Understanding large-scale deforestation in southern Jinotega, Nicaragua from 1978 to 1999 through the examination of changes in land use and land cover.
Nicaragua, home to the largest remaining extent of rainforest in Central America (total surface area) and to a significant indigenous population, has lost approximately half of its forest cover since 1950. This major and rapid loss of forest cover has been explained as the consequence of an eastward moving agricultural frontier that cuts through the region of Jinotega. If the current deforestation rate continues, the country could lose its remaining forest cover over the course of the next two decades; therefore, it is essential that the dynamics and relationships of land-use and land-cover change (LUCC) in this region are understood. To examine LUCC in Nicaragua over time, Landsat imagery from the southern portion of the region of Jinotega, taken in 1978, 1987, and 1999 was utilized. A remote-sensing method, supervised classification, which allows for the grouping of spectrally similar values for each year, followed by an image change detection analysis (postclassification comparison) was conducted. Groundtruthing (field validation) was conducted in 2006 to validate the data, which yielded increasing overall accuracy rates of 71.68% for 1978, 82.35% for 1987, and 84.38% for 1999. The classification and change detection results showed that if the agricultural cultivation overtook this region, it happened before 1978. Therefore, the possibility that either deforestation did not actually occur along an agricultural frontier or that it was located further east exists; this would be an interesting subject for future studies. There was, however, clear evidence of increased forest cover from 1987 to 1999 near the urban center, correlating with the enforced reforestation law in the city of Jinotega.


Influence of isoproterenol and cholestyramine on acute gastric mucosal ulcerogenesis.
One thesis concerning the pathogenesis of "stress ulcer" states that the combination of (1) bile acid-induced H+ "back diffusion" and (2) gastric mucosal ischemia is acutely Hg) to induce ischemia, this thesis was further tested by selectively mitigating either the ischemic or the back diffusion components of the model. Vascularized wedges of proximal canine gastric wall mounted on Lucite chambers were studied. With the mucosa directly visualized, control group A (6 dogs) was subjected sequentially to (1) topical acid test solution alone (ATS), (2) ATS + S, and (3) ATS + S + topical 5 mM Na taurocholate (TC). Study group B (6 dogs): (1) ATS, (2) ATS + S + the beta adrenergic agonist, isoproterenol, 1.5 microng per kg-min infused into the splenic artery, and (3) ATS + S + TC + isoproterenol. Study group C (6 dogs): (1) ATS, (2) ATS + S + the bile acid binding resin, cholestyramine (C), 4 g per liter, and (3) ATS + S + TC + C. During each period the net flux of H+, the electrical potential difference, and the aminopyrine clearance (AC) were determined. Mucosal damage (intramucosal hemorrhage, erosions, and ulcers, graded 0 to 5) was assessed blindly by an independent observer using photographs. The results indicate (1) that, despite H+ back diffusion comparable to ATS + S + TC, intraarterial isoproterenol significantly protects against lesion formation by increasing AC, and (2) that, despite a reduction in AC comparable to ATS + S + TC, topical C significantly protects against lesion formation by preventing excessive back diffusion of H+.


Plastic bowing, torus and greenstick supracondylar fractures of the humerus: radiographic clues to obscure fractures of the elbow in children.
The anterior humeral line is a valuable aid in the search for supracondylar fractures in children. When it is abnormal other signs of fracture should be carefully sought. The AHL was normal in only 5.8% of the cases reviewed (4 of 68 cases). There was other evidence of fracture in each case. Comparison of the AHLs on both sides is helpful when the AHL is normal since it may disclose subtle displacement of the line on the affected side. In children younger than 2 1/2 years the AHL may pass through the anterior third of the capitellum due to the small size of the ossification center; in these patients comparison with the opposite side may also be helpful.


Yap/Taz transcriptional activity in endothelial cells promotes intramembranous ossification via the BMP pathway.
Osteogenesis is categorized into two groups based on developmental histology, intramembranous and endochondral ossification. The role of blood vessels during endochondral ossification is well known, while their role in intramembranous ossification, especially the intertissue pathway, is poorly understood. Here, we demonstrate endothelial Yap/Taz is a novel regulator of intramembranous ossification in zebrafish. Appropriate blood flow is required for Yap/Taz transcriptional activation in endothelial cells and intramembranous ossification. Additionally, Yap/Taz transcriptional activity in endothelial cells specifically promotes intramembranous ossification. BMP expression by Yap/Taz transactivation in endothelial cells is also identified as a bridging factor between blood vessels and intramembranous ossification. Furthermore, the expression of Runx2 in pre-osteoblast cells is a downstream target of Yap/Taz transcriptional activity in endothelial cells. Our results provide novel insight into the relationship between blood flow and ossification by demonstrating intertissue regulation.


Fate of uncomplicated acute type B aortic dissection and impact of concurrent aortic dilatation on remote aortic events.
This study aimed to describe the reliable prognostic factors of mortality and subsequent aortic events during the follow-up of uncomplicated type B acute aortic dissection. From January 2004 to December 2014, 255 patients with uncomplicated type B acute aortic dissection were admitted to our hospital. Cox proportional hazards analysis was performed to identify risk factors for all-cause mortality, aorta-related mortality, and aortic events. In-hospital mortality was observed in 7 patients (2.7%). The rates of 5-year freedom from all-cause mortality, aorta-related mortality, and aortic events were 79.4% ± 2.9%, 93.3% ± 2.0%, and 71.7% ± 3.4%, respectively. The rate of 5-year freedom from aortic events was significantly lower among those with a patent false lumen (P = .006). Age and descending aorta diameter were independent risk factors of all-cause and aorta-related mortality (hazard ratio [HR], 1.08 and 1.13; 95% confidence interval [CI], 1.04-1.10 and 1.03-1.24; P = .0001 and .007, respectively). Independent risk factors for aortic events were descending aorta diameter, false lumen thickness, and dilatation of abdominal aorta (HR, 1.06; 95% CI, 1.02-1.12; P = .006; HR, 1.07; 95% CI, 1.04-1.11; P = .00002; HR, 2.01; CI, 1.20-3.38; P = .008). In uncomplicated type B acute aortic dissection, the age and dilatation of the thoracic aorta were associated with a higher risk of death, whereas false lumen thickness and concurrent abdominal aortic dilatation augment the risk for aortic events.


The COVID-19 Pandemic and Mental Health Concerns on Twitter in the United States.
During the COVID-19 pandemic, mental health concerns (such as fear and loneliness) have been actively discussed on social media. We aim to examine mental health discussions on Twitter during the COVID-19 pandemic in the US and infer the demographic composition of Twitter users who had mental health concerns. COVID-19-related tweets from March 5th, 2020, to January 31st, 2021, were collected through Twitter streaming API using keywords (i.e., "corona," "covid19," and "covid"). By further filtering using keywords (i.e., "depress," "failure," and "hopeless"), we extracted mental health-related tweets from the US. Topic modeling using the Latent Dirichlet Allocation model was conducted to monitor users' discussions surrounding mental health concerns. Deep learning algorithms were performed to infer the demographic composition of Twitter users who had mental health concerns during the pandemic. We observed a positive correlation between mental health concerns on Twitter and the COVID-19 pandemic in the US. Topic modeling showed that "stay-at-home," "death poll," and "politics and policy" were the most popular topics in COVID-19 mental health tweets. Among Twitter users who had mental health concerns during the pandemic, Males, White, and 30-49 age group people were more likely to express mental health concerns. In addition, Twitter users from the east and west coast had more mental health concerns. The COVID-19 pandemic has a significant impact on mental health concerns on Twitter in the US. Certain groups of people (such as Males and White) were more likely to have mental health concerns during the COVID-19 pandemic.


The Use of ctDNA for BRAF Mutation Testing in Routine Clinical Practice in Patients with Advanced Melanoma.
Assessment of BRAF mutation status is mandatory in advanced, treatment-naïve melanoma patients. Liquid biopsy can be an alternative in cases with inadequate or unavailable tumor tissue. The aim of our study was to evaluate the clinical utility of plasma circulating tumor DNA analysis for BRAF mutation testing and to assess outcomes of therapy with BRAF/MEK inhibitors initiated based on the liquid biopsy results. This was a retrospective single-center analysis of 46 patients (21 female, 25 male) with advanced melanoma who underwent circulating tumor DNA (ctDNA) BRAF mutation testing. A BRAF mutation was found in 45.7% (21/46) of liquid biopsies and 44.8% (13/29) of tissue samples. In patients with both ctDNA and tissue samples (n = 29), the concordance between the results of both tests was 82.8%. A BRAF mutation was detected in 7/17 (41.2%) patients with only ctDNA analysis. In 18 patients, therapy with BRAF/MEK inhibitors was initiated on the basis of the result of liquid biopsy. The objective response rate was 77.8 %, and the median PFS was 6.0 months. Our study confirms the clinical utility of BRAF mutation detection in plasma ctDNA. This study provides initial real-world data showing that treatment with BRAF/MEK inhibitors could be commenced based on liquid biopsy results.


Review: Tertiary cell wall of plant fibers as a source of inspiration in material design.
The review summarizes the plant lifehacks on material design on the example of the impressive cellulose-enriched cell wall deposited by fibers of many plants. This specific cell wall type is called tertiary since it is deposited after the secondary cell wall and is very distinct in the machinery of formation and function. The basic principles of tertiary cell wall performance include: 1) original composition (two major players - cellulose microfibrils and the version of rhamnogalacturonan I that forms specific supramolecular structures); 2) original cell wall design with axial orientation of all cellulose microfibrils, pronounced lateral interactions between them and the presence of the entrapped rhamnogalacturonan I; 3) dynamic changes in cell wall supramolecular organization due to rhamnogalacturonan I modifications in muro in the course of fiber maturation; 4) the built-in sensors that trace the cell wall state; 5) incorporation of tertiary cell wall into the system with higher level of organization.


Cognitive and Attentional Function in Children with Hypoplastic Left Heart Syndrome: A Pilot Study.
While survival for children with hypoplastic left heart syndrome (HLHS) has improved, compromised cardiac output and oxygen delivery persist, and children show cognitive deficits. Most research has assessed young children on broad cognitive indices; less is known about specific indices in older youth. In this pilot study, cognitive function and attention in youth ages 8 to 16 years with HLHS (n = 20) was assessed with the Wechsler Intelligence Scale for Children - Fifth Edition (WISC-V) and NIH Toolbox Cognition Battery (NTCB); parents completed the Child Behavior Checklist. Children scored significantly lower than normative means on the WISC-V Full Scale IQ, Verbal Comprehension, Visual Spatial, Working Memory, and Processing Speed indices, and the NTCB Fluid Cognition Composite; effect sizes ranged from medium to large. Attention problems had a large significant effect. Child age corresponded to lower visual spatial scores. Findings highlight the importance of assessing multiple cognitive indices for targeted intervention and investigating age and disease factors as potential correlates in larger samples.


Premedication with intravenous dexmedetomidine-midazolam suppresses fentanyl-induced cough.
The incidence of fentanyl-induced cough (FIC) occurs frequently during induction of general anesthesia, and methods to prevent it are needed. In this study, we hypothesized that premedication with intravenous dexmedetomidine-midazolam can suppress FIC effectively. A total of 440 patients of ASA I or II, aged 18-65 years, weighing 41-90 kg, undergoing elective surgery were randomized into four groups of 110 each, using computer-generated random numbers. Group S + S: normal saline 0.15 ml/kg + normal saline 0.06 ml/kg; Group S + M: normal saline 0.15 ml/kg + midazolam 0.06 mg/kg; Group D + S: dexmedetomidine 0.6 μg/kg + normal saline 0.06 ml/kg; Group D + M: dexmedetomidine 0.6 μg/kg + midazolam 0.06 mg/kg. After receiving the above-mentioned drugs, all patients received i.v. fentanyl (3 μg/kg). After fentanyl administration, the onset time and the severity of cough for 1 min were recorded. Severity of coughing was graded as mild (1-2), moderate (3-5) and (>5) based on the number of cough per minute. Forty-five (40.9%) patients had cough in Group S + S, 70 (63.6%) in Group S + M and 25 (22.7%) in Group D + S. None of the patients in Group D + M had any cough. The total incidence of cough was significantly higher (P < 0.01) in Group S + M in comparison to that in other groups. The onset time of cough was significantly shorter in Group S + M (13.8 ± 3.8 s) than in Group S + S (18.7 ± 3.9 s, P < 0.01) or Group D + S. (18.2 ± 3.2 s, P < 0.01). However, there was no significant difference among groups in cough severity. Pretreatment with dexmedetomidine-midazolam could completely suppress FIC caused by fentanyl 3 μg/kg injection within 2 s.


Extrachromosomal inheritance in Schizosaccharomyces pombe. IV. Isolation and genetic characterization of mutants resistant to chloramphenicol and erythromycin using the mutator properties of mutant anar-8.
Spontaneous chloramphenicol (capr)- and erythromycin (eryr)-resistant mutants were isolated from strain ade7-50 h- and the antimycin-resistant mutant anar-8 ade 7-50 h- of Schizosaccharomyces pombe (Sch. p.). By mitotic segregation analysis all 154 capr- and 120 eryr-mutants derived from ade 7-50 h- proved to be recessive chromosomal, whereas all 108 capr- and 200 eryr-mutants originating from anar-8 were extrachromosomally inherited. The rate of spontaneous capr- and eryr-mutants was about hundredfold in anar-8 compared to ade 7-50 h-. Growth of capr- and eryr-mutants was not inhibited by chloramphenicol or erythromycin, respectively, in glucose-medium and only slightly in glycerol-medium at concentrations which completely inhibited anar-8. By mitotic segregation-, tetrad-, and mitotic haploidization-analysis the extrachromosomal inheritance of mutants derived from anar-8 was established. Segregational patterns of capr- and eryr-determinants during mitosis, meiosis, and mitotic haploidization of diploids are discussed.


[Epithelioid angiomatosis and HIV infection. A neoplastic or infectious proliferative disease?].
A case of "epithelioid angiomatosis" detected in a homosexual patient with positive seric HIV is presented. The skin lesions cytoplasm rich, closed y clumped together, with scanty stromal compound. Warthin-Starry staining [correction of tintions] did not show Bacillus causing "cat scratch disease". We review and analyse the features of this type of proliferation in patients infected with HIV.


Induction of ornithine decarboxylase in rat liver by phorbol ester is mediated by prostanoids from Kupffer cells.
Administration of phorbol 12-myristate 13-acetate (PMA) to rats in vivo resulted in the induction of ornithine decarboxylase activity in the liver which could be blocked by preinjection of indomethacin, a cyclooxygenase inhibitor. In vitro administration of PMA to primary cultures of rat parenchymal cells did not lead to an induction of ornithine decarboxylase activity. It was investigated to what extent non-parenchymal liver cells could play an intermediary role in the expression of the PMA effect on ornithine decarboxylase activity in parenchymal liver cells. Addition of conditioned medium from PMA-activated Kupffer cells to cultured parenchymal cells led to the induction of ornithine decarboxylase activity in parenchymal cells. This effect was not observed with conditioned medium from untreated Kupffer cells or from Kupffer cells treated with PMA plus indomethacin. Conditioned media from PMA-treated or untreated endothelial liver cells were ineffective in the induction of ornithine decarboxylase activity in parenchymal liver cells. Prostaglandin D2, the main eicosanoid produced by Kupffer cells, was able to stimulate the synthesis of ornithine decarboxylase in parenchymal liver cells (up to 40-fold) in a dose-dependent way. Prostaglandin (PG) D2 appeared to be a more potent inducer of ornithine decarboxylase activity in parenchymal cells than PGE1 and PGE2. It is concluded that intercellular communication inside the liver mediated by prostaglandins derived from activated Kupffer cells may form a mechanism to induce synthesis of specific proteins in parenchymal cells.


A survey of attitudes to parent-doctor conflicts over treatment for children.
To investigate professional and public attitudes to the intervention of the law when parents and doctors disagree about the medical treatment of children. A cross-sectional survey of academic staff at the University of Otago. Random samples of academic medical practitioners and non-Health Sciences academic staff completed written questionnaires, including open and closed questions. Questions focussed on the Liam Williams-Holloway (W-H) and Tovia Laufau (TL) cases. The response rate was 107/164 (65%) of eligible staff. Support for doctors seeking treatment orders was strong (77% in the W-H case, and in the TL case, 70% believed an order should have been sought). Women were less likely than men to support a treatment order, significantly in the W-H case. There were no significant differences between medical and non-medical respondents. Court processes were viewed as confrontational and a last resort only after mediation failed. Scientific evidence was rated as the most important consideration in treatment decisions, followed by likely outcome, establishment of trust between parents and doctors, and the age of the child. Among this highly educated group there was strong support for seeking treatment orders in the child's best interests. But various mediation options were preferred and should be explored further. More evidence is needed on the success of treatment orders and on the attitudes of a more representative sample of the population.


Two dipolar α-helices within hormone-encoding regions of proglucagon are sorting signals to the regulated secretory pathway.
Proglucagon is expressed in pancreatic α cells, intestinal L cells, and some hypothalamic and brainstem neurons. Tissue-specific processing of proglucagon yields three major peptide hormones as follows: glucagon in the α cells and glucagon-like peptides (GLP)-1 and -2 in the L cells and neurons. Efficient sorting and packaging into the secretory granules of the regulated secretory pathway in each cell type are required for nutrient-regulated secretion of these proglucagon-derived peptides. Our previous work suggested that proglucagon is directed into granules by intrinsic sorting signals after initial processing to glicentin and major proglucagon fragment (McGirr, R., Guizzetti, L., and Dhanvantari, S. (2013) J. Endocrinol. 217, 229-240), leading to the hypothesis that sorting signals may be present in multiple domains. In the present study, we show that the α-helices within glucagon and GLP-1, but not GLP-2, act as sorting signals by efficiently directing a heterologous secretory protein to the regulated secretory pathway. Biophysical characterization of these peptides revealed that glucagon and GLP-1 each encode a nonamphipathic, dipolar α-helix, whereas the helix in GLP-2 is not dipolar. Surprisingly, glicentin and major proglucagon fragment were sorted with different efficiencies, thus providing evidence that proglucagon is first sorted to granules prior to processing. In contrast to many other prohormones in which sorting is directed by ordered prodomains, the sorting determinants of proglucagon lie within the ordered hormone domains of glucagon and GLP-1, illustrating that each prohormone has its own sorting "signature."


Brain functional connectivity during the first day of coma reflects long-term outcome.
In patients with disorders of consciousness (DOC), properties of functional brain networks at rest are informative of the degree of consciousness impairment and of long-term outcome. Here we investigate whether connectivity differences between patients with favorable and unfavorable outcome are already present within 24 h of coma onset. We prospectively recorded 63-channel electroencephalography (EEG) at rest during the first day of coma after cardiac arrest. We analyzed 98 adults, of whom 57 survived beyond unresponsive wakefulness. Functional connectivity was estimated by computing the 'debiased weighted phase lag index' over epochs of five seconds duration. We evaluated the network's topological features, including clustering coefficient, path length, modularity and participation coefficient and computed their variance over time. Finally, we estimated the predictive value of these topological features for patients' outcomes by splitting the patient sample in training and test datasets. Group-level analysis revealed lower clustering coefficient, higher modularity and path length variance in patients with favorable compared to those with unfavorable outcomes (p < 0.01). Within all features, the path length variance in the network provided the best positive predictive value (PPV) for favorable outcome and specificity for unfavorable outcome in the test dataset (PPV: 0.83, p < 0.01; specificity: 0.86, p < 0.01) with above-chance negative predictive value and accuracy. Of note, the exclusion of patients with epileptiform activity (20 in total) eliminates all false positive predictions (n = 6) for path length variance. Topological features of functional connectivity differ as a function of long-term outcome in patients on the first day of coma. These differences are not interpretable in terms of consciousness levels as all patients were in a deep unconscious state. The time variance of path length is informative of comatose patients' outcome, as patients with favorable outcome exhibit a richer repertoire of path length than those with unfavorable outcomes.


Inhibition skills in children with developmental coordination disorder.
Inhibition (Response Inhibition - RI and Interference Control - IC) have been inconsistently examined in Developmental Coordination Disorder (DCD) with response modalities often not considered. To examine RI and IC in children with DCD. Twenty-five children 6-10 years with DCD, plus 25 matched typically developing peers completed motor and verbal RI and IC tasks. . Children with DCD made significantly more errors in the motor and verbal RI tasks, had slower movement time and RT in the motor IC task, and longer completion time in the verbal IC task. Children with DCD have RI and IC difficulties in motor and verbal responses.


Mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanoparticles loaded with ruthenium(II) complex nanoparticles: Fluorometric sensing and cellular imaging of temperature by upconversion and of oxygen by downconversion.
Accurate detection of temperature and oxygen concentration at the cellular level is important in tumor diagnosis. Multifunctional nanocomposites are described that consist of upconversion luminescent nanoparticles capped with mesoporous silica and loaded with an oxygen-sensitive luminescent ruthenium complex. The nanocomposites of type NaYF4:Yb,Er@NaYF4@mSiO2-Ru have two modes of operation: Its red downconversion luminescence (at excitation/emission peaks of 455/606 nm) is quenched by oxygen (O2), and this is used to sense and image O2. The green upconversion luminescence (typically acquired at excitation/emission wavelengths of 980/525 and 544 nm), in turn, is used to measure temperature. The nanocomposites were then applied to dual mode in-vitro imaging of temperature and O2 in hepatocellular carcinoma cells (HepG-2). Graphical abstract A new multifunctional nanocomposite of mesoporous silica coating NaYF4:Yb,Er@NaYF4 upconversion nanopaticless loaded with ruthenium (II) complex has been designed with both green upconversion and red downconversion luminescence for temperature detection, oxygen sensing and dual mode cell imaging.


Acute toxicity of sodium formononetin-3'-sulphonate (Sul-F) in Sprague-Dawley rats and Beagle dogs.
Sodium formononetin-3'-sulphonate (Sul-F, C16H12O7SNa), a water-soluble derivate of formononetin, provided significant neuroprotective and cardioprotective effects in vitro and in vivo. The aim of this study was to evaluate acute toxicity of Sul-F after intravenous administration in rats and dogs. Animals were intravenously administered Sul-F at the maximum dosage of 2000 mg/kg and 1000 mg/kg in rats and dogs, respectively. After treatment, rats and dogs were monitored for 14 days. Body weight, clinical signs, the hematological and biochemical findings, and pathological examination were performed. The results showed that no Sul-F related clinical signs of toxicity or mortality were observed in rats. Of note, the transient vomiting was found in dogs after Sul-F administration 15-20 min. In addition, a white crystal, non-metabolic Sul-F, was found after urine volatilization in Sul-F treated animals (rats and dogs). However, neither biochemical findings nor histopathological changes due to Sul-F treatment were found in tests. In summary, the present study results provided practical guidance for selecting a safe dosage for Sul-F further studies and clinical trials in the future.


Airway Management: A Structured Curriculum for Critical Care Transport Providers.
Airway assessment and management are vital skills for the critical care transport provider. Nurses and paramedics often enter a transport program with limited or no exposure to airway management. Many programs lack a structured curriculum to show skill competence. Optimal methods in the development of airway management competence and the frequency of training needed to maintain skills have not been clearly defined. Because of this lack of standardization, the actual level of competence in both new and experienced critical care transport providers is unknown. A pretest, post-test repeated measures approach using an online curriculum combined with a deliberate practice model was used. Competence in airway management was measured using 3 evaluation points: static mannequin head, simulation scenario, and the live patient. A convenience sample of critical care transport providers participated (N = 9). Knowledge improvement was significant, with a higher percentage of participants scoring above 85% on the post-test compared with the pretest (P = .028). Mean scores in completion of the airway checklist pre- versus postintervention were significantly increased on all 3 evaluation points (P < .001 for all comparisons). Significant changes were noted in the response profile evaluating participants' confidence in their ability to verbalize indications for endotracheal intubation (P < .05). The development of a standardized, blended learning curriculum combined with deliberate simulation practice and rigorous assessment showed improvements in multiple areas of airway assessment and management.


Transient receptor potential ankyrin 1 agonists improve intestinal transit in a murine model of postoperative ileus.
Stimulation of transient receptor potential ankyrin 1 (TRPA1), which abundantly expressed in enterochromaffin cells (ECC), has been reported to exert apparently contradictory results in in vitro contractility and in vivo gastrointestinal (GI) transit evaluations. The pharmaceutical-grade Japanese traditional medicine daikenchuto (TU-100) has been reported to be beneficial for postoperative ileus (POI) and accelerate GI transit in animals and humans. TU-100 was recently shown to increase intestinal blood flow via stimulation of TRPA1 in the epithelial cells of the small intestine (SI). The effects of various TRPA1 agonists on motility were examined in a manipulation-induced murine POI model, in vitro culture of SI segments and an ECC model cell line, RIN-14B. Orally administered TRPA1 agonists, aryl isothiocyanate (AITC) and cinnamaldehyde (CA), TU-100 ingredients, [6]-shogaol (6S) and γ-sanshool (GS), improved SI transit in a POI model. The effects of AITC, 6S and GS but not CA were abrogated in TRPA1-deficient mice. SI segments show periodic peristaltic motor activity whose periodicity disappeared in TRPA1-deficient mice. TU-100 augmented the motility. AITC, CA and 6S increased 5-HT release from isolated SI segments and the effects of all these compounds except for CA were lost in TRPA1-deficient mice. 6S and GS induced a release of 5-HT from RIN-14B cells in a dose- and TRPA1-dependent manner. Intraluminal TRPA1 stimulation is a potential therapeutic strategy for GI motility disorders. Further investigation is required to determine whether 5-HT and/or ECC are involved in the effect of TRPA1 on motility.


Advances and Future Directions of Neuromodulation in Neurologic Disorders.
"Deep brain stimulation is a safe and effective therapy for the management of a variety of neurologic conditions with Food and Drug Administration or humanitarian exception approval for Parkinson disease, dystonia, tremor, and obsessive-compulsive disorder. Advances in neurophysiology, neuroimaging, and technology have driven increasing interest in the potential benefits of neurostimulation in other neuropsychiatric conditions including dementia, depression, pain, Tourette syndrome, and epilepsy, among others. New anatomic or combined targets are being investigated in these conditions to improve symptoms refractory to medications or standard stimulation."


Music, neuroscience, and the psychology of well-being: a précis.
In Flourish, the positive psychologist Seligman (2011) identifies five commonly recognized factors that are characteristic of human flourishing or well-being: (1) "positive emotion," (2) "relationships," (3) "engagement," (4) "achievement," and (5) "meaning" (p. 24). Although there is no settled set of necessary and sufficient conditions neatly circumscribing the bounds of human flourishing (Seligman, 2011), we would mostly likely consider a person that possessed high levels of these five factors as paradigmatic or prototypical of human flourishing. Accordingly, if we wanted to go about the practical task of actually increasing our level of well-being, we ought to do so by focusing on practically increasing the levels of the five factors that are characteristic of well-being. If, for instance, an activity such as musical engagement can be shown to positively influence each or all of these five factors, this would be compelling evidence that an activity such as musical engagement can positively contribute to one's living a flourishing life. I am of the belief that psychological research can and should be used, not only to identify and diagnose maladaptive psychological states, but identify and promote adaptive psychological states as well. In this article I advance the hypothesis and provide supporting evidence for the claim that musical engagement can positively contribute to one's living a flourishing life. Since there has not yet been a substantive and up-to-date investigation of the possible role of music in contributing to one's living a flourishing life, the purpose of this article is to conduct this investigation, thereby bridging the gap and stimulating discussion between the psychology of music and the psychology of well-being.


Options in camera technology for the bone scan: role of SPECT.
Planar imaging with current generation gamma cameras and tomographic imaging with current generation rotating camera single photon emission computed tomography (SPECT) systems provide excellent spatial resolution and good fidelity between image quantitation and activity levels. Their use in imaging the localization and clearance of skeletal imaging agents such as the Tc-99m labeled diphosphonates, Ga-67 citrate, and In-111 leukocytes offers a sensitive and accurate means to detect occult disease and to investigate skeletal blood flow, metabolism, and pathology. SPECT progressively plays an increasingly important role in imaging studies of joint disease, infection, avascular necrosis, bone growth, developmental abnormalities and the effects of weight bearing, exercise, and other forms of treatment on skeletal repair processes.


Bilateral phrenic neuropathies in a diabetic patient responsive to intravenous immunoglobulin: a case report.
Bilateral phrenic neuropathy is an uncommon complication of diabetes mellitus. We present a patient with diabetes mellitus who developed dyspnea from diaphragmatic paresis secondary to bilateral phrenic neuropathies on the background of subclinical generalized polyneuropathy documented by electrodiagnostic studies. The patient was treated with intravenous immunoglobulin with improved diaphragmatic function. Phrenic neuropathy is a rare but important complication of diabetes mellitus. We report the first case of the beneficial use of intravenous immunoglobulin in diabetic phrenic neuropathy.


Design and validation of a universal influenza virus enrichment probe set and its utility in deep sequence analysis of primary cloacal swab surveillance samples of wild birds.
Influenza virus infections in humans and animals are major public health concerns. In the current study, a set of universal influenza enrichment probes was developed to increase the sensitivity of sequence-based virus detection and characterization for all influenza viruses. This universal influenza enrichment probe set contains 46,953 120nt RNA biotin-labeled probes designed based on all available influenza viral sequences and it can be used to enrich for influenza sequences without prior knowledge of type or subtype. Marked enrichment was demonstrated in influenza A/H1N1, influenza B, and H1-to-H16 hemagglutinin plasmids spiked into human DNA and in cultured influenza A/H2N1 virus. Furthermore, enrichment effects and mixed influenza A virus infections were revealed in wild bird cloacal swab samples. Therefore, this universal influenza virus enrichment probe system can capture and enrich influenza viral sequences selectively and effectively in different samples, especially ones with degraded RNA or containing low amount of influenza RNA.


Teacher-student relationships and adolescent behavioral engagement and rule-breaking behavior: The moderating role of dopaminergic genes.
This study examined whether the dopamine transporter DAT1 and the dopamine receptor DRD4 genes moderate the effect of student-reported teacher-student relationship affiliation or dissatisfaction on parent-reported adolescent rule-breaking behavior and behavioral engagement. The sample included 1053 adolescents (51% boys, Mage=13.79) from grades 7 to 9. Regression analyses were conducted using Mplus while controlling for multiple testing and nested data. Adolescents who experienced stronger affiliation with their teachers were more engaged in school, whereas greater dissatisfaction predicted more rule-breaking behavior. In addition, a significant gene-environment interaction was found for both genes examined. The link between low teacher-student affiliation and low engagement was more pronounced for DAT1-10R homozygotes. The link between high teacher-student dissatisfaction and more rule-breaking was stronger for DRD4 non-long carriers. Implications for understanding the role of teacher-student relationships in adolescence and suggestions for future research are outlined.


Evaluating alert fatigue over time to EHR-based clinical trial alerts: findings from a randomized controlled study.
Inadequate participant recruitment is a major problem facing clinical research. Recent studies have demonstrated that electronic health record (EHR)-based, point-of-care, clinical trial alerts (CTA) can improve participant recruitment to certain clinical research studies. Despite their promise, much remains to be learned about the use of CTAs. Our objective was to study whether repeated exposure to such alerts leads to declining user responsiveness and to characterize its extent if present to better inform future CTA deployments. During a 36-week study period, we systematically documented the response patterns of 178 physician users randomized to receive CTAs for an ongoing clinical trial. Data were collected on: (1) response rates to the CTA; and (2) referral rates per physician, per time unit. Variables of interest were offset by the log of the total number of alerts received by that physician during that time period, in a Poisson regression. Response rates demonstrated a significant downward trend across time, with response rates decreasing by 2.7% for each advancing time period, significantly different from zero (flat) (p<0.0001). Even after 36 weeks, response rates remained in the 30%-40% range. Subgroup analyses revealed differences between community-based versus university-based physicians (p=0.0489). CTA responsiveness declined gradually over prolonged exposure, although it remained reasonably high even after 36 weeks of exposure. There were also notable differences between community-based versus university-based users. These findings add to the limited literature on this form of EHR-based alert fatigue and should help inform future tailoring, deployment, and further study of CTAs.


Hyperactivity and attention problems in a Swiss sample of school-aged children: effects of school achievement, child gender, and informants.
The sensitivity and tolerance regarding ADHD symptoms obviously differ from one culture to another and according to the informants (parents, teachers, or children). This stimulates the comparison of data across informants and countries. Parents and teachers of more than 1,000 school-aged Swiss children (5 to 17 years old) fill in Conners's questionnaires on ADHD. Children who are older than 10 years old also fill in a self-report questionnaire. Results are compared to data from a North American sample. Swiss parents and teachers tend to report more ADHD symptoms than American parents and teachers as far as the oldest groups of children are concerned. Interactions are evidenced between school achievement, child gender, and informants. A relatively low rate of agreement between informants is found. These results strengthen the importance to take into account all informants in the pediatric and the child psychiatry clinic, as well as in the epidemiological studies.


Comparative transcriptome analysis of Zea mays upon mechanical wounding.
Mechanical wounding (MW) is mainly caused due to high wind, sand, heavy rains and insect infestation, leading to damage to crop plants and an increase in the incidences of pathogen infection. Plants respond to MW by altering expression of genes, proteins, and metabolites that help them to cope up with the stress. In order to characterize maize transcriptome in response to mechanical wounding, a microarray analysis was executed. The study revealed 407 differentially expressed genes (DEGs) (134 upregulated and 273 downregulated). The upregulated genes were engaged in protein synthesis, transcription regulation, phytohormone signaling-mediated by salicylic acid, auxin, jasmonates, biotic and abiotic stress including bacterial, insect, salt and endoplasmic reticulum stress, cellular transport, on the other hand downregulated genes were involved in primary metabolism, developmental processes, protein modification, catalytic activity, DNA repair pathways, and cell cycle. The transcriptome data present here can be further utilized for understanding inducible transcriptional response during mechanical injury and their purpose in biotic and abiotic stress tolerance. Furthermore, future study concentrating on the functional characterization of the selected key genes (Bowman Bird trypsin inhibitor, NBS-LRR-like protein, Receptor-like protein kinase-like, probable LRR receptor-like ser/thr-protein kinase, Cytochrome P450 84A1, leucoanthocyanidin dioxygenase, jasmonate O-methyltransferase) and utilizing them for genetic engineering for crop improvement is strongly recommended.


Circulating enterolactone and prostate cancer risk: a Nordic nested case-control study.
Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case-control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow-up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (+/-2 years), date of blood collection (+/-2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th-75th percentile = 4.5-15.0] vs. 8.5 nmol/L [25th-75th percentile = 4.3-15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96-1.52), 1.16 (95% CI = 0.91-1.47) and 1.08 (95% CI = 0.83-1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91-1.60), 1.02 (95% CI = 0.59-1.76) and 0.87 (95% CI = 0.45-1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.


Spontaneous spinal epidural hematoma presenting as paraplegia after cardiac surgery.
An 86-year-old woman was scheduled to undergo aortic valve replacement and coronary artery bypass graft. On postoperative day 3, she developed sudden-onset neck pain followed by weakness in the right arm. Her symptoms worsened with time, and she developed paraplegia. At 60 h after the first complaint, spontaneous spinal epidural hematoma (SSEH) from C2 to C6 with spinal cord compression was diagnosed from a magnetic resonance image of the cervical region. We decided on conservative therapy because operative recovery was impossible. Delayed diagnosis led to grievous results in the present case. When neurological abnormalities follow neck or back pain after open heart surgery, SSEH must be considered in the differential diagnosis. Further, if it is suspected, early cervical computed tomography/magnetic resonance imaging and surgery should be considered.


High-mobility group box 1 exacerbates concanavalin A-induced hepatic injury in mice.
High-mobility group box 1 (HMGB1) is a nuclear factor released extracellularly as an early endogenous alarmin of inflammation following injury and as a late mediator of lethality in sepsis. Although HMGB1 has been implicated in acute lung injury, rheumatoid arthritis, and allograft rejection, its role in T-cell mediated hepatitis remains obscure. Here, we investigated the role and the underlying mechanisms of HMGB1 in concanavalin A (Con A) induced hepatic injury. We demonstrate that high levels of HMGB1 were detected in the necrotic area and in the cytoplasm of hepatocytes after Con A treatment. Administration of exogenous recombinant HMGB1 enhanced Con A-induced hepatitis, while blockade of HMGB1 protected animals from T cell-mediated hepatitis as evidenced by decreased serum transaminase, associated with reduced hepatic necrosis and mortality. Blockade of HMGB1 by a neutralizing antibody inhibited proinflammatory cytokine production, NFκB activity, and the late stage of T/NKT cell activation. These finding thus suggest a pivotal factor of HMGB1 in Con A-induced hepatitis. Blockage of extracellular HMGB1 may represent a novel therapeutic strategy to prevent hepatic injury in T cell-mediated hepatitis.


Effects of mammalian target of rapamycin inhibitors on fibrosis after trabeculectomy.
Glaucoma, the second leading cause of blindness worldwide, is characterized by aberrant elevations of intraocular pressure (IOP), which can damage the optic nerve. IOP reduction is the only effective therapy for prevention of visual impairment and blindness in both hypertensive and normotensive individuals, and in some cases, trabeculectomy is a major surgical procedure that can lower IOP in patients with glaucoma. No matter how surgical technique and postoperative care advances, excessive scarring and tissue fibrosis could result from increased human conjunctival fibroblast (HCF) proliferation and extracellular matrix (ECM) deposition of the subconjunctival tissue and scleral flaps would persist after trabeculectomy. And these issues are major impediments to IOP reduction and filtering of bleb formations, so the modulation of the factors which can induce fibrosis could used as a novel strategy to control scarring after trabeculectomy. In this study, we examined the effects of mammalian target of rapamycin (mTOR) inhibitors (rapamycin or Torin1) on the fibrotic response induced by transforming growth factor-beta 1 (TGF-β1) in cultured human conjunctival fibroblast (HCF) cells. The study also examined the effects of mTOR inhibitor on fibrosis after trabeculectomy in rabbit eyes. In in vitro studies, we stimulated HCFs with TGF-β1, and confirmed that the expression levels of fibronectin, collagen type I alpha 1 chain (COL1A1), and α-smooth muscle actin (SMA) were significantly upregulated in HCFs with TGF-β1, by means of quantitative real-time polymerase chain reaction and immunocytochemistry. And those TGF-β1-induced changes were significantly attenuated with mTOR inhibitors, rapamycin or Torin1. Additionally the migration rate of HCFs was examined under conditions of TGF-β1 induction, TGF-β1-induced changes were significantly attenuated with mTOR inhibitors. A rabbit model of trabeculectomy was examined in vivo, and the effects of topical mTOR inhibitor were also examined, and found that topical treatment with mTOR inhibitor significantly suppressed collagen deposition in rabbit eyes after trabeculectomy. These results have demonstrated that mTOR inhibitors may provide a novel treatment modality for reducing the fibrotic response in HCFs and improving bleb scarring after filtration surgery.


Urokinase increases the content and activity of matrix metalloproteinases 2 and 9 during in vivo constrictive arterial remodeling.
Perivascular application of urokinase to ballooned artery stimulating the formation of neointima and constrictive arterial remodeling increased the content and activity of matrix metalloproteinases 2 and 9 in vivo. Application of recombinant tissue plasminogen produced no such changes. It was demonstrated that urokinase stimulates expression of matrix metalloproteinases in vivo.


The changing panorama of infantile hydrocephalus and cerebral palsy over forty years--a Swedish survey.
The time trends and background of infantile hydrocephalus (IH) and cerebral palsy (CP) are surveyed. The changes in live birth prevalence, disability patterns, associated neuroimpairments and distribution of etiologies are analysed. Both the risk of IH and that of CP sharply increase with decreasing birth weight and gestational age. It is concluded that the remarkably enhanced survival of particularly very preterm infants, those at the highest risk of long-term morbidity, implies an increasing number of impaired children as long as the outcome of survivors is not drastically improved. The data presented are thought to be of relevance as to reconsideration of the effectiveness of perinatal care for preterm babies.


Interaction of plasma colloid osmotic pressure and joint fluid pressure across the endothelium-synovium layer: significance of extravascular resistance.
Fluid exchanges between blood and a synovial joint cavity across two membranes in series--synovial capillary wall (fenestrated) and synovial intima (modified connective tissue). The relation between transsynovial absorption of intraarticular Krebs solution (flow Qs) and plasma colloid osmotic pressure pi p was investigated in rabbit knees perfused at constant blood pressure. Intraarticular pressure Pj was independently controlled. Linear relations between transsynovial flow and plasma colloid osmotic pressure established that transsynovial flow obeys the Starling hypothesis. However osmotic conductance, dQs/d pi p, increased 3.9 times when Pj was raised from 6 cm H2O or subatmospheric pressure to 18 cm H2O--the "yield phenomenon." Comparison of the effects of pi p and capillary pressure revealed no major change in the osmotic reflection coefficient of the blood-joint barrier to albumin upon raising Pj. The large increase in osmotic conductance was predicted quantitatively by a previous model (prediction 3.8 X) based on increases in extravascular (intimal) conductance as a function of extravascular pressure. It is argued that capillary endothelium is not the sole significant hydraulic resistance in this pathway. In the terminology of Intaglietta and de Plomb (1973) synovial capillaries are functionally intermediate between "tubes" and "tunnels."


The anticatabolic effect of neuraxial blockade after hip surgery.
Although the protein-sparing effect of neuraxial blockade after abdominal surgery is well established, its metabolic effect after operations on the lower extremities remains unclear. In this study, we tested the hypothesis that combined spinal and epidural blockade (CSE) inhibits amino acid oxidation after hip surgery. Sixteen patients undergoing hip replacement surgery received either general anesthesia followed by IV patient-controlled analgesia with piritramide (control; n = 8) or CSE using bupivacaine 0.5% for spinal anesthesia and ropivacaine 0.2% with 0.5 microg/mL of sufentanil for postoperative epidural analgesia (CSE; n = 8). Glucose and protein kinetics were assessed by stable isotope tracer technique ([6,6-2H2]glucose, L-[1-13C]leucine) on the day before and one day after surgery. Plasma concentrations of glucose, lactate, free fatty acids, cortisol, glucagon, and insulin were also determined. CSE prevented the increase in plasma glucose concentration during and immediately after the operation (60 min after skin incision: CSE 4.9 +/- 0.7 versus control 6.2 +/- 0.7 mmol/L; P < 0.05; postanesthesia care unit: CSE 5.0 +/- 0.9 versus control 7.3 +/- 1.1 mmol/L; P < 0.05). Intraoperative cortisol plasma concentrations were smaller in the CSE group than in the control group. One day after the operation, however, glucose plasma concentration, glucose production, and glucose clearance were comparable in both groups. CSE inhibited the postoperative increase in leucine oxidation rate (CSE 30 +/- 12 versus control 43 +/- 8 micromol.kg(-1).h(-1); P < 0.05). There were no differences between the groups in protein breakdown, whole body protein synthesis, and plasma concentrations of lactate, free fatty acids, insulin, and glucagon. In conclusion, CSE prevents hyperglycemia during hip surgery and inhibits protein catabolism thereafter. We studied the effect of combined spinal/epidural blockade (CSE) on protein and glucose metabolism during and after hip surgery. In comparison to general anesthesia followed by intravenous patient-controlled analgesia, CSE inhibits the increase in glucose plasma concentration during surgery and prevents protein loss on the first postoperative day.


Geocoding of worldwide patent data.
The dataset provides geographic coordinates for inventor and applicant locations in 18.8 million patent documents spanning over more than 30 years. The geocoded data are further allocated to the corresponding countries, regions and cities. When the address information was missing in the original patent document, we imputed it by using information from subsequent filings in the patent family. The resulting database can be used to study patenting activity at a fine-grained geographic level without creating bias towards the traditional, established patent offices.


The effect of nitric oxide on vaccinia virus-encoded ribonucleotide reductase.
Growth inhibition of the DNA virus vaccinia (VACV) by NO is known to occur at the level of DNA synthesis. This inhibition is partially reversed by addition of deoxyribonucleosides, suggesting that NO or NO-related species inhibit viral ribonucleotide reductase (RR). However, the effect of NO on VACV-encoded RR or other DNA-synthesizing enzymes has not been demonstrated. In order to study the effects of NO on VACV-encoded RR, DNA polymerase (DNA pol) and thymidine kinase (TK), we generated a VACV recombinant expressing murine macrophage iNOS under control of a VACV early/late promoter p7.5. Using this recombinant, we demonstrate that expression of iNOS and the resulting production of NO inhibit activity of the viral RR, but not of viral DNA pol and TK. This NO-mediated inhibition of viral RR occurred around the same time as the increase of ADP levels, while it preceded the block in VACV DNA synthesis and the decrease of ATP levels. In addition, we tested the effects of DPTA/NONOate on the growth of different VACV mutants. Fold-inhibition of the growth of VACV deletion mutant for TK was comparable to that of wild-type VACV. VACV containing amplification of the gene for the small subunit of RR appeared to be least sensitive to DPTA/NONOate, while VACV deletion mutant for the large subunit of RR was most sensitive. The results provide a direct evidence for NO-mediated inhibition of VACV-encoded RR.


Oil-in-water emulsification using confined impinging jets.
A confined impinging jet mixing device has been used to investigate the continuous sunflower oil/water emulsification process under turbulent flow conditions with oil contents between 5% (v/v) and 10% (v/v). Various emulsifiers (Tween20, Span80, Whey Protein, Lecithin and Sodium Dodecylsulphate) varying in molecular weights have been studied. Mean droplet sizes varied with the emulsifiers used and smallest droplets were obtained under fully turbulent flow regime, i.e. at the highest jet flow rate and highest jet Reynolds Number conditions. Sodium Dodecylsulfate (SDS) produced droplets in the range of 3.8 μm while 6 μm droplets were obtained with Whey Protein. Similar droplet sizes were obtained under fully turbulent flow conditions (610 mL/min; Reynolds Number=13,000) for oil content varying between 5% (v/v) and 10% (v/v). To investigate the smallest droplet size possible in the device, the emulsion was passed through the geometry multiple times. Multi-pass emulsification resulted in reduction in droplet size indicating that longer residence in the flow field under high shear condition allowed for breakage of droplets as well as the time for the emulsifier to stabilize the newly formed droplets, decreasing the impact of coalescence. This was confirmed by timescale analysis of the involved process steps for the droplet data obtained via experiments. Dependence of mean droplet size on the o/w interfacial tension and peak energy dissipation was also investigated.


Patients with falls from standing height and head or neck injury may not require body CT in the absence of signs or symptoms of body injury.
To determine the rate of clinically impactful body injury among patients who had a fall from standing height with an associated head/neck injury, but without evidence of body injury on physical exam or plain radiographs. We also examine surgical/endovascular intervention related to body injury and mortality rates for head/neck and body injury. Retrospective study of 288 patients with CT evidence of acute head/neck injury that underwent body CT despite the absence of clinical or radiographic evidence of body injury. Predictor variables were age, sex, race/ethnicity, and body mass index (BMI). There were 11.5% (n = 33) with body injury on CT (n = 33). There were 3.1% (n = 9) with clinically impactful body injury. No patient had either surgical/endovascular intervention or mortality related to body injury. Additionally, 8.7% (n = 25) had mortality from head/neck injury. Increased age (OR = 1.05, 95% CI: 1.01, 1.08, p = 0.01) and overweight BMI (25-29.99 kg/m2) (OR = 2.85, 95% CI: 1.07, 7.62, p = 0.04) were each significantly associated with increased odds for mortality from head/neck injury. Patients with falls from standing height and known head/neck injury had a low rate of clinically impactful body injury. None of the studied variables were associated with increased risk of body injury in this patient population. The low rate of clinically impactful body injury and the lack of any mortality, procedure, or transfusion resulting from body injury suggest that body CT may not be necessary in patients with head/neck injury in the absence of clinical or radiographic evidence of body injury.


Completely obstructive colorectal cancer.
Forty-five patients with obstructing carcinoma of the colon and rectum were compared with 176 patients with nonobstructing tumor diagnosed over a 10-year period. The age and sex distribution did not differ between the two groups. The site of greatest risk for obstruction was the splenic flexure and descending colon (50%); median survival in these patients was one-half that for other sites. In the obstructed group no patient had Dukes' stage A vs. 9.6% in the nonobstructed patients, and 22% of the obstructed patients had Dukes' D vs. 14% of the nonobstructed patients. The 5-year survival in Dukes' A was 82%, while no survivors were found for Dukes' D. The crude 5-year survival rate was 22.4% in the obstructed patients and 49.1% in the nonobstructed patients; in-hospital mortality was 22.4% and 6.8%, respectively, and the adjusted actuarial survival was 39% vs. 64%, respectively. Curative resection was performed in 68% of the obstructed and 83% of the nonobstructed patients. The adjusted actuarial 5-year survival rates for these patients were 53% and 76%, respectively. The criteria for the tumor grade tested in this study, which included differentiation of the tumor cells, size, and the presence of perforation, did not influence the survival. Twenty-one patients underwent primary resection, 15 had stage resection, and 9 had diversion procedures. The in-hospital mortality rates were 35% for primary resection and diversion procedures and 7% for stage resection. The crude 5-year survival was 32% for primary resection, 42% for stage resection (not statistically significant), and 0 for diversion procedures. The poor prognosis for the obstructed patients in our study was mainly related to 1) high in-hospital mortality, 2) the lower rate of curative resection, 3) unequal distribution of the tumor site, and 4) to a small extent, the difference in Dukes' stage.


Sociodemographic factors associated with low intake of bioavailable iron in preschoolers: National Health and Nutrition Survey 2012, Mexico.
Children < 5 years of age are at risk of developing an iron deficiency due to a low intake of bioavailable iron (FeBio). Few studies have estimated dietary FeBio in children at a national level in relation to sociodemographic characteristics. This study aimed to estimate FeBio intake and its association with sociodemographic factors among Mexican children aged 12-59 months. A cross-sectional study was carried out. Information on serum ferritin and diet was obtained from a national survey and representative sample of 1012 Mexican children aged 12-59 months. We used a 24-h recall to estimate total iron, heme and non-heme iron, vitamin C, phytates, calcium, and meat intake. We calculated FeBio intake using an algorithm. Differences in FeBio intake were analyzed by area of residence (rural/urban), country region (north, center, south), and socioeconomic status (SES), using linear regression models by age subgroups (12-23 and 24-59 months) and total population, while adjusting for study design. Total iron intake was 9.2 ± 6.7 mg/d. The estimated average of total FeBio fluctuated between 0.74-0.81 mg/d, with a bioavailability of 9.15-12.03% of total iron. Children aged 12-23 months residing in rural areas consumed less FeBio than those in urban areas (β = - 0.276) (p < 0.05). Children aged 24-59 months with high SES consumed more FeBio (β = 0.158 mg/d) than those of a low SES (p < 0.05). FeBio is low in Mexican preschoolers. Being from a rural area and having low SES were negatively associated with FeBio intake. These results can benefit interventions seeking to improve iron status.


Cytotoxicity, genotoxicity and antibacterial activity of poly(vinyl alcohol)-coated silver nanoparticles and farnesol as irrigating solutions.
To evaluate the cytotoxicity, genotoxicity and antibacterial activity of poly(vinyl alcohol)-coated silver nanoparticles (AgNPs-PVA) and farnesol (FAR). The cytotoxicity (% of cell viability) was evaluated by MTT assay and the genotoxicity (% of DNA in the tail) was evaluated by Comet assay. Root canal disinfection with different irrigating protocols was evaluated ex vivo in human teeth contaminated with Enterococcus faecalis for 21days. Three microbiological samples were collected: initial (after contamination); post-irrigation (after irrigation); and final (after 7days). After each sample, the number of log 10 CFU mL-1 was determined. Statistical analyses was performed using two-way ANOVA and Bonferroni post-hoc tests for MTT assay, Kruskal-Wallis and Dunn post-hoc tests for Cometa and antibacterial assays (α=0.05). The MTT assay showed that AgNPs and FAR were less cytotoxic that sodium hypochlorite (NaOCl) and showed a lower% of DNA in the tail, in comparison with H2O2 (positive control - C+). In the post-irrigation microbiological sample, all the irrigating protocols were more effective than C+ (without irrigation). NaOCl/saline, NaOCl/saline/AgNPs-PVA and NaOCl/saline/FAR led to complete bacterial elimination (p >0.05). In comparison with the initial sample, both the post-irrigation and the final samples showed microbial reduction (p < 0.05). AgNPs-PVA and FAR showed low cytotoxicity and genotoxicity, and exhibit potential for use as a final endodontic irrigation protocols.


Evaluation of male external genital diseases in the emergency room setting.
This article briefly discusses various diseases of the external genitalia as they pertain to the emergency physician. Conditions emphasized include penile and scrotal trauma, Fournier's gangrene, and the "acute" scrotum. Practical advice regarding diagnosis and treatment is offered.


Production of herbicide-resistant medicinal plant Salvia miltiorrhiza transformed with the bar gene.
In this study, we successfully performed Agrobacterium-mediated genetic transformation of Salvia miltiorrhiza and produced herbicide-resistant transformants. Leaf discs of S. miltiorrhiza were infected with Agrobacterium tumefaciens EHA105 harboring pCAMBIA 3301. The pCAMBIA 3301 includes an intron-containing gus reporter and a bar selection marker. To increase stable transformation efficiency, a two-step selection was employed which consists of herbicide resistance and gus expression. Here, we put more attention to the screening step of herbicide resistance. The current study provides an efficient screening system for the transformed plant of S. miltiorrhiza harboring bar gene. To determine the most suitable phosphinothricin concentration for plant selection, non-transformed leaf discs were grown on selection media containing six different phosphinothricin concentrations (0, 0.2, 0.4, 0.6, 0.8, and 1.0 mg/l). Based on the above results of non-transformed calluses, the sensitivity of phosphinothricin (0, 0.4, 0.8, 1.2, 1.6 mg/l) was tested in the screening of transgenic S. miltiorrhiza. We identified that 0.6 mg/l phosphinothricin should be suitable for selecting putatively transformed callus because non-transformed callus growth was effectively inhibited under this concentrations. When sprayed with Basta, the transgenic S. miltiorrhiza plants were tolerant to the herbicide. Hence, we report successful transformation of the bar gene conferring herbicide resistance to S. miltiorrhiza.


The UK case-control study of cerebral oedema complicating diabetic ketoacidosis in children.
Cerebral oedema complicating diabetic ketoacidosis (DKA) remains the major cause of morbidity and mortality in children with type 1 diabetes, but its aetiology remains unknown. Our objective was to determine the impact of baseline biochemical factors and of treatment-related variables on risk of the development of cerebral oedema in children with DKA. This was a national UK case-control study. Through the British Paediatric Surveillance Unit we identified 43 cases of cerebral oedema. Through a parallel reporting system, we also identified 2,940 episodes of DKA and selected 169 control subjects on the basis of comparable age, sex, numbers of new or known cases of diabetes and date of admission. Baseline biochemical data and treatment-related variables were extracted from the clinical notes of cases and control subjects. Allowing for differences in age, sex and new or known diabetes, cases were more acidotic at diagnosis of DKA (odds ratio [OR] for events in the least acidotic compared with the most acidotic tertile=0.02 [95% CI: 0.002-0.15], p<0.001). In addition, cases had higher potassium and urea levels at baseline. Calculated osmolality and baseline glucose were not significantly different. After allowing for severity of acidosis, insulin administration in the first hour (OR 12.7 [1.41-114.5], p=0.02) and volume of fluid administered over the first 4 h (OR 6.55 [1.38-30.97], p=0.01) were associated with risk. Low baseline plasma sodium and an elevated p(a)CO(2) also contributed to risk in the final regression model. Bicarbonate administration was not associated with increased risk of an event when corrected for acidosis. In this case-control study of DKA, baseline acidosis and abnormalities of sodium, potassium and urea concentrations were important predictors of risk of cerebral oedema. Additional risk factors identified were early administration of insulin and high volumes of fluid. These observations should be taken into account when designing treatment protocols.


Role of nitrite and nitrate as a redox couple in the rat colon. Implications for diarrheal conditions.
Colonic levels of nitrite and circulating levels of nitrate are elevated in subjects with chronic diarrhea. The role of colonic epithelial cells in oxidation-reduction of nitrite and consequent control of nitrite and nitrate levels is unknown. Isolated rat colonocytes and isolated loops of colon were used to study oxidation and reduction of nitrate and nitrite. Colonocytes oxidized nitrite to nitrate at a rate of 162 +/- 33 nmol/min.g (dry wt) (n = 6) over 0-20 min, a value increased by addition of 5 mM glucose and 1 mM nicotinamide adenine dinucleotide (p = less than 0.01), but not altered by antibiotics. Nitrite oxidation correlated linearly with the dry weight of isolated colonocytes (r = 0.92), indicating a cellular reaction. Nitrite was absorbed at a rate of 0.28 nmol/min.cm2 (n = 9) from the colonic lumen, which reflected 74% absorption of the available nitrite. Of the absorbed nitrite, 14.3% reappeared in the colonic lumen as nitrate. Colonocytes may be important in oxidizing nitrite to nitrate, thus preventing excess nitrite from entering into the circulation and returning some nitrate to the colonic lumen for respiration by anaerobic bacteria. The interaction of nitrites and colonocytes deserves further study with regard to the oxidation-reduction of nitrite and to the development of colonic neoplasia in chronic diarrheal conditions.


Effect of electroacupuncture for Pisa syndrome in Parkinson's disease: A case report.
Pisa syndrome (PS) refers to marked lateral flexion of the trunk with a Cobb angle greater than 10°, which is typically mobile and can be resolved by lying down. PS is one of the most common postural deformities secondary to Parkinson's disease (PD) and can aggravate scoliosis in the advanced stages of PD. Here, we present the case of a 53-year-old woman who presented with lateral curvature for 6 mo. Full spine X-ray films in the correct position showed that the thoracolumbar spine was bent to the right without any rotation of the vertebrae. The patient was diagnosed with Pisa syndrome. After receiving a month's treatment with electroacupuncture, the Cobb angle decreased from 18.14° to 13.41°. This case demonstrates that electroacupuncture can effectively improve Pisa syndrome secondary to PD with few side effects and a low risk of recurrence. Additionally, early accurate diagnosis and timely intervention are meaningful for the prognosis of PS.


Use of free flaps with supermicrosurgery for oncological reconstruction of the maxillofacial region.
Supermicrosurgery involves the dissection and anastomosis of vessels<0.8 mm in diameter with minimal donor site morbidity. This study evaluated the feasibility and outcomes of free flaps using supermicrosurgery to repair oncological defects in the maxillofacial region. Forty-two patients were treated with supermicrosurgery to repair oncological defects in the maxillofacial region between December 2015 and February 2021. The supermicrosurgery technique was used for different types of free flap, including 24 superficial circumflex iliac artery perforator flaps, seven anterolateral thigh flaps, three peroneal artery perforator flaps, five medial femoral condyle osteo-adipofascial flaps, and three profunda artery perforator flaps. An artery-to-artery approach was used in 38 patients; venous grafts for anastomosis were used in four patients to resolve an arterial discrepancy. Forty-one flaps (97.6%) survived. Thirty-six patients (85.7%) healed without any complications; three flaps required revision surgery including one lost, one demonstrated wound dehiscence, and two demonstrated wound infection. Supermicrosurgery is a useful complement to conventional microsurgery in head and neck reconstruction.


Large aortopulmonary collateral artery exclusively supplying the lower lobe of left lung in an infant with common arterial trunk with aortic dominance with confluent pulmonary arteries.
Common arterial trunk with aortic dominance has well-developed bilateral pulmonary arterial arborization without any essential major aortopulmonary collateral arteries (MAPCAs), whereas "solitary" arterial trunk is characterized by collateral arterial supply to all bronchopulmonary segments and absent pulmonary arteries. We report a term female neonate with common arterial trunk with aortic dominance with confluent pulmonary arteries with a large MAPCA as the sole blood supply to the lower lobe of the left lung. Initial diagnostic workup missed this MAPCA from the descending thoracic aorta. It was suspected during surgery due to massive left atrial return and confirmed by cardiac catheterization study in the early postoperative period and treated successfully by unifocalization. A large essential MAPCA supplying an entire lobe in the common arterial trunk with aortic dominance has not been described. It can present as heart failure and inability to wean off the ventilator in the early postoperative period following intracardiac repair. This is a case hitherto undescribed and possibly falling outside the well-entrenched classifications of the common arterial trunk and a large MAPCA could be an addition to the list of lesion modifiers. Our experience with this case underlines the importance of a thorough and open-minded approach to the initial imaging assessment of even well-described conditions.


Violent deaths: the hidden face of maternal mortality.
To review pregnancy-related deaths due to injuries, to identify the characteristics of these women and to compare the magnitude of injury-related maternal deaths to that of other causes of maternal death. A retrospective study was performed during a five-year period (1991-1995), covering deaths from injuries, including suicide, homicide and accidents in Maputo, Mozambique. Department of Forensic Medicine at the Maputo Central Hospital, Mozambique. The pregnant or recently pregnant (post-abortion and postpartum) population of Maputo city, the national capital of Mozambique. Twenty-seven cases of pregnancy-related deaths caused by injuries were identified. Proportion of deaths due to homicide, suicide, and accidents in pregnant women or within 42 days after termination of pregnancy. Ten cases were due to alleged homicide, nine to alleged suicide and six to alleged accident. Fifty-nine percent (16/27) of women suffering an injury-related maternal death were younger than 25 years of age. Eighty-five percent of pregnancies were less than 28 weeks of gestational age. The magnitude of the problem of violence-related maternal deaths compares with the magnitude of pregnancy-induced hypertension as the fourth cause of maternal death at Maputo Central Hospital. The contribution of violence-related deaths tomaternal mortality is significant and must not be neglected.


Accurate detection of autism using Douglas-Peucker algorithm, sparse coding based feature mapping and convolutional neural network techniques with EEG signals.
Autism Spectrum Disorders (ASD) is a collection of complicated neurological disorders that first show in early childhood. Electroencephalogram (EEG) signals are widely used to record the electrical activities of the brain. Manual screening is prone to human errors, tedious, and time-consuming. Hence, a novel automated method involving the Douglas-Peucker (DP) algorithm, sparse coding-based feature mapping approach, and deep convolutional neural networks (CNNs) is employed to detect ASD using EEG recordings. Initially, the DP algorithm is used for each channel to reduce the number of samples without degradation of the EEG signal. Then, the EEG rhythms are extracted by using the wavelet transform. The EEG rhythms are coded by using the sparse representation. The matching pursuit algorithm is used for sparse coding of the EEG rhythms. The sparse coded rhythms are segmented into 8 bits length and then converted to decimal numbers. An image is formed by concatenating the histograms of the decimated rhythm signals. Extreme learning machines (ELM)-based autoencoders (AE) are employed at a data augmentation step. After data augmentation, the ASD and healthy EEG signals are classified using pre-trained deep CNN models. Our proposed method yielded an accuracy of 98.88%, the sensitivity of 100% and specificity of 96.4%, and the F1-score of 99.19% in the detection of ASD automatically. Our developed model is ready to be tested with more EEG signals before its clinical application.


Chronic hemodynamic overload of the atria is an important factor for gap junction remodeling in human and rat hearts.
The expression and distribution of connexins is abnormal in a number of cardiac diseases, including atrial fibrillation, and is believed to favor conduction slowing and arrhythmia. Here, we studied the role of atrial structural remodeling in the disorganization of gap junctions and whether redistributed connexins can form new functional junction channels. Expression of connexin-43 (Cx43) was characterized by immunoblotting and immunohistochemistry in human right atrial specimens and in rat atria after myocardial infarction (MI). Gap junctions were studied by electron and 3-D microscopy, and myocyte-myocyte coupling was determined by Lucifer yellow dye transfer. In both chronically hemodynamically overloaded human atria in sinus rhythm and in dilated atria from MI-rats, Cx43 were dephosphorylated and redistributed from the intercalated disc to the lateral cell membranes as observed during atrial fibrillation. In MI-rats, the gap junctions at the intercalated disc were smaller (20% decrease) and contained very little Cx43 (0 or 1 gold particle vs. 42 to 98 in sham-operated rats). In the lateral membranes of myocytes, numerous connexon aggregates comprising non-phosphorylated Cx43 were observed. These connexon aggregates were in no case assembled into gap junction plaque-like structures. However, N-cadherin was well organized in the intercalated disc. There was very little myocyte-myocyte coupling in MI-rat atria and no myocyte-fibroblast coupling. Regression of the atrial remodeling was associated with the normalization of Cx43 localization. Structural alteration of the atrial myocardium is an important factor in the disorganization of connexins and gap junction. Moreover, redistributed Cx43 do not form junction channels.


Urodynamic changes after tension-free sling procedures: Mycromesh-Plus vs TVT sling.
Assortments of suburethral sling procedures have become increasingly important in the treatment of stress urinary incontinence (SUI). This study compared a consecutive series of patients undergoing two types of no-tension, midurethral sling procedures: a traditional pubovaginal technique and graft (modified polytetrafluoroethylene graft; Mycromesh-Plus [MMP]) and the more recently introduced tension-free vaginal tape (TVT) sling. We observed for differences in success rates, urodynamic parameters, and complications of the two procedures. One group received a MMP sling, which was placed at the midurethra without tension. The other group underwent a minimally invasive TVT sling. Multichannel urodynamic studies were performed pre- and postoperatively. Cure rates for SUI were similar for the two groups (95 vs 95%). Urgency and urge incontinence symptoms improved substantially in both groups. Comparison of pre- and postoperative urodynamic indices demonstrated no differences in changes in average functional urethral lengths, changes in maximum urethral closure pressures, or improvement in pressure transmission ratios. Both groups showed a decrease in urethral mobility postoperatively. However, the TVT group demonstrated a lesser degree of change. While the TVT group did spontaneously void earlier than the MMP group (5.7 vs 9.7 days, p < 0.05), this did not result in significantly different postvoid residual volumes (71 vs 101 mL). Complications, including need for self-catheterization and sling revision or removal, and urinary tract infections also were fewer in the TVT group. This study demonstrated that the TVT sling affords an equivalent cure of SUI with similar urodynamic changes but significantly fewer complications than the more traditional MMP sling.


Augmentation of human immunodeficiency virus type 1 gene expression by tumor necrosis factor alpha.
It is now well established that cytokines are involved in the regulation of gene expression from HIV-1 LTR. The present study provides evidence that TNF-alpha stimulates HIV-1 gene expression and that the enhancer sequence within the HIV-1 LTR is involved in the stimulation. These results support the idea that immunologic stimulation and infection may trigger the development of clinical AIDS in individuals latently infected with HIV-1.


Antiarrhythmic effects and ionic mechanisms of allicin on myocardial injury of diabetic rats induced by streptozotocin.
The aim of this study was to evaluate the antiarrhythmic effect of allicin (AL) on streptozotocin (STZ)-induced diabetic rats and explore the possible mechanisms. Hyperglycemia was induced in rats by single intraperitoneal injection of STZ (40 mg/kg). Three days after STZ treatment, the hyperglycemic rats (plasma glucose levels≥16.7 mM) were administered with AL (4, 8, and 16 mg/kg) by intraperitoneal injection daily for 28 days. The fasting blood glucose levels were measured on every seventh day during the 28 days of treatment. The body weight and blood glucose levels were detected after 28 days. Antiarrhythmic effect of AL was observed in the diabetic rats induced by BaCl2. To determine the ionic mechanism in rat ventricular myocytes of AL, action potential duration (APD), L-type calcium current (ICa-L), and inward rectifier potassium current (IK1) were recorded by the whole cell-patch clamp technique. The expressions of L-type calcium channel protein α1C mRNA and cell potassium channels protein Kir2.1 mRNA were studied by RT-PCR. AL normalized the RR interval and QT interval in diabetic rats. AL obviously delayed the onset of ventricular arrhythmia and reduced the score of arrhythmia induced by BaCl2. Electrophysiological experiment revealed that AL could shorten APD through inhibition of ICa-L and enhancement of IK1. RT-PCR analysis indicated that long-term treatment with AL could decrease the expression of α1C mRNA and increase the expression of Kir2.1 mRNA. AL has antiarrhythmic effect in STZ-induced diabetic rats. It is tempting for the application of AL to be a useful therapeutic approach in diabetes with ventricular arrhythmia.


Sinusoidal spread of liver metastases from renal cell carcinoma: simulation of diffuse liver disease on MR imaging.
Rarely, hepatic metastases can simulate hepatic infiltrative diseases. We present a case of a patient with advanced metastatic renal cell carcinoma who developed hepatomegaly and clinical signs of hepatocellular injury. On magnetic resonance imaging, the injury simulated a diffuse process, e.g., acute fulminant viral or chemical hepatitis or drug toxicity. Despite its high resolution, magnetic resonance imaging might not depict focal lesions in patients with extensive metastases. In correlation with clinical history, malignant disease should be considered when diffusely abnormal hepatic signal intensity is noted.


Cortical visual evoked potentials during the sleep wakefulness cycle of the freely moving cat. Characterization and statistical comparisons.
Visual evoked potentials (VEPs) were obtained during the stages of wakefulness (W), slow sleep (SS) and paradoxical sleep (PS) by means of a light-emitting diode chronically implanted in the frontal sinus of the freely moving cat. Statistical analysis of the variables: latencies, latency intervals and amplitudes, between each of the mentioned stages shows that, for the first components, variations occurred only in the first interval of latency during SS vs. W. Lengthening of VEP latencies and increase of VEP amplitudes were observed for all secondary components in the comparisons between both SS and W, and SS and PS. PS-VEPs vs. W-VEPs showed shortening of latencies and decrease of amplitudes of all secondary components of the former case. The results confirm that in the freely moving cat, the secondary VEP response is more intensely affected by sleep than the primary VEP response, but indicate that there are different mechanisms in the generation of the VEP during SS and PS.


Pharmacological modulations on the nociceptive flexion reflex in man.
Pharmacological actions on the nociceptive flexion flexes of the hindlimb were investigated in 14 normal subjects. These reflexes were used as an index of pain and were recorded in the biceps femoris muscle, elicited by electrical stimulation of the ipsilateral sural nerve (RIII,su) and of the skin in the distal receptive field of this nerve (RIII,Cu). The ratio of the threshold of RIII,Cu/RIII,Su was calculated since it gives an indication on the mechanism and the efficacy of the drug. During control periods, the mean values of RIII,Su threshold (10 mA) and of RIII,Cu threshold (5 mA) remained stable, as RIII,Cu/RIII,Su threshold (50%). Cutaneous application of naphthalene provoked a decrease in the RIII,Cu threshold and relative pain threshold, whereas lignocaine increased them. No changes in the RIII,Su, threshold and relative pain were observed. The ratio RIII,Cu/RIII,Su threshold and relative pain were observed. The ratio RIII,Cu/RIII,Su was lowered to 10% with naphthalene and increased to 110% with lignocaine. Intravenous injection of acetylsalicylic acid increased only the RIII,Cu threshold and relative pain threshold. The ratio RIII,Cu/RIII,Su was 90% at the maximal effect of the drug. In contrast, pethidine provoked a decrease in the RIII,Su threshold and an increase in RIII,Cu threshold, parallel with an increase in pain threshold sensation. The ratio was found to be 190% at the maximal effect. Practical implications of these results, concerning a method for testing the efficacy and mechamisms of an analgesic, are then discussed.


Singlet oxygen quantum yields of potential porphyrin-based photosensitisers for photodynamic therapy.
The singlet oxygen formation quantum yield (Phi(Delta)) for solutions of the di-cation, free-base and metallated forms of hematoporphyrin derivative (HpD), hematoporphyrin IX (Hp9) and a boronated protoporphyrin (BOPP) are reported using the method of direct detection of the characteristic phosphorescence following polychromatic excitation. Values of Phi(Delta) for the free-base form of all the porphyrins and the di-cation forms of Hp9 and HpD are in the range of 0.44 to 0.85 in the solvents investigated. Incorporation of zinc ions into the macrocycle reduces Phi(Delta) for all three porphyrins. BOPP facilitates the coordination of certain transition metals (Mn, Co and Cu) compared to Hp9 and HpD and results in a dramatic decrease in Phi(Delta). The experimental data suggest the introduction of low energy charge transfer states associated with the disruption of the planarity of the macrocyclic ring provides alternative non-radiative deactivation pathways. In BOPP, this non-planarity is augmented by the large closo-carborane peripheral substituent groups.


Production and structure elucidation of di- and oligosaccharide lipids (biosurfactants) from Tsukamurella sp. nov.
The bacterium Tsukamurella sp. nov., isolated from soil, was found to produce novel glycolipids when grown on sunflower oil as the sole carbon source. The glycolipids were isolated by chromatography on silica columns and their structures elucidated using a combination of multidimensional NMR and MS techniques. The three main components are 2,3-di-O-acyl-alpha-D-glucopyranosyl-(1-1)-alpha-D-glucopyranose, 2,3-di-O-acyl-beta-D-glucopyranosyl-(1-2)-4,6-di-O-acyl-alpha-D- glucopyranosyl-(1-1)-alpha-D-glucopyranose and 2,3-di-O-acyl-beta-D-glucopyranosyl-(1-2)-beta-D-galactopyranosyl- (1-6)-4,6-di-O-acyl-alpha-D-glucopyranosyl-(1-1)-alpha-D- glucopyranosyl which are linked to fatty acids varying in chain length from C4 to C18. The glycolipids are mainly extracellular but are also found attached to the cell walls. During the cultivation the composition of the glycolipids changed from disaccharide- to tri- and tetrasaccharide lipids. The glycolipids show good surface-active behaviour and have antimicrobial properties.


Chronic cholesterol depletion increases F-actin levels and induces cytoskeletal reorganization via a dual mechanism.
Previous work from us and others has suggested that cholesterol is an important lipid in the context of the organization of the actin cytoskeleton. However, reorganization of the actin cytoskeleton upon modulation of membrane cholesterol is rarely addressed in the literature. In this work, we explored the signaling crosstalk between cholesterol and the actin cytoskeleton by using a high-resolution confocal microscopic approach to quantitatively measure changes in F-actin content upon cholesterol depletion. Our results show that F-actin content significantly increases upon chronic cholesterol depletion, but not during acute cholesterol depletion. In addition, utilizing inhibitors targeting the cholesterol biosynthetic pathway at different steps, we show that reorganization of the actin cytoskeleton could occur due to the synergistic effect of multiple pathways, including prenylated Rho GTPases and availability of membrane phosphatidylinositol 4,5-bisphosphate. These results constitute one of the first comprehensive dissections of the mechanistic basis underlying the interplay between cellular actin levels and cholesterol biosynthesis. We envision these results will be relevant for future understating of the remodeling of the actin cytoskeleton in pathological conditions with altered cholesterol.


Factors relating to coagulation, fibrinolysis and hepatic damage after liver resection.
A survey of the blood of twenty-two patients who had undergone hepatic resection was performed. Serum levels of alpha-2 plasmin inhibitor-plasmin complex initially decreased from 1.58 +/- 0.31 microgram/ml on the preoperative day (PREOP), to 0.92 +/- 0.14 mu/ml on the first postoperative day (POD 1), and then increased to 3.13 +/- 0.92 micrograms/ml on the seventh postoperative day (POD 7) (mean +/- SE)). Thrombin-anti-thrombin III complex (14.2 +/- 4.3 ng/ml on PREOP and 26.0 +/- 4.1 ng/ml on POD 7 (mean +/- SE)) and D-dimer (335 +/- 96 ng/ml on PREOP and 1859 +/- 258 ng/ml on POD 7 (mean +/- SE)) increased in the early postoperative stage. The level of 6-keto-prostaglandin F1 alpha increased after the operations (from 13.2 +/- 1.8 pg/ml on PREOP to 37.8 +/- 12.8 pg/ml on POD 7 (mean +/- SE)). The level of thromboxane B-2 decreased at first, and then gradually increased and returned to its preoperative level on POD 7 (144.7 +/- 43.8 pg/ml on PREOP, 57.6 +/- 27.5 pg/ml on POD 1 and 152.5 +/- 58.4 pg/ml on POD 7 (mean +/- SE)). Superoxide dismutase activity increased at first, and then gradually decreased, postoperatively (2.8 +/- 0.5 NU/ml on PREOP, 4.8 +/- 0.8 NU/ml on POD 1 and 2.6 +/- 0.3 NU/ml on POD 7 (mean +/- SE)). That is, biodefensive reactions which protect patients against the shift to disseminated intravascular coagulation (DIC) were inferred with by the increase in antiplatelet aggregation, despite the activation of coagulation and fibrinolytic mechanisms after hepatic resection.


Seven-year review of paediatric bacteraemias diagnosed in a Spanish university hospital.
This study analysed the clinical and bacteriological patterns of paediatric bacteraemia in a university hospital, by a review of 213 episodes over a period of 7 y. Streptococcus pneumoniae was the most frequent aetiological agent after the neonatal period and Streptococcus agalactiae in neonatal sepsis. Almost half of pneumococci and meningococci were penicillin non-susceptible. Four neonatal deaths attributed to bacteraemia were recorded. Streptococcus pneumoniae is the leading cause of community-acquired bacteraemia. Mortality due to bacteraemia in children without underlying conditions is rare.


UP-HILIC-MS/MS to Determine the Action Pattern of Penicillium sp. Dextranase.
Investigation of the action pattern of enzymes acting on carbohydrates is challenging, as both the substrate and the digestion products are complex mixtures. Dextran and its enzyme-derived oligosaccharides are widely used for many industrial applications. In this work, a new method relying on ultra-performance hydrophilic interaction liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UP-HILIC-Q/TOF-MS/MS) was developed to analyze a complex mixture of dextran oligosaccharide products to determine the action pattern of dextranase. No derivatization of oligosaccharides was required and the impact of the α- and β-configurations of the native oligosaccharides on the chromatographic separation was eliminated. The 1→6, 1→3, 1→4 backbone linkages and the branch linkages of these oligosaccharides were all distinguished from diagnostic ions in their MS/MS spectra, including fragments corresponding to (0,2)A, (0,3)A, (0,4)A, B-H2O, (2,5)A, and (3,5)A. The sequences of the oligosaccharide products were similarly established. Thus, the complex oligosaccharide mixtures in dextran digestion products were profiled and identified using this method. The more enzyme-resistant structures in dextran were established using much less sample, labor, time, and uncertainty than in previous studies. This method provides an efficient, sensitive, and straightforward way to monitor the entire process of digestion, establish the action pattern of the dextranase from Penicillium sp., and to support the proper industrial application of dextranase.


Redox regulation of the tumor suppressor PTEN by the thioredoxin system and cumene hydroperoxide.
Intracellular redox status influences the oxidation and enzyme activity of the tumor suppressor phosphatase and tensin homolog on chromosome 10 (PTEN). Cumene hydroperoxide (CuHP), an organic hydroperoxide, is a known tumor promoter. However, molecular targets and action mechanism of CuHP in tumor promotion have not been well characterized. In this study, we investigated the effect of CuHP on the redox state of PTEN in HeLa cells. In addition, the intracellular reducing system of oxidized PTEN was analyzed using a biochemical approach and the effect of CuHP on this reducing system was also analyzed. While PTEN oxidized by hydrogen peroxide is progressively converted to its reduced form, PTEN was irreversibly oxidized by exposure to CuHP in HeLa cells. A combination of protein fractionation and mass analysis showed that the reducing system of PTEN was comprised of NADPH, thioredoxin reductase (TrxR), and thioredoxin (Trx). Although CuHP-mediated PTEN oxidation was not reversible in cells, CuHP-oxidized PTEN was reactivated by the exogenous Trx system, indicating that the cellular Trx redox system for PTEN is inactivated by CuHP. We present evidence that PTEN oxidation and the concomitant inhibition of thioredoxin by CuHP results in irreversible oxidation of PTEN in HeLa cells. In addition, ablation of peroxiredoxin (Prdx) enhanced CuHP-induced PTEN oxidation in cells. These results provide a new line of evidence that PTEN might be a crucial determinant of cell fate in response to cellular oxidative stress induced by organic hydroperoxides.


Deep sclerectomy with Nd:YAG laser trabeculotomy ab interno: two-stage procedure.
We performed almost the same procedure as Weber's two-stage Nd:YAG laser trabeculotomy. Our technique, developed without knowledge of Weber's findings, also is composed of two stages. In Stage 1, under conjunctival and thin scleral flaps, the deep (4 x 2 mm) scleral block containing the outer wall of Schlemm's canal is removed. Stage 2, the puncturing of the remaining trabeculum with Q-switched Nd:YAG laser, is performed the next day. We evaluated the technique in 16 eyes of 11 patients with medically uncontrolled phakic open-angle glaucoma and one eye of a pseudophakic patient with a Binkhorst 2-loop lens. All eyes had unacceptable intraocular pressures (IOPs), despite maximum tolerated medical therapy, and two 360 degrees argon laser trabeculoplasties. The mean preoperative and final postoperative IOPs were 38.3 +/- 19.1 mm Hg and 16.9 +/- 5.3 mm Hg, respectively. Follow-up time was at least 12 months and the results of a 12-month postoperative period were used in all cases. Final postoperative IOP was less than 21 mm Hg in 12 eyes (70%). The only complication during intraoperative and postoperative periods was extremely slight bleeding from the trabeculum or Schlemm's canal in Stage 2; this bleeding was completely absorbed by the following day.


Climate change: the importance of place.
Climate change-related risks are place-specific and path-dependent. Accordingly, location is an important determinant of hazardous exposure, and certain places will bear more risk than others. This article reviews the major environmental exposures associated with risky places in the U.S., including coastal regions, islands, the desert Southwest, vectorborne and zoonotic disease border regions, cities, and the U.S. Arctic (Alaska), with emphasis on exposures and vulnerable populations of concern. In addition to these hotspots, this study considers the ways in which the concept of place--the sense of human relationship with particular environments--will play a key role in motivating, developing, and deploying an effective public health response. In considering the importance of place, we highlight the concepts of community resilience and risk management, key aspects of a robust response to climate change in public health and other sectors.


Dietary nitrate supplementation for preventing and reducing the severity of winter infections, including COVID-19, in care homes (BEET-Winter): a randomised placebo-controlled feasibility trial.
Infections cause considerable care home morbidity and mortality. Nitric oxide (NO) has broad-spectrum anti-viral, bacterial and yeast activity in vitro. We assessed the feasibility of supplementing dietary nitrate (NO substrate) intake in care home residents. We performed a cluster-randomised placebo-controlled trial in UK residential and nursing care home residents and compared nitrate containing (400 mg) versus free (0 mg daily) beetroot juice given for 60 days. Outcomes comprised feasibility of recruitment, adherence, salivary and urinary nitrate, and ordinal infection/clinical events. Of 30 targeted care homes in late 2020, 16 expressed interest and only 6 participated. 49 residents were recruited (median 8 [interquartile range 7-12] per home), mean (standard deviation) age 82 (8) years, with proxy consent 41 (84%), advance directive for hospital non-admission 8 (16%) and ≥ 1 doses of COVID-19 vaccine 37 (82%). Background dietary nitrate was < 30% of acceptable daily intake. 34 (76%) residents received > 50% of juice. Residents randomised to nitrate vs placebo had higher urinary nitrate levels, median 50 [18-175] v 18 [10-50] mg/L, difference 25 [0-90]. Data paucity precluded clinical between-group comparisons; the outcome distribution was as follows: no infection 32 (67%), uncomplicated infection 0, infection requiring healthcare support 11 (23%), all-cause hospitalisation 5 (10%), all-cause mortality 0. Urinary tract infections were most common. Recruiting UK care homes during the COVID-19 pandemic was partially successful. Supplemented dietary nitrate was tolerated and elevated urinary nitrate. Together, infections, hospitalisations and deaths occurred in 33% of residents over 60 days. A larger trial is now required. ISRCTN51124684. Application date 7/12/2020; assignment date 13/1/2021.