till placental shedding. Placental samples were taken from the non-responsive cows after the course of treatment and examined to observe the histopathological changes in each group. Results revealed that the time of placental dropping showed a significant decrease in group II compared to other groups. Histopathological examination of group II shows that collagen was found as fewer fibres in scattered areas and necrosis appeared as numerous areas widespread in the foetal villi. A few inflammatory cells were infiltrated in the placental tissue and the vascular changes appear as mild vasculitis and mild oedema. Cows in group II have rapid uterine involution, decreased risk of post-partum metritis and improved reproductive performance. It is concluded that PGF2α in combination with α- chemotrypsin is the recommended treatment for RP in dairy cows. This recommendation is warranted, as this treatment was successful in achieving rapid placental shedding, rapid uterine involution, a decreased risk of post-partum metritis and improved reproductive performance.


Surface chemistry and spectroscopic studies of the native phenylalanine dehydrogenase Langmuir monolayer at the air/aqueous NaCl interface.
This study investigates the main aspects of the surface behavior of the native phenylalanine dehydrogenase (PheDH) enzyme at the air/aqueous interface employing a saline subphase to induce the enzyme surface activity. Surface chemistry experiments were performed in order to determine the surface packing and stability of the formed layer, while spectroscopic experiments provided information regarding its secondary structure conformation. It was found that the PheDH enzyme forms a fluid film, which is quite homogeneous throughout its entire compression, being stable for long periods of time with no significant evidence of aggregates or irreversible domains during interfacial compression/decompression processes. The main secondary structures of the interfacial PheDH film were accessed via in situ reflectance-absorbance infrared spectroscopy, indicating a majority presence of α-helices, which were maintained after the film transfer to solid muscovite supports. The immobilized films presented a homogeneous and regular deposition, with controlled roughness and a mean thickness in the range of 8-10 nm.


Regression of intracardiac heparin-induced thrombosis after aortic root surgery.
Heparin-induced thrombocytopenia and thrombosis syndrome (type II) is associated with thromboembolic complications and a mortality rate up to 30%. We describe a patient who developed intracardiac and aortic Dacron prosthesis heparin-induced thrombosis after aortic root conservative surgery. Successive transoesophageal echocardiographies demonstrated a progressive regression of intracardiac thrombosis with oral anticoagulation by warfarin and antiplatelet therapy combining aspirin and clopidogrel.


[History of the textbook].
The textbook "Dermatologie und Venerologie" originated with the 1st (1961) and 2nd (1969) German editions by Keining and Braun-Falco from the Departments of Dermatology at the Universities of Mainz and Marburg. The 3rd German edition was written by Braun-Falco, Plewig and Wolff (1984). The three authors became editors with the 4th German edition. Until now three English and several other foreign editions appeared. New editors are now Plewig, Burgdorf, Landthaler, Ruzicka and Hertl. Not only in German speaking countries but also in many other parts of the world the textbook is frequently used by students, residents, and dermatologists. With this retrospective view, the story of the revised editions of the book and its distribution is told.


A novel poly(ADP-ribose) polymerase inhibitor, ABT-888, radiosensitizes malignant human cell lines under hypoxia.
The chemo- and radioresponse of tumor cells can be determined by genetic factors (e.g., those that modify cell cycle arrest, DNA damage repair or cell death) and microenvironmental factors, such as hypoxia. Poly(ADP-ribose) polymerase (PARP) is a nuclear enzyme that rapidly recognizes and binds to DNA breaks to facilitate DNA strand break repair. Pre-clinical data suggest that PARP inhibitors (PARPi) may potentiate the effects of radiotherapy and chemotherapy. However, it is unclear as to whether PARPi are effective against hypoxic cells. We therefore tested the role for a novel PARPi, ABT-888, as a radiosensitizing agent under hypoxic conditions. Using human prostate (DU-145, 22RV1) and non-small cell lung (H1299) cancer cell lines, we observed that ABT-888 inhibited both recombinant PARP activity and intracellular PARP activity (86% to 92% decrease in all 3 cells lines following 2.5 microM treatment). ABT-888 was toxic to both oxic and hypoxic cells. When ABT-888 was combined with ionizing radiation (IR), clonogenic radiation survival was decreased by 40-50% under oxic conditions. Under acute hypoxia, ABT-888 radiosensitized malignant cells to a level similar to oxic radiosensitivity. To our knowledge, this is the first study to demonstrate that inhibition of PARP activity can sensitize hypoxic cancer cells and the combination of IR-PARPi has the potential to improve the therapeutic ratio of radiotherapy.


Adverse cardiac responses to alpha-lipoic acid in a rat-diabetic model: possible mechanisms?
Alpha-lipoic acid (ALA) is widely used as an antioxidant for the treatment of diabetes and its complications; however, the pro-oxidant potential of ALA has recently been reported. This study was designed to investigate whether ALA supplementation could have pro-oxidant effects on cardiac tissues in normal and diabetic rats. Diabetes was induced by a single dose of streptozotocin (STZ; 55 mg/kg (intraperitoneal). Diabetic and normal rats were treated with ALA (100 mg kg(-1) day(-1)) for 45 days. ALA supplementation resulted in oxidative protein damage as evident by significant reduction in the cardiac levels of protein thiol in ALA-treated normal rats (P < 0.01) together with a significant elevation (P < 0.001) in the plasma levels of advanced oxidation protein products in ALA-treated normal rats and in ALA + STZ-diabetic rats compared with the normal control rats. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has emerged as the major source of superoxide anion and enhanced oxidative damage in heart failure. ALA supplementation increased the myocardial immunoreactivity of p47phox subunit of NADPH oxidase in both normal nondiabetic and diabetic rats reflecting its pro-oxidant effect. Data showed that ALA supplementation failed to prevent cardiac complications in diabetic rats and led to cardiac toxicity in normal rats as indicated by pathological changes (cellular infiltration, fibrosis, and degeneration) and by the elevation of serum cardiac biomarkers compared with normal controls. The pro-oxidant effects of ALA suggest that careful selection of appropriate doses of ALA in reactive oxygen species-related diseases are critical.


Neurocognitive outcomes of children secondary to mild iodine deficiency in pregnant women.
Iodine deficiency is the most important preventable cause of brain damage worldwide. During pregnancy, severe iodine deficiency causes endemic cretinism, whereas mild-to-moderate iodine deficiency impairs neurocognitive function of the offspring. Numerous reports demonstrate the impact of iodine supplementation on prevention of cretinism, and recent studies evaluate the effects of iodine prophylaxis on neurocognitive development in children of women with mild-to-moderate iodine deficiency. Iodine prophylaxis is generally well tolerated without side effects for the pregnant women and the offspring. In France, the iodine status was recently considered as satisfactory in children and adult population, but regional studies conducted during the last two decades have shown that healthy women are mild-to-moderately iodine deficient during pregnancy. According to recent World Heath Organization guidelines, systematic iodine prophylaxis is recommended in women planning a pregnancy, during gestation and lactation in order to prevent maternal, neonatal and infantile consequences of mild-to-moderate iodine deficiency.


Muscle surface membranes: preparative methods affect apparent chemical properties and neurotoxin binding.
Considerable disagreement exists between results reported by various authors for lipid composition and enzyme activity in purified muscle membrane fractions presumed to be sarcolemma, although an explanation for these discrepancies has not been presented. We have prepared muscle light surface membrane fractions of comparable density (1.050--1.120) by a low-salt sucrose method and by an LiBr-KCl extraction procedure and compared them for density profile, total lipid and cholesterol content, protein composition and ATPase activity. In addition, sodium channels characteristic of excitable membranes have been quantitated in each preparation using [3H]saxitoxin binding assays, and the density of acetylcholine receptors determined in fractions from control and denervated muscle using alpha-[125I]bungarotoxin. Although both fractions contain predominantly surface membrane, the LiBr fraction consistently shows the higher specific activity of p-nitrophenylphosphatase, higher free cholesterol content, and higher density of sodium channels and acetylcholine receptors. The density distribution of sodium channels appears uniform throughout both fractions. Quantitative differences were seen between sodium dodecyl sulfate polyacrylamide gel electrophoresis patterns of membrane proteins from the two preparations although most bands are represented in both. A majority of the low-salt sucrose light membrane proteins were accessible in varying degrees to labelling with diazotized diiodosulfanylic acid in intact muscle. These results suggest that light surface membrane fractions may be mixtures of sarcolemma and T-tubular membranes. Using our preparative methods, the LiBr fraction may contain predominantly sarcolemma while low-salt sucrose light membranes may be enriched in T-tubular elements.


The survival rate among endovascular and open surgical repair of abdominal aortic aneurysms.
A best evidence topic has been constructed using a described protocol. The three-part question addressed was: In patients with Infrarenal abdominal aortic aneurysm (AAA), Does endovascular abdominal aortic repair (EVAR), AS compared to open surgical repair (OSR), has higher Survival rates? The outcomes assessed were the overall survival rates in both techniques. The best evidence showed that there is no statistically significant difference between EVAR and OSR in survival rates.


Retraction Note: Urinary Cross-linked N-telopeptides of Type I Collagen Levels in Patients with Rheumatoid Arthritis.
The Editors-in-Chief have retracted this article [1]. Serious concerns have been raised about the data presented [2], and after careful consideration and additional investigation the Editors-in-Chief no longer have confidence in this article. All authors were contacted and did not respond to correspondence about this retraction.


Pneumoscrotum in patient with pneumothorax: A case report.
Pneumoscrotum is a rare clinical condition that might be a secondary of another serious, life-threatening condition. In pneumoscrotum, the scrotum enlarged due to the presence of air in the scrotal sac, either in the subcutaneous tissue or tunica vaginalis. We report a 40-year-old male presented to the emergency room, with a shortness of breath. From the examination, the patient was diagnosed with left pneumothorax and performed Water Sealed Drainage (WSD) on the left hemithorax. After the installation of WSD, pneumoscrotum was obtained and conservative treatment was performed in the patient to treat the pneumoscrotum.


Biallelic variants in ETV2 in a family with congenital heart defects, vertebral abnormalities and preaxial polydactyly.
The combination of congenital heart defects and vertebral anomalies with or without additional abnormalities has been reported in many genetic disorders. We describe a family in which four consecutive pregnancies were characterized by the combination of fetal congenital heart malformations and vertebral anomalies. In addition, preaxial polydactyly was detected in one of the fetuses. Reanalysis of the non-diagnostic clinical exome data revealed compound heterozygous variants c.350del, p.(Gly117AlafsTer90) and c.757G > T, p.(Asp253Tyr) in ETV2 which have previously not been known to be associated with a phenotype in humans. In mice, Etv2 encodes an obligatory transcription factor involved in the generation of hematopoietic and endothelial cells. Its homozygous disruption results in embryonic lethality due to severe blood and vessel defects. The Etv2 promoter may be bound by Nkx2-5, a key transcription factor in heart development. Pathogenic variants in the NKx2-5 homolog in humans (NKX2-5) are related to congenital heart defects. The identification of additional fetuses or live-born individuals with biallelic pathogenic variants in ETV2 will shed further light on this presumably novel gene-phenotype association and on the full phenotypic spectrum.


Woake's syndrome. A case report in a teenager.
Woake's syndrome was described for the first time in the European literature in 1885 and features necrotic ethmoiditis, nose broadening due to polyps in early childhood, frontal sinus aplasia, bronchiectasis and production of highly viscous mucus (dyscrinia). A case is reported and the literature is reviewed.


Allantoin racemase: a new enzyme from Pseudomonas species.
1. Allantoin racemase is a novel enzyme which catalyzes the conversion of S(+)-and R(minus)-allantoin into the racemate. 2. The enzyme is present in Pseudomonas testosteroni, Pseudomonas putida and five biotypes of Pseudomonas fluorescens, but absent in a number of other Pseudomonas species. 3. The enzyme of Ps. testosteroni was purified 133-fold and exposes optimal activity at pH 8.0-8.2 and 50 degrees C. The enzyme is stable on heating for 15 min at 70 degrees C. 4. The enzyme appeared to be specific for the optical isomers of allantoin and no cofactors are involved in the reaction. 5. The optical aspecificity of allantoinase of Proteus rettgeri was reaffirmed.


Allogenous cartilage graft versus autogenous cartilage graft in augmentation rhinoplasty: a decade of clinical experience.
Cartilage grafts have great value in augmentation rhinoplasty. For most surgeons, an autogenous cartilage graft is the first choice in rhinoplasty because of its resistance to infection and resorption. On the other hand, an allogenous cartilage graft might be preferred over an autogenous graft to avoid additional morbidity and lengthened operating time. Allogenous cartilage grafts not only have the advantage of averting donor site morbidity but also are resistant to infection, resembling autogenous cartilage grafts. The authors present their experience with 41 patients who underwent augmentation rhinoplasty using 22 autogenous and 19 allogenous cartilage grafts between June 1994 and August 2004. For evaluation of adequate augmentation rates, photographic analyses were performed on preoperative, early postoperative, and late postoperative photographs from all the patients. To assess patient satisfaction, the Facial Appearance Sorting Test (FAST) was applied preoperatively and late postoperatively in both groups. These results were compared, and it was concluded that in terms of resorption, there was no difference in the early and late postoperative follow-up data between allogenous and autogenous cartilage grafts. Evaluation of the preoperative and early postoperative photographic outcomes showed statistically significant differences with respect to adequate augmentation rates between the two groups. The FAST scores showed statistically significant differences between preoperative and late postoperative outcomes. There were no infections in the two groups of patients.


The effect of prescription opioid injection on the risk of non-fatal overdose among people who inject drugs.
Prescription opioid (PO) use by people who inject drugs (PWID) is a growing public health concern. Non-fatal overdose remains a leading source of morbidity among PWID, however, little is known about the relationship between PO injection and non-fatal overdose in this population. In this study we sought to examine the impact of PO injection on non-fatal overdose among PWID from Vancouver, Canada. Data were derived from two open prospective cohorts of PWID for the period of December, 2005 to May, 2014. Multivariable generalized estimating equations were used to examine the odds of overdose among those who injected: POs; heroin; and POs and heroin. In total, 1660 PWID (33.7% women) participated in this study. In multivariable analyses, in comparison to those who were injecting non-opioid drugs, exclusive PO injection was not significantly associated with non-fatal overdose (adjusted odds ratio [AOR]: 1.17, 95% confidence interval [CI]: 0.74-1.86). The odds of non-fatal overdose were elevated for heroin injection (AOR: 1.72, 95% CI: 1.31-2.27), but were greatest for those who injected both heroin and POs (AOR: 2.46, 95% CI: 1.83-3.30). Compared to injecting non-opioids, injecting POs exclusively did not increase risk of non-fatal overdose; however, injecting both POs and heroin doubled the risk. This may reflect consistencies in drug potency and composition when POs are used, as well as unique characteristics of exclusive PO injectors. Our findings call for the continued scale-up of evidence-based overdose prevention interventions for people who inject opioids, including POs.


Patient perspectives on states worse than death: A qualitative study with implications for patient-centered outcomes and values elicitation.
Seriously ill patients rate several health outcomes as states worse than death. It is unclear what factors underlie such valuations, and whether consideration of such states is useful when making medical decisions. We sought to (1) use qualitative approaches to identify states worse than death, (2) identify attributes common to such undesirable health states, and (3) determine how participants might use information on these states in making medical decisions. Qualitative study of semi-structured interviews utilizing content analysis with constant comparison techniques. We interviewed adults age 65 or older with serious illnesses after discharge home from one of two urban, academic hospitals. Eligible patients were purposively sampled to achieve balance in gender and race. Of 29 participants, 15 (52%) were female, and 15 were white (52%), with a median age of 72 (interquartile range 69, 75). Various physical, cognitive, and social impairments were identified as states worse than death. The most commonly reported attributes underlying states worse than death were perceived burden on loved ones and inability to maintain human connection. Patients believed information on states worse than death must be individualized, and were concerned their opinions could change with time and fluctuations in health status. Common factors underlying undesirable states suggest that for care to be patient-centered it must also be family-centered. Patients' views on using states worse than death in decision making highlight barriers to using avoidance of such states as a quality measure, but also suggest opportunities for eliciting patients' values.


Quality assessment and assurance in diagnostic imaging. Theoretical and practical considerations and a quality audit of the excretory urogram.
Concepts necessary to an understanding of the basics of quality assurance audits are presented. Included are specific examples that bridged theory and practice by applying the protocol to a real-life diagnostic imaging situation. This method meets the present requirements of the Joint Commission of the Accrediation of Hospitals.


The dorsomedial hypothalamic nucleus in autonomic and neuroendocrine homeostasis.
Median eminence and ventromedial hypothalamus have in the past been the principal foci of research in neuroendocrine and neurovisceral control mechanisms. The present report provides an overview of work involving the dorsomedial hypothalamic nucleus (DMV). This structure is located dorsal to the ventromedial hypothalamic nucleus (VMN) to the plane of the dorsal premammillary nucleus. Fibers from the DMN pass with the periventricular system and the dorsal longitudinal fasciculus of Schütz and have been traced to the midbrain tegmentum and reticular formation. Intrahypothalamic connections involve intensive networks between DMN, lateral hypothalamic nucleus (LHN) and VMN. Regarding neurotransmitters, recent studies indicate that the DMN receives noradrenergic innervation along two pathways, a dorsal and a ventral one. Monoamine-containing systems approach the DMN From the lateral hypothalamus and the bulk of these fibers are carried in the medium forebrain bundle from their cells of origin in the brain stem. Studies of the vascular supply indicate that both VMN and DMN receive their blood supply from the internal carotid artery...


Detection of bacterial vaginosis, Trichomonas vaginalis infection, and vaginal Candida infection: a comparative study of methods of extracting exudates, with and without a speculum, during pregnancy.
To compare the collection of vaginal exudates with and without the use of a speculum to diagnose vaginal infections. We examined 45 patients with vaginal discharge. Two vaginal swabs were taken, one with and the other without a speculum. Both were examined by wet mount microscopy to detect bacterial vaginosis (BV), Trichomonas vaginalis, and the presence of blastospores with or without pseudomycelium. A total of 90.9% of patients whose vaginal exudates were negative for BV when extracted with a speculum were also negative in the swab taken without a speculum. In the case of BV-positive exudates using a speculum, the correspondence was 90.5% with the swabs taken without a speculum. Among those exudates obtained with a speculum that were negative for Candida, 92.6% of those obtained without a speculum tested negative. In patients with pseudomycelium, when a speculum was used, 100% also presented a diagnosis of pseudomycelium from the swabs taken without a speculum. A concordance test between the techniques involving the use or nonuse of a speculum was performed for each of the diagnoses showed a good agreement according to the observed Kappa statistics (0.8467 and 0.8396 for BV and Candida, respectively). A very good agreement between the results obtained with and without the use of a speculum was observed. Swabbing without the use of a speculum is especially convenient for pregnant women who require frequent testing for these types of infections during their pregnancies.


A dual-function fluorescence 'turn-on' probe that allows Zn (II) bioimaging and quantification of water in the organic solvent.
Herein, a Eugenol-derived fluorescence 'turn-on' probe FLHE was synthesized by condensing 2-((3-(trifluoromethyl)phenyl)amino)benzohydrazide with 5-allyl-2-hydroxy-3-methoxybenzaldehyde. FLHE demonstrated very low fluorescence in the studied organic solvents of varying polarities. However, upon titration with Zn2+ in HEPES buffer (pH = 7.4, 50% ACN, v/v), FLHE showed 40-fold higher fluorescence signals indicating the formation of the FLHE-Zn2+ complex. The fluorescence turn-on phenomenon upon FLHE-Zn2+ complex formation results from a chelation-enhanced fluorescence (CHEF) effect. The FLHE-Zn2+ complexation demonstrated a stokes shift of 156 nm (λex = 350 nm, λem = 506 nm) and an about 33-fold increase in the quantum yield (FLHE, Φ = 0.007; FLHE-Zn2+ complex, Φ = 0.23). The binding constant (Ka) determined by the Benesi-Hildebrand plot for interaction between FLHE and Zn2+ was 5.33 × 103 M-1. FLHE demonstrated a LOD of 31.8 nM for detecting Zn2+ in the environmental samples without interference from other cations and anions. FLHE-based paper strip (FLHE-PS) assay was developed to quantify the Zn2+ ions in water and the water content of organic solvent. FLHE-PS allows the detection of Zn2+ in aqueous solutions with a LOD of 63.2 nM and quantifying water in acetonitrile with a LOD of 0.14%. These results indicate that the FLHE has high applicability for detecting Zn2+ in living cells and environmental samples and detecting the presence of water in the organic solvents.