A review of evidence for transmission of HIV from children to breastfeeding women and implications for prevention.
Child-to-breastfeeding woman transmission (CBWT) of HIV occurs when an HIV-infected infant transmits the virus to an HIV-uninfected woman through breastfeeding. Transmission likely occurs as a result of breastfeeding contact during a period of epithelial disruption, such as maternal skin fissures and/or infant stomatitis. Despite extensive epidemiologic and phylogenetic evidence, however, CBWT of HIV continues to be overlooked. This article summarizes the available evidence for CBWT from nosocomial outbreaks, during which nosocomially HIV-infected infants transmitted the virus to their mothers through breastfeeding. This article also explores the CBWT risk associated with HIV-infected orphans and their female caretakers, and the lack of guidance regarding CBWT prevention in infant feeding recommendations. We searched online databases including PubMed and ScienceDirect for English language articles published from January 1975 to January 2011 using the search terms "HIV," "perinatal," "child-to-mother" and "breastfeeding." The citations from all selected articles were reviewed for additional studies. We identified 5 studies documenting cases of CBWT. Two studies contained data on the number of HIV-infected women, as well as the proportion breastfeeding. Rates of CBWT ranged from 40% to 60% among women reporting breastfeeding after their infants were infected. Poor infection control practices, especially in areas of high HIV prevalence, have resulted in pediatric HIV infections and put breastfeeding women at risk for CBWT. Current infant feeding guidelines and HIV prevention messages do not address CBWT, and fail to provide strategies to help women reduce their risk of acquiring HIV during breastfeeding.


Immunomodulatory agents in myelofibrosis.
The treatment options for patients with myelofibrosis (MF) remain limited. Anemia, thrombocytopenia, extramedullary hematopoiesis, constitutional symptoms, and disease progression are the primary causes of morbidity and mortality. Traditional non-transplant therapies remain non-curative. Moreover, in the JAK2 inhibitor era, no single pharmacologic agent has been shown to improve all MF-related clinical manifestations. Immunomodulatory agents (IMiDs), such as thalidomide and lenalidomide, have been useful in the treatment of some MF patients while newer IMiDs such as pomalidomide are showing promise in MF. This review focuses on the biologic rationales of IMiDs and the clinical results supporting their use in MF. It includes data on the new IMiD, pomalidomide and also explores the possible utility of combining IMiDs with other agents. A PubMed search of articles related to IMiDs and myelofibrosis were conducted. Relevant studies and clinical studies with sample size of > 15 were included. In the JAK2 inhibitor era, IMiDs are alternative treatments in managing splenomegaly and constitutional symptoms. They remain useful in the treatment of cytopenias. Pomalidomide's good anemia response may lead to its inclusion as one of the frontline anemia therapies in MF. Molecular biomarkers may allow us to identify patients who will respond to IMiDs.


Risk factors for body dissatisfaction in adolescent boys and girls: a prospective study.
Despite evidence that body dissatisfaction predicts the onset of eating pathology and depression, few prospective studies have investigated predictors of body dissatisfaction. We examined risk factors for body dissatisfaction using prospective data from 531 adolescent boys and girls. Elevations in body mass, negative affect, and perceived pressure to be thin from peers, but not thin-ideal internalization, social support deficits, or perceived pressure to be thin from family, dating partners, or media, predicted increases in body dissatisfaction. Gender moderated the effect of body mass on body dissatisfaction and revealed a significant quadratic component for boys, but not girls. Gender also moderated negative affect. Results support the assertion that certain sociocultural, biologic, and interpersonal factors increase the risk for body dissatisfaction, but differ for boys and girls. Results provided little support for other accepted risk factors for body dissatisfaction.


Review of the GAS3 Family of Proteins and their Relevance to Cancer.
The GAS3 family of tetraspan proteins has recently been implicated in the progression of cancer. Currently, six members of the GAS3 family have been identified in humans and mice, and while their expressions in disease vary, data suggest that they play a role in epithelial cell structure and function. In this review, we highlight the studies implicating four of the members in disease pathogenesis as well as probe the structural similarities between the family members. Finally, the impact of targeting select members of the family such as PMP22 and EMP2 is discussed.


[Cystic papillary tumors of the pancreas: 3 new cases].
Three cases of papillary cystic tumor of the pancreas (PCTP) are described. They were observed in two female patients aged 42 and 39, and in a male patient aged 55. A fine-needle ultrasound-guided aspiration biopsy was performed in the man. The cytologic and histologic features turned out to be diagnostic and in compliance with literature data. In the three cases immunohistochemical analyses showed positive reaction to vimentin and alpha-1-antitrypsin. Two cases expressed neuron-specific enolase. Ultrastructural examination revealed similarities between neoplastic cells and normal centroacinar cells of the pancreas. Flow cytometric study revealed a diploid G0/1 peak in two cases. The patients underwent wide surgical excision of the neoplasia. No recurrences or metastases are found with follow-up of 10 years, 8 years and 10 month respectively.


A de novo dual-targeting supramolecular self-assembly peptide against pulmonary metastasis of melanoma.
Despite recent advances in treatment, overall survival rates for metastatic melanoma, especially those that invade the lungs, continue to be low, with 5-year survival rates of only 3% to 5%. It was recently discovered that Wnt/β-catenin signaling pathways and MAPK/ERK signaling pathways are involved in melanoma metastasis. Methods: Herein, a bifunctional supramolecular peptide termed HBBplus@CA was constructed by a self-assembling RGD-modified MAPK/ERK peptide inhibitor (HBBplus) and a small molecule catenin inhibitor (carnosic acid (CA)). Results: Expectedly, the HBBplus@CA could internalize melanoma cells, accumulate in the tumor-bearing lung, and be biosafe. As designed, HBBplus@CA simultaneously suppressed both Wnt/β-catenin and MAPK/ERK signaling pathways and suppressed melanoma cell proliferation, migration, and invasion in more action than CA or HBBplus monotherapy. More importantly, HBBplus@CA demonstrated potent inhibition of lung metastasis in mice bearing metastatic melanoma of B16F10 and significantly prolonged their survival. Conclusion: In summary, a supramolecular peptide-based strategy was not only developed to suppress pulmonary metastasis of melanoma, but it also renewed efforts to identify cocktail drugs that act on intracellular targets in various human diseases, including cancer.


[Conservative treatment of fractures of the scaphoid bone--indications].
Healing-up of the bone is achieved by immobilization in 96 to 98% of all recent scaphoid fractures. The average immobilization period is eleven weeks. Different methods of immobilization are used. The majority of authors apply an upper arm plaster cast including the thumb for a period of six weeks and then a forearm plaster cast. Even fractures showing a delayed healingup of the bone can be cured in more than two thirds of the cases by prolonged immobilization. In case of dislocated and not reducible fractures as well as fractures with great fragment diastases, conservative treatment with a fist plaster cast should only be performed exceptionally, for example if there is an increased anesthesia risk. In case of negative X-ray findings (four planes) and only clinical suspicion of scaphoid fracture, an initial fracture therapy is recommended with repeated X-ray examination 14 days later. Most of the fractures which have not healed up are vertical oblique fractures within the proximal third, fractures with great diastases, or fractures which have not been immobilized long enough.


The intravenous pyelogram in acute pyelonephritis.
In a cohort of 67 otherwise healthy patients with acute pyelonephritis that was severe enough to warrant hospitalization and uroradiography, 8% had a genitourinary abnormality that influenced management. Consequently, over 90% of patients had studies that did not alter their care. In an attempt to identify clinical clues that might increase specificity without compromising sensitivity of the intravenous pyelogram in acute pyelonephritis, only the fever curve was statistically useful. Confined to patients who were febrile through 72 hours of appropriate antibiotic treatment, the yield of urography in demonstrating anomalies of immediate clinical significance rose from 8% to 36%. The likelihood of an acutely important abnormality was also increased fivefold in both diabetic patients and patients with a urinary pathogen other than ampicillin-sensitive Escherichia coli, but small numbers precluded statistical significance. Bacteremia was common (27%), but not helpful other than in confirming the microbiological diagnosis. Nonacute structural abnormalities were present in 43% of the patients, three to nine times more frequently than in reported cases without upper tract infection.


Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.
Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability. We therefore carried out a genome-wide association study of AMD in the UK population with 893 cases of advanced AMD and 2199 controls. This showed an association with the well-established AMD risk loci ARMS2 (age-related maculopathy susceptibility 2)-HTRA1 (HtrA serine peptidase 1) (P =2.7 × 10(-72)), CFH (complement factor H) (P =2.3 × 10(-47)), C2 (complement component 2)-CFB (complement factor B) (P =5.2 × 10(-9)), C3 (complement component 3) (P =2.2 × 10(-3)) and CFI (P =3.6 × 10(-3)) and with more recently reported risk loci at VEGFA (P =1.2 × 10(-3)) and LIPC (hepatic lipase) (P =0.04). Using a replication sample of 1411 advanced AMD cases and 1431 examined controls, we confirmed a novel association between AMD and single-nucleotide polymorphisms on chromosome 6p21.3 at TNXB (tenascin XB)-FKBPL (FK506 binding protein like) [rs12153855/rs9391734; discovery P =4.3 × 10(-7), replication P =3.0 × 10(-4), combined P =1.3 × 10(-9), odds ratio (OR) = 1.4, 95% confidence interval (CI) = 1.3-1.6] and the neighbouring gene NOTCH4 (Notch 4) (rs2071277; discovery P =3.2 × 10(-8), replication P =3.8 × 10(-5), combined P =2.0 × 10(-11), OR = 1.3, 95% CI = 1.2-1.4). These associations remained significant in conditional analyses which included the adjacent C2-CFB locus. TNXB, FKBPL and NOTCH4 are all plausible AMD susceptibility genes, but further research will be needed to identify the causal variants and determine whether any of these genes are involved in the pathogenesis of AMD.


[Cerebral blood flow in patients with thalamic hemorrhage (Part 2): Etiological analysis of decreased cerebral blood flow in acute stage].
In twenty-nine patients with thalamic hemorrhage, single photon emission CT (SPECT) and CT were performed in the acute stage. Measurement of cerebral blood flow (CBF) was performed by the 133-Xe inhalation method using SPECT (Tomomatic 64). CT findings such as hematoma volume, involvement of internal capsule, ventricular hematoma and topographical localization of hematoma were investigated. We studied etiological analysis of decreased CBF in the acute stage. CBF values in the group of large-volume hematoma (greater than or equal to 10 ml) decreased moderately on the hematoma side and mildly on the nonhematoma side. CBF values in the group of small-volume hematoma (less than 10 ml) decreased mildly on the hematoma side but didn't decrease on the nonhematoma side. CBF values of the former on the hematoma side decreased significantly compared with the latter. Linear correlation between hematoma volume and CBF was significant. As to topographical localization, CBF values of the group which involved medial thalamus decreased significantly compared with the other group. Factors of involvement of internal capsule and ventricular hematoma didn't affect CBF values. In conclusion, major factors which affected decreased CBF in the acute stage were hematoma volume and tomographical localization.


Endoscopic Sphincterotomy Using the Rendezvous Technique for Choledocholithiasis during Laparoscopic Cholecystectomy: A Case Report.
A 50-year-old male was examined at another hospital for fever, general fatigue and slight abdominal pain. He was treated with antibiotics and observed. However, his symptoms did not lessen, and laboratory tests revealed liver dysfunction, jaundice and an increased inflammatory response. He was then admitted to our hospital and underwent an abdominal computed tomography scan and magnetic resonance cholangiopancreatography (MRCP), which revealed common bile duct (CBD) stones. He was diagnosed with mild acute cholangitis. As the same time, he was admitted to our hospital and an emergency endoscopic retrograde cholangiopancreatography was performed. Vater papilla opening in the third portion of the duodenum and presence of a peripapillary duodenal diverticulum made it difficult to perform cannulation of the CBD. In addition, MRCP revealed that the CBD was extremely narrow (diameter 5 mm). We therefore performed laparoscopic cholecystectomy and endoscopic sphincterotomy using the rendezvous technique for choledocholithiasis simultaneously rather than laparoscopic CBD exploration. After the operation, the patient was discharged with no complications. Although the rendezvous technique has not been very commonly used because several experts in the technique and a large operating room are required, this technique is a very attractive and effective approach for treating choledocholithiasis, for which endoscopic treatment is difficult.


TEM observation and study of three-layer Al2O3/ZrO2 ceramics.
The micrograph and the crystal orientation relationship of Al2O3/ZrO2 laminated ceramics were studied with the help of transmission electronic microscope (TEM). The experiment results showed that: the Al2O3 and ZrO2 grain sizes were small and the links among the crystals were good. No flaws such as pores or micro-cracks were observed in the micro-structure. Further TEM analyses and electronic diffraction spot calculation proved that interface compressive stress could greatly restrain the transformation of the tetragonal phase and increase the contents of transformable tetragon, but did not change the orientation relation between the tetragonal and monoclinic phase, while (100),m//(010), still exist in the three-layer ZrO2 ceramics.


Evolution of viral DNA-dependent DNA polymerases.
DNA viruses as their host cells require a DNA-dependent DNA polymerase (Pol) to faithfully replicate their genomic information. Large eukaryotic DNA viruses as well as bacterial viruses encode a specific Pol equipped with a proofreading 3'-5'-exonuclease, and other replication proteins. All known viral Pol belong to family A and family B Pol. Common to all viral Pol is the conservation of the 3'-5'-exonuclease domain manifested by the three sequence motifs Exo I, Exo II, and Exo III. The polymerase domain of family A and B Pol is clearly distinguishable. Family A Pol share 9 distinct consensus sequences, only two of them are convincingly homologous to sequence motif B of family B Pol. The putative sequence motifs A, B, and C of the polymerase domain are located near the C-terminus in family A Pol and more central in family B Pol. Thus, family A Pol show a significant greater spacing between the Exo III motif and the Pol motif A that is especially extended in the case of the mitochondrial Pol gamma. From each host and virus family whenever possible the consensus sequences of two distantly related polymerase species were aligned for assessment of phylogenetic trees, using both maximum parsimony and distance methods, and evaluated by bootstrap analysis. Three alternative methods yielded trees with identical major groupings. A subdivision of viral family B Pol was achieved resulting in a branch with Pol carrying out a protein-primed mechanism of DNA replication, including adenoviruses, bacteriophages and linear plasmids of plant and fungal origin. Archaebacterial Pol and cellular Pol epsilon were consistently found at the base of this branch. Another major branch comprised alpha- and delta-like viral Pol from mammalian herpesviruses, fish lymphocystis disease virus, insect ascovirus, and chlorella virus. Due to a lower branch integrity Pol of T-even bacteriophages, poxviruses, African swine fever virus, fish herpesvirus, and baculoviruses were not clearly resolved and placed in alternate groupings. A composite and rooted tree of family A and B Pol shows that viral Pol with a protein-priming requirement represent the oldest viral Pol species suggesting that the protein-primed mechanism is one of the earliest modes of viral DNA replication.


Performance Prediction of Fundamental Transcriptional Programs.
Transcriptional programming leverages systems of engineered transcription factors to impart decision-making (e.g., Boolean logic) in chassis cells. The number of components used to construct said decision-making systems is rapidly increasing, making an exhaustive experimental evaluation of iterations of biological circuits impractical. Accordingly, we posited that a predictive tool is needed to guide and accelerate the design of transcriptional programs. The work described here involves the development and experimental characterization of a large collection of network-capable single-INPUT logical operations─i.e., engineered BUFFER (repressor) and engineered NOT (antirepressor) logical operations. Using this single-INPUT data and developed metrology, we were able to model and predict the performances of all fundamental two-INPUT compressed logical operations (i.e., compressed AND gates and compressed NOR gates). In addition, we were able to model and predict the performance of compressed mixed phenotype logical operations (A NIMPLY B gates and complementary B NIMPLY A gates). These results demonstrate that single-INPUT data is sufficient to accurately predict both the qualitative and quantitative performance of a complex circuit. Accordingly, this work has set the stage for the predictive design of transcriptional programs of greater complexity.


Indirect chiral separation of new recreational drugs by gas chromatography-mass spectrometry using trifluoroacetyl-L-prolyl chloride as chiral derivatization reagent.
New recreational drugs such as amphetamine-, cathinone, and benzofury derivatives gained high popularity on the drug market in recent years. They can be purchased via the Internet from different providers and online portals. Most of these compounds are chiral, which makes the development of chiral separation methods necessary. Besides this, it is useful to find out if the compounds were sold as racemic mixtures. Also, it is important to check whether the new psychoactive compounds contain further ingredients or impurities. The aim of this research was the continuation of the application of a method for indirect chiral separation of 24 new psychoactive compounds recently purchased via the Internet. After derivatization with the chiral derivatization reagent trifluoroacetyl-L-prolyl chloride, chromatographic separation of diastereomers was achieved using a 30 m HP5-MS capillary column. As carrier gas, helium was used with a constant flow of 1.0 ml/min. Three different column temperature programs were tested. Under optimum conditions 13 out of 24 compounds were successfully resolved into their enantiomers obtaining Rs values up to 7.0. The use of a single quadrupole mass spectrometer as the detector allowed the identification of the compounds in multicomponent samples.


Transmission roles of symptomatic and asymptomatic COVID-19 cases: a modelling study.
Coronavirus disease 2019 (COVID-19) asymptomatic cases are hard to identify, impeding transmissibility estimation. The value of COVID-19 transmissibility is worth further elucidation for key assumptions in further modelling studies. Through a population-based surveillance network, we collected data on 1342 confirmed cases with a 90-days follow-up for all asymptomatic cases. An age-stratified compartmental model containing contact information was built to estimate the transmissibility of symptomatic and asymptomatic COVID-19 cases. The difference in transmissibility of a symptomatic and asymptomatic case depended on age and was most distinct for the middle-age groups. The asymptomatic cases had a 66.7% lower transmissibility rate than symptomatic cases, and 74.1% (95% CI 65.9-80.7) of all asymptomatic cases were missed in detection. The average proportion of asymptomatic cases was 28.2% (95% CI 23.0-34.6). Simulation demonstrated that the burden of asymptomatic transmission increased as the epidemic continued and could potentially dominate total transmission. The transmissibility of asymptomatic COVID-19 cases is high and asymptomatic COVID-19 cases play a significant role in outbreaks.


Phase-locked generation and field-resolved detection of widely tunable terahertz pulses with amplitudes exceeding 100 MV/cm.
Phase-locked terahertz transients with peak electric fields of 108 MV/cm and center frequencies continuously tunable from 10 to 72 THz are generated via difference-frequency mixing of two parametrically amplified pulse trains from a single white-light seed. Free space electro-optic sampling with 8 fs gating pulses from a two-branch Er:fiber laser allows us to monitor all transients directly in the time domain. We identify extreme terahertz nonlinearities in the detector crystal with subcycle resolution.


Animal models for disc degeneration-an update.
Intervertebral disc degeneration is considered a major cause of back pain that places a heavy burden on society, both because of its effect on the physiology of individuals and its consequences on the world economy. During the past few decades, research findings in the pre-clinical setting have led to a significant increase in the understanding of intervertebral disc degeneration, although many aspects of the disease remain unclear. The goal of this review is to summarize existing animal models for disc degeneration studies and the difficulties that are associated with the use of such models. A firm understanding of the cellular and molecular events that ensue as a result of injuries, as well as environmental factors, could be instrumental in the development of targeted therapies for the treatment of intervertebral disc degeneration.


Efficacy of chitosan oligosaccharide as aquatic adjuvant administrated with a formalin-inactivated Vibrio anguillarum vaccine.
Vaccine is one of the efficient candidates to prevent fish disease through activating host immune response in aquaculture. Actually, several vaccines are often administered with adjuvants to increase immunostimulation, especially for some water-based formalin-killed vaccines. However, side effects are inevitable after vaccination of some adjuvants. Therefore, exploration for effective and harmless aquatic adjuvants is urgently needed. In this study, immunoprotection of a formalin-inactivated Vibrio anguillarum vaccine applied with chitosan oligosaccharide (COS) was analyzed. High levels of protection were achieved in zebrafish and turbot vaccinated with inactivated vaccine and COS (RPS of 89.0 ± 4.5% and 80.0 ± 6.9%) compared with fish vaccinated with inactivated vaccine alone (RPS of 47.8 ± 6.6% and 64.7 ± 5.8%) at 4 week post vaccination. Moreover, high antibody reaction and cross-protection against Vibrio alginolyticus and Vibrio harveyi were observed of turbot vaccinated with inactivated vaccine and COS. In conclusion, COS can enhance immunoprotection of a formalin-inactivated V. anguillarum vaccine, significantly activate humoral immune response of host, and be benefit for inhibition against pathogens. Therefore, COS would be a potential adjuvant for aquatic vaccine design in the future.


Short-term experience with a new absorbable composite cage (β-tricalcium phosphate-polylactic acid) in patients after stand-alone anterior cervical discectomy and fusion.
Prospective clinical single center series with 50 patients to include, with planned follow-up intervals at 3 and 12 months postoperative. Absorbable cages were developed with the purpose to enhance fusion rates and to reduce the rate of cage subsidence. The gradual increase of load transfer during cage degradation facilitates new bone formation, which possibly leads to higher arthrodesis rates. Absorbable cages consisting of a mixture of polylactic and polyglycolic acid (PLLA-PGLA) or poly (L-lactide-co-D, L-lactide) experimentally showed disappointing results with formation of cartilage and fibrous tissue components, which was much less pronounced using composite cages consisting of a polymer and calciumphosphate. Patients showing degenerative cervical mono- or bi-level pathology were prospectively included. Using anteroposterior and lateral radiographs, segmental height of the treated segments was determined quantitatively. Cage characteristics were described qualitatively. Clinical data such as the Neck Disability Index, pain severity on the visual analogue scale were collected at all time points separately for neck and arm. A total of 33 patients were included, with a mean age of 51.9 ± 9 years. As cage dislocations occurred in 4 out of 33 patients (12.1%), the study was prematurely discontinued. All patients with cage dislocations were surgically revised. Clinical outcome of the remaining patients showed significant improvement of visual analogue scale neck pain from 6.0 ± 2.5 to 2.8 ± 2.3 (P < 0.005), visual analogue scale arm pain from 5.3 ± 2.7 to 1.6 ± 1.6 (P < 0.005), and Neck Disability Index from 21.2 ± 8.6 to 12.5 ± 9.6 (P < 0.005) after surgery. Because of the high rate of cage dislocations, the use of the present composite cage cannot be recommended as a stand-alone device unless implant fixation will not be improved significantly. Evaluation of clinical and radiological long-term effects is essential to estimate the potential benefit of composite cages. 2.


Rapid Review to Inform the Rehabilitation and Reintegration of Child Returnees from the Islamic State.
An estimated 49,000 women and children who lived in the Islamic State are being held in the Al-Hol refugee camp in Syria. Several countries have repatriated some of these women and children, though most have thus far refused to do so. Many countries are asking whether it is possible to successfully rehabilitate and reintegrate this group and how the evidence base could inform their approach. The overall objective of this paper is to inform the rehabilitation and reintegration of child returnees from the Islamic State by rapidly reviewing the evidence on children exposed to trauma and adversity. A rapid review was conducted to identify pertinent evidence regarding outcomes, risk and protective factors, and interventions and to build a framework that could guide policies and practices. Prior work in the areas of refugee children, war-impacted children, child criminal gang members, child victims of maltreatment, and child victims of sex trafficking was reviewed. Evidence was collected and analyzed from 31 prior reviews and studies. The Rehabilitation and Reintegration Intervention Framework (RRIF) incorporates five levels (individual, family, educational, community, and societal) and identifies five primary goals: 1) promoting individual mental health and well-being; 2) promoting family support; 3) promoting educational success; 4) promoting community support; and 5) improving structural conditions and protecting public safety. Implementing this framework requires public-private partnership with extensive civil society involvement. Rehabilitation and reintegration programs should be based on the evidence of prior work with children exposed to trauma and adversity. RRIF defines a multi-level approach that encompasses promoting individual mental health and well-being, family support, educational success, community support, structural conditions, and public safety. Further multi-disciplinary research is needed to develop evidence in several identified areas concerning child health and developmental problems, family custody, faith and religiosity, and violent extremism assessment and prevention.


Light-emitting-diode induced retinal damage and its wavelength dependency in vivo.
To examine light-emitting-diode (LED)-induced retinal neuronal cell damage and its wavelength-driven pathogenic mechanisms. Sprague-Dawley rats were exposed to blue LEDs (460 nm), green LEDs (530 nm), and red LEDs (620 nm). Electroretinography (ERG), Hematoxylin and eosin (H&E) staining, transmission electron microscopy (TEM), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), and immunohistochemical (IHC) staining, Western blotting (WB) and the detection of superoxide anion (O2-·), hydrogen peroxide (H2O2), total iron, and ferric (Fe3+) levels were applied. ERG results showed the blue LED group induced more functional damage than that of green or red LED groups. H&E staining, TUNEL, IHC, and TEM revealed apoptosis and necrosis of photoreceptors and RPE, which indicated blue LED also induced more photochemical injury. Free radical production and iron-related molecular marker expressions demonstrated that oxidative stress and iron-overload were associated with retinal injury. WB assays correspondingly showed that defense gene expression was up-regulated after the LED light exposure with a wavelength dependency. The study results indicate that LED blue-light exposure poses a great risk of retinal injury in awake, task-oriented rod-dominant animals. The wavelength-dependent effect should be considered carefully when switching to LED lighting applications.


Adjunctive antimicrobial photodynamic treatment of experimentally induced periodontitis in rats with ovariectomy.
The aim of this study is to compare antimicrobial photodynamic therapy (aPDT) as an adjunctive therapy to scaling and root planing (SRP) for the treatment of experimentally induced periodontitis in rats with ovariectomy (OVX) that are or are not treated with estrogen replacement. A total of 270 female rats were divided into three groups: 1) normal rats; 2) rats with OVX; and 3) rats with OVX with estrogen replacement. Periodontal disease was induced through the introduction of a cotton thread around the mandibular left first molar. After 7 days, the ligature was removed, and the rats were randomly divided into the following treatment groups: 1) SRP plus saline solution; 2) SRP plus low-level laser therapy (LLLT); and 3) SRP plus toluidine blue O irrigation followed by LLLT. Ten rats from each group were euthanized at days 7, 15, and 30 after dental treatment. Bone loss (BL) in the furcation region was evaluated using histometric and immunohistochemical analyses. aPDT treatment resulted in reduced BL compared with SRP treatment at all time points. Additionally, rats treated with aPDT exhibited reduced numbers of tartrate-resistant acid-phosphatase-positive cells and more proliferating cell nuclear antigen-positive cells in all treatment groups regardless of estrogen status. Whereas rats treated with aPDT showed weak immunoreactivity to the receptor activator of nuclear factor-κ B ligand at day 7 post-treatment, strong osteoprotegerin immunoreactivity was observed at day 15 post-treatment. aPDT is an effective adjunctive therapy for the treatment of periodontitis in rats with OVX that are or are not given estrogen replacement therapy.


[Effect of Moxibustion on Delayed Memory and Expression of Hippocampal Nestin and Doublecortin Proteins in Dementia Rats].
To observe the effect of "Huayu Tongluo"(Blood-stasis Dispersing and Meridian-collateral Dredging) moxibustion on the delayed memory and expression of Nestin and Doublecortin (DCX) proteins in the hippocampus in vascular dementia (VD) rats in the view of neurogenesis produced by intracerebral transplantation of neural stem cells (NSCs) and endothelial progenitor cells (EPCs). Healthy male Wistar rats were randomized into control group, VD model group,NSCs+EPCs group and NSCs+EPCs moxibustion group. The VD model was established by using a modified 2-vessels occlusion method, and neurogenesis was produced by transplantation of NSCs+EPCs (2×106cell/10 µL) into the lateral ventricle for rats of the NSCs+EPCs groups 3 days after successful VD-modeling. Moxibustion was applied to "Dazhui" (GV 14), "Baihui" (GV 20) and "Shenting" (GV 24) once daily for 21 days with an interval of one day between every two 7 days. The Morris Water Maze was used to test the rat's delayed memory ability before and 24 h after the treatment. The expression of Nestin and DCX proteins in the hippocampus tissues was detected using double-labeled immunofluorescence technique. Following modeling, Morris Water Maze tests showed that the average escape latency of location navigation task was significantly prolonged in VD rats(P<0.008)and the times of target platform crossing (spatial probing task) within 120 s were remarkably reduced in VD rats (P<0.008). Compared with pre-treatment in the same one group, the escape latency of NSCs+EPCs and NSCs+EPCs moxibustion groups were considerably reduced (P<0.05), and the average times of target platform crossing of the NSCs+EPCs moxibustion group were markedly increased(P<0.05). The effect of NSCs+EPCs moxibustion was evidently superior to that of simple NSCs+EPCs in shortening the escape latency (P<0.008). The expression levels of Nestin protein were significantly higher in the NSCs+EPCs moxibustion group after 1 and 3 period treatment than those in the NSCs+EPCs group (P<0.05).. Moxibustion intervention is able to improve the delayed memory in VD rats, which may be related to its effect in up-regulating the expression of hippocampal Nestin and DCX proteins within 15 days via accelerating neurogenesis.


HIGH-DIMENSIONAL FACTOR REGRESSION FOR HETEROGENEOUS SUBPOPULATIONS.
In modern scientific research, data heterogeneity is commonly observed owing to the abundance of complex data. We propose a factor regression model for data with heterogeneous subpopulations. The proposed model can be represented as a decomposition of heterogeneous and homogeneous terms. The heterogeneous term is driven by latent factors in different subpopulations. The homogeneous term captures common variation in the covariates and shares common regression coefficients across subpopulations. Our proposed model attains a good balance between a global model and a group-specific model. The global model ignores the data heterogeneity, while the group-specific model fits each subgroup separately. We prove the estimation and prediction consistency for our proposed estimators, and show that it has better convergence rates than those of the group-specific and global models. We show that the extra cost of estimating latent factors is asymptotically negligible and the minimax rate is still attainable. We further demonstrate the robustness of our proposed method by studying its prediction error under a mis-specified group-specific model. Finally, we conduct simulation studies and analyze a data set from the Alzheimer's Disease Neuroimaging Initiative and an aggregated microarray data set to further demonstrate the competitiveness and interpretability of our proposed factor regression model.


Structures of ternary complexes of aspartate-semialdehyde dehydrogenase (Rv3708c) from Mycobacterium tuberculosis H37Rv.
Aspartate-semialdehyde dehydrogenase (Asd; ASADH; EC 18.104.22.168) is the enzyme that lies at the first branch point in the biosynthetic pathway of important amino acids including lysine and methionine and the cell-wall component diaminopimelate (DAP). The enzymatic reaction of ASADH is the reductive dephosphorylation of aspartyl-β-phosphate (ABP) to aspartate β-semialdehyde (ASA). Since the aspartate pathway is absolutely essential for the survival of many microbes and is absent in humans, the enzymes involved in this pathway can be considered to be potential antibacterial drug targets. In this work, the structure of ASADH from Mycobacterium tuberculosis H37Rv (Mtb-ASADH) has been determined in complex with glycerol and sulfate at 2.18 Å resolution and in complex with S-methyl-L-cysteine sulfoxide (SMCS) and sulfate at 1.95 Å resolution. The overall structure of Mtb-ASADH is similar to those of its orthologues. However, in the Mtb-ASADH-glycerol complex structure the glycerol molecule is noncovalently bound to the active-site residue Cys130, while in the Mtb-ASADH-SMCS complex structure the SMCS (Cys) is covalently linked to Cys130. The Mtb-ASADH-SMCS complex structurally mimics one of the intermediate steps in the proposed mechanism of ASADH enzyme catalysis. Comparison of the two complex structures revealed that the amino acids Glu224 and Arg249 undergo conformational changes upon binding of glycerol. Moreover, the structures reported here may help in the development of species-specific antibacterial drug molecules against human pathogens.


[On the nervous system of a parasitic cnidarian Polypodium hydriforme].
Nerve cells in a parasitic cnidarian Polypodium hydriforme at the parasitic and free-living stages of the life cycle have been localized immunocytochemically using antibodies to FMRF-amide, and their ultrastructure has been described. Ganglion cells form a net under epidermis consisting of bi- and tripolar neurons which cross the mesoglea and usually contact muscle cells and cnidocytes. Fusiform sensory and neurosecretory cells, especially characteristic to sensory tentacles, are interspersed among epidermal cells. All three types of nerve cells have dense cored vesicles about 80-120 nm in diameter. The sensory cells demonstrate a sensory flagellum-like immobile structure. Neurosecretory and sensory cells form septate junctions with epidermal cells. Ganglion cells show gap junctions between them. A centriole encircled by a fragment of nuclear envelope which is a marker of ectodermal lineage cells in Polypodium has been described in the cytoplasm of a sensory cell, thus proving the ectodermal nature of the nervous system.


Bioinformatics Analysis Combined With Experiments Predicts PUDP as a Potential Prognostic Biomarker for Hepatocellular Carcinoma Through Its Interaction With Tumor Microenvironment.
Hepatocellular carcinoma (HCC) is one of the deadliest tumors in the world and is notorious for poor prognosis. There is mounting evidence that pseudouridine performs key functions in the initiation and progression of several cancers. A previous study demonstrated that Pseudouridine 5'-phosphatase (PUDP) may be a novel prognostic biomarker in colorectal cancer. However, in the past, we have paid little attention to PUDP and we are still not clear about its function and role in cancer. In this study, a pan-cancer analysis of PUDP expression and prognosis was performed firstly using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data and we found that PUDP may be a potential oncogene for HCC. Then the most potential upstream microRNA contributing to PUDP was identified as let-7c-5p through expression analysis, correlation analysis, and survival analysis. Subsequently, the result of single cell RNA sequencing (scRNA-seq) demonstrated that PUDP was significantly highly expressed on malignant cells. In addition, there are significantly positive correlations between PUDP and tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression, especially with tumor-promoting immune cells such as T cell regulatory (Treg), Myeloid-derived suppressor cell (MDSC), cancer-associated fibroblast (CAF). Moreover, we found the methylation level of three loci was positively correlated with PUDP expression and four loci were negatively correlated. 15 pairs of HCC and normal adjacent tissues from HCC patients who were treated at our center were used to verify the results of the bioinformatics analysis and the results of experiments are similar to the bioinformatics analysis. Our study demonstrated that HCC patients with high PUDP expression are less likely to benefit from immunotherapy, and in addition, we explored the relationship between PUDP and anticancer drugs. Finally, we explored the clinical relevance of PUDP, identified PUDP as an independent risk factor for HCC patients and constructed a prognostic model, used International Cancer Genome Consortium (ICGC) data to do external validation. Collectively, our study demonstrated that high expression of PUDP suggested a poor prognosis and low response to immunotherapy, providing new insight into the treatment and prognosis of HCC.


Molecular orientation of ultrahigh molecular weight polyethylene induced by various sliding motions.
Wear and wear debris of ultrahigh molecular weight polyethylene (UHMWPE) in joint replacements have been recognized as one of the major contributors to the failure of orthopedic implants. The detailed wear mechanism of polyethylene under biomechanic motions is not well understood. In simulation wear bench tests, it was found that unidirectional sliding produces the least amount of wear, reciprocating motion increases wear significantly, and cross-shear motion (similar to hip and knee joint motion in the human body) produces the highest amount of wear. Conventional wear theories are inadequate to explain this observation. This study utilizes resonant absorption of linearly polarized soft X-rays at a synchrotron radiation beam line to measure the molecular orientation of a UHMWPE surface layer subjected to different wear motions. Carbon-K-edge partial-electron-yield X-ray absorption measurements were done on the worn UHMWPE samples. X-ray absorption measurements show conclusively that the molecular chains of UHMWPE align preferentially parallel to the direction of sliding. Examination under various wear motions showed that unidirectional shear produced the maximum chain orientation, whereas cross-shear wear motions produced the least amount of orientation. When polymeric chains align, the surface layer tends to be more brittle and hard, thus resisting wear. When they do not align, loose chains may be subjected to both Mode I and Mode II fracture, hence increasing the wear rate. This molecular alignment observation may offer an explanation of why different wear motions have different wear characteristics.


Cloning of the human DOPAchrome tautomerase/tyrosinase-related protein 2 gene and identification of two regulatory regions required for its pigment cell-specific expression.
We have cloned and sequenced the human genomic DNA segments encoding the 5'-flanking region and the first two exons of the DOPAchrome tautomerase (DT)/tyrosinase-related protein 2 (TRP-2) gene. The DT gene is a member of the tyrosinase gene family and specifically expressed in melanin-producing cells. A transcriptional initiation site of the DT gene was identified by S1 nuclease-mapping and primer-extension analyses using RNA prepared from human pigmented melanoma cells. To study the mechanism for pigment cell-specific expression of the human DT gene, we analyzed the promoter function of its 5'-flanking region by transient expression assays. The fusion genes, containing the DT gene promoter upstream from a firefly luciferase reporter gene, were introduced into human pigmented melanoma cells and HeLa cells, and the pigment cell-specific promoter activity was evaluated by comparing the luciferase activity expressed in both cell lines. A series of 5' deletion studies of the human DT gene promoter revealed that the 32-bp element, located between -447 and -415, is sufficient to confer pigment cell-specific expression of a reporter gene on a homologous promoter, but not on a heterologous simian virus 40 promoter. Internal deletion studies using a homologous or a heterologous promoter revealed that the pigment cell-specific expression of a reporter gene mediated by the 32-bp element is dependent on the presence of another region of the DT gene spanning from -268 to -56, which was termed the proximal region. However, the proximal region by itself is not sufficient to confer cell type-specific expression. These results indicate that the presence of two regulatory regions, the 32-bp element and the proximal region, is required for pigment cell-specific expression of the DT gene. Both regulatory regions contain a CANNTG motif, a well known binding site for a large family of transcription factors possessing a basic helix-loop-helix structure.


X-linked dyskeratosis congenita: restrictive pulmonary disease and a novel mutation.
Dyskeratosis congenita (DC) is a rare inherited multisystem disorder characterised by lesions of the skin and appendages. Bone marrow failure occurs in 80% of patients. The gene for the X-linked form of DC has been identified on Xq28 and designated as DKC1. Pulmonary manifestations have rarely been reported. It is not known whether there is a respiratory disease peculiar to these patients and, if so, whether it is associated with a specific genetic mutation. A 40 year old Egyptian man with pulmonary disease and his symptom free 35 year old brother both presented with mucocutaneous lesions characteristic of DC. In the older brother chest imaging revealed generalised intralobular interstitial thickening and honeycombing. Pulmonary function tests showed a restrictive pattern. Open lung biopsy specimens of lung tissue showed various degrees of fibrosis consistent with usual interstitial pneumonia of chronic idiopathic pulmonary fibrosis. The younger brother was free of pulmonary lesions. Both had a novel missense mutation 5C-->T in exon 1 of the DKC1 gene. It is concluded that pulmonary disease in DC may be underestimated, possibly because most patients die at an early age of bone marrow failure. No relationship between genotype and phenotype could be established in the patients studied. The genetic diagnosis of DC is now available, which may enable it to be diagnosed in patients with restrictive pulmonary disease and minimal cutaneous signs.


A blue kidney--chronic renal failure as a consequence of siderosis in paroxysmal nocturnal hemoglobinuria?
Acute renal failure is a known complication during hemolytic crisis in paroxysmal nocturnal hemoglobinuria (PNH). However, chronic renal failure is rare despite the well-known spectacular hemosiderosis of the kidneys due to chronic hemolysis. Here, we report about a 74-year-old man with PNH who developed acute on chronic renal failure after an episode of intercurrent urinary tract infection and subsequent hemolytic crisis. Mild chronic hemolysis, well-documented over the past decade, had long been considered the cause of a constantly declining glomerular filtration rate. Accordingly, magnetic resonance imaging during admission demonstrated marked siderosis of both kidneys, supporting the hypothesis that chronic renal failure (CRF) was likewise related to PNH. However, a renal biopsy revealed acute tubular necrosis and distinct renal siderosis, as expected. Additionally, tubulointerstitial injury and global glomerular sclerosis, best classified as arterionephrosclerosis, were present. In retrospect, these findings were explained by a 15-year history of hypertension and a 4-year medication with cyclosporine. Careful diagnostic workup including a renal biopsy is mandatory, given a misleadingly suggestive correlation between chronic hemolysis and CRF. Chronic renal failure in PNH is a diagnosis of exclusion, even if radiologic evidence of heavy siderosis draws off the physician's attention.


Machine-learning accelerated geometry optimization in molecular simulation.
Geometry optimization is an important part of both computational materials and surface science because it is the path to finding ground state atomic structures and reaction pathways. These properties are used in the estimation of thermodynamic and kinetic properties of molecular and crystal structures. This process is slow at the quantum level of theory because it involves an iterative calculation of forces using quantum chemical codes such as density functional theory (DFT), which are computationally expensive and which limit the speed of the optimization algorithms. It would be highly advantageous to accelerate this process because then one could do either the same amount of work in less time or more work in the same time. In this work, we provide a neural network (NN) ensemble based active learning method to accelerate the local geometry optimization for multiple configurations simultaneously. We illustrate the acceleration on several case studies including bare metal surfaces, surfaces with adsorbates, and nudged elastic band for two reactions. In all cases, the accelerated method requires fewer DFT calculations than the standard method. In addition, we provide an Atomic Simulation Environment (ASE)-optimizer Python package to make the usage of the NN ensemble active learning for geometry optimization easier.


Pleiotropic consequences of metabolic stress for the major histocompatibility complex class II molecule antigen processing and presentation machinery.
Hyperglycemia and hyperlipidemia are often observed in individuals with type II diabetes (T2D) and related mouse models. One dysmetabolic biochemical consequence is the non-enzymatic reaction between sugars, lipids, and proteins, favoring protein glycation, glycoxidation, and lipoxidation. Here, we identified oxidative alterations in key components of the major histocompatibility complex (MHC) class II molecule antigen processing and presentation machinery in vivo under conditions of hyperglycemia-induced metabolic stress. These modifications were linked to epitope-specific changes in endosomal processing efficiency, MHC class II-peptide binding, and DM editing activity. Moreover, we observed some quantitative and qualitative changes in the MHC class II immunopeptidome of Ob/Ob mice on a high-fat diet compared with controls, including changes in the presentation of an apolipoprotein B100 peptide associated previously with T2D and metabolic syndrome-related clinical complications. These findings highlight a link between glycation reactions and altered MHC class II antigen presentation that may contribute to T2D complications.


Renal infection with Mycobacterium chelonei.
A case of renal infection with Mycobacterium chelonei is described. The infection probably occurred via haematogenous spread from an infected arteriovenous shunt in a uraemic woman. Prolonged treatment with intravenous cefoxitin combined with oral erythromycin and rifampicin eradicated the organism from the urine. Although renal function stabilised for one year, gradual deterioration to end-stage renal failure occurred.


Molecular biology and the radiation oncologist.
An overview is provided of several recent advances in our understanding of the molecular events that occur when cells are exposed to ionizing radiation. A basic knowledge of molecular radiobiology is necessary so that the radiation oncologist can (i) screen cancer patients for an abnormally reduced or exaggerated response to radiotherapy; and (ii) devise novel ways to counter the molecular pathways that sustain malignant progression.


Pharmacological Management of Psychiatric Symptoms in Frontotemporal Dementia: A Systematic Review.
Psychiatric symptoms in patients with frontotemporal dementia (FTD) are highly prevalent and may complicate clinical management of these patients. Purpose of the present article is to present and discuss available data about the pharmacological treatment of psychiatric symptoms in patients with FTD. A research in the main database sources has been conducted to obtain an overview of the pharmacological management of psychiatric symptoms in patients with FTD. The search strategy included the following terms-"FTD and psychiatry," "FTD and behavioural disturbances," and "FTD and treatment". Pathophysiology of psychiatric symptoms in FTD is different from other types of dementia. Although drugs for Alzheimer disease appear to be ineffective for the treatment of psychiatric symptoms of FTD, preliminary evidence supports a possible usefulness of serotonergic antidepressants for these patients. Data are too scanty to draw definitive conclusions, but antidepressant treatment, particularly with serotonergic compounds, may improve psychiatric symptoms in patients with FTD. Large observational studies are needed to confirm this preliminary evidence, and a lot of effort and collaboration between neurologists and psychiatrists will be definitely crucial for future research of effective treatments for FTD.


The Lived Experience of Midlife Women With Major Depression.
Midlife, a significant developmental phase for women, is a period of biological, psychological, and social role changes. However, not all women transition smoothly into middle age, with those who experience depression typically bearing significantly greater physical and psychological discomforts in midlife. Despite the expanding body of research on women and depression, little is understood about how depressed women handle the midlife transition. The aim of this study was to gain a deeper understanding about the lived experience of middle-aged women with major depression. This study used a phenomenological design. Four women between 43 and 55 years old with a diagnosis of major depression were interviewed. There were seven transcripts in total. A 62-year-old depressed woman was also interviewed to verify the results. After data analysis, "a harder life" emerged as the core of these women's experiences. Two themes with two respective subthemes were identified. The theme "struggling to redefine the self" was associated with the subthemes "taking pills in the dump" and "the inane life." The theme "swinging to develop new social interactions" was associated with the subthemes "being alienated from former social contacts" and "starting new social interactions." Results indicate that the participants encountered greater challenges in adapting to middle age than their nondepressed peers. Much adaptation and help are needed for depressed women to experience a smooth transition into midlife. In caring for these women, their interpersonal relationships with others should be the main target. Meanwhile, nurses must understand what challenges depressed women typically encounter in midlife based on the developmental perspective and then assess how pharmaceutical treatments impact the view of self of women.


[Prevalence of pressure sores in a university hospital in 2003].
To determine the prevalence of pressure sores in a university hospital and to assess the risk of developing a pressure sore. A one-day survey was performed in all hospitalized patients, day hospital excepted. The Garches scale was used to assess the severity of pressure sores and the Braden scale was used to measure the patient's risk for the development of pressure ulcers. One thousand six hundred and eleven patients were included, mean age was 62+/-23 years and 53.3% were over 65 years old. In hospitalized patients, 64% were in acute care, 29% in intermediate medicine and long-term care and 7% in intensive care units. We have found 675 pressure sores in 268 patients, mean age of 76 years; 263 decubitus ulcers were acquired during hospitalization. The most frequent sites were heels (46%) and sacrum (26%). Stage 1 pressure ulcers showed 33% of the total. The total prevalence was 16.6%, 95% CI (14.9-18.6), the hospital acquired pressure sores prevalence was 7.5%, all stages included. A Braden score less than or equal to 15 was found in 29.1% of hospitalized patients. Standard mattresses were used in 37% of patients with pressure sores. Multivariate analysis showed that age and a Braden score less than or equal to 15 were significantly associated with pressure sores. Pressure sores are still an important problem in hospital; occurrence must be considered as an iatrogenic event and management requires a multidisciplinary approach.


Seasonal associations with urban light pollution for nocturnally migrating bird populations.
The spatial extent and intensity of artificial light at night (ALAN) has increased worldwide through the growth of urban environments. There is evidence that nocturnally migrating birds are attracted to ALAN, and there is evidence that nocturnally migrating bird populations are more likely to occur in urban areas during migration, especially in the autumn. Here, we test if urban sources of ALAN are responsible, at least in part, for these observed urban associations. We use weekly estimates of diurnal occurrence and relative abundance for 40 nocturnally migrating bird species that breed in forested environments in North America to assess how associations with distance to urban areas and ALAN are defined across the annual cycle. Migratory bird populations presented stronger than expected associations with shorter distances to urban areas during migration, and stronger than expected association with higher levels of ALAN outside and especially within urban areas during migration. These patterns were more pronounced during autumn migration, especially within urban areas. Outside of the two migration periods, migratory bird populations presented stronger than expected associations with longer distances to urban areas, especially during the nonbreeding season, and weaker than expected associations with the highest levels of ALAN outside and especially within urban areas. These findings suggest that ALAN is associated with higher levels of diurnal abundance along the boundaries and within the interior of urban areas during migration, especially in the autumn when juveniles are undertaking their first migration journey. These findings support the conclusion that urban sources of ALAN can broadly effect migratory behavior, emphasizing the need to better understand the implications of ALAN for migratory bird populations.


Sources of variability in reflectance measurements on normal cadaver ears.
The development of acoustic reflectance measurements may lead to noninvasive tests that provide information currently unavailable from standard audiometric testing. One factor limiting the development of these tests is that normal-hearing human ears show substantial intersubject variations. This work examines intersubject variability that results from measurement location within the ear canal, estimates of ear-canal area, and variations in middle-ear cavity volume. Energy reflectance (ER) measurements were made on nine human-cadaver ears to study three variables. (1) ER was measured at multiple ear-canal locations. (2) The ear-canal area at each measurement location was measured and the ER was calculated with the measured area, a constant area, and an acoustically estimated area. (3) The ER was measured with the middle-ear cavity in three conditions: (1) normal, (2) the mastoid widely opened (large air space), and (3) the mastoid closed off at the aditus ad antrum (small air space). Measurement-location effects are generally largest at frequencies below about 2000 Hz, where in some ears reflectance magnitudes tend to decrease systematically as the measurement location moves away from the tympanic membrane but in other ears the effects seem minimal. Intrasubject variations in reflectance due to changes in either measurement location within the ear canal or differences in the estimate of the ear-canal area are smaller than variations produced by large variations in middle-ear cavity air volume or intersubject differences. At frequencies below 2000 Hz, large increases in cavity volume systematically reduce the ER, with more variable changes above 2000 Hz. ER measurements depend on all variables studied: measurement location, ear-canal cross-sectional area, and middle-ear cavity volume. Variations within an individual ear in either measurement location or ear-canal cross-sectional area result in relatively small effects on the ER, supporting the notion that diagnostic tests (1) need not control for measurement location and (2) can assume a constant ear-canal area across most subjects. Variations in cavity volume produce much larger effects in ER than measurement location or ear-canal area, possibly explaining some of the intersubject variation in ER reported among normal ears.


Thrombin generation and procoagulant phospholipids in patients with essential thrombocythemia and reactive thrombocytosis.
Thrombocytosis is a commonly encountered clinical scenario and can be either a secondary process (reactive thrombocytosis), or due to clonal disorder (i.e., essential thrombocythemia). This distinction is important as it carries implications for evaluation, prognosis and treatment. In this study we compared procoagulant potential in essential thrombocythemia and reactive thrombocytosis by measuring the thrombin generation and the level of circulating procoagulant phospholipids with functional tests. Twenty nine patients with essential thrombocythemia and 24 with reactive thrombocytosis were studied. Thrombin generation was determined by calibrated automated thrombography. Procoagulant phospholipids were detected by a chronometric standardised method (STA-Procoag-PPL). Patients with reactive thrombocytosis had a longer lag time, higher endogenous thrombin potential, peak of thrombin generation and velocity index than patients with essential thrombocythemia. The level of circulating procoagulant phospholipids was increased in patients with essential thrombocythemia as observed with the procoagulant phospholipids assay. Each parameter was analysed using ROC curves. Highest areas under the curve (AUC) were found for lag time and procoagulant phospholipids ratio (0.817 and 0.853, respectively), associated with high negative predictive value for ET (92.3% and 80%, respectively). In conclusion, patients with essential thrombocythemia and reactive thrombocytosis displayed significant differences in terms of thrombin generation and levels of procoagulant phospholipids. Among these parameters, lag time and procoagulant phospholipids ratio could help to differentiate between reactive thrombocytosis and essential thrombocythemia patients.


Disentangling above- and below-ground facilitation drivers in arid environments: the role of soil microorganisms, soil properties and microhabitat.
Nurse plants promote establishment of other plant species by buffering climate extremes and improving soil properties. Soil biota plays an important role, but an analysis to disentangle the effects of soil microorganisms, soil properties and microclimate on facilitation is lacking. In three microhabitats (gaps, small and large Retama shrubs), we placed six microcosms with sterilized soil, two per soil origin (i.e. from each microhabitat). One in every pair received an alive, and the other a sterile, inoculum from its own soil. Seeds of annual plants were sown into the microcosms. Germination, survival and biomass were monitored. Soil bacterial communities were characterized by pyrosequencing. Germination in living Retama inoculum was nearly double that of germination in sterile inoculum. Germination was greater under Retama canopies than in gaps. Biomass was up to three times higher in nurse than in gap soils. Soil microorganisms, soil properties and microclimate showed a range of positive to negative effects on understory plants depending on species identity and life stage. Nurse soil microorganisms promoted germination, but the effect was smaller than the positive effects of soil properties and microclimate under nurses. Nurse below-ground environment (soil properties and microorganisms) promoted plant growth and survival more than nurse microhabitat.


[The histaminergic system: a target for innovative treatments of cognitive deficits].
The central effects of histamine are mediated by H(1), H(2) and H(3) receptors. The H(3) receptor inhibits histamine release in brain. Therefore, H(3) receptor inverse agonists, by suppressing this brake, enhance histamine neuron activity. The histaminergic system plays a major role in cognition and H(3) receptor inverse agonists are expected to be a potential therapeutics for cognitive deficits of Alzheimer's disease (AD). They are eagerly awaited inasmuch as other treatments of the disease, such as tacrine or memantine, also enhance, through different mechanisms, histaminergic neurotransmission. An important loss of histaminergic neurons has been observed in AD. In contrast, levels of the histamine metabolite in the CSF of AD patients show that their global activity is decreased by only 25%. This indicates that activating histamine neurons in AD can be envisaged.


Minimal Invasive Plate Osteosynthesis (MIPO) Technique Using Anterolateral Approach for Treating Closed Proximal Humerus Fracture.
Proximal humerus fracture is the second most common fracture of the upper extremity and presents several unique problems such as anatomical complexity, high risk of avascular necrosis, minimal bone stock for purchase, significant morbidity, and lack of a universally accepted treatment. Recent treatments for proximal humerus fractures include use of minimally invasive plate osteosynthysis (MIPO). The aim of this cross-sectional study was to evaluate the outcomes of our less invasive technique using a modified anterolateral approach for treatment of proximal humerus fractures. Ten such operative procedures were performed in patients of varying age and with varied mechanism of injury from 2002-2011. All cases were conducted in an acute setting. There were no cases of infection and the functional outcome scores were good. This approach represents an alternative treatment for closed proximal humerus fracture but more extensive studies are needed. Proximal humerus fracture, MIPO, less invasive,anterolateral approach.


Engaging Healthcare Staff and Stakeholders in Healthcare Simulation Modeling to Better Translate Research Into Health Impact: A Systematic Review.
Objective: To identify processes to engage stakeholders in healthcare Simulation Modeling (SM), and the impacts of this engagement on model design, model implementation, and stakeholder participants. To investigate how engagement process may lead to specific impacts. Data Sources: English-language articles on health SM engaging stakeholders in the MEDLINE, EMBASE, Scopus, Web of Science and Business Source Complete databases published from inception to February 2020. Study Design: A systematic review of the literature based on a priori protocol and reported according to PRISMA guidelines. Extraction Methods: Eligible articles were SM studies with a health outcome which engaged stakeholders in model design. Data were extracted using a data extraction form adapted to be specific for stakeholder engagement in SM studies. Data were analyzed using summary statistics, deductive and inductive content analysis, and narrative synthesis. Principal Findings: Thirty-two articles met inclusion criteria. Processes used to engage stakeholders in healthcare SM are heterogenous and often based on intuition rather than clear methodological frameworks. These processes most commonly involve stakeholders across multiple SM stages via discussion/dialogue, interviews, workshops and meetings. Key reported impacts of stakeholder engagement included improved model quality/accuracy, implementation, and stakeholder decision-making. However, for all but four studies, these reports represented author perceptions rather than formal evaluations incorporating stakeholder perspectives. Possible process enablers of impact included the use of models as "boundary objects" and structured facilitation via storytelling to promote effective communication and mutual understanding between stakeholders and modelers. Conclusions: There is a large gap in the current literature of formal evaluation of SM stakeholder engagement, and a lack of consensus about the processes required for effective SM stakeholder engagement. The adoption and clear reporting of structured engagement and process evaluation methodologies/frameworks are required to advance the field and produce evidence of impact.


Predictive value of the results of a first in-vitro fertilization cycle on the outcome of subsequent cycles.
This study examines the relationship between the first cycle of in-vitro fertilization (IVF) and subsequent cycles. The results of all IVF cycles conducted at The Hammersmith Hospital or The Royal Masonic Hospital between 1988 and 1995 were studied including those cycles where egg recovery was abandoned due to poor ovarian response. All patients underwent a standardized treatment protocol. Of those women who achieved a clinical pregnancy during their first IVF attempt, 33% achieved a pregnancy during their second cycle, statistically significantly different from the 24% of patients conceiving during a second cycle who had failed to conceive during their first. 36% of those who achieved a biochemical pregnancy in their first cycle became pregnant in their second. Age was an important factor in the success of IVF treatment, with pregnancy rates of 48% in the 20-25 year age group falling to 8% in those aged > or =41 years. Cumulative pregnancy rates were 26% after one cycle, increasing to 43% after two cycles and reached 80% after seven cycles. A previous pregnancy significantly improved a couple's probability of conception in a later IVF cycle. Overall pregnancy rates per cycle were constant for the first three attempts. Cumulative pregnancy rates continued to rise to 72% after six cycles. Thus the more cycles a couple undergo (up to six) the greater their chance of a pregnancy.


The neuron-astrocyte-microglia triad in a rat model of chronic cerebral hypoperfusion: protective effect of dipyridamole.
Chronic cerebral hypoperfusion during aging may cause progressive neurodegeneration as ischemic conditions persist. Proper functioning of the interplay between neurons and glia is fundamental for the functional organization of the brain. The aim of our research was to study the pathophysiological mechanisms, and particularly the derangement of the interplay between neurons and astrocytes-microglia with the formation of "triads," in a model of chronic cerebral hypoperfusion induced by the two-vessel occlusion (2VO) in adult Wistar rats (n = 15). The protective effect of dipyridamole given during the early phases after 2VO (4 mg/kg/day i.v., the first 7 days after 2VO) was verified (n = 15). Sham-operated rats (n = 15) were used as controls. Immunofluorescent triple staining of neurons (NeuN), astrocytes (GFAP), and microglia (IBA1) was performed 90 days after 2VO. We found significantly higher amount of "ectopic" neurons, neuronal debris and apoptotic neurons in CA1 Str. Radiatum and Str. Pyramidale of 2VO rats. In CA1 Str. Radiatum of 2VO rats the amount of astrocytes (cells/mm(2)) did not increase. In some instances several astrocytes surrounded ectopic neurons and formed a "micro scar" around them. Astrocyte branches could infiltrate the cell body of ectopic neurons, and, together with activated microglia cells formed the "triads." In the triad, significantly more numerous in CA1 Str. Radiatum of 2VO than in sham rats, astrocytes and microglia cooperated in the phagocytosis of ectopic neurons. These events might be common mechanisms underlying many neurodegenerative processes. The frequency to which they appear might depend upon, or might be the cause of, the burden and severity of neurodegeneration. Dypiridamole significantly reverted all the above described events. The protective effect of chronic administration of dipyridamole might be a consequence of its vasodilatory, antioxidant and anti-inflammatory role during the early phases after 2VO.


Chirality transfer from silicon to carbon.
The exploitation of the asymmetry at silicon in stereoselective synthesis is an exceptionally challenging task. Initially, silicon-stereogenic silanes have been utilized to elucidate the stereochemical course of substitution reactions at silicon. Apart from these mechanistic investigations, only a handful of synthetic applications with an asymmetrically substituted silicon as the stereochemical controller have been reported to date. In these transformations the chiral silicon functions as a chiral auxiliary. Conversely, a direct transfer of chirality from silicon to carbon during bond formation and cleavage at silicon has remained open until its recent realization in both inter- and intramolecular reactions. In this Concept, the pivotal considerations in relation to the nature of suitable silanes as well as mechanistic prerequisites for an efficient chirality transfer will be discussed.


Sonographic evaluation of the rotator cuff. Accuracy in patients without prior surgery.
Since 1982 a sonographic technique has been devised to evaluate the integrity of the rotator cuff. In a series of 139 shoulders in 134 consecutive patients without prior surgery, sonographic results were correlated with surgical findings and/or arthrography. When sonography was compared with surgical findings (n = 90 shoulders), the overall accuracy was 95%. The sonographic diagnosis was the same as the arthrographic diagnosis in 91% of the cases (n = 50). Cuff lesions were also created in two cadavers, and images were made to confirm sonographic appearances. Because in the authors' experience sonography is accurate, safe, painless, rapid, and inexpensive, it has now been adopted as the primary study for the examination of the rotator cuff at the authors' institution. Arthrography is recommended in cases in which sonography is negative but there is significant clinical evidence of rotator cuff tear.


The complete mitochondria genome of Sarcophaga africa (Diptera: Sarcophagidae).
Sarcophaga africa (S. africa) is a significant medical and forensic insect which belongs to the Sarcophagidae. The species identification of the forensically important genus Sarcophaga is difficult and requires strong morphology and taxonomic expertise. With the sequencing technique improved, we report the complete mitochondrial genome of the S. africa for the first time to assist species identification. The 37 genes presented in the 15,144 bp circular genome has been found which include 13 protein-coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes. The array of the genes has much resemblance with other discovered insects. The overall base compositions of A, G, C and T are 39.43%, 9.64%, 14.61% and 36.31% respectively. The complete mitochondrial genome of S. africa could be valuable to enriching the Dipteran mitochondrial genomes and be helpful for entomologists to screen reliable molecular markers in the species identifications with forensic entomology purposes or phylogenetic analysis.


[Multidetector computed tomography coronarography: preliminary experience in real life settings].
Multidetector computed tomography coronarography (MDCT) is a promising tool, offering non invasive anatomic evaluation of coronary arteries. We relate in this article our impressions after our first two years experience. Retrospective study of the 328 patients who underwent MDCT examination between January 2005 and December 2006 at our community hospital. Per patient comparative analysis of the anatomical findings versus percutaneous angiography (PCA) in 61 cases. Out of 328 patients 61 (18.5%) underwent PCA. In these patients we found a sensibility, specificity, positive predictive value and negative predictive value of 100%, 54%, 59% and 100% for MDCT. The main factor responsible for inconclusive vessel analysis was excessive calcification. In routine use, MDCT enables one to rule out significant stenosis non invasively, with high sensitivity in an unselected patient population.


Paramecium species of the upper and lower Volga River basin, Russia.
The Volga, which is the largest river in Europe (3690 km long), flows from the north (Tver' region) to the south (Caspian Sea), and its extensive basin (1380 km2) includes very different biotopes. Thus, analysis ofthe occurrence of Paramecium species along this large river basin may significantly enhance our understanding of species distribution according to temperature regime, food richness and other possible factors. The present paper concerns the occurrence of species of the P. aurelia complex in the sampling areas of the Upper Volga River, and a comparison with the occurrence of species of the P. aurelia complex in the Lower Volga region. In the Upper Volga basin, P. biaurelia was the most abundant among species of the complex recorded (among P. triaurelia, P. decaurelia, P. dodecaurelia), in the Lower Volga region eight species of the complex were recorded (P. primaurelia, P. biaurelia, P. triaurelia, P. pentaurelia, P. sexaurelia, P. septaurelia, P. novaurelia, P. decaurelia).


Predictors of intellectual performance in adults with intractable temporal lobe epilepsy.
The relationships of medical, developmental, social, and familial variables to intellectual performances (IQ scores) were assessed in a sample of 242 adult patients with intractable lateralized temporal lobe epilepsy. Lower IQ scores were associated with low patient and parent education. In addition to the significant contributions of nonneurological social and familial factors to IQ, early age at onset of regular seizures and presence of primary neurological dysfunction in the left cerebral hemisphere were also both independently related to lower IQ. The obtained results suggest that the occurrence of regular seizures during a critical period in early childhood neural maturation poses the greatest risk to cognitive development in the epilepsy population. Total duration of seizures, history of severe convulsive episodes, and the occurrence of another nonepileptic neurological problem in early childhood do not contribute significantly to delayed cognitive development.


Rapid Identification of Soybean Varieties by Terahertz Frequency-Domain Spectroscopy and Grey Wolf Optimizer-Support Vector Machine.
Different soybean varieties vary greatly in their nutritional value and composition. Screening for superior varieties is also essential for the development of the soybean seed industry. The objective of the paper was to analyze the feasibility of terahertz (THz) frequency-domain spectroscopy and chemometrics for soybean variety identification. Meanwhile, a grey wolf optimizer-support vector machine (GWO-SVM) soybean variety identification model was proposed. Firstly, the THz frequency-domain spectra of experimental samples (6 varieties, 270 in total) were collected. Principal component analysis (PCA) was used to analyze the THz spectra. After that, 203 samples from the calibration set were used to establish a soybean variety identification model. Finally, 67 samples from the test set were used for prediction validation. The experimental results demonstrated that THz frequency-domain spectroscopy combined with GWO-SVM could quickly and accurately identify soybean varieties. Compared with discriminant partial least squares (DPLS) and particles swarm optimization support vector machine, GWO-SVM combined with the second derivative could establish a better soybean variety identification model. The overall correct identification rate of its prediction set was 97.01%.


Brca1 Mutations Enhance Mouse Reproductive Functions by Increasing Responsiveness to Male-Derived Scent.
We compared the gene expression profiles of ovarian granulosa cells harboring either mutant or wild type Brca1 to follow up on our earlier observation that absence of a functional Brca1 in these important regulators of menstrual/estrous cycle progression leads to prolongation of the pre-ovulatory phase of the estrous cycle and to increased basal levels of circulating estradiol. Here we show that ovarian granulosa cells from mice carrying a conditional Brca1 gene knockout express substantially higher levels of olfactory receptor mRNA than granulosa cells from wild type littermates. This led us to hypothesize that reproductive functions in mutant female mice might be more sensitive to male-derived scent than in wild type female mice. Indeed, it is well established that isolation from males leads to complete cessation of mouse estrous cycle activity while exposure to olfactory receptor ligands present in male urine leads to resumption of such activity. We found that Brca1-/- female mice rendered anovulatory by unisexual isolation resumed ovulatory activity more rapidly than their wild type littermates when exposed to bedding from cages where males had been housed. The prime mediator of this increased responsiveness appears to be the ovary and not olfactory neurons. This conclusion is supported by the fact that wild type mice in which endogenous ovaries had been replaced by Brca1-deficient ovarian transplants responded to male-derived scent more robustly than mutant mice in which ovaries had been replaced by wild type ovarian transplants. Our findings not only have important implications for our understanding of the influence of olfactory signals on reproductive functions, but also provide insights into mechanisms whereby genetic risk factors for breast and extra uterine Müllerian carcinomas may influence menstrual activity in human, which is itself an independent risk factor for these cancers.


Maxillary molar vertical control with the use of transpalatal arches.
Upper molar eruption and its clinical significance to vertical control were measured in a retrospective cephalometric study of 40 patients (20 with and 20 without transpalatal arches) treated in a private practice. Pretreatment and posttreatment cephalometric values were compared to determine how well the patients were matched. No statistically significant differences were noted between control and test groups for the following variables: maxillary and mandibular molar vertical eruption per year, maxillary complex vertical growth per year, effective horizontal condylar growth per year, ratio of effective horizontal pogonion movement to effective vertical pogonion movement, ratio of effective vertical condylar growth to the summation of maxillary, and mandibular vertical molar eruption plus maxillary complex vertical growth, beginning age, and ending age. The control group exhibited statistically greater forward positioning of pogonion and greater effective vertical condylar growth than did the treatment group.


Gaucher disease: N370S glucocerebrosidase gene frequency in the Portuguese population.
In the Portuguese population the most frequent form of Gaucher disease is type 1. The N370S glucocerebrosidase gene mutation accounts for 63% of mutated alleles. The frequency of this mutation was accurately determined in the Portuguese population, which does not present an Ashkenazi Jewish genetic background. A gene frequency of 0.0043, with 95% confidence limits between 0.0023 and 0.0063, was obtained studying the genomic DNA of 2000 blood cards randomly sampled from the national neonatal screening program. On the basis of this frequency a significantly high number of homozygotes for the N370S mutation should be expected in the Portuguese population. This finding supports the idea that the majority of homozygotes for this mutation present a very mild clinical phenotype and remain undiagnosed.


Speech intelligibility and recall of first and second language words heard at different signal-to-noise ratios.
Free recall of spoken words in Swedish (native tongue) and English were assessed in two signal-to-noise ratio (SNR) conditions (+3 and +12 dB), with and without half of the heard words being repeated back orally directly after presentation [shadowing, speech intelligibility (SI)]. A total of 24 word lists with 12 words each were presented in English and in Swedish to Swedish speaking college students. Pre-experimental measures of working memory capacity (operation span, OSPAN) were taken. A basic hypothesis was that the recall of the words would be impaired when the encoding of the words required more processing resources, thereby depleting working memory resources. This would be the case when the SNR was low or when the language was English. A low SNR was also expected to impair SI, but we wanted to compare the sizes of the SNR-effects on SI and recall. A low score on working memory capacity was expected to further add to the negative effects of SNR and language on both SI and recall. The results indicated that SNR had strong effects on both SI and recall, but also that the effect size was larger for recall than for SI. Language had a main effect on recall, but not on SI. The shadowing procedure had different effects on recall of the early and late parts of the word lists. Working memory capacity was unimportant for the effect on SI and recall. Thus, recall appear to be a more sensitive indicator than SI for the acoustics of learning, which has implications for building codes and recommendations concerning classrooms and other workplaces, where both hearing and learning is important.


Pulmonary edema formation after myocardial infarction and coronary reperfusion: intravascular and extravascular pulmonary fluid volumes. IV.
Two studies were performed to assess the importance of coronary reperfusion on pulmonary capillary endothelial permeability in 34 anesthetized dogs. The response of intravascular pulmonary blood volume (PBV) and extravascular lung water (EVLW) was examined using indicator-dilution and postmortem (wet weight/dry weight) techniques. In the first study, six dogs served as sham controls, seven were occluded (LAD) for 45 min, and seven occluded for 45 min and reperfused for 15 min. While PBV was similar in each group, EVLW was greater in the reperfused than nonreperfused dogs (9.5 +/- 0.7 cc/kg vs 8.1 +/- 0.8 cc/kg; P less than .05), and both occluded groups were greater (P less than .01) than the control animals (7.0 +/- 1.0 cc/kg). Similar trends in postmortem wet weight/dry weight data were observed when compared with the in vivo EVLW data. In a second study of 14 open-chest dogs, an LAD ligation was held for 45 min in 14 dogs. In seven dogs, reperfusion was allowed for 15 min. A left atrial (LA) balloon was then inflated in all 14 dogs, increasing left atrial pressure to 25 mmHg in each dog for 90 min. Once again, PBV was similar in both groups, but EVLW was greater at the matched level of LA pressure elevation (14.6 +/- 3.2 cc/kg nonreperfused vs 18.7 +/- 4.1 cc/kg reperfused dogs; P less than .01). Again, postmortem data confirmed these data. Thus, we conclude coronary occlusion accelerates EVLW formation independent of LA pressure. Edema formation is worsened by coronary reperfusion, suggesting that the washout of myocardial toxins from the ischemic myocardium alters endothelial permeability.(ABSTRACT TRUNCATED AT 250 WORDS)


Lignification in beech (Fagus sylvatica) grown at elevated CO2 concentrations: interaction with nutrient availability and leaf maturation.
Beech (Fagus sylvatica L.) seedlings were grown in an ambient or elevated CO2 concentration ([CO2]) either in small stands in microcosms for three to four seasons or individually in pots fertilized at different nutrient supply rates. Leaves at different stages of development, as well as stems and roots at the end of the growing season, were used for analysis of structural biomass and lignin. In elevated [CO2], lignification of leaves was slightly retarded compared with structural biomass production and showed a strong correlation with the activities of ionically, cell-wall-bound peroxidases but not with total soluble peroxidases or covalently wall-bound peroxidases. The effect of elevated [CO2] on lignin concentration of mature tissues was dependent on nutrient supply rate. In leaves and roots, elevated [CO2] increased the lignin concentration in dry mass in N-limited plants. In seedlings grown with high nutrient supply, the lignin concentration in dry mass was unaffected or diminished by elevated [CO2]. Because elevated [CO2] enhanced seedling growth in the high nutrient supply treatments, the total amount of lignin produced per seedling was higher in these treatments. We predict that long-term sequestration of carbon will increase as long as biomass production is stimulated by elevated [CO2] and that tissue quality will change depending on developmental stage and nutrient availability.


Streak artefacts of the thoracic aorta: pseudodissection.
Streak artefacts running across images of the aorta can mimic aortic dissection on CT. We have compared 12 patients suffering from dissection with 45 others. Some artefacts were found in every patient. Such misleading appearances were more obtrusive in dissectors. However, we have found several pointers that help distinguish true intimal flaps from artefacts. Flaps are usually thin structures showing mild curvature. Artefacts are generally linear and vary in thickness. Their orientation may change markedly from one CT section to the next; they frequently extend beyond the confines of the aorta. In the ascending aorta, artefacts usually run at an angle of approximately 66 degrees to the coronal plane; especial care should be taken before diagnosing a straight intimal flap in that orientation. Careful study of images on the monitor rather than on film is a further help in the important distinction between artefact and intimal flap.


Paddle-based rotating-shield brachytherapy.
The authors present a novel paddle-based rotating-shield brachytherapy (P-RSBT) method, whose radiation-attenuating shields are formed with a multileaf collimator (MLC), consisting of retractable paddles, to achieve intensity modulation in high-dose-rate brachytherapy. Five cervical cancer patients using an intrauterine tandem applicator were considered to assess the potential benefit of the P-RSBT method. The P-RSBT source used was a 50 kV electronic brachytherapy source (Xoft Axxent™). The paddles can be retracted independently to form multiple emission windows around the source for radiation delivery. The MLC was assumed to be rotatable. P-RSBT treatment plans were generated using the asymmetric dose-volume optimization with smoothness control method [Liu et al., Med. Phys. 41(11), 111709 (11pp.) (2014)] with a delivery time constraint, different paddle sizes, and different rotation strides. The number of treatment fractions (fx) was assumed to be five. As brachytherapy is delivered as a boost for cervical cancer, the dose distribution for each case includes the dose from external beam radiotherapy as well, which is 45 Gy in 25 fx. The high-risk clinical target volume (HR-CTV) doses were escalated until the minimum dose to the hottest 2 cm(3) (D(2cm(3)) of either the rectum, sigmoid colon, or bladder reached their tolerance doses of 75, 75, and 90 Gy3, respectively, expressed as equivalent doses in 2 Gy fractions (EQD2 with α/β = 3 Gy). P-RSBT outperformed the two other RSBT delivery techniques, single-shield RSBT (S-RSBT) and dynamic-shield RSBT (D-RSBT), with a properly selected paddle size. If the paddle size was angled at 60°, the average D90 increases for the delivery plans by P-RSBT on the five cases, compared to S-RSBT, were 2.2, 8.3, 12.6, 11.9, and 9.1 Gy10, respectively, with delivery times of 10, 15, 20, 25, and 30 min/fx. The increases in HR-CTV D90, compared to D-RSBT, were 16.6, 12.9, 7.2, 3.7, and 1.7 Gy10, respectively. P-RSBT HR-CTV D90-values were insensitive to the paddle size for paddles angled at less than 60°. Increasing the paddle angle from 5° to 60° resulted in only a 0.6 Gy10 decrease in HR-CTV D90 on average for five cases when the delivery times were set to 15 min/fx. The HR-CTV D90 decreased to 2.5 and 11.9 Gy10 with paddle angles of 90° and 120°, respectively. P-RSBT produces treatment plans that are dosimetrically and temporally superior to those of S-RSBT and D-RSBT, although P-RSBT systems may be more mechanically challenging to develop than S-RSBT or D-RSBT. A P-RSBT implementation with 4-6 shield paddles would be sufficient to outperform S-RSBT and D-RSBT if delivery times are constrained to less than 15 min/fx.


Triple Combination Therapy for Global Cardiovascular Risk: Atorvastatin, Perindopril, and Amlodipine.
Statins, angiotensin-converting enzyme (ACE) inhibitors, and calcium channel blockers (CCBs) have markedly changed the clinical progression of patients with coronary artery disease (CAD). The goal of this paper is to review the rationale and evidence for combining these three drug classes in hypertensive patients with hypercholesterolemia or CAD. Data sources include a literature search for publications on the use of a statin combined with various antihypertensive drugs in patients with hypertension and hypercholesterolemia or stable CAD. Hypercholesterolemia and hypertension constitute major physiological risk factors of ischemic heart disease. Current guidelines recommend a global approach to risk management, using agents that address as many risk factors as possible. Dual combination therapies are an important component of guideline-recommended therapy in hypertension. Our review of the literature indicates that triple therapy with a statin, ACE inhibitor, and CCB is associated with a significant reduction in major cardiovascular events. For example, a post hoc analysis in 1056 patients with stable CAD participating in the EUROPA trial indicated that the addition of perindopril to a CCB and a lipid-lowering agent was associated with a 46 % reduction in the composite of cardiovascular death, myocardial infarction, and resuscitated cardiac arrest (p = 0.023). In addition, single pill formulations are known to result in better adherence to the treatment. Single-pill formulations that combine a statin, an ACE inhibitor, and a CCB appear to offer an effective approach to the management of global cardiovascular risk.


Racial Bias in Neural Response for Pain Is Modulated by Minimal Group.
Whether empathic racial bias could be modulated is a subject of intense interest. The present study was carried out to explore whether empathic racial bias for pain is modulated by minimal group. Chinese/Western faces with neutral expressions receiving painful (needle penetration) or non-painful (Q-tip touch) stimulation were presented. Participants were asked to rate the pain intensity felt by Chinese/Western models of ingroup/outgroup members. Their implicit racial bias were also measured. Two lines of evidence indicated that the anterior cingulate cortex (ACC) was modulated by racial bias: (1) Chinese models elicited stronger activity than Western did in the ACC, and (2) activity in the ACC was modulated by implicit racial bias. Whereas the right anterior insula (rAI) were modulated by ingroup bias, in which ingroup member elicited stronger activity than outgroup member did. Furthermore, activity in the ACC was modulated by activity of rAI (i.e., ingroup bias) in the pain condition, while activity in the rAI was modulated by activity of ACC (i.e., racial bias) in the nopain condition. Our results provide evidence that there are different neural correlates for racial bias and ingroup bias, and neural racial bias for pain can be modulated by minimal group.


Evidence of the Impact of the Tips From Former Smokers Campaign: Results From the Behavioral Risk Factor Surveillance System.
The Tips From Former Smokers campaign (Tips) has demonstrated significant impact as a population-based intervention for smoking cessation in the United States. Since 2012, evaluations of Tips have relied on web-panel data to attribute the campaign to smoking cessation outcomes. We re-examined the relationship between market-level doses of the campaign and quit attempts by using Behavioral Risk Factor Surveillance System (BRFSS) data to triangulate prior findings. We found that Tips was associated with increased quit attempts among smokers, which validates prior evaluation research on the impact of Tips. These results suggest that continued investments in Tips may help sustain its impact on cessation-related outcomes.


The Impact of IL-16 3'UTR Polymorphism rs859 on Lung Carcinoma Susceptibility among Chinese Han Individuals.
Lung carcinoma is the most common cancer and cause of cancer deaths among both males and females in China. Previously, genetic variants located in gene untranslated region have been well established as interfering factors in mRNA translation and confirmed playing critical roles in lung oncogenesis. However, the correlation between polymorphisms in gene 3' untranslated region and lung cancer risk is less reported in China Han population. In this study, polymorphisms in 3'-untranslated region of IL-16, CYP24A1, and FBN1 were determined in 322 lung cancer patients and 384 healthy controls with the usage of Sequenom MassARRAY. The correlation between selected variants and lung cancer risk was examined by unconditional logistic regression analysis with or without adjustments for age, gender, smoking status, and alcohol drinking status. Additionally, stratification analysis was applied to detect the associations of SNPs with lung cancer in different subgroups. As the results, significant relationships were found between IL-16 rs859 and lung cancer susceptibility in recessive model (OR= 0.65, 95% CI: 0.44-0.96, P= 0.029) and log-additive model (OR= 0.76, 95% CI: 0.60-0.96, P= 0.019). Moreover, adjusted stratified analysis also revealed the important effects of IL-16 rs859 on lung cancer risk among individuals aged older than 50, males, and nondrinkers. IL-16 rs859 showed statistically significant evidence associated with susceptibility to lung adenocarcinoma and lung small cell carcinoma in Chinese Han population as well. Our research demonstrated that genetic variant rs859 of IL-16 3'UTR was associated with lung cancer risk in Chinese Han population and the result might be exploited as a new biomarker for lung cancer assessment and prevention.