Immunohistochemical Expression Status of p53, CD44v9, and Ki-67 in a Series of Fallopian Tube Lesions of High-grade Serous Carcinoma.
Pelvic high-grade serous carcinoma (HGSC) has been postulated to arise via a stepwise accumulation of (epi)genetic alterations from normal epithelium to secretory cell outgrowth (SCOUT), p53 signature, and serous tubal intraepithelial carcinoma (STIC) to invasive HGSC. The aim of this study is to investigate alterations in p53 and CD44v9 expression and the status of Ki-67 labeling index in a series of fallopian tube lesions of HGSC patients. A total of 45 specimens were analyzed in 16 patients with HGSC, and their lesions were categorized as follows: morphologically normal fallopian tube epithelium (FTE, n=6 samples), SCOUT (n=5), p53 signature (n=4), dormant STIC (n=8), active STIC (n=6), and HGSC (n=16). Morphologic features and immunohistochemical expression patterns of the p53 protein, CD44v9 protein, and Ki-67 antigen were blindly evaluated by 2 pathologists. Increased nuclear p53 protein accumulation was observed in p53 signature, dormant STIC, active STIC and HGSC compared with normal FTE and SCOUT (P<0.001). Immunohistochemistry scores of CD44v9 protein expression were significantly higher in normal FTE, SCOUT, and p53 signature than in dormant STIC, active STIC, and HGSC (P<0.001). Both active STIC and HGSC had significantly higher Ki-67 labeling indices than normal FTE, SCOUT, p53 signature and dormant STIC (P<0.001). CD44v9 loss contributes to the stepwise progression of p53 signature to dormant STIC. In conclusion, p53 mutation followed by CD44v9 loss may be involved in the evolution of STIC, which may confer positive clonal selection with a growth and survival advantage.


Enuresis Management in the Primary Care Pediatrics Clinic.
Enuresis is a frequent complaint not always volunteered by parents or patients. The pediatric clinician has to inquire about enuresis to break the secrecy surrounding this symptom that could be related to a more serious underlying renal, endocrine, or psychosocial disease. Determining the type of enuresis is crucial to offer optimal treatment. We present a review for the pediatric clinician to optimize their care of the child with monosymptomatic enuresis. [Pediatr Ann. 2018;47(10):e390-e395.].


Cardioprotective effects of tilianin in rat myocardial ischemia-reperfusion injury.
Tilianin, the main effective flavonoid monomer enriched from Dracocephalum moldavuca L., has been shown to have cardioprotective effects. However, the mechanism of tilianin cardioprotection remains largely unknown. The present study aimed to investigate the effects of tilianin preconditioning on myocardial ischemia/reperfusion injury and to analyze the possible mechanism of action. A total of 48 male Sprague Dawley rats were randomized into sham, model myocardial ischemia/reperfusion injury (MI/RI), propranolol hydrochloride positive control, and high‑, medium‑ and low‑dose tilianin groups (n=8 each). The rats in the tilianin groups were perfused with either 1.5, 2.5 or 5.0 mg/kg/d tilianin a week prior to surgery. The positive control group were perfused with 25 mg/kg/d propranolol. Saline was administered to the sham surgery and the MI/RI groups. The MI/RI model was established by ligating the left anterior descending coronary artery for 30 min, which was subsequently removed and the mice were observed for 120 min prior to sacrifice. Na+‑K+‑ATPase, Ca2+‑ATPase, nitric oxide (NO), nitric oxide synthase (NOS) and endothelial system‑related factors were analyzed using the respective detection kits. Immunohistochemistry was used to determine the expression levels of Bcl‑2 and Bax. Caspase‑3 activity was measured by quantitative polymerase chain reaction. The results showed that tilianin preconditioning significantly increased ATPase activity (P<0.01 and P<0.05) as compared with the model group. With regards to the regulation of endothelial function, significant decreases (P<0.01 and P<0.05) were detected in the serum NO levels and myocardial NOS activity when tilianin was administered to MI/RI rats, as compared with the model group, . In addition, the tilianin drug groups exhibited dose‑dependent reductions in the serum levels of endothelin 1 and thromboxane B2, and increases in the serum levels of calcitonin gene‑related peptide and 6‑keto prostaglandin F1a as compared with the model group (P<0.01 and P<0.05). Notably, the administration of tilianin significantly inhibited apoptosis, as evidenced by an increase in Bcl‑2 expression, and reductions in Bax and caspase‑3 mRNA expression levels (P<0.01 and P<0.05). These data indicate that pretreatment with tilianin exerts potent cardioprotective effects in rats with MI/RI. The anti‑MI/RI effects comprised relieving calcium overload, correction of energy metabolism, improvement of endothelial function and inhibiting cell apoptosis.


Medial flap middle turbinoplasty for solid middle turbinate hypertrophy: improving airway, speeding healing and preserving olfaction.
The techniques to be performed for bullous middle turbinates are well-defined and widely accepted in the literature. However, in the case of solid middle turbinate hypertrophy, information on surgical techniques that take into account function and sense of smell is very limited in the literature. The aim of this study was to compare the airway patency and olfaction results of patients diagnosed with solid middle turbinate hypertrophy, who underwent subtotal (transverse) resection or medial flap turbinoplasty of the middle turbinates. Thirty-five adult patients who were diagnosed with solid middle turbinate hypertrophy were divided into two groups, namely medial flap middle turbinoplasty (study group = 17) and transverse resection to the middle turbinate (control group = 18). Acoustic rhinometry, anterior rhinomanometry, peak nasal inspiratory flowmeter test, odor identification test, and n-butanol threshold measurements were performed before and 3 months after the surgery. In addition, preoperative and postoperative nasal obstruction and olfactory senses of the patients were evaluated with visual analog scale and nasal obstruction symptom evaluation scale. Visual analog scores for olfaction were significantly higher in the study group compared to the control group. In odor identification test, a significant improvement was observed in the study group, while a decrease was observed in the control group. While there was a decrease in the n-butanol thresholds values in the study group, there was an increase in the control group. Medial mucosal flap technique is an effective and functional turbinoplasty technique that can be used in solid hypertrophy of the middle turbinate, which offers advantages in terms of enhanced airway healing and olfactory results.


Definition of the ethical values and ethics codes for Turkish midwifery: a focused group study in kocaeli.
The independent roles of midwives have not been properly defined, and midwifery ethical values and moral codes proper to Turkish culture have not been developed. The absence of legal regulations concerning midwifery has negatively affected midwifery in the process of professionalization. The purpose of this study was to identify the professional values of midwifery in Turkey. A focus group was created with the participation of nine midwives working at two state hospitals and a university hospital that provide birth service for women in Kocaeli, which is the most important industrial city in Turkey. The opinions of the midwives on the characteristics that a good midwife should possess and the professional values that a good midwife should observe were collected via in-depth interviews. The interviews were recorded. A total of three meetings were held with the participants. Finally, the notes taken by the reporter during these interviews were rearranged, and the recordings were transcribed by the researchers. THE CHARACTERISTICS SUGGESTED BY THE PARTICIPANTS WERE CLASSIFIED INTO THREE CATEGORIES: professional, personal, and interpersonal. Professional competence, capacity to properly inform interested parties, trustworthiness, respect for individuals and human dignity, and empathy were the most commonly named characteristics. As for the professional values of midwifery, professional competence, trustworthiness, responsibility, maximum benefit, and protection of privacy were the most often identified. Midwives also reported that most of the difficulties they faced in the exercise of daily tasks concerned protecting the privacy of their patients as well as the integrity and prestige of the profession, achieving the maximum benefit and least harm for patients, and providing a just and equal service. The professional values were mentioned by participant midwives were similar to the values proposed by international professional organizations. But there were some differences perhaps due to cultural differences.


Diagnostic Accuracy of Sixty Four Multi-Slice CT Angiography in Assessment of Arterial Cut-Off and Run-Off in Comparison with Surgical Findings.
The accurate anatomic mapping and determination of the severity of arterial disease, an important health problem of the elderly, is of great significance. We aimed to determine the diagnostic value of 64-multislice CT angiography (MSCTA) in run-off and cut-off sites of arterial disease. Throughout the study, MSCTA followed by an operative intervention was carried out on a total of 38 patients with clinical signs and symptoms suggestive of arterial disease (AD) all of whom had the indication for vascular surgery. The mean age of patients was 34±15.86 (range, 23 to 93) years. MSCTA was executed using a 64-slice CT scanner, during the arterial phase of injecting the nonionic, contrast medium with a power injector at the rate of 5 ml/sec into the antecubital vein and exploration and revascularization of peripheral arterial disease was performed intraoperatively. Atherosclerosis and arterial disease, the most common causes of vascular occlusion, were more common in the lower extremities. According to MSCTA findings, the most frequent site of stenosis was the superficial femoral artery. Spearman's correlation coefficient showed a high degree of agreement amongst the raters. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and the accuracy of MSCTA compared to surgery were 83.8%, 96%, 96.8%, 81.3% and 89%, respectively. MSCTA findings were compared with surgery as a standard of reference, which showed concordance in the majority of cases (81.6%). Cut-off sites were correctly identified by MSCTA in 97.3% of the patients and the most common sites of discordance were the run-off sites (18.2%). MSCTA angiography as a novel diagnostic modality may be a suitable alternative and a viable choice for routine clinical diagnosis.


Identification of Rickettsial Infections (Rickettsia sp. TH2014) in Ctenocephalides orientis Fleas (Siphonaptera: Pulicidae).
Rickettsia felis (Rickettsiales: Rickettsiaceae) is an emergent human pathogen that causes febrile illnesses in various parts of the world. This study describes the identification and growth characteristics of a R. felis-like organism (designated as Rickettsia sp. TH2014) cultured from Ctenocephalides orientis fleas in rural Malaysia. In this study, culturing of rickettsiae from filtered triturated flea lysates was performed in Aedes albopictus C6/36 cells. Cytopathic effects were observed from one of the samples 4 d post-inoculation. Electron microscopy revealed actively replicating intracytosolic coccobacillary organisms in the rickettsia-infected cells. Sequence analysis of amplified citrate synthase (gltA) gene fragment shows complete match of the rickettsia with Rickettsia sp. Rf31 in Southeast Asia, and 'Candidatus Rickettsia senegalensis' strain PU01-02 in Africa. The whole-genome sequence of Rickettsia sp. TH2014 was determined and assembled. The estimated genome size and guanine + cytosine content of the rickettsia are 1.37 Mb and 32.9%, respectively. The high values of average nucleotide identity and tetra-nucleotide signature correlation index obtained from pairwise genome comparison study suggest the identification of the rickettsia as R. felis. The whole-genome single-nucleotide polymorphism analysis demonstrates close genetic relatedness of the rickettsia with R. felis and Rickettsia asemboensis. However, based on sequence analyses of rickettsial genes (16S rDNA, gltA, ompB, and sca4), Rickettsia sp. TH2014 is found to be distinct from R. felis and R. asemboensis. The sequence analyses reveal that Rickettsia sp. TH2014 is highly similar to 'Ca. Rickettsia senegalensis' detected in fleas from Africa, Asia, and North America. Further investigation to provide insights on pathogenic potential and transmission dynamics of the rickettsia is warranted.


LOCAL POPULATION DIFFERENTIATION FOR COMPATIBILITY IN AN ANNUAL LEGUME AND ITS HOST-SPECIFIC FUNGAL PATHOGEN.
Severe attack by the fungal pathogen Synchytrium decipiens frequently occurs in natural populations of the annual plant Amphicarpaea bracteata (Leguminosae) in eastern North America. Field transplant experiments indicate that there is significant population differentiation in the plant-fungus association over distances of 1 km or greater: plants transplanted back into their population of origin become heavily infected, while foreign plants from populations 1 or 100 km away experience little or no infection, even though these foreign plants are subject to heavy fungal attack in their native populations. To investigate the fine structure of population differentiation, progeny of A. bracteata plants collected at six sites at 30 m intervals along a transect were inoculated with a single strain of S. decipiens in a controlled environment. Fungal lesions were initiated in all 36 plant progeny groups tested, yet there was highly significant, 5-fold variation among plants from different sites in the mean number of fungal lesions developing per plant. In addition, all fungal lesions aborted without maturing spores on all plants from one site on the transect. Fungal lesion abortion rates averaged only 9% on plants from the other five sites. Such local population differentiation in plant-pathogen compatibility may be related to A. bracteata's high degree of self-pollination. Limited long-distance recombination in A. bracteata due to self-pollination and spatially restricted pollen flow may be a major factor preventing the evolution of increased plant resistance to fungal attack.


Unraveling the Roles of Regulatory Genes during Domestication of Cultivated Camellia: Evidence and Insights from Comparative and Evolutionary Genomics.
With the increasing power of DNA sequencing, the genomics-based approach is becoming a promising resolution to dissect the molecular mechanism of domestication of complex traits in trees. Genus Camellia possesses rich resources with a substantial value for producing beverage, ornaments, edible oil and more. Currently, a vast number of genetic and genomic research studies in Camellia plants have emerged and provided an unprecedented opportunity to expedite the molecular breeding program. In this paper, we summarize the recent advances of gene expression and genomic resources in Camellia species and focus on identifying genes related to key economic traits such as flower and fruit development and stress tolerances. We investigate the genetic alterations and genomic impacts under different selection programs in closely related species. We discuss future directions of integrating large-scale population and quantitative genetics and multiple omics to identify key candidates to accelerate the breeding process. We propose that future work of exploiting the genomic data can provide insights related to the targets of domestication during breeding and the evolution of natural trait adaptations in genus Camellia.


Diffuse Myocardial Calcifications Caused by Leptospirosis.
Severe leptospirosis is defined by multiple organ failure. Cardiac involvement is an uncommon complication in patients with leptospirosis, and the pathophysiology of it is not well understood. Diffuse myocardial calcifications connected with sepsis are infrequent, and their effect on heart function is hard to predict. They can lead to conduction disorders and arrhythmias, thereby causing sudden death. Myocardial calcifications are usually revealed incidentally by radiological investigations such as computed tomography (CT) scan in patients with or after sepsis and are commonly unidentified in practice because most cases progress gradually. This case report involves a 51-year-old male who presented to the emergency department with sepsis. The patient was diagnosed with leptospirosis, causing septic cardiomyopathy and diffuse calcifications of the myocardium of the left ventricle. This case highlights the importance of multimodality imaging and a multidisciplinary approach to diagnoses since early recognition and treatment are essential. Follow-up of such patients is necessary to monitor the systolic function of the left ventricle and cardiac arrhythmia.


[Role of membrane protectors and antioxidants in the process of perfusion and preservation of donor lungs].
Comparative study of the effect of four perfusion and preservation solutions on lung function, conducted in experiments on 69 inbred dogs, revealed the following regular features. Euro-Collins and electrolyte solutions cause a marked increase of the capillary-hydrostatic pressure, a significant decrease of colloido-osmotic pressure of the plasma, and, as a result, reduction of the ient between them. This is manifested by edema of the lungs. The use of LPD solution is attended by moderate edema of the lungs in moderately increased capillary hydrostatic pressure and mildly reduced colloido-osmotic pressure of the plasma. Perfusion and preservation of the lungs with the LPD solution, containing membrane protectors and antioxidants, for 12 hours is marked by practically unchanged indices of capillary-hydrostatic pressure, plasma coloido-osmotic pressure, and the gradient between them. Edema of the lungs does not develop in this case.


Argon Plasma Induced Phase Transition in Monolayer MoS2.
In this work, we report a facile, clean, controllable and scalable phase engineering technique for monolayer MoS2. We found that weak Ar-plasma bombardment can locally induce 2H→1T phase transition in monolayer MoS2 to form mosaic structures. These 2H→1T phase transitions are stabilized by point defects (single S-vacancies) and the sizes of induced 1T domains are typically a few nanometers, as revealed by scanning tunneling microscopy measurements. On the basis of a selected-area phase patterning process, we fabricated MoS2 FETs inducing 1T phase transition within the metal contact areas, which exhibit substantially improved device performances. Our results open up a new route for phase engineering in monolayer MoS2 and other transition metal dichalcogenide (TMD) materials.


Sequence variability in four mitochondrial genes among pinworm Aspicularis tetraptera isolates from laboratory mice in four provinces, China.
This research aimed at exploring sequence variability in four mitochondrial (mt) genes, namely, cytochrome c oxidase subunit 1 (cox1), cytochrome b (cytb) and NADH dehydrogenase subunits 1 and 5 (nad1 and nad5), among pinworm Aspicularis tetraptera isolates from laboratory mice in four different provinces, China. A part of the cox1 (pcox1), cytb (pcytb), nad1 and nad5 genes (pnad1 and pnad5) were amplified separately from individual pinworms by polymerase chain reaction (PCR) and sequenced to determine sequence variations and examine their phylogenetic relationships. Herein, the intra-specific sequence variations within A. tetraptera were 0-0.5% for pcox1, 0-1.4% for pcytb, 0-1.8% for pnad1 and 0-1.7% for pnad5, respectively. In contrast, the inter-specific sequence differences among members of the Oxyuridae were significantly higher, being 13.7-17.0% for pcox1, 24.5-34.7% for pcytb, 26.6-29.6% for pnad1 and 24.4-25.5% for pnad5, respectively. Three methods, namely, Bayesian inference (BI), maximum likelihood (ML) and maximum parsimony (MP), were used for phylogenetic analyses based on the combined sequences of the four mt gene sequences, and the results indicated that all A. tetraptera samples form monophyletic groups, but samples from the same geographical origin did not always cluster together. This study demonstrated the existence of low-level intra-specific variation in four mtDNA sequences among A. tetraptera isolates from laboratory mice in different geographic regions in China, indicating no obvious geographical distinction among A. tetraptera isolates in China. These findings have important implications for studying systematics, molecular epidemiology and population genetics of A. tetraptera.


How to study the effects of inflammation on coronary vasomotion and their clinical relevance.
In patients with acute coronary syndromes systemic inflammation is associated with an enhanced vasoreactivity of the culprit coronary lesion. In the complex scenario of the mechanisms responsible for myocardial ischemia, the increased coronary vasoreactivity at the site of the culprit lesion may represent an important pathogenetic factor by limiting coronary blood flow. Systemic inflammation and epicardial vessel vasomotion can be easily measured in humans although, at present, the clinical relevance of such association has not been assessed in clinical trial. In the future, the development of drugs capable of blocking inflammatory molecules, in particular C-reactive protein and endothelin-1, will provide new tools to establish whether inflammation directly contributes to the pathogenesis of the enhanced coronary vasoreactivity and, more importantly, whether these drugs will be capable of positively affecting the prognosis of patients with acute coronary syndromes.


Following Up Crack Users after Hospital Discharge Using Record Linkage Methodology: An Alternative to Find Hidden Populations.
This paper presents the probabilistic record linkage (PRL) methodology as an alternative way to find or follow up hard-to-reach population as crack users. PRL was based on secondary data from public health information systems and the strategy used from standardization; phonetic encoding and the rounds of matching data were described. A total of 293 patient records from medical database and two administrative datasets obtained from Ministry of Health Information Systems were used. Patient information from the medical database was the identifiers to the administrative datasets containing data on outpatient treatment and hospital admissions. 40% of patient records were found in the hospital database and 12% were found in the outpatient database; 95% of the patients were hospitalized up to 5 times, and only 10 out of them had outpatient information. The record linkage methodology by linking government databases may help to address research questions about the path of patients in the care network without spending time and financial resources with primary data collection.


Pharmacokinetics of caspofungin acetate to guide optimal dosing in cats.
Cats are the most common mammal to develop invasive fungal rhinosinusitis caused by cryptic species in Aspergillus section Fumigati that are resistant to azoles but susceptible to caspofungin. In this study nonlinear mixed-effects pharmacokinetic modeling and simulation was used to investigate caspofungin pharmacokinetics and explore dosing regimens in cats using caspofungin minimum effective concentrations (MECs). Plasma concentrations in healthy cats were determined using HPLC-MS/MS after administration of a single and seven consecutive daily intravenous doses of 1 mg/kg caspofungin. In the final pharmacokinetic model an optimum maximum concentration (Cmax): MEC ratio of 10-20 was used to guide caspofungin efficacy. Simulations were performed for dosing regimens (doses 0.25-2 mg/kg and 6-72 h dosing intervals) with and without inclusion of a loading dose. Using a 1 mg/kg dose Cmax first dose was 14.8 μg/mL, Cmax at steady state was 19.8 μg/mL, Cmin was 5 μg/mL and Cmax: MEC was >20 in 42.6% of cats after multiple doses. An optimal Cmax: MEC ratio was achieved in caspofungin simulations using 0.75 mg/kg q 24 h or 1 mg/kg q 72h. However, at 1 mg/kg q 72h, Cmin was < MEC (<1 μg/mL) in over 95% of the population. Using a loading dose of 1 mg/kg and a daily dose of 0.75 mg/kg thereafter, the Cmax: MEC was optimal and Cmin was > 2.5 μg/mL for 98% of the population. Based on the modeling data this dosing regimen is likely to achieve target therapeutic concentrations, meet the proposed Cmax: MEC window and provide consistent exposure between doses.


A Permutation-Randomization Approach to Test the Spatial Distribution of Plant Diseases.
The analysis of the spatial distribution of plant diseases requires the availability of trustworthy geostatistical methods. The mean distance tests (MDT) are here proposed as a series of permutation and randomization tests to assess the spatial distribution of plant diseases when the variable of phytopathological interest is categorical. A user-friendly software to perform the tests is provided. Estimates of power and type I error, obtained with Monte Carlo simulations, showed the reliability of the MDT (power > 0.80; type I error < 0.05). A biological validation on the spatial distribution of spores of two fungal pathogens causing root rot on conifers was successfully performed by verifying the consistency between the MDT responses and previously published data. An application of the MDT was carried out to analyze the relation between the plantation density and the distribution of the infection of Gnomoniopsis castanea, an emerging fungal pathogen causing nut rot on sweet chestnut. Trees carrying nuts infected by the pathogen were randomly distributed in areas with different plantation densities, suggesting that the distribution of G. castanea was not related to the plantation density. The MDT could be used to analyze the spatial distribution of plant diseases both in agricultural and natural ecosystems.


[The patients of the psychiatric office of a polyclinic: patients undetected by the clinic or a new contingent?].
Epidemiology study of patients in primary care settings has shown prevalence of borderline mental disorders (41.58 per 1000 population) in comparison with patients of psychiatric outpatient clinic (11.4 per 1000). The question arises were those undetected by psychiatric out-patient clinics (those who didn't visit psychiatrist for individual reasons) or they represented another contingent. Comparative analysis of groups standardized on nosological, syndromal and educational levels revealed that there were various contingents of patients. The main difference was determined by different duration of disease before the first visit to psychiatrist, that reflected various severity of the disease (less severity of the disease was observed in patients of primary care institutions).


Predicting responsiveness to a depressive mood induction procedure.
Inducing various mood states -- sad or depressed mood in particular -- has become a widely employed and accepted means of experimentally examining the link between emotion and cognition, particularly with research on cognitive theory and depression. Using various criteria, studies utilizing mood induction procedures (MIPs) have reported successful induction of the desired mood in participants at rates ranging from 50 to 75%, clearly reflecting substantial individual variation. Individual differences in response to MIPs, however, have received little attention. Drawing on both theory and previous research, the present study identified and examined a range of possible predictors of response to depressive mood induction in a sample of 100 undergraduate students. Results indicated that of the examined predictors, experience with recent negative events prior to the mood induction and participant mood state, including self-reported symptoms of anxiety, significantly predicted reported mood state following the MIP. The implications of these results for models of vulnerability and resilience to negative mood states are discussed, and future research directions are provided.


Prevalence of chronic kidney disease in patients with chronic hepatitis B: A cross-sectional survey.
Renal safety is a major concern during long-term antiviral treatment for chronic hepatitis B (CHB). This study aimed to investigate the prevalence of chronic kidney disease (CKD) in patients with CHB that had been treated with antiviral therapy. This was a single-centre, cross-sectional study in a real-life cohort in which all patients received antiviral treatment. Serum creatinine-based equations from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) were used to estimate the glomerular filtration rate (GFR). CKD was defined as an eGFR <60 mL/min/1.73 m² or a urinary albumin to creatinine ratio ≥ 3 mg/mmol (defined as albuminuria). Univariate and multivariate analyses were conducted to determine the risk factors of CKD. A total of 1985 patients were included in the analysis from February 2015 to December 2015. The mean age and median duration of antiviral treatment was 42.20 years and 17.05 months, respectively. The overall prevalence of CKD was 7.9% (157/1985), with 44 patients experiencing decreased renal function (eGFR less than 60 mL/min/1.73 m²) and 129 patients with albuminuria. Patients with cirrhosis had a higher prevalence of a decreased GFR (4.3% vs 1.6%, P<.001) and albuminuria (11.1% vs 5.2%, P<.001) than those without cirrhosis. In the multivariate analysis, hypertension (Odds Ratio [OR] 4.564, P<.001), diabetes mellitus (OR 2.688, P<.001) and cirrhosis (OR 1.918, P<.001) were independent factors associated with the presence of CKD. CKD was a clinically significant comorbidity in patients with CHB. Special attention should be paid to cirrhotic patients and patients with the metabolic syndrome.


12. Timing of surgery for breast cancer.
Several studies have now shown that premenopausal women with early breast cancer have a significantly better prognosis if their tumours are excised during the luteal phase of the cycle. The 10-year survival for node positive cases undergoing follicular phase surgery was 33% compared with 78% in those having surgery at other times of the menstrual cycle. Further work has shown that there is an improved survival in those with plasma progesterone levels >4 ng/ml(-1), associated with the luteal phase. Luteal phase surgery is also associated with a decreased risk of vascular invasion, implying that the tumour is more cohesive at that time. Similarly, in the heaviest quartile of postmenopausal patients, with the highest endogenous oestrogen levels, there was vascular invasion around tumours in 45% compared with only 11% of the lightest quartile. Changing the hormonal milieu at the time of surgery for breast cancer may have the ability to improve the prognosis for some patients with early breast cancer.


Effect of naturally reduced ovarian function on plasma lipoprotein and 27-hydroxycholesterol levels in baboons (Papio sp.).
Female baboons over 15 years of age develop irregular menstrual cycles, an indication of declining ovarian function similar to that occurring in perimenopausal women. To determine the effect of declining ovarian function on plasma lipoprotein metabolism and plasma oxysterols, we measured plasma lipoprotein and 27-hydroxycholesterol levels in 86 female baboons from 15-28 years of age with regular (n = 51) and irregular (n = 35) menstrual cycles. We sampled blood and liver while they were consuming a basal diet and after consuming a high cholesterol and high fat diet for 7 weeks. On the basal diet, baboons with irregular cycles had higher VLDL + LDL/HDL cholesterol ratios (P = 0.034). After consuming the HCHF diet for 7 weeks, total plasma (P < 0.001) and VLDL + LDL (P < 0.001) cholesterol concentrations and VLDL + LDL/HDL sterol ratios (P < 0.001) increased in both cycle groups; whereas HDL cholesterol concentrations increased only in baboons with regular cycles (P = 0.009). As a result, HDL cholesterol concentrations (P = 0.006) were lower and VLDL + LDL/HDL cholesterol ratios (P = 0.002) were higher in baboons with irregular cycles on the HCHF diet. Plasma 27-hydroxycholesterol concentrations were higher in baboons with regular cycles than in those with irregular cycles on both basal (P = 0.018) and HCHF (P = 0.037) diets and were positively correlated (P < 0.001) with hepatic sterol 27-hydroxylase activities on both diets. Hepatic sterol 27-hydroxylase activities were negatively correlated with the VLDL + LDL/HDL cholesterol ratios on the HCHF diet (r = -0.342, P = 0.033). These results suggest that declining ovarian function changes the plasma lipoprotein pattern to one that is more atherogenic. Ovarian failure is also associated with decreased concentrations of plasma 27-hydroxycholesterol (the major oxysterol of plasma), and the decrease in plasma 27-hydroxycholesterol concentration was due to the decrease in hepatic sterol 27-hydroxylase activity. The effects of ovarian failure on plasma lipoprotein metabolism and plasma 27-hydroxycholesterol may be mediated by the decreased production of estrogen in perimenopausal baboons. Thus, the perimenopausal baboon is an excellent model for menopause and can be used for studies that cannot be conducted in women.


The regulatory role of serum response factor pathway in neutrophil inflammatory response.
Neutrophils rapidly migrate to sites of injury and infection. Egress of neutrophils from the circulation into tissues is a highly regulated process involving several distinct steps. Cell-cell interactions mediated by selectins and integrins and reorganization of the actin cytoskeleton are key mechanisms facilitating appropriate neutrophil recruitment. Neutrophil function is impaired in inherited and acquired disorders, such as leukocyte adhesion deficiency and myelodysplasia. Since the discovery that deletion of all or part of chromosome 5 is the most common genetic aberration in myelodysplasia, the roles of several of the deleted genes have been investigated in hematopoiesis. Several genes encoding proteins of the serum response factor (SRF) pathway are located on 5q. This review focuses, in particular, on the role of SRF in myeloid maturation and neutrophil function. SRF and its pathway fulfill multiple complex roles in the regulation of the innate and adaptive immune system. Loss of SRF leads to defects in B-cell and T-cell development. SRF-deficient macrophages fail to spread, transmigrate, and phagocytose bacteria, and SRF-deficient neutrophils show defective chemotaxis in vitro and in vivo with failure of inside-out activation and trafficking of the Mac1 integrin complex. Loss of the formin mammalian Diaphanous 1, a regulator of linear actin polymerization and mediator of Ras homolog family member A signaling to SRF, results in aberrant myeloid differentiation and hyperactivity of the immune system. SRF is an essential transcription factor in hematopoiesis and mature myeloid cell function. SRF regulates neutrophil migration, integrin activation, and trafficking. Disruption of the SRF pathway results in myelodysplasia and immune dysfunction.


Reconstructing tumor genome architectures.
Although cancer progression is often associated with genome rearrangements, little is known about the detailed genomic architecture of tumor genomes. The attempt to reconstruct the genomic organization of a tumor genome recently resulted in the development of the End Sequence Profiling (ESP) technique, and the application of this technique to human MCF7 tumor cells. We formulate the ESP Genome Reconstruction Problem, and develop an algorithm to solve this problem in the case of sparse ESP data. We apply our algorithm to analyze human MCF7 tumor cells, and obtain the first reconstruction of the putative architecture of human MCF7 tumor genome. Our results assist in the ongoing ESP analysis of MCF7 tumors by suggesting additional ESP experiments for the completion of a reliable reconstruction of the MCF7 tumor genome, and by focusing BAC re-sequencing efforts.


Structural MRI Brain Alterations in Borderline Personality Disorder and Bipolar Disorder.
Bipolar disorder (BD) and borderline personality disorder (BPD) share many behavioral features, such as periods of marked affective lability and instability. Although there is a symptomatic overlap, the two disorders may be differentiated based on longitudinal course, phenomenology, and treatment responsiveness. In addition, the emotional changes in BPD are generally influenced by interpersonal factors, whereas BD episodes tend to be more sustained. We performed a literature review on the structural MRI features of both disorders and compared the findings. There are differences in areas of white and gray matter volumes and thickness in BP and BPD. BPD primarily affects the fronto-limbic network, in particular, the amygdala, hippocampus, and orbitofrontal cortex, whereas BP affects both cortical and subcortical areas. There are a limited number of large studies, and many studies examined in this review did not adjust for confounding factors or motion artifacts, which limit the utility of current data.


Pancreatic stromal tumor of nerve sheath origin treated by pancreatoduodenectomy.
A pancreatic sarcoma of nerve sheath origin is reported in a 28-year-old female patient, who presented with melaena. Preoperative imaging showed an 8.5 cm diameter mass in the head of pancreas. There was bleeding from the papilla of Vater at endoscopy and a highly vascular lesion on arteriography. The patient was submitted to proximal pancreatoduodenectomy and remains symptom-free at 1 year follow-up.


Effects of chestnut tannins on performance and antioxidative status of transition dairy cows.
This study was conducted to evaluate the effects of chestnut tannins (CT) on performance and antioxidative status of transition dairy cows. Twenty multiparous Chinese Holstein cows in late gestation were paired according to expected calving date and randomly assigned either to a diet supplemented with CT (CNT, 10 g of CT/kg of diet, dry matter basis) or to an unsupplemented control (CON) diet from 3 wk prepartum to 3 wk postpartum. Blood samples were taken on d -21, 1, 7, and 21 relative to calving for analysis of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), and malondialdehyde (MDA). Liver samples were taken by puncture biopsy on d 1 and 21 relative to calving for analysis of SOD, GSH-Px, and MDA. Data were analyzed for a completely randomized block design with repeated measures. The addition of CT had no significant effects on dry matter intake, body weight, body condition score, milk yield, 3.5% fat-corrected milk yield, and milk composition but did decrease milk MDA and somatic cell score in transition dairy cows. Dry matter intake decreased from d -21 to 0 and increased from d 1 to 21 relative to calving across treatments. During the experimental period, body weight and body condition score decreased, whereas milk MDA and somatic cell score increased across treatments. A time effect was also observed for plasma MDA, which peaked on d 1 relative to calving and remained higher than that on d -21 relative to calving across treatments. Addition of CT decreased MDA concentrations in plasma and liver. Neither time nor CT × time effects were observed for SOD and T-AOC in plasma and SOD and GSH-Px in liver; a time effect was observed for plasma GSH-Px, which peaked on d 1 relative to calving and remained higher than those on d -21 relative to calving across treatments. Addition of CT increased SOD, GSH-Px, and T-AOC activities in plasma and SOD and GSH-Px activities in liver. In conclusion, addition of CT might inhibit lipid peroxidation and increase antioxidant enzymes activities in plasma and liver of transition dairy cows. Supplementation of CT may be a feasible means to improve the antioxidative status of transition dairy cows.


Navigating the manyverse of skin conductance response quantification approaches - A direct comparison of trough-to-peak, baseline correction, and model-based approaches in Ledalab and PsPM.
Raw data are typically required to be processed to be ready for statistical analyses, and processing pipelines are often characterized by substantial heterogeneity. Here, we applied seven different approaches (trough-to-peak scoring by two different raters, script-based baseline correction, Ledalab as well as four different models implemented in the software PsPM) to two fear conditioning data sets. Selection of the approaches included was guided by a systematic literature search by using fear conditioning research as a case example. Our approach can be viewed as a set of robustness analyses (i.e., same data subjected to different processing pipelines) aiming to investigate if and to what extent these different quantification approaches yield comparable results given the same data. To our knowledge, no formal framework for the evaluation of robustness analyses exists to date, but we may borrow some criteria from a framework suggested for the evaluation of "replicability" in general. Our results from seven different SCR quantification approaches applied to two data sets with different paradigms suggest that there may be no single approach that consistently yields larger effect sizes and could be universally considered "best." Yet, at least some of the approaches employed show consistent effect sizes within each data set indicating comparability. Finally, we highlight substantial heterogeneity also within most quantification approaches and discuss implications and potential remedies.


Palinacousis leading to the diagnosis of temporal lobe seizures in a patient with schizophrenia.
Palinacousis is a rarely reported symptom of temporal lobe dysfunction. Especially in psychiatric patients it may be misdiagnosed if it is not differentiated from the auditory hallucinations of psychotic illness. We report the case of a 20-year-old patient with the previously established diagnosis of paranoid schizophrenia who presented with the symptom of palinacousis. She was not psychotic at that time, her only complaints being recurrent auditory sensations. Repeated EEG recordings showed a left temporal theta focus with spikes. The diagnosis of temporal lobe seizures was made. Treatment with carbamazepine led to complete recovery.


Black or red phosphorus yields the same blue phosphorus film.
After the discovery of graphene, many other 2D materials have been predicted theoretically and successfully prepared. In this context, single-sheet black phosphorus - phosphorene - is emerging as a viable contender in the field of (2D) semiconductors. Phosphorene offers high carrier mobility and an anisotropic structure that gives rise to a modulation of physical and chemical properties. This opens the way to many novel and fascinating applications related to field-effect transistors and optoelectronic devices. In previous studies, a single layer of blue phosphorene intermixed with Au atoms was grown using purified black phosphorus as a precursor. Starting from the observation that phosphorus vapor mainly consists of P clusters, in this work we aimed at obtaining blue phosphorus using much less expensive purified red phosphorus as an evaporant. By means of microscopy, spectroscopy and diffraction experiments, we show that black or red phosphorus deposition on Au(111) substrates yields the same blue phosphorus film.


Bone Regeneration Using Adipose-Derived Stem Cells with Fibronectin in Dehiscence-Type Defects Associated with Dental Implants: An Experimental Study in a Dog Model.
To determine the bone regeneration potential of a ceramic biomaterial coated with fibronectin and adipose-derived stem cells covered in three-wall critical-size defects associated with dental implants. In a total of 18 dogs, four dehiscence-type and critical-size defects were created surgically in the edentulous alveolar ridge with the simultaneous placement of dental implants. Defects were randomly regenerated using biomaterials coated with particulate ß-tricalcium phosphate (β-TCP), β-TCP with fibronectin (Fn) (β-TCP-Fn), and β-TCP with a combination of Fn and autologous adipose-derived stem cells (ADSCs) (β-TCP-Fn-ADSCs), leaving one defect as the control. The animals were divided into three groups according to the time of euthanasia (1, 2, or 3 months). Statistically significant differences between the three study groups (β-TCP, β-TCP-Fn, β-TCP-Fn-ADSCs) and the control group in the total area of bone regeneration and mineralized and nonmineralized tissue at 1, 2, and 3 months of healing were not observed. At 2 months, defects treated with β-TCP-Fn-ADSCs showed a significant decrease in the percentage of bone-to-implant contact (BIC) as compared with the β-TCP-Fn (P = .041) and control (P = .012) groups. At 3 months of healing, however, significant differences in BIC between the three study groups and controls were not found (P = .388). The use of ADSCs in the bone regeneration processes of dehiscencetype defects associated with simultaneous implant insertion does not seem to improve the area of bone regeneration or the percentage of BIC compared with other biomaterials or the control alveolar defect.


Polyomavirus middle T antigen as a probe for T cell antigen receptor-coupled signaling pathways.
Stimulation of the T cell antigen receptor (TCR) triggers a complex series of signaling events that culminate in T cell activation and proliferation. The complex structure of the TCR has hindered efforts to link specific signaling events induced by TCR cross-linkage to downstream activation responses, such as interleukin-2 (IL-2) gene transcription. Previous studies have shown that the polyomavirus-derived oncoprotein, middle T antigen (mT), transforms rodent fibroblasts by interacting with and activating several cytoplasmic signaling proteins (Src kinases, phospholipase C (PLC)-gamma1, Shc, and phosphoinositide 3-kinase (PI3-K) implicated in cell growth control. In this study, we demonstrate that expression of mT activates Jurkat T cells, as measured by increases in IL-2 promoter- and NFAT (nuclear factor of activated T cells)-dependent reporter gene transcription. The transcriptional response provoked by mT was blocked by the immunosuppressive drug FK506, a potent inhibitor of TCR-mediated IL-2 gene expression. Mutations that disrupted the binding of mT to Src kinases or PLC-gamma1 abrogated the ability of mT to deliver the signals needed for IL-2 promoter activation. In contrast, a mT mutant that failed to bind PI3-K induced a markedly elevated transcriptional response in Jurkat cells, whereas mutation of the Shc binding site in mT had little effect on the transactivating potential of this viral oncoprotein. Additional studies demonstrated that the association of mT with PLC-gamma1 was necessary and sufficient to activate both Ca2+- and Ras-dependent signaling cascades in Jurkat cells. These results indicate that PLC-gamma1 activation plays pivotal and pleiotropic roles in the stimulation of IL-2 gene expression, whereas activation of PI3-K negatively modulates this response in Jurkat T cells.


Physicians' antibiotic prescribing habits for upper respiratory tract infections in Turkey.
The aim of this study was to evaluate the antibiotic prescription rates for upper respiratory tract infections (uRTIs) by primary care physicians in Samsun, Turkey. Data were obtained from the records of 2,083 visits to 8 primary care areas. Trained research students were stationed on site at each of the 8 primary care areas during the study period. Clinical features of patients were documented on a standardized form. Patients who had acute pharyngitis, acute sinusitis, acute otitis media (AOM) and common cold were included in the study. This survey was conducted between June 1, 1999 and July 1, 1999. A total of 2,083 office visits were recorded and 502 (24.1%) of the patients had uRTIs. Physicians approached these conditions empirically, with only 2.9% of patients having a diagnostic test at initial examination. Antibiotics were prescribed for 461 patients (91.8%) with uRTIs (common cold: 41.9%, acute pharyngitis: 94.7%, acute sinusitis: 94.1% and AOM: 100%). 11.5% of the antibiotic prescriptions were inconsistent with current recommendations derived from the literature. Inadequate antibiotic prescribing was documented in 29.7% of antibiotic prescriptions. Errors were frequent in relation to dosage, dosage interval and duration of therapy. Overuse of antibiotics is widespread in our geographic area. Both administrative and educational intervention should be implemented to improve antibotic prescribing habits at the primary health care level to reduce the unnecessary use of antimicrobial agents.


Posttranslational effects of protein kinase C and insulin on red cell membrane phosphorylation and cation heteroexchange in hypertension.
In the red blood cell membrane, sodium-proton exchange (NHE-1) exchanges intracellular H(+), Li(+), and Na(+) with extracellular Na(+). In hypertensives (HT), the maximal velocity of translocation (V max)of Na(+)/H(+) and of Na(+)/Li(+) exchange modes are higher, while apparent affinity for external Na(+) of Na(+)/Li(+) exchange and Hill's coefficient for H(+) activation of Na(+)/H(+) exchange are lower than in normotensive subjects (NT). We have therefore examined the effects of protein kinase C (PKC) and insulin on red blood cell membrane phosphorylation and on the kinetic properties of cation heteroexchange. In red cell from NT, PMA-induced activation of PKC reduced K(m) for H(+) of NHE but it did not affect V(max) and K(m) for Na(+). In red cell from HT, PMA-induced a greater PKC stimulation and membrane phosphorylation of band 3,4.1,4.9 than in NT and it did not significantly reduced K(m) for H(i). On the contrary, in HT PKC activation significantly increased Hill's coefficient of NHE. The larger activation of PKC in HT could be due to downregulation secondary to higher membrane calpain activity. Incubation of red cells with insulin decreases K(m) for external Na(+) and increases V(max) of Na(+)/Li(+) exchange. Therefore, we have examined the relationships between Na(+)-activation kinetics of Na(+)/Li(+) exchange and fasting insulin levels. Na(+)-stimulated Li(+) efflux was studied by raising Na(+)up to 300 mM isoosmotically to measure K(m) for Na(+) and V (max). Li(+) efflux saturated at 150 mM external Na(+)in NT but not in HT because in HT it exhibited a two fold higher Na(+) Km. V(max) was higher in HT than in NT. In hyperinsulinemic (fasting insulin > 10 mu U/ml) HT, V(max) and Na(+) Km were higher than in normoinsulinemic HT. In NT, hyperinsulinemia was not associated to abnormal kinetic properties of Na(+)/Li(+)exchange. Stepwise multiple regression analysis confirmed that the main determinants of a high Km were blood pressure and insulin. Our results show that posttranslational effects of PKC and insulin affect the kinetic properties of NHE-1 in red blood cells and suggest that the differences observed between hypertensives and normotensive subjects can be accounted for by PKC activation and insulin exposure.


Consensus report of a joint NCI thoracic malignancies steering committee: FDA workshop on strategies for integrating biomarkers into clinical development of new therapies for lung cancer leading to the inception of "master protocols" in lung cancer.
On February 2, 2012, the National Cancer Institute (NCI) sponsored a 2-day workshop with the NCI Thoracic Malignancies Steering Committee and the Food and Drug Administration to bring together leading academicians, clinicians, industry and government representatives to identify challenges and potential solutions in the clinical development of novel targeted therapies for lung cancer. Measures of success are rapidly evolving from a scientific and regulatory perspective and the objectives of this workshop were to achieve initial consensus on a high priority biomarker-driven clinical trial designed to rapidly assess the activity of targeted agents in molecularly defined lung cancer subsets and to facilitate generation of data leading to approval of these new therapies. Additionally, the meeting focused on identification of the barriers to conduct such a trial and the development of strategies to overcome those barriers. The "Lung Master Protocols" recently launched by NCI were the direct outcome of this workshop.


Significant antitumor effects obtained by autologous tumor cell vaccine engineered to secrete interleukin (IL)-12 and IL-18 by means of the EBV/lipoplex.
The EBV/lipoplex is a nonviral gene delivery system composed of a cationic lipid and Epstein-Barr virus (EBV)-based plasmid vector that carries the EBV oriP and EBV nuclear antigen 1 (EBNA1) gene. Because the EBNA1 supports retention, nuclear localization, and transcriptional upregulation of the oriP-bearing plasmid, cells transfected with the EBV/lipoplex express the transgene at a very high level. We hypothesized that tumor cells genetically manipulated with the EBV/lipoplex may be used as a tumor vaccine without drug selection, strongly contributing to immunotherapy of patients with malignancies. The cytokines interleukin (IL)-12 and IL-18 exert a variety of immune-regulatory functions including interferon (IFN)-gamma production and cytotoxic T lymphocyte (CTL) and natural killer (NK) activation. Here, we investigated the possible therapeutic effects of an autologous tumor cell vaccine in the B16 melanoma model. The vaccine was engineered to secrete IL-12 and IL-18 by means of the EBV/lipoplex. B16 cells were subcutaneously implanted into syngenic mice followed by repetitive immunization with irradiated B16 cells that had been transfected 3 days earlier by TFL2-3, a novel cationic lipid, with EBV-plasmid vectors encoding IL-12 and/or IL-18 genes (B16/mIL-12, B16/mIL-18, and B16/mIL-12+mIL-18). The mice vaccinated with B16/mIL-12 underwent strong tumor suppression accompanied by a high IFN-gamma production. Both CTL and NK activities were significantly elevated in these mice. When the tumor cell vaccine was prepared by means of conventional (non-EBV) plasmid vectors combined with the same cationic lipid, the therapeutic outcome was not as good, suggesting the superiority of the EBV-based plasmid in engineering these types of tumor vaccines. Vaccination with B16/mIL-18 was not effective in suppressing tumors, whereas B16/mIL-12+mIL-18 showed comparable antitumor therapeutic validity as B16/mIL-12 did. When IFN-gamma mutant (IFN-gamma(-/-) mice were treated, B16/mIL-12 vaccine did not show any therapeutic activity, suggesting the necessity of IFN-gamma in the anti-melanoma immune responses. In contrast, the antitumor effect was not affected by NK depletion in mice that received repetitive injections with anti-asialo GM1 antibody. Furthermore, vaccination with B16/mIL-12 significantly suppressed pulmonary metastases in mice that had been intravenously injected with parental B16. Our results suggest that the EBV/lipoplex is quite useful in generating an autologous tumor cell vaccine and that IL-12 is an important component of the vaccine.


Bone formation in the normal human otic capsule.
Postmoretem examination of undecaicified temporal bones from five patients treated with tetracycline during adult life for unrelated disease showed the uptake of tetracycline label within the endochondral bone the otic capsule. Adult endochondral bone is histologically woven (nonlamellar) in character, and has been assumed to be metabolically inert in the healthy state. The strong perlvascular labelling seen suggests that new bone is normally deposited in the otic capsule and that this new bone is lamellar in character. Continuous new bone formation in the presence of a constant net volume of bone implies that resorption must also occur normally within the otic capsule.


Referral patterns of primary care physicians for chronic kidney disease in general population and geriatric patients.
Late referral of patients with chronic kidney disease (CKD) by primary care physicians (PCPs) is associated with poor outcomes. We sought to assess factors influencing PCPs referral patterns in the general population and in geriatric patients, and compared their perceptions to the referral patterns. We retrospectively reviewed 268 patients with Stage 3 CKD (early referral) and 280 with Stage 4 CKD (appropriate referral) seen in renal clinic and compared them to 268 randomly selected non-referred Stage 4 CKD patients from primary care physicians office records. We also surveyed 400 regional PCPs on factors influencing their referral for CKD. Non-referred patients were significantly (p < 0.05) more likely to be over 65 years (OR: 3.5; 95% CI: 2.3 - 5.2), females (OR: 1.4; 95% CI: 1.0 - 2.0) and of non-white race (OR: 2.6; 95% CI: 1.5 - 4.5) after adjusting for relevant confounding variables. Charlson comorbidity index greater than 4 was associated with non-referral when the non-referral group was compared to the early referral group. Among geriatric patients, women and a higher comorbidity index were associated with non-referral. 25% of PCPs completed the survey and 62% PCPs were unfamiliar with K/DOQI referral guidelines. Age > 75 years, limited life expectancy, patient noncompliance or refusal to consider dialysis influenced PCPs decision to refer. Our study shows that elderly women, minorities and patients with multiple comorbidities are at risk for non-referral for CKD care. Educating PCPs on the appropriate referral of CKD patients, especially those at risk for late or non-referral to a nephrologist is warranted, as are trials assessing different educational strategies.


Lithium borate TLD for determining the backscatter factors for low-energy x rays: comparison with chamber-based and Monte Carlo derived values.
Recently, new backscatter factors for low-energy x rays derived from Monte Carlo calculations have been recommended in the UK code of practice for kilovoltage dosimetry published by (IPEMB). As these data, presented as a function of half-value layer, do not take account of the variation of the x-ray spectra for a given HVL, we have undertaken an experimental study in order to determine BSG for the beam qualities provided by a Darpac 2000 therapy unit. A RTL detector such as Li2B4O7:Cu and parallel-plate ion chambers specially designed for low-energy x-ray dosimetry have been used. The results obtained show very good agreement between the TLD and the Monte Carlo calculations, confirming values obtained by other authors with lithium borate TLD. On the contrary, the results obtained with plane-parallel ion chambers show discrepancies up to 9% that are discussed.


Relative potencies for acute effects of pyrethroids on motor function in rats.
The prevalence of pyrethroids in insecticide formulations has increased in the last decade. A common mode-of-action has been proposed for pyrethroids based on in vitro studies, which includes alterations in sodium channel dynamics in nervous system tissues, consequent disturbance of membrane polarization, and abnormal discharge in targeted neurons. The objective of this work was to characterize individual dose-response curves for in vivo motor function and calculate relative potencies for eleven commonly used pyrethroids. Acute oral dose-response functions were determined in adult male Long Evans rats for five Type I (bifenthrin, S-bioallethrin, permethrin, resmethrin, tefluthrin), five Type II (beta-cyfluthrin, lambda-cyhalothrin, cypermethrin, deltamethrin, esfenvalerate) and one mixed Type I/II (fenpropathrin) pyrethroids (n = 8-18 per dose; 6-11 dose levels per chemical, vehicle = corn oil, at 1 ml/kg). Motor function was measured using figure-8 mazes. Animals were tested for 1 h during the period of peak effects. All pyrethroids, regardless of structural class, produced dose-dependent decreases in motor activity. Relative potencies were calculated based on the computed ED30s. Deltamethrin, with an ED30 of 2.51 mg/kg, was chosen as the index chemical. Relative potency ratios ranged from 0.009 (resmethrin) to 2.092 (esfenvalerate). Additional work with environmentally-based mixtures is needed to test the hypothesis of dose-additivity of pyrethroids.


Detection of HER2 amplification in breast carcinomas: comparison of Multiplex Ligation-dependent Probe Amplification (MLPA) and Fluorescence In Situ Hybridization (FISH) combined with automated spot counting.
In this study the detection of HER2 gene amplification was evaluated using Fluorescence In Situ Hybridization (FISH; PathVysion) in comparison with Multiplex Ligation-dependent Probe Amplification (MLPA), a PCR based technique. These two methods were evaluated on a series of 46 formalin fixed paraffin embedded breast carcinomas, previously tested for protein overexpression by HercepTest (grouped into Hercep 1+, 2+ and 3+). HER2 gene amplification (ratio > or =2.0) by FISH was found in 9/10, 10/30 and 0/6 in IHC 3+, 2+ and 1+/0 cases, respectively. Digitalized automated spot counting performed with recently developed CW4000 CytoFISH software was 100% concordant with manual FISH scoring. Using MLPA 18/46 samples showed a clear HER2 amplification. Comparing MLPA and IHC showed the same results as for FISH and IHC. All but one FISH positive cases (18/19) were confirmed by MLPA for the presence of the gene amplification. The overall concordance of detection of Her2 gene amplification by FISH and MLPA was 98% (45/46). Furthermore, both the level of amplification and equivocal results correlated well between both methods. In conclusion, MLPA is a reliable and reproducible technique and can be used as an either alternative or additional test to determine HER2 status in breast carcinomas.


Extinction of insulin-like growth factor-I mitogenic signaling by antiestrogen-stimulated Fas-associated protein tyrosine phosphatase-1 in human breast cancer cells.
Steroidal (ICI 182, 780) and nonsteroidal hydroxytamoxifen (OH-Tam) antiestrogens inhibit growth factor-mitogenic activity in MCF 7 estrogen receptor-positive human breast cancer cells. Cell inhibition is correlated with an increase in membrane protein tyrosine phosphatase (PTP) activity, and the addition of orthovanadate prevents OH-Tam inhibition. After RT-PCR cloning of PTPs expressed in MCF 7 cells with primers to their catalytic domains, we have shown, by differential screening, that the expression of two enzymes, leukocyte common antigen-related PTP (LAR) and Fas-associated PTP-1 (FAP-1), was modulated by antiestrogens. By comparative RT-PCR, in situ hybridization, and Northern blot, LAR and FAP-1 mRNAs accumulation was found to be dose- and time-dependently increased by antiestrogens. To further demonstrate that PTPs were key mediators of antiestrogen-inhibitory action on the growth factor pathway, a panel of stable FAP-1 transfectants expressing low to high levels of antisense mRNAs was established. In these clones, the level of antisense RNA expression was correlated with a reduction in basal levels and a complete inhibition of antiestrogen-stimulated values of PTP activity. When FAP-1 expression was abolished, OH-Tam was no longer able to block insulin-like growth factor I mitogenic activity even though it remained strongly antiestrogenic. However, ICI 182,780 was still inhibitory, indicating that its effect was not exclusively mediated by PTP. Our data first demonstrate that a specifically regulated phosphatase (FAP-1) is implicated in the triggering of negative proliferation signals in breast cancer cells.


Effects of breathy voice source on ratings of hypernasality.
To investigate the effects of breathy voice sources on ratings of hypernasality using synthesized speech. Speech samples were obtained from children with cleft palates who demonstrated varying degrees of hypernasality and from a child with a voice disorder. Sources with 6 degrees of breathiness were created: a breathy source and five synthesized sources with lowered harmonics-to-noise ratio (HNR) values by the addition of impulses. These sources and each original (clear) source were combined with three kinds of filters: mild, moderate, and severely hypernasal. Consequently, 21 ([6 + 1] x 3) stimuli for each vowel (/a/ and /i/) were obtained for ratings. Thirteen speech pathologists with academic training and various clinical experiences with cleft palate speech rated hypernasality of the stimuli on a 5-point scale. Ratings of hypernasality for breathy and clear stimuli were analyzed using a repeated measures analysis of variance. The effects of breathy source on ratings of hypernasality were significant for the following filters: mild hypernasal /a/, severe hypernasal /a/, mild hypernasal /i/, and moderate hypernasal /i/. A post-hoc comparison test demonstrated that the more breathy sources (BH0 or BH2) generally increased the hypernasality score for mild hypernasal filters and decreased it for moderate and severe hypernasal filters. The less breathy sources (BH3, BH4, and BH5) hardly affected the ratings. The effects of breathiness on ratings of hypernasality seem to moderate rather than to mask perceived hypernasality. That is, breathiness raises slight hypernasality, whereas it reduces severe hypernasality.


The experiences and support needs of siblings of people with mucopolysaccharidosis.
The mucopolysaccharidoses (MPS) are a group of rare genetic disorders characterized by progressive multisystem disease. We sought to identify the perceptions and support needs of siblings, who often have lifelong relationships and assume important roles for their brothers and sisters with MPS. We designed an online survey to ask siblings about their experiences through a series of Likert statements and open-ended questions. A mixed methods approach was used to analyze the results. We analyzed eligible responses from 97 participants, ages 18.1-61.2 years, who have brothers and sisters with MPS I, II, III, IV, and VI. Participants reported serving as caregivers for their siblings with MPS, at all ages. While over 62% of siblings often felt sad because they have a brother or sister with MPS, over 90% of siblings reported that they like their brothers and sisters and expressed feelings of pride. Siblings wanted information about MPS, guidance for caregiving activities, genetic counseling, and opportunities to connect with other siblings. Families and professionals should acknowledge the unique experiences and needs of siblings, include siblings in medical conversations and care plans when appropriate, and connect siblings to resources for informational and emotional support.


Enantioselective synthesis of cyclic and linear diamines by imine cycloadditions.
Imine is one of the most versatile functional groups in chemistry and biochemistry fields. Although many biochemical reactions involve imine formation, the inherently unstable property of N-alkyl-α,β-unsaturated imines still hindered their utilization in organic synthesis. In this article, we described that the N-alkyl-α,β-unsaturated imines, which prepared from alkylamines and acrolein, could smoothly react through [4 + 4] cycloaddition to give eight-membered diazacyclooctane derivatives in excellent yields. Under a similar condition, in the presence of formaldehyde, the [4 + 2] and [4 + 2 + 2] cycloadditions could lead to the formation of six-membered hexahydropyrimidine or eight-membered triazacyclooctanes, depending on the substituent of aldehydes. Moreover, an easy functional group manipulation of the cyclic products obtained from these cycloadditions can provide variously substituted chiral linear diamines. We can utilize these novel reactivities to reveal the unknown and essential properties of many biological processes that involve N-alkyl-unsaturated imines.


World Trade Center-related asthma: clinical care essentials.
Asthma is defined as a heterogeneous disease with respiratory symptoms (wheeze, shortness of breath, chest tightness and cough) that vary over time and intensity, and variable expiratory airflow limitation. Environmental and occupational exposures contribute to its causation. WTC-related or aggravated asthma is considered a World Trace Center (WTC) Health Program certifiable disease. Criteria include defined exposures to the WTC dust and fumes, the presence of symptoms, or aggravated symptoms that are present within 5 years after the last potential for WTC dust/fume exposures (the last 9/11 exposures occurred on July 31, 2002), and a WTC-provider diagnosis of asthma. Asthma is the 3rd most common non-cancer certification among WTC responders and survivors. In this review we provide evidence-based information on the evaluation, diagnosis, and treatment of patients with WTC-related or aggravated asthma and include peer-reviewed research findings in WTC-exposed populations.


Prevalence and Disease Expression of Pathogenic and Likely Pathogenic Variants Associated With Inherited Cardiomyopathies in the General Population.
Pathogenic and likely pathogenic variants associated with arrhythmogenic right ventricular cardiomyopathy (ARVC), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy (HCM) are recommended to be reported as secondary findings in genome sequencing studies. This provides opportunities for early diagnosis, but also fuels uncertainty in variant carriers (G+), since disease penetrance is incomplete. We assessed the prevalence and disease expression of G+ in the general population. We identified pathogenic and likely pathogenic variants associated with ARVC, DCM and/or HCM in 200 643 UK Biobank individuals, who underwent whole exome sequencing. We calculated the prevalence of G+ and analyzed the frequency of cardiomyopathy/heart failure diagnosis. In undiagnosed individuals, we analyzed early signs of disease expression using available electrocardiography and cardiac magnetic resonance imaging data. We found a prevalence of 1:578, 1:251, and 1:149 for pathogenic and likely pathogenic variants associated with ARVC, DCM and HCM respectively. Compared with controls, cardiovascular mortality was higher in DCM G+ (odds ratio 1.67 [95% CI 1.04; 2.59], P=0.030), but similar in ARVC and HCM G+ (P≥0.100). Cardiomyopathy or heart failure diagnosis were more frequent in DCM G+ (odds ratio 3.66 [95% CI 2.24; 5.81], P=4.9×10-7) and HCM G+ (odds ratio 3.03 [95% CI 1.98; 4.56], P=5.8×10-7), but comparable in ARVC G+ (P=0.172). In contrast, ARVC G+ had more ventricular arrhythmias (P=3.3×10-4). In undiagnosed individuals, left ventricular ejection fraction was reduced in DCM G+ (P=0.009). In the general population, pathogenic and likely pathogenic variants associated with ARVC, DCM, or HCM are not uncommon. Although G+ have increased mortality and morbidity, disease penetrance in these carriers from the general population remains low (1.2-3.1%). Follow-up decisions in case of incidental findings should not be based solely on a variant, but on multiple factors, including family history and disease expression.


Deep Representation Learning with Sample Generation and Augmented Attention Module for Imbalanced ECG Classification.
Developing an efficient heartbeat monitoring system has become a focal point in numerous healthcare applications. Specifically, in the last few years, heartbeat classification for arrhythmia detection has gained considerable interest from researchers. This paper presents a novel deep representation learning method for the efficient detection of arrhythmic beats. To mitigate the issues associated with the imbalanced data distribution, a novel re-sampling strategy is introduced. Unlike the existing oversampling methods, the proposed technique transforms majority-class samples into minority-class samples with a novel translation loss function. This approach assists the model in learning a more generalized representation of crucially important minority class samples. Moreover, by exploiting an auxiliary feature, an augmented attention module is designed that focuses on the most relevant and target-specific information. We adopted an inter-patient classification paradigm to evaluate the proposed method. The experimental results of this study on the MIT-BIH arrhythmia database clearly indicate that the proposed model with augmented attention mechanism and over-sampling strategy significantly learns a balanced deep representation and improves the classification performance of vital heartbeats.


Heparin-Induced Thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin therapy. The use of heparin to flush some vascular access devices makes HIT a concern for infusion nurses. This article reviews the risk factors for, pathophysiology of, and management of HIT.


Sympathetic Nervous System Regulation of Auditory Function.
The auditory system processes how we hear and understand sounds within the environment. It comprises both peripheral and central structures. Sympathetic nervous system projections are present throughout the auditory system. The function of sympathetic fibers in the cochlea has not been studied extensively due to the limited number of direct projections in the auditory system. Nevertheless, research on adrenergic and noradrenergic regulation of the cochlea and central auditory system is growing. With the rapid development of neuroscience, auditory central regulation is an extant topic of focus in research on hearing. As such, understanding sympathetic nervous system regulation of auditory function is a growing topic of interest. Herein, we review the distribution and putative physiological and pathological roles of sympathetic nervous system projections in hearing. In the peripheral auditory system, the sympathetic nervous system regulates cochlear blood flow, modulates cochlear efferent fibers, affects hair cells, and influences the habenula region. In central auditory pathways, norepinephrine is essential for plasticity in the auditory cortex and affects auditory cortex activity. In pathological states, the sympathetic nervous system is associated with many hearing disorders. The mechanisms and pathways of sympathetic nervous system modulation of auditory function is still valuable for us to research and discuss.


Synthesis of the C9-C23 (C9'-C23') fragment of the dimeric natural product rhizopodin.
A stereoselective assembly of the C9-C23 (C9'-C23') fragment of rhizopodin, a 38-membered bis-lactone natural product, has been developed. A highly efficient approach to this fragment assembles >50% of the carbon skeleton and the stereochemical elements present in the natural product.


Complete blood count parameters and neutrophil-to-lymphocyte ratio values as markers for differentiation between systemic infectious and non-infectious uveitis.
To compare complete blood count (CBC) parameters and neutrophil/lymphocyte ratio (NLR) between patients with infectious uveitis (IU) and those with non-infectious uveitis (NIU) during the first acute uveitis attack (AUA). The records of 119 patients admitted with the first AUA between 2016 and 2019 and whose diagnosis was unknown at the time of admission were retrospectively reviewed. The patients were divided into two groups, IU and NIU according to diagnoses after ocular and systemic workup. The IU group was also divided into subgroups as uveitis associated with local ocular infections and systemic infections. The complete blood count and associated indices of patients calculated from samples taken during the attack were compared between the groups. A total of 60 NIU cases (mean age: 43.5 ± 11.6 years) and 59 IU cases (43.3 ± 14.7 years) were examined. Twenty-six of the NIU cases were female and 34 were male, while 32 of the IU cases were female and 27 were male. The localization of uveitis was similar in the IU and NIU groups (anterior: 11 vs. 18, intermediate: 3 vs. 6, posterior: 28 vs. 14, panuveitis: 17 vs. 22). The NLR values were significantly increased in patients with IU compared to those with NIU (p = 0.047). When the NLR is compared between NIU and subgroups of IU, this value was only found significantly increased in uveitis due to a systemic infection (n = 12) (p < 0.001). The mean white blood cell (WBC) count (p < 0.001) and neutrophil values (p < 0.001) were also observed significantly higher in the uveitis associated with systemic infectious diseases when compared with uveitis associated with local ocular infections and NIU group. In the current study, NLR values are compared with autoimmune uveitis and systemic infectious uveitis for the first time in patients with AUA. This ratio has been found significantly higher in uveitis associated with systemic infections. The use of CBC parameters and indices, especially the NLR, may be instrumental in assessing patients presenting with first AUA, particularly when there is no clear explanation or underlying cause.


Tubal pregnancy treated by salpingectomy using operative culdoscopy.
A case of unruptured Ampullary pregnancy in the 7th postmenstrual week is presented, which was diagnosed and treated at the same time by operative culdoscopy. The indication and advantages of this method are discussed.


The role of extracellular matrix in normal liver.
Sustained expression of liver-specific function by hepatocytes in culture requires a basement membrane-like matrix as the culture substratum. Individual components of the matrix cannot substitute for the complex. The implications of these findings for the intact liver include the possibility that the extracellular matrix helps maintain normal parenchymal cell function and that alteration of the matrix underlies the loss of hepatocellular function that occurs in acute inflammation. Moreover, the low level of DNA synthesis by hepatocytes on the complex substratum, in contrast to that of cells cultured on collagen, suggests that extracellular matrix also modulates hepatocyte proliferation.


Inappropriate prehospital ventilation in severe traumatic brain injury increases in-hospital mortality.
In the setting of acute brainstem herniation in traumatic brain injury (TBI), the use of hyperventilation to reduce intracranial pressure may be life-saving. However, undue use of hyperventilation is thought to increase the incidence of secondary brain injury through direct reduction of cerebral blood flow. This is a retrospective review determining the effect of prehospital hyperventilation on in-hospital mortality following severe TBI. All trauma patients admitted directly to a single level 1 trauma center from January 2000 to January 2007 with an initial Glasgow Coma Scale (GCS) score <or=8 were included in the study (n = 77). Patients without documented or with late (>20 min) arterial blood gas at presentation (n = 12) were excluded from the study. The remaining population (n = 65) was sorted into three groups based on the initial partial pressure of carbon dioxide: hypocarbic (Pco(2) < 35 mm Hg), normocarbic (Pco(2) 35-45 mm Hg), and hypercarbic (Pco(2) > 45 mm Hg). Outcome was based on mortality during hospital admission. Survival was found to be related to admission Pco(2) in head trauma patients requiring intubation (p = 0.045). Patients with normocarbia on presenting arterial blood gas testing had in-hospital mortality of 15%, significantly improved over patients presenting with hypocarbia (in-hospital mortality 77%) or hypercarbia (in-hospital mortality 61%). Although there are many reports of the negative impact of prophylactic hyperventilation following severe TBI, this modality is frequently utilized in the prehospital setting. Our results suggest that abnormal Pco(2) on presentation after severe head trauma is correlated with increased in-hospital mortality. We advocate normoventilation in the prehospital setting.


PTSD's risky behavior criterion: Relation with DSM-5 PTSD symptom clusters and psychopathology.
A new symptom criterion of reckless and self-destructive behaviors (E2) was recently added to posttraumatic stress disorder's (PTSD) diagnostic criteria in DSM-5, which is unsurprising given the well-established relation between PTSD and risky behaviors. Researchers have questioned the significance and incremental validity of this symptom criterion within PTSD's symptomatology. Unprecedented to our knowledge, we aim to compare trauma-exposed groups differing on their endorsement status of the risky behavior symptom on several psychopathology constructs (PTSD, depression, distress tolerance, rumination, anger). The sample included 123 trauma-exposed participants seeking mental health treatment (M age=35.70; 68.30% female) who completed self-report questionnaires assessing PTSD symptoms, depression, rumination, distress tolerance, and anger. Results of independent samples t-tests indicated that participants who endorsed the E2 criterion at a clinically significant level reported significantly greater PTSD subscale severity; depression severity; rumination facets of repetitive thoughts, counterfactual thinking, and problem-focused thinking; and anger reactions; and significantly less absorption and regulation (distress tolerance facets) compared to participants who did not endorse the E2 criterion at a clinically significant level. Results indicate the utility of the E2 criterion in identifying trauma-exposed individual with greater posttraumatic distress, and emphasize the importance of targeting such behaviors in treatment.


High-performance triethylsilylethynyl anthradithiophene transistors prepared without solvent vapor annealing: the effects of self-assembly during dip-coating.
Solution-processable small-molecule organic semiconductors have recently attracted significant attention for use as the active channel layers in organic field-effect transistors due to their good intrinsic charge carrier mobility and easy processability. Dip-coating is a good method for optimizing the film morphology and molecular ordering of the small-molecular semiconductors because the drying speed can be quantitatively controlled at the air-solution-substrate contact line. Here, we report the preparation of highly crystalline triethylsilylethynyl-anthradithiophene (TES-ADT) crystal arrays that exhibit an excellent field-effect mobility (up to 1.8 cm(2)/(V s)) via an optimized one-step dip-coating process. High-quality TES-ADT crystals were grown without solvent vapor annealing postprocessing steps, which were previously thought to be essential for improving the morphology, crystallinity, and electrical characteristics of TES-ADT thin films. An interesting correlation between the optimal pull-out rate and the self-assembly tendencies of some soluble acene semiconductors was observed, and the origin of the correlation was investigated. Our work demonstrates an alternative simple approach to achieving highly crystalline TES-ADT thin films, and further proposes a prospective method for optimizing the formation of thin films via the molecular self-assembly of soluble acenes.


Translation initiation and surface plasmon resonance: new technology applied to old questions.
Translation initiation in eukaryotes is a complicated process involving some of the largest cellular structures, the ribosomes, together with approx. 11 initiation factors, and a poorly characterized set of other proteins. The concerted action of all these components ultimately results in the formation of an 80 S ribosomal complex on the AUG codon of an mRNA, which is competent to start polypeptide production. In this brief overview, we describe the strategies developed by our laboratory to apply surface plasmon resonance (SPR)-based technology to the problem of elucidating kinetic aspects of substeps within the translation-initiation reaction. We then review how other groups have used similar SPR-based techniques to study related interactions.


Evaluation of integrated positron emission tomography and computed tomography accuracy in detecting lymph node metastasis in patients with adenocarcinoma vs squamous cell carcinoma.
The aim of our study was to analyze the specificity and sensitivity of integrated positron emission tomography and computed tomography (PET/CT) in detecting nodal metastasis according to histology (adenocarcinoma vs squamous cell carcinoma), and to identify the factors related to false-negative findings. A retrospective, single-institution review of 353 consecutive patients with suspected or pathologically proven, potentially resectable non-small-cell lung cancer (NSCLC) who had integrated PET/CT scanning at the same centre. Lymph node staging was pathologically confirmed on tissue specimens obtained at mediastinoscopy and/or thoracotomy. Statistical evaluation of PET/CT results was performed on a per-patient and per-nodal-station basis. A total of 2286 nodal stations (1643 mediastinal, 333 hilar and 310 intrapulmonary) were evaluated. Adenocarcinoma was the final diagnosis in 244 patients and squamous carcinoma in 109 patients. Nodes were positive for malignancy in 80 (32.8%) of 244 patients with adenocarcinoma (N1 = 31; N2 = 48 and N3 = 1) and in 32 (29.3%) of 109 with squamous carcinoma (N1 = 21 and N2 = 11). PET/CT in the adenocarcinoma group had a sensitivity, specificity and accuracy of 53.8, 91.5 and 79.1%, and in the squamous cell group, of 87.5, 81.8 and 83.5%, respectively in a per-patient analysis. In the analysis for N2 disease on a per-patient basis, the sensitivity, specificity and accuracy were 38.8, 97.4, and 85.7% for the adenocarcinoma group and 81.8, 91.8 and 90.8% in the squamous cell group. In the adenocarcinoma group, the mean diameter of false-negative lymph nodes was 7 mm (standard deviation [SD] ± 2.5 mm) compared with the diameter of true-positive lymph nodes of 12.5 (SD ± 4 mm; P < 0.00001). In the squamous cell group, the mean diameter of false-negative lymph nodes was 7.4 mm (SD ± 2.8 mm) compared with the diameter of true-positive lymph nodes of 14.7 (SD ± 6 mm; P < 0.005). In the adenocarcinoma group, false-negative lymph nodes were statistically correlated with the presence of vascular invasion and in the squamous cell group only with the maximum standardized uptake value (SUV(max)) < 5.4. The sensitivity of PET/CT in detecting nodal metastasis in patients with adenocarcinoma is too low to avoid any further invasive staging procedure. Ultrasound-guided needle biopsy or mediastinoscopy is still necessary in staging patients undergoing lung resection for adenocarcinoma.


Nucleotide sequence analysis of the L gene of Newcastle disease virus: homologies with Sendai and vesicular stomatitis viruses.
The nucleotide sequence of the L gene of the Beaudette C strain of Newcastle disease virus (NDV) has been determined. The L gene is 6704 nucleotides long and encodes a protein of 2204 amino acids with a calculated molecular weight of 248822. Mung bean nuclease mapping of the 5' terminus of the L gene mRNA indicates that the transcription of the L gene is initiated 11 nucleotides upstream of the translational start site. Comparison with the amino acid sequences of the L genes of Sendai virus and vesicular stomatitis virus (VSV) suggests that there are several regions of homology between the sequences. These data provide further evidence for an evolutionary relationship between the Paramyxoviridae and the Rhabdoviridae. A non-coding sequence of 46 nucleotides downstream of the presumed polyadenylation site of the L gene may be part of a negative strand leader RNA.


Optimized Method for Measuring Persistence in Escherichia coli with Improved Reproducibility.
Monitoring persister cells can be extremely difficult due to their transient and stochastic nature, their low abundance, and their resemblance to Viable But Non-Culturable Cells (VBNCs). To date, the predominant method consists of determining the survival rate of a bacterial population after antibiotic treatment as a function of time or antibiotic concentration. Unfortunately, this method is limited, as it shows high levels of dispersion of the data around the mean, making interpretation difficult. Furthermore, additional reproducibility problems arise from the lack of a standard method, different research groups using different protocols. Here, we describe a standard and optimized method for monitoring E. coli persister cells at the population level allowing for maximal reproducibility.


The Influence of the Plant Growth Regulator Maleic Hydrazide on Egyptian Broomrape Early Developmental Stages and Its Control Efficacy in Tomato under Greenhouse and Field Conditions.
Broomrapes (Phelipanche spp. and Orobanche spp.) are holoparasitic plants that cause tremendous losses of agricultural crops worldwide. Broomrape control is extremely difficult and only amino acid biosynthesis-inhibiting herbicides present an acceptable control level. It is expected that broomrape resistance to these herbicides is not long in coming. Our objective was to develop a broomrape control system in tomato (Solanum lycopersicum L.) based on the plant growth regulator maleic hydrazide (MH). Petri-dish and polyethylene-bag system experiments revealed that MH has a slight inhibitory effect on Phelipanche aegyptiaca seed germination but is a potent inhibitor of the first stages of parasitism, namely attachment and the tubercle stage. MH phytotoxicity toward tomato and its P. aegyptiaca-control efficacy were tested in greenhouse experiments. MH was applied at 25, 50, 75, 150, 300, and 600 g a.i. ha-1 to tomato foliage grown in P. aegyptiaca-infested soil at 200 growing degree days (GDD) and again at 400 GDD. The treatments had no influence on tomato foliage or root dry weight. The total number of P. aegyptiaca attachments counted on the roots of the treated plants was significantly lower at 75 g a.i. ha-1 and also at higher MH rates. Phelipanche aegyptiaca biomass was close to zero at rates of 150, 300, and 600 g a.i. ha-1 MH. Field experiments were conducted to optimize the rate, timing and number of MH applications. Two application sequences gave superior results, both with five split applications applied at 100, 200, 400, 700, and 1000 GDD: (a) constant rate of 400 g a.i. ha-1; (b) first two applications at 270 g a.i. ha-1 and the next three applications at 540 g a.i. ha-1. Based on the results of this study, MH was registered for use in Israel in 2013 with the specified protocol and today, it is widely used by most Israeli tomato growers.


Complementary PTM Profiling of Drug Response in Human Gastric Carcinoma by Immunoaffinity and IMAC Methods with Total Proteome Analysis.
Gaining insight into normal cellular signaling and disease biology is a critical goal of proteomic analyses. The ability to perform these studies successfully to extract the maximum value and discovery of biologically relevant candidate biomarkers is therefore of primary importance. Many successful studies in the past have focused on total proteome analysis (changes at the protein level) combined with phosphorylation analysis by metal affinity enrichment (changes at the PTM level). Here, we use the gastric carcinoma cell line MKN-45 treated with the c-Met inhibitor SU11274 and PKC inhibitor staurosporine to investigate the most efficient and most comprehensive strategies for both total protein and PTM analysis. Under the conditions used, total protein analysis yielded few changes in response to either compound, while analysis of phosphorylation identified thousands of sites that changed differentially between the two treatments. Both metal affinity and antibody-based enrichments were used to assess phosphopeptide changes, and the data generated by the two methods was largely complementary (non-overlapping). Label-free quantitation of peptide peak abundances was used to accurately determine fold-changes between control and treated samples. Protein interaction network analysis allowed the data to be placed in a biologically relevant context, and follow-up validation of selected findings confirmed the accuracy of the proteomic data. Together, this study provides a framework for start-to-finish proteomic analysis of any experimental system under investigation to maximize the value of the proteomic study and yield the best chance for uncovering actionable target candidates.


The clinical utility of a comprehensive periodic assessment form for the geriatric rehabilitation patient.
The Comprehensive Periodic Assessment Form is a new format used to document a patient's rehabilitation progress. It is a nonnarrative, semi-graphical form in which is digested on one page many sheets of progress notes from a variety of disciplines. Mobility, ADL, mental, and medical status overtime can be ascertained at a glance. The form has special utility for the aged patient experiencing rehabilitation treatment.


Boundary and impurity effects on the entanglement of Heisenberg chains.
We study entanglement of a pair of qubits and the bipartite entanglement between the pair and the rest within open-ended Heisenberg XXX and XY models. The open boundary condition leads to strong oscillations of entanglements with a two-site period, and the two kinds of entanglements are 180 degrees out of phase with each other. The mean pairwise entanglement and ground-state energy per site in the XXX model are found to be proportional to each other. We study the effects of a single bulk impurity on entanglement, and find that there exist threshold values of the relative coupling strength between the impurity and its nearest neighbors, after which the impurity becomes pairwise entangled with its nearest neighbors.


Gene polymorphism in angiotensin-I-converting enzyme and physical activity among normotensive Chinese.
The angiotensin-I-converting enzyme (ACE) I/D gene polymorphism has been studied for its role in determining habitual physical activity level, but there is no information from Asian populations. The objective of this study was to determine whether this ACE gene polymorphism was associated with physical activity level among Chinese in Singapore. In this cross-sectional study, 110 normotensive Chinese in Singapore, age 21-61 yr, completed the short-form version of the International Physical Activity Questionnaire and contributed buccal cell samples for genotyping of the ACE I/D gene polymorphism using polymerase chain-reaction amplification. They also provided demographic information and underwent anthropometric measurements. Physical activity level was expressed as continuous (in kcal/wk) and categorical (low, moderate, or high) data. The 3 genotypes of ACE were DD (homozygous for the deletion allele), II (homozygous for the insertion allele), and ID. Among the participants, 28.2% reported low, 49.1% moderate, and 22.7% high physical activity level. Frequencies of the genotypes were 11.8% for DD, 42.7% for ID, and 45.5% for II. ACE genotype was independently associated with physical activity level. After age, gender, and body-mass index were adjusted for, individuals with DD or ID genotypes were more likely to report insufficient or low physical activity level than those with II genotypes (odds ratio = 6.88; 95% confidence interval: 2.26, 20.94). In conclusion, the I/D polymorphism of the ACE gene is significantly associated with self-reported physical activity level in normotensive Chinese Singaporeans.


Thymic Carcinoma Treated by CyberKnife Stereotactic Body Radiotherapy.
The standard treatment for advanced thymic carcinoma has not yet been established. Most patients have no symptoms until the advanced stage. Radiation therapy has been used for advanced stage cancer, usually in combination with surgery or chemotherapy; however, the survival rates are 30%-50%. We performed hypofractionated stereotactic radiotherapy with CyberKnife (Accuray, Sunnyvale, CA, USA) for 10 cases of advanced thymic cancer. All cases reached at least partial remission (PR) in two months with progression-free irradiated lesions and minimal radiation-related toxicity. It took only seven to 12 days for each therapy that did not require admission. CyberKnife is beneficial for patients even at the terminal stage.


Mitochondria-related lncRNAs: predicting prognosis, tumor microenvironment and treatment response in lung adenocarcinoma.
Lung cancer is the most common type of malignant tumor that affects people in China and even across the globe, as it exhibits the highest rates of morbidity and mortality. Lung adenocarcinoma (LUAD) is a type of lung cancer with a very high incidence. The purpose of this study was to identify potential biomarkers that could be used to forecast the prognosis and improve the existing therapy options for treating LUAD. Clinical and RNA sequencing data of LUAD patients were retrieved from the TCGA database, while the mitochondria-associated gene sets were acquired from the MITOMAP database. Thereafter, Pearson correlation analysis was carried out to screen mitochondria-associated lncRNAs. Furthermore, univariate Cox and Lasso regression analyses were used for the initial screening of the target lncRNAs for prognostic lncRNAs before they could be incorporated into a multivariate Cox Hazard ratio model. Then, the clinical data, concordance index, Kaplan-Meier (K-M) curves, and the clinically-relevant subjects that were approved by the Characteristic Curves (ROC) were employed for assessing the model's predictive value. Additionally, the differences in immune-related functions and biological pathway enrichment between high- and low-risk LUAD groups were examined. Nomograms were developed to anticipate the OS rates of the patients within 1-, 3-, and 5 years, and the differences in drug sensitivity and immunological checkpoints were compared. In this study, 2175 mitochondria-associated lncRNAs were screened. Univariate, multivariate, and Lasso Cox regression analyses were carried out to select 13 lncRNAs with an independent prognostic significance, and a prognostic model was developed. The OS analysis of the established prognostic prediction model revealed significant variations between the high- and low-risk patients. The AUC-ROC values after 1, 3, and 5 years were seen to be 0.746, 0.692, and 0.726, respectively. The results suggested that the prognostic model riskscore could be used as an independent prognostic factor that differed from the other clinical characteristics. After analyzing the findings of the study, it was noted that both the risk groups showed significant differences in their immune functioning, immunological checkpoint genes, and drug sensitivity. The prognosis of patients with LUAD could be accurately and independently predicted using a risk prediction model that included 13 mitochondria-associated lncRNAs.