QUest for the Arrhythmogenic Substrate of Atrial fibRillation in Patients Undergoing Cardiac Surgery (QUASAR Study): Rationale and Design.
The heterogeneous presentation and progression of atrial fibrillation (AF) implicate the existence of different pathophysiological processes. Individualized diagnosis and therapy of the arrhythmogenic substrate underlying AF may be required to improve treatment outcomes. Therefore, this single-center study aims to identify the arrhythmogenic areas underlying AF by intra-operative, high-resolution, multi-site epicardial mapping in 600 patients with different heart diseases. Participants are divided into 12 groups according to the underlying heart diseases and presence of prior AF episodes. Mapping is performed with a 192-electrode array for 5-10 s during sinus rhythm and (induced) AF of the entire atrial surface. Local activation times are converted into activation and wave maps from which various electrophysiological parameters are derived. Postoperative cardiac rhythm registrations and a 5-year follow-up will show the incidence of postoperative and persistent AF. This project provides the first step in the development of a tool for individual AF diagnosis and treatment.


Endoscopic Sleeve Gastroplasty: A Practice Pattern Survey.
Obesity is a complex, chronic disease that is strongly associated with complications which cost the US healthcare system billions of dollars per year. Endoscopic sleeve gastroplasty (ESG) has emerged as a safe and effective procedure for treatment of obesity, but without practice guidelines there are likely to be variations practice. We sought to describe current practice patterns amongst endoscopists who perform ESG to help define areas of focus for future research and guideline development. We conducted an anonymous cross-sectional survey to examine practice patterns related to ESG. The survey was organized in 5 sections: Endoscopic Practice, Training, and Resources; Pre-ESG Evaluation and Payment Model; Perioperative/Operative Period; Post-operative Period; and Endobariatric Practice Other Than ESG. A variety of exclusion criteria were reported by physicians performing ESG. Most respondents (n = 21/32, 65.6%) would not perform ESG for BMI under 27, and 40.6% (n = 13/32) would not perform ESG on patients with BMI over 50. The majority of respondents (74.2%, n = 23/31) reported ESG was not covered in their region, and most reported patients covered residual costs (67.7%, n = 21/31). We found significant variability with respect to practice setting, exclusion criteria, pre-procedural evaluation, and medication use. Without guidelines for the selection of patients or standards for pre- and post-ESG care, substantial barriers to coverage will remain, and ESG will remain limited to those who can meet out-of-pocket costs. Larger studies are needed to confirm our findings, and future research should be focused on establishing patient selection criteria and standards in practices to provide guidance for endobariatric programs.


Predictive parameters of CyberKnife fiducial-less (XSight Lung) applicability for treatment of early non-small cell lung cancer: a single-center experience.
To determine which parameters allow for CyberKnife fiducial-less tumor tracking in stereotactic body radiation therapy (SBRT) for early-stage non-small cell lung cancer. A total of 133 lung SBRT patients were preselected for direct soft-tissue tracking based on manufacturer recommendations (peripherally located tumors ≥1.5 cm with a dense appearance) and staff experience. Patients underwent a tumor visualization test to verify adequate detection by the tracking system (orthogonal radiographs). An analysis of potential predictors of successful tumor tracking was conducted looking at: tumor stage, size, histology, tumor projection on the vertebral column or mediastinum, distance to the diaphragm, lung-to-soft tissue ratio, and patient body mass index. Tumor visualization was satisfactory for 88 patients (66%) and unsatisfactory for 45 patients (34%). Median time to treatment start was 6 days in the success group (range, 2-18 days) and 15 days (range, 3-63 days) in the failure group. A stage T2 (P=.04), larger tumor size (volume of 15.3 cm(3) vs 6.5 cm(3) in success and failure group, respectively) (P<.0001), and higher tumor density (0.86 g/cm(3) vs 0.79 g/cm(3)) were predictive of adequate detection. There was a 63% decrease in failure risk with every 1-cm increase in maximum tumor dimension (relative risk for failure = 0.37, CI=0.23-0.60, P=.001). A diameter of 3.6 cm predicted a success probability of 80%. Histology, lung-to-soft tissue ratio, distance to diaphragm, patient's body mass index, and tumor projection on vertebral column and mediastinum were not found to be predictive of success. Tumor size, volume, and density were the most predictive factors of a successful XSight Lung tumor tracking. Tumors >3.5 cm have ≥80% chance of being adequately visualized and therefore should all be considered for direct tumor tracking.


Thoracoscopic Anatomical Sublobar Resection Including Subsegmentectomy for Non-Small Cell Lung Cancer.
Among anatomical sublobar resection techniques for non-small cell lung cancer (NSCLC), the clinical benefit of subsegmentectomy remains unclear. We investigated whether anatomical sublobar resection including subsegmentectomy-segmental resection with subsegmental additional resection or subsegmental resection alone-is an effective and feasible surgical procedure for NSCLC. We retrospectively reviewed data of 285 patients with clinical stage I NSCLC who underwent anatomical sublobar resection at our institution from January 2013 to March 2021 and compared surgical outcomes between patients who underwent anatomical sublobar resection including (IS; n = 50) and excluding (ES; n = 235) subsegmentectomy. No significant intergroup differences were noted in terms of age, sex, smoking, comorbidities, tumor size or location, consolidation tumor ratio, and preoperative pulmonary function. The IS group had more preoperative computed tomography-guided markings (34 vs. 15%; p = .004) and smaller resected lung volumes converted to the total subsegment number [3 (2-4) vs. 3 (3-6); p = .02] than the ES group. No significant differences in margin distance [mm, 20 (15-20) vs. 20 (20-20); p = .93], readmission rate (2% vs. 3%; p > .99), and intraoperative (8% vs. 7%; p = .77) or postoperative (8% vs. 10%; p = .80) complication rates were observed, and the 5-year local recurrence-free survival (91% vs. 90%; p = .92) or postoperative pulmonary function change were comparable between both groups. Although further investigations are required, anatomical sublobar resection including subsegmentectomy for clinical stage I NSCLC could be an acceptable therapeutic option.


QSAR analysis and molecular docking simulation of norepinephrine transporter (NET) inhibitors as anti-psychotic therapeutic agents.
The norepinephrine transporter (NET) is a Na+/Cl- coupled neurotransmitter transporter responsible for reuptake of released norepinephrine (NE) into nerve terminals in the brain, a key therapeutic used in the treatment of psychiatric disorders. A quantitative structural activity relationship (QSAR) study was performed on 50 compounds of NET inhibitors to investigate their inhibitory potencies against norepinephrine transporter as novel drugs for anti-psychotic disorders. The compounds were optimized by employing Density functional theory (DFT) with basis set of B3LYP/6-31G*. The genetic function Algorithm (GFA) approach was used to generate a highly predictive and statistically significant model with good correlation coefficient R2 Train = 0.952 Cross validated coefficient Q2 cv = 0.870 and adjusted squared correlation coefficient R2 adj = 0.898. The predictability and accuracy of the developed model was evaluated through external validation using test set compound, Y-randomization and applicability domain techniques. The results of Molecular docking analysis by using two neurotransmitter transporters PDB ID 2A65 (resolution = 1.65 Å) and PDB ID 4M48 (resolution = 2.955 Å) showed that two of the ligands (compound 12 and 44) having higher binding affinity were observed to inhibit the targets by forming hydrogen bonds and hydrophobic interactions with amino acids of the two receptors respectively. The results of these studies would provide important new insight into the molecular basis and structural requirements to design more potent and more specific therapeutic anti-psychotic drugs/agents.


Pretreatment depression as a prognostic indicator of survival and nutritional status in patients with head and neck cancer.
The emotional status of cancer patients is associated with disease course and treatment outcomes. In this study, the authors evaluated associations between the presence of pretreatment depression and pretreatment quality of life (QOL), nutritional status, and survival outcomes in patients with head and neck squamous cell carcinoma (HNSCC). For this prospective study, 241 patients with previously untreated HNSCC who underwent curative treatments were enrolled. Patients completed the Beck Depression Inventory (BDI)-II, the European Organization for Research and Treatment of Cancer (EORTC) 30-item Core QOL Questionnaire (QLQ-C30), and the EORTC QLQ Head and Neck Cancer module (QLQ-H&N35). EORTC QLQ scores were compared between depressive and nondepressive patients, as determined according to pretreatment BDI-II scores ≥ 14 and <14, respectively. Univariate and multivariate analyses were performed to assess whether the presence of depression was associated with overall survival, disease-free survival (DFS), or posttreatment changes in nutritional status and laboratory data. Pretreatment depression was present in 60 patients (24.9%). In depressive and nondepressive patients, the 3-year overall survival rates were 70.8% and 82.7%, respectively (P = .045), and the 3-year DFS rates were 63.5% and 79.1%, respectively (P = .015). After controlling for clinical factors, the presence of depression was predictive of 3-year DFS (P = .032). EORTC QLQ-C30 and QLQ-HN35 scores on all items except feeding tube, nutritional supplement, and problem with mouth opening differed between depressive and nondepressive patients (P < .05). Depressive patients had lower pretreatment serum albumin levels than nondepressive patients (P < .05). There was a significant correlation between pretreatment depression and pretreatment QOL, nutritional status, and survival outcomes in patients with HNSCC.


Physical exercise enhances protein kinase C delta activity and insulin receptor tyrosine phosphorylation in diabetes-prone psammomys obesus.
We recently reported that physical exercise prevents the progression of type 2 diabetes mellitus in Psammomys obesus, an animal model of nutritionally induced type 2 diabetes mellitus. In the present study we characterized the effect of physical exercise on protein kinase C delta (PKC delta) activity, as a mediator of the insulin-signaling cascade in vivo. Three groups of Psammomys obesus were exposed to a 4-week protocol: high-energy diet (HE/C), high-energy diet and exercise (HE/EX), or low-energy diet (LE/C). None of the animals in the HE/EX group became diabetic, whereas all the animals in the HE/C group became diabetic. After overnight fast, intraperitoneal (IP) insulin (1U) caused a greater reduction in blood glucose levels in the HE/EX and LE/C groups compared to the HE/C group. Tyrosine phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and phosphatidylinositol 3 kinase (PI3 kinase) was significantly higher in the HE/EX and LE/C groups compared with the HE/C group. Finally, IR-associated PKC delta was higher in the HE/EX and LE/C groups compared to the HE/C group. Coprecipitation of PKC delta with IR was higher in the HE/EX and LE/C groups compared to the HE/C group. Thus, we suggest that 4 weeks of physical exercise results in improved insulin-signaling response in Psammomys obesus accompanied by a direct connection between PKC delta and IR. We conclude that this mechanism may be involved in the preventive effect of exercise on type 2 diabetes mellitus in Psammomys obesus.


Knife cut marks inflicted by different blade types and the changes induced by heat: a dimensional and morphological study.
Detailed information on skeletal trauma analysis of burned bone is important to ascertain the manner and cause of death in forensic casework. This research used three different knife types, one with a non-serrated blade, one a fine-serrated blade, and one a coarse-serrated blade, to inflict trauma to manually macerated Sus scrofa ribs (n = 240), and these ribs were later exposed to heat. Qualitative and quantitative analyses were conducted using macroscopic and microscopic techniques to assess specific characteristics of the cut marks. Differences in cut mark dimension and morphology of the ribs were investigated. After heat exposure, the cut marks on the rib samples remained recognisable and did not alter considerably. A level of dimensional and morphological preservation was reliant on the cutting action and the features of the knife blade as well as surrounding bone injury. The cut marks inflicted by the non-serrated blade remained recognisable despite exposure to the burning process. However, the cut marks inflicted by the coarse-serrated blade were likely to change significantly when exposed to heat. This study leads to two important results: (1) identification of pre-existing cut marks prior to heat exposure is possible in reconstructed burned bone fragments, and (2) cut marks from different types of knife blades showed dissimilar responses to heat. The outcomes obtained in this study stressed the need to adopt great care with the effects of heat on skeletal trauma analysis.


Molecular mechanisms of osteoporotic hip fractures in elderly women.
A common manifestation of age-related bone loss and resultant osteoporosis are fractures of the hip. Age-related osteoporosis is thought to be determined by a number of intrinsic factors including genetics, hormonal changes, changes in levels of oxidative stress, or an inflammatory status associated with the aging process. The aim of this study was to investigate gene expression and bone architecture in bone samples derived from elderly osteoporotic women with hip fractures (OP) in comparison to bone samples from age matched women with osteoarthritis of the hip (OA). Femoral heads and adjacent neck tissue were collected from 10 women with low-trauma hip fractures (mean age 83±6) and consecutive surgical hip replacement. Ten bone samples from patients undergoing hip replacement due to osteoarthritis (mean age 80±5) served as controls. One half of each bone sample was subjected to gene expression analysis. The second half of each bone sample was analyzed by microcomputed tomography. From each half, samples from four different regions, the central and subcortical region of the femoral head and neck, were analyzed. We could show a significantly decreased expression of the osteoblast related genes RUNX2, Osterix, Sclerostin, WNT10B, and Osteocalcin, a significantly increased ratio of RANKL to Osteoprotegerin, and a significantly increased expression of the enzymes superoxide dismutase 2 (SOD2) and glutathione peroxidase GPX3, and of the inflammatory cytokine IL6 in bone samples from hip fracture patients compared to controls. Major microstructural changes in OP bone were seen in the neck and were characterized by a significant decrease of bone volume, trabecular number, and connectivity density and a significant increase of trabecular separation. In conclusion, our data give evidence for a decreased expression of osteoblast related genes and increased expression of osteoclast related genes. Furthermore, increased expression of SOD2 and GPX3 suggest increased antioxidative activity in bone samples from elderly osteoporotic women with hip fractures.


The Rancho EMG analyzer: a computerized system for gait analysis.
This paper describes a computer system which accurately defines the EMG patterns of the lower extremities during gait. Footswitches are used to identify the temporal relationships and determine the phases of the gait cycle. Fine wire electrodes, inserted in the desired muscles of the patient being tested, provide EMG signals for comparison with a normal database. The system is also usable with surface electrodes when an appropriate normal database for surface electrodes is incorporated. Descriptive qualifiers (such as 'premature onset', 'delayed cessation', 'no clinically significant EMG', 'continuous activity' etc.) are used to produce a clinically relevant printed (textual) report. The intensity filtered average (IFA) of the EMG is shown graphically with the representative profile of each stride. The IFAs for all muscles tested can be plotted together (up to six on a page) and the graphic representation of the 'raw' EMG can be produced. The methods of generating the normal database by creating time-adjusted mean profiles (TAMP) are enumerated. The clinical use of the system is discussed. A detailed analysis of 31 of the most recent patient tests for which the system was used provides an indication of its accuracy. For 86% of the 428 muscle tests examined, the EMG analyser was considered to have given the correct result as compared with a visual analysis of the raw EMG record by a trained expert. Recommendations for the use and future improvements of the EMG analyser are made.


Effect of multiple stress factors (thermal, nutritional and pregnancy type) on adaptive capability of native ewes under semi-arid environment.
This study was conducted to evaluate the effect of multiple stress factors (thermal, nutritional and pregnancy type) on two different native track breeds of ewes as reflected by their adaptive capability under semi-arid environment. The multiple stressor experiment was conducted in twenty-four ewes (12 Santa Inês and 12 Morada Nova ewes). Both heat stress and pregnancy stress was common to all four groups. However, the animals were divided into further two groups within each breed on the basis of nutrition regimen. According the groupings were: Group 1 (Six Santa Ines ewes; heat stress; nutrition at 0.5% of BW; single pregnancy); Group 2 (Six Santa Ines ewes; heat stress; nutrition at 1.5% BW; twin pregnancy); groups Group 3 (Six Morada Nova ewes; heat stress; nutrition at 0.5% of BW; single pregnancy); Group 4 (Six Morada Nova ewes; heat stress; nutrition at 1.5% BW; twin pregnancy). All the animals in the experiment were pregnant. Heat stress was induced by exposing all animals to summer heat stress in outside environment while the nutritional regimen followed was at 0.5% and 1.5% level of body weight (BW) respectively in each breed. The experiment was conducted in a completely randomized design with two breeds, two nutritional treatments and two pregnancy types, 10 repetitions for physiological parameters and six for blood parameters, with repeated measures over time. Physiological parameters (respiratory rate, pulse rate and rectal temperature) were measured with the animals at rest in the morning and afternoon, 0600-0700 and 1300-1400h, respectively, every seven days. Blood samples were collected every 14d for determination of serum glucose, triglycerides, cholesterol, urea and creatinine. We found interaction effect between breed and pregnancy type on respiratory rate and rectal temperature with greater values in Santa Inês ewes than Morada Nova ewes. However, there was no significant fixed effect of pregnancy type and supplementation level on physiological responses of breeds. Environmental factor (period of the day) had influenced the physiological responses of ewes during all gestational period. Santa Inês ewes had greater serum glucose concentration at 105d and 120d of gestation compared to the Morada Nova ewes. Morada Nova ewes had greater concentrations of triglycerides, urea at 120d, 150d and also greater cholesterol at 105d, 135d and 150d of gestation compared with Santa Inês ewes. The present result indicates that thermal condition was most important factor that modified the physiological responses of ewes in a semi-arid tropical environment.


Infrared and theoretical calculations in 2-halocycloheptanones conformational analysis.
2-Halocycloheptanones (Halo=F, Cl, Br and I) were synthesized and their conformational analysis was performed through infrared spectroscopy data. The corresponding conformers geometries and energies were obtained by theoretical calculations at B3LYP/aug-cc-pVDZ level of theory in the isolated state and in solution. It was observed, by both approaches, that the conformational preferences were very sensitive to the solvent polarity, since its increase led to an increase in the population of the more polar conformer. An analysis of these conformational equilibria showed they suffer also the influence of stereoelectronic effects, like hyperconjugation and steric effects. These results were interpreted using natural bond orbital (NBO) analysis, which indicated that the electronic delocalization to the orbital π*(C=O) is directly involved in the stability increase of conformers I and II. The relative effect of the period of the halogen can also be noted, with changes in the conformational preferences and in the energies involved in the interactions of NBO.


Artificial Intelligence-Guided Prediction of Dental Doses Before Planning of Radiation Therapy for Oropharyngeal Cancer: Technical Development and Initial Feasibility of Implementation.
The aim was to develop a novel artificial intelligence (AI)-guided clinical decision support system, to predict radiation doses to subsites of the mandible using diagnostic computed tomography scans acquired before any planning of head and neck radiation therapy (RT). A dose classifier was trained using RT plans from 86 patients with oropharyngeal cancer; the test set consisted of an additional 20 plans. The classifier was trained to predict whether mandible subsites would receive a mean dose >50 Gy. The AI predictions were prospectively evaluated and compared with those of a specialist head and neck radiation oncologist for 9 patients. Positive predictive value (PPV), negative predictive value (NPV), Pearson correlation coefficient, and Lin concordance correlation coefficient were calculated to compare the AI predictions to those of the physician. In the test data set, the AI predictions had a PPV of 0.95 and NPV of 0.88. For 9 patients evaluated prospectively, there was a strong correlation between the predictions of the AI algorithm and physician (P = .72, P < .001). Comparing the AI algorithm versus the physician, the PPVs were 0.82 versus 0.25, and the NPVs were 0.94 versus 1.0, respectively. Concordance between physician estimates and final planned doses was 0.62; this was 0.71 between AI-based estimates and final planned doses. AI-guided decision support increased precision and accuracy of pre-RT dental dose estimates.


KIAA1549 promotes the development and chemoresistance of colorectal cancer by upregulating ERCC2.
Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Chemotherapy is the mainstay of treatment for patients with CRC in II-IV stages. Resistance to chemotherapy occurs commonly, which results in treatment failure. Therefore, the identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and developing new therapeutic strategies. Herein, we assessed the roles of KIAA1549 in promoting tumor development and chemoresistance in colorectal cancer. As a result, we found that KIAA1549 expression is up-regulation in CRC. Public databases revealed a progressive up-regulation of KIAA1549 expression from adenomas to carcinomas. Functional characterization uncovered that KIAA1549 promotes tumor malignant phenotypes and boosts the chemoresistance of CRC cells in an ERCC2-dependent manner. Inhibition of KIAA1549 and ERCC2 effectively enhanced the sensitivity to chemotherapeutic drugs oxaliplatin and 5-fluorouracil. Our findings suggest that endogenous KIAA1549 might function as a tumor development-promoting role and trigger chemoresistance in colorectal cancer partly by upregulating DNA repair protein ERCC2. Hence, KIAA1549 could be an effective therapeutic target for CRC and inhibition of KIAA1549 combined with chemotherapy might be a potential therapeutic strategy in the future.


Effect of chronic renal failure on high-density lipoprotein kinetics.
Plasma lipid and lipoprotein concentration and high density lipoprotein (HDL) kinetics were determined in control subjects and patients with chronic renal failure (CRF). Results demonstrated that plasma triglyceride (TG) concentration was significantly higher (P less than 0.001) in patients with CRF, associated with a significant increase in plasma VLDL-cholesterol (P less than 0.002) and a significant decrease (P less than 0.05) in plasma HDL-cholesterol concentration. The rate of removal of 125I-apoAI/HDL from plasma was slower (P less than 0.001) in the patients with CRF, resulting in an increase in the residence time of 125I-apoAI/HDL (P less than 0.001) and a decrease in the fractional catabolic rate (P less than 0.001). Since plasma apoAI concentration was lower in patients with CRF, total apoAI/HDL synthetic rate was also significantly (P less than 0.05) decreased. These data provide support for the view that low plasma HDL-cholesterol concentrations in patients with CRF are related to decreases in the synthetic rate of apoAI/HDL.


Sequelae of storage in Fabry disease--pathology and comparison with other lysosomal storage diseases.
To evaluate the sequelae of the lysosomal storage of globotriaosylceramide (Gb3) in a series of patients with Fabry disease. Biopsy and post-mortem samples from 12 patients with Fabry disease were examined microscopically, including, in some cases, immunohistochemistry and electron microscopy. Where possible, comparisons were made with other lysosomal storage disorders. Storage of Gb3 in cardiocytes leads commonly to progressive hypertrophy, which is a non-specific phenomenon also observed in other lysosomal storage disorders. Capillary endothelial storage was associated with a tendency for capillary basement membrane multiplication. In the single angiokeratoma studied, the basement membrane was rudimentary. Sinusoids in the adrenal cortex and liver displayed either a slight degree of storage or were unaffected. The glomeruli of the kidney exhibited focal hyalinization starting in the mesangial region. Proximal tubular cells were essentially free of lysosomal accumulation, including protein absorption droplets, despite the presence of proteinuria. In only one case, an autopsied Fabry heterozygote, were the proximal tubular cells loaded with protein absorption droplets. The arterial wall in large muscular arteries (coronary, renal and intrarenal) displayed arteriopathy with pronounced involvement of the smooth muscle cells in the media. Arteriopathy started with storage, followed by cell degeneration and breakdown, extracellular matrix deposition and, often, calcification (confined to the muscular layer). Smooth muscle cells occasionally exhibited shrinkage-type necrosis, with dispersion of the stored lipid into the dense cytoplasmic mass. Intimal and mitral valve fibroblasts exhibited variable storage, which was associated with cell loss and necrosis. Intensive storage was found in Leydig cells and in the epididymal epithelium. These long-term sequelae of Gb3 storage are mostly irreversible. Some may interfere with enzyme replacement therapy. It is important, therefore, to consider starting enzyme replacement therapy as early as possible.


Observation of elevated fasting blood glucose and functional outcome after ischemic stroke in patients with and without diabetes.
During May 2015 to October 2016, this prospective study enrolled a total of 438 patients with acute ischemic stroke(AIS), meanwhile, records regarding the severity of initial stroke and neurological outcomes at three months, as well as other examination were completed in patients on admission, as well as the measurement and evaluation of fasting blood glucose(FBG) levels. At admission, the median FBG levels in patients with a minor stroke (n=124), [P<0.001]) was significantly lower than that observed in patients with other degrees of stroke. The poor functional outcome distribution across the FBG quartiles ranged from 13.8 % (first quartile) to 59.6% (fourth quartile), with P <0.001. Compared with the reference category (first quartile), patients in the highest quartile had a relative risk of 3.12 (95% confidence interval [CI], 1.88-6.15; P<0.001) while those in the second and third quartiles had relative risks of 1.76 (95% CI, 1.21-3.03; P=0.035) and 2.23 (95% CI, 1.50-3.69; P=0.010), respectively. Furthermore, in the patients without diabetes, FBG level was observed to be increased and indicated an increased risk of disability (odds ratio [OR]: 1.30 (95%CI 1.13-1.61), P=0.002), however, similar result was not detected in patients with prior diabetes (P=0.089). In conclusion, elevated FBG levels after stroke may suggest poor functional outcome at 3-month in patients without a previous history of diabetes.


Age affects intraocular lens attributes preference in cataract surgery.
The aim of this study is to analyze the effects of age on intraocular lens (IOL) attributes preference. We enrolled 4213 eyes that underwent smooth phacoemulsification and IOL implantation between January 2005 and June 2018. Patients were subdivided into six groups according to their ages, i.e.,≤40, 41-50, 51-60, 61-70, 71-80, and ≥ 81 years old. The difference in preference of IOL attributes regarding age, gender, and year of surgery was analyzed separately. The analyzed IOL attributes included asphericity, astigmatism-correction, presbyopia-correction, and blue-blocking function. The patients averaged 68.3 ± 11.6 years old at the time of surgery. There was no significant difference in age between males and females. There were 1980 patients (47.0%) selected aspheric IOL, 822 patients (19.5%) selected multifocal (MF) IOL, 93 patients (2.2%) selected toric IOL, and 859 patients (20.4%) selected blue-blocking IOL. Adoption of aspheric and MF IOL increased significantly during the study (P < 0.001 for both attributes). There were more young patients selected aspheric and MF IOL (P < 0.001 for both), and the change in the trend of adoption over the years was also most significant in the young group (P < 0.001 for both). The proportion of patients that selected blue-blocking IOL decreased significantly after 2011 (P < 0.001). There was no gender preference in aspheric, MF, and toric IOL selection. However, there were more male patients selected blue-blocking IOL (P = 0.018). The adoption of IOLs with emerging technologies increased significantly over the years. Younger adults tended to adopt advanced technology IOL more than the older ones.


Design and synthesis of arylaminoethyl amides as noncovalent inhibitors of cathepsin S. Part 1.
A series of Nalpha-acyl-alpha-amino acid-(arylaminoethyl)amides were found to be potent and noncovalent cathepsin S inhibitors. Compound 20 possessed high cathepsin S affinity (Ki=3.3 nM) and showed excellent selectivity over cathepsin K, L, F, and V. Molecular modeling, design, synthesis, and in vitro activity are described.


Primary diaphyseal osteosarcoma in long bones: imaging features and tumor characteristics.
This study aims to assess retrospectively the imaging features of diaphyseal osteosarcoma and compare its characteristics with that of metaphyseal osteosarcoma. Eighteen pathologically confirmed diaphyseal osteosarcomas were reviewed. Images of X-ray (n=18), CT (n=12) and MRI (n=15) were evaluated by two radiologists. Differences among common radiologic findings of X-ray, CT and MRI, and between diaphyseal osteosarcomas and metaphyseal osteosarcomas in terms of tumor characteristics were compared. The common imaging features of diaphyseal osteosarcoma were bone destruction, lamellar periosteal reaction with/without Codman triangle, massive soft tissue mass/swelling, neoplastic bone and/or calcification. CT and MRI had a higher detection rate in detecting bone destruction (P=0.001) as compared with that of X-ray. X-ray and CT resulted in a higher percentage in detecting periosteal reaction (P=0.018) and neoplastic bone and/or calcification (P=0.043) as compared with that of MRI. There was no difference (P=0.179) in detecting soft tissue mass among three imaging modalities. When comparing metaphyseal osteosarcoma to diaphyseal osteosarcoma, the latter had the following characteristics: a higher age of onset (P=0.022), a larger extent of tumor (P=0.018), a more osteolytic radiographic pattern (P=0.043). As compared with metaphyseal osteosarcoma, diaphysial osteosarcoma is a special location of osteosarcoma with a lower incidence, a higher age of onset, a larger extent of tumor, a more osteolytic radiographic pattern. The osteoblastic and mixed types are diagnosed easily, but the osteolytic lesion should be differentiated from Ewing sarcoma. X-ray, CT and MRI can show imaging features from different aspects with different detection rates.


Simultaneous determination of ten ginsenosides in panacis quinquefolii radix by ultra performance liquid chromatography and quality evaluation based on chemometric methods.
A rapid, sensitive and reliable method based on ultra performance liquid chromatography coupled with a photodiode array detector (UPLC-PAD) was developed for both the quantitative analysis of ten bioactive ginsenosides and a chemical-fingerprint analysis. The chromatography was performed on an ACQUITY UPLC BEH C18 column using a gradient elution with acetonitrile/water as the mobile phase. To compare the UPLC fingerprints and to evaluate their quality, chemometric methods including similarity analysis (SA) and hierarchical-clustering analysis (HCA) were implemented when classifying the Panacis Quinquefolii Radix samples. The Panacis Quinquefolii Radix samples were successfully grouped in accordance with their geographic origins.


Nitrosoguanidine-induced adaptive repair in Pseudomonas aeruginosa.
Error-proof adaptive repair has been demonstrated in Pseudomonas aeruginosa. Cells of actively replicating wild-type Ps. aeruginosa (ATCC27853) and its auxotrophic derivative PAO 286 were subjected to stepwise adaptation (up to 1 microgram ml-1) by nitrosoguanidine (MNNG). Such cells resisted lethal and mutagenic effects of MNNG-challenge (lethal) doses more efficiently than those of nonadapted cultures. Similarly, reactivation of alkylated Pseudomonas phages was enhanced in adapted cells only. Induction of adaptive repair enzymes was sensitive to chloramphenicol (protein synthesis-inhibiting antibiotic) during adaptation treatment only. Protein extract from adapted cells showed increased levels in sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE).


Chromosome-specific painting in Thinopyrum species using bulked oligonucleotides.
Chromosome-specific painting probes were developed to identify the individual chromosomes from 1 to 7E in Thinopyrum species and detect alien genetic material of the E genome in a wheat background. The E genome of Thinopyrum is closely related to the ABD genome of wheat (Triticum aestivum L.) and harbors genes conferring beneficial traits to wheat, including high yield, disease resistance, and unique end-use quality. Species of Thinopyrum vary from diploid (2n = 2x = 14) to decaploid (2n = 10x = 70), and chromosome structural variation and differentiation have arisen during polyploidization. To investigate the variation and evolution of the E genome, we developed a complete set of E genome-specific painting probes for identification of the individual chromosomes 1E to 7E based on the genome sequences of Th. elongatum (Host) D. R. Dewey and wheat. By using these new probes in oligonucleotide-based chromosome painting, we showed that Th. bessarabicum (PI 531711, EbEb) has a close genetic relationship with diploid Th. elongatum (EeEe), with five chromosomes (1E, 2E, 3E, 6E, and 7E) maintaining complete synteny in the two species except for a reciprocal translocation between 4 and 5Eb. All 14 pairs of chromosomes of tetraploid Th. elongatum have maintained complete synteny with those of diploid Th. elongatum (Thy14), but the two sets of E genomes have diverged. This study also demonstrated that the E genome-specific painting probes are useful for rapid and effective detection of the alien genetic material of E genome in wheat-Thinopyrum derived lines.


Automated lumen definition from 30 MHz intravascular ultrasound images.
One prerequisite for standard clinical use of intravascular ultrasound imaging is rapid evaluation of the data. The main quantities to be extracted from the data are the size and the shape of the lumen. Until now, no accurate, robust and reproducible method to obtain the lumen boundaries from intravascular ultrasound images has been described. In this study, 21 different (semi-)automated binary-segmentation methods for determining the lumen are compared with manual segmentation to find an alternative for the laborious and subjective procedure of manual editing. After a preprocessing step in which the catheter area is filled with lumen-like grey values, all approaches consist of two steps: (i) smoothing the images with different filtering methods and (ii) extracting the lumen by an object definition method. The combination of different filtering methods and object definition methods results in a total of 21 methods and 80 experiments. The results are compared with a reference image, obtained from manual editing, by use of four different quality parameters--two based on squared distances and two based on Mahalanobis distances. The evaluation has been carried out on 15 images, of which seven are obtained before balloon dilation and eight after balloon dilation. While for the post-dilation images no definite conclusions can be drawn, an automated contour model applied to images smoothed with a large kernel appears to be a good alternative to manual contouring. For pre-dilation images a fully automated active contour model, initialized by thresholding, preceded by filtering with a small-scale median filter is the best alternative for manual delineation. The results of this method are even better than manual segmentation, i.e. they are consistently closer to the reference image than the average distance of all individual manual segmentations.


Heavy metal ion influence on the photosynthetic growth of Rhodobacter sphaeroides.
The potential of purple non-sulphur bacteria for bioremediation was assessed by investigating the ability of Rhodobacter sphaeroides strain R26.1 to grow photosynthetically in heavy metal contaminated environments. Bacterial cultures were carried out in artificially polluted media, enriched with the transition metal ions Hg2+, Cu2+, Fe2+, Ni2+, Co2+, MoO4(2-), and CrO4(2-) in millimolar concentration range. For each investigated ion the effect on growth parameters was evaluated. The analysis of concentration-effect curves revealed a differentiated response, indicating that diverse mechanisms of tolerance and/or resistance are involved. Adaptation or selection procedures were not applied, leading to assess intrinsic abilities of coping with these contaminants. The microorganism proved to be highly tolerant to heavy metal exposure, especially towards Co2+, Fe2+ and MoO4(2-). In addition Ni2+ and Co2+ were found to decrease the cellular content of light harvesting complexes. A characteristic behavior was observed with mercuric ions, which produced a significant increase of the lag-phase.


Duplex Doppler ultrasound of the hepatic artery in patients with acute alcoholic hepatitis.
Acute alcoholic hepatitis (AAH) is a clinical diagnosis associated with increased hepatic artery diameter and flow. Duplex Doppler ultrasound (DDU) has been shown to accurately measure arterial flow in both liver and kidney transplant patients. The authors conducted a blinded, controlled study to evaluate the accuracy of measuring hepatic artery parameters with DDU in diagnosing AAH. Duplex Doppler ultrasound was performed by an investigator, blinded to group makeup, on 22 consecutive hospital inpatients with the clinical diagnosis of AAH. The diagnosis of AAH was based on specific criteria, including the following: recent alcohol abuse, hyperbilirubinemia, prolonged prothrombin time, leukocytosis, hepatomegaly, hepatic bruit, and marked redistribution of isotope on 99mTc-sulfur colloid liver-spleen scan. Controls were 12 cirrhotic patients without AAH and 17 healthy volunteers. Duplex Doppler ultrasound measurements were obtained most consistently from the proximal right hepatic artery. Measured parameters included the following: peak systolic velocity (PSV); resistive index = (PSV - end diastolic velocity [EDV])/PSV; pulsatility index = (PSV - EDV)/mean velocity; and hepatic artery diameter. The mean hepatic artery diameter was significantly larger in patients with AAH (3.55 +/- 0.72 mm) than in patients with cirrhosis (2.75 +/- 0.69 mm; p = 0.003) and healthy controls (2.68 +/- 0.69 mm; p = 0.001). The mean PSV was significantly higher in patients with AAH (187 +/- 52 cm/s) compared with cirrhotic (67 +/- 51 cm/s) and healthy (66 +/- 51 cm/s) controls (p = 0.0001). The mean resistive index was lower in AAH patients (0.60 +/- 0.11) compared with cirrhotic (0.69 +/- 0.10; p value was not significant) and healthy controls (0.72 +/- 0.11; p = 0.004). The mean pulsatility index was lower in AAH patients (1.04 +/- 0.47) compared with cirrhotic (1.36 +/- 0.45; p value was not significant) and healthy controls (1.53 +/- 0.45; p = 0.01). In the appropriate clinical setting, an elevated hepatic artery diameter or PSV measurement is suggestive of AAH. Duplex Doppler ultrasound offers a noninvasive test to assist in the diagnosis of AAH.


The scleractinian coral Pocillopora damicornis relies on neuroendocrine regulation to cope with polycyclic aromatic hydrocarbons under heat stress.
Polycyclic aromatic hydrocarbons (PAHs) are highly toxic environmental pollutants and are threatening scleractinian corals. In this study, PAHs treatment did not induce significant physiological responses of the coral Pocillopora damicornis and its algal symbionts, but biological processes including response to toxin, drug metabolic, and oxidation reduction were triggered at the mRNA level. These results implied that PAHs could be a group of slow-acting environmental toxicants, whose effects were moderate but persistent. Besides, it was interesting to find that PAHs activated the neuroendocrine system in the coral by triggering the expression of monoaminergic and acetylcholinergic system related genes, indicating that PAHs might function as environmental hormones. Moreover, the combined treatments of PAHs and heat caused a much obvious effect on the coral and its algal symbionts by elevating antioxidant activity and suppressing photosynthesis in the symbionts. Results from the transcriptome data further indicated that corals might perform stress responses upon PAHs and heat challenges through the TNF and apoptosis pathways, which perhaps was modulated by the neuroendocrine system of corals. Collectively, our survey demonstrates that the PAHs can function as environmental hormones and activate the neuroendocrine regulation in scleractinian corals, which may contribute to the stress responses of symbiotic association by modulating photosynthesis, antioxidation, and apoptosis.


Immunocytochemical study of membrane skeletons in abnormally shaped erythrocytes as revealed by a quick-freezing and deep-etching method.
Ultrastructures of membrane skeletons in spherocytic and elliptocytic erythrocytes were investigated immunocytochemically. Erythrocytes obtained from patients with hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) were split open mechanically to obtain exposed cytoplasmic sides of erythrocyte membranes and were immunostained with anti-spectrin antibody. Replica membranes were prepared by a quick-freezing and deep-etching method and were checked by electron microscopy. The in situ membrane skeletons of normal erythrocytes consisted mainly of reticular patterns of spectrin filaments, which formed networks on the cytoplasmic sides of the cell membrane. In contrast, the membrane skeletons of abnormally shaped erythrocytes (HS and HE) were much less filamentous and more granular than those of normal erythrocytes. This abnormal organization in erythrocyte membrane skeletons may be one of the factors that induce abnormally shaped erythrocytes in HS and HE patients.


Survey on the prevalence of intestinal parasites in domestic cats (Felis catus Linnaeus, 1758) in central Nepal.
Cats (Felis catus) are the only felines that live in close contact with humans. Since cats can act as vectors, carriers, reservoirs and definitive hosts of many gastrointestinal (GI) parasites, parasitic assessment could contribute to their survival and well-being. The current study aimed to assess the diversity and prevalence of GI parasites in domestic and feral cats from Ratnanagar in Chitwan in Central Nepal. A total of 107 fresh faecal samples of cats (90 household cats and 17 feral cats) of varied ages and sex were collected and transported to the laboratory. The copromicroscopic examination was carried out following direct wet mount, formalin-ethyl acetate sedimentation, saturated salt flotation, acid-fast staining and sporulation techniques. Furthermore, associated risk factors were evaluated to ascertain the predictor of risks for parasitic acquisition. The current study revealed an overall 95.3% prevalence rate with a 100% rate in feral cats and 94.4% in household cats. Altogether, 18 (17 known and one unknown) different species of GI parasites were reported with the helminths (95.3%; 11 species) and the protozoa (55.1%; seven species). Besides age and sex, outdoor lifestyle, absence or unknown history of medication and hunting behaviour of the felines are the predictors of risk. Furthermore, mixed infection was comparatively higher than single infection in the faecal samples. Cats harbour a higher prevalence and greater diversity of GI parasites, and parasitism varies with age and sex. This finding can be essential for veterinarians and public health authorities for strategic treatment and for assessing the zoonotic transmission of the parasites from these felines. Importantly, an effective medication strategy for cats and owners is recommended.


Ulnar impaction syndrome in the ulnar negative and neutral wrist. Diagnosis and pathoanatomy.
Although the ulnar impaction syndrome occurs most commonly in the ulnar positive wrist, it can also occur in wrists with either ulnar negative or neutral variance. Dynamic increases in ulnar variance may accompany forceful grip and pronation, but diagnosis of the ulnar impaction syndrome can be difficult nonetheless. This report further substantiates the occurrence of this problem in wrists with neutral and negative variance, and provides a description of diagnostic findings and pathoanatomy.


Enhanced iodide sequestration by 3-biphenyl-5,6-dihydroimidazo[2,1-b]thiazole in sodium/iodide symporter (NIS)-expressing cells.
The ability of the sodium/iodide symporter (NIS) to take up iodide has long provided the basis for cytoreductive gene therapy and cancer treatment with radioiodide. One of the major limitations of this approach is that radioiodide retention in NIS-expressing cells is not sufficient for their destruction. We identified and characterized a small organic molecule capable of increasing iodide retention in HEK293 cells permanently transfected with human NIS cDNA (hNIS-HEK293) and in the rat thyroid-derived cell line FRTL-5. In the presence of 3-biphenyl-4'-yl-5,6-dihydroimidazo[2,1-b]thiazole (ISA1), the transmembrane iodide concentration gradient was increased up to 4.5-fold. Our experiments indicate that the imidazothiazole derivative acts either by inhibiting anion efflux mechanisms, or by promoting the relocation of iodide into subcellular compartments. This new compound is not only an attractive chemical tool to investigate the mechanisms of iodide flux at the cellular level, but also opens promising perspectives in the treatment of cancer after NIS gene transfer.


Long-term sublingual immunotherapy for Japanese cedar pollinosis and the levels of IL-17A and complement components 3a and 5a.
Allergen-specific immunotherapy is the only treatment that can alter the natural course of allergic disease. We performed long-term sublingual immunotherapy (SLIT) for patients with seasonal allergic rhinitis caused by Japanese cedar pollen (SAR-JCP), screened molecules as candidate biomarkers, and investigated serum IL-17A and complement components 3a (C3a) and C5a in order to evaluate whether these molecules show changes correlated to symptom scores. In this study, we found that the long-term SLIT reduced the serum levels of IL-17A and C3a and C5a. The levels of C3a in the patients significantly decreased from year 1 compared with those at the baseline, and their levels of IL-17A significantly decreased from year 2 compared with those at baseline. The levels of IL-17A, C3a, and C5a at year 4 of SLIT were significantly lower than not only those at baseline, but also those at year 1. A significant positive correlation was found between the symptom medication scores and the levels of IL-17A at year 4. The symptom medication scores in the group in which IL-17A levels decreased at year 4 were significantly lower than those in the group without such a decrease. The serum level of IL-17A might prove useful as a biological parameter to ascertain the effectiveness of SLIT for patients with SAR-JCP. It is necessary to produce new therapeutics for non-responders in whom serum IL-17A levels are still higher against long-term SLIT.


Carbon emission reduction effects of intellectual property institution construction in China.
Institutions are the fundamental determinants of carbon emission performance. However, the environmental impact of intellectual property institution, especially its impact on carbon emissions, has been paid little attention. Therefore, the main purpose of this study is to assess the effect of intellectual property institution on carbon emission reduction, revealing a new solution to control carbon emissions. To achieve the goal, this study regards the National Intellectual Property Demonstration City (NIPDC) policy in China as a quasi-natural experiment of intellectual property institution construction and exploits the difference in difference approach to objectively evaluate the impact of intellectual property institution on carbon emission reduction based on the panel data of China's cities. The study draws the following important conclusions. First, compared with non-pilot cities, the NIPDC policy has reduced urban carbon emissions by 8.64% in pilot cities. In particular, the "carbon emission reduction dividend" of the NIPDC policy is in the long term but not in the short term. Second, the influence mechanism analysis shows that the NIPDC policy can promote carbon emission reduction by stimulating technology innovation, especially breakthrough innovation. Third, the space overflow analysis reveals that the NIPDC policy can mitigate carbon emissions in adjacent areas, resulting in obvious spatial radiation effect. Fourth, the heterogeneity analysis confirms that the carbon emission reduction effect of the NIPDC policy is more obvious in low administrative hierarchic cities, small and medium-sized cities, and western cities. As a result, Chinese policymakers should orderly promote the construction of NIPDCs, strengthen technology innovation, give full play to the spatial radiation role of NIPDCs, and optimize the role of government, so as to better release the carbon emission abatement effect of intellectual property institution.


Impact assessment of chromite mining on groundwater through simulation modeling study in Sukinda chromite mining area, Orissa, India.
The pre-Cambrian chromites ore deposits in Sukinda valley, Jajpur District, Orissa, India, are well known for chromite ore deposits. The exploitation of the ore is carried out through open cast mining method since the last few decades. In the process, the overburden and ore dumps are stored on ground surface, where leaching of chromite and other toxic element takes place particularly during monsoon seasons. This leachate may cause threat to groundwater in the vicinity. An integrated approach has been adopted to evaluate possibility of pollution due to mine seepage and leachate migration on groundwater regime. The approach involves geophysical, hydrogeological, hydro-chemical and aquifer modeling studies. The investigation has the significance as many habitats surround the mining area facing groundwater problems.


[Pre- and postoperative manometeric findings in the esophagus in proximal selective vagotomy].
15 patients with duodenal ulcer underwent clinical and manometric studies to assess distal esophageal function before and after proximal selective vagotomy. Position, pressure and function of distal esophageal high pressure zone were not altered by the operation. No rationale has been found for the trend to combine proximal selective vagtomy with antireflux procedures.


[Vascular optic neuropathies].
This paper presents a survey of the clinical, aetiological, pathogenetic, diagnostic and therapeutic features of vascular optic neuropathies.


Comparing single vehicle and multivehicle fatal road crashes: a joint analysis of road conditions, time variables and driver characteristics.
The difference between single vehicle crashes and multivehicle crashes was investigated in a collection of fatal crashes from six European countries. Variables with respect to road conditions, time variables, and participant characteristics were studied separately at first and then jointly in a logistic multiple regression model allowing to weigh different accounts of single vehicle as opposed to multivehicle crash occurrence. The most important variables to differentiate between single and multivehicle crashes were traffic flow, the presence of a junction and the presence of a physical division between carriageways. Heavy good vehicles and motorcycles were less likely to be involved in single vehicle crashes than cars. Moreover crashes of impaired drivers with more passengers were more likely to be single vehicle crashes than those of other drivers. Young drivers, rural roads, nights and weekends were all shown to have a higher proportion of single vehicle crashes but in the multivariate analysis these effects were demonstrated to be mediated by the road conditions named above.


Bardach's triple-legged rotation flap as single-staged 3D helical upper-third reconstruction: A technical note.
Reconstruction of the helical upper-third is often technically demanding, especially when the defect is huge and the ear is severely deformed. The aim of this short communication was to present an alternative technique to rebuild this difficult task, using a modification of the Bardach's three-legged rotation flap for scalp closure. To achieve the flap design, we raised the retro- and supraauricular tissue with the Dieffenbach's postauricular advancement fl ap. The Gillies' V-Y advancement fl ap helped to develop the preauricular fl ap, and the Mustardé's otoplastik technique was used to reduce the gap between the resected ear cartilage and the temple. This flap technique appears simple and quick; thereby, it can be used as a single-staged reconstruction alternative in aging patients with multiple comorbidities.


Cell cycle-related changes in number of T-lymphocyte receptors for glucocorticoids and insulin.
Enriched human peripheral T-lymphocytes were stimulated with PHA and examined for variations in insulin and glucocorticoid (dexamethasone) receptor numbers during the early phases of the cell cycle. Cells in G0, G1a and G1b phases, where the G1a - G1b transition is an Interleukin 2 dependent event, were quantitated by flow cytometry. Few but significant numbers of glucocorticoid receptors (2700/cell) and no insulin receptors (-1/cell) were found in the resting (G0) phase. As cells entered the G1a phase the specific binding of dexamethasone increased and of insulin took place. Although the specific binding further increased as T-cells entered the G1b phase (as measured at 44 h of incubation and using hydroxyurea-treated cells), the major changes in the specific binding of dexamethasone took place during the period 16 - 20 h after stimulation. Based on these findings, it is concluded that both receptor types (cell membrane and cytoplasmic receptors) are being formed and increased at G1 phase prior to cell proliferation, indicating the importance of G1 phase in immunoregulation.


Cephradine (Velosef) penetration of mandibular bone.
The concentration of cephradine in serum and mandibular bone was assayed in 28 patients undergoing 3rd molar surgery following a single 1 g intravenous injection. Serum and cortical bone samples taken simultaneously, contained mean cephradine concentrations of 42.11 micrograms/ml and 2.61 micrograms/g respectively. These results, when compared with those reported for other bony sites including the femoral head and knee, show a reduced bone penetration with a bone-to-serum ratio of approximately 0.06:1.


Immunogenetic markers associated with a naturally acquired humoral immune response against an N-terminal antigen of Plasmodium vivax merozoite surface protein 1 (PvMSP-1).
Humoral immune responses against proteins of asexual blood-stage malaria parasites have been associated with clinical immunity. However, variations in the antibody-driven responses may be associated with a genetic component of the human host. The objective of the present study was to evaluate the influence of co-stimulatory molecule gene polymorphisms of the immune system on the magnitude of the humoral immune response against a Plasmodium vivax vaccine candidate antigen. Polymorphisms in the CD28, CTLA4, ICOS, CD40, CD86 and BLYS genes of 178 subjects infected with P. vivax in an endemic area of the Brazilian Amazon were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The levels of IgM, total IgG and IgG subclasses specific for ICB2-5, i.e., the N-terminal portion of P. vivax merozoite surface protein 1 (PvMSP-1), were determined by enzyme-linked immuno assay. The associations between the polymorphisms and the antibody response were assessed by means of logistic regression models. After correcting for multiple testing, the IgG1 levels were significantly higher in individuals recessive for the single nucleotide polymorphism rs3116496 in CD28 (p = 0.00004). Furthermore, the interaction between CD28 rs35593994 and BLYS rs9514828 had an influence on the IgM levels (p = 0.0009). The results of the present study support the hypothesis that polymorphisms in the genes of co-stimulatory components of the immune system can contribute to a natural antibody-driven response against P. vivax antigens.


Ectopic PLAG1 induces muscular dystrophy in the mouse.
Even though various genetic mutations have been identified in muscular dystrophies (MD), there is still a need to understand the biology of MD in the absence of known mutations. Here we reported a new mouse model of MD driven by ectopic expression of PLAG1. This gene encodes a developmentally regulated transcription factor known to be expressed in developing skeletal muscle, and implicated as an oncogene in certain cancers including rhabdomyosarcoma (RMS), an aggressive soft tissue sarcoma composed of myoblast-like cells. By breeding loxP-STOP-loxP-PLAG1 (LSL-PLAG1) mice into the MCK-Cre line, we achieved ectopic PLAG1 expression in cardiac and skeletal muscle. The Cre/PLAG1 mice died before 6 weeks of age with evidence of cardiomyopathy significantly limiting left ventricle fractional shortening. Histology of skeletal muscle revealed dystrophic features, including myofiber necrosis, fiber size variation, frequent centralized nuclei, fatty infiltration, and fibrosis, all of which mimic human MD pathology. QRT-PCR and Western blot revealed modestly decreased Dmd mRNA and dystrophin protein in the dystrophic muscle, and immunofluorescence staining showed decreased dystrophin along the cell membrane. Repression of Dmd by ectopic PLAG1 was confirmed in dystrophic skeletal muscle and various cell culture models. In vitro studies showed that excess IGF2 expression, a transcriptional target of PLAG1, phenocopied PLAG1-mediated down-regulation of dystrophin. In summary, we developed a new mouse model of a lethal MD due to ectopic expression of PLAG1 in heart and skeletal muscle. Our data support the potential contribution of excess IGF2 in this model. Further studying these mice may provide new insights into the pathogenesis of MD and perhaps lead to new treatment strategies.


Excision of an enlarging vaginal epidermal inclusion cyst during pregnancy: a case report.
The study aimed to report the case of a patient with an enlarging and symptomatic epidermal inclusion cyst during pregnancy that required surgical excision. This study was a case report of a 28-year-old woman (gravida 8, para 5, aborta 2) at a gestational age of 18 weeks 5 days who reported a tender vaginal mass that had grown larger for more than a week. An enlarging symptomatic cystic mass was surgically excised. Histopathologic findings of the excised mass were consistent with an epidermal inclusion cyst with surrounding moderate chronic inflammation and cyst rupture. The patient's symptoms resolved completely by her postoperative visit. Although most epithelial inclusion cysts are asymptomatic and can be managed expectantly, cysts that enlarge or become symptomatic should be excised surgically.


Intra-articular lipoma arborescens of the knee: A report of two cases with bilateral localization.
Lipoma arborescens is a very rare pseudo-tumoral lesion of unknown etiology, characterized by lipomatous infiltration of subsynovial stroma, bilateral involvement is exceptional, only eight cases are reported in the literature. We report the very rare case of two men presented at our department with complaints of swelling of both knees and intermittent joint effusion, Surgical biopsy revealed Lipoma arborescens in both cases. Open total synovectomy was performed. Follow-up evaluation showed no signs of recurrence. Lipoma arborescens is a rare entity, the unilateral form affecting the knee is the most common, with a predilection for suprapellar recess. Magnetic resonance imaging (MRI) is the examination of choice showing multiple villous proliferation of the synovium and fat-like cells, with a fatty signal on all sequences. Treatment by open or arthroscopic synovectomy offers the best outcomes.


Ribosome recycling, diffusion, and mRNA loop formation in translational regulation.
We explore and quantify the physical and biochemical mechanisms that may be relevant in the regulation of translation. After elongation and detachment from the 3' termination site of mRNA, parts of the ribosome machinery can diffuse back to the initiation site, especially if it is held nearby, enhancing overall translation rates. The elongation steps of the mRNA-bound ribosomes are modeled using exact and asymptotic results of the totally asymmetric exclusion process. Since the ribosome injection rates of the totally asymmetric exclusion process depend on the local concentrations at the initiation site, a source of ribosomes emanating from the termination end can feed back to the initiation site, leading to a self-consistent set of equations for the steady-state ribosome throughput. Additional mRNA binding factors can also promote loop formation, or cyclization, bringing the initiation and termination sites into close proximity. The probability distribution of the distance between the initiation and termination sites is described using simple noninteracting polymer models. We find that the initiation, or initial ribosome adsorption binding required for maximal throughput, can vary dramatically depending on certain values of the bulk ribosome concentration and diffusion constant. If cooperative interactions among the loop-promoting proteins and the initiation/termination sites are considered, the throughput can be further regulated in a nonmonotonic manner. Experiments that can potentially test the hypothesized physical mechanisms are discussed.


Suppression of delayed cutaneous hypersensitivity and inflammatory cell delivery by sterile barium peritonitis.
We have previously shown that experimental peritonitis secondary to fecal bacteria plus barium sulfate suppresses delayed cutaneous hypersensitivity (DCH) in rats. We examined herein the role of barium sulfate. In a series of experiments presensitized rats were simultaneously skin tested with intradermal keyhole limpet hemocyanin and given an intraperitoneal injection of either (1) a mixture of four fecal bacteria in their nutrient broths, (2) bacteria and broths plus barium sulfate, (3) sterile broths plus barium, (4) sterile barium alone, (5) nutrient broths, or (6) saline. In rats given sterile barium we measured phagocyte delivery to subcutaneous polyvinyl alcohol sponges. We found that (1) the coadministration of barium sulfate was necessary for rats given bacteria to die (P = 0.03) or develop abdominal abscesses (P less than 0.005), (2) suppression of DCH occurred in 70% of rats receiving sterile barium sulfate vs 0% in saline controls (P = 0.0001), (3) early suppression of DCH was associated with subsequent death and abscess formation in rats given bacteria plus barium (P = 0.00002) and with intraabdominal barium collections in rats given barium alone (P less than 0.02), (4) barium sulfate administration caused suppression of phagocyte delivery to subcutaneous sponges: 23.2 X 10(6) cells/site vs 43.1 X 10(6) cells/site in saline controls (P less than 0.005). We conclude that barium sulfate itself has profound systemic effects in the rat model of intraabdominal sepsis. Early suppression of DCH is associated with a poor outcome in septic rats.


Recurrent Nicolau syndrome associated with subcutaneous glatiramer acetate injection--a case report.
Glatiramer acetate is worldwide used as first line treatment in relapsing remitting multiple sclerosis. Local skin reactions associated with glatiramer acetate are common, however, only isolated cases of severe local injection site reactions known as Nicolau Syndrome have been reported so far. We describe the case of a recurrent Nicolau Syndrome occurred during longstanding glatiramer acetate treatment in a woman with multiple sclerosis. The haemorrhagic patch necrotized and was treated locally as a deep second degree burn with excision of dead skin tissue and was healed. Treatment with glatiramer acetate was definitely suspended. GA injections can be complicated by isolated or recurrent Nicolau Syndrome, a potentially life-threatening condition of which neurologists should be aware.


Who's at greatest risk? Latent profiles of alcohol and cannabis use and related consequences among college students.
There is significant heterogeneity in alcohol and cannabis use patterns among college students, with some engaging in use patterns that heighten their risk for adverse consequences. Person-centered approaches can help identify those subgroups of students with riskier use patterns. Latent Profile Analyses (LPA) were conducted to identify subgroups based on alcohol and cannabis use frequency and quantity, to explore demographic covariates and to examine mean differences across subgroups on alcohol- and cannabis-related consequences, simultaneous use, and other substance use. Participants were 2,423 college students (Mage = 20.1; 72 % female) recruited from seven US universities who endorsed past-month alcohol and cannabis use and completed an online survey of substance use behaviors. A four-profile solution was the best fitting model. Profile 1 represented "light, infrequent alcohol and cannabis use" (73.8 %), Profile 2 represented "heavy, infrequent alcohol and moderate, frequent cannabis use" (15.9 %), Profile 3 represented "moderate, frequent alcohol and cannabis use" (5.6 %) and Profile 4 represented "very heavy, frequent alcohol and heavy, frequent cannabis use" (4.7 %). Students who identify as male, White non-Hispanic, and/or Greek-affiliated were more likely to be in the heavy alcohol use profiles. Profiles 3 and 4 represent high-risk profiles, with both having a higher likelihood of simultaneous use, Profile 3 endorsing more cannabis consequences, and Profile 4 endorsing more alcohol consequences. Results suggest that heavy alcohol or heavy co-use heightens risk for serious adverse consequences.


Microanalytical study of thorium 232 deposits in bone marrow and liver.
Analytical microscopy was used to study the distribution and chemical composition of thorium deposits in bone marrow and liver after injection of thorium dioxide and thorium nitrate. Thorotrast (thorium dioxide) was identified as being localized in bone marrow macrophages of a patient who had undergone cerebral arteriography forty two years ago. Large thorotrast deposits were also present in liver cells. We show that non-colloidal thorium (thorium nitrate) injected in rats concentrates in a non soluble form in bone marrow macrophages, hepatocytes and Kupffer cells. These deposits of thorium associated with phosphorus can be explained by the formation of thorium phosphate in lysosomes and we demonstrate that they remain in tissue for a long time. Microanalysis was performed with ion microscopy, and electron probe microanalysis by X ray spectrometry, which can identify and localize thorium and associated elements at cellular or intracellular level.


Circulating Dendritic Cells, Farm Exposure and Asthma at Early Age.
Farm environment has been shown to protect from childhood asthma. Underlying immunological mechanisms are not clear yet, including the role of dendritic cells (DCs). The aim was to explore whether asthma and farm exposures are associated with the proportions and functional properties of DCs from 4.5-year-old children in a subgroup of the Finnish PASTURE birth cohort study. Myeloid DCs (mDCs), plasmacytoid DCs (pDCs) and CD86 expression on mDCs ex vivo (n = 100) identified from peripheral blood mononuclear cells (PBMCs) were analysed using flow cytometry. MDCs and production of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) by mDCs were analysed after 5 h in vitro stimulation with lipopolysaccharide (LPS) (n = 88). Prenatal and current farm exposures (farming, stables, hay barn and farm milk) were assessed from questionnaires. Asthma at age 6 years was defined as a doctor's diagnosis and symptoms; atopic sensitization was defined by antigen-specific IgE measurements. Asthma was positively associated with CD86 expression on mDCs ex vivo [adjusted odds ratio (aOR) 4.83, 95% confidence interval (CI) 1.51-15.4] and inversely with IL-6 production in mDCs after in vitro stimulation with LPS (aOR 0.19, 95% CI 0.04-0.82). In vitro stimulation with LPS resulted in lower percentage of mDCs in the farm PBMC cultures as compared to non-farm PBMC cultures. Our results suggest an association between childhood asthma and functional properties of DCs. Farm exposure may have immunomodulatory effects by decreasing mDC proportions.


The kiss of death.
The programmed cell death (PCD) of neurons is generally thought to be cell autonomous and not to require a death signal from other cells. A recent study by Marín-Teva et al., in this issue of Neuron, brings this theory into question and suggests that neighboring microglia actively participate in the PCD of Purkinje cells in the cerebellum.


Does graded motor imagery benefit individuals with knee pain: A systematic review and meta-analysis.
Evaluate how Graded Motor Imagery (GMI) may be used in those with knee pain, if individuals with knee pain present with a central nervous system (CNS) processing deficit, and if GMI is associated with improved outcomes. An electronic database search was conducted of PubMed, SPORTDiscus, CINHAL, MEDLINE, Google Scholar, and Sports Medicine Education Index using keywords related to GMI and knee pain. This review was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Out of the 13,224 studies reviewed, 14 studies were included that used GMI for knee pain. Effect sizes were reported with standardized mean differences (SMD). Individuals with knee osteoarthritis demonstrated poor performance with correctly identifying images of left or right knees, and GMI improved performance. In contrast, individuals with an anterior cruciate ligament injury demonstrated no evidence of CNS processing deficit and mixed outcomes with GMI. Meta-analysis was limited to individuals post total knee arthroplasty showing low certainty that GMI can improve quadriceps force production [SMD 0.64 (0.07,1.22)], but evidence of no effect to reduce pain or improve Timed up and Go performance and self-reported function. Graded motor imagery may be an effective intervention for individuals with knee osteoarthritis. However, there was limited evidence that GMI was effective for an anterior cruciate ligament injury.


Cystic nephroma (so-called polycystic Wilms' tumor) of childhood: a CT-pathologic study.
The unique CT features, heretofore unreported, of a case of cystic nephroma of childhood are presented. The concept that cystic nephroma is part of thc diagnosis of cystic nephroma can be made utilizing excretory urography and computerized tomography.


Design and synthesis of peptide derivatives of a 3-deoxy-D-manno-2-octulosonic acid (KDO) analogue as novel antibacterial agents acting upon lipopolysaccharide biosynthesis.
On the basis of the knowledge that the amino acid 3 (8-amino-2,6-anhydro-3,8-dideoxy-D-glycero-D-talo-octonic acid) is a potent inhibitor of 3-deoxy-manno-octulosonate cytidylyltransferase, attempts were made to design derivatives that would act as antibacterials against Gram-negative bacteria by inhibiting lipopolysaccharide biosynthesis. Compound 3 and the derivatives 15 and 16 containing an additional amino acid were not lethal to bacteria. However, compounds 17-22, which contain a N-terminally linked dipeptide, exhibited good antibacterial activity in vitro on testing against strains of the Gram-negative bacteria Escherichia coli and Salmonella typhimurium. They have no activity against Gram-positive bacteria such as Staphylococcus aureus.


Interposition of extensor digitorum tendon in distal radius fracture mimicking a compartment syndrome.
A 14-year-old boy sustained a dorsally displaced Salter-Harris Type II fracture of the distal radius. A single attempt at closed reduction failed. After this closed reduction, the patient was unable to passively or actively extend or flex his fingers. He had increasing pain and compartment pressures were abnormally elevated. Dorsal fasciotomy was done, and during the open reduction, entrapment of the dorsal extensor retinaculum and extensor digitorium communis within the fracture was found. After removal of these structures, fracture reduction was easily accomplished and his fingers had a full range of motion. Postoperative recovery was uneventful.


Time of appearance and tissue distribution of a cell surface antigen in early chick development.
The distribution of the antigen defined by monoclonal antibody 224-1A6-A1 in the early chick embryo was studied. The antigen is unequivocally present in the rudimentary neural tube as early as the 12 somite stage (approximately 40 h of incubation). The antigen appears on some but not all derivatives of the ectoderm and mesoderm, but appears to be absent on endodermal derivatives. Monoclonal antibody 224-1A6-A1 therefore serves as a marker for early events in the developmental sequence leading toward the formation of the nervous system.


Medical practitioners in outpatient care: who is interested in participating in EBM courses? Results of a representative postal survey in Germany.
We surveyed the attitudes of medical practitioners towards evidence-based medicine (EBM) and characterized those with an interest in participating in EBM courses. A random sample of 900 outpatient care doctors stratified by level and field of specialization was surveyed by means of a postal questionnaire. Importance of knowledge on information management, a positive attitude towards EBM and not yet doing critical appraisal were significant predictors of interest in participating in EBM courses. Low participation rates of outpatient care doctors in EBM courses are not due to attitudinal or general motivational problems. Although possible predictors of interest in participation could be specified, further factors contributing to actual participation need to be identified.


Neurogenethics: An emerging discipline at the intersection of ethics, neuroscience, and genomics.
The analysis of ethical, legal, and social implications (ELSI) associated with genetics ("genethics") has focused on traditional concerns in bioethics, such as privacy and informed consent. The analysis of ELSI associated with neuroscience ("neuroethics") has focused on concerns related to personhood, such as free will or cognitive enhancement. With neurogenomics coming of age, this is an appropriate time to attend to the set of novel concerns that arises when we consider the confluence of these two lines of research. I call this area of ethics inquiry "neurogenethics", map out the problem space, and highlight future areas of inquiry related to genome editing and gene therapy, optogenetics and memory manipulation, and genomic identity and online communities.


Perplexity of Preoperative Multimodal Investigations in a Case of Parotid MALToma.
Mucosa-associated lymphoid tissue(MALT) lymphoma is a distinct subtype of lymphoma, presenting as a diffuse gland involvement or a discrete mass. Pre-operative diagnosis is a challenge as Fine Needle Aspiration Cytology is often inconclusive and presently no radiological investigation is confirmatory, therefore final diagnosis is made after surgical resection and immunohistopathology. We report a case of MALT lymphoma, which clinically presented as a unilateral large diffuse swelling of the parotid gland with a diagnostic dilemma eventually underwent total parotidectomy to be finally diagnosed as MALT lymphoma of parotid gland and received field radiotherapy with complete cure and no recurrence in a 2-year follow-up.


UV absorption by silicate cloud precursors in ultra-hot Jupiter WASP-178b.
Aerosols have been found to be nearly ubiquitous in substellar atmospheres1-3. The precise temperature at which these aerosols begin to form in exoplanets has yet to be observationally constrained. Theoretical models and observations of muted spectral features indicate that silicate clouds play an important role in exoplanets between at least 950 and 2,100 K (ref. 4). Some giant planets, however, are thought to be hot enough to avoid condensation altogether5,6. Here we report the near-ultraviolet transmission spectrum of the ultra-hot Jupiter WASP-178b (approximately 2,450 K), which exhibits substantial absorption. Bayesian retrievals indicate the presence of gaseous refractory species containing silicon and magnesium, which are the precursors to condensate clouds at lower temperatures. SiO, in particular, has not previously, to our knowledge, been detected in exoplanets, but the presence of SiO in WASP-178b is consistent with theoretical expectations as the dominant Si-bearing species at high temperatures. These observations allow us to re-interpret previous observations of HAT-P-41b and WASP-121b that did not consider SiO, to suggest that silicate cloud formation begins on exoplanets with equilibrium temperatures between 1,950 and 2,450 K.


Fibrous Pseudotumor of the Penis - An Unusual Finding During Repair of Fractured Penis.
Fibrous pseudotumors of the testis and penis are a rare phenomenon, forming a spectrum of heterogeneous lesions. To the best of our knowledge, there has been only 1 previous report arising from the penis. We present a case of fibrous pseudotumor of the penis, incidentally found during the surgical repair of a fractured penis. These benign lesions have been described in the literature and are most commonly referred to as pseudotumors. They should be distinguished from potentially malignant lesions, including fibrosarcomas, squamous cell carcinoma, and polypoid urothelial carcinoma. Being aware of this pathology is important to prevent unnecessary radical surgery.


Long-term effects of mycophenolic acid on the immunoglobulin and inflammatory marker-gene expression in sheep white blood cells.
Mycophenolic acid (MPA) is an active secondary metabolite from Penicillium roqueforti found frequently in contaminated silage for sheep in a temperate climate. The main objective of this study was to evaluate the long-term effect of MPA on mRNA expression of immunoglobulins and cytokines in white blood cells (WBC). Administration of 300 mg MPA per sheep and day was compared with untreated animals for 9 weeks. As immunological markers, the expression levels of immunoglobulins (Igα, Igε, Igμ and Igγ2) and pro-inflammatory cytokines (TNFα, IL1α, IL1β, IL2 and IL6) in WBC were determined. A real-time reverse-transcription polymerase chain reaction (qRT-PCR) with an efficiency-corrected quantification model, named REST, was used to quantify the mRNA expression changes. No effects of MPA administration were found on leucocyte total RNA content. No significant influence of MPA on Igα, Igμ, Igε, Igγ2 gene expression could be found. IL2 and IL6 showed a constant expression pattern over the entire time of the investigation. TNFα was up-regulated in week 1, while down-regulation was detected for IL1α mRNA expression in weeks 2 and 5. According to our data, oral uptake of silage extremely contaminated with a very high concentration of MPA did not have a significant influence on immunoglobulins and cytokines in WBC.


Dysfunction of aged liver of male albino rats and the effect of intermitted fasting; Biochemical, histological, and immunohistochemical study.
Intermittent fasting exerts beneficial effects on most age-related degenerative changes throughout the body. This study aimed to investigate the possible protective effects and mechanism of intermittent fasting on aged liver in male albino rats. Forty male albino rats were used in this study and were divided into four equal groups; Group I served as control ; rats aged 1 month sacrfied when they reached age of 4 month. Group II; rats aged 1 month with intermittent fasting for 3 months. The rats sacrfied when they reached age of 4 mounth Group III; rats aged 15-month fed an ad-libitum diet. The rats sacrified when they reached age of 18 month. Group IV; 15 month rats with intermittent fasting for 3 months. The rats sacrified when they reached age of 18 month. Liver specimens were excised and processed for biochemical, histological, and immunohistochemical study. Blood samples were collected for biochemical study. The result showed a significant increase in liver injury, oxidative stress, and inflammatory markers with a marked decrease in the autophagy marker in group III if compared with both group I and II. Additionally, group III showed hepatic vacuolations, cellular filtration, and congestion in both central and portal veins. A highly significant increase in the mean color intensity of positive immunochemical reaction for anti caspase 3 and anti-TNFα as well as a highly significant increase in the surface area fraction of collagen fibers were noticed in group III if compared with group I and II. Interestingly, intermittent fasting (group IV) remarkably reduced the previous alternation that that occurred in group III. It could be concluded that various biochemical, histological, and immunohistochemical alterations were observed in liver rat in group III. Beneficial effects of fasting on these changes were recorded in group IV through its anti-inflammatory, anti-apoptotic effect as well as its effect in modulating autophagy in aged liver cells. This might open the gate for further research and provide a new line for therapeutic intervention in aged liver. These data lead to speculate that sporadic fasting might represent a simple, safe, and inexpensive means to fight the changes occurred in the aged liver.


Missense variants of the alanine:glyoxylate aminotransferase 2 gene are not associated with Japanese schizophrenia patients.
Alanine:glyoxylate aminotransferase 2 (AGXT2) is the only enzyme that degrades D-3-aminoisobutyrate (D-AIB), which is an intermediate product of thymine, and 30-40% of Japanese lack AGXT2 activity genetically and excrete high amounts of D-AIB in their urine. Recently, AGXT2 is reported to metabolize asymmetric dimethyl arginine (ADMA), a competitive inhibitor of nitric oxide (NO) synthase. Since AGXT2 is expressed in the central nervous system, the loss of AGXT2 activity will be related to the vulnerability for neuropsychiatric disorders related to the NO system. In this study, we recruited 85 Japanese subjects to discover loss variants of the AGXT2 gene with the amount of D-AIB excretion in their urine. From the statistical relevance between them, we found three missense polymorphisms (rs37370, rs37369, and rs180749) independently related to AGXT2 activity (P<0.0001). Then, we performed a case-control association analysis of its missense polymorphisms with 1136 schizophrenia and 1908 control subjects because the NO system may be involved in the vulnerability of schizophrenia processes. We could not find any associations of three functional SNPs with schizophrenia pathogenesis in the analyses of either genotypic or allelic models. We concluded that the AGXT2 gene is not associated with schizophrenia in Japanese subjects.


The cost-effectiveness of introducing nucleic acid testing to test for hepatitis B, hepatitis C, and human immunodeficiency virus among blood donors in Sweden.
The purpose of this study was to estimate the cost-effectiveness of using individual-donor nucleic acid testing (ID-NAT) in addition to serologic tests compared with the sole use of serologic tests for the identification of hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) among blood donors in Sweden. The two strategies analyzed were serologic tests and ID-NAT plus serologic tests. A health-economic model was used to estimate the lifetime costs and effects. The effects were measured as infections avoided and quality-adjusted life-years (QALYs) gained. A societal perspective was used. The largest number of viral transmissions occurred with serologic testing only. However, the risks for viral transmissions were very low with both strategies. The total cost was mainly influenced by the cost of the test carried out. The cost of using ID-NAT plus serologic tests compared to serologic tests alone was estimated at Swedish Krona (SEK) 101 million (USD 12.7 million) per avoided viral transmission. The cost per QALY gained was SEK 22 million (USD 2.7 million). Using ID-NAT for testing against HBV, HCV, and HIV among blood donors leads to cost-effectiveness ratios that are far beyond what is usually considered cost-effective. The main reason for this is that with current methods, the risks for virus transmission are very low in Sweden.


Construction and application of a high precision 3D simulation model for geomechanics of the complex coal seam.
The high-precision 3D simulation model for geomechanics of a complex coal seam is the necessary premise for the research on intelligent shearer and unmanned mining. However, at present, a simulation model for geomechanics of a complex coal seam generally has the problems of simplifying complex geological structures and low accuracy for structures. In order to meet the needs of a coal seam simulation model in the mining process of an intelligent shearer, it is necessary to optimize the simplified model of a coal seam. Therefore, based on a 3D simplified simulation model constructed with discrete element technology, the complex coal seam application plug-in was compiled with the help of an Application Program Interface. Moreover, according to the geological characteristics, new attributes were added to the structures to complete the construction of the model of a complex coal seam. Finally, the model was verified with laboratory experiments. The results showed that the high-precision 3D simulation model for geomechanics of a complex coal seam effectively improved the accuracy of the modeling. The real-time transmission and the real-time sharing of multi-source data were realized by considering the 3D simulation model for geomechanics of a complex coal seam as the core. Additionally, the purpose of the real-time sensing of the coal cutting state was achieved in order to lay the foundation for the realization of unmanned mining.


Consumption rate and functional response of the predaceous mite Kampimodromus aberrans to two-spotted spider mite Tetranychus urticae in the laboratory.
Prey stage preference of female Kampimodromus aberrans (Oudemans) (Phytoseiidae) at constant densities of different stages of Tetranychus urticae Koch (Tetranychidae), functional response types and parameters of the predator females to the varying densities of eggs, larvae, protonymphs and deutonymps of T. urticae were determined in order to establish its potential for the mite biological control. Experiments were conducted at 25 ± 1 °C, 65 ± 10% RH and 16:8 (L:D) photoperiod. Our results indicated that the predator consumed significantly more prey larvae than other prey stages. Functional response type of predator was determined by a logistic regression model. The predator exhibited a Type II response on all prey stages. The attack rate (α) and handling time (T ( h )) coefficients of a Type II response were estimated by fitting a "random-predator" equation to the data. The lowest estimated value α and the highest value of T ( h ) (including digestion) were obtanined for the predator feeding on deutonmph. The lowest value of T ( h ) were obtained for the predator feeding on prey larvae, but the attack rate value obtained on larva wasn't different than that obtained on egg and protonymph. According to our results, K. aberrans could be an efficient biological control agent of T. urticae at least at low prey densities. However, further field based studies are needed to draw firm conclusions.


Oral antiviral therapy improves the diagnostic accuracy of alpha-fetoprotein levels in patients with chronic hepatitis B.
Analysis of alpha-fetoprotein (AFP) levels affords limited diagnostic accuracy because of the high false-positive rates, especially in those with active chronic hepatitis B (CHB). We measured AFP levels before and after commencement of oral antiviral therapy and explored the utility of these data in terms of early detection of hepatocellular carcinoma (HCC) in patients with CHB. A total of 207 patients with CHB who were treated with an oral antiviral agent were consecutively included. Dynamic changes in AFP levels and the diagnostic utility of such changes for HCC detection during the therapy were explored. The proportions of patients showing elevated AFP levels (≥ 20 ng/mL) were 22.2%, 5.5%, and 1.3% at baseline; and at 6 and 12 months after commencement of antiviral therapy, respectively. All patients who did not suffer from HCC exhibited normalization of AFP levels at 12 months. The cumulative incidence of HCC was 9.5% during 36 months of follow-up. If AFP levels were over 20 ng/mL after 12 months of antiviral treatment, the probability of HCC development approached certainty. The positive predictive value for HCC development remained at 100% in patients prescribed long-term (≥ 12 months) antiviral therapy, if AFP levels persistently or abruptly elevated more than 12 ng/mL. In the era of oral antiviral agents, AFP might be a useful biomarker for HCC surveillance in patients with CHB.


Gastrointestinal dysmotility in 5-fluorouracil-induced intestinal mucositis outlasts inflammatory process resolution.
To evaluate gastrointestinal motility during 5-fluorouracil (5-FU)-induced intestinal mucositis. Wistar rats received 5-FU (150 mg kg(-1), i.p.) or saline. After the 1st, 3rd, 5th, 15th and 30th day, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage, apoptotic and mitotic indexes, MPO activity and GSH concentration. In order to study gastrointestinal motility, on the 3rd or 15th day after 5-FU treatment, gastric emptying in vivo was measured by scintilographic method, and stomach or duodenal smooth muscle contractions induced by CCh were evaluated in vitro. On the third day of treatment, 5-FU induced a significant villi shortening, an increase in crypt depth and intestinal MPO activity and a decrease in villus/crypt ratio and GSH concentration. On the first day after 5-FU there was an increase in the apoptosis index and a decrease in the mitosis index in all intestinal segments. After the 15th day of 5-FU treatment, a complete reversion of all these parameters was observed. There was a delay in gastric emptying in vivo and a significant increase in gastric fundus and duodenum smooth muscle contraction, after both the 3rd and 15th day. 5-FU-induced gastrointestinal dysmotility outlasts intestinal mucositis.


Speech intelligibility and perceptions of communication effectiveness by speakers with dysarthria following traumatic brain injury and their communication partners.
This study examined differences in perceived communicative effectiveness between a group of eight participants with chronic dysarthria following TBI and their nominated communication partners (TBIP). The relationship between communicative effectiveness and listener ratings of speech intelligibility was also examined. Group comparison design. The Communicative Effectiveness Survey was completed by the participants with TBI and their communication partner. Speech intelligibility of the eight adults with dysarthria was rated by nine naive listeners using direct magnitude estimation. The participants with TBI tended to rate their communicative effectiveness higher than their TBIP; however, this trend was not significant. No significant differences were noted between the TBI and TBIP groups in ratings of communicative effectiveness in various communication settings. No significant relationship was found between conversation level intelligibility and perceptions of communicative effectiveness, as rated by individuals with TBI and TBIP. The findings of this study highlight the need for collaborative participation in the therapeutic process by all stakeholders. The lack of correlation between speech intelligibility and perceived communicative effectiveness highlights the need for careful examination of activity and participation during assessment and goal-setting.


Effects of vertebrate prolactins and growth hormones on thyroxine 5'-monodeiodination in the eel (Anguilla anguilla): a potential bioassay for growth hormone.
Growth hormones (GHs) and prolactins (Prls) purified from representatives of each vertebrate class from bony fish onwards were tested for their ability to stimulate in vivo peripheral deiodination of labeled thyroxine (T4*) into triiodo-L-thyronine (T3*) in the eel. Plasma T3*/T4* ratio was used as parameter. All GHs significantly increased T3*/T4*, the magnitude of the response being unrelated to the phylogenic position of species. No significant stimulation was shown with the various Prl, with the exception of ovine Prl, suggesting a heterosomatotropic effect of this preparation in the eel. Furthermore, both tilapia and ovine GH produced a dose-related effect on plasma T3*, T4*, and T3*/T4*. The stimulation of the peripheral deiodination of T4* into T3* estimated in vivo in the eel could become a specific, sensitive, and rapid fish bioassay for GH.


High Acuity of Postoperative Consults to Emergency General Surgery at an Urban Safety Net Hospital.
Emergency general surgery (EGS) has high rates of morbidity, mortality, and readmission. Therefore, it might be expected that an EGS service fields many consultations for postoperative patients. However, with the known overutilization of emergency department visits for nonurgent conditions, we hypothesized most postoperative consults received by an EGS service would be nonurgent and could be appropriately managed as an outpatient. We reviewed all EGS consults at a single urban safety net hospital over a 12-month period, screening for patients who had undergone surgery in the previous 12 mo. This included consultations from the emergency room and inpatient setting. Demographics, admission status, procedures performed, and other details were abstracted from the chart and Vizient reports. Consultation questions were categorized and then reviewed by an expert panel to determine if conditions could have been managed as an outpatient. The EGS service received a total of 1112 consults, with 99 (9%) for a postoperative condition. Overall, 85% of postoperative consults were admitted after consultation, 19% underwent surgery and 21% underwent a procedure with gastroenterology or interventional radiology. Expert review classified slightly over one-third (36%) of consults as nonurgent. Most postoperative consults seen at our urban safety net hospital represent true morbidity that required admission, intervention, or surgery. Despite this high acuity, one-third of postoperative consults could have been managed as an outpatient. Efforts to improve discharge instructions and set patient expectations could limit unnecessary postoperative emergency department visits.