Addition of Nasal Cannula Can Either Impair or Enhance Preoxygenation With a Bag Valve Mask: A Randomized Crossover Design Study Comparing Oxygen Flow Rates.
A critical safety component of emergency anesthesia is the avoidance of hypoxemia during the apneic phase of a rapid sequence intubation. Preoxygenation with a bag valve mask (BVM) or anesthetic circuit may be improved with supplemental oxygen by nasal cannula (NC) if there is a mask leak. In addition, NC is recommended for apneic oxygenation after induction and may be placed before preoxygenation. However, the optimum NC flow rate for preoxygenation or whether the presence of NC alone creates a mask leak remains unclear. We performed a randomized crossover study on healthy volunteers comparing BVM alone and BVM with NC flow rates of 0 (NC-0), 5 (NC-5), 10 (NC-10), and 15 (NC-15) liters per minute (lpm). Our primary outcome was end-tidal oxygen (ETO2) after 3-minute preoxygenation. There was no difference in ETO2 between NC-15, NC-10, or BVM-only at 3 minutes. NC-0 and NC-5 recorded significantly lower ETO2 at all times compared with NC-15, NC-10, or BVM-only (least difference NC-5, -7% [95% confidence interval {CI}, -4% to -10%), NC-0, 16% [95% CI, 13%-19%]). There was a difference in ETO2 between NC-15 and BVM-only at 1 minute (7%; 95% CI, 5%-9%), but not at 2 or 3 minutes. There was no difference in ETO2 between NC-10 and NC-15. Our study found that NC at 0 and 5 lpm with a BVM is deleterious to preoxygenation and should be avoided. In addition, a lack of difference between NC-10 and BVM-only demonstrates that NC at flows of at least 10 lpm should not impair the preoxygenation process. While NC-15 may offer a benefit by reaching maximal ETO2 at 1 minute, this would need to be balanced against patient comfort.


R2 Relaxometry of SABRE-Hyperpolarized Substrates at a Low Magnetic Field.
Nuclear magnetic resonance (NMR) relaxometry at a low magnetic field, in the milli-Tesla range or less, is enabled by signal enhancements through hyperpolarization. The parahydrogen-based method of signal amplification by reversible exchange (SABRE) provides large signals in a dilute liquid for the measurement of R2 relaxation using a single-scan Carr-Purcell-Meiboom-Gill (CPMG) experiment. A comparison of relaxation rates obtained at high and low fields indicates that an otherwise dominant contribution from chemical exchange is excluded in this low-field range. The SABRE process itself is based on exchange between the free and polarization transfer catalyst-bound forms of the substrate. At a high magnetic field of 9.4 T, typical conditions for producing hyperpolarization including 5 mM 5-fluoropyridine-3-carboximidamide as a substrate and 0.5 mM chloro(1,5-cyclooctadiene)[4,5-dimethyl-1,3-bis(2,4,6-trimethylphenyl)imidazol-2-ylidene]iridium(I) as a polarization transfer catalyst precursor resulted in an R2 relaxation rate as high as 3.38 s-1. This relaxation was reduced to 1.19 s-1 at 0.85 mT. A quantitative analysis of relaxation rates and line shapes indicates that milli-Tesla or lower magnetic fields are required to eliminate the exchange contribution. At this magnetic field strength, R2 relaxation rates are indicative primarily of molecular properties. R2 relaxometry may be used for investigating molecular interactions and dynamics. The SABRE hyperpolarization, which provides signal enhancements without requiring a high magnetic field or large instrumentation, is ideally suited to enable these applications.


Self-Supervised Multi-Scale Cropping and Simple Masked Attentive Predicting for Lung CT-Scan Anomaly Detection.
Anomaly detection has been widely explored by training an out-of-distribution detector with only normal data for medical images. However, detecting local and subtle irregularities without prior knowledge of anomaly types brings challenges for lung CT-scan image anomaly detection. In this paper, we propose a self-supervised framework for learning representations of lung CT-scan images via both multi-scale cropping and simple masked attentive predicting, which is capable of constructing a powerful out-of-distribution detector. Firstly, we propose CropMixPaste, a self-supervised augmentation task for generating density shadow-like anomalies that encourage the model to detect local irregularities of lung CT-scan images. Then, we propose a self-supervised reconstruction block, named simple masked attentive predicting block (SMAPB), to better refine local features by predicting masked context information. Finally, the learned representations by self-supervised tasks are used to build an out-of-distribution detector. The results on real lung CT-scan datasets demonstrate the effectiveness and superiority of our proposed method compared with state-of-the-art methods.


Ureteroceles vs. pseudoureteroceles in adults. Urographic diagnosis.
Simple ureteroceles discovered in adults on excretory urography have long been regarded as congenital anomalies, usually innocuous. Pseudoureteroceles are acquired dilatations of the submucosal portion of the distal ureter that mimic simple ureteroceles. The authors compared 5 pseudoureteroceles and 13 simple ureteroceles and found that the former were distinguished by asymmetry of the dilated ureteral lumen, moderate to severe obstruction of the upper tract, and evidence of an acquired cause such as a calculus or abnormal vesical mucosal pattern. The distinction is important, since most pseudoureteroceles were related to malignancy involving the bladder.


Genomic organization and characterization of the white locus of the Mediterranean fruitfly, Ceratitis capitata.
An approximately 14-kb region of genomic DNA encoding the wild-type white eye (w+) color gene from the medfly, Ceratitis capitata has been cloned and characterized at the molecular level. Comparison of the intron-exon organization of this locus among several dipteran insects reveals distinct organizational patterns that are consistent with the phylogenetic relationships of these flies and the dendrogram of the predicted primary amino acid sequence of the white loci. An examination of w+ expression during medfly development has been carried out, displaying overall similarity to corresponding studies for white gene homologues in Drosophila melanogaster and other insects. Interestingly, we have detected two phenotypically neutral allelic forms of the locus that have arisen as the result of an apparently novel insertion or deletion event located in the large first intron of the medfly white locus. Cloning and sequencing of two mutant white alleles, w1 and w2, from the we,wp and M245 strains, respectively, indicate that the mutant conditions in these strains are the result of independent events--a frameshift mutation in exon 6 for w1 and a deletion including a large part of exon 2 in the case of w2.


The occupational therapist on a geriatric rehabilitation team.
This article describes a rehabilitation services team at a skilled nursing facility. The objectives were to explore what occupational therapy can offer nursing home residents and to provide a model in the delivery of rehabilitation services to the institutionalized elderly. Emphasis is placed upon program structure and rationale, staff interrelationships, and the role of the occupational therapist on the team.


Disparities in Psychosis Risk Symptoms for New Zealand Māori May Be Explained by Systemic Stressors and Inappropriate Conceptualization of Culturally Normative Experiences.
Māori, the indigenous peoples of New Zealand, experience increased rates of psychotic disorders and first-episode psychosis. However, it is unclear whether they also present with increased psychosis risk symptoms, such as subclinical psychotic-like experiences (PLEs). Measurement of risk symptoms is key for early intervention. Further, it is unclear if systemic factors such as the increased rates of social adversity and discrimination or cultural biases contribute to this disparity in psychosis rates. This study surveyed 466 18- to 30-year olds in New Zealand, and compared Māori to non-Māori participant responses on the Prodromal Questionnaire Brief, alongside the history of childhood trauma, discrimination, and financial adversity. Māori reported a higher number of PLEs compared to non-Māori-however, this was not associated with increased distress related to these experiences. The increased number of psychosis-like experiences reported by Māori was likely explained by systemic factors such as childhood trauma, discrimination, and financial stress. Māori were more likely to report that the PLEs were positive. Measurement of psychosis risk for Māori is nuanced, and increased scores on these tools may reflect pathologizing potentially normative experiences for Māori, such as spiritual encounters or discrimination, alongside the impact of increased rates of systemic discrimination, trauma, and financial stress.


Composition of the ancient north american crust.
Geochemical studies of Wyoming Precambrian graywackes derived from continental crust older than 3.2 x 10(9) years indicate that their source area was at least as highly differentiated as most younger Precambrian crust. The composition of this early crust (approximately that of calcium-rich granite) is not unlike that of the 2.5 to 3.2 x 10(9) year old North American crust. Limited geochemical data suggest that the composition of North America may not have changed significantly during the last 3.0 to 3.5 x 10(9) years.


[Comparison of intensive and moderate individual life-style intervention programs for overweight or obese persons with fasting glucose levels of 95-125 mg/dl in Japan].
There are considerable differences in individual health education programs for persons at high risk of type 2 diabetes between ordinary Japanese life-style modification programs and the Diabetes Prevention Program in the US, the former being relatively moderate and the latter more intensive. We therefore compared the effectiveness of intensive and moderate intervention, focusing on the frequency of individual educational classes. The subjects were men and women aged 44-69 years living in Nishiaizu town, Fukushima prefecture in Japan. Their fasting plasma glucose concentration was between 95 and 125 mg/dl at health examinations conducted in 2002 or 2003. They also had a body mass index (BMI) of 23.0 or higher, a fasting plasma glucose concentration of 125 mg/dl or lower and a post-load plasma glucose concentration (2 h) of 199 mg/dl or lower in the 2004 survey. We assigned the subjects according to their residences to an intensive life-style intervention group (two education classes per month; n = 11) or a moderate intervention group (one education class per month; n = 14). The main outcome measure was the change in body weight after 6 months of intervention. The loss of body weight was -3.5 kg (P< .0001) in the intensive intervention group and -1.8 kg (P = 0.02) in the moderate group, and the net difference in body weight loss between the groups was -2.0 kg (95% confidence interval -4.0 to -0.05; P = 0.045) after adjustment for age, sex, and baseline body weight. BMI and subcutaneous fat area showed similar results. The post-load plasma glucose concentration (2 h) and other tested values showed no significant net change between the two groups. Intensive and moderate intervention both reduced body weight in overweight or obese persons at high risk of type 2 diabetes. The intensive intervention, two sessions of individual education classes per month, was significantly more effective than the moderate one for reducing body weight.


Childhood psychiatric disorders. Focus on conduct disorders.
The high prevalence of child and adolescent psychiatric disorders in general and of aggressive behaviors in particular presents a serious problem. Recent social, economic and demographic trends suggest that the problem is likely to grow in degree of seriousness. It is recommended that the broad social and economic policies that impact on risk factors be evaluated and that greater emphasis be placed upon prevention efforts. These efforts need to particularly strengthen the social, emotional, and economic supports that provide an important protective factor for children and families. Practices in education, employment, health, and human services need to be examined to insure that they provide support. Perhaps the most encouraging development is the growth of children's services councils. There needs to be support for their continuing growth and for the development of more effective partnerships between state and local government. A particular focus should be upon strengthening neighborhoods and local communities, involving schools and school-based services as a source of support for families, and the increasing involvement of local civic and religious groups.


Scaling agricultural mechanization services in smallholder farming systems: Case studies from sub-Saharan Africa, South Asia, and Latin America.
There is great untapped potential for farm mechanization to support rural development initiatives in low- and middle-income countries. As technology transfer of large machinery from high-income countries was ineffective during the 1980s and 90s, mechanization options were developed appropriate to resource poor farmers cultivating small and scattered plots. More recently, projects that aim to increase the adoption of farm machinery have tended to target service providers rather than individual farmers. This paper uses the Scaling Scan tool to assess three project case studies designed to scale different Mechanization Service Provider Models (MSPMs) in Mexico, Zimbabwe, and Bangladesh. It provides a useful framework to assess the gap between international lessons learned on scaling captured in forty tactical questions over ten "scaling ingredients" as perceived by stakeholders involved in the projects, as well as private sector actors and government employees. Although at first sight the case studies seem to successfully reach high numbers of end users, the assessment exposes issues around the sustainable and transformative nature of the interventions. These are highly influenced by the design of the projects and by the environment and context of the intervention areas. Across the three case studies, large-scale adoption of the models was found to be hampered by lack of finance to set up MSPMs and insufficient collaboration among the value chain actors to strengthen and foster Mechanization Service Provider (MSP) entrepreneurs. Applying a scaling perspective on each case study project exposed important lessons on minimizing project dependencies. Positive examples include integration of capacity development materials in vocational training centers in Zimbabwe, promotion of MSPMs by other donors in East Africa and levering of nearly USD six million of private sector investment in appropriate machinery in Bangladesh. On the other hand, there is still a high dependency on the projects in terms of coaching of service providers, facilitating collaboration along the value chain, and provision of leadership and advocacy to address issues at governance level. These results have important implications for similar development interventions aimed at increasing smallholder access to mechanization services at scale and is to our knowledge the first cross-continental assessment of these issues to date.


[Influence of diet and physical activity on the course and therapy of osteoporosis].
Osteoporosis is a disease, the course of which is dependent among others on diet and physical activity. The aim of study was to find correlation between these factors and changes in bone density measured in lumbar spine. The project comprised 82 women with primary postmenopausal or senile osteoporosis treated with calcitonin, hormone replacement therapy and vitamin D. Bone density was measured by DEXA method before and after 12 month therapy. The patients were divided into four groups depending upon amount of ingested calcium and time of physical activity performed daily. Only in the group of women (n = 32) who were physically active and presented high dietary calcium intake (over 500 mg daily) statistically significant improvement in bone density was found: T-score increased by +0.23 (p = 0.010449). No statistically significant difference of bone density in other subgroups was found. Daily dietary calcium intake over 500 mg and physical activity performed for over 45 minutes every day provides higher bone density increase during pharmacotherapy of osteoporosis compared to pharmacotherapy alone or pharmacotherapy associated with only one of the above mentioned elements.


Trap distribution and mechanism for near infrared long-afterglow material AlMgGaO4:Cr3.
Near infrared (NIR) long-afterglow materials have attracted much attention due to their high penetration and low destruction in biological tissues. Here, a series of deep red and near infrared materials, AlMgGaO4:xCr3+, were successfully synthesized by a high temperature solid state method. AlMgGaO4 was selected as the host considering its rich antisite defects, which can effectively capture electrons. The emission spectra of AlMgGaO4:xCr3+ range from 680 nm to 1100 nm, which can be nicely decomposed into four Gaussian bands with peaks centered at 706 nm, 723 nm, 916 nm, and 938 nm, respectively. At low temperature (10 K), the emission spectra show there are four emission peaks: a sharp line (peak 1) and broad emission band (peak 2) come from Cr3+ substituting for the regular octahedron [AlO6], and two broad emission bands (peaks 3 and 4) which originate from the spin-allowed transition 4T2(4F) → 4A2(4F) of Cr3+ in the disordered [GaO6] and [MgO6] octahedra, respectively. Remarkably, after removing the excitation source, it exhibited more than 10 hours of afterglow emission which decreased sharply in the first 30 min and then decreased slowly. With an increase in the Cr3+ concentration, the trap depth became shallower due to the generation of the electronic trap centers . The distribution of trap centers and the mechanism of the persistent luminescence have been carefully analyzed and are also discussed.


Comparison of efficacy and toxicity of traditional Chinese medicine (TCM) herbal mixture LQ and conventional chemotherapy on lung cancer metastasis and survival in mouse models.
Unlike Western medicine that generally uses purified compounds and aims to target a single molecule or pathway, traditional Chinese medicine (TCM) compositions usually comprise multiple herbs and components that are necessary for efficacy. Despite the very long-time and wide-spread use of TCM, there are very few direct comparisons of TCM and standard cytotoxic chemotherapy. In the present report, we compared the efficacy of the TCM herbal mixture LQ against lung cancer in mouse models with doxorubicin (DOX) and cyclophosphamide (CTX). LQ inhibited tumor size and weight measured directly as well as by fluorescent-protein imaging in subcutaneous, orthotopic, spontaneous experimental metastasis and angiogenesis mouse models of lung cancer. LQ was efficacious against primary and metastatic lung cancer without weight loss and organ toxicity. In contrast, CTX and DOX, although efficacious in the lung cancer models caused significant weight loss, and organ toxicity. LQ also had anti-angiogenic activity as observed in lung tumors growing in nestin-driven green fluorescent protein (ND-GFP) transgenic nude mice, which selectively express GFP in nascent blood vessels. Survival of tumor-bearing mice was also prolonged by LQ, comparable to DOX. In vitro, lung cancer cells were killed by LQ as observed by time-lapse imaging, comparable to cisplatinum. LQ was more potent to induce cell death on cancer cell lines than normal cell lines unlike cytotoxic chemotherapy. The results indicate that LQ has non-toxic efficacy against metastatic lung cancer.


Infarct Patterns in Patients with Atherosclerotic Vertebrobasilar Disease in Relation to Hemodynamics.
Distal territory blood flow is independently associated with subsequent strokes in symptomatic vertebrobasilar atherosclerotic disease. We aimed to assess infarct patterns in relation to hemodynamic status in the prospective Vertebrobasilar Flow Evaluation and Risk of Transient Ischemic Attack and Stroke (VERiTAS) study. Distal territory blood flow was measured using quantitative magnetic resonance angiography (MRA) in 72 patients with symptomatic atherosclerotic vertebrobasilar disease, and then dichotomized into normal (n = 54) and low (n = 18) flow. Patients were followed longitudinally on standard medical management. Two observers blinded to flow status independently reviewed the imaging performed at the time of subsequent strokes, in order to adjudicate the likely mechanism based on infarct patterns. The frequency of stroke mechanisms was qualitatively compared based on flow status. During a median follow-up period of 23 months, 10/72 patients had a subsequent stroke; 5 of these had low distal flow. Infarct patterns were adjudicated to be consistent with hemodynamic (n = 2), embolic (n = 4), and junctional plaque/perforator (n = 4) infarcts. Hemodynamic infarcts were seen in 40% (2/5) low-flow patients, in comparison to 0% (0/5) normal-flow patients. In contrast to normal-flow patients, those with low distal flow seem to be uniquely susceptible to hemodynamic infarctions, although other patterns of infarction can also be seen in these hemodynamically impaired patients.


Survival trends and outcomes among preterm infants with congenital diaphragmatic hernia.
The objective of this study was to use current national data to evaluate the characteristics and survival trends of preterm infants born with CDH from 2004 to 2014. Data was queried from the National Inpatient Sample (NIS) and KID database from 2004 to 2014. Infants were included if diagnosed with CDH by ICD-9 coding and gestational age <37 weeks. Descriptive statistics, chi-square, and trend analysis were completed. We identified 2356 infants born prematurely with CDH. The overall survival rate was 49%. The survival range is 21.2-62.3% for gestational age <26 weeks to 35-36 weeks, respectively. Total mortality was 1183; of them, 1052 (89%) were not repaired and 363 (30.7%) did not receive mechanical ventilation. Surgical repair occurred in 55.1% of infants. Preterm infants have lower survival compared with term infants. Survival rates decrease with lower gestational age and have improved over time.


[Epidemiological and clinical aspects of extrapulmonary tuberculosis in North-Western Russia].
North-western Russia is characterized by poor extrapulmonary tuberculosis (EPT) epidemiological trends. There is an increase in the incidence of EPT mainly in childhood and youth. Due to incomplete and untimely detection of extrapulmonary tuberculosis, the decreased level of recorded parameters and its severe clinical pattern are observed in most areas.


The Interplay of Cohesin and the Replisome at Processive and Stressed DNA Replication Forks.
The cohesin complex facilitates faithful chromosome segregation by pairing the sister chromatids after DNA replication until mitosis. In addition, cohesin contributes to proficient and error-free DNA replication. Replisome progression and establishment of sister chromatid cohesion are intimately intertwined processes. Here, we review how the key factors in DNA replication and cohesion establishment cooperate in unperturbed conditions and during DNA replication stress. We discuss the detailed molecular mechanisms of cohesin recruitment and the entrapment of replicated sister chromatids at the replisome, the subsequent stabilization of sister chromatid cohesion via SMC3 acetylation, as well as the role and regulation of cohesin in the response to DNA replication stress.


Crohn's disease of the colon. II. Controversial aspects of hemorrhage, anemia and rectal involvement in granulomatous disease involving the colon.
In 160 cases with granulomatous colitis or ileocolitis, blood was found in the stool in 72 or 45%. Massive bleeding occurred in four patients (25%); overt bleeding in 51 (32%) and occult bleeding, repeated guaiac positive stools, in 17 (11%). Thus, clinically obvious bleeding occurred in about one patient in three. Of the four patients with massive hemorrhage one required subtotal colectomy, one right hemicolectomy and the other two were controlled by medical measures including blood transfusion. In each of the surgical cases, the massive bleeding originated in the region of the cecum. An additional patient, not in the series, required proctectomy as a life-saving measure following subtotal colectomy. Clinically obvious rectal bleeding in Crohn's colitis is approximately ten times as frequent as in regional enteritis but only one-third as frequent as in ulcerative colitis. There was no correlation between rectal bleeding and rectal involvement determined radiologically or by signoidoscopy, in the whole series but there was a strong association in the small group of Crohn's colitis with rectal involvement (86% with bleeding) and a significantly greater proportion of patients with colitis with rectal involvement and hemorrhage (P smaller than 0.02). Anemia is common in both groups but in Crohn's colitis it is almost always, 75%, associated with rectal blood loss, whereas in ileocolitis this association is much less marked, 40%, indicating other important causes of anemia when there is small bowel disease. The bleeding patient with Crohn's colitis should be managed medically initially. Uncontrollable, continuous, or massive hemorrhage may require angiography and early surgical intervention.


Reexamination of the role of the leucine/isoleucine zipper residues of phospholamban in inhibition of the Ca2+ pump of cardiac sarcoplasmic reticulum.
Phospholamban is a small phosphoprotein inhibitor of the Ca(2+)-pump in cardiac sarcoplasmic reticulum, which shows a distinct oligomeric distribution between monomers and homopentamers that are stabilized through Leu/Ile zipper interactions. A two-faced model of phospholamban inhibition of the Ca(2+)-pump was proposed, in which the Leu/Ile zipper residues located on one face of the transmembrane alpha-helix regulate the pentamer to monomer equilibrium, whereas residues on the other face of the helix bind to and inhibit the pump. Here we tested this two-faced model of phospholamban action by analyzing the functional effects of a new series of Leu/Ile zipper mutants. Pentameric stabilities of the mutants were quantified at different SDS concentrations. We show that several phospholamban mutants with hydrophobic amino acid substitutions at the Leu/Ile zipper region retain the ability to form pentamers but at the same time give the same or even stronger (i.e. L37I-PLB) inhibition of the Ca(2+)-pump than do mutants that are more completely monomeric. Steric constraints prevent the Leu/Ile zipper residues sequestered in the interior of the phospholamban pentamer from binding to the Ca(2+)-pump, leading to the conclusion that the zipper residues access the pump from the phospholamban monomer, which is the active inhibitory species. A modified model of phospholamban transmembrane domain action is proposed, in which the membrane span of the phospholamban monomer maintains contacts with the Ca(2+)-pump around most of its circumference, including residues located in the Leu/Ile zipper region.


Treatment of hemolytic disease of the newborn caused by anti-Kell antibody with recombinant erythropoietin.
Recent data suggest that antibody-mediated suppression of erythroid progenitors may contribute to the anti-Kell-induced alloimmune hemolytic disease of the newborn (HDN). A 32-week-old girl who was positive for Kell was born to a mother who was negative for Kell but known to have anti-Kell antibodies. After birth, the baby had HDN and hyperbilirubinemia develop (peak bilirubin 21 mg/dL at day 9 of life). which was treated with phototherapy. Although the hyperbilirubinemia resolved, she became progressively anemic (hematocrit 22%) with an inappropriately low reticulocyte response (1.1%) and erythropoietin (EPO) level (20 mU/mL). To avoid the need for a blood transfusion, she was treated with recombinant erythropoietin (rEPO) and oral iron supplements. One week after starting EPO, the reticulocyte count increased to 9.1%. Erythropoietin therapy was continued for a total of 9 weeks, with resolution of her anemia at the end of therapy (hematocrit 35%). Thus, we were able to successfully treat the anemia with rEPO with avoidance of blood transfusion. This patient demonstrates that the antibody-mediated erythroid suppression in Kell alloimmune anemia can be overcome by rEPO. Recombinant erythropoietin should therefore be considered in the management of infants with severe or hypoproliferative anti-Kell-associated anemia.


A diet with 35% of energy from protein leads to kidney damage in female Sprague-Dawley rats.
High-protein (HP) diets for weight loss remain popular despite questions surrounding overall safety. In a recent study using the pig model, we showed that long-term intakes from whole proteins at 35 % energy (en %) cause moderate renal histological damage. To examine whether this observation may be species specific or more generalisable, the effect of this diet in rats was examined. Using plant and animal whole proteins, 70-d-old female Sprague-Dawley rats were randomised to either a normal-protein (NP; 15 en %) or a HP (35 en %) diet for 4, 8, 12 and 17 months. Renal function was assessed by creatinine clearance and urinary protein levels, and pathology was assessed by examination of glomerular hypertrophy, glomerulosclerosis and tubulointerstitial fibrosis. Rats consuming the HP diet had 17 % higher kidney weights (P < 0·0001), three times higher proteinuria (P < 0·0001) and 27 % higher creatinine clearance (P = 0·0012) compared with those consuming the NP diet. Consistent with this, HP-fed rats had larger glomeruli (P < 0·0001) and more glomerulosclerosis (P = 0·0003) compared with NP-fed rats. The HP diet also resulted in altered levels of free monocyte chemoattractant protein-1 (P < 0·0001). The histological changes are consistent with those observed in the pig model. In contrast to the pig model, the elevated proteinuria and creatinine clearance observed in the rat model are also usually observed with HP consumption in human subjects. These results indicate that the rat is a useful model for HP effects on the kidney and, along with previous results using the pig model, suggest that long-term intake of high levels of protein may be detrimental to renal health.


Calcitonin receptor regulation and responsiveness to calcitonin in human osteoclast-like cells prepared in vitro using receptor activator of nuclear factor-kappaB ligand and macrophage colony-stimulating factor.
Using mouse osteoclast-like cells (OCs), we have shown that short exposure to calcitonin (CT) resulted in prolonged reduction of CT binding by inhibiting de novo CT receptor (CTR) synthesis. Additionally, CT-treated OCs demonstrated resistance to CT rechallenge on the inhibitory effect of CT in osteoclastic bone resorption. There is, however, scant information on CT effects on human osteoclasts. In this study, we examined the features of CTR down-regulation and its recovery after short exposure to CT of human OCs. OCs were prepared by treatment of peripheral blood mononuclear cells in vitro with osteoclast differentiation factor and macrophage colony-stimulating factor. Treatment of OCs with salmon CT (sCT) and human CT (hCT) resulted in a dose-dependent reduction in [125I]sCT binding capacity. Continued receptor occupancy by ligand was excluded by using a glycine-acid washing procedure. Treatment with sCT reduced CTR messenger RNA expression, suggesting that CTR down-regulation is, at least partly, attributable to an inhibition of de novo CTR synthesis. To investigate the intracellular signal transduction pathways that mediate these effects, we examined the effects of activation of the protein kinase (PK)A, PKC, and Ca2+-calmodulin-dependent kinases. Treatment with PKC activators mimicked CT, whereas neither activation of PKA nor elevation of intracellular Ca2+ did so. We further investigated the intracellular signaling pathways responsible for the inhibitory effects of CT on bone resorption, which showed that treatment with PKC activators reproduced the effects of CT. These data suggest that the PKC pathway plays an important role in homologous CTR down-regulation, as well as inhibition of bone-resorbing activity by CT, in human OCs. Short exposure of OCs to CT (10(-9) M, 1 h) reduced [125I]sCT-specific binding for a prolonged period, as we have shown previously in mouse OCs. The reduced specific binding, CTR messenger RNA levels, and CT-sensitive adenylate cyclase responsiveness returned to the control levels by 96 h after removal of CT. These results strongly support the notion that escape from CT inhibition of osteoclastic bone resorption in humans is attributable to the development of resistance by OCs to CT. This study also showed that even short exposure to CT induced prolonged desensitization to CT rechallenge, although the OCs eventually regained responsiveness to sCT rechallenge.


Humoral and cellular immunity against diverse SARS-CoV-2 variants.
Since the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has rapidly spread worldwide. This has led to an unprecedented global pandemic, marked by millions of COVID-19 cases and a significant number of fatalities. Over a relatively short period, several different vaccine platforms were developed and deployed for use globally to curb the pandemic. However, the genome of SARS-CoV-2 continuously undergoes mutation andor recombination, resulting in the emergence of several variants of concern (VOC). These VOCs can elevate viral transmission and evade the neutralizing antibodies induced by vaccines, leading to reinfections. Understanding the impact of the SARS-CoV-2 genomic mutation on viral pathogenesis and immune escape is crucial for assessing the threat of new variants to public health. This review focuses on the emergence and pathogenesis of VOC, with particular emphasis on their evasion of neutralizing antibodies. Furthermore, the memory B cell, CD4+, and CD8+ T cell memory induced by different COVID-19 vaccines or infections is discussed, along with how these cells recognize VOC. This review summarizes the current knowledge on adaptive immunology regarding SARS-CoV-2 infection and vaccines. Such knowledge may also be applied to vaccine design for other pathogens.


The multidimensional health locus of control scales: testing the factorial structure in sample of African American medical patients.
A fifth subscale was recently added to the widely used multidimensional health locus of control (MHLC) measure, and little is known about the factor structure of the MHLC with the new scale among African Americans from disadvantaged backgrounds. Also, few studies have examined differences in Health Locus of Control (HLOC) beliefs across medical patients from similar demographic backgrounds. We asked participants to complete a survey about HLOC beliefs and extracted biological markers from their medical charts. Participants were drawn from patients of internal medicine and infectious disease clinics at a charity hospital in Baton Rouge, Louisiana. In total, we surveyed 186 African American patients who were diagnosed with HIV/AIDS or type 2 diabetes. Confirmatory factor analysis could not confirm a 5-factor structure; however, a new 3-factor structure was produced that includes 1) internal health beliefs, 2) external health beliefs, and 3) God health beliefs. Patients with HIV/AIDS reported more external and God HLOC beliefs than did patients with type 2 diabetes. The factor structures that emerged from previous research may not be appropriate to use when conducting research with individuals from a low SES who are also from an ethnic/racial minority background. Our findings suggest a new 3-factor structure for the MHLC. Future research should examine whether patients with HIV/AIDS may benefit from interventions that target external beliefs to improve health behavior.


Sexual dimorphism in the dioecious willow Salix purpurea.
The evolution of sex chromosomes is driven by sexual dimorphism, yet it can be challenging to document sexually dimorphic traits in dioecious plant species. At the genetic level, sexual dimorphism can be identified through sequence variation between females and males associated with sexually antagonistic traits and different fitness optima. This study aims to examine sexual dimorphism for 26 traits in three populations of Salix purpurea (a diversity panel and F1 and F2 populations) and determine the effect of the traits on biomass yield, a key trait in Salix bioenergy crops across multiple years, locations, and under manipulated growth conditions. Sexual dimorphism was evaluated for morphological, phenological, physiological, and wood composition traits in a diversity panel of unrelated S. purpurea accessions and in full-sib F1 and F2 families produced through controlled cross pollinations and grown in replicated field trials. We observed sexual dimorphism in the timing of development for several traits that were highly predictive of biomass yield across three populations of S. purpurea. Across all populations and years surveyed, males had significantly shallower branching angle. Male plants highly predictive of biomass yield across three populations of S. purpurea also accumulated more nitrogen under fertilizer amendment as measured by SPAD in the diversity panel and had greater susceptibility to the rust fungus Melampsora americana in the F2 family. Allometric modelling of biomass yield showed an effect of sex and of location on the interaction between yield and stem height. These results provide evidence of sexual dimorphism for certain traits in S. purpurea that may be involved in sex chromosome evolution.


The dietary intake of Laminaria, a brown seaweed, and breast cancer prevention.
Based on epidemiological and biological data, Laminaria, a brown kelp seaweed, is proposed as an important factor contributing to the relatively low breast cancer rates reported in Japan. Several possible mechanisms for the influence of Laminaria on breast cancer are proposed: Laminaria is a source of nondigestible fiber, thereby increasing fecal bulk and decreasing bowel transit time; it changes the posthepatic metabolism of sterols; it contains an antibiotic substance that may influence fecal ecology; it contains 1-3 beta glucan, which alters enzymatic activity of fecal flora; and it stimulates the host-mediated immune response. It is suggested that Laminaria may play a role in preventing either the initiation of breast cancer or its promotion by endogenous physiological factors.


The effect of antibacterial photodynamic therapy with diode laser on chromogenic bacteria associated with dental black staining: An in-vitro study.
Aggregatibacter actinomycetemcomitan (A.a) and Actinomyces naeslundii (A.n) are two gram-negative chromogenic bacteria involved in the formation of dental black stainings. Our study aimed to investigate the antibacterial effect of photodynamic therapy (aPDT) using two photosensitizers, Methylene Blue (MB) and Indocyanine Green (ICG). In this in-vitro study, two isolates of each selected bacterium were cultured and treated as follows; Negative control with no treatment; CHX as a positive control; ICG; MB; ICG with 808 nm laser activation; and MB with 660 nm laser activation. The number of colonies (CFU/mL) was determined to compare the groups. The qualitative evaluation of biofilm formation was done by scanning electron microscopy of treated enamel pieces. The logarithmic values of the colony counts were compared using One-way ANOVA and the Welch test Tukey HSD and Games-Howell tests were used for multiple comparisons. P-values of less than 0.05 were considered statistically significant. The use of ICG alone or along with laser irradiation at the wavelength of 808 nm significantly reduced the number of colonies of A.a and A.n bacteria. Comparing the colony counts in the MB group with the positive control showed no significant decrease in bacterial load. On the contrary, activation of MB with 660 nm radiation of diode laser showed a significant antibacterial effect. The density of bacterial biofilm was significantly lower in the groups treated with MB and ICG without laser activation than in the control group; however, the reduction in bacteria biofilm density was more robust using photodynamic therapy with ICG. aPDT using MB with 660 nm laser and ICG with 808 nm laser significantly reduced the number of chromogenic A.a and A.n bacteria, and photodynamic therapy with ICG was proven to be significantly more effective than MB with or without laser radiation.


[Geometry of the complexes between horseradish peroxidase and aromatic substrates].
Geometry of the complexes between horse radish peroxidase and aromatic substrates was studied by means of new technique of precision measurement of NMR shifts. Weak dipolar shifts of hydroquinone and parametoxiphenole PMR in the presence of high spin peroxidase were recorded. Polar and azimuth angles in coordinate axes of peroxidase hem for the binding site on the enzyme of the aromatic part of the substrate molecule were estimated for the first time.


The Oral Bacterium Fusobacterium nucleatum Binds Staphylococcus aureus and Alters Expression of the Staphylococcal Accessory Regulator sarA.
Staphylococcus aureus, an opportunistic pathogen member of the nasal and skin microbiota, can also be found in human oral samples and has been linked to infectious diseases of the oral cavity. As the nasal and oral cavities are anatomically connected, it is currently unclear whether S. aureus can colonize the oral cavity and become part of the oral microbiota, or if its presence in the oral cavity is simply transient. To start addressing this question, we assessed S. aureus ability to directly bind selected members of the oral microbiota as well as its ability to integrate into a human-derived complex oral microbial community in vitro. Our data show that S. aureus forms aggregates with Fusobacterium nucleatum and Porphyromonas gingivalis and that it can incorporate into the human-derived in vitro oral community. Further analysis of the F. nucleatum-S. aureus interaction revealed that the outer-membrane adhesin RadD is partially involved in aggregate formation and that the RadD-mediated interaction leads to an increase in expression of the staphylococcal global regulator gene sarA. Our findings lend support to the notion that S. aureus can become part of the complex microbiota of the human mouth, which could serve as a reservoir for S. aureus. Furthermore, direct interaction with key members of the oral microbiota could affect S. aureus pathogenicity contributing to the development of several S. aureus associated oral infections.


Isolation, oxygen sensitivity, and virulence of NADH oxidase mutants of the anaerobic spirochete Brachyspira (Serpulina) hyodysenteriae, etiologic agent of swine dysentery.
Brachyspira (Serpulina) hyodysenteriae, the etiologic agent of swine dysentery, uses the enzyme NADH oxidase to consume oxygen. To investigate possible roles for NADH oxidase in the growth and virulence of this anaerobic spirochete, mutant strains deficient in oxidase activity were isolated and characterized. The cloned NADH oxidase gene (nox; GenBank accession no. U19610) on plasmid pER218 was inactivated by replacing 321 bp of coding sequence with either a gene for chloramphenicol resistance (cat) or a gene for kanamycin resistance (kan). The resulting plasmids, respectively, pCmDeltaNOX and pKmDeltaNOX, were used to transform wild-type B. hyodysenteriae B204 cells and generate the antibiotic-resistant strains Nox-Cm and Nox-Km. PCR and Southern hybridization analyses indicated that the chromosomal wild-type nox genes in these strains had been replaced, through allelic exchange, by the inactivated nox gene containing cat or kan. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western immunoblot analysis revealed that both nox mutant cell lysates were missing the 48-kDa Nox protein. Soluble NADH oxidase activity levels in cell lysates of Nox-Cm and Nox-Km were reduced 92 to 96% compared to the activity level in parent strain B204. In an aerotolerance test, cells of both nox mutants were at least 100-fold more sensitive to oxygen exposure than were cells of the wild-type parent strain B204. In swine experimental infections, both nox mutants were less virulent than strain B204 in that fewer animals were colonized by the mutant cells and infected animals displayed mild, transient signs of disease, with no deaths. These results provide evidence that NADH oxidase serves to protect B. hyodysenteriae cells against oxygen toxicity and that the enzyme, in that role, contributes to the pathogenic ability of the spirochete.


Determination of phenylephrine hydrochloride by flow injection analysis with chemiluminescence detection.
A new method is proposed for the determination of phenylephrine hydrochloride by flow injection analysis with direct chemiluminescence detection. The method is based on the oxidation of the drug by potassium permanganate in sulfuric acid medium at 80 degrees C. The calibration graph is linear over the range 0.03-8 ppm phenylephrine hydrochloride, with a relative standard deviation (n = 51, 0.5 ppm) of 1.1% and sample throughput of 134/h. The influence of 38 different foreign compounds was tested, and the method was applied to the determination of phenylephrine hydrochloride in 8 different pharmaceutical formulations.


Wellness management through Web-based programmes.
We established a Web-based programme called the 'Wellness Online Program' or WOLP. The programme runs for six weeks. It aims to help individuals manage their own wellness regardless of geographical location. WOLP is based on a holistic approach to health and consists of six wellness dimensions: physical (exercise and diet), emotional, social, intellectual, spiritual and occupational. A total of 150 volunteers from the general public were recruited online for this study and data were collected at three intervals: at the beginning of the programme (week 1), mid-programme (week 3) and at the end of the programme (week 6). Ninety of the participants (60%) completed the six-week programme. Acceptance of WOLP, measured by the frequency of individual usage, increased from the start to the end of the programme. Overall personal wellness management improved after six weeks on the wellness programme (5-10%). The study shows that personal wellness management, which had been demonstrated in the narrower confines of the corporate sector, is also possible in the public domain.


Probabilistic Tractography to Predict the Position of Cranial Nerves Displaced by Skull Base Tumors: Value for Surgical Strategy Through a Case Series of 62 Patients.
Predicting the displacement of cranial nerves by tumors could make surgery safer and the outcome better. Recent advances in imaging and processing have overcome some of the limits associated with cranial nerve tractography, such as spatial resolution and fiber crossing. Among others, probabilistic algorithms yield to a more accurate depiction of cranial nerve trajectories. To report how cranial nerve probabilistic tractography can help the surgical strategy in a series of various skull base tumors. After distortion correction and region of interest seeding, a probabilistic tractography algorithm used the constrained spherical deconvolution model and attempted the reconstruction of cranial nerve trajectories in both healthy and displaced conditions. Sixty-two patients were included and presented: vestibular schwannomas (n = 33); cerebellopontine angle meningiomas (n = 15); arachnoid or epidermoid cysts (n = 6); cavernous sinus and lower nerves schwannomas (n = 4); and other tumors (n = 4). For each patient, at least one 'displaced' cranial nerve was not clearly identified on classical anatomical MRI images. All 372 cranial nerves were successfully tracked on each healthy side; among the 175 cranial nerves considered 'displaced' by tumors, 152 (87%) were successfully tracked. Among the 127 displaced nerves of operated patients (n = 51), their position was confirmed intraoperatively for 118 (93%) of them. Conditions that led to tractography failure were detailed. On the basis of tractography, the surgical strategy was adjusted for 44 patients (71%). This study reports a cranial nerve probabilistic tractography pipeline that can: predict the position of most cranial nerves displaced by skull base tumors, help the surgical strategy, and thus be a pertinent tool for future routine clinical application.


Alkaline Sodium Hypochlorite Irrigant and Its Chemical Interactions.
Endodontic irrigating solutions may interact chemically with one another. This is important, because even when solutions are not admixed, they will come into contact with one another during an alternating irrigation technique, forming unwanted by-products, which may be toxic or irritant. Mixing or alternating irrigants can also reduce their ability to clean and disinfect the root canal system of teeth by changing their chemical structure with subsequent loss of the active agent, or by inducing precipitate formation in the root canal system. Precipitates occlude dental tubules, resulting in less penetration of antimicrobials and a loss of disinfection efficacy. Sodium hypochlorite is not only a very reactive oxidizing agent, but is also the most commonly used endodontic irrigant. As such, many interactions occurring between it and other irrigants, chelators and other antimicrobials, may occur. Of particular interest is the interaction between sodium hypochlorite and the chelators EDTA, citric acid and etidronate and between sodium hypochlorite and the antimicrobials chlorhexidine, alexidine, MTAD and octenisept.


The use of water-jet dissection in open and laparoscopic liver resection.
We intend to give an overview of our experiences with the implementation of a new dissection technique in open and laparoscopic surgery. Our database comprises a total of 950 patients who underwent liver resection. Three hundred and fifty of them were performed exceptionally with the water-jet dissector. Forty-one laparoscopic partial liver resections were accomplished. Using the water-jet dissection technique it was possible to reduce the blood loss, the Pringle- and resection time in comparison to CUSA and blunt dissection. In the last five years we could reduce the Pringle-rate from 48 to 6% and the last 110 liver resections were performed without any Pringle's manoeuvre. At the same time, the transfusion-rate decreased from 1.86 to 0.46 EC/patient. In oncological resections, the used dissection technique had no influence on long-time survival. The water-jet dissection technique is fast, feasible, oncologically safe and can be used in open and in laparoscopic liver surgery.


Cardiovascular Disease Risk Profile and Readiness to Change in Blue- and White-Collar Workers.
This study provides a health and risk profile of blue- (BCWs) and white-collar workers (WCWs). Health screening data (n = 603; age 38.2 ± 9.7 years) included cholesterol and glucose finger-prick test, blood pressure, body mass index, and self-reported stress levels and readiness to change. Blue-collar workers were significantly older and had higher blood pressure readings and were more likely to develop hypertension (odds ratio [OR]: 1.72; 95% confidence interval [CI]: 1.05-2.81; P = .03), but less likely to present with hypercholesterolemia (OR: 0.50; 95% CI: 0.31-0.81; P = .01) and overweight/obesity (OR: 0.65; 95% CI: 0.42-0.99; P = .047). White-collar workers showed significantly higher cholesterol and stress levels. This study highlights the importance of occupation type in workplace health screening and intervention planning.


Adenocarcinoma arising within a tailgut cyst: clinicopathological description and follow up of an unusual case.
Full clinicopathological details and clinical follow up of a case of malignant transformation within a tailgut cyst are presented. A 43 year old woman presented with signs and symptoms of an imminent threatened abortion. Routine examination identified a coincidental, asymptomatic retrorectal/presacral mass. Following imaging studies, surgical resection was carried out and an adenocarcinoma arising within a pre-existent tailgut cyst was identified by microscopy. Four years later the patient presented with neurological symptoms consistent with local recurrence of the tumour. Surgical biopsies confirmed this diagnosis and she was subsequently started on chemotherapy. She died soon after from a cause unrelated to the disease, after declining further active intervention. Differential diagnosis of such cases includes (cystic) teratoma, epidermal cyst, rectal duplication cyst, anal gland cyst and carcinoma, extension of local carcinoma, and metastatic disease. It is recommended that these lesions be completely excised when detected incidentally.


Inter- relationship between rheumatoid arthritis and periodontitis.
Periodontal medicine defines a rapidly emerging branch of Periodontology focusing on establishing a strong relationship between periodontal health and systemic health. It is speculated that the major common dysregulation which links Periodontitis with Rheumatoid arthritis (RA) is being played by the mediators of immune inflammatory response. To determine whether there is any relationship between periodontal disease and Rheumatoid arthritis. A total of 100 patients were included for the present study which was divided into two groups: one group (cases) included 50 patients attending the Department of Orthopedics, Kasturba Medical College, Manipal who were diagnosed of Rheumatoid arthritis. Another subject population included 50 patients as controls attending the Department of Oral Medicine, Manipal College of Dental Sciences, Manipal with age and gender matched with those of rheumatoid arthritis group. Specific measures for periodontitis included plaque index, gingival index, number of missing teeth, and radiographic alveolar bone loss scores. Measures of rheumatoid arthritis included health assessment questionaires, levels of C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Various periodontal parameters were compared between the cases and controls. The average alveolar bone loss was statistically more severe in Rheumatoid arthritis (RA) group than in the controls although there were similar plaque index in both the groups. The gingival index was statistically higher in the RA group. The Erythrocyte Sedimentation Rate (ESR) and C- Reactive Protein (CRP) levels of RA patients were also significantly associated with the severity of periodontal disease. There was a significant association between Rheumatoid arthritis and Periodontitis which may be due to a common underlying deregulation of the inflammatory response in these individuals.


Intracellular calcium changes associated with in vitro lymphokine-activated killer and natural killer cell cytotoxicity.
Interleukin 2-activated peripheral blood lymphocytes (lymphokine-activated killer [LAK] cells) have been shown to lyse tumor cells in a nonspecific fashion. Although the mechanisms involved in this cell-mediated lysis are unknown, previous work has shown that T-lymphocyte-mediated cytolysis is associated with massive fluctuations in the intracellular calcium concentration within target cells. Studies were undertaken to determine whether intracellular calcium concentration changes were associated with LAK-mediated cytotoxicity and to determine the effects of calcium channel blockade on in vitro cell-mediated cytotoxicity. Natural killer (NK) and LAK cell cytotoxicity in vitro were measured against head and neck squamous cell carcinoma (UMSCC-11a and UMSCC-38) and Daudi cell lines. Assays were performed in parallel with flow cytometry to measure changes in intracellular calcium concentration within the target cells. Compared with NK cells, LAK cells showed enhanced cytotoxicity against the UMSCC-11a and Daudi lines but not the UMSCC-38 cell line. Both NK and LAK cell cytotoxicity against all the target cell lines directly paralleled significant increases in calcium concentration in the target cells. The addition of verapamil hydrochloride inhibited the rise in intracellular calcium concentration in the sensitive target cells and significantly inhibited both NK and LAK cell cytotoxicity in all the cell lines. The NK cell activity was more sensitive than LAK cell activity to verapamil inhibition. These data suggest that changes in the target cell calcium concentration are early and important events in both NK and LAK cell cytotoxicity in vitro.


[Comparison between 2 elution methods for biological testing of materials].
The possibility of separating the eluate and the actual biologic test for determining tissue tolerance was studied using two cements containing copper and two cements without copper. Both the materials and the two eluates obtained according to the different procedures were tested immediately. Distilled water was added to one sample of the material, and the mixture was placed in an autoclave for one hour. A second sample was leached in nutrient solution for 24 hours at 37 C. Uniform results were obtained with the copper-free material. Results with the material containing copper however varied; the results of the eluate obtained after one hour in the autoclave were different from the results obtained after 24 hours in the nutrient solution or after direct testing. The test results for the last two procedures were similar. Comparison of the two elution methods indicates that extraction in physiologic nutrient solution is better than the autoclave method using distilled water.


Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer.
A large body of evidence suggests that cyclooxygenase-2 (COX-2) is important in gastrointestinal cancer. The purpose of this study was to determine whether COX-2 was expressed in adenocarcinoma of the human pancreas. Quantitative reverse transcription-PCR, immunoblotting, and immunohistochemistry were used to assess the expression of COX-2 in pancreatic tissue. Levels of COX-2 mRNA were increased by >60-fold in pancreatic cancer compared to adjacent nontumorous tissue. COX-2 protein was present in 9 of 10 cases of adenocarcinoma of the pancreas but was undetectable in nontumorous pancreatic tissue. Immunohistochemical analysis showed that COX-2 was expressed in malignant epithelial cells. In cultured human pancreatic cancer cells, levels of COX-2 mRNA and protein were induced by treatment with tumor-promoting phorbol esters. Taken together, these results suggest that COX-2 may be a target for the prevention or treatment of pancreatic cancer.


Distorted probability operator for dynamic portfolio optimization in times of socio-economic crisis.
A robust optimal control of discrete time Markov chains with finite terminal T and bounded costs or wealth using probability distortion is studied. The time inconsistency of these distortion operators and hence its lack of dynamic programming are discussed. Due to that, dynamic versions of these operators are introduced, and its availability for dynamic programming is demonstrated. Based on dynamic programming algorithm, existence of the optimal policy is justified and an application of the theory to portfolio optimization along with a numerical study is also presented.


Recurrent genomic alterations in sequential progressive leukoplakia and oral cancer: drivers of oral tumorigenesis?
A significant proportion (up to 62%) of oral squamous cell carcinomas (OSCCs) may arise from oral potential malignant lesions (OPMLs), such as leukoplakia. Patient outcomes may thus be improved through detection of lesions at a risk for malignant transformation, by identifying and categorizing genetic changes in sequential, progressive OPMLs. We conducted array comparative genomic hybridization analysis of 25 sequential, progressive OPMLs and same-site OSCCs from five patients. Recurrent DNA copy number gains were identified on 1p in 20/25 cases (80%) with minimal, high-level amplification regions on 1p35 and 1p36. Other regions of gains were frequently observed: 11q13.4 (68%), 9q34.13 (64%), 21q22.3 (60%), 6p21 and 6q25 (56%) and 10q24, 19q13.2, 22q12, 5q31.2, 7p13, 10q24 and 14q22 (48%). DNA losses were observed in >20% of samples and mainly detected on 5q31.2 (35%), 16p13.2 (30%), 9q33.1 and 9q33.29 (25%) and 17q11.2, 3p26.2, 18q21.1, 4q34.1 and 8p23.2 (20%). Such copy number alterations (CNAs) were mapped in all grades of dysplasia that progressed, and their corresponding OSCCs, in 70% of patients, indicating that these CNAs may be associated with disease progression. Amplified genes mapping within recurrent CNAs (KHDRBS1, PARP1, RAB1A, HBEGF, PAIP2, BTBD7) were selected for validation, by quantitative real-time PCR, in an independent set of 32 progressive leukoplakia, 32 OSSCs and 21 non-progressive leukoplakia samples. Amplification of BTBD7, KHDRBS1, PARP1 and RAB1A was exclusively detected in progressive leukoplakia and corresponding OSCC. BTBD7, KHDRBS1, PARP1 and RAB1A may be associated with OSCC progression. Protein-protein interaction networks were created to identify possible pathways associated with OSCC progression.


Salutary effect of aurintricarboxylic acid on endotoxin- and sepsis-induced changes in muscle protein synthesis and inflammation.
Small molecule nonpeptidyl molecules are potentially attractive drug candidates as adjunct therapies in the treatment of sepsis-induced metabolic complications. As such, the current study investigates the use of aurintricarboxylic acid (ATA), which stimulates insulinlike growth factor 1 receptor and AKT signaling, for its ability to ameliorate the protein metabolic effects of endotoxin (lipopolysaccharide [LPS]) + interferon γ (IFN-γ) in C2C12 myotubes and sepsis in skeletal muscle. Aurintricarboxylic acid dose- and time-dependently increases mTOR (mammalian or mechanistic target of rapamycin)-dependent protein synthesis. Pretreatment with ATA prevents the LPS/IFN-γ-induced decrease in protein synthesis at least in part by maintaining mTOR kinase activity, whereas posttreatment with ATA is able to increase protein synthesis when added up to 6 h after LPS/IFN-γ. Aurintricarboxylic acid also reverses the amino acid resistance, which is detected in response to nutrient deprivation. Conversely, ATA decreases the basal rate of protein degradation and prevents the LPS/IFN-γ increase in proteolysis, and the latter change is associated reduced atrogin 1 and MuRF1 mRNA. The ability of ATA to antagonize LPS/IFN-γ-induced changes in protein metabolism was associated with its ability to prevent the increases in interleukin 6 and nitric oxide synthase 2 and decreases in insulinlike growth factor 1. In vivo studies indicate ATA acutely increases skeletal muscle, but not cardiac, protein synthesis and attenuates the loss of lean body mass over 5 days. These data suggest ATA and other small molecule agonists of endogenous anabolic hormones may prove beneficial in treating sepsis by decreasing the inflammatory response and improving muscle protein balance.


Public interest in medical assistance in dying and palliative care.
Medical assistance in dying (MAiD) is legal in an increasing number of countries, but there are concerns that its availability may compromise access to palliative care. We assessed public interest in MAiD, palliative care, both, or neither, and examined characteristics associated with this interest. We surveyed a representative sample of the adult Canadian public, accessed through a panel from May to June 2019. Weighted generalised multinomial logistic regression analyses were used to determine characteristics associated with interest in referral to palliative care, MAiD, or both, in the event of diagnosis with a serious illness. Of 1362 participants who had heard of palliative care, 611 (44.8% weighted (95% CI 42.1% to 47.5%)) would be interested in both MAiD and palliative care, 322 (23.9% (95% CI 21.5% to 26.2%)) palliative care alone, 171 (12.3% (95% CI 10.5% to 14.1%)) MAiD alone and 258 (19.0% (95% CI 16.9% to 21.2%)) neither. In weighted multinomial logistic regression analyses, interest in both MAiD and palliative care (compared with neither) was associated with better knowledge of the definition of palliative care, older age, female gender, higher education and less religiosity; interest in palliative care alone was associated with better knowledge of the definition of palliative care, older age, female gender and being married/common law; interest in MAiD alone was associated with less religiosity (all p<0.05). There is substantial public interest in potential referral to both MAiD and palliative care. Simultaneous availability of palliative care should be ensured in jurisdictions where MAiD is legal, and education about palliative care should be a public health priority.


Surgical management of medically refractory epilepsy due to early childhood stroke.
OBJECT.: The risk of developing epilepsy after perinatal stroke, hypoxic/ischemic injury, and intracerebral hemorrhage is significant, and seizures may become medically refractory in approximately 25% of these patients. Surgical management can be difficult due to multilobar or bilateral cortical injury, nonfocal or poorly lateralizing video electroencephalography (EEG) findings, and limited functional reserve. In this study the authors describe the surgical approaches, seizure outcomes, and complications in patients with epilepsy due to vascular etiologies in the perinatal period and early infancy. The records were analyzed of 19 consecutive children and adults with medically refractory epilepsy and evidence of perinatal arterial branch occlusions, hypoxic/ischemic insult, or hemorrhagic strokes, who underwent surgery at the Comprehensive Epilepsy Center of Beth Israel Medical Center and St. Luke's-Roosevelt Hospital Center. Preoperative findings including MRI, video EEG, functional MRI, and neuropsychological testing were analyzed. The majority of patients underwent staged operations with invasive mapping, and all patients had either extra- or intraoperative functional mapping. In 7 patients with large porencephalic cysts due to major arterial branch occlusions, periinsular functional hemispherotomy was performed in 4 children, and in 3 patients, multilobar resections/disconnections were performed, with 1 patient undergoing additional resections 3 years after initial surgery due to recurrence of seizures. All of these patients have been seizure free (Engel Class IA) after a mean 4.5-year follow-up (range 15-77 months). Another 8 patients had intervascular border-zone ischemic infarcts and encephalomalacia, and in this cohort 2 hemispherotomies, 5 multilobar resections/disconnections, and 1 focal cortical resection were performed. Seven of these patients remain seizure free (Engel Class IA) after a mean 4.5-year follow-up (range 9-94 months), and 1 patient suffered a single seizure after 2.5 years of seizure freedom (Engel Class IB, 33-month follow-up). In the final 4 patients with vascular malformation-associated hemorrhagic or ischemic infarction in the perinatal period, a hemispherotomy was performed in 1 case, multilobar resections in 2 cases, and in 1 patient a partial temporal lobectomy was performed, followed 6 months later by a complete temporal and occipital lobectomy due to ongoing seizures. All of these patients have had seizure freedom (Engel Class IA) with a mean follow-up of 4.5 years (range 10-80 months). Complications included transient monoparesis or hemiparesis in 3 patients, transient mutism in 1 patient, infection in 1 patient, and a single case of permanent distal lower-extremity weakness. Transient mood disorders (depression and anxiety) were observed in 2 patients and required medical/therapeutic intervention. Epilepsy surgery is effective in controlling medically intractable seizures after perinatal vascular insults. Seizure foci tend to be widespread and rarely limited to the area of injury identified through neuroimaging, with invasive monitoring directing multilobar resections in many cases. Long-term functional outcomes have been good in these patients, with significant improvements in independence, quality of life, cognitive development, and motor skills, despite transient postoperative monoparesis or hemiparesis and occasional mood disorders.


Diabetes in the Bio-Breeding/Worcester rat. Induction and acceleration by spleen cell-conditioned media.
Injections of media conditioned by concanavalin A-activated spleen cells from acutely diabetic rats accelerated the appearance of diabetes in young Bio-Breeding/Worcester (BB/W) rats. Activity was also found in media conditioned by spleen cells from nondiabetic, W-line Wistar Furth and Buffalo rats. Unconditioned media containing mitogen had no activity. Conditioned media also induced diabetes in resistant W-line BB/W rats but not in Wistar Furth rats. A soluble factor may activate a BB lymphocyte population that promotes diabetes.


Fetal hemopoiesis in diffusion chamber cultures. I. The pattern of pluripotent stem cell growth.
The growth pattern of fetal liver (FL), normal adult bone marrow (NABM) and regenerating (post Velban treatment) adult bone marrow (RABM) colony forming units (CFU) cultured in diffusion chambers (DC) was studied. When twenty CFU were implanted into DC the recovery of CFU after 4 days with FL, NABM or RABM was 133 +/- 7, 19 +/- 2 and 34 +/- 2 CFU, respectively. The transplantation fraction of CFU from NABM decreased from 10-4% on day 0 to 6-9% on day 4; that of FL did not change from the initial 6-2%. The growth rate of CFU derived from FL was substantially greater than that from NABM. The relative growth of FL and RABM CFU was clearly inhibited when the concentration of cells cultured was increased. Spleen colonies from FL cells before culture were larger (P less than 0-005) than colonies from NABM but after 7 days of culture there was no difference between the two groups. Histological examination of spleen colonies showed that after DC culture FL and NABM CFU were differentiating along the three normal pathways. These data suggest that intrinsic differences exist between fetal and adult stem cells in the in vivo diffusion chamber culture system.


Historical influences dominate the population genetic structure of a sedentary marine fish, Atlantic wolffish (Anarhichas lupus), across the North Atlantic Ocean.
Genetic variation was assessed in Atlantic wolffish, Anarhichas lupus, across the North Atlantic Ocean using microsatellite and amplified fragment length polymorphism (AFLP) markers. Despite unusual life history attributes such as large benthic eggs, large larvae, a limited pelagic stage and relatively sedentary adults, which suggest potential for strong population structure, range-wide FST values were comparable to other marine fishes (≤0.035). Nevertheless, both significant genetic differentiation among regions and isolation by distance were observed, suggesting limited dispersal in this species. AFLP loci, evaluated on a subset of samples, revealed slightly higher FST values, but similar patterns of differentiation and isolation-by-distance estimates, compared to microsatellites. The genetic structure of Atlantic wolffish has likely been shaped by its post-glacial history of recolonization, North Atlantic current patterns and continuity of habitat on continental shelves.


The impact of Severe Maternal Morbidity on probability of subsequent birth in a population-based study of women in California from 1997-2017.
Complications during pregnancy and birth can impact whether an individual has more children. Individuals experiencing SMM are at a higher risk of general and reproductive health issues after pregnancy, which could reduce the probability of a subsequent birth. To examine whether experiencing SMM during an individual's first birth affects their probability of having an additional birth, and whether this effect varies by maternal factors. This retrospective cohort study US linked vital records and maternal discharges from 1997 to 2017 to identify all California births. The exposure, Severe Maternal Morbidity (SMM) was identified using a Centers for Disease Control and Prevention index. Individuals whose first birth was a singleton live birth were followed until their second birth or December 31, 2017, whichever came first. Hazard ratios for having a subsequent birth were estimated using Cox proportional hazard regression models. This association was assessed overall and stratified by maternal factors of a priori interest: age, race/ethnicity, and payer. Of the 3,916,413 individuals in our study, 51,872 (1.3%) experienced SMM at first birth. Compared to those who do not experience SMM, individuals who had SMM had a lower hazard, or instantaneous rate, of subsequent birth (adjusted HR 0.83, 95% CI: 0.82, 0.84); this association was observed in all levels of stratification (for example, adjusted HR range for known race/ethnicity: 0.78, 95% CI: 0.76, 0.80 for non-Hispanic White to 0.90, 95% CI: 0.88, 0.92 for Hispanic) and all indicators of SMM (0.24, 95% CI: 0.17, 0.35 for cardiac arrest/ventricular fibrillation to 0.84, 95% CI: 0.80, 0.87 for eclampsia). Our findings suggest that individuals who experience SMM at the time of their first birth are less likely to have a subsequent birth as compared to those who do not experience SMM at the time of their first birth. While the reasons for these findings are unclear, they could inform reproductive life planning discussions for individuals experiencing SMM. Future directions include studies exploring the reasons for not having a subsequent birth.


Fatal house fires in an urban population.
House fires kill about 5,000 Americans annually, at a rate (2/100,000) that has remained almost constant for the past 50 years. House-fire deaths were studied in Baltimore, where 55 residents died during a three-year period. More than half of the deaths resulted from cigarette-ignited fires; 39% of the people who died in such fires were not the cigarette smokers themselves. For both blacks and whites, the death rate was highest in census tracts where property rental values were low. The death rate from fires ignited by heating or electrical equipment was nine times as high in the lowest-value census tracts as in the highest.


Role of non-invasive objective markers for the rehabilitative diagnosis of central sensitization in patients with fibromyalgia: A systematic review.
Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed to relate to central sensitization in humans, that is, Human Assumed Central Sensitization (HACS). The aims of this systematic review were to identify non-invasive objective markers of HACS and the instruments to assess these markers in patients with fibromyalgia (FM). A systematic review was conducted with the following inclusion criteria: (1) adults, (2) diagnosed with FM, and (3) markers and instruments for HACS had to be non-invasive. Data were subsequently extracted, and studies were assessed for risk of bias using the quality assessment tools developed by the National Institute of Health. 78 studies (n= 5234 participants) were included and the findings were categorized in markers identified to assess peripheral and central manifestations of HACS. The identified markers for peripheral manifestations of HACS, with at least moderate evidence, were pain after-sensation decline rates, mechanical pain thresholds, pressure pain threshold, sound 'pressure' pain threshold, cutaneous silent period, slowly repeated evoked pain sensitization and nociceptive flexion reflex threshold. The identified markers for central manifestations of HACS were efficacy of conditioned pain modulation with pressure pain conditioning and brain perfusion analysis. Instruments to assess these markers are: pin-prick stimulators, cuff-algometry, repetitive pressure stimulation using a pressure algometer, sound, electrodes and neuroimaging techniques. This review provides an overview of non-invasive markers and instruments for the assessment of HACS in patients with FM. Implementing these findings into clinical settings may help to identify HACS in patients with FM.


Contribution of NMDA and AMPA receptors to temporal patterning of auditory responses in the inferior colliculus.
Although NMDA receptors (NMDARs) are associated with synaptic plasticity, they form an essential part of responses to sensory stimuli. We compared contributions of glutamatergic NMDARs and AMPA receptors (AMPARs) to auditory responses in the inferior colliculus (IC) of awake, adult mustached bats. We examined the magnitude and temporal pattern of responses to tonal signals in single units before, during, and after local micro-iontophoretic application of selective antagonists to AMPARs [NBQX (1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide)] and NMDARs [CPP ((+/-)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid)]. Combined blockade of AMPARs and NMDARs eliminated excitatory responses in nearly all neurons, whereas separate blockade of each receptor was quantitatively similar, causing substantial (> 50%) spike reductions in approximately 75% of units. The major result was that effects of receptor blockade were most closely related to the first-spike latency of a unit. Thus, AMPAR blockade substantially reduced spikes in all short-latency units (< 12 ms) but never in long-latency units (> or = 12 ms). NMDAR blockade had variable effects on short-latency units but reduced spikes substantially for all long-latency units. There were no distinct contributions of AMPARs and NMDARs to early and late elements of responses. Thus, AMPAR blockade reduced early (onset) spikes somewhat more effectively than NMDAR blockade in short-latency units, but NMDAR blockade reduced onset spikes more effectively in long-latency units. AMPAR and NMDAR blockade were equally effective in reducing later elements of sustained responses in short-latency units, whereas NMDAR blockade was much more effective in long-latency units. These results indicate that NMDARs play multiple roles for signal processing in adult IC neurons.


Molecular cloning of canalicular multispecific organic anion transporter defective in EHBR.
Several organic anions are excreted into the bile via a canalicular multispecific organic anion transporter (cMOAT), which is hereditarily defective in mutant rats, such as the Eisai hyperbilirubinemic rat (EHBR) and TR- rat. In the present study, we cloned cMOAT from the Sprague-Dawley rat liver cDNA library based on the homology with human multidrug resistance-associated protein (hMRP). cMOAT was encoded by 4,623-base pair (bp) cDNA with a homology of 53.0 and 46.3% with hMRP at the cDNA and deduced amino acid level, respectively. The deduced amino acid sequence was the same as that cloned in Wistar rats (C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L. Sceffer, P. Borst, and R. P. Oude Elferink. Science Wash. DC 271: 1126, 1996) except for four amino acid substitutions. By screening the library, three kinds of cDNA species for cMOAT with the same open reading frame and different 3'-untranslated region lengths (0.2, 1.5, and 3.5 kbp) were isolated. The Northern blot analysis of poly(A)+ RNA from the liver revealed that the expression of plural bands (approximately 5, 6, and 8 kb) was defective in EHBR, and this may be due to the presence of these cDNA species. Expression of cMOAT was observed almost exclusively in the liver and to a lesser extent in the duodenum, kidney, and jejunum. Reverse transcription-polymerase chain reaction (RT-PCR) and subsequent sequence analysis of EHBR liver, kidney, duodenum, and jejunum revealed that 1-bp replacement from G to A at nucleotide 2564 resulted in the introduction of the premature stop codon in all tissues examined. This mutation was different from that observed in TR (C. C. Paulusma, P. J. Bosma, G. J. Zaman, C. T. Bakker, M. Otter, G. L. Sceffer, P. Borst, and R. P. Oude Elferink. Science Wash. DC 271: 1126, 1996). Because EHBR and TR- are allelic mutants and both strains exhibit an autosomal recessive inheritance in the biliary excretion of organic anions it was concluded that the impaired expression of this particular protein is related to the pathogenesis of hyperbilirubinemia in the mutant animals.


Clinicopathologic case report: ultrastructure of the epithelial dystrophy of Meesmann.
As in previous studies of Meesmann dystrophy, intense vacuolation of the epithelium was observed. However, neither histochemical nor electron microscopical examination of the specimens showed any evidence of abnormal quantities of glycogen or the electron dense peculiar substance of Kuwabara and Ciccarelli. Electron microscopy indicated that the basic alteration leading to the manifestations of the dystrophy was electron dense bodies in the cytoplasm of the basal epithelial cells. These electron dense bodies appeared similar to lysosomes. In the more superficial cell layers, the electron dense bodies were engulfed by vacuoles that gradually increased in number and size to fill the cytoplasm and, finally, destroyed the most superficial cells.


Isolation and preparation of bacterial cell walls for compositional analysis by ultra performance liquid chromatography.
The bacterial cell wall is critical for the determination of cell shape during growth and division, and maintains the mechanical integrity of cells in the face of turgor pressures several atmospheres in magnitude. Across the diverse shapes and sizes of the bacterial kingdom, the cell wall is composed of peptidoglycan, a macromolecular network of sugar strands crosslinked by short peptides. Peptidoglycan's central importance to bacterial physiology underlies its use as an antibiotic target and has motivated genetic, structural, and cell biological studies of how it is robustly assembled during growth and division. Nonetheless, extensive investigations are still required to fully characterize the key enzymatic activities in peptidoglycan synthesis and the chemical composition of bacterial cell walls. High Performance Liquid Chromatography (HPLC) is a powerful analytical method for quantifying differences in the chemical composition of the walls of bacteria grown under a variety of environmental and genetic conditions, but its throughput is often limited. Here, we present a straightforward procedure for the isolation and preparation of bacterial cell walls for biological analyses of peptidoglycan via HPLC and Ultra Performance Liquid Chromatography (UPLC), an extension of HPLC that utilizes pumps to deliver ultra-high pressures of up to 15,000 psi, compared with 6,000 psi for HPLC. In combination with the preparation of bacterial cell walls presented here, the low-volume sample injectors, detectors with high sampling rates, smaller sample volumes, and shorter run times of UPLC will enable high resolution and throughput for novel discoveries of peptidoglycan composition and fundamental bacterial cell biology in most biological laboratories with access to an ultracentrifuge and UPLC.


Scenarios reveal pathways to sustain future ecosystem services in an agricultural landscape.
Sustaining food production, water quality, soil retention, flood, and climate regulation in agricultural landscapes is a pressing global challenge given accelerating environmental changes. Scenarios are stories about plausible futures, and scenarios can be integrated with biophysical simulation models to explore quantitatively how the future might unfold. However, few studies have incorporated a wide range of drivers (e.g., climate, land-use, management, population, human diet) in spatially explicit, process-based models to investigate spatial-temporal dynamics and relationships of a portfolio of ecosystem services. Here, we simulated nine ecosystem services (three provisioning and six regulating services) at 220 × 220 m from 2010 to 2070 under four contrasting scenarios in the 1,345-km2 Yahara Watershed (Wisconsin, USA) using Agro-IBIS, a dynamic model of terrestrial ecosystem processes, biogeochemistry, water, and energy balance. We asked (1) How does ecosystem service supply vary among alternative future scenarios? (2) Where on the landscape is the provision of ecosystem services most susceptible to future social-ecological changes? (3) Among alternative future scenarios, are relationships (i.e., trade-offs, synergies) among food production, water, and biogeochemical services consistent over time? Our results showed that food production varied substantially with future land-use choices and management, and its trade-offs with water quality and soil retention persisted under most scenarios. However, pathways to mitigate or even reverse such trade-offs through technological advances and sustainable agricultural practices were apparent. Consistent relationships among regulating services were identified across scenarios (e.g., trade-offs of freshwater supply vs. flood and climate regulation, and synergies among water quality, soil retention, and climate regulation), suggesting opportunities and challenges to sustaining these services. In particular, proactive land-use changes and management may buffer water quality against undesirable future climate changes, but changing climate may overwhelm management efforts to sustain freshwater supply and flood regulation. Spatially, changes in ecosystem services were heterogeneous across the landscape, underscoring the power of local actions and fine-scale management. Our research highlights the value of embracing spatial and temporal perspectives in managing ecosystem services and their complex interactions, and provides a system-level understanding for achieving sustainability of the food-water-climate nexus in agricultural landscapes.


Polyamine Oxidase Triggers H2O2-Mediated Spermidine Improved Oxidative Stress Tolerance of Tomato Seedlings Subjected to Saline-Alkaline Stress.
Saline-alkaline stress is one of several major abiotic stresses in crop production. Exogenous spermidine (Spd) can effectively increase tomato saline-alkaline stress resistance by relieving membrane lipid peroxidation damage. However, the mechanism through which exogenous Spd pre-treatment triggers the tomato antioxidant system to resist saline-alkaline stress remains unclear. Whether H2O2 and polyamine oxidase (PAO) are involved in Spd-induced tomato saline-alkaline stress tolerance needs to be determined. Here, we investigated the role of PAO and H2O2 in exogenous Spd-induced tolerance of tomato to saline-alkaline stress. Results showed that Spd application increased the expression and activities of superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), glutathione reductase (GR), and the ratio of reduced ascorbate (AsA) and glutathione (GSH) contents under saline-alkaline stress condition. Exogenous Spd treatment triggered endogenous H2O2 levels, SlPAO4 gene expression, as well as PAO activity under normal conditions. Inhibiting endogenous PAO activity by 1,8-diaminooctane (1,8-DO, an inhibitor of polyamine oxidase) significantly reduced H2O2 levels in the later stage. Moreover, inhibiting endogenous PAO or silencing the SlPAO4 gene increased the peroxidation damage of tomato leaves under saline-alkaline stress. These findings indicated that exogenous Spd treatment stimulated SlPAO4 gene expression and increased PAO activity, which mediated the elevation of H2O2 level under normal conditions. Consequently, the downstream antioxidant system was activated to eliminate excessive ROS accumulation and relieve membrane lipid peroxidation damage and growth inhibition under saline-alkaline stress. In conclusion, PAO triggered H2O2-mediated Spd-induced increase in the tolerance of tomato to saline-alkaline stress.


Influence of environmental changes in the north-western Atlantic Ocean on a parasite, Echinorhynchus gadi (Acanthocephala) of Atlantic cod ( Gadus morhua) occurring off coastal Labrador, Canada.
A study was conducted to determine the influence of environmental change on an endoparasite, Echinorhynchus gadi (Acanthocephala) of Atlantic cod (Gadus morhua) over a 30-year period off the coast of Labrador in the north-western Atlantic, North Atlantic Fisheries Organization subareas 2J-3K. Cod, once an abundant fish species that had been commercially exploited for many decades, declined precipitously during the mid-1980s onwards. This decline was attributed to climatic changes that affected the entire food chain from zooplankton to fish, sea birds and marine mammals. A monitoring programme was introduced, sampling cod by otter trawling using research vessels. The fish, after capture, were frozen at - 20 degrees C, subsequently thawed and the digestive tract removed and examined for the parasite in 2006. Data from samples taken in 1976, 1980-81, 1986, 1990, 2000 and 2003 were compared statistically with those collected in 2006. The results indicate a decline in the prevalence and mean abundance of E. gadi in 1986 with a minimum in 2000 but increasing gradually in 2003 and 2006. These changes were coincident initially with a decline of oceanic temperature and the entire food web, including capelin (Mallotus villosus), a preferred prey of cod and primary source of E. gadi. The increase in prevalence and mean abundance of the parasite in 2006 were associated with an increase of oceanic temperature and the return of small schools of capelin to offshore areas. Cod older than 4 years harboured a greater abundance of E. gadi than younger fish, while no difference was observed between the sexes. The results suggest that the abundance of E. gadi can be useful as a bioindicator of environmental changes in the north-western Atlantic.


Synthesis and assembly of the cytoskeleton of Naegleria gruberi flagellates.
When Naegleria gruberi flagellates were extracted with nonionic detergent and stained by the indirect immunofluorescence method with AA-4.3 (a monoclonal antibody against Naegleria beta-tubulin), flagella and a network of cytoskeletal microtubules (CSMT) were seen. When Naegleria amebae were examined in the same way, no cytoplasmic tubulin-containing structures were seen. Formation of the flagellate cytoskeleton was followed during the differentiation of amebae into flagellates by staining cells with AA-4.3. The first tubulin containing structures were a few cytoplasmic microtubules that formed at the time amebae rounded up into spherical cells. The formation of these microtubules was followed by the appearance of basal bodies and flagella and then by the formation of the CSMT. The CSMT formed before the cells assumed the flagellate shape. In flagellate shaped cells the CSMT radiate from the base of the flagella and follow a curving path the full length of the cell. Protein synthetic requirements for the formation of CSMT were examined by transferring cells to cycloheximide at various times after initiation. One-half the population completed the protein synthesis essential for formation of CSMT 61 min after initiation of the differentiation. This is 10 min after the time when protein synthesis for formation of flagella is completed and 10-15 min before the time when the protein synthesis necessary for formation of the flagellate shape is completed.


Nurse staffing ratios: trends and policy implications for hospitalists and the safety net.
Mandated minimum nurse-to-patient staffing ratio legislation was passed in California in 1999 and implemented January 1, 2004. Nurse staffing legislation is being considered in at least 25 other states. The objectives of this study were: (1) to evaluate nurse staffing trends in California from 1993 to 2004, (2) to identify types of hospitals below minimum staffing ratios and staffing changes in 2004, the first year post-implementation; and (3) to discuss possible implications of nurse staffing on hospitalists and their hospital-based initiatives. We analyzed data from the medical-surgical units of all short-term acute-care general hospitals in California from 1993 to 2004. The annual hospital staffing ratio is composed of the combined hours of registered nurses and licensed vocational nurses and total number of patient days on medical-surgical units. Nurse staffing ratios were relatively unchanged from 1993 to 1999 and then increased significantly from 1999 to 2004, with the largest increase in 2004, the year the nurse staffing ratio was implemented. Types of hospitals more likely to be below minimum ratios had a high Medicaid/uninsured patient population and were government owned, nonteaching, urban, and in more competitive markets. Most hospitals below ratios were considered part of the health care "safety net." Nurse staffing legislation may increase nurse staffing. However, mandated nurse staffing ratios without mechanisms to help achieve ratios may force hospitals, especially safety-net hospitals, to make tradeoffs in other services or investments with unintended negative consequences for patients. Nurse staffing likely influences the outcomes of hospitalist-led quality initiatives, but these effects need to be explored further.


[Changes in the pharmacodynamic properties of promedol, droperidol and dimedrol in burn shock and combined radiation-thermal injury].
Toxic and pharmacological properties of promedol, droperidol and dimedrol were studied during burn shock and combined radiation and thermal injury (CRTI). Acute toxicity and analgesic effect of promedol were shown to increase in the given period Droperidol analgesic effect enhanced in burn and CRTI, cataleptic action enhanced only in CRTI. A decrease of antihistaminic activity of dimedrol was more pronounced in CRTI.


An Efficient Test for Gene-Environment Interaction in Generalized Linear Mixed Models with Family Data.
Gene-environment (GE) interaction has important implications in the etiology of complex diseases that are caused by a combination of genetic factors and environment variables. Several authors have developed GE analysis in the context of independent subjects or longitudinal data using a gene-set. In this paper, we propose to analyze GE interaction for discrete and continuous phenotypes in family studies by incorporating the relatedness among the relatives for each family into a generalized linear mixed model (GLMM) and by using a gene-based variance component test. In addition, we deal with collinearity problems arising from linkage disequilibrium among single nucleotide polymorphisms (SNPs) by considering their coefficients as random effects under the null model estimation. We show that the best linear unbiased predictor (BLUP) of such random effects in the GLMM is equivalent to the ridge regression estimator. This equivalence provides a simple method to estimate the ridge penalty parameter in comparison to other computationally-demanding estimation approaches based on cross-validation schemes. We evaluated the proposed test using simulation studies and applied it to real data from the Baependi Heart Study consisting of 76 families. Using our approach, we identified an interaction between BMI and the Peroxisome Proliferator Activated Receptor Gamma (PPARG) gene associated with diabetes.


DisCoTune: versatile auxiliary plasmids for the production of disulphide-containing proteins and peptides in the E. coli T7 system.
Secreted proteins and peptides hold large potential both as therapeutics and as enzyme catalysts in biotechnology. The high stability of many secreted proteins helps maintain functional integrity in changing chemical environments and is a contributing factor to their commercial potential. Disulphide bonds constitute an important post-translational modification that stabilizes many of these proteins and thus preserves the active state under chemically stressful conditions. Despite their importance, the discovery and applications within this group of proteins and peptides are limited by the availability of synthetic biology tools and heterologous production systems that allow for efficient formation of disulphide bonds. Here, we refine the design of two DisCoTune (Disulphide bond formation in E. coli with tunable expression) plasmids that enable the formation of disulphides in the highly popular Escherichia coli T7 protein production system. We show that this new system promotes significantly higher yield and activity of an industrial protease and a conotoxin, which belongs to a group of disulphide-rich venom peptides from cone snails with strong potential as research tools and pharmacological agents.


Subgingival bacteria associated with hydroxylapatite-coated dental implants: morphotypes and trypsin-like enzyme activity.
This study investigated the colonization of teeth and hydroxylapatite-coated dental implants by different groups of oral bacteria. Periodontal and gingival health were assessed and subgingival plaque samples were taken. Bacterial morphotypes in subgingival plaque samples were enumerated and expressed as percent of bacteria counted, and presence of trypsin-like enzymes was detected by hydrolysis of benzoyl-arginine naphthylamide (BANA). For both pooled and separate implant and teeth data, positive correlations were found between pocket depth and both BANA hydrolysis and percent spirochetes, and a negative correlation was found between pocket depth and percent cocci. With one exception, analysis of variance revealed no significant differences between implants and teeth for presence of bacterial morphotypes when considering both periodontal and gingival health.