Treatment of oroantral fistula with autologous bone graft and application of a non-reabsorbable membrane.
The aim of the current report is to illustrate an alternative technique for the treatment of oroantral fistula (OAF), using an autologous bone graft integrated by xenologous particulate bone graft. Acute and chronic oroantral communications (OAC, OAF) can occur as a result of inadequate treatment. In fact surgical procedures into the maxillary posterior area can lead to inadvertent communication with the maxillary sinus. Spontaneous healing can occur in defects smaller than 3 mm while larger communications should be treated without delay, in order to avoid sinusitis. The most used techniques for the treatment of OAF involve buccal flap, palatal rotation - advancement flap, Bichat fat pad. All these surgical procedures are connected with a significant risk of morbidity of the donor site, infections, avascular flap necrosis, impossibility to repeat the surgical technique after clinical failure, and patient discomfort. We report a 65-years-old female patient who came to our attention for the presence of an OAF and was treated using an autologous bone graft integrated by xenologous particulate bone graft. An expanded polytetrafluoroethylene titanium-reinforced membrane (Gore-Tex) was used in order to obtain an optimal reconstruction of soft tissues and to assure the preservation of the bone graft from epithelial connection. This surgical procedure showed a good stability of the bone grafts, with a complete resolution of the OAF, optimal management of complications, including patient discomfort, and good regeneration of soft tissues. The principal advantage of the use of autologous bone graft with an expanded polytetrafluoroethylene titanium-reinforced membrane (Gore-Tex) to guide the bone regeneration is that it assures a predictable healing and allows a possible following implant-prosthetic rehabilitation.


Social determinants of rest deprivation amongst Ghanaian women: national and urban-rural comparisons with data from a cross-sectional nationally representative survey.
Rest deprivation (rest/napping/sleep 6 or less hours daily) is a clinically recognised risk factor for poor health, but its epidemiology is little studied. This study reports prevalence's and social correlates of rest deprivation in Ghana. Data are from the 2008 Ghana Demographic and Health Survey. Women ages 15-49 were recruited in a national sampling design. Respondents were 4,916 women in the national sample, a sub-sample of 530 women in the three northernmost rural regions and a sub-sample of 853 women in urban Greater Accra. Prevalence's of rest deprivation were 0.13% nationally, 14.5% in Greater Accra and 16.8% in the North. The significant correlates nationally were age, education, wealth index, Christian religion and literacy. In Accra, they were age, wealth index, having household electricity, and possession of a refrigerator, a stove and a mobile phone. In the North, they were education, occupation, drinking water source, possession of motorcycle/scooter, Christian religion, literacy, and possession of a clock and a cupboard. In logistic regression analyses controlling for age in the national sample, the significant odds ratios were 1.40 for no education compared to secondary and higher education, 0.78-0.43 for the four poorer wealth quintiles compared to the richest wealth index quintile, and 0.55 for Christian religion compared to all others.Also controlling for age, the significant odds ratios in Accra were 2.15 for the second richest wealth quintile compared to the richest quintile and 0.16 for possession of a mobile phone. In the North they were 0.49 for Christian religion compared to all others, 1.87 for having a protected compared to an unprotected water source, and 0.41 for having a cupboard in the home. Education, wealth and religion were related to rest deprivation nationally but not in the urban and rural regions (except for religion in the North). This suggests caution in generalising about the social correlates of rest deprivation at a regional level, based on national-level data. Qualitative research in local contexts is needed in order to illuminate the social determinants of rest pattern, and to provide guidance about better ways to measure such determinants in future survey research.


The presence of nuclear families in prehistoric collective burials revisited: the bronze age burial of Montanissell Cave (Spain) in the light of aDNA.
Ancient populations have commonly been thought to have lived in small groups where extreme endogamy was the norm. To contribute to this debate, a genetic analysis has been carried out on a collective burial with eight primary inhumations from Montanissell Cave in the Catalan pre-Pyrenees. Radiocarbon dating clearly placed the burial in the Bronze Age, around 3200 BP. The composition of the group-two adults (one male, one female), one young woman, and five children from both sexes-seemed to represent the structure of a typical nuclear family. The genetic evidence proves this assumption to be wrong. In fact, at least five out of the eight mitochondrial haplotypes were different, denying the possibility of a common maternal ancestor for all of them. Nevertheless, 50% of the inhumations shared haplogroup J, so the possibility of a maternal relationship cannot be ruled out. Actually, combining different analyses performed using ancient and living populations, the probability of having four related J individuals in Montanissell Cave would range from 0.9884 to 0.9999. Owing to the particularities of this singular collective burial (small number of bodies placed altogether in a hidden cave, the evidence of non-simultaneous interments, close dating and unusual grave goods), we suggest that it might represent a small group with a patrilocal mating system.


The Prognostic Value of Central Venous-to-Arterial CO2 Difference/Arterial-Central Venous O2 Difference Ratio in Septic Shock Patients with Central Venous O2 Saturation ≥80.
It is a great challenge for physician to assess the relationship between O2 delivery and O2 consumption in septic shock patients with high ScvO2. Recently, the venous-to-arterial CO2 difference/arterial-central venous O2 difference ratio (P(v-a)CO2/C(a-v)O2) has shown potential for reflecting anaerobic metabolism. Therefore, we evaluated the value of using the P(v-a)CO2/C(a-v)O2 ratio to predict mortality and assess anaerobic metabolism in septic shock patients with high ScvO2 (≥ 80%). This was a clinical investigation of septic shock patients on the P(v-a)CO2/C(a-v)O2 ratio in the intensive care unit (ICU) department. The patients' arterial and central venous blood gas levels were measured simultaneously at enrollment (T0) and 24 h (T24) after resuscitation. A total of 61 patients with high ScvO2 at T24 after resuscitation were selected for analysis. The ICU mortality rate in the septic shock patients was 20% (12/61). The nonsurvivors had a significantly higher P(v-a)CO2, P(v-a)CO2/C(a-v) O2 ratio, arterial lactate level and lower lactate clearance at T24 after resuscitation. The P(v-a)CO2/C(a-v)O2 ratio had the biggest the areas under the receiver operating characteristic (AUC) for predicting ICU mortality. For predicting ICU mortality, a threshold of P(v-a)CO2/C(a-v)O2 ratio ≥1.6 was associated with a sensitivity of 83% and a specificity of 63%. Multivariate analysis showed P(v-a)CO2/C(a-v)O2 ratio at both T0 (RR 5.597, P = 0.024) and T24 (RR 5.812, P = 0.031) was an independent predictor of ICU mortality. Including the ratio into the regression model showed a bigger AUC than without the ratio (0.886 vs. 0.833). The P(v-a)CO2/C(a-v)O2 ratio is an independent predictor of ICU mortality in septic shock patients with high ScvO2 after resuscitation. It is worthy of consideration to recruit microcirculation to correct the high ratio in high ScvO2 case.


Living bioethics, theories and children's consent to heart surgery.
This analysis is about practical living bioethics and how law, ethics and sociology understand and respect children's consent to, or refusal of, elective heart surgery. Analysis of underlying theories and influences will contrast legalistic bioethics with living bioethics. In-depth philosophical analysis compares social science traditions of positivism, interpretivism, critical theory and functionalism and applies them to bioethics and childhood, to examine how living bioethics may be encouraged or discouraged. Illustrative examples are drawn from research interviews and observations in two London paediatric cardiac units. This paper is one of a series on how the multidisciplinary cardiac team members all contribute to the complex mosaic of care when preparing and supporting families' informed consent to surgery. The living bioethics of justice, care and respect for children and their consent depends on theories and practices, contexts and relationships. These can all be undermined by unseen influences: the history of adult-centric ethics; developmental psychology theories; legal and financial pressures that require consent to be defined as an adult contract; management systems and daily routines in healthcare that can intimidate families and staff; social inequalities. Mainstream theories in the clinical ethics literature markedly differ from the living bioethics in clinical practices. We aim to contribute to raising standards of respectful paediatric bioethics and to showing the relevance of virtue and feminist ethics, childhood studies and children's rights.


Engagement of Traditional Healers and Birth Attendants as a Controversial Proposal to Extend the HIV Health Workforce.
"Medical pluralism" is the use of multiple health systems and is common among people living with HIV/AIDS in sub-Saharan Africa. Healers and traditional birth attendants (TBAs) often are a patient's first and/or preferred line of treatment; this often results in delayed, interrupted, or abandoned diagnosis and therapy. Literature from the study of medical pluralism suggests that HIV care and treatment programs are infrequently and inconsistently engaging healers around the world. Mistrust and misunderstanding among patients, clinical providers, and traditional practitioners make the development of effective partnerships difficult, particularly regarding early HIV diagnosis and antiretroviral therapy. We provide recommendations for the development of successful collaboration health workforce efforts based on both published articles and case studies from our work in rural Mozambique.


A Novel Surgical Approach for Treatment of Class II Furcation Defects Using Marginal Periosteal Membrane.
This study was designed to describe and evaluate the use of a vascularized marginal periosteal barrier membrane (MPM) harvested by a semilunar incision, alone or combined with a bone graft, in treatment of class II furcation defects in mandibular molars, compared to open flap debridement (OFD). Thirty class II furcation defects in mandibular molars were randomly assigned into three equal groups: Group I included OFD, Group II included defects treated with MPM, and Group III consisted of defects treated with MPM after applying demineralized freeze-dried bone allograft (DFDBA). At baseline and 6-month follow-up, vertical probing depth (VPD), clinical attachment level (CAL) measurements, along with a radiographic measurement of bone height (BH), were obtained for each defect. Transmission electron microscopy (TEM) was used for further evaluation of the histological changes associated with gingival samples related to each line of treatment. Both Groups II and III reflected significant favorable outcomes in all the assessed parameters compared to OFD. A non-significant difference was found between both groups regarding VPD, while significant improvement in CAL and BH were detected in Group III (p ≤ 0.05). Favorable histological findings were also noticed in the test groups, with more improvement in Group III. Placement of a vascularized MPM as a barrier membrane, using a semilunar incision, demonstrated a significant improvement in both clinical and histological outcomes of class II furcation defects in lower molars. When it was combined with DFDBA, a meaningful difference was found with regard to early wound healing and gain in CAL and BH.


MucR is necessary for galactoglucan production in Sinorhizobium meliloti EFB1.
Sinorhizobium meliloti can produce two types of acidic exopolysaccharides, succinoglycan and galactoglucan, that are interchangeable for infection of alfalfa nodules. Strain SU47 and derivatives produce only succinoglycan, unless it grows under phosphate limitation or carries a mutation in either of two regulatory loci, mucR or expR. It has been proposed that MucR acts as a transcriptional repressor that blocks the expression of the exp genes responsible for galactoglucan production. Strain EFB1 simultaneously produces both exopolysaccharides. Heterologous expression of lacZ transcriptional fusions of the expE promoters has shown that genetic background is more important that promoter sequence for exp gene expression, since expE promoters from both strains are expressed at high level in EFB1 and not in SU47. We have found that mucR is present in mucoid and nonmucoid strains, and in EFB1 differs from SU47 in only one conservative amino acid change. MucR proteins from both strains are interchangeable. An mucR mutant of EFB1 cannot produce galactoglucan and does not express mucS.


Data on sand fly fauna (Diptera, Psychodidae, Phlebotominae) in Itatiaia National Park, Rio de Janeiro State, Brazil.
The sand fly fauna in Itatiaia National Park, Rio de Janeiro, Brazil, was investigated in different habitats ranging from sylvatic areas to those altered by human activity related to ecotourism, specifically identifying species that have been suggested as potential leishmaniasis vectors. Sand flies were captured from June 2002 to March 2004, using CDC light traps and Shannon traps. A total of 1,256 sand fly specimens were captured, from species belonging to genera Lutzomyia and Brumptomyia: Brumptomyia guimaraesi, B. troglodytes, Lutzomyia (Lutzomyia) amarali, L. lanei, L. migonei, L. sallesi, L. edwardsi, L. tupynambai, L. (Pintomyia) pessoai, L. (P.) bianchigalatie, L. rupicola, L. (Psathyromyia) shannoni, L. pascalei, L. (Psychodopygus) matosi, L. (P.) davisi, L. (P.) hirsuta hirsuta, L. (P.) ayrozai, L. peresi, L. monticola, and L. misionensis. Worthy of special attention were four species that are considered potential vectors for cutaneous leishmaniasis in Brazil: L. ayrozai, L. hirsuta hirsuta, L. migonei, and L. davisi, representing 19.19% of the specimens captured in this study.


Ascites in Ovarian Carcinoma - Reliability and Limitations of Cytological Analysis.
The objective of this study was to examine the validity of ascitic fluid cytology in the detection of pathological findings, to examine the percentage of false positive and false negative results in the cytology of ascitic fluid and to determine the validity of peritoneal cytology in relation to the histopathological type of the ovarian tumour. This retrospective study included 170 peritoneal cytology findings. The study was conducted from January 2010 to December 2012. The experimental group included 76 cytology findings obtained from patients diagnosed with ovarian carcinoma, whereas the control group was composed of 94 cytology findings of benign ovarian tumours and liver cirrhosis ascites. The patients with ovarian carcinoma had grades III, as well as grades I and IIc but only in cases where operative and pathological finding indicated a ruptured or perforated tumour capsule. The sensitivity of peritoneal cytology is 68.92%, specificity is 93.61%, positive predictive value is 89.65% and negative predictive value is 78.57%. In 30.02% of patients, the peritoneal cytology showed false negative results, while in 6.38%, the results were false positive. The highest percentage of false negative findings was 77%, found in endometrioid carcinoma. Peritoneal cytology of ascitic fluid is highly specific but has relatively low sensitivity, particularly in the case of endometrioid ovarian carcinoma. In order to increase sensitivity, peritoneal cytology should be combined with monoclonal antibodies and other biochemical and immunohistochemical markers.


Sensitivity to ultraviolet radiation in a dominantly inherited form of xeroderma pigmentosum.
An Australian family is described in which a mild form of xeroderma pigmentosum (XP) is inherited as an autosomal dominant trait. Studies of lymphoblastoid cells and fibroblasts from affected persons demonstrated cellular sensitivity to ultraviolet (UV) light as judged by diminished clonogenicity and higher frequencies of UV induced chromosome aberrations compared to normal controls. After UV irradiation of dominant XP cells, replicative DNA synthesis was depressed to a greater extent than normal and the level of UV induced DNA repair synthesis was lower than that in normal cells. The level of sister chromatid exchanges and the numbers of 6-thioguanine resistant mutants induced by UV irradiation were equal to those found in normal controls. Although two subjects in the family had skin cancers, this dominant form of XP is not apparently associated with high risk, or large numbers, of skin cancers in affected persons.


Diagnosis and treatment: drugs five years later. Amoxicillin.
Amoxicillin is an aminopenicillin available in the United States only for oral use. It has an antibacterial activity and spectrum similar to that of ampicillin and is destroyed by gram-positive and gram-negative beta-lactamases. It is more active against enterococci and salmonellae than ampicillin, but less active against Shigella. It is better absorbed than ampicillin from the gastrointestinal tract with blood levels two to two and one half times those of ampicillin. Amoxicillin is an excellent agent to treat otitis media, bacterial sinusitis, bacterial exacerbations of bronchitis, acute lower-urinary-tract infections, gonorrhea, and typhoid. In special settings it may be useful as oral therapy of endocarditis, septic arthritis, and osteomyelitis and as prophylaxis to prevent endocarditis. When the cost of amoxicillin approaches that of ampicillin, it should replace that agent as the oral aminopenicillin of first choice.


Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits.
Height and other anthropometric measures are consistently found to associate with differential cancer risk. However, both genetic and mechanistic insights into these epidemiological associations are notably lacking. Conversely, inherited genetic variants in tumour suppressors and oncogenes increase cancer risk, but little is known about their influence on anthropometric traits. By integrating inherited and somatic cancer genetic data from the Genome-Wide Association Study Catalog, expression Quantitative Trait Loci databases and the Cancer Gene Census, we identify SNPs that associate with different cancer types and differential gene expression in at least one tissue type, and explore the potential pleiotropic associations of these SNPs with anthropometric traits through SNP-wise association in a cohort of 500,000 individuals. We identify three regulatory SNPs for three important cancer genes, FANCA, MAP3K1 and TP53 that associate with both anthropometric traits and cancer risk. Of particular interest, we identify a previously unrecognised strong association between the rs78378222[C] SNP in the 3' untranslated region (3'-UTR) of TP53 and both increased risk for developing non-melanomatous skin cancer (OR=1.36 (95% 1.31 to 1.41), adjusted p=7.62E-63), brain malignancy (OR=3.12 (2.22 to 4.37), adjusted p=1.43E-12) and increased standing height (adjusted p=2.18E-24, beta=0.073±0.007), lean body mass (adjusted p=8.34E-37, beta=0.073±0.005) and basal metabolic rate (adjusted p=1.13E-31, beta=0.076±0.006), thus offering a novel genetic link between these anthropometric traits and cancer risk. Our results clearly demonstrate that heritable variants in key cancer genes can associate with both differential cancer risk and anthropometric traits in the general population, thereby lending support for a genetic basis for linking these human phenotypes.


Optical sensing by transforming chromophoric silver clusters in DNA nanoreactors.
Bifunctional DNA oligonucleotides serve as templates for chromophoric silver clusters and as recognition sites for target DNA strands, and communication between these two components is the basis of an oligonucleotide sensor. Few-atom silver clusters exhibit distinct electronic spectra spanning the visible and near-infrared region, and they are selectively synthesized by varying the base sequence of the DNA template. In these studies, a 16-base cluster template is adjoined with a 12-base sequence complementary to the target analyte, and hybridization induces structural changes in the composite sensor that direct the conversion between two spectrally and stoichiometrically distinct clusters. Without its complement, the sensor strand selectively harbors ~7 Ag atoms that absorb at 400 nm and fold the DNA host. Upon association of the target with its recognition site, the sensor strand opens to expose the cluster template that has the binding site for ~11 Ag atoms, and absorption at 720 nm with relatively strong emission develops in lieu of the violet absorption. Variations in the length and composition of the recognition site and the cluster template indicate that these types of dual-component sensors provide a general platform for near-infrared-based detection of oligonucleotides in challenging biological environments.


Treatment of Osteochondrosis Dissecans of the Canine Stifle Using Synthetic Osteochondral Resurfacing.
This article aimed to describe the use and evolution of a synthetic osteochondral resurfacing (SOR) implant in the treatment of osteochondrosis dissecans (OCD) of the femoral condyle and to report the clinical, radiographic, computed tomography and magnetic resonance imaging outcomes of this technique. Medical records of dogs that were treated with first-generation (G1) and second-generation (G2) SOR at a single institute were reviewed. Surgical reports and clinical examinations as well as the preoperative, postoperative, and follow-up radiographs, computed tomographic images and magnetic resonance imaging images were reviewed. Fourteen stifles (nine dogs) were included in the study. G1-SOR implants were employed in six stifles of four dogs and G2-SOR implants in eight stifles of five dogs. Osteochondrosis dissecans of the medial femoral condyle was confirmed as the sole pathology in all dogs treated with G1-SOR. Only one of eight OCD lesions was located on the medial condyle in the G2-SOR group with the remaining seven lesions affecting the lateral femoral condyle. At 12 weeks, 13 of 14 stifles displayed implant stability, with no subchondral bone changes or evidence of lucency around any implant. Eight of nine dogs achieved a good-excellent clinical outcome. Complications included one minor surgical site infection and one infective arthritis which required implant removal. In this cohort of dogs, both G1-SOR and G2-SOR were successful and repeatable surgical procedures for dogs with OCD of the femoral condyle.


Efficient perovskite light-emitting diodes based on a solution-processed tin dioxide electron transport layer.
To achieve high-performance perovskite light-emitting diodes (PeLEDs), an appropriate functional layer beneath the perovskite emissive layer is significantly important to modulate the morphology of the perovskite film and to facilitate charge injection and transport in the device. Herein, for the first time, we report efficient n-i-p structured PeLEDs using solution-processed SnO2 as an electron transport layer. Three-dimensional perovskites, such as CH(NH2)2PbI3 and CH3NH3PbI3, are found to be more chemically compatible with SnO2 than with commonly used ZnO. In addition, SnO2 shows good transparency, excellent morphology and suitable energy levels. These properties make SnO2 a promising candidate in both three- and low-dimensional PeLEDs, among which a high external quantum efficiency of 7.9% has been realized. Furthermore, interfacial materials that are widely used to improve the device performances of ZnO-based PeLEDs are also applied on SnO2-based PeLEDs and their effects have been systematically studied. In contrast to ZnO, SnO2 modified by these interfacial materials shows detrimental effects due to photoluminescence quenching.


Mitochondrial Fragmentation Due to Inhibition of Fusion Increases Cyclin B through Mitochondrial Superoxide Radicals.
During the cell cycle, mitochondria undergo regulated changes in morphology. Two particularly interesting events are first, mitochondrial hyperfusion during the G(1)-S transition and second, fragmentation during entry into mitosis. The mitochondria remain fragmented between late G(2)- and mitotic exit. This mitotic mitochondrial fragmentation constitutes a checkpoint in some cell types, of which little is known. We bypass the 'mitotic mitochondrial fragmentation' checkpoint by inducing fragmented mitochondrial morphology and then measure the effect on cell cycle progression. Using Drosophila larval hemocytes, Drosophila S2R(+) cell and cells in the pouch region of wing imaginal disc of Drosophila larvae we show that inhibiting mitochondrial fusion, thereby increasing fragmentation, causes cellular hyperproliferation and an increase in mitotic index. However, mitochondrial fragmentation due to over-expression of the mitochondrial fission machinery does not cause these changes. Our experiments suggest that the inhibition of mitochondrial fusion increases superoxide radical content and leads to the upregulation of cyclin B that culminates in the observed changes in the cell cycle. We provide evidence for the importance of mitochondrial superoxide in this process. Our results provide an insight into the need for mitofusin-degradation during mitosis and also help in understanding the mechanism by which mitofusins may function as tumor suppressors.


Documenting Cancer Information Seeking Behavior and Risk Perception in the Hualapai Indian Community to Inform a Community Health Program.
Cancer incidence among American Indians (AIs) is low, yet their 5-year relative survival rate is the second lowest of all U.S. populations. Culturally relevant cancer prevention education is key to achieve health equity. This collaborative project of the Hualapai Tribe and University of Arizona modified the National Cancer Institute's 2003 Health Information National Trends Survey (HINTS) to yield a more culturally relevant cancer information survey to document the health seeking behaviors and perceptions of cancer risks and preventability of AI adults residing in the Hualapai Indian community. A team of health care providers, educators and cancer survivors (six native and three non-natives) completed the adaptation. Four trained native surveyors administered the survey using a random household survey design. The Hualapai HINTS was well accepted (<5% refusal rate) and was completed by 205 adults (20.5% of all adult residents). Respondents reported a preference for and a trust in verbal cancer information and communication with health care professionals (77.1% preference; 57.4% trust) and at workshops (75.2% preference; 45.5% trust). Respondents were aware of some health behaviors associated with a reduced cancer risk, e.g., avoid tobacco use and need for screening. Respondents were less well informed about the role of diet and exercise. These findings were used to inform local cancer prevention education efforts and to develop a series of monthly workshops that engaged local health professionals to reinforce and discuss pathways of the primary role of lifestyle related factors, specifically diet and exercise in reducing cancer risk.


Quinuronium induced hepatotoxicity in rats.
Two groups of 6 rats each received subcutaneous injections of 2.3 mg/kg or 5.0 mg/kg of quinuronium, respectively, on two consecutive days, while 5 rats injected with physiological saline served as controls. Clinical signs of muscular tremors, jumps, enlarged and hyperemic eyeballs, lacrimation, depression and anorexia were observed following administration of quinuronium. One rat receiving 5 mg/kg died before termination of the study. When killed 48 h after the first injection, the quinuronium-treated rats had a higher liver weight/body weight ratio compared to the controls. Quinuronium resulted in hepatic centrilobular fatty degeneration, but no depletion of hepatic glutathione (GSH). The present findings suggest that glutathione depletion does not seem to be involved in quinuronium hepatotoxicity.


Childhood obesity: Can electronic medical records customized with clinical practice guidelines improve screening and diagnosis?
The purpose of this project was to determine if customization of the electronic medical record (EMR) using evidence-based practice guidelines developed by the National Association of Pediatric Nurse Practitioners and the Expert Panel recommendations for the prevention, screening, and treatment of childhood and adolescent overweight and obesity would improve the rate of screening and diagnosis of obesity in children, 7 to 18 years of age. A retrospective review of encounters before and after implementation of customized EMR was conducted in a community health center. Data collected were compared for documentation of body mass index (BMI), completion of growth charts, scoring of risk questionnaire, and diagnosis of overweight or obesity. There was a clear increase in the frequency of recording BMI, completing BMI growth charts, and scoring questionnaires between written and electronic medical records. The number of children diagnosed with overweight or obesity increased with customized EMR but still remains well below the rates of obesity for this community. Customizing EMR with clinical practice guidelines improved adherence to recommendations for screening and identification of childhood overweight and obesity. Increased recognition and diagnosis will lead to improved interventions and improve outcomes for childhood obesity.


Blood-Based Proteomic Biomarkers of Alzheimer's Disease Pathology.
The complexity of Alzheimer's disease (AD) and its long prodromal phase poses challenges for early diagnosis and yet allows for the possibility of the development of disease modifying treatments for secondary prevention. It is, therefore, of importance to develop biomarkers, in particular, in the preclinical or early phases that reflect the pathological characteristics of the disease and, moreover, could be of utility in triaging subjects for preventative therapeutic clinical trials. Much research has sought biomarkers for diagnostic purposes by comparing affected people to unaffected controls. However, given that AD pathology precedes disease onset, a pathology endophenotype design for biomarker discovery creates the opportunity for detection of much earlier markers of disease. Blood-based biomarkers potentially provide a minimally invasive option for this purpose and research in the field has adopted various "omics" approaches in order to achieve this. This review will, therefore, examine the current literature regarding blood-based proteomic biomarkers of AD and its associated pathology.


Stress chaperone GRP78/BiP confers chemoresistance to tumor-associated endothelial cells.
The tumor vasculature is essential for tumor growth and survival and is a key target for anticancer therapy. Glioblastoma multiforme, the most malignant form of brain tumor, is highly vascular and contains abnormal vessels, unlike blood vessels in normal brain. Previously, we showed that primary cultures of human brain endothelial cells, derived from blood vessels of malignant glioma tissues (TuBEC), are physiologically and functionally different from endothelial cells derived from nonmalignant brain tissues (BEC) and are substantially more resistant to apoptosis. Resistance of TuBEC to a wide range of current anticancer drugs has significant clinical consequences as it represents a major obstacle toward eradication of residual brain tumor. We report here that the endoplasmic reticulum chaperone GRP78/BiP is generally highly elevated in the vasculature derived from human glioma specimens, both in situ in tissue and in vitro in primary cell cultures, compared with minimal GRP78 expression in normal brain tissues and blood vessels. Interestingly, TuBEC constitutively overexpress GRP78 without concomitant induction of other major unfolded protein response targets. Resistance of TuBEC to chemotherapeutic agents such as CPT-11, etoposide, and temozolomide can be overcome by knockdown of GRP78 using small interfering RNA or chemical inhibition of its catalytic site. Conversely, overexpression of GRP78 in BEC rendered these cells resistant to drug treatments. Our findings provide the proof of principle that targeting GRP78 will sensitize the tumor vasculature to chemotherapeutic drugs, thus enhancing the efficacy of these drugs in combination therapy for glioma treatment.


Lymphohaematopoietic malignancies and quantitative estimates of exposure to benzene in Canadian petroleum distribution workers.
To evaluate the relation between mortality from lymphohaematopoietic cancer and long term, low level exposures to benzene among male petroleum distribution workers. This nested case control study identified all fatal cases of lymphohaematopoietic cancer among a previously studied cohort. Of the 29 cases, 14 had leukaemia, seven multiple myeloma, and eight non-Hodgkin's lymphoma. A four to one matching ratio was used to select a stratified sample of controls from the same cohort, controlling for year of birth and time at risk. Industrial hygienists estimated workplace exposures for benzene and total hydrocarbons, without knowledge of case or control status, for combinations of job, location, and era represented in all work histories. Average daily benzene concentrations ranged from 0.01 to 6.2 parts per million (ppm) for all jobs. Company medical records were used to abstract information on other potential confounders such as cigarette smoking, although the data were incomplete. Odds ratios (ORs) were calculated with conditional logistic regression techniques for several exposure variables. Risks of leukaemia, non-Hodgkin's lymphoma, and multiple myeloma were not associated with increasing cumulative exposure to benzene or total hydrocarbons. For leukaemia, the logistic regression model predicted an OR of 1.002 (P < 0.77) for each ppm-y of exposure to benzene. Duration of exposure to benzene was more closely associated with risk of leukaemia than other exposure variables. It was not possible to completely control for other risk factors, although there was suggestive evidence that smoking and a family history of cancer may have played a part in the risk of leukaemia. This study did not show a relation between lymphohaematopoietic cancer and long term, low level exposures to benzene. The power of the study to detect low-such as twofold-risks was limited. Thus, further study on exposures to benzene in this concentration range are warranted.


Studies on sex-organ development. Prenatal effect of oestrogenic hormone on tubular-gland cell morphogenesis and ovalbumin-gene expression in the chick Müllerian duct.
The effects of diethylstilboestrol on morphogenesis and cyto-differentiation of the chick-embryo left Müllerian duct were examined. Embryos were treated at different stages of development with maximal-responsive doses of diethylstilboestrol over a 5-day interval. The shell gland and magnum regions of the Müllerian duct were then assayed for growth and histological morphogenesis. The results were correlated with diethylstilboestrol-induced ovalbumin-gene expression as measured by ovalbumin-mRNA (mRNAov) accumulation and the relative rate of ovalbumin synthesis. Treatment of the embryo from day 10 to day 15 of incubation induces morphogenesis of tubular-gland cells in the Müllerian-duct magnum. Although these cells constitute 10% of the total cell population and contain an average of 8000 molecules of mRNAov per cell, ovalbumin synthesis is only 0.85% of total magnum protein synthesis. The Müllerian-duct magnum of embryos treated from day 13 to day 18 of incubation contains about 30% tubular-gland cells, which have accumulated an average of 7000 molecules of mRNAov per cell, but ovalbumin synthesis is only 3.25% of total magnum protein synthesis. The Müllerian-duct magnum of embryos treated from day 16 to day 21 of incubation contains about 50% tubular-gland cells, which have accumulated an average of 6500 mRNAov molecules per cell, and ovalbumin synthesis is 10% of total magnum protein synthesis. Oestrogen responsiveness develops simultaneously in the Müllerian-duct magnum and shell-gland regions. Compared with the rate of diethylstilboestrol-induced oviduct growth, the relative rate of diethylstilboestrol-induced Müllerian-duct growth increases with embryonic age, from 20-fold lower in the 10-day embryo to only 3-fold lower in the 16-day embryo. All results are discussed in comparison with the responses to oestrogen of the immature chick oviduct, and in terms of the ontogeny of hormone-competent epithelial and stromal components of the Müllerian duct. It is concluded that the development of oestrogenic competence in the embryonic Müllerian duct is a multiphasic phenomenon. A dramatic increase in hormone responsiveness in the Müllerian duct occurs between days 10 and 16 of development, and a less dramatic final maturation of oestrogen responsiveness occurs between day 16 of development and 1 week after hatching.


T-cell-depleted reduced-intensity transplantation followed by donor leukocyte infusions to promote graft-versus-lymphoma activity results in excellent long-term survival in patients with multiply relapsed follicular lymphoma.
Follicular lymphoma (FL) is an indolent disorder that is treatable but considered incurable with chemotherapy alone. The curative potential of allogeneic transplantation using conventional myeloablative conditioning has been demonstrated, but this approach is precluded in the majority of patients with FL because of excessive toxicity. Thus, reduced-intensity conditioning regimens are being explored. This study reports the outcome of 82 consecutive patients with FL who underwent transplantation using fludarabine, melphalan, and alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated, having received a median of four lines of prior therapy, and 26% had experienced treatment failure with previous autologous transplantation. Median patient age was 45 years, and 52% of patients received stem cells from unrelated donors. With a median follow-up time of 43 months, the nonrelapse mortality was 15% at 4 years (8% for sibling and 22% for unrelated donor transplantations), acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%, this was significantly reduced where mixed chimerism had been converted to full donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In addition, 10 (77%) of 13 patients given DLI for relapse after transplantation experienced remission, with nine of these responses being sustained. Current progression-free survival at 4 years was 76% for the whole cohort (90% for those with sibling donors and 64% for those with unrelated donors). The excellent long-term survival with associated low rates of GVHD and the frequency and durability of DLI responses make this an extremely encouraging strategy for the treatment and potential cure of FL.


In vitro and in vivo anticancer properties of a Calcarea carbonica derivative complex (M8) treatment in a murine melanoma model.
Melanoma is the most aggressive form of skin cancer and the most rapidly expanding cancer in terms of worldwide incidence. Chemotherapeutic approaches to treat melanoma have had only marginal success. Previous studies in mice demonstrated that a high diluted complex derived from Calcarea carbonica (M8) stimulated the tumoricidal response of activated lymphocytes against B16F10 melanoma cells in vitro. Here we describe the in vitro inhibition of invasion and the in vivo anti-metastatic potential after M8 treatment by inhalation in the B16F10 lung metastasis model. We found that M8 has at least two functions, acting as both an inhibitor of cancer cell adhesion and invasion and as a perlecan expression antagonist, which are strongly correlated with several metastatic, angiogenic and invasive factors in melanoma tumors. The findings suggest that this medication is a promising non-toxic therapy candidate by improving the immune response against tumor cells or even induce direct dormancy in malignancies.


Retroperitoneal schwannoma: an atypical presentation.
Schwannoma is a rare tumour arising from Schwann cells in myelinated neural sheath of the nerves. They can arise in various places like head, neck, extremities, adrenal, retro peritoneum, psoas muscle. We here present a case of 33-year-old male who came with features of acute pancreatitis, with incidentally detected mass in presacral region on ultrasonography. Investigations like CECT and MRI were suggestive of neurofibroma, radical excision of the mass was done which showed solitary encapsulated tumour and cut sections showed areas of necrosis, and histopathologically it was proven as schwannoma. Most of the schwannoma's are benign, but rarely malignant transformation can occur. It can be associated with von Recklinghausen disease. Benign tumours have excellent prognosis, malignant tumours can present at later date with metastasis after excision also. Radiology plays a key role in diagnosis and follows up. Treatment is radical excision of tumour; recurrence is most common and has to be carefully followed up.


Recommendations for assessing patient-reported outcomes and health-related quality of life in patients with urticaria: a GA(2) LEN taskforce position paper.
The aim of this Global Allergy and Asthma European Network (GA(2)LEN) consensus report is to provide recommendations and suggestions for assessing patient-reported outcomes (PROs) including health-related quality of life in patients with urticaria. We recommend that PROs should be used both in clinical trials and routine practice for the evaluation of urticaria patients. We suggest that PROs should be considered as the primary outcome of future clinical trials. Two validated and disease-specific instruments for assessing PROs are available, the urticaria activity score (for symptoms) and the chronic urticaria questionnaire on quality of life CU-Q(2)oL. This latter tool, CU-Q(2)oL, is available in many languages and should be preferred, where available, over more generic instruments for assessing urticaria-specific effects on quality of life. CU-Q(2)oL is only suited for the investigation of patients with chronic spontaneous urticaria. Similar instruments for other forms of urticaria have yet to be developed and validated. Also, tools for assessing other chronic spontaneous urticaria PROs besides quality of life and symptoms are needed.


Advances in Sensor Technologies in the Era of Smart Factory and Industry 4.0.
The evolution of intelligent manufacturing has had a profound and lasting effect on the future of global manufacturing. Industry 4.0 based smart factories merge physical and cyber technologies, making the involved technologies more intricate and accurate; improving the performance, quality, controllability, management, and transparency of manufacturing processes in the era of the internet-of-things (IoT). Advanced low-cost sensor technologies are essential for gathering data and utilizing it for effective performance by manufacturing companies and supply chains. Different types of low power/low cost sensors allow for greatly expanded data collection on different devices across the manufacturing processes. While a lot of research has been carried out with a focus on analyzing the performance, processes, and implementation of smart factories, most firms still lack in-depth insight into the difference between traditional and smart factory systems, as well as the wide set of different sensor technologies associated with Industry 4.0. This paper identifies the different available sensor technologies of Industry 4.0, and identifies the differences between traditional and smart factories. In addition, this paper reviews existing research that has been done on the smart factory; and therefore provides a broad overview of the extant literature on smart factories, summarizes the variations between traditional and smart factories, outlines different types of sensors used in a smart factory, and creates an agenda for future research that encompasses the vigorous evolution of Industry 4.0 based smart factories.


Dual p38/JNK mitogen activated protein kinase inhibitors prevent ozone-induced airway hyperreactivity in guinea pigs.
Ozone exposure causes airway hyperreactivity and increases hospitalizations resulting from pulmonary complications. Ozone reacts with the epithelial lining fluid and airway epithelium to produce reactive oxygen species and lipid peroxidation products, which then activate cell signaling pathways, including the mitogen activated protein kinase (MAPK) pathway. Both p38 and c-Jun NH2 terminal kinase (JNK) are MAPK family members that are activated by cellular stress and inflammation. To test the contribution of both p38 and JNK MAPK to ozone-induced airway hyperreactivity, guinea pigs were pretreated with dual p38 and JNK MAPK inhibitors (30 mg/kg, i.p.) 60 minutes before exposure to 2 ppm ozone or filtered air for 4 hours. One day later airway reactivity was measured in anesthetized animals. Ozone caused airway hyperreactivity one day post-exposure, and blocking p38 and JNK MAPK completely prevented ozone-induced airway hyperreactivity. Blocking p38 and JNK MAPK also suppressed parasympathetic nerve activity in air exposed animals, suggesting p38 and JNK MAPK contribute to acetylcholine release by airway parasympathetic nerves. Ozone inhibited neuronal M2 muscarinic receptors and blocking both p38 and JNK prevented M2 receptor dysfunction. Neutrophil influx into bronchoalveolar lavage was not affected by MAPK inhibitors. Thus p38 and JNK MAPK mediate ozone-induced airway hyperreactivity through multiple mechanisms including prevention of neuronal M2 receptor dysfunction.


Hormone factors play a favorable role in female head and neck cancer risk.
Due to lower female incidence, estimates of exogenous and endogenous hormonal factors in head and neck cancers (HNCs, comprising cancers of the oral cavity, oropharynx, hypopharynx, and larynx) among women have been inconsistent and unable to account for key HNC risk factors. We pooled data from 11 studies from Europe, North America, and Japan. Analysis included 1572 HNC female cases and 4343 controls. Pooled odds ratios (ORs) estimates and their 95% confidence intervals (CIs) were calculated using multivariate logistic regression models adjusting for tobacco smoking and alcohol drinking. Lower risk was observed in women who used hormone replacement therapy (HRT) (OR = 0.58; 95% CI: 0.34-0.77). Pregnancy (OR = 0.61; 95% CI: 0.42-0.90) and giving birth (OR = 0.59; 95% CI: 0.38-0.90) at <35 years of age were inversely associated with HNCs. An inverse association with HNC was observed with age at start of HRT use (OR = 0.59; 95% CI: 0.39-0.90) for each additional 10 years and with duration of use (OR = 0.87; 95% CI: 0.76-0.99 for every 3 years). Exogenous female hormone use is associated with a nearly twofold risk reduction in female HNCs. The lower female HNC incidence may, in part, be explained by endogenous and exogenous estrogen exposures.


Evaluation of ICA512As in combination with other islet cell autoantibodies at the onset of IDDM.
The ICA512 pancreatic islet autoantigen is a putative tyrosine phosphatase that is co-identified with the earlier described 40-kDa autoantigen. We report the frequency of autoantibodies to islet cell antigen 512 (ICA512As) in recent-onset IDDM and compare this with other islet cell autoantibodies, including those to GAD (GADAs), insulin (IAAs), and islet cell cytoplasm (ICAs) identified by immunofluorescence. Sera from 232 children aged between 9 months and 14.9 years collected within 14 days of diagnosis were tested for ICA512As by a radioimmunoprecipitation assay. The results were compared with previously reported data for GADAs (n = 232), IAAs (n = 167), and ICAs (n = 230). The frequency of a positive result for ICA512As in children with newly diagnosed IDDM was 60%. The frequency was greater for children with an age of onset between 5 and 10 years (69%) than for children aged < 5 years (49%) and aged between 10 and 15 years (56%). The frequencies for other autoantibody reactivities were 69% for GADAs, 65% for IAAs, and 70% for ICAs. A combination of positive results for ICA512As, GADAs, and IAAs gave a sensitivity for the diagnosis of childhood IDDM of 95%, which was not significantly increased by a positive result for ICAs (96%). Our results further establish that positivity in a combination of tests is more valuable for the prediction of IDDM than a result for any single autoantibody and that the age of the patient should be considered when selecting the combination of tests to use.


Core journals that publish clinical trials of physical therapy interventions.
The objective of this study was to identify core journals in physical therapy by identifying those that publish the most randomized controlled trials of physical therapy interventions, provide the highest-quality reports of randomized controlled trials, and have the highest journal impact factors. This study was an audit of a bibliographic database. All trials indexed in the Physiotherapy Evidence Database (PEDro) were analyzed. Journals that had published at least 80 trials were selected. The journals were ranked in 4 ways: number of trials published; mean total PEDro score of the trials published in the journal, regardless of publication year; mean total PEDro score of the trials published in the journal from 2000 to 2009; and 2008 journal impact factor. The top 5 core journals in physical therapy, ranked by the total number of trials published, were Archives of Physical Medicine and Rehabilitation, Clinical Rehabilitation, Spine, British Medical Journal (BMJ), and Chest. When the mean total PEDro score was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, Journal of the American Medical Association (JAMA), Stroke, Spine, and Clinical Rehabilitation. When the mean total PEDro score of the trials published from 2000 to 2009 was used as the ranking criterion, the top 5 journals were Journal of Physiotherapy, JAMA, Lancet, BMJ, and Pain. The most highly ranked physical therapy-specific journals were Physical Therapy (ranked eighth on the basis of the number of trials published) and Journal of Physiotherapy (ranked first on the basis of the quality of trials). Finally, when the 2008 impact factor was used for ranking, the top 5 journals were JAMA, Lancet, BMJ, American Journal of Respiratory and Critical Care Medicine, and Thorax. There were no significant relationships among the rankings on the basis of trial quality, number of trials, or journal impact factor. Physical therapists who are trying to keep up-to-date by reading the best available evidence on the effects of physical therapy interventions have to read more broadly than just physical therapy-specific journals. Readers of articles on physical therapy trials should be aware that high-quality trials are not necessarily published in journals with high impact factors.


The challenges of genome analysis in the health care setting.
Genome sequencing is now a sufficiently mature and affordable technology for clinical use. Its application promises not only to transform clinicians' diagnostic and predictive ability, but also to improve preventative therapies, surveillance regimes, and tailor patient treatment to an individual's genetic make-up. However, as with any technological advance, there are associated fresh challenges. While some of the ethical, legal and social aspects resulting from the generation of data from genome sequencing are generic, several nuances are unique. Since the UK government recently announced plans to sequence the genomes of 100,000 Health Service patients, and similar initiatives are being considered elsewhere, a discussion of these nuances is timely and needs to go hand in hand with formulation of guidelines and public engagement activities around implementation of sequencing in clinical practice.


Natural Phytochemicals in the Treatment and Prevention of Dementia: An Overview.
The word dementia describes a class of heterogeneous diseases which etiopathogenetic mechanisms are not well understood. There are different types of dementia, among which, Alzheimer's disease (AD), vascular dementia (VaD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD) are the more common. Currently approved pharmacological treatments for most forms of dementia seem to act only on symptoms without having profound disease-modifying effects. Thus, alternative strategies capable of preventing the progressive loss of specific neuronal populations are urgently required. In particular, the attention of researchers has been focused on phytochemical compounds that have shown antioxidative, anti-amyloidogenic, anti-inflammatory and anti-apoptotic properties and that could represent important resources in the discovery of drug candidates against dementia. In this review, we summarize the neuroprotective effects of the main phytochemicals belonging to the polyphenol, isothiocyanate, alkaloid and cannabinoid families in the prevention and treatment of the most common kinds of dementia. We believe that natural phytochemicals may represent a promising sources of alternative medicine, at least in association with therapies approved to date for dementia.


Configural information is processed differently in perception and recognition of faces.
Several previous studies have stressed the importance of processing configural information in face recognition. In this study the perception of configural information was investigated. Large overestimations were found when the eye-mouth distance and the inter-eye distance had to be estimated. Whereas configural processing is disrupted when inverted faces have to be recognized the perceptual overestimations persisted when faces were inverted. These results suggest that processing configural information is different in perceptual as opposed to recognition tasks.


Propofol Increases Host Susceptibility to Microbial Infection by Reducing Subpopulations of Mature Immune Effector Cells at Sites of Infection.
Anesthetics are known to modulate host immune responses, but separating the variables of surgery from anesthesia when analyzing hospital acquired infections is often difficult. Here, the bacterial pathogen Listeria monocytogenes (Lm) was used to assess the impact of the common anesthetic propofol on host susceptibility to infection. Brief sedation of mice with physiologically relevant concentrations of propofol increased bacterial burdens in target organs by more than 10,000-fold relative to infected control animals. The adverse effects of propofol sedation on immune clearance of Lm persisted after recovery from sedation, as animals given the drug remained susceptible to infection for days following anesthesia. In contrast to propofol, sedation with alternative anesthetics such as ketamine/xylazine or pentobarbital did not increase susceptibility to systemic Lm infection. Propofol altered systemic cytokine and chemokine expression during infection, and prevented effective bacterial clearance by inhibiting the recruitment and/or activity of immune effector cells at sites of infection. Propofol exposure induced a marked reduction in marginal zone macrophages in the spleens of Lm infected mice, resulting in bacterial dissemination into deep tissue. Propofol also significantly increased mouse kidney abscess formation following infection with the common nosocomial pathogen Staphylococcus aureus. Taken together, these data indicate that even brief exposure to propofol severely compromises host resistance to microbial infection for days after recovery from sedation.


A Descriptive Study of Chaplains' Code Blue Responses.
Family presence during resuscitation is the compassionate practice of allowing a patient's family to witness treatment for cardiac or respiratory arrest (code blue event) when appropriate. Offering family presence during resuscitation as an interprofessional practice is consistent with patient- and family-centered care. In many institutions, the role of family facilitator is not formalized and may be performed by various staff members. At the large academic institution of this study, the family facilitator is a member of the chaplain staff. To examine the frequency of family presence during code blue events and describe the role of chaplains as family facilitators. Chaplain staff documented information about their code responses daily from January 2012 through April 2020. They documented their response time, occurrence of patient death, presence of family at the event, and services they provided. A retrospective data review was performed. Chaplains responded to 1971 code blue pages during this time frame. Family members were present at 53% of code blue events. Chaplains provided multiple services, including crisis support, compassionate presence, spiritual care, bereavement support, staff debriefing, and prayer with and for patients, families, and staff. Family members are frequently present during code blue events. Chaplains are available to respond to all such events and provide a variety of immediate and longitudinal services to patients, families, and members of the health care team. Their experience in crisis management, spiritual care, and bereavement support makes them ideally suited to serve as family facilitators during resuscitation events.


Pulmonary vasculitis: diagnosis and endovascular therapy.
Pulmonary vasculitides are caused by a heterogeneous group of diseases with different clinical features and etiologies. Radiologic manifestations depend on the predominant type of vessel involved, which are grouped into large, medium, or small-sized vessels. Diagnosing pulmonary vasculitides is a challenging task, and radiologists play an important role in their management by providing supportive evidence for diagnosis and opportunities for minimally invasive therapy. This paper aims to present a practical approach for understanding the vasculitides that can affect the pulmonary vessels and lungs. We will describe and illustrate the main radiologic findings, discussing opportunities for minimally invasive treatment.


A minK-HERG complex regulates the cardiac potassium current I(Kr).
MinK is a widely expressed protein of relative molecular mass approximately 15K that forms potassium channels by aggregation with other membrane proteins. MinK governs ion channel activation, regulation by second messengers, and the function and structure of the ion conduction pathway. Association of minK with a channel protein known as KvLQT1 produces a voltage-gated outward K+ current (I[sK]) resembling the slow cardiac repolarization current (I[Ks]). HERG, a human homologue of the ether-a-go-go gene of the fruitfly Drosophila melanogaster, encodes a protein that produces the rapidly activating cardiac delayed rectifier (I[Kr]). These two potassium currents, I(Ks) and I(Kr), provide the principal repolarizing currents in cardiac myocytes for the termination of action potentials. Although heterologously expressed HERG channels are largely indistinguishable from native cardiac I(Kr), a role for minK in this current is suggested by the diminished I(Kr) in an atrial tumour line subjected to minK antisense suppression. Here we show that HERG and minK form a stable complex, and that this heteromultimerization regulates I(Kr) activity. MinK, through the formation of heteromeric channel complexes, is thus central to the control of the heart rate and rhythm.


Rational design and optimization of selenophenes with basic side chains as novel potent selective estrogen receptor modulators (SERMs) for breast cancer therapy.
To increase the diversity of estrogen receptor (ER) ligands having novel structures and activities, series of selenophene derivatives with a basic side chain (BSC) were synthesized and their biological activity as subtype-selective antagonists for the ER was explored. Compared with the selenophenes without a BSC, most compounds showed an increase in binding affinity, and several compounds displayed enhanced antagonist potency and antiproliferative activity. Especially, compound 16c exhibited excellent transcriptional activity for ERα (IC50 = 13 nM) which made this compound the most potent antagonist for ERα of the whole series and is 66-fold better than the best selenophene compound without a BSC. Moreover, several compounds showed values of IC50 better than that of 4-hydroxytamoxifen in breast cancer MCF-7 cells. The modeling study indicated that the basic side chain might contribute to their increased antagonist potency and antiproliferative activity. These new ligands have the potential to be further developed as novel agents to improve therapeutics that target the estrogen receptor.


Single-nucleotide polymorphism detection by denaturing high-performance liquid chromatography and direct sequencing in genes in the MHC class III region encoding novel cell surface molecules.
The class III region of the human major histocompatibility complex (MHC) contains approximately 59 genes, many of which encode polypeptides with a variety of different functions. Eight of these genes are of particular interest because they encode novel surface molecules that could be involved in immune and/or inflammatory responses and are excellent candidates as disease susceptibility loci. These molecules are members of two different superfamilies, the immunoglobulin superfamily (1C7, G6B, and G6F genes) and the leucocyte antigen-6 superfamily (G6C, G6D, G6E, G5C, and G5B genes). Some level of variation was found when overlapping genomic DNAs from different haplotypes were compared. The present work describes a systematic search for single-nucleotide polymorphisms (SNPs) in these genes using direct sequencing and denaturing high-performance liquid chromatography (DHPLC) in 24 unrelated healthy individuals. We validated the DHPLC methodology by first studying the 1C7 gene. This gene was directly sequenced in all 24 samples, and DHPLC was found to resolve all the polymorphic sites present in the heterozygote samples tested. We screened the rest of the genes by DHPLC only, and only those chromatograms that revealed a polymorphic profile were sequenced. We detected one SNP every 489 bp in the 18 kb of DNA studied, corresponding to theta = 4.61x10-4. The diversity in noncoding regions is 1 SNP/560 bp, but a higher frequency was detected in coding regions with 1 SNP/423 bp corresponding to theta =5.33x10-4. Of the coding SNPs, 63.6% caused amino acid substitutions. The power of this study is emphasized by the fact that of the 37 SNPs/indels detected, only 6 can be found in the SNP database at the NCBI.


Association of bone attrition with knee pain, stiffness and disability: a cross-sectional study.
Bone pathologies as detected on MRI are associated with the presence of pain in knee osteoarthritis (OA). The authors examined whether bone attrition assessed on x-rays was associated with pain, stiffness and disability. The authors analysed x-rays of 1326 knees with OA from 783 individuals participating in the cross-sectional population-based Somerset and Avon Survey of Health. The diagnosis of OA was defined by the presence of osteophytes in anteroposterior (AP) or lateral views. Bone attrition was graded from 0 (no attrition) to 3 (severe attrition >10 mm) and Kellgren and Lawrence (K/L) scores were assigned on AP views. Logistic regression models adjusted for gender, age, body mass index, effusion and K/L scores were used to determine whether bone attrition was associated with pain, stiffness and disability. Pain was reported in 84 knees (74%) with radiographic bone attrition compared with 505 (42%) without bone attrition (adjusted OR 2.22, 95% CI 1.29 to 3.80). The adjusted OR was increased for day pain but not for night pain (p for interaction <0.001). Stiffness was reported for 85 knees with bone attrition (75%) and 437 knees without (36%) (adjusted OR 3.23, 95% CI 1.85 to 5.64). Disability was reported by 40 individuals with bone attrition (50%) and 140 individuals without (24%) (adjusted OR 2.09, 95% CI 1.19 to 3.68). Bone attrition detected on conventional x-rays using a simple cheap technique is strongly associated with the presence of day pain, stiffness and disability in knee OA.


The regulation of autophagy - unanswered questions.
Autophagy is an intracellular lysosomal (vacuolar) degradation process that is characterized by the formation of double-membrane vesicles, known as autophagosomes, which sequester cytoplasm. As autophagy is involved in cell growth, survival, development and death, the levels of autophagy must be properly regulated, as indicated by the fact that dysregulated autophagy has been linked to many human pathophysiologies, such as cancer, myopathies, neurodegeneration, heart and liver diseases, and gastrointestinal disorders. Substantial progress has recently been made in understanding the molecular mechanisms of the autophagy machinery, and in the regulation of autophagy. However, many unanswered questions remain, such as how the Atg1 complex is activated and the function of PtdIns3K is regulated, how the ubiquitin-like conjugation systems participate in autophagy and the mechanisms of phagophore expansion and autophagosome formation, how the network of TOR signaling pathways regulating autophagy are controlled, and what the underlying mechanisms are for the pro-cell survival and the pro-cell death effects of autophagy. As several recent reviews have comprehensively summarized the recent progress in the regulation of autophagy, we focus in this Commentary on the main unresolved questions in this field.


Whole body hyperthermia and preconditioning of the heart: basic concepts, complexity, and potential mechanisms.
Whole body hyperthermia (WBH) is a distinctive pathophysiological condition with significant impact on tissue metabolism and organ functions. WBH has been investigated as a promising adjunct therapy to the conventional chemo- or radiotherapy for treating certain types of cancer. Numerous studies have shown that WBH is associated with induction of heat shock proteins (HSPs), which in turn modulate cellular survival or death. A brief period of WBH (40-42 degrees C; 15-20 min) can induce delayed protection against lethal endotoxemia as well as various forms of injury in brain, heart, liver, lungs, small intestine, and skeletal muscle. This review article focuses on discussing the WBH-induced myocardial protection against ischemia/reperfusion injury. Most recently, possible involvement of protein kinase C, mitogen-activated protein kinases, nitric oxide, ATP-sensitive potassium channels, and neural peptides in the signal transduction pathways has been demonstrated. On the other hand, whether HSPs or antioxidant enzymes are the primary end-effector of the cardioprotection continues to be a matter of ongoing debates. It has also been recognized that the complex nature of WBH may be the responsible factor for the discordant results among various studies, especially across different animal species or strains, in terms of the time course and potency of WBH-induced cardioprotection. Nevertheless, a better understanding of the WBH-elicited myocardial ischemic resistance may have a wide spectrum of clinical implications as well as insightful inputs into the hyperthermic biology.


Myc and Max homologs in Drosophila.
The proteins encoded by the myc proto-oncogene family are involved in cell proliferation, apoptosis, differentiation, and neoplasia. Myc acts through dimerization with Max to bind DNA and activate transcription. Homologs of the myc and max genes were cloned from the fruit fly Drosophila melanogaster and their protein products (dMyc and dMax) were shown to heterodimerize, recognize the same DNA sequence as their vertebrate homologs, and activate transcription. The dMyc protein is likely encoded by the Drosophila gene diminutive (dm), a mutation in which results in small body size and female sterility caused by degeneration of the ovaries. These findings indicate a potential role for Myc in germ cell development and set the stage for genetic analysis of Myc and Max.


Yellow to blue switching of fluorescence by the tuning of the pentaphenylphosphole structure: phosphorus electronic state vs. ring conjugation.
The interaction between diphenylacetylene and dichlorophenylphosphine under various conditions is a simple method for the preparation of pentaphenylphosphole derivatives exhibiting fluorescence properties. Depending on the electronic state of the various centers of the phospholic structure, it was possible to obtain molecules with fluorescence, as in the blue area for 1,2,3,4,5-pentaphenyl-2,5-dihydro-phosphole-1-oxide (H2PPPO), in the yellow area for 1,2,3,4,5-pentaphenylphosphole-1-oxide (PPPO) and in the cyan area for 1,2,3,4,5-pentaphenylphosphole (PPP). The effect of the structure and π-conjugation on the optical properties of these compounds was studied using PPP derivatives as examples. Unusual changes in the optical properties of PPP derivatives in solution and in the crystalline state are explained. In the case of agglomeration of PPPO and PPP molecules, the effect of aggregation-induced emission (AIE) was observed to have weak fluorescence in solution and strong fluorescence in the aggregated state. However, for H2PPPO, the AIE effect remains mild. With the help of experimental studies, supported by theoretical calculations, the main mechanism of the optical properties of pentaphenylphosphole derivatives has been revealed. It was observed that the intramolecular motions of PPPO and PPP are more limited in the solid state than the motions of H2PPPO, which is associated with less conjugation of the phenyl rotors of H2PPPO. The analysis of the structure and distribution of electron density showed why hydrogenation of the phosphole ring leads to a sharp change in the optical properties of pentaphenylphosphole derivatives, while the oxidation of phosphorus does not lead to the disappearance of the AIE effect and to a lesser extent affects the change in the fluorescence wavelength. Thus, it was shown how the regulation of various structural features of the phospholic ring helps to control the optical properties of such compounds.


Small bites versus large bites for closure of abdominal midline incisions (STITCH): a double-blind, multicentre, randomised controlled trial.
Incisional hernia is a frequent complication of midline laparotomy and is associated with high morbidity, decreased quality of life, and high costs. We aimed to compare the large bites suture technique with the small bites technique for fascial closure of midline laparotomy incisions. We did this prospective, multicentre, double-blind, randomised controlled trial at surgical and gynaecological departments in ten hospitals in the Netherlands. Patients aged 18 years or older who were scheduled to undergo elective abdominal surgery with midline laparotomy were randomly assigned (1:1), via a computer-generated randomisation sequence, to receive small tissue bites of 5 mm every 5 mm or large bites of 1 cm every 1 cm. Randomisation was stratified by centre and between surgeons and residents with a minimisation procedure to ensure balanced allocation. Patients and study investigators were masked to group allocation. The primary outcome was the occurrence of incisional hernia; we postulated a reduced incidence in the small bites group. We analysed patients by intention to treat. This trial is registered at Clinicaltrials.gov, number NCT01132209 and with the Nederlands Trial Register, number NTR2052. Between Oct 20, 2009, and March 12, 2012, we randomly assigned 560 patients to the large bites group (n=284) or the small bites group (n=276). Follow-up ended on Aug 30, 2013; 545 (97%) patients completed follow-up and were included in the primary outcome analysis. Patients in the small bites group had fascial closures sutured with more stitches than those in the large bites group (mean number of stitches 45 [SD 12] vs 25 [10]; p<0·0001), a higher ratio of suture length to wound length (5·0 [1·5] vs 4·3 [1·4]; p<0·0001) and a longer closure time (14 [6] vs 10 [4] min; p<0·0001). At 1 year follow-up, 57 (21%) of 277 patients in the large bites group and 35 (13%) of 268 patients in the small bites group had incisional hernia (p=0·0220, covariate adjusted odds ratio 0·52, 95% CI 0·31-0·87; p=0·0131). Rates of adverse events did not differ significantly between groups. Our findings show that the small bites suture technique is more effective than the traditional large bites technique for prevention of incisional hernia in midline incisions and is not associated with a higher rate of adverse events. The small bites technique should become the standard closure technique for midline incisions. Erasmus University Medical Center and Ethicon.


AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY DISEASE STATE CLINICAL REVIEW: THE INCREASING INCIDENCE OF THYROID CANCER.
(1) Describe current epidemiology of thyroid cancer in the United States; (2) evaluate hypothesized causes of the increased incidence of thyroid cancer; and (3) suggest next steps in research and clinical action. Analysis of data from Surveillance, Epidemiology and End Results System and the National Center for Vital Statistics. Literature review of published English-language articles through December 31, 2013. The incidence of thyroid cancer has tripled over the past 30 years, whereas mortality is stable. The increase is mainly comprised of smaller tumors. These facts together suggest the major reason for the increased incidence is detection of subclinical, nonlethal disease. This has likely occurred through: health care system access, incidental detection on imaging, more frequent biopsy, greater volumes of and extent of surgery, and changes in pathology practices. Because larger-size tumors have increased in incidence also, it is possible that there is a concomitant true rise in thyroid cancer incidence. The only clearly identifiable contributor is radiation exposure, which has likely resulted in a few additional cases annually. The contribution of the following causes to the increasing incidence is unclear: iodine excess or insufficiency, diabetes and obesity, and molecular disruptions. The following mechanisms do not currently have strong evidence to support a link with the development of thyroid cancer: estrogen, dietary nitrate, and autoimmune thyroid disease. Research should focus on illuminating which thyroid cancers need treatment. Patients should be advised of the benefits as well as harms that can occur with treatment of incidentally identified, small, asymptomatic thyroid cancers.


Metastasis-directed therapy of regional and distant recurrences after curative treatment of prostate cancer: a systematic review of the literature.
The introduction of novel imaging modalities has increased the detection of oligometastatic prostate cancer (PCa) recurrence, potentially justifying the use of a metastasis-directed therapy (MDT) with surgery or radiotherapy (RT) rather than a systemic approach. To perform a systematic review of MDT for oligometastatic PCa recurrence. This systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. We searched the Medline and Embase databases from 1946 to February 2014 for studies reporting on biochemical or clinical progression and/or toxicity or complications of MDT (RT or surgery). Reports were excluded if these end points could not be ascertained or separately analysed, or if insufficient details were provided. Methodological quality was assessed using an 18-item validated quality appraisal tool for case series. Fifteen single-arm case series reporting on a total of 450 patients met the inclusion criteria. Seven studies were considered of acceptable quality. Oligometastatic PCa recurrence was diagnosed with positron emission tomography with coregistered computed tomography in most of the patients (98%). Nodal, bone, and visceral metastases were treated in 78%, 21%, and 1%, respectively. Patients were treated with either RT (66%) or lymph node dissection (LND) (34%). Adjuvant androgen deprivation was given in 61% of patients (n=275). In the case of nodal metastases, prophylactic nodal irradiation was administered in 49% of patients (n=172). Overall, 51% of patients were progression free 1-3 yr after salvage MDT, with most of them receiving adjuvant treatment. For RT, grade 2 toxicity was observed in 8.5% of patients, with one case of grade 3 toxicity. In the case of LND, 11% and 12% of grade 2 and grade 3 complications, respectively, were reported. MDT is a promising approach for oligometastatic PCa recurrence, but the low level of evidence generated by small case series does not allow extrapolation to a standard of care. We performed a systematic review to assess complications and outcomes of treating oligometastatic prostate cancer recurrence with surgery or radiotherapy. We concluded that although this approach is promising, it requires validation in randomised controlled trials.


Use of thiolated oligonucleotides as anti-fouling diluents in electrochemical peptide-based sensors.
We incorporated short thiolated oligonucleotides as passivating diluents in the fabrication of electrochemical peptide-based (E-PB) sensors, with the goal of creating a negatively charged layer capable of resisting non-specific adsorption of matrix contaminants. The E-PB HIV sensors fabricated using these diluents were found to be more specific and selective, while retaining attributes similar to the sensor fabricated without these diluents. Overall, these results highlight the advantages of using oligonucleotides as anti-fouling diluents in self-assembled monolayer-based sensors.


Investigating mitochondrial dysfunction to increase drug safety in the pharmaceutical industry.
Drug-induced mitochondrial dysfunction is a contributor to both late-stage compound attrition and post-market drug withdrawals. This review outlines the mechanisms which lead to drug-induced mitochondrial dysfunction and discusses the tremendous advances that have been made in the development of in vitro methods to identify mitochondrial impairment. Potentially useful animal models and in vivo methods to detect drug-induced mitochondrial impairment are also discussed.


National Database Analysis of Single-Level versus Multilevel Sleep Surgery.
Objective Recent evidence suggests that multilevel sleep surgery improves outcomes when compared with palate surgery alone for most patients. The study objective was to compare demographic and outcomes data for palate surgery (uvulopalatopharyngoplasty [UPPP]) alone versus multilevel surgery through a national insurance claims database. Study Design Retrospective cohort study. Setting National insurance claims database. Subjects and Methods An adult cohort undergoing single-level UPPP versus UPPP with nasal and/or tongue/hypopharyngeal surgery was identified in the Truven Health Analytics MarketScan Research Databases for the years 2010 through 2012. Demographic and outcomes data were assessed at short-term (≤14 days), intermediate (15-60 days), and long-term (61-183 days) intervals via a multivariate regression model adjusted for age, sex, geographic region, insurance type, and the Charlson-Deyo comorbidity score. The primary long-term complication considered was positive airway pressure (PAP) equipment supply, implying possible treatment failure. Results The cohort included 14,633 patients: 7559 (51.6%), UPPP alone; 5219 (35.7%), UPPP + nasal surgery; 1164 (7.95%), UPPP + tongue/hypopharyngeal surgery; and 691 (4.7%), UPPP + nasal + tongue/hypopharyngeal surgery. Demographic data were similar among the groups. UPPP alone had lower rates of postoperative bleeding than UPPP + tongue/hypopharyngeal surgery (4.31% vs 6.19%, P = .004). Multivariate modeling indicated that the addition of either nasal surgery (odds ratio = 1.21, 95% CI = 1.10-1.34, P < .001) or tongue/hypopharyngeal surgery (odds ratio = 1.15, 95% CI = 1.00-1.32, P = .048) to UPPP was associated with increased odds of postoperative continuous positive airway pressure. Conclusions UPPP alone is currently the predominant form of sleep surgery in the United States. Multilevel surgery had greater odds of postoperative bleeding and positive airway pressure equipment supply than UPPP alone. Dedicated studies formally evaluating single- versus multilevel sleep surgery and the impact of possible surgeon/patient selection bias should be a priority.


Automated multifilter rotating shadow-band radiometer: an instrument for optical depth and radiation measurements.
The multifilter rotating shadow-band radiometer is a ground-based instrument that uses independent interference-filter-photodiode detectors and the automated rotating shadow-band technique to make spectrally resolved measurements at seven wavelength passbands (chosen at the time of manufacture between 350 nm and 1.7 µm) of direct-normal, total-horizontal, and diffuse-horizontal irradiances. This instrument achieves an accuracy in direct-normal spectral irradiance comparable with that of tracking radiometers, and it is more accurate than conventional instruments for the determination of the diffuse and total-horizontal spectral irradiances because the angular acceptance function of the instrument closely approximates the ideal cosine response, and because the measured direct-normal component can be corrected for the remaining angular acceptance error. The three irradiance components are measured with the same detector for a given wavelength. Together with the automated shadow-band technique, this guarantees hat the calibration coefficients are identical for each, thus reducing errors when one compares them (as opposed to measurements made with independent instruments). One can use the direct-normal component observations for Langley analysis to obtain depths and to provide an ongoing calibration against the solar constant by extrapolation to zero air mass. Thus the long-term stability of all three measured components can be tied to the solar constant by an analysis of the routinely collected data.


Olfaction and topography, but not magnetic cues, control navigation in a pelagic seabird: displacements with shearwaters in the Mediterranean Sea.
Pelagic seabirds wander the open oceans then return accurately to their habitual nest-sites. We investigated the effects of sensory manipulation on oceanic navigation in Scopoli's shearwaters (Calonectris diomedea) breeding at Pianosa island (Italy), by displacing them 400 km from their colony and tracking them. A recent experiment on Atlantic shearwaters (Cory's shearwater, Calonectris borealis) breeding in the Azores indicated a crucial role of olfaction over the open ocean, but left open the question of whether birds might navigate by topographical landmark cues when available. Our experiment was conducted in the Mediterranean sea, where the availability of topographical cues may provide an alternative navigational mechanism for homing. Magnetically disturbed shearwaters and control birds oriented homeward even when the coast was not visible and rapidly homed. Anosmic shearwaters oriented in a direction significantly different from the home direction when in open sea. After having approached a coastline their flight path changed from convoluted to homeward oriented, so that most of them eventually reached home. Beside confirming that magnetic cues appear unimportant for oceanic navigation by seabirds, our results support the crucial role of olfactory cues for birds' navigation and reveal that anosmic shearwaters are able to home eventually by following coastal features.


Diversity in genomic organisation, developmental regulation and distribution of the murine PR72/B" subunits of protein phosphatase 2A.
Protein phosphatase 2A (PP2A) is a serine/threonine-specific phosphatase displaying vital functions in growth and development through its role in various signalling pathways. PP2A holoenzymes comprise a core dimer composed of a catalytic C and a structural A subunit, which can associate with a variable B-type subunit. The importance of the B-type subunits for PP2A regulation cannot be overestimated as they determine holoenzyme localisation, activity and substrate specificity. Three B-type subunit families have been identified: PR55/B, PR61/B' and PR72/B", of which the latter is currently the least characterised. We deduced the sequences and genomic organisation of the different murine PR72/B" isoforms: three genes encode nine isoforms, five of which are abundantly expressed and give rise to genuine PP2A subunits. Thereby, one novel subunit was identified. Using Northern blotting, we examined the tissue-specific and developmental expression of these subunits. All subunits are highly expressed in heart, suggesting an important cardiac function. Immunohistochemical analysis revealed a striated expression pattern of PR72 and PR130 in heart and skeletal muscle, but not in bladder smooth muscle. The subcellular localisation and cell cycle regulatory ability of several PR72/B" isoforms were determined, demonstrating differences as well as similarities. In contrast to PR55/B and PR61/B', the PR72/B" family seems evolutionary more divergent, as only two of the murine genes have a human orthologue. We have integrated these results in a more consistent nomenclature of both human and murine PR72/B" genes and their transcripts/proteins. Our results provide a platform for the future generation of PR72/B" knockout mice.


A systematic review into the efficacy of static stretching as part of a warm-up for the prevention of exercise-related injury.
A systematic review of the literature was undertaken to assess the efficacy of static stretching as part of the warm-up for the prevention of exercise-related injuries. Computer-aided literature search for articles post-1990 and pre-January 2008 related to static stretching and injury prevention using MEDLINE, SPORT Discus, PubMed, and ScienceDirect databases. All relevant randomised clinical trials (RCTs) and controlled clinical trials (CCTs) satisfying inclusion/exclusion criteria were evaluated by methodological assessment to score the studies using accredited criteria. Seven out of 364 studies met the inclusion/exclusion criteria. All four RCTs concluded that static stretching was ineffective in reducing the incidence of exercise-related injury, and only one of the three CCTs concluded that static stretching did reduce the incidence of exercise-related injury. Three out of the seven studies noted significant reductions in musculotendinous and ligament injuries following a static stretching protocol despite nonsignificant reductions in the all-injury risk. All RCTs scored over 50 points (maximum possible score = 100), whereas all CCTs scored under 45 points. There is moderate to strong evidence that routine application of static stretching does not reduce overall injury rates. There is preliminary evidence, however, that static stretching may reduce musculotendinous injuries.


The influence of crystalloid and colloid replacement solutions in acute normovolemic hemodilution: a preliminary survey of hemostatic markers.
Acute normovolemic hemodilution (ANH), in which blood for autologous use is collected immediately before the onset of surgical blood loss, is a recommended autologous blood procurement technique for blood conservation. Both crystalloid and colloid replacement fluids have been used to maintain normovolemia during ANH, but few data are available to justify the use of a particular replacement fluid. Therefore, we designed a prospective, randomized study to determine if the replacement fluid choice affects various coagulation variables and perioperative blood loss. Forty adult patients, ASA physical status 1-3, scheduled for ANH during radical prostatectomy were randomly assigned to one of four replacement fluid groups: (a) Ringer's lactate, (b) 5% albumin, (c) 6% dextran 70 (DEX), or (d) 6% hetastarch (HES). After the induction of a standardized general anesthetic, all patients underwent ANH to a final hemoglobin level of 9 g/dL. Complete blood count, prothrombin time, partial thromboplastin time, fibrinogen, factors V and VIII levels, bleeding time, and thromboelastography (TEG measurements were obtained at similar time points in the procedure. When compared with baseline, activated partial thromboplastin time decreased and factor VIII levels increased in the postanesthesia care unit in both the Ringer's lactate and 5% albumin groups. The DEX and HES groups demonstrated a decrease in TEG maximum amplitude between preoperative and postanesthesia care unit measurements and TEG alpha (angle) was decreased from baseline in the DEX group. The changes in factor VIII, activated partial thromboplastin time, and TEG measurements indicate that HES and DEX may attenuate the hypercoagulability related to surgery.


Evaluation of Predictability of Suitable Implant Lengths as related to Accurate Treatment Planning using Recent Roentgenographic Measures: A Key to Success.
Selection of suitable length of dental implants is very subjective and largely depends on clinical evidences and operator's expertise. The present study was aimed to assess the role of cone beam computed tomography (CBCT) and cephalograms as far as the selection of right implant length is concerned. The study includes 220 patients for whom radiographic and follow-up records were obtained. There were 105 males and 115 females in the age range of 22 to 58 years. A total of 98 implant sites in different edentulous areas were studied. Length of implant was predicted at treatment planning and compared with finally placed implant at surgical stages. It also includes the in-depth exploration of (1) number of implants placed per patient, (2) implant per edentulous areas, (3) implant location, and (4) implant region. For prediction of implant lengths, CBCT results were obtained and compared with cephalometric findings. Accuracies of implant lengths as planned by CBCT and cephalometric images were also studied at treatment planning and surgical stages. Statistical analysis and results: Upon statistical comparisons, we found that larger implant lengths chosen at treatment planning stage did not change in 65.5% of patients. In addition, the smaller length implants were just about the same as that with larger dimensions. The CBCT results were satisfactory (up to 98.5%). Cephalometry was performed well in this prediction, especially in posterior mandible (87.9%). However, its performance in anterior maxillary region was not satisfactory (69.6%). Intergroup comparisons of CBCT and cephalometric results at different regions were significant (p < 0.001). Our study results show insignificant changes in the length of implants that was exactly planned using CBCT scans. Therefore, accurate prediction of implant lengths can be done using CBCT scans as they have superior and advanced tools that facilitate presurgical decision-making. Lateral cephalometric evaluation has been shown as an imperative radiographic tool for determining implant lengths as it confirmed the significance bone resorption on the selection of implant length at different sites. The CBCT and lateral cephalogram offer excellent anatomical details that can be judiciously applied for treatment planning and other clinical decision-making, including selection of correct implant length. Our study advocates thorough cephalometric evaluations of mandible wherein implants are to be placed for implant-supported overdentures.


Strategy-dependent dissociation of the neural correlates involved in pain modulation.
Cognitive strategies are a set of psychologic behaviors used to modulate one's perception or interpretation of a sensation or situation. Although the effectiveness of each cognitive strategy seems to differ between individuals, they are commonly used clinically to help patients with chronic pain cope with their condition. The neural basis of commonly used cognitive strategies is not well understood. Understanding the neural correlates that underlie these strategies will enhance understanding of the analgesic network of the brain and the cognitive modulation of pain. The current study examines patterns of brain activation during two common cognitive strategies, external focus of attention and reappraisal, in patients with chronic pain using functional magnetic resonance imaging. Behavioral results revealed interindividual variability in the effectiveness of one strategy versus another in the patients. Functional magnetic resonance imaging revealed distinct patterns of activity when the two strategies were used. During external focus of attention, activity was observed mainly in cortical areas including the postcentral gyrus, inferior parietal lobule, middle occipital gyrus, and precentral gyrus. The use of reappraisal evoked activity in the thalamus and amygdala in addition to cortical regions. Only one area, the postcentral gyrus, was observed to be active during both strategies. The results of this study suggest that different cognitive behavioral strategies recruit different brain regions to perform the same task: pain modulation.


Expression of FGF2 in the limb blastema of two Salamandridae correlates with their regenerative capability.
Limb regenerative potential in urodeles seems to vary among different species. We observed that Triturus vulgaris meridionalis regenerate their limbs significantly faster than T. carnifex, where a long gap between the time of amputation and blastema formation occurs, and tried to identify cellular and molecular events that may underlie these differences in regenerative capability. Whereas wound healing is comparable in the two species, formation of an apical epidermal cap (AEC), which is required for blastema outgrowth, is delayed for approximately three weeks in T. carnifex. Furthermore, fewer nerve fibres are present distally early after amputation, consistent with the late onset of blastemal cell proliferation observed in T. carnifex. We investigated whether different expression of putative blastema mitogens, such as FGF1 and FGF2, in these species may underlie differences in the progression of regeneration. We found that whereas FGF1 is detected in the epidermis throughout the regenerative process, FGF2 onset of expression in the wound epidermis of both species coincides with AEC formation and initiation of blastemal cell proliferation, which is delayed in T. carnifex, and declines thereafter. In vitro studies showed that FGF2 activates MCM3, a factor essential for DNA replication licensing activity, and can be produced by blastemal cells themselves, indicating an autocrine action. These results suggest that FGF2 plays a key role in the initiation of blastema growth.


Sexual and reproductive health risks amongst female adolescents who use amphetamine-type stimulants and sell sex: a qualitative inquiry in Yunnan, China.
China, as other Southeast Asian countries, has witnessed an increased use in amphetamine-type stimulants (ATS) amongst urban youth. Amongst female adolescents who both sell sex and use ATS, risk behaviours are compounded resulting in even poorer health outcomes. However, limited knowledge exists on ATS use patterns and ATS-related risk behaviours, particularly in this context. This research aimed to improve the understanding of these issues amongst female adolescents who use ATS and sell sex, and to inform future programming. This study utilised monthly focus group discussions (four in total) with the same study participants in Yunnan, China. From within a drug-treatment programme, female adolescents who reported both a history of drug use and selling sex were purposively enrolled in the study. Participating adolescent females were aged 17-19 years and were all internal-migrants with low literacy. All reported polydrug use (mainly methamphetamine and heroin, whereas ecstasy and ketamine have been infrequently employed). Being less informed about risks of drug use and lack of sexual and reproductive health knowledge seemed to contribute to problematic drug use, rough and prolonged sexual intercourse, inconsistent condom use and ineffective contraceptive practice. For their income, participants largely relied on selling sex, which was frequently coupled with drug sharing services to clients. However, despite the practices, women did not self-identify as sex workers, and therefore did not think that existing intervention services targeting female sex workers were relevant to them. Moreover, criminalization and stigmatisation of drug use and selling sex impeded their access to care services. Current harm reduction and HIV/sexually transmitted infection (STI) prevention services are unlikely to address the demand of female adolescents engaged in drug use and commercial sex. Our findings highlight that a comprehensive and coordinated harm reduction and sexual and reproductive health response should be conducted involving these most vulnerable adolescents.