Comparison of the long-term effects of single-dose methotrexate and salpingectomy on ovarian reserve in terms of anti-müllerian hormone levels.
The aim of this study was to compare the effects of single-dose methotrexate (MTX) and salpingectomy on ovarian reserve in women with ectopic pregnancy in the late post-treatment period. A total of 181 patients were included in the study; 56 of them received a single-dose of MTX, 45 of them had undergone salpingectomy treatment for ectopic pregnancy in the previous 12-18 months, and 80 healthy women constituted an age-matched control group. The anti-müllerian hormone (AMH), follicle stimulating hormone (FSH) and oestrogen (E2) levels, as well as antral follicle counts (AFC) of the patients were evaluated. The average age was similar in both groups (p = 0.094) and there was no statistically significant difference in the smoking status of the patients (p = 0.949). None of the three groups displayed a significant difference in terms of AFC (p = 0.528), AMH (p = 0.147), FSH (p = 0.393) and E2 levels (p = 0.117). In the treatment of ectopic pregnancy neither the single-dose MTX application nor the salpingectomy had any permanent detrimental effect on the ovarian reserve; serum AMH levels and AFC are unaltered in the long term following single-dose MTX or salpingectomy.


[Correlation between body composition and exercise capacity in patients with coronary heart disease].
To provide the evidence for more accurately assessing the patient's body composition, predicting exercise capacity and guiding rehabilitation exercise by analyzing the body compositions in patients with coronary heart disease, and to study the correlation between body compositions and exercise capacity. The study enrolled 663 patients with coronary heart disease in NYHA I-II stages, who underwent coronary intervention therapy between December 2013 and August 2014. Between 15th and 20th days of the onset, cardiopulmonary exercising testing (CPET, Bruce Protocol) was conducted, and the body composition was measured with the Inboby720 body composition analyzer before CPET. All the patients completed the body composition evaluation and the CPET. According to the three indicators of body mass index (BMI), percentage of body fat (PBF), waist-hip ratio (WHR), the diagnostic rate of obesity was 22.8%, 63.3%, and 72.7%, respectively. There was a good negative correlation between PBF and exercise capacity (r=-0.306, P<0.001). Compared with non-obesity patients, the exercise capacity of obesity group decreased according to PBF (P<0.01). The patients were divided into low, moderate and high exercise capacity groups according to METs, and the difference was only the PBF among the three groups (P<0.05). PBF, measured by body composition, is a more accurate diagnosis of obesity and has a good negative correlation with exercise capacity, which can be used as an important indicator to predict the exercise capacity in patients with coronary heart disease and guide the rehabilitation exercise.


Psychosocial factors limit outcomes after trauma.
Psychological morbidity compromises return to work after trauma. We demonstrate this relationship and present methods to identify risks for significant psychological morbidity. Thirty-five adults were evaluated prospectively for return to functional employment after injury using demographic data, validated psychological and health measures, and the Michigan Critical Events Perception Scale. Evaluation was conducted at admission and at 1 and 5 months after injury. Poor return to work at 5 months was attributable to physical disability (p < 0.05) and psychological disturbance (p < 0.05) in a regression model that controlled for preinjury employment and psychopathologic factors as well as injury severity. A high score on the Impact of Events Scale administered during acute admission predicted development of acute stress disorder at 1 month (p < 0.01, odds ratio (OR) = 9.4) and posttraumatic stress disorder at 5 months (p < 0.05, OR = 6.7). Peritraumatic dissociation on the Michigan Critical Events Perception Scale was predictive for development of acute stress disorder (p < 0.05, OR = 5.8) at 1 month and posttraumatic stress disorder (p < 0.05, OR = 7.5) at 5 months. Psychological morbidity after injury compromises return to work independent of preinjury employment and psychopathologic condition, Injury Severity Score, or ambulation. A high Impact of Events Scale score or peritraumatic dissociation at admission predicts this morbidity.


Operation of controls on consumer products by physically impaired users.
The self-reliance of the physically impaired can be seriously jeopardized by their inability to operate everyday products, especially if both upper extremities are impaired. To determine the difficulties impaired users encounter in operating consumer product controls, on-site video recordings were made of subjects suffering from arthritis or a muscular disease. Subjects' force exertion was compared with that of a group of nonimpaired users. The resulting inventory allowed the analysis of the manipulation problems faced by impaired subjects and the development of design recommendations. In this study the force exerted by the subjects and that required to operate the controls were measured. A comparison of the results of these force measurements led to a number of conclusions. This study led to the following design recommendations: the amount of force required to operate controls should be kept as low as possible; the user should not be required to make two manipulations at the same time, such as simultaneously pushing and rotating a control device; pushing is preferable to rotating; and there should be a great degree of freedom to manipulate controls.


Mutation analysis in a Chinese family with multiple endocrine neoplasia type 1.
Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant cancer syndrome which is caused by germline mutations of the tumor suppressor gene MEN1. This study aimed to identify mutations in a Chinese pedigree with MEN1. A large Chinese family with MEN1 was collected. All of the coded regions and their adjacent sequences of the MEN1 gene were amplified and sequenced. In this family, a heterozygous cytosine insertion in exon 10 (c.1546_1547insC) inducing a frame shift mutation of MEN1 was found in the proband and the other two suffering members of his family. This mutation was linked to a novel single nucleotide polymorphism (SNP) in intron 3 (IVS3 + 18C > T). The mutation in exon 10 of MEN1 gene might induce development of parathyroid hyperplasia and pituitary adenoma and cosegregate with MEN1 syndrome. The significance of the new found IVS3 + 18C > T of MEN1 needs a further investigation.


Marital functioning in early versus late-onset alcoholic couples.
Current knowledge about alcohol and marital functioning is limited by restrictive sample selection, inattention to the literature on individual-based alcoholic subtypes, and lack of research linking individual differences among alcoholics to marital functioning. The present study was designed to study marital functioning of alcoholics in light of current alcohol typologies. Subjects were part of a larger study on conjoint treatment of alcoholic males and their female partners. Four typologies-including Type 1/2, In-Home/Out-of-home, Steady/Episodic, and Early/Late Onset-were tested for replicability and discriminant validity before linking them to marital functioning. Discriminant validity was found only for the Early (59%)-versus Late (41%)-Onset typology;thus, further analyses linked only this typology with marital functioning. At baseline, Early-Onset couples reported more marital instability, and the females in these couples were more distressed. During treatment, Early-Onset couples reported higher daily marital satisfaction than Late-Onset couples. Regardless of age of onset, males reported higher marital satisfaction than their spouses during treatment, but their satisfaction did not increase during treatment. Female partners' marital satisfaction increased during treatment. Female partners of Late-Onset males reported particularly low marital satisfaction during treatment. Parsing the sample according to the early-/late-onset typology yielded different predictors of marital satisfaction for males and females within each subtype. For female partners of Early-Onset alcoholics, psychological distress unrelated to her partner's drinking severity was most associated with her own marital satisfaction, whereas marital adjustment of female partners of Late-Onset alcoholics was most associated with the male's level of perceptual accuracy regarding her needs. This pattern was reversed for the males; marital adjustment of Early-Onset alcoholics was most associated with his partner's perceptual accuracy of his needs, whereas marital functioning of Late-Onset alcoholics was best accounted for by his own psychological distress.


Methodology to develop and evaluate a semantic representation for NLP.
Natural language processing applications that extract information from text rely on semantic representations. The objective of this paper is to describe a methodology for creating a semantic representation for information that will be automatically extracted from textual clinical records. We illustrate two of the four steps of the methodology in this paper using the case study of encoding information from dictated dental exams: (1) develop an initial representation from a set of training documents and (2) iteratively evaluate and evolve the representation while developing annotation guidelines. Our approach for developing and evaluating a semantic representation is based on standard principles and approaches that are not dependent on any particular domain or type of semantic representation.


Metachronal Coordination of Multiple Appendages for Swimming and Pumping.
As a strategy for creating fluid flow, metachronal motion is widespread across sizes and species, including a broad array of morphologies, length scales, and coordination patterns. Because of this great diversity, it has not generally been viewed holistically: The study of metachrony for swimming and pumping has historically been taxonomically siloed, in spite of many commonalities between seemingly disparate organisms. The goal of the present symposium was to bring together individuals from different backgrounds, all of whom have made substantial individual contributions to our understanding of the fluid dynamics of metachronal motion. Because these problems share a common physical-mathematical basis, intentionally connecting this community is likely to yield future collaborations and significant scientific discovery. Here, we briefly introduce the concept of metachronal motion, present the benefits of creating a research network based on the common aspects of metachrony across biological systems, and outline the contributions to the symposium.


Long-term antimicrobial effectiveness of a silver-impregnated foil on high-touch hospital surfaces in patient rooms.
The hospital environment has got more attention as evidence as source for bacterial transmission and subsequent hospital-acquired infection increased. Regular cleaning and disinfection have been proposed to lower the risk of infection, in particular for gram-positive bacteria. Auto-disinfecting surfaces would allow to decrease survival of pathogens, while limiting resource to achieve a safe environment in patient rooms. A controlled trial to evaluate the antimicrobial effectiveness of a polyvinyl chloride foil containing an integrated silver-based agent (containing silver ions 2%) on high-touch surfaces in patient rooms. The overall log reduction of the mean values was 1.8 log10 CFU, the median 0.5 log10 CFU comparing bioburden of control vs antimicrobial foil (p < 0.01). Important pathogens were significantly less likely recovered from the foil, in particular enterococci. These effects were present even after 6 months of in-use. A foil containing an integrated silver-based agent applied to high-touch surfaces effectively results in lower recovery of important pathogens from such surfaces over a 6-month study period.


Assessment of resampling methods for causality testing: A note on the US inflation behavior.
Different resampling methods for the null hypothesis of no Granger causality are assessed in the setting of multivariate time series, taking into account that the driving-response coupling is conditioned on the other observed variables. As appropriate test statistic for this setting, the partial transfer entropy (PTE), an information and model-free measure, is used. Two resampling techniques, time-shifted surrogates and the stationary bootstrap, are combined with three independence settings (giving a total of six resampling methods), all approximating the null hypothesis of no Granger causality. In these three settings, the level of dependence is changed, while the conditioning variables remain intact. The empirical null distribution of the PTE, as the surrogate and bootstrapped time series become more independent, is examined along with the size and power of the respective tests. Additionally, we consider a seventh resampling method by contemporaneously resampling the driving and the response time series using the stationary bootstrap. Although this case does not comply with the no causality hypothesis, one can obtain an accurate sampling distribution for the mean of the test statistic since its value is zero under H0. Results indicate that as the resampling setting gets more independent, the test becomes more conservative. Finally, we conclude with a real application. More specifically, we investigate the causal links among the growth rates for the US CPI, money supply and crude oil. Based on the PTE and the seven resampling methods, we consistently find that changes in crude oil cause inflation conditioning on money supply in the post-1986 period. However this relationship cannot be explained on the basis of traditional cost-push mechanisms.


[Combined use of talinolol and beta adrenergic stimulants in status asthmaticus. Report on 3 patients].
Experiences in combined use of beta-adrenergic stimulants and cardioselective beta-receptor blocker Talinolol are reported in 3 patients in Status Asthmaticus. High dose Aminophyllintreatment in these 3 severe cases was insufficient, in 1 case it had to be finished because of toxic side effects respectively. For adrenergic stimulation in two cases Orciprenalin i.v. was given initially, in one case Terbutalinsulfat i.v. By cardioselective adrenergic blockade with low dose Talinolol it became possible to prevent cardiotoxic side effects in preexisting tachycardia and premature ventricular contractions. This combination treatment was continued successfully with Terbutalin and Talinolol p.o.


Cloning of human and mouse brain cDNAs coding for S1, the second member of the mammalian elongation factor-1 alpha gene family: analysis of a possible evolutionary pathway.
We previously reported the cloning of a rat S1 cDNA whose deduced amino acid sequence shares high similarity (92%) with that of mammalian elongation factor-1 alpha (EF-1 alpha), a protein involved in the binding of aminoacyl-tRNA to the ribosome during peptide synthesis. We report here the isolation of a full-length cDNA from a mouse brain library and a partial-length cDNA from a human hippocampus library which share extensive sequence similarity to rat S1 cDNA. We show that, as with mammalian EF-1 alpha S, the predicted primary amino acid sequences of rat, mouse, and human S1 are almost identical, except for one conservative substitution. These results indicate that mouse and man contain a second member of the EF-1 alpha gene family, the S1 gene. They also suggest that our result obtained in rat may be extrapolated to mouse and man.


Predictors of fetal outcome in pregnant trauma patients: a five-year institutional review.
Injury Severity Score (ISS) and lactate are controversial in predicting fetal outcome. A retrospective review was conducted to determine whether ISS and lactate are valuable in predicting fetal survival in injured pregnant patients. Injured pregnant women were identified by ICD-9 codes from our Trauma Registry, Emergency Department Registry, and hospital medical records. Records were reviewed for demographic data, mechanism of injury, ISS, Glascow Coma Scale, lactate, vital signs, and maternal/fetal outcome. To determine statistical analysis, chi2 and t test analysis was performed. From 2001 to 2005, 294 women reported injuries. Most patients (51.7%) were discharged from the Emergency Department, yet 18 per cent were admitted to Trauma Surgery. The average maternal and gestational age was 23.4 years and 19.6 weeks, respectively. Seventy-two (33.3%) patients were in the first trimester. The majority of patients (88.1%) were involved in blunt trauma, and 10 (3.9%) had poor fetal outcome (nine fetal deaths and one hydrops fetalis). There were no maternal deaths. Maternal age, first trimester, elevated lactate, and high ISS were significant risk factors for poor fetal outcome (P = 0.044, P = 0.0173, P = 0.0001, and P = 0.0001, respectively). Specific parameters (ISS, lactate, maternal age, and gestational age) may be helpful in predicting poor fetal outcome and directing patient management.


Inner and outer segment junction (IS/OS line) integrity in ocular Behçet's disease.
In this study, we examined the spectral domain optical coherence tomography (OCT) findings of ocular Behçet's disease (OB) in patients with inactive uveitis. Specifically, we analyzed the inner and outer segment junction (IS/OS line) integrity and the effect of disturbed IS/OS line integrity on visual acuity. Patient files and OCT images of OB patients who had been followed-up between January and June of the year 2013 at the Dicle University Eye Clinic were evaluated retrospectively. Sixty-six eyes of 39 patients were included the study. OCT examination of the patients with inactive OB revealed that approximately 25% of the patients had disturbed IS/OS and external limiting membrane (EML) line integrity, lower visual acuity (VA), and lower macular thickness than others. Linear regression analysis revealed that macular thickness was not an independent variable for VA. In contrast, the IS/OS line integrity was an independent variable for VA in inactive OB patients. In this study, we showed that the IS/OS line integrity was an independent variable for VA in inactive OB patients. Further prospective studies are needed to evaluate the integrity of the IS/OS line in OB patients.


[Effect of the x-ray tube anode current on the intensity and energy spectrum of the radiation].
Operating modes of the X-ray equipment that determine the energy spectrum of the X-radiation have been experimentally studied. Based on the spectrum analysis performed with a multichannel analyzer and a computer the quantitative relations are derived demonstrating the impact of the current and voltage waveform upon the effective radiation energy for several types of X-ray devices. The correlation tables of the X-ray equipment voltage for various rectification circuits are presented.


Eutrophication and the dietary promotion of sea turtle tumors.
The tumor-forming disease fibropapillomatosis (FP) has afflicted sea turtle populations for decades with no clear cause. A lineage of α-herpesviruses associated with these tumors has existed for millennia, suggesting environmental factors are responsible for its recent epidemiology. In previous work, we described how herpesviruses could cause FP tumors through a metabolic influx of arginine. We demonstrated the disease prevails in chronically eutrophied coastal waters, and that turtles foraging in these sites might consume arginine-enriched macroalgae. Here, we test the idea using High-Performance Liquid Chromatography (HPLC) to describe the amino acid profiles of green turtle (Chelonia mydas) tumors and five common forage species of macroalgae from a range of eutrophic states. Tumors were notably elevated in glycine, proline, alanine, arginine, and serine and depleted in lysine when compared to baseline samples. All macroalgae from eutrophic locations had elevated arginine, and all species preferentially stored environmental nitrogen as arginine even at oligotrophic sites. From these results, we estimate adult turtles foraging at eutrophied sites increase their arginine intake 17-26 g daily, up to 14 times the background level. Arginine nitrogen increased with total macroalgae nitrogen and watershed nitrogen, and the invasive rhodophyte Hypnea musciformis significantly outperformed all other species in this respect. Our results confirm that eutrophication substantially increases the arginine content of macroalgae, which may metabolically promote latent herpesviruses and cause FP tumors in green turtles.


Differing susceptibility of young and adult hamster lungs to injury with pancreatic elastase.
A study was undertaken to determine whether there are differences in the initial response of the lungs of young (28 days) and adult (105 days) hamsters to pancreatic elastase treatment. The elastase was given intratracheally (0.1 mg/100 g body weight), and the animals were studied 24 h later. The mean linear intercept of the lungs of young animals increased less than that of adult animals (p less than 0.05). Adult body weights decreased significantly with elastase treatment, whereas those of young elastase-treated animals did not. The lungs of young animals gained proportionately less weight than those of adult animals, suggesting they experienced less hemorrhage and edema. When the volumes, at given transpulmonary pressures, of fluid-filled lungs were expressed as percent predicted, the values for young animals were significantly less than those for adult animals. The most pronounced differences were at low transpulmonary pressures (1 to 3 cm H2O). Volume-pressure hysteresis was not altered by elastase treatment in either the young or adult animals. We conclude that the lungs of adult hamsters are more susceptible to elastase injury than the lungs of young hamsters.


Bariatric surgery in older adults: Should there be an age limit?
Obesity has become one of the most significant health problems worldwide, affecting more than one-third of the global population. The elderly population is not immune to this proportional increase in obesity. To date, there is no cure for obesity, but surgery is the most effective treatment available today.We analyzed the results of bariatric surgery in elderly patients for a period of 3 years. Patients 65 years old and older were included in the study, 451 older adults were included. The mean age of the study group was 67.92 years old (min. 65, max. 84). The mean body mass index (BMI) was 40.32 Kg/m (min. 34 and max. 59). Sleeve gastrectomy (SG) was the most common procedures, and were conducted in 346 (76.72%) patients, gastric bypasses (GBPs) in 53 (11.75%) of which 33 were roux en y GBP (7.32%) and 20 mini GBPs (4.43%), gastric banding in 48 (10.64%), and duodenal switching in 4 (0.89%) cases.There were 40 (8.86%) patients with perioperative complications, 6 (1.33%) required re-operations, 12 (2.66) patients with operative complications were treated conservatively, 8 (1.77%) re-admission 5 of them with intrabdominal abscess, and 14 (3.10%) with co-morbidities complications. More than 76% of the patients had co-morbidities, 1 year after surgery the average remission of diseases was 34.74%, the improvement was49.67% and no changes in the co-morbidities was 15.59%. There were no deaths reported in this cohort.The mean excess body weight (EBW) loss among the patients was 70.76% (from 32% to 92%). No failure of weight loss (less than 25% of EBW loss) was observed after the first postoperative year.Bariatric surgery offers obese elderly patients an acceptable result, and it can be offered to improve the quality of life of these patients. A new consensus conference panel is needed to set appropriate recommendations regarding criteria that limit bariatric surgery in older adults.


[Antiperistaltic esophago-jejuno-duodenostomy after total gastrectomy].
Total gastrectomy forms an essential part of surgical management of gastric carcinoma. The various operations proposed for reconstruction of the alimentary tract are reviewed, reflux oesophagitis, dehiscence of suture. Lastly, the advantages offered by oesophago-jejuno-duodenostomy are illustrated.


Effects of 25-Min Nap Opportunity during Ramadan Observance on the 5-m Shuttle Run Performance and the Perception of Fatigue in Physically Active Men.
We aimed to investigate the effects of a 25-min nap opportunity on physical performance during the 5-m shuttle run test (5mSRT), feelings (i.e., evaluated by the feeling scale), attention (i.e., evaluated by the digit cancellation test) and the perception of fatigue (i.e., recorded by the rating of perceived exertion (RPE)) during Ramadan observance. Twelve physically active men (age: 21.1 ± 3.2 yrs, height: 1.76 ± 0.05 m, body-mass: 71.2 ± 9.3 kg) voluntarily participated in five test sessions: 15 days before Ramadan (BR), the first 10 days of Ramadan (FR), the last 10 days of Ramadan (ER), 10 days after Ramadan (10AR) and 20 days after Ramadan (20AR). During each test session, participants performed the digit cancellation test, a 5-min standard warm-up, the 5mSRT (6 × 30-s with 35-s intervals-between) and the rating of perceived exertion (RPE) after no-nap (N0) and 25-min nap opportunity (N25) conditions. Participants also completed the Pittsburgh Sleep Quality Index (PSQI) during each period. The total distance covered during the 5mSRT did not differ significantly before, during or after Ramadan, but was significantly greater after N25 compared to N0 at 10AR (687.5 ± 23.0 m vs. 725.6 ± 41.1 m; p = 0.018) and 20AR (698.3 ± 19.8 m vs. 742.6 ± 58.3 m; p = 0.003). The attention scores were higher after N25 in comparison with N0 at 10AR (p = 0.04) and 20AR (p = 0.02). RPE scores were not significantly different between N25 and N0 conditions. Feelings scores were higher after N25 compared to N0 during both FR (p = 0.007) and 20AR (p = 0.04). A significant deterioration of sleep quality was recorded during Ramadan (i.e., PSQI scores were significantly higher during and after compared to BR (p < 0.0005)). A 25-min nap opportunity was beneficial for physical and cognitive performance after Ramadan observance; however, any effect is insufficient to show significant beneficial impacts during Ramadan.


Obestatin-mediated proliferation of human retinal pigment epithelial cells: regulatory mechanisms.
In this work, we have evaluated the effect of the new discovered peptide obestatin on cell proliferation in primary cultures of human retinal epithelial cells (hRPE cells). The results showed that this peptide induced, in a dose-dependent manner, cell proliferation by MEK/ERK 1/2 phosphorylation. A sequential analysis of the obestatin transmembrane signaling pathway showed that the ERK 1/2 activity is partially blocked after preincubation of the cells with pertussis toxin (PTX), as well as by wortmannin (an inhibitor of PI3K), claphostin C (an inhibitor of PKC), and PP2 (which inhibits the non receptor tyrosine kinase Src). Upon administration of obestatin, the intracellular levels of phospho-PKCepsilon-, theta-, and micro-isoenzymes rise with different time courses, from which PKCepsilon might be responsible for ERK 1/2 response. Based on the experimental data, a signaling pathway involving the consecutive activation of Gi, PI3K, novel PKC (probably PKCepsilon), and Src for ERK 1/2 activation is proposed. These results incorporate a new mitogenic factor to the group of factors that regulate proliferation of hRPE cells.


Aggressiveness of the tall cell variant of papillary thyroid carcinoma is independent of the tumor size and patient age.
The tall cell variant (TCV) of papillary thyroid carcinoma (PTC) is characterized by tall columnar cells with a height of at least three times their width. TCV usually presents at an older age, has a larger size and exhibits more extrathyroidal extension and metastases than classical PTC. The current study compared TCV with the classical and follicular variants (CaFVs) of PTC to determine if, irrespective of the age at diagnosis and tumor size, TCV is more aggressive than its classical and follicular counterparts. A total of 16 (3.66%) patients with TCV were identified in a series of 437 patients with PTC from the Clinical University Hospital (Santiago de Compostela, Spain) between 1990 and 2010. The patient clinicopathological features and B-Raf proto-oncogene (BRAF)V600E mutational status were compared with 34 cases of CaFVs of PTC matched for tumor size and patient age. The TCV series included 11 females and 5 males aged 15-74 years (median, 57 years). In total, 15 (93.8%) patients underwent total or near-total thyroidectomy, 1 underwent lobectomy and 5 (31.3%) underwent lymph node dissection. In the TCV series, the tumor size ranged from 5-45 mm (median, 19 mm). Compared with the CaFVs, the TCV of PTC exhibited a significantly higher prevalence of extrathyroidal extension [9/16 (56.3%) vs. 5/34 (14.7%) cases; P=0.007], lymph node metastases [9/16 (56.3%) vs. 9/34 (26.4%) cases; P=0.04], stage III/IV at presentation [10/16 (62.5%) vs. 7/34 (20.5%) cases; P=0.009] and BRAFV600E mutation [12/16 (80.0%) vs. 7/25 (28.0%) cases; P=0.004]. The TCV series also harbored more multifocal papillary carcinomas (50.0% vs. 26.4%), lymphovascular invasion (37.5% vs. 29.4%) and distant metastases (6.2% vs. 0.0%), as compared with the matched patient cohort. In conclusion, the TCV of PTC is frequently associated with BRAFV600E mutation and is more aggressive than the CaFVs of PTC, regardless of tumor size and patient age at diagnosis.


High-Protein Concentrated Pro-Yogurt (Pro-WPI) Enriched With Whey Protein Isolate Improved Athletic Anemia and Performance in a Placebo-Controlled Study.
Upcoming developments are attracting attention to both high-protein and probiotics supplementation for the sports community to promote good health and exercise performance. This study aimed at the production of high-protein concentrated pro-yogurt (Pro-WPI) enriched with 10 and 20% whey protein isolate (WPI) and investigation of the response of daily consumption on anthropometric, hematology parameters, and athletic performance in parallel with safety consideration assessment. Twenty-four athletes (19.6 ± 1.45 years; 175.96 ± 5.24 cm; 73.16 ± 8.65 kg) were participated in a randomized placebo-control study. They consumed Pro-WPI products with 10 (T1) and 20% (T2) WPI for treatments G1 (Pro-WPI30) and G2 (Pro-WPI60), respectively, 3 times per day/5 days per week/9 weeks. The taste of Pro-WPI products was sour and cheesy, while mouthfeel was described as soft and thick because of the increased protein content in T1 and T2 (14.15 and 22.58%). The hemoglobin of the athletes increased significantly from a baseline of 12.69 g/dl to 16 and 16.66 g/dl in G1 and G2, respectively. Furthermore, the athletic performance was enhanced in vertical jump, long jump, sprinting velocity, half squats, and pushups, which reached 58.75 cm, 255 cm, 3.5 m/s, 218.75 counts, and 85 counts, respectively in G2. The healthy gut microbiome (probiotics) in parallel with increased iron bioavailability by mineral binding (whey bioactive peptides), influenced iron status and can represent a healthy practice to improve athletic anemia and performance. On the other hand, urinary albumin exceeded the border of reference range (<30 mg/g) and reached 38.25 and 44.13 mg/g in G1 and G2, while urine pH was in the normal range (4.5-8). Increased urinary albumin might be due to high rates of protein metabolism that follow high protein intake. This study provided preliminary information on metabolic responses to high protein concentrated yogurt intake in athletes who engaged in daily exercise. Further studies are needed to determine the recommended intensity of 10 and 20% Pro-WPI product consumption to achieve its benefits and avoid implications on kidney function.


Identification of Anaplasmataceae (Haemobartonella) antigen and antibodies in systemic lupus erythematosus.
Free antigen related to Anaplasma marginale (AM) (Haemobartonella) was demonstrated in the glomeruli of one patient with lupus nephritis. Indirect fluorescent antibodies against this rickettsia were demonstrated in all of 22 lupus sera tested, with titers ranging from 1:20 to 1:1280. Geometric mean titer (GMT) was 116. Fifty-eight percent of 102 controls did not react to AM by indirect fluorescent antibody technique, and GMT of all controls was 10.7 Immunofluorescence was eliminated by neutralization and blocking techniques.


A Dark Target Detection Method Based on the Adjacency Effect: A Case Study on Crack Detection.
Dark target detection is important for engineering applications but the existing methods do not consider the imaging environment of dark targets, such as the adjacency effect. The adjacency effect will affect the quantitative applications of remote sensing, especially for high contrast images and images with ever-increasing resolution. Further, most studies have focused on how to eliminate the adjacency effect and there is almost no research about the application of the adjacency effect. However, the adjacency effect leads to some unique characteristics for the dark target surrounded by a bright background. This paper utilizes these characteristics to assist in the detection of the dark object, and the low-high threshold detection strategy and the adaptive threshold selection method under the assumption of Gaussian distribution are designed. Meanwhile, preliminary case experiments are carried out on the crack detection of concrete slope protection. Finally, the experiment results show that it is feasible to utilize the adjacency effect for dark target detection.


The epidemiology of occupational penetrating eye injuries in Ireland.
This paper is designed to establish the risk factors associated with serious occupational eye injuries so that preventive measures can be targeted at those most at risk. Few such studies have been published for the United Kingdom and the Republic of Ireland. The incidence of these occupational eye injuries is over three times that of the non-occupational category. Present preventive measures appear to be inadequate. An association with certain socio-economic groups was found. A significantly increased incidence of penetrating eye injury was noted in farm labourers and in skilled manual labourers. The left eye was significantly more at risk of serious injury than the right eye. The paper suggests improvements which should be made, particularly in the occupational setting.


Mining Sudanese Medicinal Plants for Antiprotozoal Agents.
Neglected tropical diseases are major health hazards in developing countries. Annually, up to 30 million people are affected by either Chagas disease, African trypansomiasis or leishmaniasis, and more than 200 million by malaria. Most of the currently available drugs have drawbacks in terms of toxicity, limited oral availability, development of resistance, or non-affordability. Tropical plants of the arid zones are a treasure chest for the discovery of bioactive secondary metabolites. This study aims to compile Sudanese medicinal plants, validate their antiprotozoal activities, and identify active molecules. We have performed a survey of medicinal plants of Sudan and selected 62 that are being used in Sudanese traditional medicine. From these, we collected materials such as leaves, stem, bark, or fruit. The plant materials were extracted in 70% ethanol and further fractionated by liquid-liquid partitioning using solvents of increasing polarity. This resulted in a library of 235 fractions. The library was tested in vitro against Plasmodium falciparum (erythrocytic stages), Trypanosoma brucei rhodesiense (bloodstream forms), Trypanosoma cruzi (intracellular amastigotes), and Leishmania donovani (axenic amastigotes). Active fractions were also tested for cytotoxicity. Of the 235 fractions, 125 showed growth inhibitory activity >80% at 10 μg/ml, and >50% at 2 μg/ml against at least one of the protozoan parasites. Plasmodium falciparum was the most sensitive of the parasites, followed by T. b. rhodesiense and L. donovani. Only few hits were identified for T. cruzi, and these were not selective. Contrary to expectation based on phylogeny, but in agreement with previous results, a large number of extracts displayed mutual activity against T. brucei and P. falciparum. HPLC-based activity profiling for selected active extracts was performed to identify the bioactive principles. Active compounds identified by dereplication were guieranone A from Guiera senegalensis J.F.Gmel.; pseudosemiglabrin from Tephrosia apollinea (Delile) DC; ellagic acid and quercetin from Terminalia leiocarpa (DC.) Baill.; and catechin, ethyl gallate, and epicatechin gallate from Vachellia nilotica (L.) P.J.H.Hurter & Mabb. Also the extracts of Croton gratissimus var. gratissimus and Cuscuta hyalina Roth ex Schult. exhibited promising antitrypanosomatid activity. This assessment provides a comprehensive overview of Sudanese medicinal plants and supports the notion that they are a potential source of bioactive molecules against protozoan parasites.


The Prognostic Role of Tissue Characterisation using Cardiovascular Magnetic Resonance in Heart Failure.
Despite significant advances in heart failure diagnostics and therapy, the prognosis remains poor, with one in three dying within a year of hospital admission. This is at least in part due to the difficulties in risk stratification and personalisation of therapy. The use of left ventricular systolic function as the main arbiter for entrance into clinical trials for drugs and advanced therapy, such as implantable defibrillators, grossly simplifies the complex heterogeneous nature of the syndrome. Cardiovascular magnetic resonance offers a wealth of data to aid in diagnosis and prognostication. The advent of novel cardiovascular magnetic resonance mapping techniques allows us to glimpse some of the pathophysiological mechanisms underpinning heart failure. We review the growing prognostic evidence base using these techniques.


Neonatal screening for congenital hypothyroidism in Japan.
Congenital hypothyroidism may cause irreversible intellectual disability or failure to thrive if left untreated. Because this disorder can be prevented by early identification and early treatment, newborn mass screening started in 1979 in Japan. A guideline for mass screening for this disease was prepared in 1998. Currently, approximately 100% of newborns undergo this mass screening. The screening results show significant improvement of the intellectual outcome of patients with this disease, with almost no patients having irreversible intellectual disturbance or failure to thrive. However, there are issues of a delayed increase in thyroid stimulating hormone, management of latent hypothyroidism, and detection of central hypothyroidism. In recent years, as studies on this disease have advanced at the molecular level, many causative genes have been reported, clarification of the etiology, pathology, and clinical features has progressed, and new findings have been obtained.


The role of glucagon-like peptide-1 receptor agonists in nonalcoholic fatty liver disease.
Nonalcoholic fatty liver disease (NAFLD) is a highly prevalent disease, associated with obesity, type 2 diabetes mellitus and dyslipidemia, which can lead to liver cirrhosis and hepatocellular carcinoma in some patients. Apart from lifestyle modifications, which are the cornerstone for its management, several drugs are under evaluation, including glucagon-like peptide-1 receptor agonists (GLP-R1RAs). In this review, we summarized major clinical data concerning the effects of GLP-1RAs on NAFLD, trying to highlight existing knowledge and to elucidate areas of uncertainty, thus providing clues to potential clinical implications and research. Selected clinical studies on GLP-R1As in NAFLD are presented in this narrative review. There is evidence that treatment with GLP-R1As in NAFLD has beneficial effects on NAFLD, i.e. improvement in liver function tests and histological improvement in hepatic steatosis and inflammation, but not fibrosis. Further research is required toward the early use of GLP-R1Αs, i.e. in NAFLD patients without fibrosis to evaluate whether they may prevent the progression to fibrosis, or in patients with advanced disease in combination with other medications, which may have additive or even synergistic effects on NAFLD.


Twinning and anencephalus occurrence in relation to fetus-fetus interaction.
The hypothesis proposed by Knox (1970) that an anencephalic fetus arises from a fetus-fetus interaction between two dizygous twins predicts that the twinning rate, the population incidence of anencephalus, and the female proportion of anencephalics in a population should be positively interrelated. These associations were tested using Canadian data during a long period of time and over a large geographical area. The results did not support the hypothesis.


Fractal network dimension and viscoelastic powerlaw behavior: II. An experimental study of structure-mimicking phantoms by magnetic resonance elastography.
The dynamics of the complex shear modulus, G*, of soft biological tissue is governed by the rigidity and topology of multiscale mechanical networks. Multifrequency elastography can measure the frequency dependence of G* in soft biological tissue, providing information about the structure of tissue networks at multiple scales. In this study, the viscoelastic properties of structure-mimicking phantoms containing tangled paper stripes embedded in agarose gel are investigated by multifrequency magnetic resonance elastography within the dynamic range of 40–120 Hz. The effective media viscoelastic properties are analyzed in terms of the storage modulus (the real part of G*), the loss modulus (the imaginary part of G*) and the viscoelastic powerlaw given by the two-parameter springpot model. Furthermore, diffusion tensor imaging is used for investigating the effect of network structures on water mobility. The following observations were made: the random paper networks with fractal dimensions between 2.481 and 2.755 had no or minor effects on the storage modulus, whereas the loss modulus was significantly increased about 2.2 kPa per fractal dimension unit (R = 0.962, P < 0.01). This structural sensitivity of the loss modulus was significantly correlated with the springpot powerlaw exponent (0.965, P < 0.01), while for the springpot elasticity modulus, a trend was discernable (0.895, P < 0.05). No effect of the paper network on water diffusion was observed. The gel phantoms with embedded paper stripes presented here are a feasible way for experimentally studying the effect of network topology on soft-tissue viscoelastic parameters. In the dynamic range of in vivo elastography, the fractal network dimension primarily correlates to the loss behavior of soft tissue as can be seen from the loss modulus or the powerlaw exponent of the springpot model. These findings represent the experimental underpinning of structure-sensitive elastography for an improved characterization of various soft-tissue diseases.


Relationship of vocal cord paralysis to the coil diameter of vagus nerve stimulator leads.
This investigation was done to examine, following implantation of vagus nerve stimulators, the relationship of vocal cord paralysis to the inner diameter of the coils used to attach the stimulator lead to the nerve. All data in this investigation were collected, as mandated by the FDA, by the manufacturer of vagus nerve stimulators and were made available without restrictions for analysis by the authors. The data reflect all initial device implantations in the United States for the period from 1997 through 2012. Vocal cord paralysis was reported in 193 of 51,882 implantations. In patients aged 18 years and older, the incidence of paralysis was 0.26% when the stimulator leads had coil diameters of 3 mm and 0.51% when the leads had 2-mm-diameter coils (p < 0.05). Across all age groups, the incidence of vocal cord paralysis increased with age at implantation for leads having 2-mm-diameter coils. In patients aged 18 years and older, vocal cord paralysis occurred at almost twice the rate with the implantation of vagus nerve stimulator leads having 2-mm-diameter coils than with leads having 3-mm-diameter coils. The incidence of vocal cord paralysis increases with patient age at implantation.


Children's cortisol and the quality of teacher--child relationships in child care.
Teacher-child relationships were examined as predictors of cortisol change in preschool children. Saliva for assays was collected from one hundred and ninety-one 4-year-olds (101 boys) in the mornings and afternoons on 2 days at child care, and before and after a series of challenging tasks and a teacher-child interaction session outside the classroom. Parents reported on children's temperament, teachers and children reported on teacher-child relationship quality, and observers rated group-level teacher insensitivity. Teacher-reported relationship conflict predicted cortisol increases during teacher-child interaction and teacher-reported overdependence predicted cortisol increases from morning to afternoon, even after controlling for individual teacher, child, and classroom characteristics. The findings extend earlier work by suggesting that cortisol change across the child-care day is influenced by teacher-child relationship characteristics.


Impedance spectroscopy of reduced monoclinic zirconia.
Zirconia doped with low-valent cations (e.g. Y3+ or Ca2+) exhibits an exceptionally high ionic conductivity, making them ideal candidates for various electrochemical applications including solid oxide fuel cells (SOFC) and oxygen sensors. It is nevertheless important to study the undoped, monoclinic ZrO2 as a model system to construct a comprehensive picture of the electrical behaviour. In pure zirconia a residual number of anion vacancies remains because of contaminants in the material as well as the thermodynamic disorder equilibrium, but electronic conduction may also contribute to the observed conductivity. Reduction of zirconia in hydrogen leads to the adsorption of hydrogen and to the formation of oxygen vacancies, with their concentration affected by various parameters (e.g. reduction temperature and time, surface area, and water vapour pressure). However, there is still little known about the reactivities of defect species and their effect on the ionic and electronic conduction. Thus, we applied electrochemical impedance spectroscopy to investigate the electric performance of pure monoclinic zirconia with different surface areas in both oxidizing and reducing atmospheres. A novel equivalent circuit model including parallel ionic and electronic conduction has previously been developed for titania and is used herein to decouple the conduction processes. The concentration of defects and their formation energies were measured using volumetric oxygen titration and temperature programmed oxidation/desorption.


Something old, something new: do genetic studies of contemporary populations reliably represent prehistoric populations of Pacific Rattus exulans?
Through our research focusing on genetic studies of both ancient and extant commensal animals in the Pacific for addressing issues of population origins and mobility in the region, we have been able to process a large number of archaeological faunal remains that we can compare to modern samples from the same islands. These comparisons shed light on and provide specific evidence for Rattus exulans population change through time. This information may provide a model for understanding human populations in the region and will illustrate the complexities of using data obtained from modern populations to infer prehistoric relationships. Two case studies are presented here-analyses of modern and archaeological populations of R. exulans from both Chatham Island and New Zealand. These two cases provide very different pictures regarding the relationship between the archaeological and the extant populations.


Streptomyces as a plant's best friend?
Here we discuss the advantages of the majority of this versatile and diverse group of microorganisms for plant health and growth as demonstrated by their contribution to disease-suppressive soils, their antifungal and antibacterial activities, their ability to produce volatile compounds and their capacity to enhance plant biomass. Although much is still to be discovered about the colonization strategies and molecular interactions between plant roots and these microorganisms, they are destined to become important players in the field of plant growth-promoting rhizobacteria for agriculture.


Immunohistochemical staining patterns of canine meningiomas and correlation with published immunophenotypes.
This study examined immunohistochemical staining patterns for several meningioma variants involving either the brain or spinal cord of dogs. Formalin-fixed, paraffin-embedded tissue from 15 tumors was obtained. The selected tumor group included seven meningothelial, three transitional, two malignant (anaplastic), one myxoid, one papillary, and one osteomatous meningiomas. Tumors were evaluated for reactivity to the following six immunohistochemical markers: vimentin, pancytokeratin, glial fibrillary acidic protein (GFAP), S100, neuron-specific enolase (NSE), and synaptophysin. Vimentin expression was detected in all meningiomas, and 14 of 15 tumors demonstrated intense vimentin staining in more than 50% of the neoplastic cells. Pancytokeratin expression was present in 11 of 15 neoplasms; however, positive staining frequently was focal and often involved a small percentage of the neoplastic cells. GFAP expression was detected in a single, anaplastic meningioma. Although expression of NSE and S100 was detected in 12 of 25 meningiomas, the intensity of the staining and the percentage of positive neoplastic cells was highly variable. Synaptophysin was uniformly negative. These results will help to establish immunohistochemical profiles for meningiomas that will improve our ability to correctly differentiate these neoplasms of meningeal origin from central nervous system tumors originating from other sites.


Intraovarian factors associated with switching of a future dominant follicle to a subordinate follicle during induced luteolysis in heifers.
The factors involved in the switching of a future dominant follicle (DF) to subordinate status were studied (n = 42) by induction of luteolysis with PGF2α (hour 0) when the largest follicle (F1) in follicular wave 2 was 7.0 or 8.5 mm. Combined for 7.0- and 8.5-mm groups, the frequency of switching was greater (P < 0.01) when F1 and CL were ipsilateral (10 of 28, 36%) than when contralateral (0 of 14). The frequency of switching in the ipsilateral relationship was greater (P < 0.002) when F1 and CL were adjacent (<3 mm apart; 10 of 17) than when separated (0 of 11). The difference in diameter between F1 and F2 was less (P < 0.005) when switching occurred (0.4 ± 0.1 mm) than when switching did not occur (ipsilateral, 1.3 ± 0.2 mm; contralateral, 1.1 ± 0.2 mm). Treatment at hour 0 when F1 was 7.0 mm and ipsilateral to the CL resulted in smaller diameter (P < 0.001) of F1 at hour 12 (7.6 ± 0.2 mm) than when treatment was not given (8.3 ± 0.1 mm). The hypotheses were supported that (1) switching from a future DF to a future subordinate is functionally related to luteolysis, and (2) factors involved in switching include an ipsilateral relationship between the largest follicle and CL and close intraovarian proximity of the follicle to the regressing CL. It is proposed that switching of the future DF to subordinate status during spontaneous luteolysis accounts for the reported greater frequency of the contralateral than ipsilateral relationships between the preovulatory follicle and CL in three-wave interovulatory intervals.


Work safety climate, personal protection use, and injuries among Latino residential roofers.
This analysis describes work safety climate, personal protective equipment (PPE) use, and injuries among Latino residential roofers, and examines the associations of work safety climate with PPE use and injuries. Eighty-nine North Carolina residential roofers completed a baseline interview and daily logs about perceptions and use of PPE, occurrence of injuries in last 12 months, and work safety climate. The mean work safety climate score was 26.5 (SD = 5.6). In the baseline interview, participants reported that the majority of employers provided PPE and that they used it most or all of the time; daily log data indicated that PPE was used for half or fewer of hours worked. 39.9% reported any injury in the last 12 months. Work safety climate was significantly correlated with the provision and use of most types of PPE, and was inversely associated with injury. Supervisors promoting safety may increase the PPE use and decrease injuries.


Prognostic significance of CD24 expression in gastric carcinoma.
The human CD24 antigen is a small heavily glycosylated cell surface protein, which is expressed in hematological malignancies, as well as in a large variety of solid tumors. Its expression is now known to be related to the prognosis of several kinds of tumors. This study is designed to examine the prognostic significance of CD24 in Korean gastric cancer patients. In the present study, we examined CD24 expression in 300 consecutive cases of gastric carcinoma by immunohistochemical staining using the tissue-array method. We also investigated the clinicopathological profiles related to CD24 expression. One hundred and three cases out of 300 (34.3%) showed the positive expression of CD24. The altered expression of CD24 was significantly associated with differentiated cancer (p=0.003), the intestinal subtype according to the Lauren classification (p<0.001), the advanced stage cancer (p=0.027), with lymphatic invasion (p=0.038) and with vascular invasion (p=0.006). The survival analysis revealed that the patients with CD24 positive expression showed significantly poorer survival than those without CD24 expression. Moreover, a combined evaluation revealed that PTEN+/CD24- cases showed the best survival compared to other groups (p=0.01). Positive CD24 expression occurs in a subset of gastric carcinomas and it correlates significantly with lymphatic invasion, blood vessel invasion and poor survival.


Perioperative anti-infective prophylaxis with teicoplanin compared to cephalosporins in orthopaedic and vascular surgery involving prosthetic material.
A meta-analysis of randomised controlled trials evaluated the effectiveness and safety of teicoplanin compared to first- or second-generation cephalosporins for perioperative anti-infective prophylaxis in orthopaedic and vascular surgery involving prosthetic material. No differences were found between teicoplanin and cephalosporins with respect to the development of infection at the site of surgery or in remote areas of the body. In addition, there were no significant differences in reported adverse effects or mortality. These findings indicate that both regimens are equally effective in preventing post-operative infections in orthopaedic and vascular surgery involving prosthetic materials.


Senescence, wound healing and cancer: the PAI-1 connection.
Prolonged propagation of primary diploid fibroblasts in culture activates an ageing process known as replicative senescence, which is considered to provide a barrier against oncogenic transformation. Remarkably, both cell autonomous tumor-suppressive and cell nonautonomous tumor-promoting effects of senescent cells have been reported. Recently, we described that the p53 target gene plasminogen activator inhibitor-1 (PAI-1) is an essential mediator of replicative senescence. PAI-1 antagonizes the protease urokinase-type plasminogen activator (uPA). Both are secreted factors and involved in heterotypic signaling processes such as wound healing, angiogenesis and metastasis. Both uPA and PAI-1 are expressed in senescent cells and their relative abundance controls proliferation downstream of p53. Here, we present data that the effects of PAI-1 and uPA in the senescence response are not strictly cell autonomous. We discuss these findings in the context of the emerging roles of PAI-1 and uPA in heterotypic cellular signaling in senescence, wound healing and metastasis.


Presentation of BMP-2 mimicking peptides in 3D hydrogels directs cell fate commitment in osteoblasts and mesenchymal stem cells.
Many strategies for controlling the fate of transplanted stem cells rely on the concurrent delivery of soluble growth factors that have the potential to produce undesirable secondary effects in surrounding tissue. Such off target effects could be eliminated by locally presenting growth factor peptide mimics from biomaterial scaffolds to control stem cell fate. Peptide mimics of bone morphogenetic protein 2 (BMP-2) were synthesized by solid phase Fmoc-peptide synthesis and covalently bound to alginate hydrogels via either carbodiimide or sulfhydryl-based coupling strategies. Successful peptide conjugation was confirmed by (1)H NMR spectroscopy and quantified by fluorescently labeling the peptides. Peptides derived from the knuckle epitope of BMP-2, presented from both 2D surfaces and 3D alginate hydrogels, were shown to increase alkaline phosphatase activity in clonally derived murine osteoblasts. Furthermore, when presented in 3D hydrogels, these peptides were shown to initiate Smad signaling, upregulate osteopontin production, and increase mineral deposition with clonally derived murine mesenchymal stem cells. These data suggest that these peptide-conjugated hydrogels may be effective alternatives to local BMP-2 release in directly and spatially eliciting osteogenesis from transplanted or host osteoprogenitors in the future.


Educational Concepts of Digital Competence Development for Older Adults-A Scoping Review.
The digital transformation of healthcare and nursing is becoming increasingly important due to demographic change and the growing shortage of skilled workers. In order to ensure the participation of senior citizens in digital assistive technologies, educational concepts and support services are needed to promote digital skills in older adults. Therefore, the specific needs and prerequisites of this target group have to be taken into consideration. This paper asks how educational programs for the support of digital competences of older adults are designed and implemented. A scoping review was conducted to systematically extract existing findings from the literature. Four databases (Cinahl, PubMed, Web of Science Social Sciences Citation Index (SSCI), ERIC) were searched using an exploratory strategy to identify studies that address educational concepts promoting digital competences for older adults. A total of 47 publications were included in the qualitative analysis and show a variety of strategies to deal with the promotion of digital competences for elderly people. In conclusion, programs dealing with the promotion of digital competences for elderly people should be flexibly adapted to the target group with its specific needs and challenges such as fears, lack of previous experience, or physical limitations. For successful implementation, social support is of outstanding importance.


Human papillomavirus vaccination disparities among U.S. college students: An intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA).
We investigated how gender identity, sexual orientation, and race/ethnicity intersect to shape the social epidemiology of HPV vaccination initiation among U.S. college students. Cross-sectional survey data were from the National College Health Assessment (Fall, 2019-Spring, 2020; N = 65,047). We conducted an intersectional Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy by nesting participants within 36 social strata defined using gender identity, sexual orientation, and race/ethnicity. Bayesian multilevel logistic regression models with random intercepts for social strata were fit for HPV vaccination initiation. Intersectional models adjusted for the additive main effects to isolate intersectional interactions, controlling for age and geographic region. Social strata that included cisgender men, transgender women, and non-binary assigned-male-at-birth individuals and strata that included racial/ethnic minorities had a significantly lower likelihood of HPV vaccination initiation relative to strata including cisgender women and non-Hispanic White individuals, respectively, while strata including lesbian/gay and bisexual/pansexual/queer individuals had a significantly higher likelihood of HPV vaccination initiation relative to strata including heterosexual individuals. We also observed substantial between-stratum inequities in the predicted prevalence of HPV vaccination initiation, with estimates ranging from 59.2% for heterosexual, racial/ethnic minority, cisgender men to 87.1% for bisexual/pansexual/queer, racial/ethnic minority, non-binary assigned-female-at-birth individuals. That being said, the majority of the observed between-stratum variance was driven by additive rather than intersectional interaction effects and the discriminatory accuracy of intersectional stratification with respect to predicting HPV vaccination initiation was low. Collectively, our findings point to a need for more universal guidelines and clinician recommendations that promote HPV vaccine uptake for all adolescents, regardless of race/ethnicity, gender identity, sex-assigned-at-birth, or sexual orientation; however, utilizing an intersectional lens will ensure that resulting public health interventions address inequities and center the needs and experiences of multiply marginalized adolescents.


Revascularization of symptomatic subacute cerebrovascular occlusions with a self-expanding intracranial stent system.
In some patients, collateral circulation may preserve the viability of brain parenchyma distal to an intracranial arterial occlusion for hours or days after the presenting event. These patients may be good candidates for revascularization, even when they present outside of the accepted 6-hour time window for stroke intervention. Three patients were revascularized with the Wingspan stent system (Boston Scientific/Target, Fremont, CA) after presenting with subacute occlusions of intracranial arteries and progressive ischemic symptoms despite maximal medical therapy. All pre- and postprocedural imaging data and clinical records were reviewed. Three patients (mean age, 64 years; 2 women, 1 man) presented with symptomatic intracranial occlusions of the internal carotid artery (n = 2) and vertebrobasilar system (n = 1). All 3 patients presented more than 6 hours after symptom onset, and no intravenous or intra-arterial thrombolysis had been instituted. In all cases, despite supportive medical therapy (anticoagulation and antiplatelet therapy and induced hypertension), the patients continued to demonstrate progressive ischemia, both clinically and on diffusion magnetic resonance imaging. All patients were successfully revascularized without periprocedural complications and improved clinically after revascularization. In selected patients, symptomatic subacute occlusions of intracranial arteries may be revascularized using the Wingspan stent system.


Establishment of a Liver Transplant Patient-derived Tumor Xenograft (PDX) Model Using Cryopreserved Pancreatic Ductal Adenocarcinoma.
There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.


The method of expected number of deaths, 1786-1886-1986.
"The method of expected number of deaths is an integral part of standardization of vital rates, which is one of the oldest statistical techniques. The expected number of deaths was calculated in 18th century actuarial mathematics...but the method seems to have been forgotten, and was reinvented in connection with 19th century studies of geographical and occupational variations of mortality.... It is noted that standardization of rates is intimately connected to the study of relative mortality, and a short description of very recent developments in the methodology of that area is included." (SUMMARY IN FRE)


NLRC5 silencing ameliorates cardiac fibrosis by inhibiting the TGF‑β1/Smad3 signaling pathway.
The proliferation of cardiac fibroblasts (CFs) and excessive deposition of extracellular matrix are the predominant pathological characteristics of cardiac fibrosis. As the largest member of the nucleotide‑binding domain and leucine‑rich repeat (NLR) family, NLRC5 has been shown to be pivotal in the development of hepatic fibrosis. However, whether NLRC5 is involved in the pathogenesis of cardiac fibrosis remains to be elucidated. The present study aimed to investigate the role of NLRC5 and its mechanisms in regulating cardiac fibrosis. CFs were stimulated with transforming growth factor (TGF)‑β1 for various times and the mRNA and protein expression of NLRC5 was assessed using reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively. In addition, CFs were transfected with small interfering (si)RNA targeting NLRC5 or scramble siRNA for 24 h and then stimulated with TGF‑β1 for 24 h. Subsequently, cell proliferation was measured using an MTT assay, whereas cell migration was evaluated using a Transwell migration assay. The protein expression levels of α‑smooth muscle actin, collagen I, connective tissue growth factor, phosphorylated‑Smad3 and Smad3 were measured using western blot analysis. The results demonstrated that NLRC5 was upregulated in TGF‑β1‑induced CFs. The knockdown of NLRC5 significantly inhibited cell proliferation and migration, and suppressed myofibroblast differentiation and the expression of pro‑fibrotic molecules in TGF‑β1‑treated CFs. Furthermore, the knockdown of NLRC5 attenuated TGF‑β1‑induced phosphorylation of small mothers against decapentaplegic (Smad)3 in the CFs. The results of the present study indicated that NLRC5 acted as a key regulator of pathological cardiac fibrosis, and NLRC5 silencing ameliorated cardiac fibrosis by inhibiting the TGF‑β1/Smad3 signaling pathway. These results suggested that NLRC5 may be a novel target for attenuating cardiac fibrosis.


A molecular mechanics study of spermine complexation to DNA: a new model for spermine-poly(dG-dC) binding.
Molecular mechanics calculations of the binding of spermine to a number of solvated DNA helices have led to the development of a new model for spermine complexation. The structural details of the complexes formed with d(GCGCGCGCGC)2 and d(ATATATATAT)2 decamers allowed a rationalization of the observed experimental differences for binding to these two helices. For d(ATATATATAT)2 it was concluded that spermine remains in a cross-major groove binding site. Conversely, for d(GCGCGCGCGC)2 spermine reorientation via specific ligand-base-pair hydrogen-bond formation allows complexation along the major groove. The solvent plays an important role in differentiating the two binding modes. A mechanism of spermine complexation to natural DNA is postulated from these results. Past experimental data are also considered in the context of the new model.


Routine use of filtered air as endotamponade in the management of primary rhegmatogenous retinal detachment.
To evaluate the safety and efficacy of filtered air as endotamponade in the management of primary rhegmatogenous retinal detachment (RRD) treated with pars plana vitrectomy (PPV) and complete drainage of subretinal fluid. For this retrospective study, we reviewed the medical charts of 273 patients (275 eyes) who consecutively underwent PPV, subretinal fluid drainage and filtered air tamponade to treat primary RRD between 2018 and 2022. As primary outcome we evaluated the anatomical success considered as retinal reattachment after single surgery. As secondary outcomes: final mean best corrected distance visual acuity (BCDVA), complications, and mean intraocular pressure (IOP) trends. The anatomical success was reached by 262 (95.6%) of cases. Mean BCDVA improved from 0.73 LogMAR at baseline, to 0.21 LogMAR at the end of follow-up. As complications we recorded: 5 cases of clinically relevant macular pucker, 1 full thickness macular hole, and 1 PFO bubble under the retina. The mean IOP remained on normal values during the overall follow-up period.


Local anesthetics allergy: who should be tested?
Objective. To document the test results of patients referred to our clinic for testing with local anesthetics (LAs) in real life conditions and provide data related to the necessity of these tests. Methods. All consecutive subjects who were referred to be evaluated for LA allergy during a two-year follow up were included in the analysis. All subjects underwent skin prick / intradermal tests followed by a subcutaneous provocation test with the LAs tested. Results. A total of 228 subjects were included. The main referral reason was the presence of a history of drug hypersensitivity reaction (DHR) to drugs other than LAs (n = 128; 56%), whereas a history of LA allergy constituted the second most common referral reason (n = 64, 28.1%). In the majority of cases (n = 39; 60.9%), the culprit LA was not known by the patients. Asthma was the third most common referral reason, presented in 49 cases (21.5%). Ten cases had positivity to the tested LA in skin testing / challenges. Nine out of 10 patients had a history of DHR to drugs other than LA, whereas 5 of them had also a history of DHR to LA. Six of the 10 patients had a history of multiple DHR. None of the asthma patients without any DHR history were positive in the LA tests. Eight out of 10 cases who underwent skin testing / challenge with an alternative LA, tolerated the alternative LA. Conclusion. The most common referral reason for testing with LA was a history of DHR to drugs other than LAs, whereas asthma was the third most common referral reason. Patients with a history of multiple DHR may be considered for testing with LAs. Asthmatics and those with other allergic diseases without a history of drug / LA allergy do not need to be tested with LA.


Synthesis of 2-bromoacetamidoestrone methyl ether and study of the steroid-binding site of human placental estradiol 17 beta-dehydrogenase.
To characterize further the active site of human placental estradiol 17 beta-dehydrogenase (EC 126.96.36.199), we have synthesized 2-bromoacetamidoestrone methyl ether. The affinity-labeling steroid is a substrate for the homogeneous enzyme. It inactivates the enzyme in a time-dependent, irreversible manner which follows pseudo-first order kinetics. Further, inactivation conducted with varying steroid concentration displays saturation kinetics. When 1.7 x 10(-6) M enzyme is inactivated by 2.6 x 10(-4) M 2-bromoacetamidoestrone methyl ether, the presence of an equimolar concentration of estradiol or 5.2 x 10(-4) M concentrations of NAD+, NADP+, or NADPH markedly slow the rate of inactivation. Bromoacetate (2.6 x 10(-4) M) does not inactivate the enzyme. After inactivation with 2-bromo[2'-14C]acetamidoestrone methyl ether, amino acid analysis reveals carboxymethylated derivatives of cysteine, histidine, and lysine containing 65, 25, and 8%, respectively, of the total incorporated carboxymethyl groups. The presence of estradiol, NADP+, or NADPH clearly inhibits alkylation of cysteinyl and histidyl residues and slows the rate of enzyme inactivation. Protection of these residues by both estradiol and NADPH suggests that they may actually be in the cofactor region of the active site, that this region is close to the steroid A-ring, and that binding of cofactor, by physical interposition, denies the reagent-bearing steroid access to these residues.


In vitro interactions between fluoxetine or fluvoxamine and methadone or buprenorphine.
Methadone and buprenorphine, widely used in the treatment of opioid abuse, are metabolized by cytochrome P450 3A4, while fluoxetine and fluvoxamine, both selective serotonin reuptake inhibitors, are known to be P450 2D6 and 3A4 inhibitors in vitro. This study deals with the in vitro interactions between methadone or buprenorphine and fluoxetine or fluvoxamine. Fluoxetine inhibited methadone N-demethylation (Ki = 55 microM), but conversely did not inhibit buprenorphine dealkylation. Norfluoxetine inhibited the metabolism of both methadone and buprenorphine metabolisms (Ki 13 and 100 microM, respectively). Fluvoxamine inhibited methadone N-demethylation with a Ki of 7 microM and buprenorphine dealkylation, uncompetitively, with a Ki of 260 microM. Finally, these results suggest that care should be taken when selective serotonin reuptake inhibitors are administered in the treatment of drug craving. This is particularly true in the case of fluvoxamine which is more potent than fluoxetine in inhibiting methadone and buprenorphine metabolism.


Cytotoxic efficacy and influence on cellular phospholipid metabolism of 2-hydroxy- and 2-O-acetyl-octadecylphosphocholines.
The cytotoxic efficacy and influence on phospholipid composition of the new alkylphosphocholines (APC) 2-hydroxy and 2-O-acetyl-octadecylphosphocholines both synthesised in R- and S-configuration (R/S-OH and R/S-O-acetyl) were examined in vitro using HL-60 and MDA-MB-468 cells. IC50- and LC50-values were measured by MTT- and cell count assay. All tested APC showed higher or similar cytotoxic efficacy compared to the well known APC hexadecylphosphocholine (HePC). However, while S-configured APC (IC50) revealed considerably higher cytotoxic activities, only R- (natural)-configured APC caused significant changes in the phospholipid composition of tumour cells. Further investigations revealed an increase in R-O-acyl and loss of PC up to 70% in the membrane of both cell lines. Similar to PC, R-O-acyl bears two long non-polar hydrocarbon chains and stabilises cell membranes structurally, thus, possibly explaining less cytotoxicity and lack of apoptosis induction by R-configured APC. Nevertheless, an enrichment of R-O-acyl up to 70% at the expense of PC in cell membrane is tremendous and may inhibit tumour development by influencing the intracellular lipid signalling. In conclusion, our findings reveal the antitumoral efficacy of all tested new APC and offer new perspectives in drug development targeting phospholipid metabolism.


A simplified endoscopic third ventriculostomy under local anesthesia.
The aim of this study is the analysis of our experience with awake endoscopic third ventriculostomy (ETVS) in hydrocephalic patients. From September 1994 to December 2001, 24 neuroendoscopic procedures were performed under local anesthesia. Local infiltration was administered using a bupivacaine and lidocaine mixture. Analgesics were titrated to the effect. A free-hand technique with a flexible endoscope was adopted in 24 patients with primitive and secondary (neoplastic) hydrocephalus. ETVS was performed successfully in all cases. No procedure needed to be discontinued due to seizures, bleeding or agitation. Dural incision/coagulation and Fogarty dilatation proved to be the most painful maneuvers requiring, sometimes, supplemental analgesic administration. No intraoperative complications were observed; however, two asymptomatic trajectory hematomas were incidentally discovered two and three days after the operation, respectively. Awake ETVS is a valuable alternative procedure that can be adopted in adult cooperative patients, provided that the procedure is done in an essential and fast way with the free-hand technique, by means of a flexible endoscope, and with the assistance of an anesthesiologist.


Non-achievement of clinical targets in patients with type 2 diabetes mellitus.
The study was conducted to determine whether the clinical targets for the control of diabetes recommended by American Diabetes Association can be met in the context of routine diabetes practice. This cross-sectional study was undertaken on 211 type 2 diabetic patients at the Outpatients Diabetes Clinic, Hospital Universisti Sains Malaysia (HUSM) Kubang Kerian, Kelantan between the year 2001-2002. Patients' physical examination and their medical history as well as their family history were obtained by administering a structured questionnaire. Samples of patients' venous blood during fasting were taken and analysed for plasma glucose, glycated haemoglobin and lipid profile. Analysis showed that many patients had comorbidities or complications. A large number of them had poor glycaemic control (73%). Systolic and diastolic blood pressures of 75% and 85% subjects were > or = 130 and > or = 80 mmHg, respectively. Body Mass Index (BMI) values of 66% of the patients were outside the clinical target (BMI > or = 25 in male and > or = 24 kg/m2 in female). The lipid profile showed that 96% of the patients had at least one lipid value outside the clinical target level. In this study, 70% of the patients had total cholesterol > or = 5.2 mmol/L, 87% had LDL cholesterol > or = 2.6 mmol/L, 57% had HDL cholesterol less than the normal range, < or = 1.15 mmol/L in men and < or = 1.4 mmol/L in women, while 46% had triglycerides > or = 1.71 mmol/L. Complications of diabetes were observed in 48% of the total number of patients. As for the patients' systolic blood pressure, age and duration of diabetes were found to have significant effects. Older subjects with a longer duration of diabetes were more hypertensive. Variables that had significant effects on BMI were age, duration of diabetes, glycaemic control and gender. Younger females and newly diagnosed subjects with better glycaemic control (A1C < 7%) were found to have higher BMI values. The overall clinical targets were suboptimal. The prevalence of hyperlipidaemia and hypertension was high. It is imperative that better treatment strategies and methods be adopted to enhance diabetes control and reduce long-term complications of the disease.


Reactive oxygen species-induced activation of the MAP kinase signaling pathways.
An abundance of scientific literature exists demonstrating that oxidative stress influences the MAPK signaling pathways. This review summarizes these findings for the ERK, JNK, p38, and BMK1 pathways. For each of these different MAPK signaling pathways, the following is reviewed: the proteins involved in the signaling pathways, how oxidative stress can activate cellular signaling via these pathways, the types of oxidative stress that are known to induce activation of the different pathways, and the specific cell types in which oxidants induce MAPK responses. In addition, the functional outcome of oxidative stress-induced activation of these pathways is discussed. The purpose of this review is to provide the reader with an overall understanding and appreciation of oxidative stress-induced MAPK signaling.


Refined models of New Delhi metallo-beta-lactamase-1 with inhibitors: an QM/MM modeling study.
New Delhi metallo-beta-lactamase 1 (NDM-1) has been identified as a potential target for the treatment of multi-drug resistance bacterial infections. We used molecular docking, normal MD, SIE, QM/MM MD simulations, QM/MM GBSA binding free energy, and QM/MM GBSA alanine-scanning mutagenesis techniques to investigate interactions of the NDM-1 with 11 inhibitors (Tigecycline, BAL30072, D-captopril, Penicillin G, Ampicillin, Carbenicillin, Cephalexin, Cefaclor, Nitrocefin, Meropenem, and Imipenem). From our normal MD and QM/MM simulations, the correlation coefficients between the predicted binding free energies and experimental values are .88 and .93, respectively. Then simulations, which combined QM/MM/GBSA and alanine-scanning mutagenesis techniques, were performed and our results show that two residues (Lys211 and His250) have the strongest impact on the binding affinities of the 11 NDM-1/inhibitors. Therefore, our approach theoretically suggests that the two residues (Lys211 and His250) are responsible for the selectivity of NDM-1 associated inhibitors.


A two-year survey on mosquitoes of Lebanon.
A total of 6,500 mosquitoes were identified during a two-year survey (1999-2001) in Lebanon, and these belonged to twelve species: Culex pipiens, Cx. laticinctus, Cx. mimeticus, Cx. hortensis, Cx. judaicus, Aedes aegypti, Ae. cretinus, Ochlerotatus caspius, Oc. geniculatus, Oc. pulchritarsis, Culiseta longiareolata and Anopheles claviger. Culex pipiens was the most predominant species in Lebanon, collected indoors and outdoors. It was continuously abundant and active throughout the year. Culex judaicus was a small and rare mosquito and it is reported to occur for the first time in Lebanon. On the coastal areas, Ochlerotatus caspius was very common, and proved to be a complex of species as two forms were detected. One of the vectors of malaria, Anopheles claviger, was collected from May to September, from eight sites in Lebanon. Its breeding sites were restricted to fresh, cool, and clean water in pools and wells. Most of these breeding sites were in the populated Metn County where a few indigenous cases of malaria were reported from 1997-2000. This shows that the reported malaria cases were not imported, but caused by the bites of locally infected Anopheles females.


Clostridium tepidum sp. nov., a close relative of Clostridium sporogenes and Clostridium botulinum Group I.
Obligately anaerobic, Gram-stain-positive, spore-forming bacteria indistinguishable by pulsed-field gel electrophoresis were isolated from non-dairy protein shakes in bloated bottles. One of the isolates, strain IEH 97212T, was selected for further study. The strain was closely related to Clostridium sporogenes and Clostridium botulinum Group 1 based on 16S rRNA gene sequence similarities. Phylogenetic analysis also showed that strain IEH 97212T and strain PE (=DSM 18688), a bacterium isolated from solfataric mud, had identical 16S rRNA gene sequences. Strains IEH 97 212T and DSM 18 688 were relatively more thermophilic (temperature range for growth: 30-55 °C) and less halotolerant [growth range: 0-2.5 % (w/v) NaCl] than C. sporogenes and C. botulinum. They were negative for catalase, oxidase, urease and l-pyrrolidonyl-arylamidase and did not produce indole. The strains produced acid from d-glucose, maltose and trehalose, and hydrolysed gelatin, but did not hydrolyse aesculin. The end-products of growth included acetic acid, propionic acid, butyric acid, isobutyric acid, valeric acid, isovaleric acid, isocaproic acid, phenylpropionic acid, 2-piperidinone, 2-pyrrolidinone and gas(es). The predominant fatty acids were C14 : 0, C16 : 0 and C18 : 1ω9c. The genomic DNA G+C content of strains IEH 97212T and DSM 18688 was 26.9 and 26.7 mol%, respectively. According to the digital DNA-DNA hybridization data, the relatedness of these strains was 98.4 %, while they showed only 35.7-36.0 % relatedness to C. sporogenes. Based on the results of this polyphasic study, these strains represent a novel species, for which the name Clostridium tepidum sp. nov. is proposed, with the type strain IEH 97212T (=NRRL B-65463T=DSM 104389T).


Similarity and consistency assessment of three major online drug-drug interaction resources.
The aim of this study was to explore the level of agreement on drug-drug interaction (DDI) information listed in three major online drug information resources (DIRs) in terms of: (1) interacting drug pairs; (2) severity rating; (3) evidence rating; and (4) clinical management recommendations. We extracted information from the British National Formulary (BNF), Thesaurus and Micromedex. Following drug name normalisation, we estimated the overlap of the DIRs in terms of DDI. We annotated clinical management recommendations either manually, where possible, or through application of a machine learning algorithm. The DIRs contained 51 481 (BNF), 38 037 (Thesaurus) and 65 446 (Micromedex) drug pairs involved in DDIs. The number of common DDIs across the three DIRs was 6970 (13.54% of BNF, 18.32% of Thesaurus and 10.65% of Micromedex). Micromedex and Thesaurus overall showed higher levels of similarity in their severity ratings, while the BNF agreed more with Micromedex on the critical severity ratings and with Thesaurus on the least significant ones. Evidence rating agreement between BNF and Micromedex was generally poor. Variation in clinical management recommendations was also identified, with some categories (i.e., Monitor and Adjust dose) showing higher levels of agreement compared to others (i.e., Use with caution, Wash-out, Modify administration). There is considerable variation in the DDIs included in the examined DIRs, together with variability in categorisation of severity and clinical advice given. DDIs labelled as critical were more likely to appear in multiple DIRs. Such variability in information could have deleterious consequences for patient safety, and there is a need for harmonisation and standardisation.


[Not Available].
The paper is focused on the theory of regression formulated by the Budapest School of psychoanalysis, first of all by Michael Balint, which is closely related to the idea of primary love, the dual union of the mother and the child. The contribution of the Budapest School to the establishment of object relational theory and self psychology is recapitulated. Based on the work of Freud, Ferenczi, Balint and Kohut, the history of the term regression from the initial negative connotations to its interpretation as an indispensable skill of the healthy Ego is surveyed. Finally, the issue whether regression is an enemy or a helper is addressed, its manifestations in everyday life and applicability in self psychology oriented psychoanalytic therapy are discussed. Self psychology investigates regression in the mirror of the integrity of self formation: it considers the capacity for benignant regression as an indispensable condition of the healthy self, and blames the defense against regression for certain problems, most particularly for sexual orgasm disorders. In the paper, this interpretation is traced back to the theory of Balint, postulating a close relation between self psychological approach and the Balintian theory of benignant regression. The author argues that the resulting consequnces can be directly applied in psychoanalytic therapy, and demonstrates this statment by two case reports.


Discrepancy Between Patient and Caregiver Estimate of Apathy Predicts Dementia in Patients with Amnestic Mild Cognitive Impairment.
Apathy is a frequent behavioral symptom of Alzheimer's disease (AD). The Apathy Evaluation Scale (AES) is a tool exploring the perception of apathy by both caregivers (CG-AES) and patients (PT-AES), and the discrepancy in their ratings is a proxy of patients' disease unawareness. To assess in a cohort study of patients with amnesic mild cognitive impairment (aMCI) whether apathy and awareness of apathy predict progression to dementia and timing. From the global AES scores of 110 patients with aMCI and their caregivers, we obtained two principal indices for analysis: 1) 'Apathy', the mean of PT-AES and CG-AES, and 2) 'Discrepancy', obtained by subtracting CG-AES from PT-AES. Patients were followed with visits every six months for three years or until dementia. AES indices and the principal demographical/neuropsychological variables were filtered from multicollinearity. The most robust variables entered a logistic regression model and survival analyses (Cox regression, log-rank test of Kaplan-Meier curves) to estimate which predicted the risk and timing of progression, respectively. Sixty patients (54.5%) developed dementia (57 AD) after 6.0-36.0 months, 22 (20%) remained in an MCI stage, and 28 (25.5%) dropped out. 'Discrepancy' was a robust and accurate predictor of the risk of progression (AUC = 0.73) and, after binarization according to a computed cutoff, of timing to dementia. A structured evaluation of apathy, both self-assessed and estimated by caregivers, can provide useful information on the risk and timing of progression from aMCI to dementia. The discrepancy between the two estimates is a fairly reliable index for prediction purposes as a proxy of disease unawareness.


Influence of vermicomposting on solid wastes decomposition kinetics in soils.
The effect of vermicomposting on kinetic behavior of the products is not well recognized. An incubation study was conducted to investigate C mineralization kinetics of cow manure, sugarcane filter cake and their vermicomposts. Two different soils were treated with the four solid wastes at a rate of 0.5 g solid waste C per kg soil with three replications. Soils were incubated for 56 d. The CO(2)-C respired was monitored periodically and a first-order kinetic model was used to calculate the kinetic parameters of C mineralization. Results indicated that the percentage of C mineralized during the incubation period ranged from 31.9% to 41.8% and 55.9% to 73.4% in the calcareous and acidic soils, respectively. The potentially mineralizable C (C(0)) of the treated soils was lower in the solid waste composts compared to their starting materials. Overall, it can be concluded that decomposable fraction of solid wastes has decreased due to vermicomposting.


Steroidogenic acute regulatory (StAR) protein (p25) and prohibitin (p28) from cultured rat ovarian granulosa cells.
This study has identified and characterized two intracellular proteins (25 and 28 kDa) during ongoing differentiation of rat granulosa cells isolated from preantral and early antral follicles. The identity of p25 was confirmed as the mitochondria associated StAR protein by western blotting analysis. In the culture conditions used, this protein was expressed only when granulosa cells were stimulated with FSH to produce progesterone. It is apparent that the steroidogenic differentiation of granulosa cells affects StAR expression. Amino acid sequence analysis of p28 identified it as prohibitin and was corroborated by western blot analysis with antibodies specific for rat prohibitin. During the ongoing differentiation of granulosa cells there were changes in the expression of p28/prohibitin. Although prohibitin is constitutively expressed in granulosa cells, there is an increase in the more acidic isoform of prohibitin when oestrogen concentrations are raised by increased production or exogenous addition. This increase in this acidic isoform of prohibitin is due to phosphorylation. It is possible that oestrogen induces phosphorylation of prohibitin and, thus, may be involved in the regulation of granulosa cell proliferation and the ontogeny of the ovarian follicle.


Proteostasis of polyglutamine varies among neurons and predicts neurodegeneration.
In polyglutamine (polyQ) diseases, only certain neurons die, despite widespread expression of the offending protein. PolyQ expansion may induce neurodegeneration by impairing proteostasis, but protein aggregation and toxicity tend to confound conventional measurements of protein stability. Here, we used optical pulse labeling to measure effects of polyQ expansions on the mean lifetime of a fragment of huntingtin, the protein that causes Huntington's disease, in living neurons. We show that polyQ expansion reduced the mean lifetime of mutant huntingtin within a given neuron and that the mean lifetime varied among neurons, indicating differences in their capacity to clear the polypeptide. We found that neuronal longevity is predicted by the mean lifetime of huntingtin, as cortical neurons cleared mutant huntingtin faster and lived longer than striatal neurons. Thus, cell type-specific differences in turnover capacity may contribute to cellular susceptibility to toxic proteins, and efforts to bolster proteostasis in Huntington's disease, such as protein clearance, could be neuroprotective.


Sensory impact of lowering sugar content in orange nectars to design healthier, low-sugar industrialized beverages.
The presence of added sugars (AS) in the diet is associated with increased risk of obesity and other chronic diseases. We assessed sensory impact of lowering AS in orange nectar, aiming at new WHO sugar guideline. Ideal sweetness by just-about-right (JAR) tests (60 consumers), difference and rejection thresholds (36 and 35 assessors), and acceptance and sensory profile by Check-all-that-apply (CATA) tests (100 consumers) were performed. JAR test comprised six concentrations of AS from 12% down to 4.5%. Thresholds tests comprised orange nectars at reference sugar concentration (10%) and at lower sugar levels. Acceptance and CATA tests compared reference, ideal sweetness and thresholds concentrations. There were two groups of consumers; one with ideal sweetness lower at 5.5% AS and another with ideal sweetness at standard 10.5% AS. The average ideal sweetness among all consumers was 7.3% AS. The difference threshold from the reference at 10.5% AS was at 8.5% AS and the rejection threshold was 7.2%. Overall acceptance of nectar with 8.5% and 7.2% AS was similar to reference and higher than acceptance of nectar with 5.5%. However, after cluster analysis, nectars with 5.5% AS did not differ from nectars with 8.5% or 7.2% AS, suggesting the possibility of a gradual reduction until 5.5% in the long term. Lowering AS to 7.2% or 5.5% caused significant changes in viscosity, sweet odor, bitterness and sweetness in comparison to the reference concentration. Lowering sugar from 10% to 8.5% did not affect acceptance or sensory attributes, and could be indicated for a first reduction. Results indicate that a gradual reduction to 7.2% and 5.5% would be feasible. Reductions can remove 3150-9450 tons of sugar per year from the Brazilian diet resulting in healthier beverages.


A pilot study of risk-based prevention in private practice.
Risk-based prevention is a means of ensuring that patients receive preventive treatment appropriate for their risk of disease. While straightforward, its application in private practice has not been examined. Volunteer clinicians in 15 offices participated in a six-month pilot study to test methods for a larger, risk-based prevention demonstration study operated by a dental insurer. Concomitant with oral examinations for patients of this insurer, clinicians identified patients at elevated risk of developing dental caries and periodontitis. For these patients, the reasons for elevated risk (risk indicators), as well as planned preventive treatment in response to that risk, were recorded and transmitted to the insurer via the claim form. The clinicians identified relatively small percentages of patients as being at high risk of developing caries (4 percent) and periodontitis (7 percent), with little variation across the 15 offices. Larger proportions of patients were identified as being at moderate risk of developing caries (29 percent) and periodontitis (30 percent), with more extensive variation across offices. In general, patients classified as being at elevated risk had received more disease-related treatment than patients at low risk before the classification, which provided some validation for the accuracy of risk assessment. The results of this pilot study suggest that formal, risk-based prevention can be accomplished in dental offices. Clinicians' reported risk assignments and indicators, together with their planned preventive treatments, demonstrate a good understanding of risk-based prevention. Researchers may need to clarify the criteria used to assess moderate risk of developing dental caries, and clinicians may need to emphasize greater use of fluorides and more frequent recall visits for adults at elevated risk of developing dental caries.


Complex knee injuries treated in acute phase: Long-term results using Ligament Augmentation and Reconstruction System artificial ligament.
To present the long-term results of complex knee injuries, treated early using the Ligament Augmentation and Reconstruction System (LARS) artificial ligament to reconstruct posterior cruciate ligament (PCL). From September 1997 to June 2010, thirty-eight complex knee injuries were treated, where early arthroscopic PCL reconstructions were undergone, using the LARS (Surgical Implants and Devices, Arc-sur-Tille, France) artificial ligament. Exclusion criteria were: Late (> 4 wk) reconstruction, open technique, isolated PCL reconstruction, knee degenerative disease, combined fracture or vascular injury and use of allograft or autograft for PCL reconstruction. Clinical and functional outcomes were assessed with IKDC Subjective Knee Form, KOS-ADLS questionnaire, Lysholm scale and SF-12 Health Survey. Posterior displacement (PD) was measured with the Telos Stress Device. Seven patients were excluded; two because of co-existing knee osteoarthritis and the remaining five because of failure to attend the final follow-up. The sample consisted of 31 patients with mean age at the time of reconstruction 33.2 ± 12.5 years (range 17-61). The postoperative follow-up was on average 9.27 ± 4.27 years (range 5-18). The mean average IKDC and KOS scores were 79.32 ± 17.1 and 88.1 ± 12.47% respectively. Average PD was 3.61 ± 2.15 mm compared to 0.91 ± 1.17 mm in the uninjured knees (one with grade 1 + and two with grade 2 +). Dial test was found positive in one patient, whereas the quadriceps active drawer test was positive in three patients. None was tested positive on the reverse-pivot shift test. The range of motion (ROM) was normal in thirty knees, in comparison with the contralateral one. There was no extension deficit. Osteoarthritic changes were found in three knees (9.6%). Early treatment of complex knee injuries, using LARS artificial ligament for PCL reconstruction sufficiently reduces posterior tibia displacement and provides satisfactory long-term functional outcomes.