Evaluation of friction of conventional and metal-insert ceramic brackets in various bracket-archwire combinations.
The purpose of the study was to measure and compare the level of frictional resistance generated between conventional ceramic brackets (Transcend Series 6000, 3M Unitek, Monrovia, Calif), ceramic brackets with stainless steel slot (Clarity, 3M Unitek), conventional stainless steel brackets (Victory Series, 3M Unitek), and 3 different orthodontic wire alloys: stainless steel (stainless steel, SDS Ormco, Glendora, Calif), nickel-titanium (Ni-Ti, SDS Ormco), and beta-titanium (TMA, SDS Ormco). All brackets had a 0.022-in slot, and orthodontic wire alloys were tested in 3 different sections: 0.016 in, 0.017 x 0.025 in, and 0.019 x 0.025 in. Each of the 27 bracket-archwire combinations was tested 10 times, and each test was performed with a new bracket-wire sample. Static and kinetic friction were measured on a specially designed apparatus. All data were statistically analyzed (analysis of variance and Scheffé for the bracket effect, Kruskal-Wallis and Mann Whitney for the alloy and section effects). Metal-insert ceramic brackets generated significantly lower frictional forces than did conventional ceramic brackets, but higher values than stainless steel brackets, in agreement with the findings of the few previous reports. Beta-titanium archwires had higher frictional resistances than did stainless steel and nickel-titanium archwires. No significant differences were found between stainless steel and nickel-titanium archwires. All the brackets showed higher static and kinetic frictional forces as the wire size increased. Metal-insert ceramic brackets are not only visually pleasing, but also a valuable alternative to conventional stainless steel brackets in patients with esthetic demands.


Constructing vulnerability: the historical, natural and social generation of flooding in metropolitan Manila.
Flooding is not a recent hazard in the Philippines but one that has occurred throughout the recorded history of the archipelago. On the one hand, it is related to a wider global ecological crisis to do with climatic change and rising sea levels but on the other hand, it is also the effect of more localised human activities. A whole range of socio-economic factors such as land use practices, living standards and policy responses are increasingly influencing the frequency of natural hazards such as floods and the corresponding occurrence of disasters. In particular, the reason why flooding has come to pose such a pervasive risk to the residents of metropolitan Manila has its basis in a complex mix of inter-relating factors that emphasise how the nature of vulnerability is constructed through the lack of mutuality between environment and human activity over time. This paper examines three aspects of this flooding: first, the importance of an historical approach in understanding how hazards are generated; second, the degree of interplay between environment and society in creating risk; and third, the manner in which vulnerability is a complex construction.


Clinicopathologic features of ovarian Sertoli-Leydig cell tumors.
Ovarian Stertoli-Ledig cell tumor (SLCT) is a rare type of sex cord-stromal tumor of the ovary. The present study was to evaluate clinicalopahologic features and prognosis of patients with Sertoli-Leydig cell tumor treated by surgery and adjuvant chemotherapy during short term follow-up. A total of sixteen patients with ovarian Sertoli-Leydig cell tumor treated at the Obstetrics and Gynecology Hospital, Shanghai, China, between Jan 2001 and Dec 2011 were reviewed. The clinical data, treatment and prognosis were obtained from medical records. The median age of the patients with ovarian Sertoli-Leydig cell tumor was about 27.5 years old in non-menopausal women, while the median age of menopausal women was about 63 years old. The most common complaint was with hormonal-related symptoms in the form of secondary amenorrhea and infinity, features of virilization, abdominal mass or irregular vaginal bleeding. All of sixteen patients underwent surgical staging and all were found to have stage I disease at the time of diagnosis. Eleven patients with intermediate and two patients with poorly differentiated tumors received adjuvant chemotherapy. There were differences found in operative time, blood loss and postoperative recovery time between laparotomy and laparoscopy. There were no disease-related deaths and all patients were under complete remission at the last follow-up. Ovarian Sertoli-Leydig cell tumors could happen in any period age of women. However, the tumors typically occur in the single side while still at the early stage, a favorable outcome could be achieved by surgery and adjuvant chemotherapy. Laparoscopy has similar surgical effects as laparotomy, but has a number of advantages.


Biobanking for Personalized Medicine.
A biobank is an entity that collects, processes, stores, and distributes biospecimens and relevant data for use in basic, translational, and clinical research. Biobanking of high-quality human biospecimens such as tissue, blood and other bodily fluids along with associated patient clinical information provides a fundamental scientific infrastructure for personalized medicine. Identification of biomarkers that are specifically associated with particular medical conditions such as cancer, cardiovascular disease and neurological disorders are useful for early detection, prevention, and treatment of the diseases. The ability to determine individual tumor biomarkers and to use those biomarkers for disease diagnosis, prognosis and prediction of response to therapy is having a very significant impact on personalized medicine and is rapidly changing the way clinical care is conducted. As a critical requirement for personalized medicine is the availability of a large collection of patient samples with well annotated patient clinical and pathological data, biobanks thus play an important role in personalized medicine advancement. The goal of this chapter is to explore the role of biobanks in personalized medicine and discuss specific needs regarding biobank development for translational and clinical research, especially for personalized medicine advancement.


The kidney and hypertension: over 70 years of research.
The crucial role of the kidneys in regulation of systemic blood pressure has been known for more than 70 years. A multitude of studies have described the regulatory mechanisms behind this interaction, and elucidate why kidney disease is such a rampant and difficult form of secondary hypertension. Historically, renal hypertension has primarily been described as derangements of the renin-angiotensin-aldosterone system (RAAS), and salt and volume retention. Renally mediated hypertension involves the activation of RAAS leading to angiotensin II-mediated vaso-constriction, and aldosterone-mediated salt retention. The increased sodium retention and volume expansion seen in kidney disease is accompanied by a failure to autoregulate the peripheral vasculature, leading to hypertension. An-giotensin II and aldosterone also cause increased inflammation and endothelial dysfunction, and volume retention leads to the elaboration of ouabain-like compounds that contribute to increased total peripheral resistance. More recently, studies have shown that activation of renal afferent pathways connecting with specific brain nuclei involved in the noradrenergic control of blood pressure appears to play a substantial role. This article will review the classic pa-radigms, as well as new and emerging paradigms linking the kidney with blood pressure.


Structural learning and integrative decomposition of multi-view data.
The increased availability of multi-view data (data on the same samples from multiple sources) has led to strong interest in models based on low-rank matrix factorizations. These models represent each data view via shared and individual components, and have been successfully applied for exploratory dimension reduction, association analysis between the views, and consensus clustering. Despite these advances, there remain challenges in modeling partially-shared components and identifying the number of components of each type (shared/partially-shared/individual). We formulate a novel linked component model that directly incorporates partially-shared structures. We call this model SLIDE for Structural Learning and Integrative DEcomposition of multi-view data. The proposed model-fitting and selection techniques allow for joint identification of the number of components of each type, in contrast to existing sequential approaches. In our empirical studies, SLIDE demonstrates excellent performance in both signal estimation and component selection. We further illustrate the methodology on the breast cancer data from The Cancer Genome Atlas repository.


Insulin-like growth factor-I receptor as a marker for prognosis and a therapeutic target in human esophageal squamous cell carcinoma.
Insulin-like growth factor (IGF)-I receptor (IGF-Ir) signaling is required for tumorigenicity and progression of many tumors but this pathway has not been well studied as a prognostic factor or potential therapeutic target in esophageal squamous cell carcinoma (ESCC). In this paper, the association between the expression of IGF-Ir and IGF-II ligand and prognosis was investigated immunohistochemically in 100 surgically resected ESCC. We then assessed the therapeutic effect of blocking IGF receptor signaling using dominant negative IGF-Ir (IGF-Ir/dn) in ESCC in vitro. Expression of IGF-Ir and IGF-II were detected in 60 and 50% of tumors, respectively, and were associated with invasion depth, metastasis, advanced tumor stage and recurrence. Patients with tumors expressing both IGF-Ir and IGF-II had a significantly shorter survival than those expressing either alone or neither in both single and multivariate analysis. IGF-Ir/dn suppressed proliferation and motility as well as upregulating chemotherapy-induced apoptosis through blocking ligand-induced Akt activation. We propose that detection of IGF-Ir/IGF-II in ESCC may be useful for the prediction of recurrence and poor prognosis and for selecting patients for IGF-Ir-targeted therapy. Therapeutic blockade of IGF-Ir may be a useful anticancer therapeutic for ESCC.


Risk of parenterally transmitted hepatitis following exposure to invasive procedures in Italy: SEIEVA surveillance 2000-2021.
Surgical interventions and invasive diagnostic/therapeutic procedures are known routes of transmission of viral hepatitis. Using data from the Italian surveillance system for acute viral hepatitis (SEIEVA), the aim of this study was to investigate the association between specific types of invasive procedures and the risk of acute HBV and HCV infections. Data from SEIEVA (period 2000-2021) were used. The association between acute HBV and HCV infection and potential risk factors, i.e. surgical interventions and diagnostic/therapeutic procedures (given according to the ICD-9-CM classification), was investigated in comparison to age-matched hepatitis A cases, used as controls, by conditional multiple logistic regression analysis. A total of 8,176 cases with acute HBV, 2,179 with acute HCV, and the respective age-matched controls with acute HAV infection were selected for the main analysis. Most of the procedures evaluated were associated with the risk of acquiring HBV or HCV. The strongest associations for HBV infection were: gynaecological surgery (odds ratio [OR] 5.19; 95% CI 1.12-24.05), otorhinolaryngological surgery (OR 3.78; 95% CI 1.76-8.09), and cardiac/thoracic surgery (OR 3.52; 95% CI 1.34-9.23); while for HCV infection, they were: neurosurgery (OR 11.88; 95% CI 2.40-58.85), otorhinolaryngological surgery (OR 11.54; 95% CI 2.55-52.24), and vascular surgery (OR 9.52; 95% CI 3.25-27.87). Hepatitis C was also strongly associated with ophthalmological surgery (OR 8.32; 95% CI 2.24-30.92). Biopsy and/or endoscopic procedures were significantly associated with both HCV (OR 3.84; 95% CI 2.47-5.95) and, to a lesser extent, HBV infection (OR 1.48; 95% CI 1.16-1.90). Despite the progress made in recent years, invasive procedures still represent a significant risk factor for acquiring parenterally transmitted hepatitis viruses, thus explaining the still numerous and unexpected cases diagnosed among the elderly population in Italy. Our results underline the importance of observing universal precautions to control the iatrogenic transmission of hepatitis viruses. Cases of parenterally transmitted acute viral hepatitis in the elderly population, that are difficult to explain based on the most widely recognised risk factors, continue to be diagnosed in Italy. Based on the Italian SEIEVA surveillance of acute viral hepatitis data, this study highlights an increased risk of acquiring hepatitis B and C following exposure to invasive procedures, which might explain the observed cases in elderly individuals. Furthermore, this finding emphasises the need to observe universal precautions strictly, in healthcare settings, including in the case of minor surgical procedures.


Elastic properties of monolayer graphene with different chiralities.
Using molecular mechanics simulations we investigate the in-plane elastic properties of monolayer graphene with different chirality angles under both uniaxial stretching and free-standing indentation. The effect of the loading range is also considered: the tensile strain ranges of 2% and 5% are selected. Under uniaxial stretching, all of the elastic properties including the second-order elastic stiffness (E), the Poisson's ratio (ν) and the third-order elastic constant (c(m)) are essentially not sensitive to the graphene chirality angle. The values of E are essentially not sensitive to the tensile strain range (ε), while the values of c(m) slightly increase (numerically) with the decrease of ε. Under free-standing indentation, the values of E and c(m) determined are higher than those obtained from uniaxial stretching, and this difference significantly increases with the decrease of the tensile strain, especially for c(m). The difference between the in-plane stretching results and the indentation results arises mainly from the van der Waals (VDW) interaction between the indenter tip and the graphene, and the effect of the VDW interaction rapidly decreases with the tensile strain. The VDW effect is also not sensitive to the chirality angle. Therefore, a relatively large tensile strain is required (e.g. 5%) in order to obtain more accurate results from free-standing indentation.


[Experience and results with the Loeffler operation for osteoarthritis of the knee joint (author's transl)].
A follow-up in 1975 of a group of patients that had previously been checked in 1972 after Loeffler's operation gave the following results: 1972: 40 patients where examined; of these, 90% where satisfied with the operation. 1975: 29 of the above group where re-examined; of these, 72.5% where satisfied with the operation, i.e. approximately 3 out of 4. From these result it follows that, in selected cases, there are favourable indications for the use of Loeffler's operation. Thus, modern medical practice should not forgo the use of operative methods which, at a minimum of risk to the patient, yield a considerable and long lasting positive result.


[(Th2F5)(NC7H5O4)2(H2O)][NO3]: an actinide-organic open framework.
We believe [(Th2F5)(NC7H5O4)2(H2O)][NO3] is the first three-dimensionally connected, actinide-organic framework solid. The structure is composed of thorium oxyfluoride chains, each of which connected to pyridinedicarboxylate groups to give a 3D cross-linked network with cavities containing nitrate anions.


Thoracotomy in Children: Review from a Low-Income Country.
Thoracotomy is indicated for several congenital and acquired disorders in children. It is among the surgical procedures which require a well-trained and dedicated surgical, anesthesia and critical care team which can be difficult to assemble in a low-income country setup. As the pattern and outcome of thoracotomy in children remained unreported from such setting, this study aims to shed light on this matter. A descriptive cross-sectional review was conducted. Children who have undergone thoracotomy for non-cardiac pathologies were included in the study. Demographic and clinical data were collected by chart review. Frequencies and percentages were used to describe categorical variables while mean, median, standard deviation and interquartile range were calculated for continuous variables. A total of 68 patients were operated on in the study period, out of which 44 (64.7%) were males. The mean ages of the children at the time of diagnosis and procedure were 4.05 ± 3.9 years and 4.14 ± 4.03 years, respectively. The most common indication for thoracotomy was pulmonary hydatid cyst (17; 25%) followed by congenital lobar emphysema (11; 16.2%). Muscle sparing posterolateral thoracotomy was the most common approach in 66 (97.1%) patients. The analgesic medications that were used in the post-operative period were paracetamol, diclofenac, ibuprofen, tramadol and morphine. Combined analgesics were administered in two-thirds of the patients while a single analgesic was used in the rest of the children. No regional blocks were administered post operatively as pediatric size catheters were not available. The morbidity and mortality rates were found to be 11.8% and 8.8%, respectively. The most common indication for thoracotomy in this study was pulmonary hydatid cyst. The provision of post-thoracotomy analgesia in our institution is suboptimal as evidenced by no use of regional blocks and poor practice of administering multimodal analgesia. Thoracotomy was associated with fairly high morbidity and mortality.


Computed Tomography-Based Templating of Proximal Ulna Intramedullary Screw Fixation.
Intramedullary screw fixation of the proximal ulna can be used for fixation of the ulnar component in total elbow arthroplasty. Our purpose was to use computed tomography (CT) to characterize proximal ulna anatomy with respect to intramedullary screw fixation, and then to validate this templating process by inserting intramedullary screws into 3-dimensional (3D)-printed models. Thirty elbow CT scans were reformatted in the axis of the proximal ulna. Screw placement was templated by fixing a length at 78 mm distal to the centerline of ulnohumeral rotation and measuring diameter, and then fixing the screw pitch diameter to 5.5 mm and measuring length. Three-dimensional models were printed for 5 patients, and intramedullary screws were advanced as distal as possible until endosteal fit was achieved. All patients had an anatomic limit for intramedullary screw fixation, due to dorsal angulation, varus angulation, or both. At 78 mm distal to the centerline of rotation, mean screw diameter was 5.4 mm (range, 3.2-8.0). When fixing screw diameter to 5.5 mm, the mean screw length was 79.9 mm (range, 64.2-107.9). All intramedullary screws were placed in the 3D models within 3 mm of the templated length, with correlation coefficient 0.992. This study characterized proximal ulna anatomy in the context of intramedullary screw fixation. Templating allows surgeons to predict intramedullary screw sizing, and a broad range of screw lengths and diameters is required when attempting intramedullary screw fixation for placement of the ulnar component in uncemented total elbow arthroplasty.


Comprehensive profiling of mercapturic acid metabolites from dietary acrylamide as short-term exposure biomarkers for evaluation of toxicokinetics in rats and daily internal exposure in humans using isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry.
Mercapturic acid metabolites from dietary acrylamide are important short-term exposure biomarkers for evaluating the in vivo toxicity of acrylamide. Most of studies have focused on the measurement of two metabolites, N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA) and N-acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine (GAMA). Thus, the comprehensive profile of acrylamide urinary metabolites cannot be fully understood. We developed an isotope dilution ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for the simultaneous determination of all four mercapturic acid adducts of acrylamide and its primary metabolite glycidamide under the electroscopy ionization negative (ESI-) mode in the present study. The limit of detection (LOD) and limit of quantification (LOQ) of the analytes ranged 0.1-0.3 ng/mL and 0.4-1.0 ng/mL, respectively. The recovery rates with low, intermediate and high spiking levels were calculated as 95.5%-105.4%, 98.2%-114.0% and 92.2%-108.9%, respectively. Acceptable within-laboratory reproducibility (RSD<7.0%) substantially supported the use of current method for robust analysis. Rapid pretreatment procedures and short run time (8 min per sample) ensured good efficiency of metabolism profiling, indicating a wide application for investigating short-term internal exposure of dietary acrylamide. Our proposed UHPLC-MS/MS method was successfully applied to the toxicokinetic study of acrylamide in rats. Meanwhile, results of human urine analysis indicated that the levels of N-acetyl-S-(2-carbamoylethyl)-L-cysteine-sulfoxide (AAMA-sul), which did not appear in the mercapturic acid metabolites in rodents, were more than the sum of GAMA and N-acetyl-S-(1-carbamoyl-2-hydroxyethyl)-L-cysteine (iso-GAMA). Thus, AAMA-sul may alternatively become a specific biomarker for investigating the acrylamide exposure in humans. Current proposed method provides a substantial methodology support for comprehensive profiling of toxicokinetics and daily internal exposure evaluations of acrylamide in vivo.


Extracorporeal life support for refractory ventricular tachycardia.
Extracorporeal life support (ECLS) is a very effective bridging therapy in patients with refractory ventricular tachycardia (VT) associated with cardiogenic shock. A moribund patient in extremis, is not amenable to optimization by standard ACC/AHA guidelines. New approaches and novel salvage techniques are necessary to improve outcomes in patients with refractory clinical settings such as malignant ventricular arrhythmias, cardiac arrest, cardiogenic shock and/or pulmonary failure until further management options are explored. Data base searches were done using key words such as ECLS, VT, cardiac arrest, VT ablation, venoarterial extra-corporeal membrane oxygenation (VA-ECMO). The use of ECLS has been described in a few case reports to facilitate VT ablation for incessant VT refractory to medical therapy. For patients with, out-of- hospital ventricular fibrillation (VF) and VT, Minnesota Resuscitation Consortium has implemented emergent advanced perfusion and reperfusion strategy, followed by coronary angiography and primary coronary intervention to improve outcome. The major indications for ECLS are cardiogenic shock related to acute myocardial infarction, myocarditis, post embolic acute cor pulmonale, drug intoxication and post cardiac arrest syndrome with the threat of multi-organ failure. ECLS permits the use of negative inotropic antiarrhythmic drug therapy, facilitates the weaning of catecholamine administration, thereby ending the vicious cycle of catecholamine driven electric storm. ECLS provides hemodynamic support during ablation procedure, while mapping and induction of VT is undertaken. ECLS provides early access to cardiac catheterization laboratory in patients with cardiac arrest due to shockable rhythm. The current evidence from literature, supports the use of ECLS to ensure adequate vital organ perfusion in patients with refractory VT. ECLS is a safe, feasible and effective therapeutic option when conventional therapies are insufficient to support cardiopulmonary function. A highly driven multidisciplinary team approach is essential to accomplish this task.


Reducing Stereotype Threat With Embodied Triggers: A Case of Sensorimotor-Mental Congruence.
In four experiments, we tested whether embodied triggers may reduce stereotype threat. We predicted that left-side sensorimotor inductions would increase cognitive performance under stereotype threat, because such inductions are linked to avoidance motivation among right-handers. This sensorimotor-mental congruence hypothesis rests on regulatory fit research showing that stereotype threat may be reduced by avoidance-oriented interventions, and motor congruence research showing positive effects when two parameters of a motor action activate the same motivational system (avoidance or approach). Results indicated that under stereotype threat, cognitive performance was higher when participants contracted their left hand (Study 1) or when the stimuli were presented on the left side of the visual field (Studies 2-4), as compared with right-hand contraction or right-side visual stimulation. These results were observed on math (Studies 1, 2, and 4) and Stroop (Study 3) performance. An indirect effect of congruence on math performance through subjective fluency was also observed.


Electron--atom (molecule) collision processes.
Electron-atom (molecule) collision processes at low and intermediate energies are discussed. Measurements of collision cross sections are described briefly. The experimental techniques and the interpretation of observations are illustrated by specific examples.


Role of TNF-alpha in gut mucosal changes after severe burn.
Gut epithelial cell death by apoptosis is increased in the gut epithelium after severe burn associated with mucosal atrophy. We hypothesized that tumor necrosis factor (TNF)-alpha-TNF receptor (TNFR) interaction activates apoptosis in small bowel mucosal cells after severe burn. C57BL6 mice received a 30% total body surface area scald burn and were treated with neutralizing anti-TNF-alpha. The proximal small bowel was assessed for mucosal atrophy. Proliferation and apoptosis of mucosal cells were assessed by proliferative cell nuclear antigen-immunostaining and terminal deoxyuridine nick-end labeling assay, respectively. Mucosal height and mucosal cell number decreased after burn. Anti-TNF-alpha-treated mice showed significantly less mucosal atrophy. Proliferation of intestinal cells was not changed with burn or anti-TNF-alpha treatment. An over threefold increase in apoptotic cell number was seen after burn, which was diminished by anti-TNF-alpha treatment. Changes in gut mucosal homeostasis after severe burn are affected, in part, by the activation of apoptosis by TNF-alpha-TNFR interaction.


Plant miRNA bol-miR159 Regulates Gut Microbiota Composition in Mice: In Vivo Evidence of the Crosstalk between Plant miRNAs and Intestinal Microbes.
New evidence reveals that bol-miR159, an miRNA rich in fruits and vegetables, cross-kingdomly functions in mammalian bodies. However, whether the miRNA could regulate gut microbiota remains unclear. Here, the effect of miR159 on mouse intestinal microbes was comprehensively examined. The results showed that supplementation of miR159 to the chow diet significantly enhanced the diversity of mouse gut microbiota without causing pathological lesions or inflammatory responses on the intestines. At the phylum level, miR159 increased the abundance of Proteobacteria and decreased the Firmicute-to-Bacteroidetes (F/B) ratio. miR159 had prebiotic-like effects on mouse gut microbiota, as it promoted the growth of the bacteria that is beneficial for maintaining gut health. The miRNA can target bacteria genes and get into the bacteria cells. The data provide direct in vivo evidence on the crosstalk between plant miRNAs and intestinal microbes, highlighting the potential for miRNA-based strategies that modulate gut microbes to improve host health.


Successes and failures in measles control.
The Expanded Programme on Immunization (EPI) of the World Health Organization has a global target of reducing measles incidence by 90% and mortality by 95% from pre-EPI levels by 1995. Both developed and developing countries that have given priority to measles control have substantially reduced measles morbidity and mortality, and some have come close to eliminating measles. A variety of vaccination schedules and strategies have been used, which reflect the differing program goals, health services infrastructure, and availability of resources in different countries. Failure to control measles has usually been due to a failure to implement planned strategies adequately. The highest priority in measles control is to assist countries, especially the lowest-income countries, to implement vaccination programs more effectively.


Epidemiology, diagnosis, and management of esophageal perforations: systematic review.
We performed a systematic review of epidemiological, diagnostic, and therapeutic outcomes of esophageal perforations. A systematic review was performed in PubMed database using the key-phrase 'esophageal perforation'. All studies regarding acute esophageal perforations were reviewed and parameters of epidemiology, diagnosis, and management published in the literature from 2005 up to 2015 were included in the study. Studies of postoperative esophageal leaks were excluded. Two researchers performed individually the research, while quality assessment was performed according to GRADE classification. Main outcomes and exposure were overall mortality, perforation-to-admission interval, anatomical position, cause, prevalent symptom at admission, diagnostic tests used, type of initial management (conservative or surgery), healing rate, and fistula complication. There were 1319 articles retrieved, of which 52 studies including 2,830 cases finally met inclusion criteria. Mean duration of study period was 15.2 years. Mean patient age was 58.4 years. Out of 52 studies included, there were 43 studies of very low or low quality included. The overall mortality rate according to extracted data was 13.3% (n = 214, 1,644 patients, 39 studies). Admission before 24 hours was reported in 58.1% of patients (n = 514). Position was thoracic in 72.6% of patients (n = 813, 1,120 patients, 20 studies). Mean cause of perforation was iatrogenic in 46.5% of patients (n = 899, 1,933 patients, 40 studies). Initial management was conservative in 51.3% of cases (n = 904, 1,762 patients, 41 studies) CT confirmed diagnosis in 38.7% of overall cases in which it was used as imaging diagnostic procedure (n = 266), X-ray in 36.6% (n = 231), and endoscopy in 37.4% (n = 343). Sepsis on admission was observed in 23.3% of cases (209 out of 898 patients, 16 studies). The present systematic review highlighted the significant proportion of cases diagnosed with delay over 24 hours, mortality rates ranging over 10% and no consensus regarding optimal therapeutic approach and optimal diagnostic management. As esophageal perforation represents a high-risk clinical condition without consensus regarding optimal management, there should be large multicenter prospective studies or Randomized Controlled Trial (RCT)s performed in order to advance diagnostic and therapeutic approach of such challenging pathology.


MCP-1-Functionalized, Core-Shell Gold Nanorod@Iron-Based Metal-Organic Framework (MCP-1/GNR@MIL-100(Fe)) for Photothermal Therapy.
The low vessel density and oxygen concentration in hypoxia are the main causes of reduced efficiency of anticancer therapeutics and can stimulate the tumor's relapse. Research showed that macrophages could cross the blood-vessel barriers and reach the hypoxic regions of tumors. Using macrophages in a drug delivery system has been a promising method for tumor targeting in recent years. In this work, we successfully modified monocyte chemoattractant protein-1 (MCP-1) and iron-based metal-organic framework (MIL-100(Fe)) on the photothermal agent, gold nanorods (GNRs) (i.e., MCP-1/GNR@MIL-100(Fe)), to increase cellular uptake and biocompatibility. The results of TEM, UV-vis, and FTIR all confirmed that we'd synthesized MCP-1/GNR@MIL-100(Fe) successfully, and the MCP-1/GNR@MIL-100(Fe) also showed good biocompatibility. A transwell migration assay illustrated that our material attracted macrophages, and the material uptake amount was increased by 1.5 times after MCP-1 functionalization. It also indicated that the macrophages have a tumor-targeting ability. In the in vivo experiment, we subcutaneously implanted U251 MG cells in nude mice as a xenograft model to demonstrate the photothermal activity of MCP-1/GNR@MIL-100(Fe). With successive NIR treatment, the tumor growth could be controlled, and the tumor volume still remained below 100 mm3 after laser treatment. MCP-1/GNR@MIL-100(Fe) combined with the laser treatment showed an excellent antitumor efficacy from the histology of tumor tissues, survival rates, and bioluminescence imaging.


Consideration of the effects of intense tissue heating on the RF electromagnetic fields during MRI: simulations for MRgFUS in the hip.
Due to the strong dependence of tissue electrical properties on temperature, it is important to consider the potential effects of intense tissue heating on the RF electromagnetic fields during MRI, as can occur in MR-guided focused ultrasound surgery. In principle, changes of the RF electromagnetic fields could affect both efficacy of RF pulses, and the MRI-induced RF heating (SAR) pattern. In this study, the equilibrium temperature distribution in a whole-body model with 2 mm resolution before and during intense tissue heating up to 60 °C at the target region was calculated. Temperature-dependent electric properties of tissues were assigned to the model to establish a temperature-dependent electromagnetic whole-body model in a 3T MRI system. The results showed maximum changes in conductivity, permittivity, [absolute value]B(1)(+)[absolute value] and SAR of about 25%, 6%, 2%, and 20%, respectively. Though the B1 field and SAR distributions are both temperature-dependent, the potential harm to patients due to higher SARs is expected to be minimal and the effects on the B1 field distribution should have minimal effect on images from basic MRI sequences.


[Anticonvulsive properties of enomelanin].
Antiepileptic effects of enomelanin (natural oligomer obtained from pressed grapes) were analysed on the models of focal and clonic-tonic epileptic activity (EA). Electrocorticographic and motor manifestations of EA have been studied. Enomelanin in EA models used was shown to possess marked anticonvulsive properties.


Total correction of hemophilia A mice with canine FVIII using an AAV 8 serotype.
Despite the popularity of adeno-associated virus 2 (AAV2) as a vehicle for gene transfer, its efficacy for liver-directed gene therapy in hemophilia A or B has been suboptimal. Here we evaluated AAV serotypes 2, 5, 7, and 8 in gene therapy of factor VIII (FVIII) deficiency in a hemophilia A mouse model and found that AAV8 was superior to the other 3 serotypes. We expressed canine B domain-deleted FVIII cDNA either in a single vector or in 2 separate AAV vectors containing the heavy- and light-chain cDNAs. We also evaluated AAV8 against AAV2 in intraportal and tail vein injections. AAV8 gave 100% correction of plasma FVIII activity irrespective of the vector type or route of administration.


MEASUREMENT OF THE CONCENTRATION OF 226RA, 232TH, 40K IN THE SOIL IN SETTLEMENTS ON THE COASTLINE OF LAKE VAN, TURKEY.
In this study, the natural radioactivity level and its effects on the environment of Lake Van, which is the largest lake in Turkey, were investigated extensively. Initially, 254 soil samples have been collected from the districts (Tusba, Edremit, Gevas, Tatvan, Ahlat, Adilcevaz, Ercis) located around the coastline of Lake Van in eastern Turkey. A Na(TI) detector was used to detect activity concentrations of radium (226Ra), thorium (232Th) and potassium (40K) in each collected soil sample. The obtained average results were compared with available data from Turkey and international data base. The average activity in soil samples was measured as 28.0 ± 3.7-43.6 ± 2.2 Bq/kg for 226Ra, 27.3 ± 4.1-55.4 ± 4.8 Bq/kg for 232Th and 377 ± 42- 706 ± 40 Bq/kg for 40K. It was observed that the average concentrations of 226Ra, 232Th, 40K (43.6 ± 2.2, 55.4 ± 4.8, 706 ± 40 Bq/kg, respectively) for Tatvan district and (37.0 ± 3.5, 51.4 ± 4.2, 479 ± 41 Bq/kg, respectively) for Ahlat district were higher than both national and international average value. In addition, radiological effect parameters originating from terrestrial natural radionuclides for the study area; gamma dose rate (Dout), annual effective dose equivalent (AEDE), and lifetime cancer development probability (LCR) were calculated. The Dout, AEDE, LCR (83.0 ± 3.9 nGy/h, 0.102 ± 0.005 mSv/y, 0.36 ± 0.02 x 10-3, respectively) parameters in Tatvan district were found to be above the international allowable value.


Technical Note: Single-shot phase retrieval method for synchrotron-based high-energy x-ray grating interferometry.
X-ray grating interferometry (XGI) provides substantially increased contrast over conventional absorption-based imaging methods and therefore shows great potential for future biomedical applications. In this work, we propose a single-shot phase retrieval method for synchrotron-based high-energy x-ray grating interferometry. Contrary to existing retrieval methods, the presented novel approach enables direct retrieval of the object's phase map quantitatively from a single projection image, thus significantly simplifying the experimental procedure and reducing data acquisition times. The phase retrieval method is analytically derived, based on the phase-attenuation duality of soft tissues when being imaged with high-energy x rays. The sensitivity of the retrieved phase map, quantified by the standard deviation, is evaluated as a function of the photon number. Numerical experiments are performed to validate the proposed method and provide some quantitative insight. The numerical results show that the method can provide high-quality phase images, where the well-known streak artifacts are significantly suppressed. Moreover, the retrieved phase maps confirm that the method is highly stable with respect to statistical noise. Thanks to simplified experimental procedure and reduced acquisition time and dose deposition to the sample, we believe that this new method can find its potential in biomedical imaging and in vivo studies. Future work will focus on the adaptation of the method to polychromatic x ray from tube source and to computed tomography.


Correlation between Body Mass Index and Lipid Profile in patients with Type 2 Diabetes attending a tertiary care hospital in Peshawar.
To determine the correlation between body mass index (BMI) and lipid profile in patients with Type 2 Diabetes (T2DM) attending a tertiary care hospital in Peshawar. A total of 305 patients (men, 132; women, 173) with T2DM visiting an Outpatient department in Northwest General Hospital and Research Centre, Peshawar from January 2016 to July 2016 were included in this study. The whole blood and sera were analyzed for Glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TGs), high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C). The correlation of BMI with lipid ratios and individual lipid indices were analysed. Mean of BMI was 29.29±5.23. Dyslipidemia; increased TC, increased LDL-C, increased triglyceride and decreased HDL-C were noted in 40.7%, 54.1%, 69.5% and 41% respectively. The mean difference of LDL-C (p=0.006) was significant between male and female. BMI, TC, TGs, and LDL-C showed no significant correlation where as a significant negative correlation between BMI and HDL-C was observed (r=-0.125, p=0.029, R2=0.016). The mean values of TC, TG, LDL-C, TC/ HDL-C and LDL/HDL were greater in patients with normal BMI compared to overweight and obese; however, the differences were not significant. HDL-C differed significantly in BMI groups (p=0.040). A significant negative correlation between BMI and HDL-C was observed, while the correlation between BMI and LDL-C was observed to be insignificant. HDL-C was found significantly higher in patients with normal BMI. These results are important to indicate that there is modest impact of BMI on lipid profile. Therefore, assessment and management for altered blood lipids should not be based on a patient's body weight or BMI.


Effects of taurodeoxycholate on in vivo water and solute transport in rat jejunum in absence and presence of calcium.
Bile acids and fatty acids enhance the permeability of brush-border membrane vesicles for calcium. It has been postulated that increased influx of calcium into the enterocyte might be responsible for the fluid secretion induced by dihydroxy bile acids and fatty acids. During in vivo perfusion studies of the rat jejunum, 15 mM taurodeoxycholate induced secretion of electrolytes and water (P less than 0.001), reduced glucose absorption (P less than 0.001), and enhanced the absorption of mannitol (P less than 0.0125) and calcium (P less than 0.001). Calcium absorption continued to be enhanced during perfusion of a CaCl2-containing solution following the perfusion with taurodeoxycholate (P less than 0.05). In view of the previously demonstrated enhanced permeability of the apical brush-border membrane in the presence of bile acids, it is very likely that some calcium enters the enterocyte along the steep concentration gradient in the presence of taurodeoxycholate. In spite of enhanced calcium absorption, 15 mM CaCl2 had no effect on control absorption rates or on fluid secretion induced by taurodeoxycholate. The data indicate that the effects of bile acids on intestinal transport are not mediated by an influx of calcium into the enterocyte.


Genome Sequences of Escherichia Bacteriophages Isolated from Raw Wastewater.
Somatic coliphages are alternative indicators of fecal pollution and attractive surrogates for viral pathogens. Here, we report the draft genome sequences of three replicate plaques from a novel Myoviridae bacteriophage isolated from raw wastewater. These genomes were similar to felix01virus phage and are predicted to contain up to 148 protein-coding genes.


The relationship between trait emotional intelligence, resiliency, and mental health in older adults: the mediating role of savouring.
The present study explores savouring, defined as the process of attending to positive experiences, as a mediator in the relationships between resiliency, trait emotional intelligence (EI), and subjective mental health in older adults. Following Fredrickson's Broaden and Build Theory of positive emotions, the present study aims to extend our understanding of the underlying processes that link resiliency and trait EI with self-reported mental health in older adulthood. A sample of 149 adults aged 65 and over (M = 73.72) were recruited from retirement homes and community groups. Participants completed measures of resiliency, savouring, trait EI, and subjective mental health either online or in a paper format. Path analysis revealed that savouring fully mediated the relationship between resiliency and mental health. However, trait EI did not significantly predict mental health in this sample. These findings provided partial support for the Broaden and Build Theory of positive emotions. As anticipated, savouring imitated the broadening effect of positive emotions by mediating the relationship between resiliency and mental health. However, savouring failed to reflect the undoing effect of positive emotions and did not mediate the relationship between EI and mental health. These findings have implications for positive psychology exercises and may be a simple, yet effective means of improving the life quality of older adults.


Effect of Posterior Glenoid Labral Tears at the NFL Combine on Future NFL Performance.
Posterior labral injuries have been recognized as a particularly significant clinical problem in collision and contact athletes. To evaluate the effect that posterior labral tears have on early National Football League (NFL) performance based on position, associated injuries, and operative versus nonoperative management. Cohort study; Level of evidence, 3. A retrospective review of all participants in the NFL Combine from 2009 to 2015 was performed using medical and imaging reports documented at the combine. Magnetic resonance imaging scans were analyzed for tear location, associated injuries, and evidence of previous surgical interventions. Each player's NFL draft position, as well as number of games played, number of games started, and snap percentage in his first 2 NFL seasons were collected for performance analysis and were compared with a control group of uninjured counterparts. Players with posterior labral tears were selected significantly later in the draft than those in the control group (draft position, 171.6 vs 156.1, respectively; P = .017). Although no single individual position was significantly affected by posterior labral tears, linemen (both offensive and defensive) with posterior labral tears were drafted significantly later than those without tears (draft position, 164.0 vs 137.7, respectively; P = .018) and had a significantly lower percentage of snaps in their first NFL season (23.8% vs 27.7%, respectively; P = .014). Players who underwent surgical management before the combine had a significantly higher percentage of snaps in their second NFL season than those who were managed conservatively (31.4% vs 22.3%, respectively; P = .022). None of the concomitant injuries recorded (superior labral anterior-posterior tears, glenoid bone loss, reverse Hill-Sachs lesions, rotator cuff tears, reverse humeral avulsions of the glenohumeral ligament, and posterior labral tears combined with anterior tears) significantly affected the draft position, number of games played, number of games started, or snap percentage for the cohort as a whole or any specific position. Posterior labral tears did negatively and significantly affect early NFL outcomes for collegiate football players across several different metrics, especially among linemen. While operative management did not produce significantly superior performance in most outcome measures, it may allow for better longevity of the shoulder and warrants further investigation. Concomitant shoulder injuries did not significantly affect early NFL outcomes in this cohort.


The relation between visceral adipose tissue accumulation and biochemical tests in university students.
We evaluated the visceral adipose tissue accumulation in university students in Okayama prefecture, Japan. Fifty-eight Japanese university students (10 men and 48 women, age 18.4 +/- 0.6 years)were enrolled in this study. Fat distribution was evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography (CT) scanning at umbilical levels. Anthropometric parameters,i.e., height, weight, waist circumference, hip circumference, and body fat percentage; blood examination; and blood pressure (BP) were also measured. In 58 subjects, the V area was 23.4 +/- 21.0 cm(2) and the S area was 122.5 +/- 57.9 cm(2). V areas were significantly correlated with hepatic enzymes, uric acid, triglyceride, and BP in men, while they were weakly correlated with hepatic enzymes, triglyceride, and high density lipoprotein (HDL) cholesterol in women. Correlation coefficients between V areas and clinical parameters were comparatively higher than those between other body composition parameters,i.e., S areas, weight, body mass index (BMI), body fat percentage, and clinical parameters. The present study suggests that visceral adipose tissue accumulation is important for hepatic enzymes, uric acid, triglyceride, and BP in university students.


Turkish adaptation of Wilson-Sims psychiatric fall risk assessment scale.
This study aimed to adapt the Wilson-Sims Fall Scale to Turkish and assess the levels of sensitivity and selectivity. The scale consisting of two sections and 15 items including age, gender, mental and physical status, elimination, impairments, gait/balance, falls' history, medications, and detox protocol was administered to 750 patients in psychiatric clinic. The kappa coefficient of the study (K: 0.44, p < .000) showed a moderate agreement. The sensitivity and selectivity rates of the scale were 78.5% and 77.6%, respectively. Positive and negative predictive values were 6.25% and 99.4%. The scale has acceptable sensitivity and selectivity values. It is best practice to use both Wilson-Sims and Itaki Scale simultaneously for identification of patients at risk of falling.


High adherence and low dropout rate in a virtual clinical study of atopic dermatitis through weekly reward-based personalized genetic lifestyle reports.
Clinical trials often suffer from significant recruitment barriers, poor adherence, and dropouts, which increase costs and negatively affect trial outcomes. The aim of this study was to examine whether making it virtual and reward-based would enable nationwide recruitment, identify patients with variable disease severity, achieve high adherence, and reduce dropouts. In a siteless, virtual feasibility study, individuals with atopic dermatitis (AD) were recruited online. During the 8-week study, subjects used their smartphones weekly to photograph target AD lesions, and completed patient-oriented eczema measure (POEM) and treatment use questionnaires. In return, subjects were rewarded every week with personalized lifestyle reports based on their DNA. Over the course of the 11 day recruitment period, 164 (82% women and 18% men) filled in the form to participate, of which 65 fulfilled the inclusion criteria and signed the informed consent. Ten were excluded as they did not complete the mandatory study task of returning the DNA sample. 55 (91% women, 9% men) subjects returned the DNA sample and were enrolled throughout Denmark, the majority outside the Copenhagen capital region in rural areas with relatively low physician coverage. The mean age was 28.5 (SD ±9.5 years, range 18-52 years). The baseline POEM score was 14.5±5.6 (range 6-28). Based on the POEM, 7 individuals had mild, 28 had moderate, 17 had severe, and 3 had very severe eczema. The retention rate was 96% as 53 out of 55 enrolled completed the study. The adherence was very high, and more than 90% of all study tasks were completed. Follow up of 41 subjects showed that 90% would take part again or continue if the study had been longer. A virtual trial design enables recruitment with broad geographic reach and throughout the full spectrum of disease severity. Providing personalized genetic reports as a reward seems to contribute to high adherence and retention.


Molecular electrostatic potential at the atomic sites in the effective core potential approximation.
Considering calculations of the molecular electrostatic potential at the atomic sites (MEP@AS) in the presence of effective core potentials (ECP), we found that the consequent use of the definition of MEP@AS based on the energy derivative with respect to nuclear charge leads to a formula that differs by one term from the result of simple application of Coulomb's law. We have developed a general method to analytically treat derivatives of ECP with respect to nuclear charge. Benchmarking calculations performed on a set of simple molecules show that our formula leads to a systematic decrease in the error connected with the introduction of ECP when compared to all-electron results. Because of a straightforward implementation and relatively low costs of the developed procedure we suggest to use it by default.


A French dental school programme appraisal by alumni of 5-9 years standing.
The objective of this study was to analyse the perception of the practical value of their training experience for 4 groups of alumni graduated between 1986 and 1989 at the Faculty of Odontology, University Paris 5. The 240 participants (45% response rate) perceived their training to have been adequate with respect to procedural activities. On the other hand, the graduates expressed a desire for more emphasis in emergencies, interpersonal relationship, office management and such clinical topics as fixed prosthodontics, surgery and periodontics. Surveys aimed at alumni may be useful for the evaluation of programme results and to determine which items should be added or deleted according to either health criteria or the conditions of dental practice.


Profile of Lymphadenopathy: An Institutional Based Cytomorphological Study.
Lymphadenopathy is one of the most common clinical presentations of patients attending the outdoor department of a hospital. Lymph node aspiration is of great value for the diagnosis of lymphadenitis, lymphomas, and metastatic carcinoma. In this study, we have reported the pattern of cytological diagnosis on fine-needle aspiration cytology (FNAC) of lymphadenopathy cases in Jammu region of Jammu and Kashmir state of India. The mean age of all the patients in this study was 21.67 years. The most common site of lymphadenopathy was cervical region (71.79%) followed by axillary region (11.11%). Tubercular lymphadenitis (44.02%) was the single most common cause of lymphadenopathy followed by reactive lymphadenitis (42.64%), metastatic lesions (9.40%), and malignant lymphoma (4.70%). The sensitivity of 94.49%, positive predictive value of 96.26%, and diagnostic accuracy of 91.15% was achieved in our study. This study highlights the role of FNAC as a simple, inexpensive, relatively painless, rapid, repeatable, and reliable method of investigation for lymphadenopathy, especially in outpatient departments, peripheral hospitals, and dispensaries.


Ephrin A1 induces intercellular dissociation in Ishikawa cells: possible implication of the Eph-ephrin A system in human embryo implantation.
During implantation, the human embryo invades endometrial stromal tissues, reducing the intercellular connections among epithelial cell layers. Since Eph-ephrin interaction can induce repulsive forces to control cell position and movement, we examined the possible involvement of this system in intercellular dissociation among endometrial epithelial cells. The expression of Eph A receptor on human endometrial epithelial cells and endometrial carcinoma-derived Ishikawa cells was examined by RT-PCR, immunohistochemistry and western blotting. The effects of recombinant ephrin A1 on Eph A2 phosphorylation in Ishikawa cells were also examined by western blotting. A permeability assay was performed to determine the effects of ephrin A1 on cell-to-cell adhesion. Eph A1, A2 and A4 mRNAs were detected in human endometrial epithelial cells and Ishikawa cells, and ephrin A1 was present in human blastocysts. Immunohistochemical staining showed that Eph A1, A2 and A4 receptors were expressed on the cell surface region of luminal and glandular epithelial cells in human endometrium in both the proliferative and secretory phase. The presence of Eph A2 protein in the human endometrium was confirmed by western blot analysis. Recombinant ephrin A1 was bound to Ishikawa cells and induced phosphorylation of Eph A2 expressed in Ishikawa cells. In addition, stimulation by ephrin A1 for 20 min increased the permeability of monolayer Ishikawa cells versus control cultures (P < 0.01), without affecting cell viability. This study demonstrated that the Eph-ephrin A system can promote intercellular dissociation in Ishikawa cells suggesting an important role in the initial step of embryo implantation by opening the endometrial epithelial cell barrier.


Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis.
In previous studies, the diarylquinoline R207910 (also known as TMC207) was demonstrated to have high bactericidal activity when combined with first- or second-line antituberculous drugs. Here we extend the evaluation of R207910 in the curative model of murine tuberculosis by assessing the activities of one-, two-, and three-drug combinations containing R207910 and isoniazid (INH), rifampin (RIF), pyrazinamide (PZA), or moxifloxacin (MXF) in the setting of a high initial bacillary load (7.2 log(10) CFU). Two months of treatment with the combinations R207910-PZA, R207910-PZA-INH, R207910-PZA-RIF, or R207910-PZA-MXF resulted in culture-negative lung homogenates in 70 to 100% of the mice, while mice treated with INH-RIF-PZA (the reference regimen) or RIF-MXF-PZA remained culture positive. Combinations including R207910 but not PZA (e.g., R207910-INH-RIF and R207910-MXF-RIF) were less active than R207910-PZA-containing regimens administered either alone or with the addition of INH, RIF, or MXF. These results reveal a synergistic interaction between R207910 and PZA. Three-drug combinations containing these two drugs and INH, RIF, or MXF have the potential to significantly shorten the treatment duration in patients, provided that these results can be confirmed in long-term experiments including periods of relapse.


Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease.
Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.


Central nervous system prophylaxis in patients with aggressive diffuse large B cell lymphoma: an analysis of 3,258 patients in a single center.
Central nervous system (CNS) relapse continues to be a frequent and usually fatal complication in patients with diffuse large B cell lymphoma (DLBCL). Multiple factors identify the possibility of relapse and justify neurological prophylaxis; however, most of these have not been confirmed. Thus, the use of prophylaxis has not been defined. From 1988 to 2008, 3,258 patients with DLBCL with higher clinical risks and multiple extranodal involvement that have been treated with standard anthracycline-based chemotherapy: CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP-R (CHOP plus rituximab) and that achieve complete response were retrospectively analyzed to assess the efficacy of CNS prophylaxis. One thousand five patients received different schedules for CNS prophylaxis, and 2,253 patients did not receive CNS prophylaxis. CNS relapse was similar in patients who receive prophylaxis (6 %) compared to patients who did not receive prophylaxis (5.9 %). Overall survival of patients who either receive or did not receive prophylaxis was not statistically significant: 49 % versus 53 % (p = 0.802). Thus, it seems that CNS prophylaxis did not improve outcome in this special setting of patients, and no prognostic factors to predict the presence of CNS relapse were identified. It is evident that multicentric studies are necessary to define the role of prophylaxis in order to prevent CNS relapse and that the therapeutic procedure will be carefully revised.


The role of indigenous health workers in promoting oral health during pregnancy: a scoping review.
Early childhood caries is the most common chronic childhood disease worldwide. Australian Aboriginal and Torres Strait Islander children are twice more likely to develop dental decay, and contributing factors include poor maternal oral health and underutilisation of dental services. Globally, Indigenous health workers are in a unique position to deliver culturally competent oral healthcare because they have a contextual understanding of the needs of the community. This scoping review aimed to identify the role of Indigenous health workers in promoting maternal oral health globally. A systematic search was undertaken of six electronic databases for relevant published literature and grey literature, and expanded to include non-dental health professionals and other Indigenous populations across the lifespan when limited studies were identified. Twenty-two papers met the inclusion criteria, focussing on the role of Indigenous health workers in maternal oral healthcare, types of oral health training programs and screening tools to evaluate program effectiveness. There was a paucity of peer-reviewed evidence on the role of Indigenous health workers in promoting maternal oral health, with most studies focusing on other non-dental health professionals. Nevertheless, there were reports of Indigenous health workers supporting oral health in early childhood. Although some oral health screening tools and training programs were identified for non-dental health professionals during the antenatal period, no specific screening tool has been developed for use by Indigenous health workers. While the role of health workers from Indigenous communities in promoting maternal oral health is yet to be clearly defined, they have the potential to play a crucial role in 'driving' screening and education of maternal oral health especially when there is adequate organisational support, warranting further research.


The divergent DSL ligand Dll3 does not activate Notch signaling but cell autonomously attenuates signaling induced by other DSL ligands.
Mutations in the DSL (Delta, Serrate, Lag2) Notch (N) ligand Delta-like (Dll) 3 cause skeletal abnormalities in spondylocostal dysostosis, which is consistent with a critical role for N signaling during somitogenesis. Understanding how Dll3 functions is complicated by reports that DSL ligands both activate and inhibit N signaling. In contrast to other DSL ligands, we show that Dll3 does not activate N signaling in multiple assays. Consistent with these findings, Dll3 does not bind to cells expressing any of the four N receptors, and N1 does not bind Dll3-expressing cells. However, in a cell-autonomous manner, Dll3 suppressed N signaling, as was found for other DSL ligands. Therefore, Dll3 functions not as an activator as previously reported but rather as a dedicated inhibitor of N signaling. As an N antagonist, Dll3 promoted Xenopus laevis neurogenesis and inhibited glial differentiation of mouse neural progenitors. Finally, together with the modulator lunatic fringe, Dll3 altered N signaling levels that were induced by other DSL ligands.


Psychosocial factors and excessive gestational weight gain: The effect of parity in an Australian cohort.
psychosocial variables can be protective or risk factors for excessive gestational weight gain (GWG). Parity has also been associated with GWG; however, its effect on psychosocial risk factors for GWG is yet to be determined. The aim of this study was to investigate if, and how, psychosocial factors vary in their impact on the GWG of primiparous and multiparous women. pregnant women were recruited in 2011 via study advertisements placed in hospitals, online, in parenting magazines, and at baby and children's markets, resulting in a sample of 256 women (113 primiparous, 143 multiparous). Participants completed questionnaires at 16-18 weeks' gestation and their pregravid BMI was recorded. Final weight before delivery was measured and used to calculate GWG. the findings revealed that primiparous women had significantly higher feelings of attractiveness (a facet of body attitude; p=0.01) than multiparous women. Hierarchical regressions revealed that in the overall sample, increased GWG was associated significantly with lower pre-pregnancy BMI (standardised coefficient β=-0.39, p<0.001), higher anxiety symptoms (β=0.25, p=0.004), and reduced self-efficacy to eat a healthy diet (β=-0.20, p=0.02). Although higher GWG was predicted significantly by decreased feelings of strength and fitness for primiparous women (β=-0.25, p=0.04) and higher anxiety was related significantly to greater GWG for multiparous women (β=0.43, p<0.001), statistical comparison of the model across the two groups suggested the magnitude of these effects did not differ across groups (p>0.05). the findings suggest that psychosocial screening and interventions by healthcare professionals may help to identify women who are at risk of excessive GWG, and there may be specific psychosocial factors that are more relevant for each parity group.


Utility of Tumor Capsule Thickness as a Predictor of Invasion in Encapsulated Follicular Variant of Papillary Thyroid Carcinoma and a Diagnostic Tool for Noninvasive Follicular Thyroid Neoplasm With Papillary-Like Nuclear Features.
Context. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is an extremely indolent subset of noninvasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). These lesions share certain features including a delimiting fibrous capsule, and they are distinguished by detailed histological criteria. Objective. We sought to identify whether tumor capsule thickness differs significantly between NIFTP and noninvasive EFVPTC lesions. We also compared tumor capsule thickness between noninvasive and invasive EFVPTC in order to evaluate its utility as a predictive marker of invasion. Design. Encapsulated follicular thyroid neoplasms with papillary-like nuclear features diagnosed over a 3-year period at a single institution were subcategorized into NIFTP, noninvasive EFVPTC, and invasive EFVPTC based on current diagnostic criteria. Maximum tumor capsule thickness for each lesion was measured. Results. A total of 92 lesions (39 NIFTP, 15 noninvasive EFVPTC, and 38 invasive EFVPTC) were evaluated. Tumor capsule thickness was significantly thinner in NIFTP (P = .022) and significantly thicker in invasive EFVPTC (P = .0006) when compared with noninvasive EFVPTC. Conclusions. Tumor capsule thickness may be an additional useful marker when distinguishing between NIFTP and noninvasive EFVPTC. A capsule thickness of greater than 0.2 mm should raise suspicion for EFVPTC and thus prompt more thorough review of the submitted tissue for NIFTP exclusionary criteria. Additionally, if capsular and/or vascular invasion are not present on initial slides of an entirely evaluated capsule of EFVPTC that exceeds 0.5 mm in thickness, the pathologist should order additional tissue levels to ensure that a small focus of invasion is not missed.


Laparoscopic drilling by diathermy or laser for ovulation induction in anovulatory polycystic ovary syndrome.
Surgical ovarian wedge resection was the first established treatment for women with anovulatory polycystic ovary syndrome (PCOS) but was largely abandoned both due to the risk of postsurgical adhesions and the introduction of medical ovulation induction. However, women with PCOS who are treated with medical ovulation induction, with drugs such as gonadotrophins, often have an over-production of follicles which may result in ovarian hyperstimulation syndrome and multiple pregnancies. Moreover, gonadotrophins, though effective, are costly and time-consuming and their use requires intensive monitoring. Surgical therapy with laparoscopic ovarian 'drilling' (LOD) may avoid or reduce the need for medical ovulation induction, or may facilitate its usefulness. The procedure can be done on an outpatient basis with less trauma and fewer postoperative adhesions than with traditional surgical approaches. Many uncontrolled observational studies have claimed that ovarian drilling is followed, at least temporarily, by a high rate of spontaneous ovulation and conception, or that subsequent medical ovulation induction becomes easier. To determine the effectiveness and safety of laparoscopic ovarian drilling compared with ovulation induction for subfertile women with clomiphene-resistant PCOS. We used the search strategy of the Menstrual Disorders and Subfertility Group (MDSG) to search the MDSG Trials Register, CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO. The keywords included polycystic ovary syndrome, laparoscopic ovarian drilling, electrocautery and diathermy. Searches were conducted in September 2011, and a further search of the MDSG Trials Register was made on 14 May 2012. We included randomised controlled trials of subfertile women with clomiphene-resistant PCOS who undertook laparoscopic ovarian drilling in order to induce ovulation. This is an update of a previously updated review. There were nine RCTs in the previous version; an additional 16 trials were added in the current (2012) update. All trials were assessed for quality. The primary outcomes were live birth and multiple pregnancy. The secondary outcomes were rate of miscarriage, ovulation and pregnancy rates, ovarian hyperstimulation syndrome (OHSS), quality of life and cost. Nine trials, including 1210 women, reported on the primary outcome of live birth rate per couple. Live births were reported in 34% of women in the LOD groups and 38% in other medical treatment groups. There were five different comparisons with LOD and there was no evidence of a difference in live births when compared with clomiphene citrate + tamoxifen (OR 0.81; 95% CI 0.42 to 1.53; P = 0.51, 1 trial, n = 150), gonadotrophins (OR 0.97; 95% CI 0.59 to 1.59; P = 0.89, I(2) = 0%, 2 trials, n = 318), aromatase inhibitors (OR 0.84; 95% CI 0.54 to 1.31; P = 0.44, I(2) = 0%, 2 trials, n = 407) or clomiphene citrate (OR 1.21; 95%CI 0.64 to 2.32; 1 trial, n=176, P= 0.05). There was evidence of significantly fewer live births following LOD compared with clomiphene citrate + metformin (OR 0.44; 95% CI 0.24 to 0.82; P = 0.01, I(2) = 78%, 2 trials, n = 159); the high heterogeneity in this subgroup could not be explained by population differences or differences in quality of the trials.Thirteen trials reported on multiple pregnancies (n= 1305 women). There were no cases of multiple pregnancies in either group for clomiphene citrate or aromatase inhibitors compared with LOD. The rate of multiple pregnancies was significantly lower in the LOD group compared with trials using gonadotrophins (OR 0.13; 95% CI 0.03 to 0.52; P=0.004, I(2) = 0%, 5 trials, n = 166). There was no evidence of a significant difference in rates of clinical pregnancy, live birth or miscarriage in women with clomiphene-resistant PCOS undergoing LOD compared to other medical treatments. The reduction in multiple pregnancy rates in women undergoing LOD makes this option attractive. However, there are ongoing concerns about the long-term effects of LOD on ovarian function.


Assessment of Cardiovascular Risk Factors Among University Students: The Gender Factor.
Evidence indicates that the pathophysiological process of cardiovascular (CV) disease begins at early age, though the manifestations of the disease do not appear until middle age adulthood. Risk factors for CV disease, particularly lipoprotein profiles, are affected by physiological abnormalities, and lifestyle related issues. To evaluate prevalence of CV diseases risk factors among university students and to investigate relation between number of risk factors and body anthropometric, hematological and biochemical indices parameters. In this cross sectional study, 348 students were randomly recruited. Blood glucose, cholesterol profile (total, HDL, and LDL cholesterol), and triglyceride were measured using standard protocols. Physical activity (PA) level was assessed using the short-form Arabic version of the International Physical Activity Questionnaires (IPAQ). The most commonly encountered CV disease risk factor was low levels of HDL-C, followed by physical inactivity, high levels TG, and obese BMI. When stratified by gender, females were less likely to have low HDL-C, and high TG, whereas, males were more likely to have overweight or obese BMI (P < 0.001). About 49% of the participants had at least one CV disease risk factor, where as the prevalence of having one, two and three or more CV disease risk factors were 35.7%, 9.3% and 4%, respectively. Additionally, the number of CV disease risk factors showed strong positive correlation with increases in body fat and bone percentages, glucose, total cholesterol, TG, LDL-C, BMI, and WHR (range of R2: 0.17 to 0.603). On the other hand, physical activity, percentages of body water and muscle, HDL-C showed inverse strong correlation with cardiovascular risk factors (range of R2: -0.239 to -0.412). Results indicate the high prevalence of CV disease risk factors among university students, and stress the need for early intervention programs to counteract these risks.


Sublinear information bottleneck based two-stage deep learning approach to genealogy layout recognition.
As an important part of human cultural heritage, the recognition of genealogy layout is of great significance for genealogy research and preservation. This paper proposes a novel method for genealogy layout recognition using our introduced sublinear information bottleneck (SIB) and two-stage deep learning approach. We first proposed an SIB for extracting relevant features from the input image, and then uses the deep learning classifier SIB-ResNet and object detector SIB-YOLOv5 to identify and localize different components of the genealogy layout. The proposed method is evaluated on a dataset of genealogy images and achieves promising results, outperforming existing state-of-the-art methods. This work demonstrates the potential of using information bottleneck and deep learning object detection for genealogy layout recognition, which can have applications in genealogy research and preservation.


Effect of histamine and H1 and H2 receptors antagonists on carbachol-induced wet-dog shakes in rats.
Intracerebroventricular administration of carbachol chloride induced a characteristic wet-dog shake response in rats. Histamine did not change the number of wet-dog shakes during a 60 min observation but intensified the number of episodes in the first 30 min of the experiment. Antagonists of H1 (thenalidine and antazoline) and H2 (cimetidine and ranitidine) receptors, attenuated carbachol-induced wet-dog shakes. It may be suggested that inhibition of the central histaminergic structures decreased central cholinergic activity.


Perinatal Testicular Torsion in Northern Ireland: A Nationwide 10-Year Review.
Perinatal or neonatal testicular torsion (PTT) is defined as testicular torsion within the first 30 days of life. PTT is a rare event, and bilateral PTT is even rarer. However, recent articles have advocated emergency bilateral exploration to exclude the catastrophic possibility of asymptomatic contralateral testicular torsion leading to anorchia. The aim of this study is to evaluate PTT in Northern Ireland (NI) using a nationwide population-based retrospective observational study. All boys in NI who underwent emergency scrotal exploration within their first 30 days of life for possible testicular torsion over a 10-year period (January 2010-December 2019 inclusive) were included. Intraoperative findings primarily evaluated included diagnosis and presence of synchronous or asynchronous (metachronous) contralateral testicular torsion. Secondary outcomes included correlation between intraoperative findings and any preoperative ultrasound scan (USS), and scrotal examination findings during postoperative outpatient follow-up. A total of 19 patients who underwent emergency scrotal exploration in the study period were included. An intraoperative finding confirming the diagnosis of PTT was reported in 14 (73.7%) patients. The incidence of PTT was calculated as 11.3 per 100,000 per male live births in NI, with bilateral PTT accounting for two patients (14.2% of all PTTs), divided equally between synchronous and asynchronous PTTs. Of two affected testes where preservation was felt appropriate intraoperatively, only one was still palpable at follow-up, producing a testicular salvage rate after PTT of only 7.1%. Testicular findings on preoperative USS were confirmed intraoperatively in five out of six patients, producing a concordance rate of 83.3%. This is the first nationwide population-based study to calculate more accurately the incidence of PTT, and bilateral synchronous and asynchronous bilateral PTTs, all of which seem to be significantly higher than previously estimated. However, in keeping with previous reports, this study confirms the poor salvage rate of testes undergoing perinatal torsion, and suboptimal concordance between preoperative USS findings and intraoperative diagnosis.


Xerophthalmia and vitamin A deficiency in an autistic child with a restricted diet.
We report the ocular and systemic manifestations of vitamin A deficiency in a child with a complicated medical history including autism and a restricted diet, living in a developed country. This child had significant vitamin A deficiency despite being under long-term medical care, yet the diagnosis was not considered until he had an ophthalmology review for visual deterioration.


A new measure to assess asthma's effect on quality of life from the patient's perspective.
The Asthma Impact on Quality of Life Scale (A-IQOLS) assesses the negative effect of asthma on quality of life (QoL) from the patient's perspective by using dimensions of Flanagan's Quality of Life Scale (QOLS), a measure of current QoL. We sought to determine and compare the psychometric properties of the A-IQOLS and QOLS, including their sensitivities to differences and change in asthma status. In a test-retest design (3- to 5-week interval) adults with persistent asthma underwent spirometry and were administered the A-IQOLS, other asthma outcome measures (Asthma Control Test, Asthma Symptom Utility Index, and the Marks and Juniper Asthma Quality of Life Questionnaires), and the QOLS. Participants' (n = 147) mean age was 49 years, 76% were white, 12% were Hispanic, and 65% were female. A-IQOLS and QOLS scores were significantly correlated with other asthma outcomes scores, except FEV1, but shared relatively low common variance with these measures. A-IQOLS but not QOLS score changes were significantly correlated with changes in asthma outcomes. An A-IQOLS standard error of measurement of 0.27 implies that a within-person score change of ±0.73 or greater constitutes a true change. The QOLS standard error of measurement was 0.43. A-IQOLS provides a reliable, valid, and unique assessment of the patient-perceived negative effect of asthma on QoL that is suitable for use in asthma clinical research and potentially in clinical care. Further studies are needed in diverse patient populations. QOLS, a measure of current QoL, is less sensitive to disease status changes but might be useful in characterizing study populations, in treatment adherence research, and as a clinical and research tool in patients with multiple, severe, and/or life-limiting chronic conditions.


Amyloid aggregates of the HET-s prion protein are infectious.
The [Het-s] infectious element of the filamentous fungus Podospora anserina is a prion. We have recently reported that recombinant HET-s protein aggregates in vitro into amyloid fibers. In vivo, the protein aggregates specifically in the [Het-s] prion strains. Here, we show that biolistic introduction of aggregated recombinant HET-s protein into fungal cells induces emergence of the [Het-s] prion with a high frequency. Thus, we demonstrate that prion infectivity can be created de novo, in vitro from recombinant protein in this system. Although the amyloid filaments formed from HET-s could transmit [Het-s] efficiently, neither the soluble form of the protein nor amorphous aggregates would do so. In addition, we have found that (i) [Het-s] infectivity correlates with the ability to convert HET-s to amyloids in vitro, (ii) [Het-s] infectivity is resistant to proteinase K digestion, and (iii) HET-s aggregates formed in vivo in [Het-s] strains have the ability to convert the recombinant protein to aggregates. Together, our data designate the HET-s amyloids as the molecular basis of [Het-s] prion propagation.


Homodimers of Vanillin and Apocynin Decrease the Metastatic Potential of Human Cancer Cells by Inhibiting the FAK/PI3K/Akt Signaling Pathway.
The spread of cancer cells to distant organs, in a process called metastasis, is the main factor that contributes to most death in cancer patients. Vanillin, the vanilla flavoring agent, has been shown to suppress metastasis in a mouse model. Here, we evaluated the antimetastatic potential of the food additive divanillin, the homodimer of vanillin, and their structurally related compounds, apocynin and diapocynin, in hepatocellular carcinoma cells. The Transwell invasion assay showed that the dimeric forms exhibited a potency higher than those of vanillin and apocynin in inhibiting invasion, with IC50 values of 23.3 ± 7.4 to 41.3 ± 4.2 μM for the dimers, which are 26-34-fold lower than IC50 values of vanillin and apocynin (p < 0.05). Both monomeric and dimeric forms target regulation of the invasion process by inhibiting phosphorylation of FAK and Akt. Molecular docking studies suggested that the dimers should bind more tightly than vanillin and apocynin to the Y397 pocket of the FAK FERM domain. Thus, the food additive divanillin has antimetastatic potential greater than that of the flavoring agent vanillin.


Remote Ischemic Conditioning in Cardiovascular Surgery.
The existing clinical studies on remote ischemic preconditioning in patients undergoing cardiovascular surgery are critically reviewed, with a focus on infarct size reduction and clinical outcome as end points. Confounders, notably the use of propofol anesthesia are identified. The need for better designed trials with a more targeted approach is emphasized.


Relationship between poverty and health among adolescents.
Although the effect of low socioeconomic status on the health of adolescents has been documented, the mechanism by which this occurs is not well understood. Furthermore, improving adolescent health through public health policy typically requires the presence of one or more modifiable risk factors which can be targeted for intervention. In spite of the well-documented negative associations between poverty and health, few modifiable risk factors have been identified. This study used the Evans-Stoddart Model of Health and Well-Being as a framework to examine data on 1,759 adolescents, aged 12 to 19, collected as part of the 1994 National Population Health Survey. Results not only confirm the relationship between income and health, but suggest how the pathway operates through the social environment, lifestyle differences, access to health care, and a reduced sense of self-esteem and self-mastery. Bivariate and multivariate analyses found positive associations between physical activity levels and self-esteem and mastery. We interpret these findings as preliminary evidence that it might be possible to buffer the impact of poverty on health through policies which increase physical activity levels among those living in poverty. Such policies could also include a secondary goal of increasing the activity levels among inactive adolescents who are not living in poverty, as they will derive benefits from this increase, both psychologically and physiologically.


[The nasopalatine duct cyst--epidemiology, diagnosis and therapy].
The nasopalatine duct cyst is the most frequent nonodontogenic cyst of the jaws. The cyst originates from epithelial remanents from the nasopalatine duct. The cells may be activated spontaneously during life, or are eventually stimulated by the irritating action of various agents (infection, etc.). Generally, patients present without clinical signs and symptoms. Therefore, the tentative diagnosis "nasopalatine duct cyst" is often based on a coincidental radiological finding on a routine panoramic view or occlusal radiograph. The definite diagnosis should be based on clinical, radiological and histopathologic findings. The therapy of nasopalatine duct cysts consists of an enucleation of the cystic tissue, only in rare cases a marsupialization needs to be performed. The present review of the literature presents and discusses the epidemiology, etiology, diagnostic work-up, differential diagnostic aspects, histopatholgy, and therapeutic strategies for nasopalatine duct cysts.


[Callus induction and cultivation of Camptotheca acuminata].
To study the callus induction from leaf, stem segments and stem segments with axillary's bud and the subculture conditions of callus in Camptotheca acuminata. The explants were inoculated into the media of MS with different concentrations of 6-BA, NAA and 2, 4-D by orthogonal experiment. The optimal medium for callus induction was MS with 6-BA 2 mg x L(-1), NAA 2 mg x L(-1) and 2,4-D 2 mg x L(-1). It had better effects in leaf than in other explants. The induction ratio in leaf reached above 80%. The callus subcultured on the medium of MS with 6-BA 1 mg x L(-1) and 2, 4-D 1 mg x L(-1) grew vigorous and more quickly than that in other media. It was loose, friable in consistency and suitable for cell culture.


Dietary exposure of children and teenagers to benzoates, sulphites, butylhydroxyanisol (BHA) and butylhydroxytoluen (BHT) in Beirut (Lebanon).
The acceptable daily intake (ADI) for a considered chemical is by definition the amount of that substance which can be ingested every day during the life time without appreciable health risk. The theoretical risk of exceeding the ADI for benzoates, sulphites, butylhydroxyanisol (BHA) and butylhydroxytoluen (BHT) has often been examined on the basis of worst case scenario. The aim of this paper is to assess the actual intake of the food additives listed above for a group of the Lebanese population (students aged between 9 and 18 years old) likely to be highly exposed to food additives through the consumption of processed foods. Dietary exposure was obtained by combining food consumption data with food additives levels determined by chemical analysis. Food products available in Lebanon and containing added benzoates, sulphites, BHA and BHT were identified. Overall 420 samples of foods and beverages were analysed. The determination of food additives residue levels was carried out according to the official methods adopted in "Lebanese Institute for agronomic research" (IRAL) on food as consumed. The acceptable daily intake (ADI) could be exceeded for sulphites and BHT by a fraction of the population, in particular within children of 9-13 years old. Among all food additive-containing foods, the highest contributors were: soft drinks to benzoates intake, nuts and canned juices to sulphites intake, bread and biscuits to BHA intake and chewing gum to BHT intake.


Treatment of post-burns bacterial infections by bacteriophages, specifically ubiquitous Pseudomonas spp. notoriously resistant to antibiotics.
Post-burn microbial infections are a major problem in recovering from the trauma of third-degree burns, and the survival of patients can depend upon the severity of the burn and the infections encountered. Within 24 hours, patients can start suffering from opportunistic bacterial attacks, which can vary from simple infection, such as those easily treatable by antibiotics, to more complicated types, which may have natural or acquired resistance to drugs. Infection by multiple drug-resistant bacteria can create additional complexity to the problem. As an alternative to treating bacterial infections by antibiotics, bacteriophages have been in use in certain parts of the world, such as at Tbilisi in Georgia and in Poland, and this approach has now been more widely recognized. Results have shown that phage therapy has an 80% success rate against Enterococcus infections and up to 90% against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella pneumoniae. Here it is proposed that bacteriophages can effectively be used for the treatment of post-burn infections, particularly the ubiquitous opportunistic pathogens, Pseudomonas spp., known to be notoriously resistant to a variety of antibiotics. This kind of treatment may be of particular importance in Third World countries where the incidence of burns and infections, due to lack of stringent safety regulations and proper hygiene respectively, may be more common and where cocktails of antibiotics may be less affordable. Phages that can possibly be employed in the treatment and their advantages compared to the use of antibiotics are also highlighted.


Amine oxidase activity regulates the development of pulmonary fibrosis.
In pulmonary fibrosis, an inflammatory reaction and differentiation of myofibroblasts culminate in pathologic deposition of collagen. Amine oxidase copper containing-3 (AOC3) is a cell-surface-expressed oxidase that regulates leukocyte extravasation. Here we analyzed the potential role of AOC3 using gene-modified and inhibitor-treated mice in a bleomycin-induced pulmonary fibrosis model. Inflammation and fibrosis of lungs were assessed by histologic, flow cytometric, and quantitative PCR analysis. AOC3-deficient mice showed a 30-50% reduction in fibrosis, collagen synthesis, numbers of myofibroblasts, and accumulation of CD4+ lymphocytes, NK T cells, macrophages, and type 2 innate lymphoid cells compared with wild-type control mice. AOC3-knock-in mice, which express a catalytically inactive form of AOC3, were also protected from lung fibrosis. In wild-type mice, a small-molecule AOC3 inhibitor treatment reduced leukocyte infiltration, myofibroblast differentiation, and fibrotic injury both in prophylactic and early therapeutic settings by about 50% but was unable to reverse the established fibrosis. AOC3 was also induced in myofibroblasts in human idiopathic pulmonary fibrosis. Thus, the oxidase activity of AOC3 contributes to the development of lung fibrosis mainly by regulating the accumulation of pathogenic leukocyte subtypes, which drive the fibrotic response.-Marttila-Ichihara, F., Elima, K., Auvinen, K., Veres, T. Z., Rantakari, P., Weston, C., Miyasaka, M., Adams, D., Jalkanen, S., Salmi, M. Amine oxidase activity regulates the development of pulmonary fibrosis.


Male-specific colon motility dysfunction in the TashT mouse line.
In Hirschsprung disease (HSCR), the absence of myenteric neural ganglia in the distal bowel prevents motility and thereby causes functional intestinal obstruction. Although surgical resection of the aganglionic segment allows HSCR children to survive this condition, a number of patients still suffer from impaired motility despite having myenteric ganglia in their postoperative distal bowel. Such phenomenon is also observed in patients suffering from other enteric neuropathies and, in both cases, colonic dysmotility is believed to result from abnormalities of myenteric ganglia and/or associated interstitial cells of Cajal (ICC). To better understand this, we used a recently described HSCR mouse model called TashT. Intestinal motility parameters were assessed and correlated with extent of aganglionosis and with neuronal density in ganglionated regions. The neural composition of the myenteric plexus and the status of ICC networks was also evaluated using immunofluorescence. TashT(Tg/Tg) mice display a strong male bias in the severity of both colonic aganglionosis and hypoganglionosis, which are associated with male-specific reduced colonic motility. TashT(Tg/Tg) male mice also exhibit a specific increase in nNos(+) neurons that is restricted to the most distal ganglionated regions. In contrast, Calretinin(+) myenteric neurons, Sox10(+) myenteric glial cells, and cKit(+) ICC are not affected in TashT(Tg/Tg) mice. Male-specific impairment of colonic motility in TashT(Tg/Tg) mice is associated with both severe hypoganglionosis and myenteric neuronal imbalance. Considering these parameters in the clinic might be important for the management of postoperative HSCR patients.


Interrelation between glucose, insulin, C-peptide and 3-hydroxybutyrate in plasma and amniotic fluid in last trimester diabetic women without residual betacell function.
The relationship between maternal plasma and amniotic fluid (AF) concentrations of glucose, insulin, C-peptide and 3-hydroxybutyrate (3-HB) was analysed between 45 to 140 minutes after a standardized breakfast in 8 type I diabetic women without residual betacell function and in 13 nondiabetic control women during the last trimester of gestation. AF levels of both glucose and C-peptide were slightly and AF insulin levels significantly (P less than 0.05) elevated above normal in the diabetic women. 3-HB levels in plasma and in AF were significantly (P less than 0.05) elevated in the diabetic group between 45 to 65 minutes after breakfast. AF insulin and glucose was significantly correlated in the diabetic group (r = 0.96, P less than 0.05). During the 2 hour study period AF levels of glucose, insulin and C-peptide remained essentially unchanged in both groups of women. Changes in maternal plasma 3-HB concentrations seemed to be more rapidly reflected in AF.


The Mediating Role of Forgiveness and Self-Efficacy in the Relationship Between Childhood Maltreatment and Treatment Motivation Among Malaysian Male Drug Addicts.
Studies have reported high rates of childhood maltreatment among individuals with drug addiction problems; however, investigation about the potentially protective factors to mitigate the effects of maltreatment experiences on motivation to engage in addiction treatment has received less attention. This study aims at exploring the mediating effects of forgiveness and self-efficacy on the association between childhood maltreatment and treatment motivation among drug addicts. A total of 360 male drug addicts (mean age = 33.34, SD = 7.25) were recruited from three mandatory inpatient rehabilitation centers in Malaysia. Participants completed a package of self-report questionnaires including measures of childhood maltreatment experiences, forgiveness, self-efficacy, and motivation for treatment. The analysis conducted using the structural equation model (SEM) revealed that childhood maltreatment significantly predicted lower treatment motivation, while forgiveness and self-efficacy played a fully mediating role regarding the effect of childhood maltreatment on treatment motivation. In conclusion, these findings suggest that combining the element of forgiveness and self-efficacy in treatment programs appears to benefit the drug addicts with childhood maltreatment history.


The organisation of the RAMC during the Great War.
At the 90 year anniversary of the Battle of the Somme, it is important to remember the members of the RAMC who served in the Great War, especially the more than one thousand Medical Officers who gave their lives. The RAMC during the First World War was a Corps led by some able officers such as Sir Arthur Sloggett in France and Sir Alfred Keogh in London. Sir Douglas Haig was in overall command, his leadership style impacting on the RAMC. There were problems in filling the ranks of the Corps, both before the conflict, as well as well as during the War, and a significant number of civilian medical practitioners were recruited to the RAMC. Shortages were only really addressed when the Americans joined the conflict. TRAINING OF CIVILIAN MOS: The great need for MOs meant that there was little time for formal training of civilian MOs and many felt unsuited for war work. This was recognised by the authorities, who gradually set up centres of instruction. The workhorse of the organisation was the Regimental Medical Officer, who had an important role in disease prevention and the conservation of manpower, in a type of conflict (trench) that required a ready supply of personnel. Although an important role, some doctors found the job frustrating. During the War, the RAMC managed to improvise an efficient system for handling casualties, the aim to give speedy treatment and to return the men to the front in the shortest possible time. The RAMC during the GreatWar was a highly structured and efficient organisation, geared towards maximising its available manpower, important in trench warfare.