Endoplasmic reticulum membrane potassium channel dysfunction in high fat diet induced stress in rat hepatocytes.
In a previous study we reported the presence of a large conductance K(+) channel in the membrane of endoplasmic reticulum (ER) from rat hepatocytes. The channel open probability (Po) appeared voltage dependent and reached to a minimum 0.2 at +50 mV. Channel activity in this case was found to be totally inhibited at ATP concentration 2.5 mM, glibenclamide 100 µM and tolbutamide 400 µM. Existing evidence indicates an impairment of endoplasmic reticulum functions in ER stress condition. Because ER potassium channels have been involved in several ER functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the ER potassium channel function is altered in a high fat diet model of ER stress. Male Wistar rats were made ER stress for 2 weeks with a high fat diet. Ion channel incorporation of ER stress model into the bilayer lipid membrane allowed the characterization of K(+) channel. Our results indicate that the channel Po was significantly increased at voltages above +30 mV. Interestingly, addition of ATP 7.5 mM, glibenclamide 400 µM and tolbutamide 2400 µM totally inhibited the channel activities, 3-fold, 4-fold and 6-fold higher than that in the control groups, respectively. Our results thus demonstrate a modification in the ER K(+) channel gating properties and decreased sensitivity to drugs in membrane preparations coming from ER high fat model of ER stress, an effect potentially linked to a change in ER K(+) channel subunits in ER stress condition. Our results may provide new insights into the cellular mechanisms underlying ER dysfunctions in ER stress.


Surgical management of congenital malrotation presenting in adulthood.
Intestinal malrotation is characterised by positional and congenital fixation abnormalities resulting from a failure in embryonic development in the normal 270° rotation around the axis of the superior mesenteric artery. Intestinal malrotation is primarily thought to affect neonates with an incidence of 1 in 500, however, only 1 in 6000 live births are symptomatic, and these usually present within the first month of life in 40% of cases and within the first year in over 5% of cases as an obstructive pathology or volvulus. In adults, however, the incidence has been documented at 0.2%. These patients usually present with postprandial symptoms that are intermittent such as bilious emesis, abdominal pain and malabsorption. Rarely, adults with congenital malrotation may present with acute obstruction due to volvulus, however, less than 100 adult cases are described in the literature. A high index of suspicion is required to identify cases of malrotation in the adult patient which leads to delays in diagnosis and therefore increases in morbidity can be seen.


Mechanisms of Coronary Artery Spasm.
Recent clinical trials have highlighted that percutaneous coronary intervention in patients with stable angina provides limited additional benefits on top of optimal medical therapy. This has led to much more attention being paid to coronary vasomotion abnormalities regardless of obstructive or non-obstructive arterial segments. Coronary vasomotion is regulated by multiple mechanisms that include the endothelium, vascular smooth muscle cells (VSMCs), myocardial metabolic demand, autonomic nervous system and inflammation. Over the years, several animal models have been developed to explore the central mechanism of coronary artery spasm. This review summarises the landmark studies on the mechanisms of coronary vasospasm demonstrating the central role of Rho-kinase as a molecular switch of VSMC hypercontraction and the important role of coronary adventitial inflammation for Rho-kinase upregulation in VSMCs.


BAY 41-4109 has multiple effects on Hepatitis B virus capsid assembly.
Here we report the effect of a heteroaryldihydropyrimidine (HAP) antiviral compound, BAY 41-4109, on Hepatitis B virus (HBV) capsid assembly and on preformed HBV capsids. The HBV capsid is an icosahedral complex of 120 capsid protein dimers. BAY41-4109 inhibits virus production in vivo by a mechanism that targets the viral capsid. We found that BAY 41-4109 was able to both accelerate and misdirect capsid assembly in vitro. As little as one HAP molecule for every five HBV dimers was sufficient to induce formation of non-capsid polymers. Unlike the related molecule HAP-1 (Stray et al., Proc. Natl. Acad. Sci. USA 102:8138-43, 2005), no stable assembly intermediates were observed in assembly reactions with BAY 41-4109, indicating that accelerated assembly by BAY 41-4109 was still kinetically regulated by the nucleation rate. Preformed capsids were stabilized by BAY 41-4109, up to a ratio of one inhibitor molecule per two dimers. However, at BAY 41-4109:dimer ratios of 1:1 and greater, capsids were destabilized to yield very large non-capsid polymers. These data suggest the existence of two functionally distinguishable classes of drug-binding sites on HBV capsids. Occupation of the first class of site stabilizes capsid, while binding at the second class requires or induces structural changes that cannot be tolerated without destabilizing the capsid. Our data suggest that HAP compounds may inhibit virus replication by inducing assembly inappropriately and, when in excess, by misdirecting assembly decreasing the stability of normal capsids.


Selective cyclooxygenase-2 inhibition prevents bone resorption.
The aim of the present work was to evaluate the effect of a selective cyclooxygenase-2 (COX-2) inhibitor (meloxicam) on the alveolar bone loss progression in experimentally induced periodontitis. Forty (40) Wistar rats were separated into 8 experimental groups (n = 5). Cotton ligatures were placed at the gingival margin level of the lower right first molars of some rats. Four groups were treated for 5 or 15 days with an oral dose of 15 mg/kg of body weight/day of the selective COX-2 inhibitor. The other groups were used as positive control (sham) or negative control in each experimental period. Standardized digital radiographs were taken after sacrifice at 5 and 15 days to measure the amount of bone loss at the mesial root surface of the first molar tooth in each rat. The treatment with meloxicam did not induce weight alteration or other visible systemic manifestations. One way analysis of variance (ANOVA) indicated that groups treated with meloxicam, after 5 days, had significantly less alveolar bone loss (p < 0.05) when compared with control groups. On the other hand, no significant differences in bone loss were observed after 15 days of treatment with meloxicam. These data provide evidence that systemic therapy with meloxicam can modify the progression of experimentally induced periodontitis in rats during the initial experimental period.


Evidence for decreased activity of guanine nucleotide binding protein in adenylate cyclase of cell membranes in human ACTH-unresponsive adrenocortical carcinoma.
The present investigation was performed in order to study the properties of abnormal membrane function related to ACTH receptor-adenylate cyclase system interaction in human ACTH-unresponsive adrenocortical cancer. Two tissues of adrenocortical cancer obtained from a patient with Cushing's syndrome (CS) and a case presenting no abnormal endocrinological findings (NF) were used for in vitro studies, comparing with three normal adrenal tissues. The addition of ACTH alone and ACTH plus 10(-6) M GppNHp did not enhance the adenylate cyclase (AC) activity in the CS and NF tissues. Relative insensitivity of AC to GTP, GppNHp, and cholera toxin was observed for the NF tissue, while the rate of response to GppNHp for the CS tissue which also showed relative insensitivity to GTP and cholera toxin was similar to that for the normal tissues. Forskolin which is reported to directly activate the catalytic unit of the AC complex increased the AC activity of both CS and NF tissues as well as that of the normal tissues. Therefore, the function of the catalytic unit itself may be rather well preserved in these tumor tissues. These results suggest that the lack of ACTH receptor at the cell membrane surface might be responsible for ACTH-unresponsiveness in the CS tissue, although an accelerated degradation of GTP could contribute to decreased activity of GTP-binding protein.(ABSTRACT TRUNCATED AT 250 WORDS)


Emerging histological and serological biomarkers in oral squamous cell carcinoma: Applications in diagnosis, prognosis evaluation and personalized therapeutics (Review).
Oral squamous cell carcinoma (OSCC) is the most common malignancy of the oral cavity and accounts for >90% of all oral cancers. Despite advances in diagnostic procedures and therapeutic interventions, overall survival has not improved significantly in recent decades, primarily due to late diagnosis, locoregional recurrence and treatment resistance. Identifying reliable biomarkers for early detection, prognosis evaluation and treatment response prediction is critical for improving clinical outcomes in patients with OSCC. In the present review, the prognostic and predictive utility of circulating biomarkers, such as circulating tumour cells, serological biomarkers and histological and genetic biomarkers, were explored in the context of OSCC. In addition, the potential role of immune checkpoints in the treatment of OSCC was highlighted and the rapidly evolving field of liquid biopsy and its potential to revolutionize diagnosis, prognosis evaluation and treatment were examined. The existing evidence for the clinical utility of these biomarkers was critically evaluated and the challenges and limitations associated with their introduction into routine clinical practice were addressed. In conclusion, the present review highlights the promising role of biomarkers in improving the current understanding of the pathogenesis of OSCC and offers potential avenues for improving patient care through personalized medicine approaches.


Associations between sexting motivations and consequences among adolescent girls.
Approximately 15% of adolescent girls in the United States have engaged in sexting. Although sexting frequency is similar across genders, adolescent girls report more negative consequences. To date, the majority of sexting research focuses on demographic and behavioral predictors of sexting frequency or onset and there is limited research on the associations between different sexting motivations and consequences. This cross-sectional study draws upon approach-avoidance motivation theory to examine how different sexting motivations serve as risk and protective factors related to negative sexting consequences and which motivations promote more positive experiences. A sample of 200 cisgender girls, 14-18 years, diverse with respect to race/ethnicity and geographical region, who had sexted a male recipient in the past year completed an online survey. Regression analyses indicated that avoidance motivations sexting in response to peer pressure and popularity and sexting in response to male coercion were risk factors for negative sexting consequences. Sexual subjectivity (sexual body-esteem, entitlement to sexual pleasure, and sexual self-reflection) was a protective factor against negative sexting consequences and, along with sexting for sexual or romantic reasons, an approach motivation, was associated with experiencing more positive sexting consequences. These findings support previous recommendations that schools incorporate ways to counter pressured sexting into existing cyberbullying or dating violence curricula and also align with a positive sexual development framework that acknowledges the importance of consensual and healthy sexual experiences during adolescence that minimize risks and vulnerabilities.


Comparative effects of vecuronium and pancuronium on release of lactate dehydrogenase in rat isolated diaphragm, liver, kidney and heart.
The comparative effects of two muscle relaxants, namely pancuronium and vecuronium, on the release of intracellular lactate dehydrogenase (LDH), released from four different types of tissues, namely, the heart, liver, kidney and diaphragm, were studied in the rat in vitro. The LDH and its leakage into extracellular space, was used as an indicator for cellular membrane damage, and the aim was to see if the two muscle relaxants enhanced the release of LDH, and hence, by implication, caused adverse effects, i.e., damage to cell membrane. The total amount of LDH, the neat (LDH), and the increase in LDH release caused by different concentrations of the two muscle relaxants were measured using spectrophotometric determination at 340 nm. The results showed that both muscle relaxants, in low concentrations (0.32 or 0.34 microM, a concentration which is close to a clinical dose of 0.1 mg/ml), did not significantly enhance the LDH release from any of the 4 different types of tissues studied. However, in concentrations of 10-130 times the clinical dose, both drugs significantly enhanced the LDH release in all the 4 tissues, with pancuronium being more effective than vecuronium. In addition, the diaphragm and kidney were most affected, whereas the heart and liver being the least affected. The clinical relevance and/or implications of these comparative effects are discussed, and the results are compared to those previously reported by other workers. Pancuronium and vecuronium are among the non-depolarising neuromuscular blocking drugs currently-used in clinical anaesthesia.(ABSTRACT TRUNCATED AT 250 WORDS)


Lactose load diet effect in rats.
Weanling and young adult rats were fed diets containing lactose (L) up to 50 g per 100 g diet for 15 days. The growth rats variation (W), fecal pH, net protein ratio (NPR) and protein efficiency ratio (PER) were determined. In weanling as well as in young adult rats an impairment of L was only detected for higher levels (greater than 20%), and diarrhea occurred only at 50%. The NPR and PER were partially effected by L because of the stimulation of appetite between 1 and 5 g%. The results for 10 and 20 g% of L were not different from controls. It was concluded that rats are not intolerant to levels of L less than or equal to 20%. The evaluation of protein quality in presence of L must be conducted with adapted methodology.


Opportunities and Efficiencies in Building a New Service Desk Model.
In July 2015, the Health Sciences and Human Services Library (HS/HSL) at the University of Maryland, Baltimore (UMB), merged its reference and circulation services, creating the Information Services Department and Information Services Desk. Designing the Information Services Desk with a team approach allowed for the re-examination of the HS/HSL's service model from the ground up. With the creation of a single service point, the HS/HSL was able to create efficiencies, improve the user experience by eliminating handoffs, create a collaborative team environment, and engage information services staff in a variety of new projects.


Metabolic effects of exhaustive training of athletes.
Sixteen athletes (11 men, 5 women), averaging 21 years of age, were studied before and after four weeks of daily exhaustive exercise (six days/week) during an endurance training course. In comparing blood chemistries before and after training, concentrations of blood glucose, total serum lipids, serum triglycerides, and serum cholesterol were significantly reduced; serum free fatty acid ( SFFA ) level was significantly increased; and serum protein and serum phospholipid concentrations remained unchanged. It was concluded that exhaustive training produces reduced blood glucose (but not clinically significant hypoglycemia) with increased fat utilization as a result of depletion of carbohydrate storage and that such training reduces the resting levels of serum cholesterol and serum triglycerides. The increased hematocrit, serum Na+, and serum K+ concentrations observed were presumably due to plasma water loss from excessive perspiration. Concentrations of blood urea nitrogen (BUN) and serum glutamic-oxaloacetic transaminase (SGOT) were increased significantly; serum glutamic-pyruvic transaminase (SGPT) and serum creatinine showed no significant changes. None of the athletes showed evidences of water-electrolyte deficiency syndrome, renal dysfunction, or liver cell damage, despite a persistent mild degree of dehydration and catabolic state noted after training.


Patent Foramen Ovale Closure in Obstructive Sleep Apnea Improves Blood Pressure and Cardiovascular Function.
Obstructive sleep apnea (OSA) is a frequent syndrome characterized by intermittent hypoxemia and increased prevalence of arterial hypertension and cardiovascular morbidity. In OSA, the presence of patent foramen ovale (PFO) is associated with increased number of apneas and more severe oxygen desaturation. We hypothesized that PFO closure improves sleep-disordered breathing and, in turn, has favorable effects on vascular function and arterial blood pressure. In 40 consecutive patients with newly diagnosed OSA, we searched for PFO. After initial cardiovascular assessment, the 14 patients with PFO underwent initial device closure and the 26 without PFO served as control group. Conventional treatment for OSA was postponed for 3 months in both groups, and polysomnographic and cardiovascular examinations were repeated at the end of the follow-up period. PFO closure significantly improved the apnea-hypopnea index (ΔAHI -7.9±10.4 versus +4.7±13.1 events/h, P=0.0009, PFO closure versus control), the oxygen desaturation index (ΔODI -7.6±16.6 versus +7.6±17.0 events/h, P=0.01), and the number of patients with severe OSA decreased significantly after PFO closure (79% versus 21%, P=0.007). The following cardiovascular parameters improved significantly in the PFO closure group, although remained unchanged in controls: brachial artery flow-mediated vasodilation, carotid artery stiffness, nocturnal systolic and diastolic blood pressure (-7 mm Hg, P=0.009 and -3 mm Hg, P=0.04, respectively), blood pressure dipping, and left ventricular diastolic function. In conclusion, PFO closure in OSA patients improves sleep-disordered breathing and nocturnal oxygenation. This translates into an improvement of endothelial function and vascular stiffening, a decrease of nighttime blood pressure, restoration of the dipping pattern, and improvement of left ventricular diastolic function. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01780207.


A modified rabbit model of reperfused myocardial infarction for cardiac MR imaging research.
We sought to obtain a rabbit myocardial infarction (MI) model for research with cardiac magnetic resonance imaging (cMRI) by overcoming a few technical difficulties. A novel endotracheal method was developed for intubation and ventilation. Fourteen rabbits were divided into group-1 (n = 8) with open-chest occlusion of left circumflex coronary artery and closed-chest reperfusion, and group-2 (n = 6) of non-ischemic control; and received ECG-triggered cMRI with delayed contrast enhancement (DE-cMRI) at a 1.5 T clinical scanner. The MI areas in group-1 were morphometrically compared between DE-cMRI and histochemically stained specimens. Left ventricular (LV) functions were compared between two groups.The success rate of intubation and reperfused MI was 8/8 and 6/8, respectively. Global and regional LV functions significantly decreased in group-1 as evidenced by significant hypokinesis of lateral LV-wall and wall thickening (P \ 0.001). Mean MI-area was 19.41 +/- 21.92% on DE-cMRI and 19.10 +/- 22.61% with histochemical staining (r = 0.985). Global MI-volume was 17.92 +/- 7.42% on DE-cMRI and 16.62 +/- 7.16% with histochemistry (r = 0.994). The usefulness of this model was successfully tested for assessing a new contrast agent. The present rabbit MI model may offer a practical platform for more translational research using clinical MRI-facilities.


Asthma, Food Allergy, and How They Relate to Each Other.
The association between atopic diseases is well known, and previous research has shown that having one atopic disease can predispose to having another. The link between asthma and food allergy has been well researched, but the exact relationship between the two atopic conditions is not fully understood. Food allergic infants are at increased risk for the development of asthma and are at risk of food-induced asthmatic episodes and also anaphylaxis. Having a diagnosis of both food allergy and asthma has also been shown to have an effect on the severity of a patient's disease including being at greater risk of severe asthmatic episodes. Therefore, understanding the relationship between these two conditions in order to treat and manage these children safely is crucial to clinicians.


MANAGEMENT OF ENDOCRINE DISEASE: Diagnostic and therapeutic approach of tall stature.
Tall stature is defined as a height of more than 2 standard deviations (s.d.) above average for same sex and age. Tall individuals are usually referred to endocrinologists so that hormonal disorders leading to abnormal growth are excluded. However, the majority of these patients have familial tall stature or constitutional advance of growth (generally associated with obesity), both of which are diagnoses of exclusion. It is necessary to have familiarity with a large number of rarer overgrowth syndromes, especially because some of them may have severe complications such as aortic aneurysm, thromboembolism and tumor predisposition and demand-specific follow-up approaches. Additionally, endocrine disorders associated with tall stature have specific treatments and for this reason their recognition is mandatory. With this review, we intend to provide an up-to-date summary of the genetic conditions associated with overgrowth to emphasize a practical diagnostic approach of patients with tall stature and to discuss the limitations of current growth interruption treatment options.


Attachment orientations and psychological adjustment of parents of children with cancer: A matched-group comparison.
To investigate the impact of childhood cancer on parents' adult attachment, social support, marital adjustment, anxiety, and depression. 30 parents of children with childhood cancer and 30 matched controls completed the following questionnaires: Experiences in Close Relationships-Revised, Dyadic Adjustment Scale-4, Multidimensional Scale of Perceived Social Support, State-Trait Anxiety Inventory - form Y, and Beck Depression Inventory. Parents of children with childhood cancer had a significantly lower dyadic adjustment than controls, and higher levels of insecure-avoidant attachment, state anxiety, and depression. It is important for health-care personnel to take into account these parents' propensity to show increased levels of avoidant attachment during children's treatment to foster effective communication and supportive relationships between clinicians, pediatric patients, and parents.


Photoperiodic signalling through the melatonin receptor turns full circle.
Photoperiod exerts profound influence on the physiology of mammals through the action of melatonin on the neuroendocrine system. Over the last 20 years, studies have moved away from a melatonin receptor-focused approach to understanding how photoperiod regulates neuroendocrine activity through studies of downstream effects on gene expression. This paper reviews the recent progress made in our understanding of the effects of photoperiod on gene expression in the hypothalamus, and considers how this new information can be reconciled with the species-specific location of melatonin receptors.


First Real-World Experience With Bigfoot Unity: A 6-Month Retrospective Analysis.
The Bigfoot Unity Diabetes Management System, a smart pen cap system cleared by the U.S. Food and Drug Administration in May 2021, incorporates continuous glucose monitoring data, real-time glycemic alerts, and clinician-directed dose recommendations. This study analyzed real-world clinical outcomes data for an initial cohort (n = 58, from 13 clinics) managing multiple daily injection insulin therapy using the pen cap system for 6 months. We examined glycemic control, including hypoglycemia events and interaction with and use of the pen cap system. In a cohort mainly consisting of adults with type 2 diabetes and an average age of 62 years, the results demonstrate close adherence to established glycemic targets, including a relatively short amount of time spent in the hypoglycemic range.


[Exocrine pancreatic insufficiency (author's transl)].
Exocrine pancreatic insufficiency usually does not develop before reduction of enzyme output by more than 90%. Patients with pancreatic insufficiency have a ravenous appetite but fail to thrive from malnutrition. The caloric deprivation is primarily due to fat malabsorption, recognized by the passage of bulky foul smelling greasy stools. Several isolated enzyme deficiencies can be separated from diseases with generalised pancreatic insufficiency. Under replacement therapy with pancreatic enzyme supplements most patients improve and gain weight, although fat and bile acid malabsorption are not abolished.


Iron-Nitrogen Amendment Reduced Perfluoroalkyl Acids' Phyto-Uptake in the Wheat-Soil Ecosystem: Contributions of Dissolved Organic Matters in Soil Solution and Root Extracellular Polymeric Substances.
Understanding the mechanisms underlying perfluoroalkyl acids (PFAAs) translocation, distribution, and accumulation in wheat-soil ecosystems is essential for agricultural soil pollution control and crop ecological risk assessment. This study systematically investigated the translocation of 13 PFAAs under different iron and nitrogen fertilization conditions in a wheat-soil ecosystem. Short-chain PFAAs including PFBA, PFPeA, PFHxA, and PFBS mostly accumulated in soil solution (10.43-55.33%) and soluble extracellular polymeric substances (S-EPS) (11.39-14.77%) by the adsorption to amino- (-NH2) and hydroxyl (-OH) groups in dissolved organic matter (DOM). Other PFAAs with longer carbon chain lengths were mostly distributed on the soil particle surface by hydrophobic actions (74.63-94.24%). Iron-nitrogen amendments triggered (p < 0.05) soil iron-nitrogen cycling, rhizospheric reactive oxygen species fluctuations, and the concentration increases of -NH2 and -OH in the DOM structure. Thus, the accumulation capacity of PFAAs in soil solution and root EPS was increased. In sum, PFAAs' translocation from soil particles to wheat root was synergistically reduced by iron and nitrogen fertilization through increased adsorption of soil particles (p < 0.05) and the retention of soil solution and root EPSs. This study highlights the potential of iron-nitrogen amendments in decreasing the crop ecological risks to PFAAs' pollution.


[Selective hypoaldosteronism with hyperkalemia. Clinical and physiopathological study of 22 cases with hypo- or hyperreninemia].
Twenty-two patients with selective hypoaldosteronism (SH) were studied. In 18 of them decreased levels of plasma renin activity (PRA) were associated with the syndrome: 12 patients showed the idiopathic form of SH, while in 6, the syndrome was attributable to the administration of non-steroid anti-inflammatory drugs. In the remaining 4 patients, the hypoaldosteronism was characterized by associated increased PRA levels but functional studies excluded a diagnosis of adrenocortical insufficiency. From a critical review of the literature and from the present observations it seems likely that SH is a syndrome with a heterogeneous pathogenesis. The possibility exists that the major alterations in potassium homeostasis that characterize the syndrome of SH, though mainly attributable to deficiency of aldosterone secretion may actually depend on the concurrence of underlying mechanisms, in particular on the presence of distal nephron dysfunctions.


In-Hospital Mortality Rate and Predictors of 30-Day Readmission in Patients With Heart Failure Exacerbation and Atrial Fibrillation: A Cross-Sectional Study.
Heart failure (HF) and atrial fibrillation (AF) are considered new cardiovascular epidemics of the last decade. Recent national trends show an uptrend in HF hospitalizations. We aimed to identify the 30-day readmission rate, causes, and impact on healthcare utilization in HF exacerbation with a history of AF. We utilized 2018 Nationwide readmission data and included patients aged ≥18 years with International Classification of Diseases, Tenth Revision, Clinical Modification code indicating HF exacerbation and AF were included in the study. Primary outcome is 30-day readmission rates. Secondary outcomes were mortality rates, common causes of readmission, and healthcare utilization. Independent predictors for readmission were identified using cox regression analysis. The total number of admissions in our study was 48,250. The mean age was 77.8 years (standard deviation, 12.1), and 47.74% were females. The 30-day readmission rate was 16.72%. The mortality rate at index admission and readmission was 7.28% and 8.12%, respectively. The most common cause of readmission was the hypertensive heart and kidney disease with HF. The independent predictors of readmission were low socio-economic class, Medicaid, Charlson comorbidities score. The financial burden on healthcare for all the readmission was $461 million for the year 2018. The 30-day readmission rate was 16.72%. The mortality rate increased from 7.28% to 8.12% with readmission. The financial burden for readmission during that year was $461 million. Future studies directed with interventions to prevents readmissions are warranted.


[The morbidity and mortality of residents of Kazakhstan exposed to radiation impact and their posterity].
The most part of population exposed to radiation and their offspring residing in territories bordering upon the Semipalatinsk nuclear testing area represent objects of studying aged 40 years and older because the age is the factor decreasing health indices at the expense of natural gerontological processes. In these conditions, additional radiation exposition, besides radiological biological effects, plays the role ofpotentiation of common biological and environmental risk factors. From the archives of research institute of radiation medicine and ecology the primary medical documents were retrieved containing information about established diagnoses of individuals included into elaboration of epidemiological statistical analysis of dynamics of morbidity of persons in 2008-2012. Within the same period, the acts-certificates of causes of death of specific persons included into study groups were retrieved. It is established that in 8 classes of diseases in the main group and in 5 classes of diseases in comparison group significant exceeding of average annual indices of prevalence of diseases as compared with control group was established. The common prevalence of diseases in the main group comprised 3147.5 cases, in the comparison group - 2615.6 cases and in control group - 2203.8 cases per 1000 of population (RR=1.42;1.19; p<0.05;0.05). The indices of total mortality in the main group comprised 1887.3 cases, in the comparison group - 1531.2 cases and in control group - 1155.1 cases per 100 000 of population (RR=1.58;1.36; p<0.05;0.05). Among persons in the main group in 7 classes of diseases and in the comparison group in 5 classes of diseases significant exceeding of indices of mortality was registered over same indices in control group was registered as causes of death.


Comprehensive Analysis of Peripheral Exosomal circRNAs in Large Artery Atherosclerotic Stroke.
Exosomes are crucial vehicles in intercellular communication. Circular RNAs (circRNAs), novel endogenous noncoding RNAs, play diverse roles in ischemic stroke. Recently, the abundance and stability of circRNAs in exosomes have been identified. However, a comprehensive analysis of exosomal circRNAs in large artery atherosclerotic (LAA) stroke has not yet been reported. We performed RNA sequencing (RNA-Seq) to comprehensively identify differentially expressed (DE) exosomal circRNAs in five paired LAA and normal controls. Further, quantitative real-time PCR (qRT-PCR) was used to verify the RNA-Seq results in a cohort of stroke patients (32 versus 32). RNA-Seq identified a total of 462 circRNAs in peripheral exosomes; there were 25 DE circRNAs among them. Additionally, circRNA competing endogenous RNA (ceRNA) network and translatable analysis revealed the potential functions of the exosomal circRNAs in LAA progression. Two ceRNA pathways involving 5 circRNAs, 2 miRNAs, and 3 mRNAs were confirmed by qRT-PCR. In the validation cohort, receiver operating characteristic (ROC) curve analysis identified two circRNAs as possible novel biomarkers, and a logistic model combining two and four circRNAs increased the area under the curve compared with the individual circRNAs. Here, we show for the first time the comprehensive expression of exosomal circRNAs, which displayed the potential diagnostic and biological function in LAA stroke.


[Indication of repeat prostate biopsy for the diagnosis of prostate cancer].
There is no standard criterion for repeat prostate biopsy in cases with a negative initial biopsy. We retrospectively analyzed our experience of repeat prostate biopsy to establish its indication for the diagnosis of prostate cancer. From April 1997 to March 2005, 35 consecutive patients underwent repeat prostate biopsy at the department of Urology, Asahikawa Medical College Hospital because of clinically suspicious prostate cancer despite a negative initial biopsy. We compared patients' age, number of cores obtained during repeat biopsy, digital rectal examination findings, total prostate volume, the time from the first to the last biopsy, total prostate specific antigen (PSA) value, free PSA/total PSA ratio, PSA density and PSA velocity between cancer-positive and cancer-negative groups. Prostate cancer was detected in 17 of 35 patients (49%). Fifteen patients with prostate cancer were diagnosed by the first repeat biopsy and other 2 patients were diagnosed by the second repeat biopsy. A statistically significant difference was only noted in age and PSA density. Persistently elevated total PSA and a higher PSA density in cases with a negative initial biopsy might be a good indication of repeat prostate biopsy for the diagnosis of prostate cancer.


Purification-Free MicroRNA Detection by Using Magnetically Immobilized Nanopores on Liposome Membrane.
MicroRNAs have critical roles in a number of serious diseases and, as a result, are of major interest as clinical diagnostic targets. Conventionally, microRNAs are collected from blood and urine samples and are measured by either quantitative reverse-transcription polymerase chain reaction or microarray. Recently, nanopore sensing techniques have been applied for measuring microRNAs at the single-molecule level. However, existing techniques are technically complex, needing several tools and requiring purification and/or labeling of microRNA samples prior to use. Here we report a method for microRNA detection in a simple procedure requiring neither purification nor labeling. This system utilizes magnetic beads anchored with DNA and nanopores on a liposome membrane. In the presence of the target microRNA, it forms a duplex with complementary DNA, which is then cleaved by a duplex-specific nuclease (DSN). The cleaved DNA, which harbors a liposome on its terminus, is subsequently released from the magnetic bead, fuses to the lipid bilayer on chip, and emits an electrical signal derived from the formation of a nanopore. Because of a property of the DSN, the signals derived from microRNAs are expected to be amplified in an isothermal reaction. Our system possesses the specificity to detect target microRNAs from mixtures containing >106 different microRNA sequences and readily uses blood or urine samples. Although the limit of detection is above 10 nM and needs to be improved for practical diagnosis, because purification and labeling are not required, the presented system proposes a possible schematic for the development of easy and on-site diagnosis.


Subsite-specific colorectal cancer incidence rates and stage distributions among Asians and Pacific Islanders in the United States, 1995 to 1999.
This study examined subsite-specific colorectal cancer incidence rates and stage distributions for Asians and Pacific Islanders (API) and compared the API data with data for Whites and African Americans. Data included 336,798 invasive colorectal cancer incident cases for 1995 to 1999 from 23 population-based central cancer registries, representing about two thirds of API population in the United States. Age-adjusted rates, using the 2000 U.S. standard population, and age-specific rates and stage distributions were computed by anatomic subsite, race, and gender. All rates were expressed per 100,000. SEs and rate ratios were calculated for rate comparison. A significance level of 0.05 was used for all analyses. Overall, age-adjusted colorectal cancer incidence rates were significantly lower in API than in Whites and African Americans across anatomic subsites, particularly for proximal colon cancer in which rates were 40% to 50% lower in API males and females. Exception to this pattern was the significantly (10%) higher rectal cancer incidence rate in API males than in African American males. The incidence patterns by anatomic subsite within API differed from those of Whites and African Americans. Among API, the rate of rectal cancer (19.2 per 100,000) was significantly higher than the rates of proximal (15.2 per 100,000) and distal (17.7 per 100,000) colon cancers in males, with little variations in rates across anatomic subsites in females. In contrast, among White and African American males and females, proximal colon cancer rates were over 25% higher than the rates of distal colon and rectal cancers. Increases in age-specific rates with advancing age were more striking for proximal colon cancer than for distal colon and rectal cancers in Whites and African Americans, while age-specific rates were very similar for different subsites in API with parallel increases with advancing age, especially in API males. Similar to Whites and African Americans, in API, proximal colon cancers (32% to 35%) were also less likely to be diagnosed with localized stage compared with distal colon (38% to 42%) and rectal (44% to 52%) cancers. The patterns of subsite-specific colorectal cancer incidence in API, especially API males, differ from those of Whites and African Americans. Similar to Whites and African Americans, lower percentage of localized disease in API for proximal colon cancer than for distal colon and rectal cancers was also observed.


A Streaming model for Generalized Rayleigh with extension to Minimum Noise Fraction.
The Rayleigh quotient optimization is the maximization of a rational function, or a max-min problem, with simultaneous maximization of the numerator function and minimization of the denominator function. Here, we describe a low-rank, streaming solution for Rayleigh quotient optimization applicable for big-data scenarios where the data matrix is too large to be fully loaded into main memory. We apply this for a maximization of the Signal to Noise ratio of big-data, of very large static and dynamic data. Our implementation is shown to achieve faster processing time compared to a standard data read into memory. We demonstrate the trade-offs with synthetic and real data, on different scales to validate the approach in terms of accuracy, speed and storage.


Guidelines for assessment of cardiac electrophysiology and arrhythmias in small animals.
Cardiac arrhythmias are a major cause of morbidity and mortality worldwide. Although recent advances in cell-based models, including human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM), are contributing to our understanding of electrophysiology and arrhythmia mechanisms, preclinical animal studies of cardiovascular disease remain a mainstay. Over the past several decades, animal models of cardiovascular disease have advanced our understanding of pathological remodeling, arrhythmia mechanisms, and drug effects and have led to major improvements in pacing and defibrillation therapies. There exist a variety of methodological approaches for the assessment of cardiac electrophysiology and a plethora of parameters may be assessed with each approach. This guidelines article will provide an overview of the strengths and limitations of several common techniques used to assess electrophysiology and arrhythmia mechanisms at the whole animal, whole heart, and tissue level with a focus on small animal models. We also define key electrophysiological parameters that should be assessed, along with their physiological underpinnings, and the best methods with which to assess these parameters.


New development of the yolk sac theory in diabetic embryopathy: molecular mechanism and link to structural birth defects.
Maternal diabetes mellitus is a significant risk factor for structural birth defects, including congenital heart defects and neural tube defects. With the rising prevalence of type 2 diabetes mellitus and obesity in women of childbearing age, diabetes mellitus-induced birth defects have become an increasingly significant public health problem. Maternal diabetes mellitus in vivo and high glucose in vitro induce yolk sac injuries by damaging the morphologic condition of cells and altering the dynamics of organelles. The yolk sac vascular system is the first system to develop during embryogenesis; therefore, it is the most sensitive to hyperglycemia. The consequences of yolk sac injuries include impairment of nutrient transportation because of vasculopathy. Although the functional relationship between yolk sac vasculopathy and structural birth defects has not yet been established, a recent study reveals that the quality of yolk sac vasculature is related inversely to embryonic malformation rates. Studies in animal models have uncovered key molecular intermediates of diabetic yolk sac vasculopathy, which include hypoxia-inducible factor-1α, apoptosis signal-regulating kinase 1, and its inhibitor thioredoxin-1, c-Jun-N-terminal kinases, nitric oxide, and nitric oxide synthase. Yolk sac vasculopathy is also associated with abnormalities in arachidonic acid and myo-inositol. Dietary supplementation with fatty acids that restore lipid levels in the yolk sac lead to a reduction in diabetes mellitus-induced malformations. Although the role of the human yolk in embryogenesis is less extensive than in rodents, nevertheless, human embryonic vasculogenesis is affected negatively by maternal diabetes mellitus. Mechanistic studies have identified potential therapeutic targets for future intervention against yolk sac vasculopathy, birth defects, and other complications associated with diabetic pregnancies.


Identification of ionizable groups essential for the enzyme catalysis on glutathione S-transferase P.
The pH-Vmax/KmGSH plot of glutathione S-transferase P (GST-P) showed a bell-shaped profile, indicating bifunctional catalysis for glutathione (GSH) conjugation. The ionization constant (Ke) and the heat of ionization (delta He) of the essential ionizable group in the GSH binding site were measured and the value of pKe1 was 5.9 and that of pKe2, 8.4, while the delta He1 and delta He2 were -0.2 and 7.9 kcal/mole, respectively. In a solvent containing 25% ethanol, pKe1 and pKe2 shifted to the alkaline side by 0.47 and 0.2, respectively. These kinetic results indicated that carboxyl and phenolic groups were ionizable groups essential for the GSH conjugation. Chemical modifications using aminomethane sulfonic acid and N-acetylimidazole supported the results of the kinetic studies.


Regulation of canonical Wnt signaling by Brachyury is essential for posterior mesoderm formation.
The T box transcription factor Brachyury is essential for the formation of the posterior body in all vertebrates, although its critical transcriptional targets have remained elusive. Loss-of-function studies of mouse Brachyury and the zebrafish Brachyury ortholog Ntl indicated that Brachyury plays a more significant role in higher vertebrates than lower vertebrates. We have identified a second zebrafish Brachyury ortholog (Bra), and show that a combined loss of Ntl and Bra recapitulates the mouse phenotype, demonstrating an ancient role for Brachyury in patterning all but the most anterior somites. Using cell transplantation, we show that the only essential role for Brachyury during somite formation is non-cell autonomous, and demonstrate that Ntl and Bra are required for and can induce expression of the canonical Wnts wnt8 and wnt3a. We propose that a positive autoregulatory loop between Ntl/Bra and canonical Wnt signaling maintains the mesodermal progenitors to facilitate posterior somite development in chordates.


Assessing spousal support and health in an aging population: support and strain amidst changing social dynamics.
This study examined the role of relationship quality on physical and psychological health among older adults. It included 2,298 adults aged 50 and older who participated in the Midlife in the US national longitudinal study of health and well-being. We assessed the effect of spousal support and strain on psychological and physical health, controlling for age, education, income, depression levels and prior health. Results indicated that spousal support and strain affected psychological health but not physical health. Despite prior research showing an association between marital quality and physical health, this study did not support the conceptualization that relationship quality measured by spousal support or strain has a direct effect on long-term health in this sample of older adults. This study does not preclude the presence of a mediated or moderated association between relationship quality and physical health. Higher levels of spousal support are associated with positive psychological health among adults over age 50 while spousal strain is associated with negative psychological health. This study supports the premise that relationship quality has an ongoing impact on the psychological health of mature adults, bolstering arguments to include psychological health screening and couples relationship education among health services provided to older adults.


Retrospective analysis of renal transplantation outcomes in children admitted to a paediatric intensive care unit in Brazil.
Renal transplantation has been described as the main treatment for children with end-stage renal disease. Traditionally, infants and small children represented a high-risk group with poor allograft survival. However, studies conducted mainly in developed countries have been demonstrated improvements in allograft survival rates. The aim of this study was to identify demographic characteristics of recipients and kidney donors and to analyse the outcomes of children who received postoperative care following renal transplantation in one Paediatric Intensive Care Unit (PICU). This retrospective study was carried out in a university hospital in Brazil. The data were collected through reviewing the follow up of medical records of recipients and kidney donors between 1988 and 2002. Chi-square or Fisher exact tests were used to analyse differences in outcome between living and donor transplants, whereas Mann-Whitney and Kruskal-Wallis tests were used to compare differences in outcome by age groups and by the number of complications affecting recipients. A total of 44 children were admitted for renal transplantation. Within this group, the median age was 10.1(+/-3.2) years, 63.6% were men and 38% were non-Caucasians. In contrast, the donor group had a median age of 17.5(+/-12.5) years, of which 51.3% were male, 56.8% were Caucasian and 70.5% were cadaver donors. The average length of PICU stay was 31.4 h, with complications being identified in the majority of the transplanted children. The occurrence of four or more complications was significantly associated with acute rejection (p= 0.009). In conclusion, the main outcomes of this study were similar to those observed in developed countries, in terms of acute rejections (52.3%), dialysis resumption (31.8%), graft loss (29.5%), chronic rejections (9.1%) and death (4.5%). Complications during PICU stay were significantly linked to the occurrence of acute rejection.


Establishment of a swine model of traumatic cardiac arrest induced by haemorrhage and ventricular fibrillation.
To establish and evaluate a swine model of traumatic cardiac arrest (TCA) induced by haemorrhage and ventricular fibrillation. Thirteen male pigs were divided into a sham group (n = 5) and TCA group (n = 8). Animals in the sham-operated group underwent intubation and monitoring but not haemorrhage and resuscitation, while animals in the TCA group underwent 40% blood volume haemorrhage over 20 min followed by 5 min of ventricular fibrillation and 5 min of cardiopulmonary resuscitation with fluid resuscitation. Restoration of spontaneous circulation was achieved in seven of eight animals in the TCA group. After resuscitation, the heart rate was significantly increased while the mean arterial pressure and ejection fraction were significantly decreased in the TCA group. The TCA group had significant cardiac and neurological injuries post-resuscitation and had higher serum creatinine and blood lactic acid levels and lower PaO2 than the sham group. Animals in the TCA group also exhibited significantly higher apoptotic indices and caspase-3 protein levels in the heart, brain and kidney than the sham group. Animals in this swine model of TCA exhibited high rates of successful resuscitation, significant vital organ injury and prolonged survival. The model is suitable for use in further TCA research.


[Risk of fungal infection from foods, particularly in immunocompromised patients].
The aim of our study was the evaluation of fungal contamination of food distributed in hospitals to the immunocompromised patients. 97 samples of 10 sorts of fruit, 100 samples of 17 sorts of cheeses and 56 samples of 11 sorts of smoked meat products were investigated by cultivation on Sabourand's agar at 25 degrees C for 10 days. The yeasts (Candida, Trichosporon, Saccharomyces, Rhodotorula, Aureobasidium) were found in 82% of fruit, in 13% of cheeses and in 46% of smoked meat products. The filamentous fungi (Cladosporium, Alternaria, Penicillium, Aspergillus, Mucor and Helminthosporium) were found on all samples of fruit, in 44% of cheeses and in 3% of smoked foods. Our results show that the fungal contamination of the investigated food is not negligible. The isolated strains are agents of candidoses, phaeohyphomycoses, mucormycoses and aspergilloses and can kill immunocompromised patients.


Luteolin inhibited the gene expression, production and secretion of MUC5AC mucin via regulation of nuclear factor kappa B signaling pathway in human airway epithelial cells.
Luteolin, a flavonoidal compound derived from Lonicera japonica Thunb. and Chrysanthemum indicum L., has been reported to show anti-inflammatory, anti-oxidative and anti-carcinogenic effects. In this study, we investigated whether luteolin significantly affects the secretion, production and gene expression of airway mucin. Confluent NCI-H292 cells were pretreated with luteolin for 30 min and then stimulated with EGF (epidermal growth factor) or PMA (phorbol 12-myristate 13-acetate) for 24 h or the indicated periods. The MUC5AC mucin gene expression was measured by RT-PCR. Production and secretion of MUC5AC mucin protein were measured by ELISA. To elucidate the action mechanism of luteolin, effect of luteolin on PMA-induced NF-κB signaling pathway was investigated by western blot analysis. The results were as follows: (1) Luteolin inhibited the secretion of MUC5AC mucin protein induced by EGF or PMA; (2) Luteolin inhibited the production of MUC5AC mucin protein and the expression of MUC5AC mucin gene induced by EGF or PMA; (3) Luteolin inhibited PMA-induced phosphorylation and degradation of inhibitory kappa Bα (IκBα); (4) Luteolin inhibited PMA-induced phosphorylation and nuclear translocation of nuclear factor kappa B (NF-κB) p65. This result suggests that luteolin can regulate the secretion, production and gene expression of mucin by acting on airway epithelial cells via regulation of NF-kB signaling pathway.


[SOLITARY KIDNEY - IS IT TOO LITTLE?]
Solitary functioning kidney (SFK) occurs with unilateral renal agenesis (URA) in 1/2000 live births - or after uninephrectomy for tumor, trauma, uncontrolled infections or hypertension and post-kidney donation. URA-associated states include urological, cardiac, gastrointestinal and skeletal anomalies or it might be a component of a genetic syndrome. In 10% of cases of URA another family member is affected. In any case of SFK a compensatory process is triggered consisting of glomerular hypertension with hyperfiltration which achieves 75% of two kidneys' function. In the long-run this process might be detrimental causing further loss of functioning nephrons, inability to sustain functional compensation and progressive kidney function deterioration. The risk for this chain of events is determined in the first place by the number of nephrons in the SFK, which cannot be assessed in vivo. Hints for reduced nephron number in the single kidney include prematurity or SGA-small for date birth weight, urological anomalies with or without accompanying infections, lack of increased single kidney size - compensatory hypertrophy. Age of onset of the compensatory process and acquired factors including nephrotoxin exposure, overweight/obesity, excessive salt and/or protein intake contribute to the risk of progressive renal damage. Life-long follow-up of all subjects with SFK is recommended from early age for lifestyle education: recommended diet and tailored physical activity, nephrotoxin avoidance along with early detection of renal injury signs: albuminuria, hypertension or depressed kidney function - GFR (glomerular filtration rate) targeting timely intervention for preservation of functioning renal mass.


Beta-catenin inhibits T cell activation by selective interference with linker for activation of T cells-phospholipase C-γ1 phosphorylation.
Despite the defined function of the β-catenin pathway in thymocytes, its functional role in peripheral T cells is poorly understood. We report that in a mouse model, β-catenin protein is constitutively degraded in peripheral T cells. Introduction of stabilized β-catenin into primary T cells inhibited proliferation and cytokine secretion after TCR stimulation and blunted effector cell differentiation. Functional and biochemical studies revealed that β-catenin selectively inhibited linker for activation of T cells phosphorylation on tyrosine 136, which was associated with defective phospholipase C-γ1 phosphorylation and calcium signaling but normal ERK activation. Our findings indicate that β-catenin negatively regulates T cell activation by a previously undescribed mechanism and suggest that conditions under which β-catenin might be inducibly stabilized in vivo would be inhibitory for T cell-based immunity.


Purification and characterisation of recombinant sea urchin metallothionein expressed in Escherichia coli.
Metallothioneins (MT) are metalloproteins expressed tissue specifically during the development of the sea urchin, Strongylocentrotus pururatus. To explore their structural and functional features and to compare them with those of the evolutionary distant mammalian MTs, one isoform (MTA) was obtained as the cadmium-containing form, from synthetic cDNA heterologously expressed in Escherichia coli. The purified protein was identified as the desired product by a combination of peptide-map analysis, amino acid sequence analysis and ion-spray mass spectroscopy. The existence of seven 113Cd NMR resonances revealed that the recombinant protein binds seven Cd ions/molecule. The position of the NMR resonances (605-695 ppm) and the electronic absorption features suggest that the sea urchin MTA, like the mammalian MTs, possesses tetrahedrally coordinated cadmium-thiolate clusters. With its large Stokes' radius, sea urchin MTA resembles the mammalian forms, suggesting a comparable elongated molecular shape. Measurements by spectrophotometric pH titration of cadmium binding by the recombinant protein suggest that it possesses two metal-thiolate clusters of distinctly different stability. At pH 7 the average apparent association constant for Cd2+ in the clusters is about 20-times weaker in sea urchin MTA than in rabbit MT-2.


Conservative Treatment of Distal Radius Fractures: A Prospective Descriptive Study.
Disability of the upper limb is one of the consequences of distal radius fracture (DRF). The outcome of DRF treatment is based on objective clinical variables, as strength or range of movement (ROM); sometimes these variables do not correlate with the functional level of the patient. The principal objective of our study was to assess the repercussion of conservative treatment of DRF on upper limb disability. This is a retrospective review of prospectively collected data. We collected data of 61 nonconsecutive DRFs treated conservatively from July 2007 to August 2008. Average Disabilities of the Arm, Shoulder and Hand (DASH) score before fracture was 20.8 points; average DASH score after the fracture was 42.6. There was a significant increase in the upper limb disability after 1 year of follow-up in the patients treated conservatively ( P < .001; size effect, 1.06). Average radial inclination, radial tilt, and radial length were 18.18°, 3.35°, and 5.76 mm, respectively. Average ROM for flexion-extension was 100.6° and for pronation-supination 144.0°. ROM for flexion-extension of the unaffected wrist was 128.2° and for pronation-supination 172.4°. We did not find any significant statistical correlation between the increase in disability and the decrease in the ROM ( P > .05). We did not find any significant statistical correlation between the increase in the disability and the worsening in the radiological parameters ( P > .05). Our results confirm the hypothesis that the conservative treatment of DRF produced an increase in the upper limb disability after 1 year of follow-up. Our study does not show a correlation between the increase in upper limb disability and the decrease in wrist ROM. Our study did not find a correlation between radiological measures and DASH scores.


Xyloglucan endotransglycosylase/hydrolase genes from a susceptible and resistant jute species show opposite expression pattern following Macrophomina phaseolina infection.
Two of the most widely and intensively cultivated jute species, Corchorus capsularis and Corchorus olitorius, suffer severely from a stem rot disease caused by the fungus Macrophomina phaseolina. Wild jute species, C. trilocularis, shows resistance to this pathogenic fungus. In this study, the technique of differential display was applied to identify genes which are differentially expressed, under both infected and un-infected conditions, between C. trilocularis and C. olitorius var O-72. Two xyloglucan endotransglycosylase/hydrolase (XTH) genes designated CoXTH1 (from Corchorus olitorius) and CtXTH1 (from C.trilocularis) were identified from each of the two species which show different expression patterns upon fungal infection. A steady rise in the expression of CtXTH1 in response to infection was observed by quantitative real time PCR whereas the expression of CoXTH1 was found to be downregulated. Full length sequences of these two genes were determined using primer based gene walking and RACE PCR. This study confirms the involvement of XTH in molecular interactions between M. phaseolina and jute. However, it remains to be explored whether XTH is an essential component of the signaling pathway involved in plant-fungal interaction.


Can neuropsychological tests detect the sites of cerebrovascular stenoses and occlusions?
Conventional neuropsychological data may not mirror the site of cerebrovascular stenosis in a patient with mild to moderate symptoms. In this study, three groups of cerebral revascularization candidates failed to differ on an extended Halstead-Reitan battery: patients with symptoms and angiographic results referable to the carotid arterial system, subjects with clinical signs and neuroradiological findings referable to the vertebrobasilar arterial system, and patients with symptoms of cerebral ischemia but negative angiograms. Consistent with previous work, these patients generally were mildly impaired on neuropsychological tests, even though many were not symptomatic at the time of assessment. Neuropsychological tests seem to be sensitive to the presence and severity of cerebral ischemia, but in isolation may not be sufficient to determine the loci of vascular stenoses. The incongruence between angiographic and neuropsychological findings underlines the importance of distinguishing among different levels and types of measurements in defining subgroups of cerebral revascularization candidates. Collaboration among neuroscientists will further our understanding of the interrelationships among neurodiagnostic tests.


Peripherally inserted central venous catheters: success of scalp-vein access in infants and newborns.
The authors assessed the feasibility of placing peripherally inserted central venous catheters via scalp veins in infants and newborns. In 60 newborns and infants, aged 3 days to 10 months, placement of 62 2-F peripherally inserted central venous catheters was attempted with scalpvein access. The tip location was central in 30 of the 62 catheters (48%) and long peripheral intravenous in 17 (27%); access failed in 15 (24%). Scalp-vein access for peripherally inserted central venous catheters offers a safe and effective alternative route for gaining central venous access in infants and newborns.


Inhibition of l-type amino acid transporter 1 activity as a new therapeutic target for cholangiocarcinoma treatment.
Unlike normal cells, cancer cells undergo unlimited growth and multiplication, causing them to require massive amounts of amino acid to support their continuous metabolism. Among the amino acid transporters expressed on the plasma membrane, l-type amino acid transporter-1, a Na+-independent neutral amino acid transporter, is highly expressed in many types of human cancer including cholangiocarcinoma. Our previous study reported that l-type amino acid transporter-1 and its co-functional protein CD98 were highly expressed and implicated in cholangiocarcinoma progression and carcinogenesis. Therefore, this study determined the effect of JPH203, a selective inhibitor of l-type amino acid transporter-1 activity, on cholangiocarcinoma cell inhibition both in vitro and in vivo. JPH203 dramatically suppressed [14C]l-leucine uptake as well as cell growth in cholangiocarcinoma cell lines along with altering the expression of l-type amino acid transporter-1 and CD98 in response to amino acid depletion. We also demonstrated that JPH203 induced both G2/M and G0/G1 cell cycle arrest, as well as reduced the S phase accompanied by altered expression of the proteins in cell cycle progression: cyclin D1, CDK4, and CDK6. There was also cell cycle arrest of the related proteins, P21 and P27, in KKU-055 and KKU-213 cholangiocarcinoma cells. Apoptosis induction, detected by an increase in trypan blue-stained cells along with a cleaved caspase-3/caspase-3 ratio, occurred in JPH203-treated cholangiocarcinoma cells at the highest concentration tested (100 µM). As expected, daily intravenous administration of JPH203 (12.5 and 25 mg/kg) significantly inhibited tumor growth in KKU-213 cholangiocarcinoma cell xenografts in the nude mice model in a dose-dependent manner with no statistically significant change in the animal's body weight and with no differences in the histology and appearance of the internal organs compared with the control group. Our study demonstrates that suppression of l-type amino acid transporter-1 activity using JPH203 might be used as a new therapeutic strategy for cholangiocarcinoma treatment.


Peripherally inserted central catheter in extremely preterm infants: Characteristics and influencing factors.
To evaluate the duration of catheter stay, incidence of non-elective removal and rates of complications associated with peripherally inserted central catheters (PICCs) in relation to different catheter positions in extremely preterm infants (EPT, <28 weeks of gestation). A retrospective analysis of Peripherally Inserted Central Catheters (PICCs) inserted in EPT infants over a 10-year period, from January 2004 through December 2013 (mean gestational age, 25.2 weeks; mean birth weight, 727 g). Of the 379 PICCs analyzed, the majority of lines (68%) were placed in the central position, and 259 PICCs (56%) were removed electively after fulfilment of the treatment. Significantly more PICCs in the lower extremities compared to the upper extremities were in central positions (86% vs 61%, p < 0.001, respectively). Significantly more PICCs that were removed electively after fulfilment of the treatment were in a central position compared to a non-central position (p < 0.001). Of the 166 catheters that were removed because of complications, most (71%) of them had mechanical problems, and 13% had sepsis resulting in an incidence rate of 4.4/1000 catheter days. PICCs inserted in the lower extremity were more likely to have a centrally placed tip position compared to PICC lines inserted in the upper extremities.


Forms of human milk folacin and variation patterns.
The pattern of folacin in 180 human milk samples collected from 16 women was studied before and after pteroylglutamic hydroxylase (conjugase) treatment. The differential response of Lactobacillus casei versus Streptococcus faecalis distinguishes N-5-methyltetrahydrofolate from other forms. Growth of Pediococcus cerevisiae differentiates the reduced monoglutamates, other than the N-5-methylated derivative, from oxidized folacins. Mean folacin activity with L. casei was 85.3 ng/ml. Prior to conjugase treatment of samples, mean activity was 46.9 ng/ml with this organism. The responses of S. faecalis and P. cerevisiae were 48% and 7.6%, respectively, of the total L. casei active folacins. The total L. casei active folacins increased from 76.5 ng/ml at 6 weeks of lactation to 97.1 ng/ml at 12 weeks of lactation. Increases were also observed with time of day: from morning (65.7 ng/ml), to afternoon (80.0 ng/ml), and to evening (114.7 ng/ml). Hindmilk had greater total L. casei activity (100.0 ng/ml) than foremilk (73.8 ng/ml). Although folacins active for S. faecalis and P. cerevisiae were not affected by duration of lactation, increases in folacin activity with time of day and from fore- to hindmilk were observed using both of these organisms. Values for the folacin content of human milk are therefore dependent on sampling procedures. Pteroylpolyglutamates of greater than or equal to 3 glutamic acid residues and N-5-methyltetrahydrofolate are the predominant forms of human milk folacin based on differential growth responses of L. casei, S. faecalis, and P. cerevisiae to these forms.


Divergent innervation of the olfactory bulb by distinct raphe nuclei.
The raphe nuclei provide serotonergic innervation widely in the brain, thought to mediate a variety of neuromodulatory effects. The mammalian olfactory bulb (OB) is a prominent recipient of serotonergic fibers, particularly in the glomerular layer (GL), where they are thought to gate incoming signals from the olfactory nerve. The dorsal raphe nucleus (DRN) and the median raphe nucleus (MRN) are known to densely innervate the OB. The majority of such projections are thought to terminate in the GL, but this has not been explicitly tested. We sought to investigate this using recombinant adeno-associated viruses (rAAV)-mediated expression of green fluorescent protein (GFP)-synaptophysin targeted specifically to neurons of the DRN or the MRN. With DRN injections, labeled fibers were found mostly in the granule cell layer (GCL), not the GL. Conversely, dense labeling in the GL was observed with MRN injections, suggesting that the source of GL innervation is the MRN, not the DRN, as previously thought. The two raphe nuclei thus give dual innervation within the OB, with distinct innervation patterns.


A 300 GHz collective scattering diagnostic for low temperature plasmas.
A compact and portable 300 GHz collective scattering diagnostic employing a homodyne detection scheme has been constructed and installed on the hot helicon experiment (HELIX). Verification of the homodyne detection scheme was accomplished with a rotating grooved aluminum wheel to Doppler shift the interaction beam. The HELIX chamber geometry and collection optics allow measurement of scattering angles ranging from 60 degrees to 90 degrees. Artificially driven ion-acoustic waves are also being investigated as a proof-of-principle test for the diagnostic system.


Low frequency of somatic mutations in the FH/multiple cutaneous leiomyomatosis gene in sporadic leiomyosarcomas and uterine leiomyomas.
Germline mutations in the fumarate hydratase gene at 1q43 predispose to dominantly inherited skin and uterine leiomyomata and leiomyosarcomas. The enzyme, which is a component of the tricarboxylic acid cycle, acts as a tumour suppressor. To evaluate fumarate hydratase in respective sporadic tumours, we analysed a series of 26 leiomyosarcomas and 129 uterine leiomyomas (from 21 patients) for somatic mutations in fumarate hydratase and allelic imbalance around 1q43. None of the 26 leiomyosarcomas harboured somatic mutations in fumarate hydratase. Fifty per cent of leiomysarcomas tested showed evidence of allelic imbalance at 1q, but this was not confined to the vicinity of fumarate hydratase. Only 5% (seven out of 129) of the leiomyomas showed allele imbalance at 1q42-q43 and no somatic mutations in fumarate hydratase were observed. Our findings indicate that mutations in fumarate hydratase do not play a major role in the development of sporadic leiomyosarcomas or uterine leiomyomas


Nonanaplastic follicular cell-derived thyroid carcinoma: mitosis and necrosis in long-term follow-up.
Nonanaplastic follicular cell-derived thyroid carcinoma (NAFCTC) includes differentiated- (DTC) and poorly differentiated thyroid carcinoma (PDTC). DTC has an excellent prognosis, while PDTC is situated between DTC and anaplastic carcinomas. Short-term studies suggest that PDTC patients diagnosed only on tumor necrosis and/or mitosis have a prognosis similar to those diagnosed according to the TURIN proposal. The purpose of this study was to evaluate prognosis for NAFCTC based on long-term follow-up illuminating the significance of tumor necrosis and mitosis. A cohort of 225 patients with NAFCTC was followed more than 20 years. Age, sex, distant metastasis, histology, tumor size, extrathyroidal invasion, lymph node metastasis, tumor necrosis and mitosis were examined as possible prognostic factors. Median follow-up time for patients alive was 28 years (range 20-43 years). Age, distant metastasis, extrathyroidal invasion, tumor size, tumor necrosis and mitosis were independent prognostic factors in multivariate analysis for overall survival (OS). In disease specific survival (DSS) age was not significant. Using only necrosis and/or mitosis as criteria for PDTC the 5-, 10- and 20-year OS for DTC was 87, 79 and 69%, respectively. In DSS it was 95, 92 and 90%. For PDTC the 5-, 10- and 20-year OS was 57, 40 and 25%, respectively. In DSS it was 71, 55 and 48%. Tumor necrosis and mitosis are highly significant prognostic indicators in analysis of long time survival of nonanaplastic follicular cell-derived thyroid carcinoma indicating that a simplification of the actually used criteria for poorly differentiated carcinomas may be justified.


SMRT recruitment by PPARgamma is mediated by specific residues located in its carboxy-terminal interacting domain.
The silencing mediator of retinoid and thyroid hormone receptors (SMRT) has been shown to play an important role in adipogenesis and PPARgamma transcriptional activity. SMRT contains two interacting domains that mediate interactions with nuclear receptors. Interestingly, SMRT is recruited to PPARgamma via its C-terminal interacting domain, and mutation of the proximal interacting domain does not interfere with recruitment via PPARgamma. To understand how the distal interacting domain mediates recruitment by PPARgamma, we have now mutated residues in this domain to the corresponding amino acids found in the proximal domain. We show that specific residues in this distal domain are vital for interactions with PPARgamma, but not for a related receptor, RARalpha. Furthermore, naturally-occuring SMRT isoforms that differ in interacting domain sequences have different effects on PPARgamma as opposed to RARalpha recruitment. These data suggest that PPARgamma and RARalpha interact with SMRT via distinct mechanisms. These differences will be important as ligands are designed that lead to specific patterns of nuclear receptor recruitment of corepressors.


Comparison of hemodynamic response to tracheal intubation with Macintosh and McCoy laryngoscopes.
Use of McCoy blade laryngoscope avoids the lifting force in the vallecula and theoretically should lead to a lower hemodynamic response related to laryngoscopy and tracheal intubation. The available literature on the topic is conflicting. We studied the hemodynamic response to laryngoscopy and tracheal intubation in 60 ASA 1 AND 2 adult patients using either Macintosh or McCoy laryngoscopes. The change in systolic, diastolic, mean arterial pressure, and heart rate (HR) was observed for 10 min post intubation. Arrhythmias and ST changes were also observed. The maximum change in HR was 18.7% in the Macintosh and 7.7% in the McCoy group, and in systolic arterial pressure was 22.9% in the Macintosh and 10.3% in the McCoy group. This difference between groups was significant (P < 0.0001). The change lasted for a lesser duration in the McCoy group. No arrhythmias or ST changes were observed in either group. Hemodynamic changes with use of McCoy laryngoscope were lesser in magnitude and of shorter duration.


[Thoracic outlet syndrome].
The thoracic outlet syndrome is a polymorphic clinical entity, whose nature is essentially anatomic, caused by the chronic compression of the neurovascular structures that are originated in the chest or neck and course to the upper extremity. According to the most affected structure, they can be classified as neurologic, arterial or venous syndromes, that may cause discomfort, pain and disability, sometimes definite and irreparable. Thoracic outlet syndrome are often difficult to recognize in clinical practice and it is important to emphasize some peculiar symptoms or signs that each syndrome may present, through specific maneuvers or adequate complementary studies. The great majority of patients may improve with physical therapy or postural correction, and a minority is indicated for surgical therapy. The main features of the diverse thoracic outlet syndromes, their clinical presentation, diagnosis, conventional and surgical management, surgical access, complications and prognosis are described and discussed in this paper dedicated to a complete review of the entity.


Kallikrein-related peptidase 4 contributes to the tumor metastasis of oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is a disfiguring malignancy and significantly impacts the quality of patient's life. Kallikrein-related peptidase 4 (KLK4), which is closely related to cancers, is highly expressed in OSCC. To explore the biological function of KLK4 in OSCC, a KLK4-specific shRNA was used to silence its endogenous expression, and then the migration and invasion of OSCC cells were explored. Results of our study showed that silencing KLK4 inhibited the migration and invasion of OSCC cells. The protein levels of epithelial mesenchymal transition-associated markers and proteases were also altered by KLK4 silencing. Further study showed that the phosphatidylinositol 3-kinase (PI3 K)/protein kinase B (AKT) signaling pathway was involved in the function of KLK4. Treatment with a PI3 K/AKT activator reversed the migration-inhibitory effect of KLK4 shRNA. Our study suggests that KLK4 may contribute to the metastasis of OSCC through the PI3 K/AKT signaling pathway.


Temporal effects of an infusion of dopexamine hydrochloride in horses anesthetized with halothane.
To evaluate the hemodynamic effects of a 60-minute infusion of dopexamine in horses anesthetized with halothane. 7 adult Thoroughbreds. Measurements of left ventricular function obtained by transesophageal Doppler echocardiography and cardiac catheterization. Infusion of dopexamine (4 micrograms/kg of body weight/min) significantly increased heart rate, cardiac output, maximal rates of increase and decrease of left ventricular pressure, and maximal acceleration and maximal velocity of aortic blood flow. Left ventricular ejection time significantly increased, and pre-ejection period decreased during the infusion. Cardiac output, maximal rate of increase of left ventricular pressure, and maximal acceleration continued to increase as the infusion progressed. Right ventricular end-diastolic pressure was significantly decreased after 20 minutes of infusion and decreased progressively throughout the remaining time of infusion. Many hemodynamic variables, including right ventricular end-diastolic pressure, had not returned to control values 30 minutes after the infusion was discontinued. A number of undesirable adverse effects were observed in horses receiving dopexamine infusion; during administration, profuse sweating occurred in every horse. In 6 horses, recovery from anesthesia was associated with excitement and violent shivering. Colic developed in 2 horses within 3 hours of recovery. Dopexamine (4 micrograms/kg/min) does not achieve a peak effect on many hemodynamic variables within a short period of commencing administration, and the effects of infusion may persist for extended periods after drug administration is discontinued. Dopexamine has a hemodynamic profile suited to treatment of low cardiac output in anesthetized horses; however, at the dosage rate studied (4 micrograms/kg/min), its administration was associated with a number of undesirable adverse effects which could preclude its clinical use.


[Effects of injectio Salvia miltiorrhiza on gentamicin-induced free radical formation in guinea pig cochlea].
To investigate the effects of injectio Salvia Miltiorrhiza (SM) on gentamicin (GM)-induced free radical formation in guinea pig cochlea, and to explore possible mechanisms on GM-induced ototoxicity. Biochemical assays of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in guinea pig cochlea, combined with auditory brainstem response (ABR) measurement and transmission electron microscopic observation were used in this investigation. SOD activity was significantly declined while MDA content was distinctly increased in cochlear tissues after GM injection (P < 0.01). Moreover, they were well correlated with auditory function damage (|r| > 0.7). Co-treatment with SM evidently enhanced SOD activity and decreased MDA content (P < 0.01, P < 0.05). Furthermore, auditory function was markedly ameliorated. Morphological changes of cochlea were consistent with those of hearing function. Lipid peroxidation elicited by free radical was involved in GM-induced cochleotoxicity. SM might enhance SOD activity and prevent lipid peroxidation. As the result it might alleviate GM ototoxicity, and improve auditory function.


Optimizing capillary column backflush to improve cycle time and reduce column contamination.
Interest in decreasing cycle times in capillary GC analyses has driven much of the instrumental developments of the last decade. Recent developments in GC instrumentation now make it reasonable to consider backflushing capillary columns on a routine basis. Significant reduction in analysis and total cycle times (typically 15-50% depending on the application) are readily achieved for analyses that currently require an extended temperature program and bakeout period to remove retained sample components and column contaminants. Setup and optimization of backflush conditions are relatively straight forward as long as some basic concepts are well understood. The parameters affecting capillary column backflushing are described. Examples are shown that help visualize what happens during backflush. The relationship between oven ramp rate and flow turns out to be an important variable that dictates minimum backflush times in temperature programmed CGC. Backflush times corresponding to 2-5 void volumes in the reversed direction are usually sufficient for backflushing, if performed after each temperature programmed run.


Modeled prenatal exposure to per- and polyfluoroalkyl substances in association with child autism spectrum disorder: A case-control study.
Per- and polyfluoroalkyl substances (PFAS) display neurobehavioral toxicity in laboratory animal studies. We examined associations of modeled prenatal maternal exposure to PFAS with child diagnosis of autism spectrum disorder (ASD). Participants were 453 mother-child pairs from CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based case-control study. Children underwent psychometric testing and were clinically confirmed for ASD (n = 239) or typical development (TD, n = 214). At the end of the clinic visit, maternal blood specimens were collected. We quantified nine PFAS in maternal serum samples collected when their child was 2-5 years old. As surrogate in utero exposure, we used a model built from external prospective data in pregnancy and 24 months post-partum and then reconstructed maternal PFAS serum concentrations during pregnancy in this case-control sample. We used logistic regression to evaluate associations of modeled prenatal maternal PFAS concentrations with child ASD. Modeled prenatal maternal perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were borderline associated with increased odds of child diagnosis of ASD (per nanogram per milliliter increase: odds ratio [OR] = 1.46; 95% confidence interval [CI]: 0.98, 2.18 for PFHxS, OR = 1.03; 95% CI: 0.99, 1.08 for PFOS). When compared to the lowest quartile (reference category), the highest quartile of modeled prenatal maternal PFHxS was associated with increased odds of child diagnosis of ASD (OR = 1.95; 95% CI: 1.02, 3.72). In analyses where modeled prenatal maternal PFAS serum concentrations served as in utero exposure, we observed that prenatal PFHxS and PFOS exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD. Further studies in which PFAS concentrations are prospectively measured in mothers and children at a range of developmental stages are needed to confirm these findings.


My road on interventional radiology.
The author tells a story of how he has become an expert of interventional radiotherapy from a graduate of middle school. In his childhood, he wanted to become an astronomer. However, he was forced to go to the countryside as a school graduate. In 1974, he was enrolled as a "worker-peasant-soldier" student in Henan Medical College. After graduated from the college, he was assigned to the Radiology Department of the First Affiliated Hospital of Henan Medical College where he worked hard as an assistant doctor. Then, he was transferred to Nanfang Hospital (Guangzhou, China) where he achieved great successes and thus has become an expert of interventional radiology.


A multicenter, open-label, comparative trial of two daclizumab dosing strategies vs. no antibody induction in combination with tacrolimus, mycophenolate mofetil, and steroids for the prevention of acute rejection in simultaneous kidney-pancreas transplant recipients: interim analysis.
The safety and efficacy of daclizumab (1 mg/kg/dose every 14 d for five doses) has been established in kidney and heart transplant recipients. Alternative dosing regimens based on pharmacokinetic simulation and limited clinical trials are being investigated. The purpose of this ongoing multicenter study is to determine the safety and efficacy of two dosing regimens of daclizumab as an adjunctive immunosuppressive agent compared with no antibody induction in simultaneous kidney-pancreas transplant (SKPT) recipients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and steroids as primary immunosuppression. This is an interim report of a multicenter, prospective, open-label, randomized study with a target enrolment of 290 patients. Eligible SKPT patients were randomized to one of three groups: daclizumab 1 mg/kg/dose every 14 d for five doses (Group I), daclizumab 2 mg/kg/dose every 14 d for two doses (Group II), and no antibody induction (Group III). The primary endpoint of the study is a composite of the incidence of presumed or biopsy-proven kidney or pancreas rejection, graft loss, or death within the first 6 months post-transplantation. A total of 166 patients were randomized into the three groups [Group I (n = 70), Group II (n = 74), Group III (n = 22)]. Demographic and transplant characteristics were similar among the groups. At a minimum follow-up of 3 months, patient, kidney and pancreas graft survival rates were similar among the three groups. However, the rates of acute renal allograft rejection were 18% (Group I), 8% (Group II), and 36% (Group III), p < 0.05. The probabilities of either kidney or pancreas allograft rejection were 22% (Group I), 8% (Group II), and 38% (Group III). At 3 months, the actuarial event-free survival (no acute rejection, allograft loss, or death) rates were 67, 81 and 50% in Groups I, II, and III, respectively. There were no differences in the incidence of infectious complications among the groups and no serious adverse events associated with daclizumab were observed. The two-dose regimen (Group II) appears to be as effective as the five-dose regimen (Group I) in preventing acute rejection after SKPT and is associated with the lowest acute rejection rates and the highest rate of event-free survival (no rejection or graft loss). However, the benefits of daclizumab compared with no antibody induction await larger sample size accrual.


Dental emergencies in a university-based pediatric dentistry postgraduate outpatient clinic: a retrospective study.
The purpose of this retrospective study was to determine the prevalence and types of dental emergencies occurring in a university-based, pediatric dentistry postgraduate outpatient clinic. All patients presenting for emergency dental care during scheduled clinic hours over a three year were identified, and their charts were retrieved. Each record was reviewed for demographic information, chief complaint and clinical diagnosis. Only those charts with both chief complaints and clinical diagnoses recorded were included in this study. A total of 816 patients received emergency care, representing 15.3 percent of all patient treated during the study period. The patient population had a slight female predilection (53 percent female, 47 percent male) and a mean age of 5.1 years (range 10 days to 15 years). Ethnicity (39 percent African-American, 36 percent Hispanic, 24 percent Caucasian <1 percent Asian-American) was similar to that for the clinic in general. Reimbursement for dental care was primarily via Medicaid (91 percent) with <10 percent covered by insurance or payment by responsible parents. For one quarter of the children, the emergency visit was their first dental visit. Reasons for seeking emergency included 1) pain or discomfort due to caries [30.1 percent] with 27 percent due to early childhood caries; 2) dental trauma [23 percent];3) eruption difficulties [18 percent] with 27 percent due to early childhood caries; 2) dental trauma [23 percent];3 eruption difficulties [18 percent];4) soft tissue pathoses [16 percent]; 5) problems with orthodontic appliances or space maintainers [10 percent]; and 6) lost restorations [2 percent]. Pain and bleeding were the most common reasons for seeking emergency dental care. Most causes for seeking outpatient emergency dental care are disease processes which may be avoided by infant oral health and preventive dentistry programs and early treatment intervention.


Effect of comorbidity assessed by the Charlson Comorbidity Index on the length of stay, costs, and mortality among colorectal cancer patients undergoing colorectal surgery.
Charlson Comorbidity Index (CCI) is a good predictor for hospitalization cost and mortality among patients with chronic disease. However, the impact of CCI on patients after colorectal cancer surgery is unclear. This study aims to investigate the influence of comorbidity assessed by CCI on length of stay, hospitalization costs, and in-hospital mortality in patients with colorectal cancer (CRC) who underwent surgical resection. This historical cohort study collected 10,271 adult inpatients for CRC undergoing resection surgery in 33 tertiary hospitals between January 2018 and December 2019. All patients were categorized by the CCI score into four classes: 0, 1,2, and ≥3. Linear regression was used for outcome indicators as continuous variables and logical regression for categorical variables. EmpowerStats software and R were used for data analysis. Of all 10,271 CRC patients, 51.72% had at least one comorbidity. Prevalence of metastatic solid tumor (19.68%, except colorectal cancer) and diabetes without complication (15.01%) were the major comorbidities. The highest average cost of hospitalization (86,761.88 CNY), length of stay (18.13 days), and in-hospital mortality (0.89%) were observed in patients with CCI score ≥3 compared to lower CCI scores (p < .001). Multivariate regression analysis showed that the CCI score was associated with hospitalization costs (β, 7340.46 [95% confidence interval (CI) (5710.06-8970.86)], p < .001), length of stay (β, 1.91[95%CI (1.52-2.30)], p < .001), and in-hospital mortality(odds ratio (OR),16.83[95%CI (2.23-126.88)], p = .0062) after adjusted basic clinical characteristics, especially when CCI score ≥3. Notably, the most specific complication associated with hospitalization costs and length of stay was metastatic solid tumor, while the most notable mortality-specific comorbidity was moderate or severe renal disease. The research work has discovered a strong link between CCI and clinical plus economic outcomes in patients with CRC who underwent surgical resection.


Doppler Echocardiography Assessment of Aortic Stiffness in Female Adolescents with Anorexia Nervosa.
Anorexia nervosa (AN) is associated with abnormalities in biomarkers of cardiovascular risk. Arterial stiffness, as measured by pulse-wave velocity (PWV), is also a risk factor for cardiovascular disease. The aims of this study were to determine the stiffness of the aorta in female adolescents with AN and to determine if either the severity or the type of AN was associated with PWV. This was a retrospective case-control study. Adolescent patients with a clinical diagnosis of AN were included. Aortic diameter and pulse-wave transit time over a portion of the thoracic aorta were measured using Doppler echocardiography, and PWV was calculated. There were 94 female patients with AN and 60 adolescent female control subjects. There was no significant difference in age between patients with AN and control subjects (15.5 ± 1.7 vs 15.1 ± 2.6 years, P = .220). Body mass index (16.0 ± 2.4 vs 19.7 ± 2.7 kg/m2, P < .001) and body mass index percentile (9.4 ± 15.6 vs 45.5 ± 26.2, P < .001) were significantly lower for patients with AN than control subjects. PWV (443 ± 106 vs 383 ± 77 cm/sec, P < .001) was significantly higher in patients with AN than control subjects. Similar differences from control subjects were found in patients with AN with both lower and higher body mass index percentiles and also in patients with AN with the restrictive or the binge-purge subtype. Female adolescents with AN have increased aortic stiffness compared with control subjects. This study suggests that patients with AN may be at increased risk for future cardiovascular disease. Future studies are required to determine the reversibility of these changes with weight restoration.


The difficulty with experience: does practice increase susceptibility to premature closure?
A recent review of the physician performance literature concluded that the risk of prematurely closing one's diagnostic search increases with years of experience. To minimize confounding variables and gain insight into cognitive issues relevant to continuing education, the current study was performed to test this conclusion. Physician participants were shown a series of case histories and asked to judge the probability of a pair of diagnoses. The order in which features were presented was manipulated across participants and the probabilities compared to determine the impact of information order. Two groups of participants were recruited, 1 older than and 1 younger than 60 years. The probability assigned to a diagnosis tended to be greater when features consistent with that diagnosis preceded those consistent with an alternative than when the same features followed those consistent with the alternative. Older participants revealed a greater primacy effect than less experienced participants across 4 experimental conditions. Physicians with greater experience appear to weigh their first impressions more heavily than those with less experience. Educators should design instructional activities that account for experience-specific cognitive tendencies.


Alkaline Phosphatase: Discovery and Naming of Our Favorite Enzyme.
Alkaline phosphatase can be considered "our favorite enzyme" for reasons apparent to those who diagnose and treat metabolic bone diseases or who study skeletal biology. Few might know, however, that alkaline phosphatase likely represents the most frequently assayed enzyme in all of medicine. Elevated activity in the circulation is universally recognized as a marker for skeletal or hepatobiliary disease. Nevertheless, the assay conditions in many ways are nonphysiological. The term alkaline phosphatase emerged when it became necessary to distinguish "bone phosphatase" from the phosphatase in the prostate that features an acidic pH optimum. Beginning in 1948, studies of the inborn-error-of-metabolism hypophosphatasia would identify the natural substrates and establish the physiological role of alkaline phosphatase, including in biomineralization. Here, we recount the discovery in 1923 and then eventual naming of this enzyme that remains paramount in our field. © 2017 American Society for Bone and Mineral Research.


Phosphorus-Containing Bis-allenes: Synthesis and Heterocyclization Reactions Mediated by Iodine or Copper Dibromide.
Bisphosphorylallenes were easily obtained in multigram scale from the Wittig-type rearrangement of bispropargyl alcohols. Unlike other conjugated bis-allenes, these reagents underwent a double cyclization mediated by iodine or copper dibromide leading to the formation of bis-1,2-oxaphospholenes.


Female partners' estimations of male veterans' combat-related PTSD severity.
This study investigated concordance between male Vietnam veterans' and their female partners' reports of veterans' posttraumatic stress disorder (PTSD) symptoms. Fifty male Vietnam combat veterans and their partners rated the severity of their own PTSD symptoms. Also, partners rated the severity of veterans' symptoms. Results indicated modest levels of agreement in reports of symptom presence/absence. Partner ratings of veterans' PTSD severity were positively correlated with veteran reports and partners' own self-reported PTSD symptoms. After controlling for veterans' self-reported symptoms, partners' symptoms significantly predicted their estimates of veterans' avoidance symptoms, but not veterans' reexperiencing or hyperarousal symptoms. Theoretical and practical implications of these findings are discussed.


A polylactic acid non-woven nerve conduit for facial nerve regeneration in rats.
This study developed a biodegradable nerve conduit with PLA non-woven fabric and evaluated its nerve regeneration-promoting effect. The buccal branch of the facial nerve of 8 week-old Lewis rats was exposed, and a 7 mm nerve defect was created. A nerve conduit made of either PLA non-woven fabric (mean fibre diameter 460 nm), or silicone tube filled with type I collagen gel, or an autologous nerve, was implanted into the nerve defect, and their nerve regenerative abilities were evaluated 13 weeks after the surgery. The number of myelinated neural fibres in the middle portion of the regenerated nerve was the highest for PLA tubes (mean ± SD, 5051 ± 2335), followed by autologous nerves (4233 ± 590) and silicone tubes (1604 ± 148). Axon diameter was significantly greater in the PLA tube group (5.17 ± 1.69 µm) than in the silicone tube group (4.25 ± 1.60 µm) and no significant difference was found between the PLA tube and autograft (5.53 ± 1.93 µm) groups. Myelin thickness was greatest for the autograft group (0.65 ± 0.24 µm), followed by the PLA tube (0.54 ± 0.18 µm) and silicone tube (0.38 ± 0.12 µm) groups, showing significant differences among the three groups. The PLA non-woven fabric tube, composed of randomly-connected PLA fibres, is porous and has a number of advantages, such as sufficient strength to maintain luminal structure. The tube has demonstrated a comparable ability to induce peripheral nerve regeneration following autologous nerve transplantation.