Respiratory infection of mice with mammalian reoviruses causes systemic infection with age and strain dependent pneumonia and encephalitis.
Because mammalian reoviruses are isolated from the respiratory tract we modeled the natural history of respiratory infection of adult and suckling mice with T1 Lang (T1L) and T3 Dearing (T3D) reoviruses. Adult and suckling Balb/c mice were infected by the intranasal route and were assessed for dose response of disease as well as viral replication in the lung and other organs. Viral antigen was assessed by immunofluorescence and HRP staining of tissue sections and histopathology was assessed on formalin fixed, H + E stained tissue sections. Intranasal infection of adult mice resulted in fatal respiratory distress for high doses (10(7) pfu) of T1L but not T3D. In contrast both T1L and T3D killed suckling mice at moderate viral dosages (10(5) pfu) but differed in clinical symptoms where T1L induced respiratory failure and T3D caused encephalitis. Infections caused transient viremia that resulted in spread to peripheral tissues where disease correlated with virus replication, and pathology. Immunofluorescent staining of viral antigens in the lung showed reovirus infection was primarily associated with alveoli with lesser involvement of bronchiolar epithelium. Immunofluorescent and HRP staining of viral antigens in brain showed infection of neurons by T3D and glial cells by T1L. These mouse models of reovirus respiratory infection demonstrated age and strain dependent disease that are expected to be relevant to understanding and modulating natural and therapeutic reovirus infections in humans.


Understanding the relationship between patient language and outcomes in internet-enabled cognitive behavioural therapy: A deep learning approach to automatic coding of session transcripts.
Objective: Understanding patient responses to psychotherapy is important in developing effective interventions. However, coding patient language is a resource-intensive exercise and difficult to perform at scale. Our aim was to develop a deep learning model to automatically identify patient utterances during text-based internet-enabled Cognitive Behavioural Therapy and to determine the association between utterances and clinical outcomes. Method: Using 340 manually annotated transcripts we trained a deep learning model to categorize patient utterances into one or more of five categories. The model was used to automatically code patient utterances from our entire data set of transcripts (∼34,000 patients), and logistic regression analyses used to determine the association between both reliable improvement and engagement, and patient responses. Results: Our model reached human-level agreement on three of the five patient categories. Regression analyses revealed that increased counter change-talk (movement away from change) was associated with lower odds of both reliable improvement and engagement, while increased change-talk (movement towards change or self-exploration) was associated with increased odds of improvement and engagement. Conclusions: Deep learning provides an effective means of automatically coding patient utterances at scale. This approach enables the development of a data-driven understanding of the relationship between therapist and patient during therapy.


Analysis of renal fibrosis in a rabbit model of crescentic nephritis.
The pathogenesis of renal fibrosis in crescentic nephritis is incompletely understood. To improve our understanding of this process, crescentic nephritis was induced in New Zealand White rabbits by administration of guinea pig antiglomerular basement membrane IgG after sensitization with guinea pig IgG, and their kidneys were analyzed for the development of fibrosis. Collagen synthesis in renal cortical tissue was significantly elevated by day 3, peaked at days 7-15, and returned towards baseline by day 21. Collagen content of both glomeruli and cortex were increased starting on days 14-16, and remained constant in cortex thereafter. Light microscopic analysis was much less sensitive, revealing fibrosis only after day 21. Immunofluorescence revealed that type IV collagen was distributed primarily in the glomerulus, while types I and III were increased in the glomerulus and interstitium. Thus, in this model of crescentic nephritis, fibrosis, as assessed biochemically, developed early at time points when morphologic analysis failed to detect such a development. Hence early therapeutic intervention, before morphologic evidence of fibrosis is evident, may be more successful in arresting the progression of this disease before it reaches irreversible terminal stages.


Personality traits moderate associations between word recall and subjective memory.
Cognitive gerontology research requires consideration of performance as well as perceptions of performance. While subjective memory is positively associated with memory performance, these correlations typically are modest in magnitude, leading to the need to consider whether certain people may show weaker or stronger linkages between performance and perceptions. The current study leveraged personality (NEO Big Five), memory performance (i.e., word recall), and perceptions of memory ability (i.e., metamemory in adulthood and memory decline) data from the St. Louis Personality and Aging Network (SPAN) study (n = 774, mean age: 71.52 years). Extraversion and conscientiousness held the most consistent associations with the cognitive variables of interest, as both traits were positively associated with metamemory and word recall, but negatively associated with subjective decline. Moreover, extraversion moderated associations between word recall and both memory capacity and complaints, insofar that objective-subjective associations were weaker for those adults higher in extraversion. These findings highlight the need to understand how personality influences the sources of information employed for subjective cognitive beliefs.


IgG4-related disease with elevated adenosine deaminase in pleural effusion diagnosed clinically using thoracoscopy under local anesthesia and FDG-PET-CT.
In general, we have to assume tuberculous pleurisy when a patient presents with pleural effusion and elevated adenosine deaminase (ADA). However, other diseases need to be considered, including immunoglobulin (Ig)G4-related disease (IgG4-RD). This case involved a 65-year-old asymptomatic man with right pleural effusion showing elevated ADA. He had no articular findings or rashes. Results were negative for all autoantibodies. Pleura, mediastinal lymph nodes, and areas around the aorta and vertebra showed high uptake of 18F-fluorodeoxyglucose (FDG) on positron-emission tomography-computed tomography (PET-CT). These findings were specific for IgG4-RD. Based on the results of FDG-PET-CT, we performed thoracoscopy under local anesthesia and bronchoscopy. Pleural biopsy and culture, and other examinations including sputum and blood yielded negative findings for tuberculous pleurisy. A pleural biopsy specimen showed IgG4-positive plasma cells and fibrosis without obliterative phlebitis or storiform fibrosis, and serum IgG4 was also high. The ratio of IgG4-to IgG-positive plasma cells was under 40%, and >10 IgG4-positive cells were seen in high-power fields. This case was classed as 'possible IgG4-RD' on the comprehensive diagnostic criteria for IgG4-RD, but did not meet the diagnostic criteria for IgG4-related respiratory disease. Prednisolone proved effective against the pleural effusion. We therefore clinically diagnosed IgG4-RD with pleural effusion based on the 2019 classification criteria for IgG4-RD in the United States. Although few cases of IgG4-RD with pleural effusion have been reported, this disease needs to be considered among the differential diagnoses for high-ADA pleural effusion. FDG-PET-CT and thoracoscopy under local anesthesia may be helpful for diagnosis.


Literacy for the community, by the community.
Literacy is a significant challenge in the U.S. and its territories, especially in low income communities where use of English language is non-standard. Wedeveloped the Actual Community Empowerment (ACE) Reading program for students at risk in such communities. ACE is a small-group tutoring program to support fluency, word recognition and decoding, and comprehension at the best pace of learning for individual, struggling readers. It has several variations (e.g., for different ages, different uses of technology), depending on local needs and resources. The program has been successfully implemented in 40 locations from Philadelphia to Pohnpei, with a 95% success rate for significant reading improvement. ACE tutors are community paraprofessionals or school students with backgrounds similar to the children who receive tutoring. In the first major section of this paper, the ACE Reading Program is described and empirical research demonstrating the benefits of the program for students' literacy is reviewed. The second major section presents preliminary qualitative research evidence that paraprofessional tutors progress through recognizable stages toward increased professionalism. Recommendations for future research are provided.


Gene expression study in positron emission tomography-positive abdominal aortic aneurysms identifies CCL18 as a potential biomarker for rupture risk.
Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture. Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA with-out FDG uptake (A0) and with FDG uptake (A+), both at the positive spot (A+(Pos)) and at a paired distant negative site (A+(Neg)) of the same aneurysm. Follow-up studies included reverse-transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+(Pos) compared with A+(Neg). Moreover, a series of genes (notably CCL18) was differentially expressed both in the A+(Neg) and A+(Pos) compared with the A0. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients compared with A0. In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and -negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening.


Parents' views on factors that help or hinder breast milk supply in neonatal care units: systematic review.
To synthesise what is known about the parents' views on factors that help or hinder breast milk supply during their infants' hospitalisation in neonatal intensive care units (NICU). A systematic search of PubMed, ISI WoK, PsycINFO and SciELO, targeting studies presenting original empirical data that examined parents' perspectives regarding breast milk supply experiences in NICU, was performed. Based on content analysis, three independent researchers synthesised the findings of seven studies. Categories of facilitators and barriers were identified using quotations stated in the studies: parents' breast milk supply experience; parents-professionals relationships; characteristics of the NICU; and parents' social background and expectations. The studies, five qualitative and two mixed methods, were published between 1994 and 2011. With heterogeneous study designs, fathers' perspectives were analysed in one article. Only one study defined breastfeeding. According to parents' perspectives, successful breast milk supply in NICU depends on coherent and accurate knowledge about its techniques and benefits, reinforcement of mothers' motivation and alignment between NICU's routines and parents' needs. Parents perceived issues related to their own current breast milk supply experience, simultaneously, as main facilitators and barriers. Parents-professionals relationship constituted the second group of facilitators, but the fourth of barriers. The characteristics of the NICU were more relevant as a barrier than as a facilitator. Although parents' perspectives are grounded on individual child-focused experiences, their emphasis on learning and motivation guided by short-term goals opens room to the collective intervention of experts. This may facilitate the engagement of mothers, fathers and health professionals on family-centred care.


Early radiographic diagnosis of apical root resorption during orthodontic treatment: a study of maxillary incisors.
The purpose of this study was to evaluate the sensitivity of digital radiographs for detection of (i) simulated root resorption cavities in an experimental model and (ii) orthodontically-induced apical root resorption in vivo. The severity of root resorption after 3 and 6 months treatment was studied in relation to root form. The experimental study cavities, drilled in mandibular roots in a dry skull, were recorded in conventional and digital radiographs. In vivo root resorption was evaluated on digital radiographs of 92 maxillary incisors after 3 and 6 months treatment with fixed appliances. The results showed a similar sensitivity for the two methods. Sensitivity increased significantly with cavity size. After 3 months apical root resorption was detected in only a few teeth. The number had increased significantly after 6 months. There was a higher degree of root resorption in teeth with blunt and pipette-shaped apices. In such teeth a 3-month radiographic control is recommended.


Anatomy of a properly taken toothprints thermoplastic bite impression.
The Toothprints thermoplastic bite impression technique, like most procedures in clinical practice, is technique-sensitive. The biometric information available from the thermoplastic wafer is directly proportional to the care with which the technique is performed, as well as the cooperation and understanding of the child. Although the amount of information and the detail we obtain with the impression of only a few teeth (tooth size and occlusal anatomy are able to be digitized to 50 microns), along with saliva for scent dog tracking and cellular DNA analysis, it is a properly taken full-arch bite impression that would provide the best opportunity for infinite concordant matches for identification, should the need arise. With that in mind, below are the steps for properly taking a full-arch bite impression.


Factors Determining the Rate and Selectivity of 4e-/4H+ Electrocatalytic Reduction of Dioxygen by Iron Porphyrin Complexes.
Reactivity as well as selectivity are crucial in the activation and electrocatalytic reduction of molecular oxygen. Recent developments in the understanding of the mechanism of electrocatalytic O2 reduction by iron porphyrin complexes in situ using surface enhanced resonance Raman spectroscopy coupled to rotating disc electrochemistry (SERRS-RDE) in conjunction with H/D isotope effects on electrocatalytic current reveals that the rate of O2 reduction, ∼104 to 105 M-1 s-1 for simple iron porphyrins, is limited by the rate of O-O bond cleavage of an intermediate ferric peroxide species (FeIII-OOH). SERRS-RDE probes the system in operando when it is under steady state such that any intermediate species that has a greater rate of formation relative to its rate of decay, including the rate determining species, would accumulate and can be identified. This technique is particularly well suited to investigate iron porphyrin electrocatalysts as the intense symmetric ligand vibrations allow determination of the oxidation and spin states of the bound iron with high fidelity. The rate of O2 reduction could be tuned up by 3 orders of magnitude by incorporating residues in the catalyst design that can exert "push" or "pull" effects, that is, axial phenolate and thiolate ligands and distal arginine residues. Similarly the rate of O-O bond cleavage can be enhanced by several orders of magnitude upon incorporating a distal Cu site and installing the active site in a hydrophobic protein environment in synthetic models and biosynthetic protein scaffolds. The selectivity, however, is solely determined by the site of protonation of a ferric peroxide (FeIII-OOH) intermediate and can be governed by installing preorganized second sphere residues in the distal pocket. The 4e-/4H+ reduction of O2 entails protonation of the distal oxygen of the FeIII-OOH species, while 2e-/2H+ reduction requires the proximal oxygen to be protonated. Mechanistic investigations of CO2 reduction by iron porphyrins reveal that the rate-determining step is the C-O bond cleavage of a FeII-COOH species analogous to the O-O bond cleavage step of a FeIII-OOH species in O2 reduction. The selectivity, resulting in either CO or HCOOH, is determined by the site of protonation of this species. These similarities suggests that the chemical principles governing the rate and selectivity of reduction of small molecules like O2, CO2, NOx, and SOx may be quite similar in nature.


Schistosoma induced squamous cell carcinoma of the bladder.
Schistosomiasis or Bilharziasis caused by S. hematobium is endemic in Africa, Egypt, southern tips of Europe and Japan. Though not unknown in India, it is a much less common occurrence. Schistosomiasis of the bladder is known to be a causative factor for bladder carcinoma; which is usually of the squamous type. These cancers are usually of a higher grade and the average initial stage is higher than those for transitional cell carcinomas. We present a case of schistosoma induced squamous carcinoma of the bladder as this is not a common association in India.


Maximum dislodging forces of implant overdenture stud attachments.
The aim of this study was to compare the retention and stability of the Nobel Biocare standard ball (NBS), Nobel Biocare 2.25-mm-diameter ball (NB2), Zest Anchor (ZA), Zest Anchor Advanced Generation (ZAAG), Sterngold ERA orange (SEO), and Sterngold ERA white (SEW) attachments on an implant-retained overdenture model. The attachments were tested using 2 permanently placed Brånemark System implants on a test model that was attached to an Instron machine (crosshead speed 50.8 mm/minute). Each attachment had one part embedded in a denture-like housing and the other part screwed into the implants. Dislodging tensile forces were applied to the housings in 3 directions simulating function: vertical, oblique, and anterior-posterior. Eight tests were done in 3 directions with 6 samples of each attachment. The dislodging forces generated measurements of the peak load (maximum dislodging force). A 1-way analysis of variance followed by the Tukey studentized range test was used to determine groups that were significantly different. All tests for significance were carried out at the .05 level of significance. Results showed the ZAAG attachment to be the most retentive for the peak load measurement when subjected to vertically directed forces, with mean values and standard deviations of 37.2 +/- 5.5 N. The next most retentive attachment was the NBS, followed by the SEO, NB2, SEW, and ZA. For obliquely directed forces, the ZAAG attachment was the most retentive, with mean values and standard deviations of 27.2 +/- 4.2 N. The next most retentive was the NBS, followed by the NB2, SEO, ZA, and SEW. For anterior-posteriorly directed forces, results showed the NBS had the highest measured retentive force, with mean values and standard deviations of 34.6 +/- 18.8 N, but this was not statistically different from the NB2 and ZAAG; this was followed by the SEO, SEW, and ZA. There has been a marked resurgence in the treatment of patients with overdentures using implant attachments as retentive devices. The maximum force developed (a measure of retention) as the implant stud attachments were resisting removal from the implant abutments was determined. Based on the present study, the clinician may be able to make empirical decisions on attachment selection, depending on the amount of retention desired and the specific clinical situation.


A two-stage delayed surgical approach to salvaging Essex-Lopresti tongue type calcaneal fractures.
Fractures of the calcaneus are one of the most challenging problems facing the podiatric physician today. Many attempts have been made to simplify this complex entity by categorizing calcaneal fractures and dictating treatment according to the fracture classification. However, it is now known that each calcaneal fracture injury must be given individual patient consideration for diagnosis and treatment. Included is a case presentation of a severe calcaneal fracture classified as an Essex-Lopresti tongue type with a discussion of the surgical management.


Divergent effects of actinomycin d on cortisol and on glucose stimulation of glycogenesis in mouse liver.
1. The administration of cortisol and of other glucocorticoid steroids to starved mice produced an increase in liver glycogen content, an elevation of glycogen-synthetase activity and a predominantly particulate localization of both phosphorylase and glycogen-synthetase enzymes. 2. Three daily doses of actinomycin D caused a marked glycogen depletion, a significant decrease in glycogen-synthetase activity, the solubilization of phosphorylase and glycogen synthetase and the following effects on the activities of various other enzymes: a decrease in UDP-glucose pyrophosphorylase and phosphoglucomutase, an increase in glucose 6-phosphate dehydrogenase and no change in glucose 6-phosphatase, 6-phosphogluconate dehydrogenase, pyruvate kinase and UDP-glucose dehydrogenase. 3. Glucose ingestion, but not cortisol administration, reversed the effects of actinomycin D on liver glycogen content and on the activities of phosphorylase and glycogen synthetase.


Soft, Brown Rupture: Clinical Signs and Symptoms Associated with Ruptured PIP Breast Implants.
Preoperative signs and symptoms of patients with Poly Implant Prothese (PIP) implants could be predictive of device failure. Based on clinical observation and intraoperative findings 4 hypotheses were raised: (1) Preoperative clinical signs including acquired asymmetry, breast enlargement, fullness of the lower pole, decreased mound projection, and change in breast consistency could be indicative of implant rupture. (2) Device failure correlates with a low preoperative Baker grade of capsule. (3) Brown-stained implants are more prone to implant failure. (4) The brown gel could be indicative of iodine ingression through a substandard elastomer shell. Preoperative clinical signs were compared with intraoperative findings for 27 patients undergoing PIP implant explantation. Acquired asymmetry (P = 0.0003), breast enlargement (P = 0.0002), fuller lower pole (P < 0.0001), and loss of lateral projection (P < 0.0001) were all significantly predictive of device failure. Capsule Baker grade was lower preoperatively for ruptured implants. The lack of palpable and visible preoperative capsular contracture could be secondary to the elastic nature of the capsular tissue found. Brown implants failed significantly more often than white implants. Analysis of brown gel revealed the presence of iodine, suggesting povidone iodine ingression at implantation. Preoperative signs can be predictive of PIP implant failure. Brown-stained implants are more prone to rupture. The presence of iodine in the gel suggests unacceptable permeability of the shell early in the implant's life span. A noninvasive screening test to detect brown implants in situ could help identify implants at risk of failure in those who elect to keep their implants.


Transcription factor expression in lipopolysaccharide-activated peripheral-blood-derived mononuclear cells.
Transcription factors play a key role in integrating and modulating biological information. In this study, we comprehensively measured the changing abundances of mRNAs over a time course of activation of human peripheral-blood-derived mononuclear cells ("macrophages") with lipopolysaccharide. Global and dynamic analysis of transcription factors in response to a physiological stimulus has yet to be achieved in a human system, and our efforts significantly advanced this goal. We used multiple global high-throughput technologies for measuring mRNA levels, including massively parallel signature sequencing and GeneChip microarrays. We identified 92 of 1,288 known human transcription factors as having significantly measurable changes during our 24-h time course. At least 42 of these changes were previously unidentified in this system. Our data demonstrate that some transcription factors operate in a functional range below 10 transcripts per cell, whereas others operate in a range three orders of magnitude greater. The highly reproducible response of many mRNAs indicates feedback control. A broad range of activation kinetics was observed; thus, combinatorial regulation by small subsets of transcription factors would permit almost any timing input to cis-regulatory elements controlling gene transcription.


Behavioral and Reproductive Response of White Pine Weevil (Pissodes strobi) to Resistant and Susceptible Sitka Spruce (Picea sitchensis).
White pine weevil (Pissodes strobi, Peck.) is a native forest insect pest in the Pacific Northwest of North America that attacks species of spruce (Picea spp.) and pine (Pinus spp.). Young Sitka spruce [Picea sitchensis (Bong.) Carr.] trees are particularly susceptible to weevil attack. Pockets of naturally occurring Sitka spruce resistance have been identified in high weevil hazard areas in coastal British Columbia. In this study, we characterize behavioral, physiological and reproductive responses of weevils to an extremely resistant Sitka spruce genotype (H898) in comparison to a highly susceptible genotype (Q903). The experiments relied on a large number of three-year-old clonally propagated trees and were therefore restricted to two contrasting Sitka spruce genotypes. When exposed to resistant trees, both male and female weevils were deterred during host selection and mating, females showed delayed or reduced ovary development, and successful reproduction of weevils was prevented on resistant trees.


How can good randomized controlled trials in leading journals be so misinterpreted?
The results of good randomized controlled trials (RCTs) published in leading peer-reviewed journals have been deemed the best possible basis for good medical practice. However, several limitations may decrease their value. These include flaws and weaknesses in the design and the timeliness of RCTs. Progress in a treatment method or control arm may invalidate a trial. So too can defects in patient selection, physician competence, randomization, applicability, end points, and the population being studied. Idiosyncratic flaws can also invalidate an RCT. Examples of these flaws and weaknesses are presented. Another problem with articles describing RCTs is the potential for the conclusions of the trial report to be misleading because of error or bias. This plus subsequent misinterpretation of the trial results or conclusions by others can make the effect of the trial misleading with an unintended detrimental result on medical practice. Guidelines based on such errors or bias-based conclusions and misinterpretations can further compound the problem. This article provides examples of misleading conclusions and/or misinterpretations (spinning) of trial results in articles describing RCTs in leading journals. All physicians should recognize these value-limiting processes so that RCTs can be evaluated adequately and fairly. In that way, they can be used along with good physician judgment to optimize the care delivered to individual patients and to society at large.


Adrenergic and non-adrenergic, non-cholinergic control of airways.
In addition to cholinergic neural mechanisms, airway tone is influenced by adrenergic mechanisms and by more recently described neural mechanisms which are non-adrenergic and non-cholinergic (NANC). Sympathetic innervation to human airways is very sparse and there is no functional adrenergic innervation of smooth muscle, although sympathetic fibres may supply ganglia, submucosal glands and bronchial vessels. Airway tone may be influenced by circulating adrenaline and there is some evidence that adrenaline secretion may be impaired in asthma. beta-Adrenoceptors (which are almost entirely of the beta 2-subtype) are localized to many cell types in airways and beta-agonist may be beneficial in airway obstruction, not only by directly relaxing airway smooth muscle (from trachea to terminal bronchioles), but by inhibiting mast cell mediator release, by modulating cholinergic nerves, by reducing bronchial oedema and by reversing the defect in mucociliary clearance. There is little evidence that beta-receptor function is impaired in asthma. Alpha-adrenoceptors, which are bronchoconstrictor, may be activated by inflammatory mediators and disease, and alpha-agonists cause bronchoconstriction in asthmatic patients. However, alpha-antagonists have little effect, which questions the role of alpha-receptors in asthma. NANC nerves which relax human airways have been demonstrated in vitro. Although the neurotransmitter is not certain, there is now convincing evidence that it may be vasoactive intestinal peptide (VIP) and a related peptide histidine methionine (PHM). VIP and PHM immuno-active nerves are found in human airways, and both peptides potently relay human airways in vitro (but not in vivo because of diffusion and metabolism problems).(ABSTRACT TRUNCATED AT 250 WORDS)


[Evaluation of 4 culture methods of Yersinia enterocolitica].
To establish a highly efficient culture method for detecting Yersinia enterocolitica in stool samples from diarrheic patients. Stool samples collected from 200 diarrheic patients were detected with a modified and 3 conventional methods, and the positivity rates of the bacterium were compared statistically. With the modified method, 18 positive samples for Yersinia enterocolitica were detected from 200 stool samples, while with the 3 conventional methods, only 3, 5, and 8 positive samples were identified, respectively. Statistical analysis with McNemer test suggested significant difference in the positive detection rate between the modified and the 3 conventional methods. The modified method for Yersinia enterocolitica detection has much higher sensitivity than the 3 conventional methods, and can be applied in clinical detection.


A numerical simulation of orthodontic tooth movement produced by a canine retraction spring.
Tooth movements produced by a canine retraction spring were calculated. Although a gable bend and an anti-rotational bend were incorporated into the spring, the canine tipped and rotated initially. Retraction force decreased and moment-to-force ratio increased after the spring legs closed. Then, the initial tipping and rotation began to be corrected. As a result, the canine moved almost bodily after a prolonged period of time. Such tooth movements cannot be estimated from the initial force system. The gable bend decreased tipping movement, but increased rotational movement. On the other hand, the anti-rotational bend decreased rotational movement but increased tipping movement. In other words, one bend decreased the effect of the other, when both bends were incorporated in the spring.


Mental status of patients with chronic insomnia in China during COVID-19 epidemic.
To study the sleep and mental health of chronic insomnia patients in China during coronavirus disease in 2019 (COVID-19) epidemic. A total of 764 patients with chronic insomnia were included in this study. From 17 January 2020 to 24 January 2020, insomnia, anxiety and physical symptoms were evaluated online, and they were followed up for 4 and 8 weeks. Main outcomes and indicators were assessed using the Pittsburgh Sleep Quality Index (PSQI) and each factor score, the General Anxiety Disorder-7 (GAD-7) and the Patient Health Questionnaire-15 (PHQ-15), respectively. In addition, insomnia, anxiety and physical symptoms were assessed at baseline and at the end of fourth and eighth weeks. Wilcoxon signed rank test was used to compare the changes in patients' scale scores at different time points. Among the 764 participants, there were 755 and 738 evaluators who completed the fourth and eighth weeks, respectively, and the questionnaire completion rates were 98.82% and 96.60%, respectively. Among them, there are 459 (60.0%) aged 41-60 years old, 546 (71.5%) women, 218 (28.5%) men and 313 (41%) college degrees. After 8 weeks of follow-up, the differences in sleep status, anxiety symptoms and physical symptoms were statistically significant. Among the factors of PSQI, there were differences in subjective sleep quality, sleep latency, sleep duration, sleep disturbance (disorder), sleep efficiency and daytime function. At 4 weeks of follow-up, there was a statistically significant difference in the use of hypnotic drugs; at 8 weeks of follow-up, there was no statistically significant difference in the use of hypnotic drugs. Under the influence of the COVID-19, the sleep status and anxiety of patients with chronic insomnia are affected by the epidemic.


Risk taking and novelty seeking in adolescence: introduction to part I.
Risk taking and novelty seeking are hallmarks of typical adolescent behavior. Adolescents seek new experiences and higher levels of rewarding stimulation, and often engage in risky behaviors, without considering future outcomes or consequences. These behaviors can have adaptive benefits with regard to the development of independence and survival without parental protection, but also render the adolescent more vulnerable to harm. Indeed, the risk of injury or death is higher during the adolescent period than in childhood or adulthood, and the incidence of depression, anxiety, drug use and addiction, and eating disorders increases. Brain pathways that play a key role in emotional regulation and cognitive function undergo distinct maturational changes during this transition period. It is clear that adolescents think and act differently from adults, yet relatively little is known about the precise mechanisms underlying neural, behavioral, and cognitive events during this period. Increased investigation of these dynamic alterations, particularly in prefrontal and related corticolimbic circuitry, may aid this understanding. Moreover, the investigation of mammalian animal models of adolescence-such as those examining impulsivity, reward sensitivity, and decision making-may also provide new opportunities for addressing the problem of adolescent vulnerability.


Study of permanent artificial tendon.
The aim of the present study was to develop a porous, silastic tube with filmy wall acting as permanent artificial tendon. Twelve mongrel dogs were used. Peronaeus longus and Tibialis anticus were exposed respectively, divided in two places and sutured in situ. They were covered by the above-mentioned silastic tube. One dog each was sacrificed after 1, 2, 4, 6, 8, 10, 12, 16, 20 and 24 weeks, and 11 months; specimens were removed. Each preparation was studied as follows: gross observation and light microscopy for tendon preparation; transmission electron microscopy, scanning electron microscopy and phase microscopy for the pseudosheath. Our study showed that healing of tendon was mainly extrinsic mechanism and that the pseudosheath formed by silastic tube can prevent the adhesion of the surrounding tissue; therefore, use of the artificial tendon including a tendongraft coated with a silastic tube in reconstruction of flexor digital tendon in the hand is procedure feasible. But what the appropriate porous diameter and porous distance are, must be studied further. Tendon gliding mainly depends upon the gliding plane between the composite body of the tendon and the loose connective tissues around it.


Synthesis and characterization of V1-xMo(x)O2 thermochromic coatings with reduced transition temperatures.
In this study Mo-doped VO2 thin films have successfully been grown on SiO2-coated float glass by reactive DC magnetron sputtering. Structural analyses, carried out at room temperature, revealed single-phase monoclinic VO2 with preferred crystal orientation in the (002) direction, regardless the Mo doping concentration. The surface morphology of the films revealed elongated grains dispersed randomly with decreasing sizes for higher Mo doping concentrations. The measured roughness parameters showed an opposite tendency, i.e., increased for higher Mo doping contents. The optical analyses showed films with maximum optical transparencies in the visible range from 35 to 45% and decreased IR modulation capacity from 36 to 25% with increasing Mo content from 3 to 11%. The Mo dopant concentration in the film was found to have a linear influence on the phase transition temperatures, showing a decrease of about 3 degrees C per at% of Mo. Phase transition temperatures as low as 32 degrees C were obtained.


Can Co-Activation of Nrf2 and Neurotrophic Signaling Pathway Slow Alzheimer's Disease?
Alzheimer's disease (AD) is a multifaceted disease that is hard to treat by single-modal treatment. AD starts with amyloid peptides, mitochondrial dysfunction, and oxidative stress and later is accompanied with chronic endoplasmic reticulum (ER) stress and autophagy dysfunction, resulting in more complicated pathogenesis. Currently, few treatments can modify the complicated pathogenic progress of AD. Compared to the treatment with exogenous antioxidants, the activation of global antioxidant defense system via Nrf2 looks more promising in attenuating oxidative stress in AD brains. Accompanying the activation of the Nrf2-mediated antioxidant defense system that reduce the AD-causative factor, oxidative stress, it is also necessary to activate the neurotrophic signaling pathway that replaces damaged organelles and molecules with new ones. Thus, the dual actions to activate both the Nrf2 antioxidant system and neurotrophic signaling pathway are expected to provide a better strategy to modify AD pathogenesis. Here, we review the current understanding of AD pathogenesis and neuronal defense systems and discuss a possible way to co-activate the Nrf2 antioxidant system and neurotrophic signaling pathway with the hope of helping to find a better strategy to slow AD.


Randomized test of an implementation intention-based tool to reduce stress-induced eating.
Stress may indirectly contribute to disease (e.g. cardiovascular disease, cancer) by producing deleterious changes to diet. The purpose of this study was to test the effectiveness of a stress management support (SMS) tool to reduce stress-related unhealthy snacking and to promote stress-related healthy snacking. Participants were randomized to complete a SMS tool with instruction to link stressful situations with healthy snack alternatives (experimental) or a SMS tool without a linking instruction (control). On-line daily reports of stressors and snacking were completed for 7 days. Daily stressors were associated with unhealthy snack consumption in the control condition but not in the experimental condition. Participants highly motivated towards healthy eating consumed a greater number of healthy snacks in the experimental condition on stressful days compared to participants in the experimental condition with low and mean levels of motivation. This tool is an effective, theory driven, intervention that helps to protect against stress-induced high-calorie snack consumption.


Explaining the decline in Mexico-U.S. Migration: the effect of the Great Recession.
The rate of Mexico-U.S. migration has declined precipitously in recent years. From 25 migrants per thousand in 2005, the annual international migration rate for Mexican men dropped to 7 per thousand by 2012. If sustained, this low migration rate is likely to have a profound effect on the ethnic and national-origin composition of the U.S. population. This study examines the origins of the migration decline using a nationally representative panel survey of Mexican households. The results support an explanation that attributes a large part of the decline to lower labor demand for Mexican immigrants in the United States. Decreases in labor demand in industrial sectors that employ a large percentage of Mexican-born workers, such as construction, are found to be strongly associated with lower rates of migration for Mexican men. Second, changes in migrant selectivity are also consistent with an economic explanation for the decline in international migration. The largest declines in migration occurred precisely among the demographic groups most affected by the Great Recession: namely, economically active young men with low education. Results from the statistical analysis also show that the reduction in labor demand in key sectors of the U.S. economy resulted in a more positive educational selectivity of young migrants.


Palladium-/copper-catalyzed regioselective amination and chloroamination of indoles.
A palladium-/copper-catalyzed intermolecular C-H amination reaction of indoles has been developed. This reaction proceeds in good to excellent yields to produce a variety of 2-amino-substituted indoles and exhibits excellent regioselectivity at room temperature. Furthermore, chloroamination of indoles provides a simple method for the construction of C-N and C-Cl bonds in one step.


Atrial natriuretic peptide attenuates elevations in Ca2+ and protects hepatocytes by stimulating net plasma membrane Ca2+ efflux.
Elevations in intracellular Ca(2+) concentration and calpain activity are common early events in cellular injury, including that of hepatocytes. Atrial natriuretic peptide is a circulating hormone that has been shown to be hepatoprotective. The aim of this study was to examine the effects of atrial natriuretic peptide on potentially harmful elevations in cytosolic free Ca(2+) and calpain activity induced by extracellular ATP in rat hepatocytes. We show that atrial natriuretic peptide, through protein kinase G, attenuated both the amplitude and duration of ATP-induced cytosolic Ca(2+) rises in single hepatocytes. Atrial natriuretic peptide also prevented stimulation of calpain activity by ATP, taurolithocholate, or Ca(2+) mobilization by thapsigargin and ionomycin. We therefore investigated the cellular Ca(2+) handling mechanisms through which ANP attenuates this sustained elevation in cytosolic Ca(2+). We show that atrial natriuretic peptide does not modulate the release from or re-uptake of Ca(2+) into intracellular stores but, through protein kinase G, both stimulates plasma membrane Ca(2+) efflux from and inhibits ATP-stimulated Ca(2+) influx into hepatocytes. These findings suggest that stimulation of net plasma membrane Ca(2+) efflux (to which both Ca(2+) efflux stimulation and Ca(2+) influx inhibition contribute) is the key process through which atrial natriuretic peptide attenuates elevations in cytosolic Ca(2+) and calpain activity. Moreover we propose that plasma membrane Ca(2+) efflux is a valuable, previously undiscovered, mechanism through which atrial natriuretic peptide protects rat hepatocytes, and perhaps other cell types, against Ca(2+)-dependent injury.


A case of liver abscess caused by appendicitis which was considered to be drained from hepatobronchial fistula.
A 52-year-old man was referred to our hospital complaining of right lower abdominal pain. He was diagnosed with appendicitis complicated with a liver abscess and underwent an appendectomy. After antibiotic treatment following surgery, the liver abscess penetrated the right lung, which was considered to be drained from a hepatobronchial fistula. Due to the effect of drainage, the liver abscess immediately improved and the patient was subsequently discharged.


[Surgical treatment of rheumatoid arthritis based on EBM].
Even though the advancement of pharmacotherapy, the maintenance treatment to keep the function of degenerated and destructed joint on rheumatoid arthritis and the surgical treatment for joint reconstruction are very important to prevent the patients from being bedridden and to keep the quality of life. The adaptation of operation varies among disease stage and site of bone destruction. Missing the chance of operation, it becomes impossible to perform surgical treatment. So it is important to consult with specialist finding proper opportunity.


Slips, Trips, and Falls: A Quality Improvement Initiative.
Employee safety and the reduction of Days Away, Restricted, or Transferred are a focus of the Solutions for Patient Safety Network. One significant contributor to the Days Away, Restricted, or Transferred rate at Children's National Hospital is employee slips, trips, or falls. Children's National Hospital implemented a multidisciplinary quality improvement with executive leadership vision and support. We implemented quality techniques (including Key Driver Diagrams, Pareto Charts, and continuous Plan-Do-Study-Act) and designed novel Environmental Services interventions. Children's National Hospital achieved a 44.3% reduction in monthly average reported slips, trips, or fall events from baseline and sustained over a 2-year study period. A leadership-driven multidisciplinary approach to quality initiatives with team leaders capable of making and enacting real-time policy changes led to novel interventions and a successful reduction of employee slips, trips, and falls events over time, which are broadly generalizable.


Long-term flexion-extension range of motion of the prodisc total disc replacement.
The rationale for total disc replacement is avoidance of the junctional degeneration seen after arthrodesis by preservation of segmental motion. To justify the use of disc prostheses, it is essential to document maintained range of motion (ROM) and sagittal alignment at long-term follow-up. This is a retrospective radiographic study of 42 patients who had placement of 58 first-generation Prodisc prostheses at a mean follow-up of 8.7 years. Flexion-extension ROM was measured by Cobb's method. Junctional levels were evaluated for junctional degeneration. Pre- and postoperative global and segmental lordosis were measured. Prognostic patient factors predicting ROM of <2 degrees were evaluated. We observed ROM of at least 2 degrees in 66% of Prodisc prostheses at 8.7-year follow-up, although ROM was less than that reported in asymptomatic normal individuals. Mean ROM for disc prostheses with motion was 7.5 degrees at L3-L4, 6.2 degrees at L4-L5, and 4.1 degrees at L5-S1. Mean ROM for all prostheses was 3.8 degrees. The incidence of radiographic junctional degeneration was 24%, although no patients required surgery for symptomatic junctional degeneration. Mean ROM of prostheses below a degenerated junctional disc was 1.6 degrees compared with 4.7 degrees below a normal junctional disc (P < 0.035). Females were 3.5 times more likely to have ROM of <2 degrees. This is the longest published follow-up study of a lumbar disc replacement. The data show that ROM is preserved at long-term follow-up in the majority of patients. Global and segmental sagittal alignment improve after surgery. Furthermore, there is an association between ROM of disc prostheses and the development of junctional degeneration.


Manipulation of chemical composition and architecture of non-biodegradable poly(ethylene terephthalate)/chitosan fibrous scaffolds and their effects on L929 cell behavior.
Microporous, non-woven fibrous scaffolds made of poly(ethylene terephthalate) and chitosan were produced by electrospinning. Fiber morphology, diameter, pore size, and wettability were manipulated by varying the chemical composition of the electrospinning solution, i.e. chitosan concentration and molecular weight, and by post-electrospinning treatment with glutaraldehyde. In vitro studies were conducted using a fibroblast cell line toward a comprehensive understanding of how scaffolds characteristics can modulate the cell behavior, i.e. viability, adhesion, proliferation, extracellular matrix secretion, and three-dimensional colonization. Substantial differences were found as a result of scaffold morphological changes. Higher levels of adhesion, spreading, and superficial proliferation were achieved for scaffolds with smaller fiber and pore diameters while cell penetration and internal colonization were enhanced for scaffolds with larger pores. Additionally, the available area for cell adhesion, which is related to fiber and pore size, was a crucial factor for the viability of L929 cells. This paper provides significant insights for the development and optimization of electrospun scaffolds toward an improved biological performance.


Highly efficient modulation doping: A path toward superior organic thermoelectric devices.
We investigate the charge and thermoelectric transport in modulation-doped large-area rubrene thin-film crystals with different crystal phases. We show that modulation doping allows achieving superior doping efficiencies even for high doping densities, when conventional bulk doping runs into the reserve regime. Modulation-doped orthorhombic rubrene achieves much improved thermoelectric power factors, exceeding 20 μW m-1 K-2 at 80°C. Theoretical studies give insight into the energy landscape of the heterostructures and its influence on qualitative trends of the Seebeck coefficient. Our results show that modulation doping together with high-mobility crystalline organic semiconductor films is a previosly unexplored strategy for achieving high-performance organic thermoelectrics.


Intrinsic defects and their effects on the optical properties in the nonlinear optical crystal CdSiP2: a first-principles study.
In view of their high nonlinear optical coefficients and good phase-matching properties, CdSiP2 (CSP) crystals are considered as one of the most promising materials in the field of nonlinear optical applications. However, the slight absorption losses around 1.34 μm and 1.78 μm under e-polarized light have been affecting its performance. In this study, first-principles calculations were performed to identify the effects of various charge defects on the absorption properties. Different intrinsic defects in the CSP crystal were calculated using the HSE method and compared according to the specific chemical environments in the experiments. The results show that the point defects of V, Si, and V, which can be spontaneously formed, are dominant in the Cd-poor environment. The combination of Si and V defects is the most favorable cluster in the Cd-poor case because of its relatively low formation energy. Furthermore, the antisite defect SiCd was found to be responsible for the main absorption peaks at 1.34 and 1.78 μm in the experimental spectra, whereas other defects and clusters, such as the defects Si and V, also contribute to these red shifted absorptions. Our results intend to provide a guideline for adjusting the optical absorption in CSP by modifying its defects.


Head and neck injuries in fatal motorcycle collisions as determined by detailed autopsy.
Detailed layer-by-layer autopsy of the head and neck was performed on a prospective series of 73 fatally injured motorcyclists in order to identify occult injuries, particularly soft tissue neck injuries such as hemorrhage of vertebral and carotid arteries. The fatal cases were gathered as part of a larger study of 1,082 on-scene in-depth motorcycle crash investigations in Thailand. Detailed neck dissection was done on nearly all fatal cases. Injuries were coded using the 1990 revision of the Abbreviated Injury Scale (AIS 90) and an Injury Severity Score (ISS) was determined for each case. Additional AIS codes are proposed for neck injuries that were often identified during the detailed autopsy procedures, but which are not listed explicitly among existing AIS codes. Helmet use was determined based on analysis of injury patterns and helmet damage with consideration also given to witness statements. Both helmeted and unhelmeted motorcyclists showed a high frequency of occult neck injuries such as hemorrhages in the carotid sheath or surrounding the vertebral arteries, phrenic nerve, or brachial plexus. These soft tissue neck injuries sometimes accompanied more obvious injuries to cervical vertebrae or spinal cord, but about one-third of riders had no obvious injury to suggest the presence of occult neck injury. Twenty-eight motorcyclists had been wearing a helmet at the start of the collision sequence, but only nine helmets remained in place through the entire collision event. Helmeted riders showed more severe somatic (below-the-neck) injuries than unhelmeted riders, suggesting helmeted riders are less likely to die in low-threat accidents with somatic injuries below AIS-3. The most significant finding of this study was the identification of serious internal neck injuries despite the absence of external physical evidence of trauma to the neck. Virtually all riders with significant head injuries showed some of these soft tissue neck injuries. Approximately one-third of the critically injured riders who survived at least a few hours before death showed serious occult soft tissue neck injuries.


Minimally Invasive Fixation with Dorsal Suspension Button and Volar Plate in Distal Radius Fractures with Dorsal Die Punch Fragments: A Preliminary Study.
Objective The objective of the study is to analyze the clinical and radiological results obtained using a minimally invasive fixation technique with a volar locking plate and a suspension system with a dorsal button in distal articular radius fractures with dorsal comminution. Materials and Methods Six patients with distal radius fractures, between 19 and 68 years of age, were included in the study. Mean follow-up was of 15 weeks. Range of motion (ROM) in flexion, extension, radial deviation, ulnar deviation, pronation, supination, the strength in kilograms, and values on the Visual Analog Scale (VAS), Disabilities of Arm, Shoulder and Hand (DASH), and Mayo Wrist Score (MWS) scales were evaluated at 4, 8, and 12 weeks postoperative. Correction of anteroposterior diameter of the radius and concordance between postoperative anteroposterior diameter and the contralateral wrist diameter were evaluated radiologically. Results The following mean values were obtained at 12 weeks postoperative: ROM in flexion: 40.5°, ROM in extension: 49.5°, ROM in radial deviation: 24.5°, ROM in ulnar deviation: 15°, ROM in pronation: 87°, ROM in supination: 89°, strength: 37.5 kg, pain in VAS scale: 2 points, DASH: 54.5 points, and MWS: 67.5 points. At 12 weeks postoperative, the mean correction of anteroposterior diameter was 0.49 mm. The anteroposterior diameter and that of the contralateral wrist were strongly correlated. Conclusion Fixation with the volar locking plate and dorsal suspension button could be considered an alternative to dorsal plate fixation for treatment of distal radius fractures with comminution or associated dorsal die punch fragments.


Review of pathological findings in laparoscopic sleeve gastrectomy specimens performed for morbid obesity.
Bariatric surgical procedures are employed when there is a failure of lifestyle modification in arresting obesity. Laparoscopic sleeve gastrectomy (LSG) is quickly becoming the bariatric surgical procedure of choice. LSG results in a gastric remnant that is subject to pathological examination. The objective of this paper is to review the literature in regard to histological findings identified in gastric remnants post-LSG and identify the most pertinent histological findings. A literature search was performed to identify relevant case series. Data gathered from relevant case series then underwent statistical analysis. The most common histological findings in an LSG specimen were clinically indolent findings such as no pathological abnormalities identified followed by non-specific gastritis. A minority of cases demonstrated clinically actionable findings for which Helicobacter pylori represented the majority of these findings. There is a broad spectrum of pathological findings in LSG specimens, ranging from clinically indolent to clinically actionable. The most common histological findings are clinically indolent and only a small portion are of clinical significance and, hence, actionable.


Hydroxyl radical activity in thermo-catalytically bleached root-filled teeth.
Intra-coronal bleaching of root-filled teeth has been associated with invasive cervical root resorption. It is considered that during bleaching hydrogen peroxide diffuses through the tooth structure into the cervical periodontium, resulting in periodontal tissue destruction and initiating a resorptive process. Hydrogen peroxide is capable of generating hydroxyl radical, an oxygen-derived free radical, in the presence of ferrous salts. Hydroxyl radicals are extremely reactive and have been shown to degrade components of connective tissue, particularly collagen and hyaluronic acid. The aim of the present study was to determine whether hydroxyl radicals are generated during the bleaching of root-filled teeth which have been discoloured by blood. Forty extracted human premolar teeth were root-filled with gutta-percha and AH26 sealer cement. Twenty of the teeth were experimentally discoloured by blood. All teeth were then thermo-catalytically bleached using 30% hydrogen peroxide while tooth roots were seated in a test solution of sodium salicylate. Hydroxyl radical generation was determined by the detection of reaction products of this radical with salicylate using high performance liquid chromatography with electrochemical detection (HPLC-ECD). The presence of hydroxyl radicals was detected in twenty-five of the teeth. There was a significant association between the production of hydroxyl radicals and the presence of tooth discolouration caused by blood components. Greatest yields of hydroxyl radicals occurred in teeth in which EDTA had been used to clean the pulp chamber prior to bleaching. It was concluded that hydroxyl radicals are generated during the thermo-catalytic bleaching of root-filled teeth. Generation of this toxic chemical species may be one mechanism underlying periodontal tissue destruction and root resorption after intra-coronal bleaching.


Precarious maintenance of simple DNA repeats in eukaryotes.
In this review, we discuss how two evolutionarily conserved pathways at the interface of DNA replication and repair, template switching and break-induced replication, lead to the deleterious large-scale expansion of trinucleotide DNA repeats that cause numerous hereditary diseases. We highlight that these pathways, which originated in prokaryotes, may be subsequently hijacked to maintain long DNA microsatellites in eukaryotes. We suggest that the negative mutagenic outcomes of these pathways, exemplified by repeat expansion diseases, are likely outweighed by their positive role in maintaining functional repetitive regions of the genome such as telomeres and centromeres.


Successful percutaneous drainage of pneumatoceles in an extremely low-birthweight infant.
Pneumatoceles are thin-walled, air-filled cystic lesions developing within the lung parenchyma. It used to be a relatively common entity in the presurfactant era when preterm babies were ventilated at an unacceptably high positive pressure for respiratory distress syndrome. Pneumatocele formation is a very rare complication of pneumonia in neonates. We here report a case of extremely low-birthweight (ELBW) neonate who developed large bilateral pneumatoceles after staphylococcal pneumonia. Hereby, we present a case of an ELBW infant with bilateral massive pneumatoceles who underwent successful percutaneous catheter drainage to decompress these pneumatoceles.


Activin a causes cancer cell aggressiveness in esophageal squamous cell carcinoma cells.
Expression of activin A is associated with lymph node metastasis and clinical stage in esophageal cancer. To clarify the aggressive behavior of tumors with high activin A expression, we used the beta subunit of activin A to establish stable activin betaA (Act-betaA)-transfected carcinoma cells in two human esophageal carcinoma cell lines, KYSE110 and KYSE140. The biological behavior of these cells was compared with that in mock-transfected cells from the same cell lines. We focused our attention on cell growth and tumorigenesis, and proliferation and apoptosis. Both Act-betaA-transfected carcinoma cell lines showed a higher growth rate than the mock-transfected carcinoma cells. In an in vitro invasion assay and a xenograft analysis, the Act-betaA-transfected carcinoma cells showed far higher proliferation in vitro and a higher potency for tumorigenesis in vivo, respectively. Moreover, in an analysis of apoptosis via Fas stimulation, the Act-betaA-transfected carcinoma cells showed a higher tolerance to apoptosis compared with the mock-transfected carcinoma cells. Moreover, anti-activin-neutralizing antibody-treated squamous cell cancer cell lines inhibited their migration. Collectively, these data indicate that continuous high expression of activin A in esophageal carcinoma cells is not related to tumor suppression, but rather to tumor progression in vitro and in vivo. The inhibition of activin might be one of the methods to attenuate tumor aggressiveness.


[The effects of leptin on apoptosis of airway smooth muscle cells via the PI3K/Akt signaling pathway].
To observe the effects of leptin on the expression of Akt, Pho-Akt, Bcl-2, Bax, caspase-3 and the apoptosis of airway smooth muscle cells (ASMCs), and to explore the possible mechanisms. ASMCs were derived from rat airway tissue and cultured in vitro. The cells were randomly divided into 5 groups including a control group, leptin at concentrations of 50, 100, 200 µg/L groups (group Lep50, Lep100, Lep200), and PI3K specific antagonist with Lep200 group. Then the cells of different groups were incubated for 24 h. An apoptosis detection kit was used for annexin V and PI staining. The expression of Akt, phosphorylation Akt, Bcl-2, Bax, caspase-3 were measured by Western blot. The apoptosis rates of ASMCs in group Lep50, Lep100 and Lep200 were (3.97 ± 0.39)%, (1.88 ± 0.72)% and (0.77 ± 0.11)%, respectively, all significantly lower than that in the control group (7.38 ± 0.49)% (F = 89.57, P < 0.05). Furthermore, the concentration of leptin was negatively related to the apoptosis rate (r = -0.711, P < 0.05). The apoptosis rates of PI3K specific antagonist with Lep200 group (3.29 ± 0.36)% was higher than that of group Lep200 (0.77 ± 0.11)% (F = 89.57, P < 0.01). After the intervention of leptin, the expression of Bcl-2 was upregulated and positively correlated with leptin concentration (r = 0.939, P < 0.05); Bax was downregulated and negatively related to the leptin concentration (r = -0.908, P < 0.05); while the Bcl-2/Bax ratio was raised after leptin treatment (F = 20.56, P < 0.05). Leptin inhibited the activation of caspase-3 in the negative way. (r = -0.961, P < 0.05). The results also showed that leptin significantly increased phosphorylation of Akt that positively related to leptin concentration (r = 0.958, P < 0.05). Compared with group Lep200, the expression of Pho-Akt and Bcl-2 in PI3K specific antagonist with Lep200 group were downregulated (F = 32.93, 19.48, respectively, P < 0.05), while the expression of Bax and caspase-3 was increased (F = 10.10, 29.86, respectively, P < 0.05); the Bcl-2/Bax ratio was lower in group Lep200 as compared to the PI3K specific antagonist with Lep200 group (F = 20.56, P < 0.05). Leptin can significantly inhibit ASMC apoptosis partially via the PI3K/Akt signaling pathway.


Randomization-selection analysis of snRNAs in vivo: evidence for a tertiary interaction in the spliceosome.
Putative components of the spliceosomal active site include a bulged helix between U2 and U6 snRNAs (U2-U6 helix I) and the adjacent ACAGAG hexanucleotide in U6. We have developed an in vivo, bimolecular randomization-selection method to functionally dissect these elements. Although a portion of U2-U6 helix I resembles the G-binding site of group I introns, the data are inconsistent with an analogous functional role for this structure in the spliceosome. Instead, analysis of several novel covariants supports the existence of a structure in which the helix I bulge engages in a tertiary interaction with the terminal residue of the U6 hexanucleotide (ACAGAG). Such a higher order structure, together with other known interactions, would juxtapose the two clusters of residues of the U2-U6 complex that are specifically required for the second chemical step of pre-mRNA splicing with the 3' splice site. Indeed, mutations in the residues that participate in the tertiary interaction affect both the efficiency and fidelity of 3' splice site usage.


Testing the nutritional-limitation, predator-avoidance, and storm-avoidance hypotheses for restricted sea otter habitat use in the Aleutian Islands, Alaska.
Sea otters (Enhydra lutris) inhabiting the Aleutian Islands have stabilized at low abundance levels following a decline and currently exhibit restricted habitat-utilization patterns. Possible explanations for restricted habitat use by sea otters can be classified into two fundamentally different processes, bottom-up and top-down forcing. Bottom-up hypotheses argue that changes in the availability or nutritional quality of prey resources have led to the selective use of habitats that support the highest quality prey. In contrast, top-down hypotheses argue that increases in predation pressure from killer whales have led to the selective use of habitats that provide the most effective refuge from killer whale predation. A third hypothesis suggests that current restricted habitat use is based on a need for protection from storms. We tested all three hypotheses for restricted habitat use by comparing currently used and historically used sea otter foraging locations for: (1) prey availability and quality, (2) structural habitat complexity, and (3) exposure to prevailing storms. Our findings suggest that current use is based on physical habitat complexity and not on prey availability, prey quality, or protection from storms, providing further evidence for killer whale predation as a cause for restricted sea otter habitat use in the Aleutian Islands.


Uninfected Bystander Cells Impact the Measurement of HIV-Specific Antibody-Dependent Cellular Cytotoxicity Responses.
The conformation of the HIV-1 envelope glycoprotein (Env) substantially impacts antibody recognition and antibody-dependent cellular cytotoxicity (ADCC) responses. In the absence of the CD4 receptor at the cell surface, primary Envs sample a "closed" conformation that occludes CD4-induced (CD4i) epitopes. The virus controls CD4 expression through the actions of Nef and Vpu accessory proteins, thus protecting infected cells from ADCC responses. However, gp120 shed from infected cells can bind to CD4 present on uninfected bystander cells, sensitizing them to ADCC mediated by CD4i antibodies (Abs). Therefore, we hypothesized that these bystander cells could impact the interpretation of ADCC measurements. To investigate this, we evaluated the ability of antibodies to CD4i epitopes and broadly neutralizing Abs (bNAbs) to mediate ADCC measured by five ADCC assays commonly used in the field. Our results indicate that the uninfected bystander cells coated with gp120 are efficiently recognized by the CD4i ligands but not the bNabs. Consequently, the uninfected bystander cells substantially affect in vitro measurements made with ADCC assays that fail to identify responses against infected versus uninfected cells. Moreover, using an mRNA flow technique that detects productively infected cells, we found that the vast majority of HIV-1-infected cells in in vitro cultures or ex vivo samples from HIV-1-infected individuals are CD4 negative and therefore do not expose significant levels of CD4i epitopes. Altogether, our results indicate that ADCC assays unable to differentiate responses against infected versus uninfected cells overestimate responses mediated by CD4i ligands.IMPORTANCE Emerging evidence supports a role for antibody-dependent cellular cytotoxicity (ADCC) in protection against HIV-1 transmission and disease progression. However, there are conflicting reports regarding the ability of nonneutralizing antibodies targeting CD4-inducible (CD4i) Env epitopes to mediate ADCC. Here, we performed a side-by-side comparison of different methods currently being used in the field to measure ADCC responses to HIV-1. We found that assays which are unable to differentiate virus-infected from uninfected cells greatly overestimate ADCC responses mediated by antibodies to CD4i epitopes and underestimate responses mediated by broadly neutralizing antibodies (bNAbs). Our results strongly argue for the use of assays that measure ADCC against HIV-1-infected cells expressing physiologically relevant conformations of Env to evaluate correlates of protection in vaccine trials.


Co phthalocyanine mediated electrochemical detection of the HER2 in the presence of Au and CeO2 nanoparticles and graphene quantum dots.
In this work, cobalt tetra phenoxy acetic acid phthalocyanine (CoTAPc) is investigated as an electron mediator, immobilization platform for an HB5 aptamer and to enhance the electrochemical signal for the detection of human epidermal growth factor receptor 2 (HER2). Furthermore, the CoTAPc was combined individually with sulphur/nitrogen doped graphene quantum dots (SNGQDs), gold nanoparticles (AuNPs) and cerium oxide nanoparticles (CeO2NPs), on a glassy carbon electrode (GCE) via sequential adsorption. The CoTAPc and SNGQDs were also π-π stacked, used for electrode modification similarly to the rest of the other surfaces and applied towards the electrochemical detection of HER2. The designed sensors were characterized using electrochemical impedance spectroscopy (EIS). The designed aptasensors showed detection limits as low as 6.0 pg/mL. The real life applicability of the designed aptasensors was tested in human serum samples. The aptasensors showed great storage stability, sensitivity and specificity towards HER2, implying great potential for applications in early diagnosis of breast cancer.


Current direction and advances in analytical sample extraction techniques for drugs with special emphasis on bioanalysis.
Analytical techniques may not be compatible or sufficiently sensitive to the analytes, unless it undergoes a specific sample extraction procedure. Sample extraction can be considered as one of the key steps in analysis. Analysis of a poorly treated sample may produce inferior quality of analytical data. Continuous advancement and development of newer sample extraction techniques such as solid phase microextraction, ultrasound, magnetically and microwave assisted magnetic extraction; electro-membrane extraction and dried blood spotting are to address the shortcomings of the existing techniques and to provide more automation, minimizing preparation time and make them high throughput. This review summarizes the suitability of application of the advanced sample preparation techniques available for chemical and bioanalysis in a comprehensive manner. This review also provides a scientific guidance for selecting the appropriate sample extraction technique based on sample type.


Selective Activation of CH Bonds in Polar Vinyl Olefins and Coupling of Ethylene to the Activated Carbon Atoms in Pentaruthenium Complexes.
Ru5(μ5-C)(CO)15, 1, has been found to activate CH bonds in the vinyl group of polar vinyl olefins, methyl acrylate (MA), and vinyl acetate (VAc), through a cluster opening process to yield the complexes Ru5(μ5-C)(CO)14[η2-O═C(OMe)CH═CH](μ-H), 2, and Ru5(μ5-C)(CO)14[η2-(MeCO2)C═CH2](μ-H), 4, respectively. The site of CH activation is dependent on the olefin substituent. In 2, the site of CH activation is the β-carbon atom of the vinyl group, while in 4 the CH activation has occurred exclusively at the α-carbon atom of the vinyl group. Compound 2 can be further decarbonylated to yield the complex Ru5(μ5-C)(CO)13[μ-η3-O═C(OMe)CHCH](μ-H), 3, which contains a η3-bridging acryloyl ligand. Compound 2 reacts with ethylene in the presence of Me3NO to yield three new Ru5 products: Ru5(μ5-C)(CO)13[η4-1- anti,3- syn-{O═C(OMe)}C(H)C(H)C(H)Me](μ-H), 5, Ru5(μ5-C)(CO)12(C2H4)[μ-η3- O═C(OMe)C(H)C(H)](μ-H), 6, and Ru5(μ5-C)(CO)13[η4- anti-O═C(OMe)H2CHCHCH2](μ-H), 7. Compounds 5 and 7 are isomers containing substituted η3-allyl ligands formed by the coupling of the ethylene to the CH-activated β-carbon atom of the acryloyl ligand accompanied by some metal-mediated H-shifts. Compound 6 contains an uncoupled π-coordinated ethylene ligand. Compound 7 was isomerized to 5 thermally at 80 °C. Compound 4 reacts with ethylene in the presence of Me3NO to yield two new Ru5 products: Ru5(μ5-C)(CO)13[η4-1,1- anti- syn-[(O2CMe)C(Me)CHCH2](μ-H), 8, and Ru5(μ5-C)(CO)13[η4-1- anti-CH(Me)C(O2CMe)(CH2)](μ-H), 9. Compounds 8 and 9 both contain substituted η3-allyl ligands formed by the coupling of the ethylene to the CH-activated α-carbon atom of the vinyl acetyl ligand. Compound 8 was isomerized to 9 thermally at 80 °C. All new products were characterized structurally by single-crystal X-ray diffraction analyses.


The importance of considering multiple interacting species for conservation of species at risk.
Conservation of species at risk of extinction is complex and multifaceted. However, mitigation strategies are typically narrow in scope, an artifact of conservation research that is often limited to a single species or stressor. Knowledge of an entire community of strongly interacting species would greatly enhance the comprehensiveness and effectiveness of conservation decisions. We investigated how camera trapping and spatial count models, an extension of spatial-recapture models for unmarked populations, can accomplish this through a case study of threatened boreal woodland caribou (Rangifer tarandus caribou). Population declines in caribou are precipitous and well documented, but recovery strategies focus heavily on control of wolves (Canis lupus) and pay less attention to other known predators and apparent competitors. Obtaining necessary data on multispecies densities has been difficult. We used spatial count models to concurrently estimate densities of caribou, their predators (wolf, black bear [Ursus americanus], and coyote [Canis latrans]), and alternative prey (moose [Alces alces] and white-tailed deer [Odocoileus virginianus]) from a camera-trap array in a highly disturbed landscape within northern Alberta's Oil Sands Region. Median densities were 0.22 caribous (95% Bayesian credible interval [BCI] = 0.08-0.65), 0.77 wolves (95% BCI = 0.26-2.67), 2.39 moose (95% BCI = 0.56-7.00), 2.64 coyotes (95% BCI = 0.45-6.68), and 3.63 black bears (95% BCI = 1.25-8.52) per 100 km2 . (The white-tailed deer model did not converge.) Although wolf densities were higher than densities recommended for caribou conservation, we suggest the markedly higher black bear and coyote densities may be of greater concern, especially if government wolf control further releases these species. Caribou conservation with a singular focus on wolf control may leave caribou vulnerable to other predators. We recommend a broader focus on the interacting species within a community when conserving species.


The prognostic value of S100A10 expression in cancer.
S100A10, a member of the S100 protein family, commonly forms a heterotetrameric complex with Annexin A2. This is essential for the generation of cellular plasmin from plasminogen, which leads to a cascade of molecular events crucial for tumor progression. S100A10 upregulation has been reported in a number of cancers, suggesting that it may have potential as a prognostic biomarker, as well as predicting sensitivity to anticancer drugs. This review evaluates the direct and indirect relationships between S100A10 and cancer progression by investigating its role in cancer. Research papers published on PubMed and Google Scholar between 2007-2017 were collated and reviewed. We concluded that S100A10 affects the development of the hallmarks of cancer as explained by Hanahan and Weinberg in 2011, most notably by activating the invasion and metastasis of cancer cells. However, further studies are required to explore the underlying biological mechanisms of S100A10.


International Travel as a Context for Sexual and Contraceptive Behaviors: A Qualitative Study of Young Women Traveling Outside the U.S.
International travel is popular worldwide, yet its implications for sexual and reproductive health are not fully understood. Few studies have examined the contextual factors that shape women's sexual and contraceptive behaviors-and thus, their risk of unintended pregnancy and sexually transmitted infections (STIs)-while traveling outside their home country. In this qualitative study, female university students with recent (n = 25) or upcoming (n = 19) travel outside the U.S. completed semi-structured interviews from October 2015 to March 2017. Transcripts were analyzed for themes related to contraceptive and sexual behaviors: (1) participants' pre-travel expectations of sex; (2) the circumstances surrounding sexual encounters with men while traveling; (3) negotiation about condom and contraception use with partners; and (4) factors affecting contraceptive adherence. Participants generally expected to be abstinent during travel, citing myriad rationales that included personal values, no perceived opportunities for sex, and the nature of the trip. Some travelers had unexpected sexual encounters, involving health-protecting behaviors and risk-taking (e.g., unprotected sex, substance use). New sexual partnerships were fueled by increased attention from men, situational disinhibition, and perceived heightened intimacy. International travel brought many contraceptive considerations (adequacy of supplies, access to refrigeration, time zone differences, etc.) as well as obstacles that triggered contraceptive lapses and discontinuation. Pill users described the most challenges, while travelers using intrauterine devices expressed appreciation for their maintenance-free contraception. This study suggests complex associations between international travel and young women's sexual and reproductive health. Some travelers were more vulnerable to situational risk factors, while others may have been more insulated. We identify potential intervention opportunities via clinical services, education, and policy to reduce young women's risk of adverse sexual and reproductive health outcomes while traveling abroad. We urge greater recognition of and conversations about contraceptive lapse and unintended pregnancy as potential health risks for female travelers of reproductive age, just as clinical guidelines acknowledge travel-associated STI.


The impact of oral Polypodium leucotomos extract on ultraviolet B response: A human clinical study.
There is a rationale for adding systemic photoprotective agents to the current photoprotection regimen. This study was designed to objectively evaluate the molecular and photobiologic effects of oral administration of Polypodium leucotomos extract (PLE). In all, 22 subjects with Fitzpatrick skin phototype I to III were enrolled. On day 1, subjects were irradiated with visible light, ultraviolet (UV) A1, and UVB (using 308-nm excimer laser). Evaluation was done immediately and 24 hours after irradiation. On days 3 and 4, irradiation and evaluation process was repeated after ingestion of PLE. Clinical assessments and colorimetry data showed a decrease in UVB-induced changes in 17 of 22 subjects post-PLE administration; histology findings demonstrated such a decrease in all 22 subjects. Only 2 doses of PLE were given. Furthermore, subjects with skin phototypes I to III only were studied. The results suggest that PLE can potentially be used as an adjunctive agent to lessen the negative photobiologic effects of UVB.


[Cervical flexion-induced changes of motor evoked potentials by transcranial magnetic stimulation in a patient with Hirayama disease--juvenile muscular atrophy of unilateral upper extremity].
A 16-year-old girl noticed weakness in the left hand in 1990, which gradually progressed over the next 2 years but then stabilized. Her neurologic and electrophysiological signs were compatible with juvenile muscular atrophy of unilateral upper extremity (Hirayama disease). Cine MRIs demonstrated a mild cervical cord atrophy at the C6 spine level together with an engorged epidural vein at the C4-C6 extradural spaces during neck flexion. Transcranial magnetic stimulation over the motor cortex was carried out with a pickup placed on the contralateral abductor brevis muscle. While neck flexion was maintained, the amplitude of the evoked potentials steadily attenuated and the central motor conduction time lengthened as time passed. After 8 minutes, she began to feel some dullness in the left upper limb. These phenomena were reversible and were observed only on the affected limb. The above facts not only supported the presence of a reversible cortico-efferent dysfunction in Hirayama disease, but also appeared to justify the use of neck collars to treat those afflicted with this entity.


Complete lymph node dissection or observation in melanoma patients with multiple positive sentinel lymph nodes: A single-center retrospective analysis.
Although the role of sentinel lymph node biopsy (SLNB) as a prognostic factor is well established, its consequences for therapy are controversial. The aim of this study was to analyze if complete lymph node dissection (CLND) in patients with more than one positive sentinel lymph node (SLN) significantly improves melanoma-specific survival (MSS) and progression-free survival (PFS). Medical records of patients who underwent SLNB between 2001 and 2016 at the University Hospital of Cologne were reviewed, and patients with positive SLN were identified. Patient and tumor characteristics, patterns of recurrence, progression-free and melanoma-specific survival were analyzed. Seventy-eight patients with multiple positive and 197 patients with one positive SLN were included in this study. Patients with multiple positive SLN had significantly more positive non-SLN compared with patients with only one positive SLN (26.9% vs 8.6%, P = 0.01). However, in the subgroup of patients with multiple positive SLN, CLND did not significantly improve MSS (mean MSS 95 vs 75 months, P = 0.5) and PFS (mean PFS 59 vs 68 months P = 0.167). CLND did not result in a significant improvement in PFS and MSS in patients with multiple positive SLN.


Antidepressant switching patterns in the elderly.
ABSTRACTBackground:Switching between antidepressants is complex due to potential adverse outcomes such as serotonin syndrome and antidepressant discontinuation syndrome, yet switching is often required due to non-response to initial treatment. This study aimed to examine the patterns and extent of antidepressant switching in a cohort of older adults in long-term residential care. A cohort study of medication supply data from 6011 aged care residents in 60 long-term care facilities was conducted. Incident antidepressant users were followed for 12 months and their patterns of antidepressant use determined. The type of switching from and to different antidepressant classes was determined according to National and International recommendations for antidepressant switching. In total, 11% (n = 44) of the residents were initiated on an antidepressant medication (n = 402) switched to a different antidepressant agent within 12 months. Residents commenced on a SNRI or TCA were most likely to switch antidepressants (17% in each group). Almost half of the switches (n = 21, 48% of all switches) were not implemented according to guideline recommendations. Direct switch and taper followed by wash out and switch, accounted for all of the inappropriate switching (29% and 71%, respectfully), with half occurring to mirtazapine (N = 7) or from mirtazapine (N = 3). Over one in 10 long-term aged care residents who commence an antidepressant will switch to a different antidepressant within 12 months. Current antidepressant switching practices in long-term residential aged care may be increasing the risk of harm associated with antidepressant switching, with around half of all switches not following current guideline recommendations.


Aggressive fibromatosis (fibrosarcoma) of the facial nerve.
Aggressive fibromatosis of the facial nerve is a very rare tumor. Three cases have been previously reported. The tumor is locally recurrent and often has a fatal outcome. This report is of a ten-year-old boy whose tumor originally developed in the parotid area with subsequent spread to the base of the skull, the neck and the cerebellopontine angle. Treatment was by wide surgical excision, radiation therapy and chemotherapy. Despite treatment, the patient died. The clinical features of this case will be described. Only wide surgical excision early in the course of the disease may offer a chance for cure.


Cytoprotective effects of urinary trypsin inhibitor on astrocytes injured by sustained compression.
Decreased cell membrane integrity is a primary pathological change observed in traumatic brain injury (TBI) that activates a number of complex intercellular and intracellular pathological events, leading to further neural injury. In this paper, we assessed the effects of urinary trypsin inhibitor (UTI) on astrocyte membrane integrity by determining the percentage of lactate dehydrogenase (LDH) released after sustained compression injury using a hydrostatic pressure model of mechanical-like TBI. Astrocytes isolated from SD rat pups were injured by sustained compression. At a pressure of 0.3 MPa for 5 min, a significant increase in LDH release was observed compared with control samples. Astrocytes displayed extensive structural disruption of mitochondrial cristae reflected in their swelling. Based on our initial results, injured astrocytes were treated with UTI at a final concentration of 500, 1,000, 3,000 or 5,000 U/ml for 24 h. The percentage of LDH released from injured astrocytes was significantly decreased when 1,000 and 3,000 U/ml of UTI were used. In a separate experiment, astrocytes were treated with UTI at a final concentration of 1,000 U/ml immediately, or at 30 min, 2, 6, or 24 h after sustained compression. The percentage of LDH release was significantly reduced (P < 0.05) when astrocytes were treated with UTI immediately or 30 min later. Together, our results suggest that UTI may have protective effects on astrocytes injured by sustained compression injury. Furthermore, the early administration (<2 h after injury) of UTI may result in a better outcome compared with delayed administration.


The Ilizarov Mini-External Fixator for the Treatment of First Metatarsal Fracture: A Case Report.
Forefoot fractures are frequently accompanied by severe soft tissue damage. Therefore, treatment should focus not only on fractures but also on soft tissue damage, for which external fixation can be used as a surgical option. A 63-year-old woman presented to the emergency clinic of our hospital with forefoot pain after a motorcycle accident. Comminuted fracture of the proximal part of the metatarsal was diagnosed. Because of the swollen foot and fracture comminution, an operation using the Ilizarov mini external fixator was performed to prevent further damage to the soft tissue. Weight-bearing was permitted seven weeks after the operation, and the extraction of the apparatus was performed nine weeks postoperatively. One year later, the patient had no pain and had returned to ballroom dancing, a hobby which she performed five days a week, with no difficulties. Our results suggest that the Ilizarov mini external fixator should be considered not only for temporary treatment, but also for the entire duration of treatment of first metatarsal fractures associated with severe soft tissue damage.


Acute myositis: an unusual and severe side effect of docetaxel: a case report and literature review.
Docetaxel is an antimicrotubules cytotoxic agent prescribed widely by medical oncologists in multiple tumor types (breast, lung, prostate, stomach, head, and neck). However, the side effects of docetaxel are numerous (cytopenia, peripheral edema, myalgia, arthralgia, alopecia, and sensitive neuropathy) and recent concerns have been raised about neutropenic enterocolitis in France. Here, we report the case of a 57-year-old patient with metastatic prostatic cancer, who developed a severe myositis and fasciitis grade IV 1 week after his second docetaxel infusion. We reviewed the five cases of docetaxel-related myositis described in the literature, and found that most of them occurred in patients with diabetes (n=5/5) or hypertension (n=4/5). A vascular toxicity may explain this severe complication, and patients with diabetes or hypertension should be monitored closely in the context of a docetaxel chemotherapy.


An in-triphenylaminophane.
The synthesis and characterization of the triphenylamine-capped cyclophane 3 are described. It proved to be a conformationally rigid molecular propeller, with an inwardly pyramidalized, unreactive amine.


The role of dams in development.
Dams are a major issue in sustainable management of finite water resources; they have also become the subject of vigorous public debate. This article considers them in the light of the report of the World Commission on Dams and using the example of Turkey. It is argued that economic development and population growth, particularly in arid and semi-arid regions, make plain the need for dams for hydropower and irrigation. Environmental impact assessment is essential, as are effective programmes for resettlement to avoid the impoverishment of displaced people.


The validity of using self-reported illness to measure objective health.
There is a longstanding discourse on whether self-reported health is a good measure of objective health. This has never been empirical examined in Jamaica. Study seeks to 1) examine the relationship between particular subjective and objective indexes; 2) investigate the validity of a 4-week subjective index in measuring objective indexes; 3) evaluate the differences that exist between the measurement of subjective and objective indexes by the sexes; and 4) provide policy makers, other researchers, public health practitioners as well as social workers with research information with which can be used to inform their directions. Data published by the Statistical Institute of Jamaica, and the Planning Institute of Jamaica and the Statistical Institute of Jamaica were used for this study. Descriptive statistics were used to provide background information on data. Scatter diagrams were employed to establish 1) statistical associations, and 2) linearity and non-linearity between variables under examination. Multiple regression, using the enter method, was employed to a predictive model of linear associations. A strong significant association was found between life expectancy at birth for the Jamaican population and self-reported illness (r = -0.731); and this was weaker females (r = - 0.683) than males (r = - 0.796). However, the relationship between mortality and self-reported illness was a weak non-linear one. Self-reported illness in a 4-week reference period is a good measure of objective health and that self-reported illness for males was a better measure for objective health than for females.


Ultrasound biomicroscopy in the subtypes of primary angle closure glaucoma.
To evaluate the anterior segment parameters in the subtypes of primary angle closure glaucoma (PACG) using ultrasound biomicroscopy. Five groups, each comprising 30 consecutive patients, diagnosed to have subacute PACG, acute PACG, chronic PACG, primary open angle glaucoma (POAG), and healthy controls were included in the present study. All patients underwent slit-lamp biomicroscopy, direct ophthalmoscopy, 90D fundus examination, gonioscopy, applanation tonometry, visual field testing, A-scan biometry, and ultrasound biomicroscopy (UBM). The anterior segment parameters recorded included: trabecular-iris angle, angle opening distance, trabecular ciliary process distance, and the iris thickness among other parameters. On ultrasound biomicroscopy the trabecular iris angle of control and POAG groups was more than all the subtypes of PACG (P < 0.001). The trabecular iris angle of subacute PACG (P < 0.001) and chronic PACG (P = 0.003) was more than acute PACG. Angle opening distance of controls and POAG group was significantly more than acute PACG and chronic PACG (P < 0.001). The trabecular ciliary process distance of POAG group and controls was more than subacute PACG, acute PACG, and chronic PACG. The trabecular ciliary process distance of subacute PACG (P < 0.001) and chronic PACG (P < 0.001) was more than acute PACG. Eyes with acute PACG had the least iris thickness at the three different positions tested. There was a positive correlation between the anterior chamber angle (trabecular iris angle) and the following parameters: trabecular ciliary process distance, angle opening distance, anterior chamber depth, and the axial length (r = 0.57). Eyes with primary angle closure glaucoma have a thinner iris with a shorter trabecular iris angle, angle opening distance, and trabecular ciliary process distance. The eyes with acute primary angle closure glaucoma have the narrowest angle recess.


Helicobacter pylori γ-glutamyl transpeptidase-induced Ca(2+) release via PLC-IP3 receptors in AGS cells.
In our previous study, γ-glutamyl transpeptidase (GGT) isolated from Helicobacter pylori induced apoptosis of AGS cells. Here, we investigate Ca(2+) effects on GGT-induced apoptosis. The GGT transiently and significantly increased intracellular Ca(2+) concentration ([Ca(2+)]i) in AGS cells in a dose-dependent manner (P < 0.05). The GGT-induced Ca(2+) increase resulted from Ca(2+) influx and release through the phospholipase C - inositol 1,4,5-trisphosphate (PLC-IP3) pathway. The GGT-induced apoptosis was significantly reduced by treatment with U73122 (a PLC inhibitor) and xestospongin (an IP3 receptor antagonist) (P < 0.05). These results indicate that GGT could induce apoptosis of AGS cells by high levels of [Ca(2+)]i.


QSAR, docking, ADMET, and system pharmacology studies on tormentic acid derivatives for anticancer activity.
To explore the anticancer compounds from tormentic acid derivatives, a quantitative structure-activity relationship (QSAR) model was developed by the multiple linear regression methods. The developed QSAR model yielded a high activity-descriptors relationship accuracy of 94% referred by regression coefficient (r2 = .94) and a high activity prediction accuracy of 91%. The QSAR study indicates that chemical descriptors, chiV5, T_T_Cl_7, T_2_T_4, SsCH3count, and Epsilon3 are significantly correlated with anticancer activity. This validated model was further been used for virtual screening and thus identification of new potential breast cancer inhibitors. Lipinski's rule of five, ADMET risk and synthetic accessibility are used to filter false positive hits. Filtered compounds were then docked to identify the possible target binding pocket, to obtain a set of aligned ligand poses and to prioritize the predicted active compounds. The scrutinized compounds, as well as their metabolites, were predicted and analyzed for different pharmacokinetics parameters such as absorption, distribution, metabolism, excretion, and toxicity. Finally, the top-ranked compound NB-12 was evaluated by system pharmacology approach. Later studied the metabolic networks, disease biomarker networks, pathway maps, drug-target networks and generate significant gene networks. The strategy applied in this research work may act as a framework for rational design of potential anticancer drugs.


Organotin compounds: toxicokinetic aspects.
Organotin compounds have a broad range of applications. While dialkyltin compounds are used primarily as stabilizers for plastics, trisubstituted organotins are mainly used as biocides e.g., as an active ingredient of marine antifouling paints for boats and ships. Since a number of organotin compounds have been demonstrated to be toxic, there is increasing concern that their widespread use may cause adverse effects within environmental and biological systems. Besides carcinogenic and neurotoxic effects, as well as effects on the reproductive system, the most obvious mammalian effects of both various di- and trisubstituted organotins were found on the immune system. Exposure of humans to organotin compounds can take place through consumption of contaminated fish and seafood. In human liver samples, mainly dibutyltin, the metabolite of tributyltin, could be detected indicating that organotin compounds are bioavailable after dietary exposure. The objective of this short review is to present various toxicokinetic aspects of organotin compounds in more detail. While several studies using in vitro systems investigated their metabolism especially by the monooxygenase system, various aspects of absorption, distribution, metabolism, and excretion (ADME) pathways of different organotin compounds were described by data obtained from several studies with laboratory animals. However, most of these studies were not conducted as full ADME studies but dealt only with some of these aspects. Therefore, for definitive conclusions in some cases, additional information is requested. By reviewing and updating the current literature consideration was given preferentially to those organotin compounds which have relevance with respect to human exposure and/or toxicological effects.