Characteristics of outpatients diagnosed with the selective/neophobic presentation of avoidant/restrictive food intake disorder.
Although Avoidant/Restrictive Food Intake Disorder (ARFID) has existed since the publication of DSM-5 in 2013, research on the descriptive psychopathology of treatment-seeking patients with formal ARFID diagnoses is sparse, and limited to tertiary eating disorder-focused treatment settings where most patients present with weight loss/malnutrition. In these settings, the selective/neophobic symptom presentation is rare compared to other primary eating restrictions. We aimed provide initial descriptive psychopathology of ARFID primary selective/neophobic symptom presentation in an outpatient setting, and to explore the prevalence of the core ARFID symptoms and clinical differences among patients meeting criteria based on weight/nutritional symptoms versus psychosocial impairment only. We reviewed the charts of 22 consecutive outpatients diagnosed with ARFID caused by selective/neophobic eating, and describe symptoms, impairment, illness trajectory, and demographic features. Patients who met ARFID criteria because of weight loss/nutritional problems were compared to those who met for psychosocial impairment only on demographic and clinical characteristics. Patients were predominantly male (81.8%) and school-aged (4-11 years). 81.8% had no weight/nutritional symptoms documented by a medical provider. All met criteria for significant psychosocial impairment. There were few differences between patients who did versus did not meet weight loss/nutritional criteria for ARFID; they differed only in age and in the presence of appetite disturbances consistent with another proposed presentation of ARFID. These results provide novel data on the clinical characteristics of individuals who present with a primary presentation of selective/neophobic ARFID, including support for psychosocial impairment as sufficient for fulfilling ARFID criterion A.


Enumeration of cell-infecting particles of Newcastle disease virus by the fluorescent antibody technique.
A procedure has been developed for the determination of the concentration of infective Newcastle disease virus (NDV) based on the enumeration of singly infected and distributed HeLa cells which are visualized by staining with fluorescent antibody. Infective virus assayed by the fluorescent cell-counting procedure is expressed in terms of cell-infecting units (CIU). Adsorption of NDV to HeLa cell monolayers reached a plateau 1 to 1.5 hours after inoculation of coverslip cultures, and 12 per cent of the infective particles inoculated failed to adsorb. The half-life of NDV in protein-free Eagle's medium at 37 degrees C. was 2.1 hours. There was a linear relationship between virus concentration and the number of infected cells. The coefficient of variation of the mean of replicate determinations of infective NDV was 8.2 per cent. The distribution of single infected HeLa cells in the monolayer corresponded to the Poisson distribution. With NDV the cell-infecting unit (CIU) determined in HeLa cells is equivalent to the plaque-forming unit in chick embryo cells and the egg infective dose. In experiments on the mechanism of dissemination of NDV in monolayer cultures of HeLa cells, NDV was found to spread from cell to cell through the extracellular milieu.


Identification by protein microsequencing of a proteinase-V8-cleavage site in a folding intermediate of chick muscle creatine kinase.
We have identified by protein microsequencing a glutamic acid residue (Glu-166) in a folding intermediate of chick muscle creatine kinase that is very sensitive to cleavage by staphylococcal proteinase V8. Most other glutamic acid residues, including Glu-168, are already partly protected from proteolytic attack at this stage. After the final stages of protein refolding, when enzyme activity is recovered, Glu-166 is also resistant to proteolysis.


An Enzymatic Cofactor Regeneration System for the in-Vitro Reduction of Isolated C=C Bonds by Geranylgeranyl Reductases.
Cofactor regeneration systems are of major importance for the applicability of oxidoreductases in biocatalysis. Previously, geranylgeranyl reductases have been investigated for the enzymatic reduction of isolated C=C bonds. However, an enzymatic cofactor-regeneration system for in vitro use is lacking. In this work, we report a ferredoxin from the archaea Archaeoglobus fulgidus that regenerates the flavin of the corresponding geranylgeranyl reductase. The proteins were heterologously produced, and the regeneration was coupled to a ferredoxin reductase from Escherichia coli and a glucose dehydrogenase from Bacillus subtilis, thereby enabling the reduction of isolated C=C bonds by purified enzymes. The system was applied in crude, cell-free extracts and gave conversions comparable to those of a previous method using sodium dithionite for cofactor regeneration. Hence, an enzymatic approach to the reduction of isolated C=C bonds can be coupled with common systems for the regeneration of nicotinamide cofactors, thereby opening new perspectives for the application of geranylgeranyl reductases in biocatalysis.


Predictive value of preoperative serum cholinesterase concentration in patients with liver dysfunction undergoing cardiac surgery.
There are an increasing number of patients with severe liver dysfunction subjected to open heart surgery. This retrospective study was designed to assess operative results and clarify the degree of liver injury in patients with liver dysfunction undergoing open heart surgery. In addition, determinants influencing their prognosis were assessed. In a 9-year period from 1988 to 1996, we operated on 31 patients with posthepatitis liver dysfunction and 16 with chronic passive congestion of the liver. This group was 2.3% and 1.6% of the 1368 patients undergoing cardiac surgery in the same period. We compared several perioperative factors between survivors and nonsurvivors to determine risk factors affecting mortality. In the group with posthepatitis liver dysfunction, the postoperative course of 5 patients among 31 (16.1%) was poor. Serum cholinesterase concentration was lower only in the nonsurvivor group (nonsurvivor vs survivor: 1979+/-949 vs 3515+/-1424 IU/I, p < 0.05). All patients with cholinesterase < 2000 IU/L died. The duration of CPB (212+/-53 vs 150+/-54 minutes, p < 0.03) and ACC time (151+/-38 vs 96+/-40 minutes, p < 0.02) was longer in the nonsurvivor group. In the group with chronic passive congestion, the postoperative course of 5 of 16 (31.3%) patients with valvular disease was poor. Serum cholinesterase concentration was lower only in the nonsurvivor group (nonsurvivor vs survivors: 2006+/-435 vs 3483+/-1442 IU/L, p < 0.02), and all patients with cholinesterase < 2000 IU/L died. Postoperative bleeding was greater in the nonsurvivor group (3327+/-2106 vs 1428+/-643 mL, p < 0.05). Multivariate logistic regression analysis including the described pre- and intraoperative factors identified only serum cholinesterase concentration (F = 9.18) as significant. A low value of preoperative serum cholinesterase (< 2,000 IU/L) is thought to be the predictor of prognosis after open heart surgery in patients with severe posthepatitis and congestive liver dysfunction. Operative factors (cardiopulmonary time in posthepatitis liver dysfunction and postoperative bleeding in the congestive liver dysfunction) also influenced the prognosis.


How have systematic priority setting approaches influenced policy making? A synthesis of the current literature.
There is a growing body of literature on systematic approaches to healthcare priority setting from various countries and different levels of decision making. This paper synthesizes the current literature in order to assess the extent to which program budgeting and marginal analysis (PBMA), burden of disease & cost-effectiveness analysis (BOD/CEA), multi-criteria decision analysis (MCDA), and accountability for reasonableness (A4R), are reported to have been institutionalized and influenced policy making and practice. We searched for English language publications on health care priority setting approaches (2000-2017). Our sources of literature included PubMed and Ovid databases (including Embase, Global Health, Medline, PsycINFO, EconLit). Of the four approaches PBMA and A4R were commonly applied in high income countries while BOD/CEA was exclusively applied in low income countries. PBMA and BOD/CEA were most commonly reported to have influenced policy making. The explanations for limited adoption of an approach were related to its complexity, poor policy maker understanding and resource requirements. While systematic approaches have the potential to improve healthcare priority setting; most have not been adopted in routine policy making. The identified barriers call for sustained knowledge exchange between researchers and policy-makers and development of practical guidelines to ensure that these frameworks are more accessible, applicable and sustainable in informing policy making.


Dissolution studies on paracetamol solidified melt prepared under different cooling rates.
Regulating the cooling rate of paracetamol melt resulted in the formation of different microcrystalline structures of the solidified melt. Dissolution rate studies were carried out on powdered samples prepared from fused paracetamol that was crystallized under different conditions. Rapid cooling associated with stirring the melt during crystallisation produced a fast rate of dissolution in the order of two times greater than the untreated drug. Increased dissolution rate data were masked to some extent when working with tablets prepared from the corresponsing solidified and powdered melts. The present study represent a new method of physical modification of drugs as a means of increasing rate of drug dissolution and absorption.


Molecular variability of five Cucumber mosaic virus isolates from China.
Cucumber mosaic virus (CMV) isolates are currently divided into two main groups, I and II according to their genomic sequences. The group I is further divided into two subgroups IA and IB. We performed a phylogenetic analysis of the genome regions containing 1a, 2a, 2b, coat protein (CP), and movement protein (MP) genes of 5 CMV isolates from China and other 28 CMV isolates available in the GenBank. The results indicated that CMV isolates could be genetically divided into three groups I, II, and III according to the genes encoding MP, CP, 1a, and 2a proteins and to the 2 groups according to the gene 2b. Group I could be further divided into two subgroups (IA and IB) according to the genes encoding CP, MP, 2a, and 2b proteins and to the three subgroups (IA, IB, and IC) according to the gene encoding 1a protein. Four of 5 examined Chinese CMV isolates belonged to the subgroup IB, while the remaining isolate was a natural inter-subgroup reassortant. We found that the 2b gene of CMV was under positive selection, while the other genes were under negative selection. No evidence of the selection associated with a host adaptation or geographic distribution was found.


Impaired leptomeningeal collateral flow contributes to the poor outcome following experimental stroke in the Type 2 diabetic mice.
Collateral status is an independent predictor of stroke outcome. However, the spatiotemporal manner in which collateral flow maintains cerebral perfusion during cerebral ischemia is poorly understood. Diabetes exacerbates ischemic brain damage, although the impact of diabetes on collateral dynamics remains to be established. Using Doppler optical coherent tomography, a robust recruitment of leptomeningeal collateral flow was detected immediately after middle cerebral artery (MCA) occlusion in C57BL/6 mice, and it continued to grow over the course of 1 week. In contrast, an impairment of collateral recruitment was evident in the Type 2 diabetic db/db mice, which coincided with a worse stroke outcome compared with their normoglycemic counterpart db/+, despite their equally well-collateralized leptomeningeal anastomoses. Similar to the wild-type mice, both db/+ and db/db mice underwent collateral growth 7 d after MCA stroke, although db/db mice still exhibited significantly reduced retrograde flow into the MCA territory chronically. Acutely induced hyperglycemia in the db/+ mice did not impair collateral flow after stroke, suggesting that the state of hyperglycemia alone was not sufficient to impact collateral flow. Human albumin was efficacious in improving collateral flow and outcome after stroke in the db/db mice, enabling perfusion to proximal MCA territory that was usually not reached by retrograde flow from anterior cerebral artery without treatment. Our results suggest that the impaired collateral status contributes to the exacerbated ischemic injury in mice with Type 2 diabetes, and modulation of collateral flow has beneficial effects on stroke outcome among these subjects.


Factors associated with dehiscence and mortality rates following gastrointestinal surgery in dogs.
To identify factors associated with dehiscence and mortality rates following gastrointestinal surgery in dogs. 170 client-owned dogs that underwent gastrointestinal surgery from 2010 to 2016. Medical records of all included dogs were reviewed to collect information on preoperative (breed, sex, age, body weight, American Society of Anesthesiologists [ASA] physical status classification, emergency status, and plasma lactate concentration), intraoperative (indication for surgery, type of surgery, and whether bacterial peritonitis was identified), and postoperative (development of dehiscence and survival status at 2 weeks after surgery) factors. Preoperative and intraoperative factors were evaluated for associations among each other and with postoperative factors. Univariate analyses revealed that preoperative plasma lactate concentration increased with increasing ASA status, and lactate concentrations were significantly higher for nonsurvivors (mean ± SD, 4.6 ± 3.7 mmol/L) than for survivors (2.4 ± 1.7 mmol/L). Multivariate analysis controlling for age, body weight, and plasma lactate concentration revealed that dogs with an ASA status ≥ 3 were more likely to develop dehiscence after gastrointestinal surgery than were dogs with a lower ASA status (OR, 17.77; 95% confidence interval, 2.17 to 144.06). Multivariate analysis also revealed that dogs with an ASA status ≥ 3 or high lactate concentration were less likely to survive than were other dogs. These findings regarding ASA status and preoperative plasma lactate concentration and their associations with outcome may help clinicians to determine and provide optimal perioperative care to dogs requiring gastrointestinal surgery as well as to inform owners about prognosis.


Assessment of Action Plans as a Guide for Equity-Focused Coalition Work.
Collaborative capacity within coalitions is required to promote healthy communities and create systemic change. The purpose of this study was to evaluate the quality of three Tobacco Prevention and Control Coalitions' action plans for their likely ability to address health equity through tobacco cessation efforts. To do this, the Butterfoss State Plan Index was adapted for relevance to community-oriented coalitions, with a focus on health disparities and tobacco control. This study compares three tobacco control coalitions in Texas to quantify their efforts on addressing health disparities through a standardized measurement process. The results of this assessment indicate that there are gaps in existing coalition assessment tools, and action plan norms and requirements, specifically as it pertains to addressing health disparities in a systematic way. Through a systematic analysis of coalition action plans and supporting documents, it is clear that there is a need for more standard inclusion of disparities-focused work within action plans. Community health researchers, coalition members, and coalition funders should consider action plans to be living, iterative documents that are subject to adjustments. Systems-thinking perspective should be used to develop action plans adapted to environmental, community, policy, and other changes. Lessons learned from this study can provide an example of how to incorporate strategies for reducing health disparities within coalition action planning.


Enzyme-free optical DNA mapping of the human genome using competitive binding.
Optical DNA mapping (ODM) allows visualization of long-range sequence information along single DNA molecules. The data can for example be used for detecting long range structural variations, for aiding DNA sequence assembly of complex genomes and for mapping epigenetic marks and DNA damage across the genome. ODM traditionally utilizes sequence specific marks based on nicking enzymes, combined with a DNA stain, YOYO-1, for detection of the DNA contour. Here we use a competitive binding approach, based on YOYO-1 and netropsin, which highlights the contour of the DNA molecules, while simultaneously creating a continuous sequence specific pattern, based on the AT/GC variation along the detected molecule. We demonstrate and validate competitive-binding-based ODM using bacterial artificial chromosomes (BACs) derived from the human genome and then turn to DNA extracted from white blood cells. We generalize our findings with in-silico simulations that show that we can map a vast majority of the human genome. Finally, we demonstrate the possibility of combining competitive binding with enzymatic labeling by mapping DNA damage sites induced by the cytotoxic drug etoposide to the human genome. Overall, we demonstrate that competitive-binding-based ODM has the potential to be used both as a standalone assay for studies of the human genome, as well as in combination with enzymatic approaches, some of which are already commercialized.


Prevalence and anatomic characteristics of infarct-like lesions on MR images of middle-aged adults: the atherosclerosis risk in communities study.
MR imaging has revealed putative evidence of subclinical cerebrovascular disease (CVD) as reflected by white matter signal changes and infarct-like lesions (ILLs). Nonetheless, the prevalence of this condition in the general population has been defined only to a limited extent. We herein report the prevalence and anatomic characteristics of ILLs seen on cranial MR images obtained as part of a population-based study of cardiovascular disease in middle-aged adults. These results are contrasted to those of previous similar studies, particularly those of an elderly population in the Cardiovascular Health Study (CHS). This Atherosclerosis Risk in Communities (ARIC) cohort consists of a probability sample of community-living persons who were 55 to 72 years old at the time of MR examination. MR imaging of 1890 participants was performed at two ARIC field centers, based on a common protocol. MR studies were evaluated by trained readers at the MR Reading Center using original digital data displayed on a high-resolution workstation. The measures of lesion size, anatomic location, and signal intensity were collected. The definition for an ILL was a non-mass, hyperintense region with an arterial vascular distribution on spin-density and T2-weighted images. Two hundred ninety participants had ILLs, for an overall prevalence of 15.3%. Eighty-two percent of participants with ILLs had lesions that were 3 mm or larger in maximal dimension, although 87% of these lesions were 20 mm or smaller in maximal dimension. The prevalence of ILLs increased with age, from 7.9% in the 55- to 59-year-old age group to 22.9% in the 65- to 72-year-old age group (P < .001). Lesion prevalence was greater in black (20.7%) than in white persons (10.2% [P < .0001]), but did not differ significantly between male and female participants. The basal ganglia and thalamic region was the most commonly affected anatomic site, accounting for 78.9% of the lesions. Considering that the prevalence of self-reported stroke or transient ischemic attack in ARIC participants is 1.5%, these results suggest that there is significantly more subclinical than clinical CVD in the general population. Furthermore, the prevalence of this subclinical disease increases with age, and is greater in black persons. ILLs are dominated by "lacunae" in the basal ganglia and thalamus. These results are, in general, similar to those of a comparable study of elderly participants in the CHS, except for a 60% lower prevalence of ILLs in this younger population.


Familial hypercholesterolemia and its manifestations: Practical considerations for general practitioners.
Familial hypercholesterolemia (FH) is the most common genetic disorder of lipid metabolism, affecting almost 1 in 250 individuals worldwide. It is usually inherited via the autosomal dominant way and is characterized by aberrantly high total and low-density lipoprotein cholesterol (LDL-C) concentrations from early childhood, predisposing to increased risk of premature atherosclerotic cardiovascular disease (ASCVD), mostly coronary heart disease (CHD). Despite its high prevalence in the general population and the high ASCVD risk, FH is often underdiagnosed and undertreated. Genetic diagnosis is not always necessary since specific criteria, taking into account the patient's individual and family history, clinical signs, and untreated LDL-C concentrations, may be used for prompt diagnosis. Except for CHD, which may be already evident at diagnosis, leading to increased mortality, other non-CHD morbidities, such as stroke, peripheral artery disease, carotid artery stenosis, and aortic valve calcification may be also present, substantiating the need for prompt intervention. Statins constitute the mainstay of treatment both in adults and children >8 years old. In cases of statin intolerance or not achieving the LDL-C target despite maximally tolerated statin dose, ezetimibe and/or proprotein convertase subtilisin-kexin type 9 inhibitors may be used. The advent of recently approved medications, such as inclisiran and bempedoic acid, either as monotherapy or as add-on therapy to statins, has further enhanced the therapeutic armamentarium that can be used in FH patients. The purpose of this narrative review is to provide practical considerations regarding the diagnostic and therapeutic approach to FH patients.


Changes in defense capacity to infectious hematopoietic necrosis virus (IHNv) in rainbow trout intergenerationally exposed to glyphosate.
Glyphosate, the most widely used herbicide active substance worldwide, has raised many scientific, political and public debates in the context of its recent re-registration in the European Union, highlighting in particular a lack of data concerning its potential generational effects. In this study, we investigated the intergenerational toxicity of this active substance used alone or coformulated in glyphosate-based herbicides (GBHs) on the ability of rainbow trout (Oncorhynchus mykiss) to face a viral challenge. Juvenile trout from parents exposed for eight months to four different chemical exposure conditions (non-exposed control, pure glyphosate, Roundup Innovert®, and Viaglif Jardin® were experimentally infected with the infectious hematopoietic necrosis virus (IHNv). Various enzymatic and hemato-immunological markers were assessed before and after the viral challenge. Chemical contamination with GBHs strongly modulated viral trout susceptibility. Pure glyphosate induced a cumulative mortality of 35.8%, comparable to the control (37.0%), which was significantly reduced with Roundup Innovert® (-9.9%) and increased (+14.8%) with Viaglif Jardin®. No modification was observed for the biomarkers analysed for any conditions. These results demonstrate that the nature of the co-formulants associated to glyphosate in GHBs can modulate the susceptibility of fish to pathogens.


Gastro-intestinal fistulas: the role of nutritional support.
Over the decades the advent of advanced surgical techniques, antibiotics, management of acid-base and electrolyte disorders, monitoring and support of cardiorespiratory function, have greatly implemented the treatment of patients with gastro-intestinal fistulas, resulting in most series in a mortality of approximately 20%. The apparent clinical benefit of sophisticated parenteral nutrition has not further reduced mortality because in the seventies patients in most series were older, sicker, had more advanced cancer, underwent bigger operations and were more at risk in almost every respect. In recent series mortality is almost exclusively determined by uncontrolled sepsis. It is therefore imperative to control intra-abdominal infection because ongoing sepsis ultimately nullifies the effect of other therapeutic modalities. When infection is controlled however nutritional support may serve several purposes. It may relieve malnourishment. It may decrease gastro-intestinal, biliary and pancreatic secretion allowing fistula output to diminish and sometimes fistulae to heal spontaneously. It may allow a potential future operative field to quiet down. With adequate nutritional support fistulae may heal spontaneously (lateral, no distal obstructions, no adjacent abscesses, good quality bowel). Others may be surgically treated with the patient in good nutritional state and with a favourable local situation. Crohn's fistulae heal spontaneously in a large percentage (80%) but have to be operated after closure because the cause of the fistulae is almost invariably an irreversibly stenosed fibrotic bowel segment so that fistulae may recur after resumption of oral feeding. In unfavourable fistulae (total disruption, adjacent abscesses, bad quality bowel) infection is often difficult to control.(ABSTRACT TRUNCATED AT 250 WORDS)


Jugular vein thrombosis: a rare presentation of atypical chronic myeloproliferative disorder in a young woman.
Venous thromboembolism is common in subjects with chronic myeloproliferative disorders and is a recognized presenting feature of occult myeloproliferation. We report the case of a young woman who presented with acute thrombosis in the right jugular vein and pulmonary embolism. Splenomegaly and myeloid proliferation with bone marrow fibrosis, in the absence of the criteria for typical myeloproliferative disorders, allowed a diagnosis of an atypical form of chronic myeloproliferative disorder. This form carries a high risk of thrombosis and venous thromboembolism can be the presenting feature, though the course is often indolent. Acute thrombosis in the right jugular vein has not been so far described in these subjects. The outcome of young people with myelofibrosis is unpredictable, but a normal level of hemoglobin and the absence of blast cells and constitutional symptoms at presentation identifies subjects with a low probability of rapid disease progression.


Factors determining early left atrial reverse remodeling after mitral valve surgery.
This study aimed to investigate the factors determining early left atrial (LA) reverse remodeling after mitral valve (MV) surgery. The left atrium is frequently dilated in patients with mitral stenosis (MS) or mitral regurgitation (MR). MV surgery usually results in LA volume reduction. However, the factors associated with LA reverse remodeling after MV surgery are not clearly defined. One hundred thirty-eight patients (51 men, 87 women; mean age, 53 years) underwent transthoracic echocardiography before and after MV surgery. Maximal LA volume was measured using the prolate ellipsoid model. The percentage of LA volume change was calculated. The patients were grouped according to age (<50 vs >or=50 years), predominant lesion (pure MR vs some degree of MS), type of surgery (MV repair vs MV replacement), and preoperative rhythm (sinus rhythm vs atrial fibrillation). LA volume decreased from 147+/-93 to 103+/-43 ml (p<0.001) after surgery. LA reverse remodeling was more prominent in patients who were <50 years old (percentage of LA volume change -31.2+/-17.4 vs -18.4+/-19.2, p<0.001), had pure MR (percentage of LA volume change -30.4+/-18.6 vs -17.3+/-18.2, p<0.001), and had a preoperative sinus rhythm (percentage of LA volume change -28.5+/-17.7 vs -20.5+/-20.0, p=0.019). In conclusion, on stepwise multiple regression analysis, preoperative LA volume, predominant lesion, age, and cardiac rhythm were significant predictors of LA reverse remodeling. A larger preoperative LA volume, MR rather than MS, younger age at the time of surgery, and sinus rhythm were important predictors of LA reverse remodeling after MV surgery.


Non-structural carbohydrate pools in a tropical forest.
The pool size of mobile, i.e. non-structural carbohydrates (NSC) in trees reflects the balance between net photosynthetic carbon uptake (source) and irreversible investments in structures or loss of carbon (sink). The seasonal variation of NSC concentration should reflect the sink/source relationship, provided all tissues from root to crown tops are considered. Using the Smithsonian canopy crane in Panama we studied NSC concentrations in a semi-deciduous tropical forest over 22 months. In the 9 most intensively studied species (out of the 17 investigated), we found higher NSC concentrations (starch, glucose, fructose, sucrose) across all species and organs in the dry season than in the wet season (NSC 7.2% vs 5.8% of dry matter in leaves, 8.8/6.0 in branches, 9.7/8.5 in stems, 8.3/6.4 in coarse and 3.9/2.2 in fine roots). Since this increase was due to starch only, we attribute this to drought-constrained growth (photosynthesis less affected by drought than sink activity). Species-specific phenological rhythms (leafing or fruiting) did not overturn these seasonal trends. Most of the stem volume (diameter at breast height around 40 cm) stores NSC. We present the first whole forest estimate of NSC pool size, assuming a 200 t ha(-1) forest biomass: 8% of this i.e. ca. 16 t ha(-1) is NSC, with ca. 13 t ha(-1) in stems and branches, ca. 0.5 and 2.8 t ha(-1) in leaves and roots. Starch alone (ca. 10.5 t ha(-1)) accounts for far more C than would be needed to replace the total leaf canopy without additional photosynthesis. NSC never passed through a period of significant depletion. Leaf flushing did not draw heavily upon NSC pools. Overall, the data imply a high carbon supply status of this forest and that growth during the dry season is not carbon limited. Rather, water shortage seems to limit carbon investment (new tissue formation) directly, leaving little leeway for a direct CO2 fertilization effects.


Oxidation of Acenaphthene and Acenaphthylene by Human Cytochrome P450 Enzymes.
Acenaphthene and acenaphthylene, two known environmental polycyclic aromatic hydrocarbon (PAH)pollutants, were incubated at 50 μM concentrations in a standard reaction mixture with human P450s 2A6, 2A13, 1B1,1A2, 2C9, and 3A4, and the oxidation products were determined using HPLC and LC-MS. HPLC analysis showed that P450 2A6 converted acenaphthene and acenaphthylene to several mono- and dioxygenated products. LC-MS analysis of acenaphthene oxidation by P450s indicated the formation of1-acenaphthenol as a major product, with turnover rates of 6.7,4.5, and 3.6 nmol product formed/min/nmol P450 for P4502A6, 2A13, and 1B1, respectively. Acenaphthylene oxidation by P450 2A6 showed the formation of 1,2-epoxyacenaphthene as a major product (4.4 nmol epoxide formed/min/nmol P450) and also several mono- and dioxygenated products.P450 2A13, 1B1, 1A2, 2C9, and 3A4 formed 1,2-epoxyacenaphthene at rates of 0.18, 5.3 2.4, 0.16, and 3.8 nmol/min/nmol P450, respectively. 1-Acenaphthenol, which induced Type I binding spectra with P450 2A13, was further oxidized by P450 2A13 but not P450 2A6. 1,2-Epoxyacenaphthene induced Type I binding spectra with P450 2A6 and 2A13 (K(s) 1.8 and 0.16 μM,respectively) and was also oxidized to several oxidation products by these P450s. Molecular docking analysis suggested different orientations of acenaphthene, acenaphthylene, 1-acenaphthenol, and 1,2-epoxyacenaphthene in their interactions with P450 2A6a nd 2A13. Neither of these four PAHs induced umu gene expression in a Salmonella typhimurium NM tester strain. These results suggest, for the first time, that acenaphthene and acenaphthylene are oxidized by human P450s 2A6 and 2A13 and other P450s to form several mono- and dioxygenated products. The results are of use in considering the biological and toxicological significance of these environmental PAHs in humans.


Mathematical modeling of exercise fatigability in the severe domain: A unifying integrative framework in isokinetic condition.
Muscle fatigue is the decay in the ability of muscles to generate force, and results from neural and metabolic perturbations. This article presents an integrative mathematical model that describes the decrease in maximal force capacity (i.e. fatigue) over exercises performed at intensities above the critical force Fc (i.e. severe domain). The model unifies the previous Critical Power Model and All-Out Model and can be applied to any exercise described by a changing force F over time. The assumptions of the model are (i) isokinetic conditions, an intensity domain of Fc<F, (ii) constant individual parameters of Fc, and τ, (iii) fatigability proportional to the accumulation of impulse JAC above the critical force Fc. The present study adjusted the parameters to fit previous experimental observations from three types of exercises: constant intensity, all-out, and increasing ramp exercise. This integrative model establishes a connection between the previous individual models and provides an excellent description of exercise fatigability in the severe domain. With this new integrative model, the maximal force production of the muscle can be predicted over time during both maximal and submaximal exercises.


Attitudes and Practices Regarding Responsible Beverage Service: Focus Group Discussions With Bar and Restaurant Management and Staff.
Staff and management of bars and restaurants are the key players in assuring responsible beverage service (RBS) and preventing the overservice of alcohol to intoxicated patrons. We conducted six focus group discussions ( N = 42) with management and staff from bars and restaurants about RBS. We compared findings from these current discussions to results of focus group discussions conducted in the 1990s. In comparison to the earlier focus group discussions, we found that many managers and staff members had experience with RBS training programs, establishments generally had written alcohol service policies, and managers and staff members perceived greater likelihood of facing consequences from law enforcement for serving underage youth. Managers and servers also expressed greater concern about overservice of alcohol but did not report greater concern about potential legal consequences for overservice of alcohol than participants from the 1990s focus groups. Results of this study can inform training and enforcement approaches to addressing overservice of alcohol.


Major depressive illness in women: assessment and treatment in the primary care setting.
Depressive illness in women carries with it a tremendous price to the woman's sense of well-being and health. Primary care providers who have frequent and continuous contact with women at risk for developing a depressive disorder are in an excellent position to diagnose and treat depression.


A literature review on the concept of intimacy in nursing.
This paper explores the concept of intimacy in nursing. Intimacy is an increasingly important concept in nursing and feature of the nurse-patient relationship, which is perceived to be intrinsic to the proposed therapeutic potential of nursing. The introduction to the paper highlights the theoretical enthusiasm and endorsement of intimacy, the apparent lack of conceptual clarity from a nursing perspective and little published research investigating intimacy in practice. Literature is reviewed from nursing and a variety of health-related disciplines. The paper traces the historical background of the nurse-patient relationship and intimacy and highlights the change in value from detachment and distancing to intimacy, commitment and involvement. The nature of intimacy is examined and a concept analysis based on literature from psychology and psychiatric medicine is critically analysed. Intimacy is suggested to have psychological, emotional and physical aspects, which are explored. An ethnographic research study on intimacy in nursing is reviewed, which also recognizes physical and emotional dimensions of the concept and the importance of sufficient resources to allow the close relationships advocated. Attention is drawn to the constraints on intimacy imposed by the current market-led health service. Literature and research on the implications and consequences of intimacy for the nurse are discussed. These report practical difficulties of maintaining close relationships with individual patients and the potential for over-involvement and emotional labour. The paper concludes with the increasing importance attached to intimacy in nursing and its complex, ill-defined nature. This serves to highlight the importance of research aimed at exploring and clarifying intimacy and further illustrating the therapeutic potential of nursing.


[Structural basis of the intracortical synchronization of epileptic potentials in the sensomotor region of the rat neocortex].
In control rats, penicillin-induced epileptiform discharges were completely synchronous in the neocortex sites at a distance of up to 4 mm from each other. Number of the cells decreased by 45.5% during 90 days in isolated cortical slabs and the synchronisation disappeared. The data obtained show that the loss of large pyramidal neurones of the layer V entailed a loss of the spatial synchronisation. The main axonal collaterals of large pyramidal neurones of the layer V could be followed horizontally for a distance of up to 2 mm in the somatosensory cortex. The neuronal network formed by the large pyramidal neurones of the layer V seems to provide a spatial synchronisation in the neocortex.


[Evaluation of commercially available fluoride containing toothpastes].
The role of fluorides in caries prevention has been well established in the epidemiological studies of fluoridated areas. Without water fluoridation, dentists in Taiwan face the challenge to optimize the use of other forms of fluoride products to reduce caries incidence. Toothpaste containing fluoride constitutes an effective and practical way of exposing teeth to fluoride on a regular basis. The present study evaluated 62 commercially available toothpaste products, of which 35 lacked a proper Chinese label and product information. Forty-one products contained fluorides which were sodium fluoride and/or sodium monofluorophosphate. Half of the children's toothpastes did not contain fluoride. The statement of CNS 439 only indicated that the fluoride concentration of the toothpaste was below 1000 ppm. More information about type of fluoride and its concentration must be provided for the user or dental professionals to make a proper selection. Parental supervision of their children's toothbrushing needs to be reinforced. Certain products used for dental hypersensitivity contained high concentrations of fluoride. Young children must be guarded from accidentally ingesting an overdose of fluoride.


Diabetic Kinome Inhibitors-A New Opportunity for β-Cells Restoration.
Diabetes, and several diseases related to diabetes, including cancer, cardiovascular diseases and neurological disorders, represent one of the major ongoing threats to human life, becoming a true pandemic of the 21st century. Current treatment strategies for diabetes mainly involve promoting β-cell differentiation, and one of the most widely studied targets for β-cell regeneration is DYRK1A kinase, a member of the DYRK family. DYRK1A has been characterized as a key regulator of cell growth, differentiation, and signal transduction in various organisms, while further roles and substrates are the subjects of extensive investigation. The targets of interest in this review are implicated in the regulation of β-cells through DYRK1A inhibition-through driving their transition from highly inefficient and death-prone populations into efficient and sufficient precursors of islet regeneration. Increasing evidence for the role of DYRK1A in diabetes progression and β-cell proliferation expands the potential for pharmaceutical applications of DYRK1A inhibitors. The variety of new compounds and binding modes, determined by crystal structure and in vitro studies, may lead to new strategies for diabetes treatment. This review provides recent insights into the initial self-activation of DYRK1A by tyrosine autophosphorylation. Moreover, the importance of developing novel DYRK1A inhibitors and their implications for the treatment of diabetes are thoroughly discussed. The evolving understanding of DYRK kinase structure and function and emerging high-throughput screening technologies have been described. As a final point of this work, we intend to promote the term "diabetic kinome" as part of scientific terminology to emphasize the role of the synergistic action of multiple kinases in governing the molecular processes that underlie this particular group of diseases.


The ethical leadership challenge: creating a culture of patient- and family-centered care in the hospital setting.
The growing number of medical errors and resulting preventable deaths in hospitals presents an ethical dilemma that must be addressed by health care leaders and managers. These medical errors and deaths raise questions about safety and quality issues resulting in rising public mistrust and patient dissatisfaction. Many of these medical errors and deaths could have been avoided by including the patient and family in the care. The ethical challenge for leadership is creating a culture of patient- and family-centered care as a means to improve quality, safety, patient satisfaction, and public trust. This article addresses ways to improve safety, quality, patient satisfaction, and cost and thereby reduce medical errors and deaths by implementing a patient- and family-centered care culture. The first critical step for improvement is for hospital leaders and managers to answer the ethical call to create a culture centered on patient- and family-centered care in the hospital setting.


Follow-up using fluorescence bronchoscopy for the patients with photodynamic therapy treated early lung cancer.
To evaluate the accuracy of fluorescence bronchoscopy by precise histological analysis of the photodynamic therapy (PDT) treated lesions. A retrospective study was conducted on thirteen patients (16 lesions) with centrally located early lung cancer (CLELC) had been undergone photodynamic therapy and had been followed up by fluorescence bronchoscopy. Fluorescence bronchoscopy was performed between 1 and 60 months after photodynamic therapy. Of the 16 early carcinomas treated, 14 (87.5%) had a CR, 2 (12.5%) had a NR after initial PDT. Among the 14 carcinomas achieving a CR, 4 (29%) recurred locally from 6 to 12 months after initial PDT. A total of 62 surveillance auto fluorescence bronchoscopies (average; 4.5/patient) and 47 biopsies (average; 4/patient) were performed after PDT. The addition of the SAFE-3000 examination to conventional bronchoscopy increased the sensitivity of screening from 69% to 100%, which yielded a relative sensitivity of 145% with a negative predictive value of 100%. Out of 14 CR lesions, 9 lesions finally reverted to normal fluorescence. CR cases that did not show normal fluorescence were relapsed cases or a patient with complete response whose treated lesion showed fibrosis in the sub mucosa. Histopathological finding of the complete response sites which demonstrated temporal fluorescent defect consisted of inflammatory lesions, goblet cell hyperplasia, basal cell hyperplasia, squamous metaplasia or dysplasia. our results confirm that SAFE-3000 allows accurate assessment of the quality and efficacy of PDT.


Using Petri Net tools to study properties and dynamics of biological systems.
Petri Nets (PNs) and their extensions are promising methods for modeling and simulating biological systems. We surveyed PN formalisms and tools and compared them based on their mathematical capabilities as well as by their appropriateness to represent typical biological processes. We measured the ability of these tools to model specific features of biological systems and answer a set of biological questions that we defined. We found that different tools are required to provide all capabilities that we assessed. We created software to translate a generic PN model into most of the formalisms and tools discussed. We have also made available three models and suggest that a library of such models would catalyze progress in qualitative modeling via PNs. Development and wide adoption of common formats would enable researchers to share models and use different tools to analyze them without the need to convert to proprietary formats.


Poor Health and Experiences of Being Bullied in Adolescents: Self-Perceived Overweight and Frustration with Appearance Matter.
To examine the associations between body image (actual and self-perceived weight status; feelings about appearance) and health outcomes (overall health, life satisfaction, and mental health) and between body image and experiences of being bullied. Participants included 8,303 children from 7th to 10th grade in the Health Behavior of School-Aged Children (HBSC) 2009-2010 data set, a large-scale sample in the United States. Several multiple linear regressions (with health outcomes as dependent variables) and multivariate logistic regressions (with being bullied or not as dependent variable) were conducted to investigate the associations between each dependent variable and the following independent variables: relationship with parents, frustration with appearance, and actual and self-perceived weight status. Self-perceived underweight, self-perceived overweight (OW), and frustration with appearance were positively associated with being bullied. Frustration with appearance was a risk factor, while good relationship with parents was a protective factor, especially for psychological health outcomes. Self-perceived OW had a stronger association with the experience of being bullied than actual OW. The relationship between actual OW and being bullied might be attenuated when self-perceived OW is simultaneously considered. Body image may be an important factor in the association between weight status and the experience of being bullied.


Circulating Levels of Epirubicin Cause Endothelial Senescence While Compromising Metabolic Activity and Vascular Function.
Anthracycline-based chemotherapy is a common treatment for cancer patients. Because it is delivered intravenously, endothelial cells are exposed first and to the highest concentrations, prior to diffusion to target cells. Not surprisingly, vascular dysfunction is a consequence of anthracycline therapy. While chemotherapy-induced endothelial damage at administration sites has been investigated, the effects of lower doses encountered by distant microvascular networks has not. The aim of this study was to investigate the impact of epirubicin, a widely used anthracycline, on healthy endothelial cells to elucidate its effects on microvascular physiology. Here, endothelial cells were briefly exposed to low doses of epirubicin to recapitulate levels in circulation following dilution in the blood and compound half-life in circulation. Both immediate and prolonged responses to treatment were assessed to determine changes in endothelial function. Epirubicin caused a decrease in proliferation and viability in hUVEC, with lower doses resulting in a senescent phenotype in a large proportion of cells, accompanied by a significant increase in pro-inflammatory cytokines and a significant decrease in metabolic activity. Epirubicin exposure also impaired endothelial function with delayed wound closure, reduced angiogenic potential and increased monolayer permeability downstream of VE-cadherin internalization. Primary lung endothelial cells obtained from epirubicin-treated mice similarly demonstrated reduced viability and functional impairment. In vivo, epirubicin treatment resulted in persistent reduction in lung vascular density and significantly increased infiltration of myeloid cells. Modulation of endothelial status and inflammatory tissue microenvironment observed in response to low doses of epirubicin may predict risk for long-term secondary pathologies associated with chemotherapy.


Structural characterization of solvent-based food preparation of jellyfish.
Jellyfish as a potential sustainable food material has recently gained increasing interest. However, with their soft gel-like texture and easy spoilage, it remains challenging to achieve desirable edible structures from jellyfish. The culinary preparation of jellyfish is a complex process and extends beyond conventional cooking methods. In this study, we investigate the transformation of jellyfish into crispy-like structures by manipulating their microstructural and mechanical properties through a solvent-based preparation. The study focuses on the use of "poor solvents", namely ethanol and acetone, and employs rheology measurements and quantitative microscopy techniques to analyze the effects of these solvents on the mechanical properties and microstructure of jellyfish. Our findings reveal that both ethanol and acetone lead to a significant increase in jellyfish hardness and deswelling. Notably, a micro-scale network is formed within the jellyfish matrix, and this network is then mechanically reinforced before a crispy-like texture can be obtained. Our study points to solvent polarity as also being a crucial factor for creating these effects and determines an upper polarity limit in the range of 12.2-12.9 MPa1/2 for added solvents, corresponding to approximately 60% of added ethanol or 70% of added acetone. Our study highlights that solvent-based preparation serves as a "reverse cooking" technique, where mechanical modification rather than traditional softening mechanisms are employed to stabilize and strengthen the microstructures and fibers of jellyfish. By elucidating the underlying mechanisms of solvent-induced stabilization, our findings may facilitate the development of innovative and sustainable culinary practices, paving the way for broader applications of jellyfish and other soft edible materials in the gastronomic landscape.


Emergency medical care following the great Hanshin-Awaji earthquake: practices and proposals (a report from a university hospital located in the damaged region).
The major earthquake, which hit the southern portion of Hyogo Prefecture, Japan, just before dawn on January 17, 1995, caused a tremendous amount of damage in a very short time. It killed 6,348 individuals, injured more than 33,000, destroyed about 170,000 houses, and left more than 300,000 people homeless. The central area of Kobe City was almost completely destroyed. Communication and transportation networks as well as other life lines were severed in many places. As a result, Kobe city was almost completely cut off from the outside world. This paper will outline how the emergency care unit in the Kobe University Hospital, located in the center of Kobe City, provided emergency care after the great Hanshin-Awaji earthquake, in the face of the many unfavorable conditions encountered in a major disaster. Based on our experience, we will also propose modifications for future emergency care systems coping with large-scale disasters.


Dual-responsive doxorubicin-loaded nanomicelles for enhanced cancer therapy.
The enhancement of tumor retention and cellular uptake of drugs are important factors in maximizing anticancer therapy and minimizing side effects of encapsulated drugs. Herein, a delivery nanoplatform, armed with a pH-triggered charge-reversal capability and self-amplifiable reactive oxygen species (ROS)-induced drug release, is constructed by encapsulating doxorubicin (DOX) in pH/ROS-responsive polymeric micelle. The surface charge of this system was converted from negative to positive from pH 7.4 to pH 6.8, which facilitated the cellular uptake. In addition, methionine-based system was dissociated in a ROS-rich and acidic intracellular environment, resulting in the release of DOX and α-tocopheryl succinate (TOS). Then, the exposed TOS segments further induced the generation of ROS, leading to self-amplifiable disassembly of the micelles and drug release. We confirms efficient DOX delivery into cancer cells, upregulation of tumoral ROS level and induction of the apoptotic capability in vitro. The system exhibits outstanding tumor inhibition capability in vivo, indicating that dual stimuli nano-system has great potential to function as an anticancer drug delivery platform.


Quality of consumer-targeted internet guidance on home firearm and ammunition storage.
Four storage practices protect against unintentional and/or self-inflicted firearm injury among children and adolescents: keeping guns locked (1) and unloaded (2) and keeping ammunition locked up (3) and in a separate location from the guns (4). Our aim was to mimic common Google search strategies on firearm/ammunition storage and assess whether the resulting web pages provided recommendations consistent with those supported by the literature. We identified 87 web pages by Google search of the 10 most commonly used search terms in the USA related to firearm/ammunition storage. Two non-blinded independent reviewers analysed web page technical quality according to a 17-item checklist derived from previous studies. A single reviewer analysed readability by US grade level assigned by Flesch-Kincaid Grade Level Index. Two separate, blinded, independent reviewers analysed deidentified web page content for accuracy and completeness describing the four accepted storage practices. Reviewers resolved disagreements by consensus. The web pages described, on average, less than one of four accepted storage practices (mean 0.2 (95% CL 0.1 to 0.4)). Only two web pages (2%) identified all four practices. Two web pages (2%) made assertions inconsistent with recommendations; both implied that loaded firearms could be stored safely. Flesch-Kincaid Grade Level Index averaged 8.0 (95% CL 7.3 to 8.7). The average technical quality score was 7.1 (95% CL 6.8 to 7.4) out of an available score of 17. There was a high degree of agreement between reviewers regarding completeness (weighted κ 0.78 (95% CL 0.61 to 0.97)). The internet currently provides incomplete information about safe firearm storage. Understanding existing deficiencies may inform future strategies for improvement.


Evidence for Seismogenic Hydrogen Gas, a Potential Microbial Energy Source on Earth and Mars.
The oxidation of molecular hydrogen (H2) is thought to be a major source of metabolic energy for life in the deep subsurface on Earth, and it could likewise support any extant biosphere on Mars, where stable habitable environments are probably limited to the subsurface. Faulting and fracturing may stimulate the supply of H2 from several sources. We report the H2 content of fluids present in terrestrial rocks formed by brittle fracturing on fault planes (pseudotachylites and cataclasites), along with protolith control samples. The fluids are dominated by water and include H2 at abundances sufficient to support hydrogenotrophic microorganisms, with strong H2 enrichments in the pseudotachylites compared to the controls. Weaker and less consistent H2 enrichments are observed in the cataclasites, which represent less intense seismic friction than the pseudotachylites. The enrichments agree quantitatively with previous experimental measurements of frictionally driven H2 formation during rock fracturing. We find that conservative estimates of current martian global seismicity predict episodic H2 generation by Marsquakes in quantities useful to hydrogenotrophs over a range of scales and recurrence times. On both Earth and Mars, secondary release of H2 may also accompany the breakdown of ancient fault rocks, which are particularly abundant in the pervasively fractured martian crust. This study strengthens the case for the astrobiological investigation of ancient martian fracture systems. Deep biosphere-Faults-Fault rocks-Seismic activity-Hydrogen-Mars. Astrobiology 16, 690-702.


A subpopulation of cardiomyocytes expressing alpha-skeletal actin is identified by a specific polyclonal antibody.
The NH(2)-terminal decapeptide of alpha-skeletal actin that contains a primary sequence specific for this isoform was used to raise a polyclonal antibody in rabbits. Using sequential affinity chromatography, we recovered from serum antibodies reacting exclusively with alpha-skeletal actin when tested by immunoblotting and immunofluorescence. Epitope mapping by means of competition assays with synthetic peptides indicated that the acetyl group and the first 9 amino acids are essential for specificity. The monospecific antibody was then used to investigate the distribution of alpha-skeletal actin in the myocardium of newborn and normal or hypertensive (with or without fibrotic areas) adult rats. Immunostaining of normal heart revealed that alpha-skeletal actin is diffusely distributed within practically all myocardial fibers of the newborn rat, whereas it is restricted to a small proportion of adult rat cardiomyocytes, which appear intensely stained. A correlation, albeit not complete, was found between the distribution of alpha-skeletal actin and beta-myosin heavy chain. During cardiac hypertrophy induced by aortic ligature between the renal arteries, the expressions of alpha-skeletal actin mRNA and protein were increased. The distribution of immunostaining had a focal pattern similar to that of normal adult rats, reactive fibers being more numerous and more intensely stained compared with normal myocardium. Positive fibers were particularly abundant at the periphery of fibrotic areas. Using this antibody, we have demonstrated for the first time the differential distribution of alpha-skeletal actin in heart tissues. Changes in the distribution of this isoform in hypertrophic heart provide new insight into the mechanisms by which the heart adapts to work overload. This antibody will prove useful in exploring the mechanisms of expression of alpha-skeletal actin and in defining its role in physiological and pathological situations.


[Cystic ureteritis. Presentation of a new case and review of the most recent national literature].
We report on a patient with this uncommon condition that presented without hematuria and in association with a rare abdominal and thoracic malformation known as situs inversus. A review of the literature focussing on recently reported cases in the Spanish literature revealed it to be a disease of unknown etiology whose pathogenesis is not well-established, clinical features unspecific, without treatment for the underlying cause, and is a radiologic diagnostic difficulty requiring a differential diagnosis from other filling defects in the urothelium.


Newly Developed Laparoscopic Needle Holder That Facilitates Knot Tying Makes Vaginal Cuff Suturing Easy in Single-Port Laparoscopic Hysterectomy.
To evaluate vaginal cuff closure times of a single-port laparoscopic hysterectomy using a newly developed Turkish-made laparoscopic needle holder (TMLNH) with a single-port laparoscopic hysterectomy using a laparoscopic needle holder with pistol handle (LNHPH). We retrospectively reviewed 68 patients who underwent single-port laparoscopic hysterectomy using a TMLNH (n = 38) or a LNHPH (n = 30). Patients' age, parity, body mass index, mean operating time, mean vaginal cuff suturing time, uterine weight, estimated blood loss, drop of hemoglobin level, return of bowel activity, hospital stay, conversion to multiport access, conversion to laparotomy, and postoperative and intraoperative outcomes were analyzed. The TMLNH group had a shorter operative time ( P < .001) and a shorter vaginal cuff suturing time ( P < .001) compared with the LNHPH group during a single-port laparoscopic hysterectomy. There was no difference in intraoperative and postoperative complications. The TMLNH facilitates vaginal cuff suturing and decreases operation time during a single-port laparoscopic hysterectomy. We proposed that the TMLNH is a promising technique for suturing and vaginal cuff closure in a single-port laparoscopic hysterectomy.


Principles-Focused Evaluation: A Promising Practice in the Evaluation of Continuing Professional Development.
Outcome-based evaluations still dominate in continuing professional development (CPD) despite the availability of evaluation approaches that address program processes and contexts. Our continued reliance on outcomes-based evaluation fails to respect the importance of complexity and the human element of program planning and implementation. Therefore, it is time that the field of CPD embrace complementary approaches to program evaluation that consider the complexity and maturity of programs and their contexts, while providing credible and relevant information to inform strategic decisions regarding the future of a program. Principles-focused evaluation provides a complement to traditional evaluation approaches through the articulation of a program's values that can be actioned. These "actionable values," known as principles, become the focus of the evaluation for the purposes of program decision-making. This paper describes how one CPD program, designed as a response to growing opioid-related harms, adopted a principles-focused evaluation to inform ongoing iteration of the program. The process used to design the principles, how the principles are informing the transportability of the program, and implications for CPD evaluation are discussed.


Unimolecular Photodynamic O2-Economizer To Overcome Hypoxia Resistance in Phototherapeutics.
Tumor hypoxia has proven to be the major bottleneck of photodynamic therapy (PDT) to clinical transformation. Different from traditional O2 delivery approaches, here we describe an innovative binary photodynamic O2-economizer (PDOE) tactic to reverse hypoxia-driven resistance by designing a superoxide radical (O2•-) generator targeting mitochondria respiration, termed SORgenTAM. This PDOE system is able to block intracellular O2 consumption and down-regulate HIF-1α expression, which successfully rescues cancer cells from becoming hypoxic and relieves the intrinsic hypoxia burden of tumors in vivo, thereby sparing sufficient endogenous O2 for the PDT process. Photosensitization mechanism studies demonstrate that SORgenTAM has an ideal intersystem crossing rate and triplet excited state lifetime for generating O2•- through type-I photochemistry, and the generated O2•- can further trigger a biocascade to reduce the PDT's demand for O2 in an O2-recycble manner. Furthermore, SORgenTAM also serves to activate the AMPK metabolism signaling pathway to inhibit cell repair and promote cell death. Consequently, using this two-step O2-economical strategy, under relatively low light dose irradiation, excellent therapeutic responses toward hypoxic tumors are achieved. This study offers a conceptual while practical paradigm for overcoming the pitfalls of phototherapeutics.


Aberrant presentation of HPA-reactive carbohydrates implies Selectin-independent metastasis formation in human prostate cancer.
To investigate the impact of prostate cancer cell surface glycosylation as part of the tumor cell-endothelial cell interaction in prostate cancer metastasis. Glycosyltransferase expression was profiled in metastasis-derived prostate cancer cell lines and compared with primary epithelium. Prostate cancer cells were examined for HPA- and selectin-binding and adhesion to endothelium. Spontaneous metastasis xenograft models were established to test the lectin HPA-binding sites as a marker of metastatic competence and to evaluate E-selectin-binding sites in vivo. The importance of selectins for metastasis formation was analyzed using Sele(-/-)/Selp(-/-) mice. The clinical relevance of HPA- and E-selectin-binding sites in prostate cancer was determined. Glycosyltransferases involved in the synthesis of common HPA-binding sites are downregulated in prostate cancer cells. An absence of HPA-reactive carbohydrates specifically indicates spontaneous metastatic spread of prostate cancer xenografts in vivo and a poor prognosis of patients with prostate cancer. HPA-binding sites decrease in lymph node metastases compared with corresponding primary tumors. Common selectin ligands are absent on prostate cancer cells, which do not adhere to recombinant selectins or endothelium under shear stress in vitro. Spontaneous metastasis formation is largely independent of selectins in vivo. E-selectin-binding sites are detectable in only 2% of patients with prostate cancer without prognostic significance. Prostate cancer is characterized by an inverse functional and prognostic importance of HPA-binding sites compared with other adenocarcinomas. Accordingly, this study surprisingly shows that the selectin-selectin ligand axis, which is essential for extravasation and thus metastasis formation in several malignancies, can be circumvented in prostate cancer.


Simultaneous detection of mercury(II) and silver(I) ions with picomolar sensitivity.
We develop a new method for the simultaneous detection of Hg(2+) and Ag(+) by integrating bifunctional strand displacement amplification and multiplexed short linear quencher-fluorophore probes. This method exhibits excellent specificity and high picomolar sensitivity, which is improved by up to 4 orders of magnitude compared to the current approaches for metal ion assay.


Characterization of a low-relative-molecular-mass prolyl 4-hydroxylase from the green alga Chlamydomonas reinhardii.
Prolyl 4-hydroxylase was partially purified and characterized from the unicellular green alga, Chlamydomonas reinhardii. This enzyme differed from all the animal and plant prolyl 4-hydroxylases studied so far in that its Mr was only about 40,000 by gel filtration, being thus less than one-sixth of those determined for the vertebrate and higher-plant enzymes. The algal enzyme did not hydroxylate to any significant extent chick-embryo protocollagen or triple-helical (Pro-Pro-Gly)10, whereas a low hydroxylation rate was found with denatured (Pro-Pro-Gly)10. Poly(L-proline), which is an effective inhibitor of the vertebrate enzymes but acts as a substrate for some higher-plant enzymes, was a good substrate. In the absence of poly(L-proline) the enzyme catalysed an uncoupled decarboxylation of 2-oxoglutarate. Studies of the Km values for the co-substrates and cofactors and the specificity of the 2-oxoglutarate requirement, as well as inhibition studies with selected 2-oxoglutarate analogues, suggested that the catalytic site of the algal enzyme is similar to, but not identical with, those of the vertebrate enzymes. The existence of distinct similarities was further demonstrated by an inhibition of the algal enzyme activity with a monoclonal antibody to the beta-subunit of human prolyl 4-hydroxylase. The amount of prolyl 4-hydroxylase activity in the algal cells was not altered by signals which recognize the presence or absence of the cell wall, as determined in studies on experimental cell-wall regeneration and wall-less mutants.


Amino acid sequence of bovine muzzle epithelial desmocollin derived from cloned cDNA: a novel subtype of desmosomal cadherins.
Desmosomes are cell-type-specific intercellular junctions found in epithelium, myocardium and certain other tissues. They consist of assemblies of molecules involved in the adhesion of specific cell types and in the anchorage of cell-type-specific cytoskeletal elements, the intermediate-size filaments, to the plasma membrane. To explore the individual desmosomal components and their functions we have isolated DNA clones encoding the desmosomal glycoprotein, desmocollin, using antibodies and a cDNA expression library from bovine muzzle epithelium. The cDNA-deduced amino-acid sequence of desmocollin (presently we cannot decide to which of the two desmocollins, DC I or DC II, this clone relates) defines a polypeptide with a calculated molecular weight of 85,000, with a single candidate sequence of 24 amino acids sufficiently long for a transmembrane arrangement, and an extracellular aminoterminal portion of 561 amino acid residues, compared to a cytoplasmic part of only 176 amino acids. Amino acid sequence comparisons have revealed that desmocollin is highly homologous to members of the cadherin family of cell adhesion molecules, including the previously sequenced desmoglein, another desmosome-specific cadherin. Using riboprobes derived from cDNAs for Northern-blot analyses, we have identified an mRNA of approximately 6 kb in stratified epithelia such as muzzle epithelium and tongue mucosa but not in two epithelial cell culture lines containing desmosomes and desmoplakins. The difference may indicate drastic differences in mRNA concentration or the existence of cell-type-specific desmocollin subforms. The molecular topology of desmocollin(s) is discussed in relation to possible functions of the individual molecular domains.


[Ventilation perfusion distribution: a program for personal computer (author's transl)].
Ventilation perfusion inequality, is analysed with the help of a program written in Basic language, easily implemented on a personal computer. For a gas exchange unit, the main equation describes a mass balance for oxygen, assuming absence of diffusion barrier. The use of a large number of these units allows for calculation of the resulting arterial PO2 in case of abnormal ventilation blood flow distribution. Several simulations are made to study the effect of local variations of VA/Q ratio, and oxygen inhalation upon arterial PO2.


ShrinkBayes: a versatile R-package for analysis of count-based sequencing data in complex study designs.
Complex designs are common in (observational) clinical studies. Sequencing data for such studies are produced more and more often, implying challenges for the analysis, such as excess of zeros, presence of random effects and multi-parameter inference. Moreover, when sample sizes are small, inference is likely to be too liberal when, in a Bayesian setting, applying a non-appropriate prior or to lack power when not carefully borrowing information across features. We show on microRNA sequencing data from a clinical cancer study how our software ShrinkBayes tackles the aforementioned challenges. In addition, we illustrate its comparatively good performance on multi-parameter inference for groups using a data-based simulation. Finally, in the small sample size setting, we demonstrate its high power and improved FDR estimation by use of Gaussian mixture priors that include a point mass. ShrinkBayes is a versatile software package for the analysis of count-based sequencing data, which is particularly useful for studies with small sample sizes or complex designs.


Association of lesion complexity following fibrinolytic administration with mortality in ST-elevation myocardial infarction.
Greater lesion complexity, according to the American College of Cardiology and American Heart Association, has been associated with decreased success rates of percutaneous coronary intervention. We hypothesized that greater lesion complexity after fibrinolytic administration for ST-segment elevation myocardial infarction would similarly be associated with increased mortality and other adverse events at 30 days. We studies 2,605 patients from the Thrombolysis In Myocardial Infarction 10B and 14, Integrilin and Tenecteplase in Acute Myocardial Infarction, ENTIRE, and FASTER studies. For all studies, angiographic outcomes were assessed immediately after fibrinolytic administration and clinical outcomes were assessed at 30 days. Greater lesion complexity was associated with poorer epicardial flow and decreased myocardial perfusion at 60 minutes and after percutaneous coronary intervention and with a higher risk of shock and mortality within 30 days. In a multivariate model, type C lesion complexity remained associated with an increased 30-day mortality rate.


Surveillance of the prevalence, antibiotic susceptibility, and genotypic characterization of invasive candidiasis in a teaching hospital in China between 2006 to 2011.
Invasive candidiasis is an important nosocomial infection associated with high mortality among immunosuppressive or critically ill patients. We described the incidence of invasive candidiasis in our hospital over 6 years and showed the antifungal susceptibility and genotypes of the isolated yeast. The yeast species were isolated on CHROMagar Candida medium and identified using an yeast identification card, followed by analysis of the D1/D2 domain of 26S rDNA. The susceptibilities of the isolates to flucytosine, amphotericin B, fluconazole, itraconazole, and voriconazole were tested using the ATB FUNGUS 3 system, and that to caspofungin was tested using E-test strips. C. albicans was genotyped using single-strand conformation polymorphism of CAI (Candida albicans I) microsatellite DNA combined with GeneScan data. From January 2006 to December 2011, a total of 259 isolates of invasive Candida spp. were obtained from 253 patients, among them 6 patients had multiple positive samples. Ninety-one stains were from blood and 168 from sterile fluids, accounting for 6.07% of all pathogens isolated in our hospital. Most of these strains were C. albicans (41.29% in blood/59.06% in sterile body fluids), followed by C. tropicalis (18.06%/25.72%), C. parapsilosis (17.42%/5.43%), C. glabrata (11.61%/3.99%) and other Candida spp. (11.61%/5.80%). Most Candida spp. were isolated from the ICU. The new species-specific CLSI candida MIC breakpoints were applied to these date. Resistance to fluconazole occurred in 6.6% of C. albicans isolates, 10.6% of C. tropicalis isolates and 15.0% of C. glabrata isolates. For the 136 C. albicans isolates, 54 CAI patterns were recognized. The C. albicans strains from blood or sterile body fluids showed no predominant CAI genotypes. C. albicans isolates from different samples from the same patient had the same genotype. Invasive candidiasis has been commonly encountered in our hospital in the past 6 years, with increasing frequency of non-C. albicans. Resistance to fluconazole was highly predictive of resistance to voriconazole. CAI SSCP genotyping showed that all C. albicans strains were polymorphic. Invasive candidiasis were commonly endogenous infection.


A Machine Learning Algorithm Predicting Acute Kidney Injury in Intensive Care Unit Patients (NAVOY Acute Kidney Injury): Proof-of-Concept Study.
Acute kidney injury (AKI) represents a significant global health challenge, leading to increased patient distress and financial health care burdens. The development of AKI in intensive care unit (ICU) settings is linked to prolonged ICU stays, a heightened risk of long-term renal dysfunction, and elevated short- and long-term mortality rates. The current diagnostic approach for AKI is based on late indicators, such as elevated serum creatinine and decreased urine output, which can only detect AKI after renal injury has transpired. There are no treatments to reverse or restore renal function once AKI has developed, other than supportive care. Early prediction of AKI enables proactive management and may improve patient outcomes. The primary aim was to develop a machine learning algorithm, NAVOY Acute Kidney Injury, capable of predicting the onset of AKI in ICU patients using data routinely collected in ICU electronic health records. The ultimate goal was to create a clinical decision support tool that empowers ICU clinicians to proactively manage AKI and, consequently, enhance patient outcomes. We developed the NAVOY Acute Kidney Injury algorithm using a hybrid ensemble model, which combines the strengths of both a Random Forest (Leo Breiman and Adele Cutler) and an XGBoost model (Tianqi Chen). To ensure the accuracy of predictions, the algorithm used 22 clinical variables for hourly predictions of AKI as defined by the Kidney Disease: Improving Global Outcomes guidelines. Data for algorithm development were sourced from the Massachusetts Institute of Technology Lab for Computational Physiology Medical Information Mart for Intensive Care IV clinical database, focusing on ICU patients aged 18 years or older. The developed algorithm, NAVOY Acute Kidney Injury, uses 4 hours of input and can, with high accuracy, predict patients with a high risk of developing AKI 12 hours before onset. The prediction performance compares well with previously published prediction algorithms designed to predict AKI onset in accordance with Kidney Disease: Improving Global Outcomes diagnosis criteria, with an impressive area under the receiver operating characteristics curve (AUROC) of 0.91 and an area under the precision-recall curve (AUPRC) of 0.75. The algorithm's predictive performance was externally validated on an independent hold-out test data set, confirming its ability to predict AKI with exceptional accuracy. NAVOY Acute Kidney Injury is an important development in the field of critical care medicine. It offers the ability to predict the onset of AKI with high accuracy using only 4 hours of data routinely collected in ICU electronic health records. This early detection capability has the potential to strengthen patient monitoring and management, ultimately leading to improved patient outcomes. Furthermore, NAVOY Acute Kidney Injury has been granted Conformite Europeenne (CE)-marking, marking a significant milestone as the first CE-marked AKI prediction algorithm for commercial use in European ICUs.


Can biomarkers help identify sepsis in adults?
Sepsis is increasing in incidence in the United States and is one of the most common causes of death in hospitalized patients. Sepsis affects different biochemical and immunologic pathways and can present variably. Despite efforts to unify definitions of sepsis, increase awareness, and improve treatment, mortality remains high. Because of sepsis's complex pathophysiology, diagnosis can be challenging. No diagnostic test is sensitive or specific enough to diagnose sepsis in isolation. However, three biomarkers-lactate, C-reactive protein, and procalcitonin-in combination with other diagnostics may help clinicians diagnose sepsis earlier, leading to better patient outcomes.


ptxD gene in combination with phosphite serves as a highly effective selection system to generate transgenic cotton (Gossypium hirsutum L.).
This report demonstrates the usefulness of ptxD/phosphite as a selection system that not only provides a highly efficient and simple means to generate transgenic cotton plants, but also helps address many of the concerns related to the use of antibiotic and herbicide resistance genes in the production of transgenic crops. Two of the most popular dominant selectable marker systems for plant transformation are based on either antibiotic or herbicide resistance genes. Due to concerns regarding their safety and in order to stack multiple traits in a single plant, there is a need for alternative selectable marker genes. The ptxD gene, derived from Pseudomonas stutzeri WM88, that confers to cells the ability to convert phosphite (Phi) into orthophosphate (Pi) offers an alternative selectable marker gene as demonstrated for tobacco and maize. Here, we show that the ptxD gene in combination with a protocol based on selection medium containing Phi, as the sole source of phosphorus (P), can serve as an effective and efficient system to select for transformed cells and generate transgenic cotton plants. Fluorescence microscopy examination of the cultures under selection and molecular analyses on the regenerated plants demonstrate the efficacy of the system in recovering cotton transformants following Agrobacterium-mediated transformation. Under the ptxD/Phi selection, an average of 3.43 transgenic events per 100 infected explants were recovered as opposed to only 0.41% recovery when bar/phosphinothricin (PPT) selection was used. The event recovery rates for nptII/kanamycin and hpt/hygromycin systems were 2.88 and 2.47%, respectively. Molecular analysis on regenerated events showed a selection efficiency of ~ 97% under the ptxD/Phi system. Thus, ptxD/Phi has proven to be a very efficient, positive selection system for the generation of transgenic cotton plants with equal or higher transformation efficiencies compared to the commonly used, negative selection systems.


Investigation of Turkish dentists' clinical attitudes and behaviors towards the COVID-19 pandemic: a survey study.
Currently, the whole world is under the threat of the COVID-19 pandemic, and dentists are at high risk. The aim of this study was to investigate what kind of precautions Turkish dentists take in dental clinics during the COVID-19 pandemic. The study population consisted of dentists in Turkey. An online questionnaire (23 questions-57 items) was sent to a sample of Turkish dentists from March 16 to March 20, 2020. The questionnaire comprised a series of questions about dentists' demographic characteristics, their concerns, and the measures taken in dental clinics against COVID-19. This study included a total of 1,958 Turkish dentists. A total of 1,274 (65.1%) were general dentists, and 684 (34.9%) were specialists. Five hundred twenty-two (26.7%) dentists attended an informational meeting on COVID-19. Of these dentists, 69.8% were aware of COVID-19 according to their self-assessed knowledge scores. More than 90% of the dentists were concerned about themselves and their families. Only 12% of the dentists wore an N95 mask. Although Turkish dentists took some precautionary measures, they did not take enough precautions to protect themselves, the dental staff, and other patients from COVID-19. As the number of COVID-19 cases increased, the measures taken slightly increased in dental clinics as well. Dentists are strongly recommended to take maximum precautions in the clinical setting. The guidelines about the COVID-19 pandemic should be sent to all dentists by the regional and national dental associations.


Mechanically controlled quantum interference in graphene break junctions.
The ability to detect and distinguish quantum interference signatures is important for both fundamental research and for the realization of devices such as electron resonators1, interferometers2 and interference-based spin filters3. Consistent with the principles of subwavelength optics, the wave nature of electrons can give rise to various types of interference effects4, such as Fabry-Pérot resonances5, Fano resonances6 and the Aharonov-Bohm effect7. Quantum interference conductance oscillations8 have, indeed, been predicted for multiwall carbon nanotube shuttles and telescopes, and arise from atomic-scale displacements between the inner and outer tubes9,10. Previous theoretical work on graphene bilayers indicates that these systems may display similar interference features as a function of the relative position of the two sheets11,12. Experimental verification is, however, still lacking. Graphene nanoconstrictions represent an ideal model system to study quantum transport phenomena13-15 due to the electronic coherence16 and the transverse confinement of the carriers17. Here, we demonstrate the fabrication of bowtie-shaped nanoconstrictions with mechanically controlled break junctions made from a single layer of graphene. Their electrical conductance displays pronounced oscillations at room temperature, with amplitudes that modulate over an order of magnitude as a function of subnanometre displacements. Surprisingly, the oscillations exhibit a period larger than the graphene lattice constant. Charge-transport calculations show that the periodicity originates from a combination of the quantum interference and lattice commensuration effects of two graphene layers that slide across each other. Our results provide direct experimental observation of a Fabry-Pérot-like interference of electron waves that are partially reflected and/or transmitted at the edges of the graphene bilayer overlap region.


Effects of ellagic acid pretreatment on renal functions disturbances induced by global cerebral ischemic-reperfusion in rat.
Global cerebral ischemia-reperfusion (GCIR) causes disturbances in brain functions as well as other organs such as kidney. Our aim was to evaluate the protective effects of ellagic acid (EA) on certain renal disfunction after GCIR. Adult male Wistar rats (n=32, 250-300 g) were used. GCIR was induced by bilateral vertebral and common carotid arteries occlusion (4-VO). Animal groups were: 1) received DMSO/saline (10%) as solvent of EA, 2) solvent + GCIR, 3) EA + GCIR, and 4) EA. Under anesthesia with ketamine/xylazine, GCIR was induced (20 and 30 min respectively) in related groups. EA (100 mg/kg, dissolved in DMSO/saline (10%) or solvent was administered (1.5 ml/kg) orally for 10 consecutive days to the related groups. EEG was recorded from NTS in GCIR treated groups. Our data showed that: a) EEG in GCIR treated groups was flattened. b) GCIR reduced GFR (P<0.01) and pretreatment with EA attenuated this reduction. c) BUN was increased by GCIR (P<0.001) and pretreatment with EA improved the BUN to normal level. d) Serum creatinine concentration was elevated by GCIR but not significantly, however, in EA+GCIR group serum creatinine was reduced (P<0.05). e) GCIR induced proteinuria (P<0.05) but, EA was unable to reduced proteinuria. Results indicate that GCIR impairs certain renal functions and EA as an antioxidant can improve these functions. Our results suggest the possible usefulness of ellagic acid in patients with brain stroke.


Axial Plane Deformity: How to Avoid It and How to Correct It.
Malreductions in the axial plane (ie, length and rotation) are common when managing long bone fractures. Careful attention to detail during the initial treatment can prevent these malreductions. Various fluoroscopy-based techniques exist for the prevention of malrotation and limb-length discrepancy during surgery for fracture. If malreductions do occur, a systematic clinical and radiographic evaluation can provide the necessary information to correct rotational malreduction and limb-length discrepancy.


Protective effect of Zingiber officinale extract on rat testis after cyclophosphamide treatment.
Decreasing the side effects of chemotherapy in testis has been the subjects of many studies. In this study, the protective effects of Zingiber officinale extract on rat testis were investigated after chemotherapy with cyclophosphamide. Histological and biochemical parameters were compared in cyclophosphamide-treated rats with or without ginger extract intake. Wistar male rats were randomly divided into four groups each 10. The control group received a single injection of 1 ml isotonic saline intraperitoneally. The Cyclophosphamide (CP) group received a single dose of cyclophosphamide (100 mg kg(-1) BW) intraperitoneally. CP + 300 and CP + 600 groups received orally 300 or 600 mg of ginger extract, respectively, for a period of 6 weeks after cyclophosphamide injection. The morphologic and histological structure of the testis was compared in different groups of the rats. Also, factors like malondialdehyde, reactive oxygen species, total antioxidant capacity and testosterone level were assessed in blood serum as well. Our results showed that although ginger extract could not change testis weight, malondialdehyde (MDA) and ROS, but antioxidant and testosterone levels in serum were increased significantly. Also, an obvious improved histological change was seen in CP + 300 and CP + 600 groups in comparison with CP group. These protective effects of ginger on rat testis after cyclophosphamide treatment could be attributed to the higher serum level of antioxidants.


Effect of the presence of orthodontic brackets on intraoral scans.
The need for intraoral scanning in the presence of brackets has increased for monitoring tooth movement during orthodontic treatment. The purpose of this study was to evaluate the effect of orthodontic brackets bonded to tooth surfaces on intraoral scans. Intraoral scans were performed in 30 patients using both iTero and Trios scanners before and after bonding of the brackets. The two sets of intraoral scans of each patient and intraoral scans with and without brackets were superimposed using a best-fit algorithm, and three-dimensional (3D) surface analysis was performed. In each superimposition, discrepancies in the 3D axes and arch-width measurements in the incisor and molar regions were compared. In addition, the range of distortion around the brackets was evaluated on the cross sections of each superimposition. The overall discrepancies between the intraoral scans with and without brackets were within 0.30 mm. The arch-width discrepancies in the molar region were greater than those in the incisor region, but the differences were not statistically significant (P = .972 for iTero; P = .960 for Trios). The cross sections of the superimposed intraoral scans with and without brackets showed that the deviations were within 0.40 mm in the horizontal section and within 0.35 mm in the vertical section around the brackets. The results of this study indicate that the accuracy of intraoral scans, even in the presence of brackets, is clinically acceptable, and the regions beyond 0.50 mm around the brackets should be used for superimposition on images without brackets.


[Chronic intestinal pseudo-obstruction due to intestinal neuronal dysplasia type B (IND B), concerning one case].
Intestinal neuronal dysplasia type B (IND B) is an infrequent disease due to hyperplasia of the parasympathetic submucous plexus which causes alteration of intestinal motility, giving rise to symptoms of constipation and subocclusive manifestations. The disease is difficult to diagnose. It requires high clinical suspicion and should include differential diagnosis of patients with repeated subocclusive manifestations in order to make an early and correct diagnosis and avoid complications derived from unnecessary surgery that worsens the prognosis. We present the case of a 33-year-old Moroccan male who was admitted to our hospital on 2 occasions in 11 months, requiring total parenteral nutrition (TPN) for five months. The immunohistochemical analysis of the ileostomy and colostomy stoma led to a diagnosis of IND B. Eighteen months later, the patients is leading a normal life and has recovered the 25 kilos lost following the dietary indications and with the enzymatic supplements.


Arrangement of subunits in microribbons from Giardia.
Ultrasound has been used to disperse the cytoplasm of Giardia muris and Giardia duodenalis trophozoites, releasing disk cytoskeletons for negative staining and study by electron microscopy. Sonication also breaks down the corss-bridges uniting microribbons in disks. Individual ribbons and small bundles of these structures, are found in these preparations and have been imaged both from their edges and in flat face view. The outer layers of ribbons are 2 sheets of regularly arranged globular subunits, held apart by a fibrous inner core. The axial repeat of the microribbon is 15 nm, which is also the distance separating cross-bridge sites along ribbons. Pronounced striping at this interval is a feature of ribbon faces where they are joined in bundles. Subunits in the outer layer are arranged in vertical protofilaments that are set orthogonally to the long axis of the ribbon. Protofilaments bind tannic acid and are seen clearly in sectioned ribbons. Three protofilaments fit into the 15-nm longitudinal spacing. Optical diffraction patterns from ribbon images are dominated by orders of the 15-nm periodicity, including the third-order reflexions expected from protofilaments spacings. Fourth-order reflexions indicate that the ribbon core may also be structured. Ribbon face images give rise to a strong 4-nm layer line, corresponding to the vertical spacing of subunits in protofilaments. Neighbouring protofilaments are staggered by about 0.67 nm. The lattices found in ribbons are consistent with studies of cytoskeleton composition.


Generation of leukotriene C4, leukotriene B4, and prostaglandin D2 by immunologically activated rat intestinal mucosa mast cells.
Mucosal mast cells (MMC) were isolated from the intestine of Nippostrongylus brasiliensis-infected rats and then activated with Ag or with anti-IgE in order to assess their metabolism of arachidonic acid to leukotriene (LT) C4, LTB4, and prostaglandin D2 (PGD2). After challenge of MMC preparations of 19 +/- 1% purity with five worm equivalents of N. brasiliensis Ag, the net formation of immunoreactive equivalents of LTC4, LTB4, and PGD2 was 58 +/- 8.3, 22 +/- 4.5, and 22 +/- 3.4 ng/10(6) mast cells, respectively (mean +/- SE, n = 7). When MMC preparations of 56 +/- 9% purity were activated by Ag, the net generation of immunoreactive equivalents of LTC4, LTB4, and PGD2/10(6) MMC was 107 +/- 15, 17 +/- 5.4, and 35 +/- 18 ng, respectively. These data indicate that the three eicosanoids originated from the MMC rather than from a contaminating cell. Analysis by reverse phase HPLC of the C-6 sulfidopeptide leukotrienes present in the supernatants of the activated MMC preparations of lower purity revealed LTC4, LTD4, and LTE4. In a higher purity MMC preparation only LTC4 was present, suggesting that other cell types in the mucosa are able to metabolize LTC4 to LTD4 and LTE4. The release of histamine and the generation of eicosanoids from intestinal MMC and from peritoneal cavity-derived connective tissue-type mast cells (CTMC) isolated from the same N. brasiliensis-infected rats were compared. When challenged with anti-IgE, these MMC released 165 +/- 41 ng of histamine/10(6) mast cells, and generated 29 +/- 3.6, 12 +/- 4.2, and 4.7 +/- 1.0 ng (mean +/- SE, n = 3) of immunoreactive equivalents of LTC4, LTB4, and PGD2/10(6) mast cells, respectively. In contrast, CTMC isolated from the same animals and activated with the same dose of anti-IgE released approximately 35 times more histamine (5700 +/- 650 ng/10(6) CTMC), generated 7.5 +/- 2.3 ng of PGD2/10(6) mast cells, and failed to release LTC4 or LTB4. These studies establish, that upon immunologic activation, rat MMC and CTMC differ in their quantitative release of histamine and in their metabolism of arachidonic acid to LTC4 and LTB4.


Lessons from a transplantation of zebra mussels into a small urban river: An integrated ecotoxicological assessment.
It is often difficult to evaluate the level of contamination in small urban rivers because pollution is mainly diffuse, with low levels of numerous substances. The use of a coupled approach using both chemical and biological measurements may provide an integrated evaluation of the impact of micro-pollution on the river. Zebra mussels were transplanted along a metal and organic pollution gradient in spring 2008. For two months, mussels and water samples were collected from two sites every two weeks and analyzed for metal and PAH content as well as water physicochemical parameters. Diffusive gradients in thin film (DGT) were also used to assess levels of labile metals. Exposure of mussels to contaminants and potential impact were evaluated using physiological indices and various biomarkers including condition index (CI), defense mechanisms (glutathione-S-transferase: GST), digestive enzymes (amylase and cellulase) and genotoxicity (micronucleus test: MN and comet assay: CA). For most contaminants, the water contamination was significantly higher downstream. Bioaccumulation in zebra mussels was related to water contamination in the framework of the biodynamic model, which allowed us to take into account the biological dilution that was caused by the growth of soft tissue downstream. Thus, metal influxes were on average two times higher downstream than upstream in particular for Zn, Cr, Cu and Cd. Significant differences in condition index were observed (final CI was 0.42 ± 0.03 downstream and 0.31 ± 0.03 upstream) reflecting a better food availability downstream. Moreover a significant decrease of GST activity and digestive enzymes activity in the cristalline style was observed downstream. Interpreting this decrease requires considering not only micro-pollution but also the trophic status related to the water's physicochemistry. The MN test and the CA on gill cells highlighted genotoxicity in mussels transplanted downstream compared to upstream.


Effect of interleukin-4 on orthodontic tooth movement and associated root resorption.
Interleukin-4 (IL-4) is a recognized immunomodulatory cytokine that regulates bone homeostasis. However, the influence of IL-4 on orthodontic tooth movement (OTM) and subsequent root resorption is still unknown. Therefore, the purpose of this study was to investigate the effect of IL-4 on tooth movement and its associated root resorption in a mouse model. The maxillary first molars of four male mice for each experimental group were subjected to mesial force by a nickel titanium coil spring for 12 days. Control mice were not given appliances and injections. Varying doses of IL-4 were injected locally, adjacent to the first molar. Two sets of experiments were designed. The first set was composed of three groups: the control, treatment with phosphate-buffered saline (PBS), or 1.5 µg/day of IL-4. The second set was composed of five groups: the control, treatment with 0 (PBS only), 0.015, 0.15, or 1.5 µg/day of IL-4. The distance of OTM was measured and tartrate-resistant acid phosphatase positive cells along the loaded alveolar bone and root surface were identified. The root resorption associated with OTM was evaluated by a scanning electron microscope. The amount of OTM and the number of osteoclasts were significantly decreased in the IL-4-treated mice. Moreover, IL-4 significantly suppressed force-induced odontoclasts and root resorption. IL-4 inhibits tooth movement and prevents root resorption in the mouse model. These results suggest that IL-4 could be used as a useful adjunct to regulate the extent of OTM and also to control root resorption.