Gene expression profile in flow-associated pulmonary arterial hypertension with neointimal lesions.
Pulmonary arterial hypertension (PAH) is a pulmonary angioproliferative disease with high morbidity and mortality, characterized by a typical pattern of pulmonary vascular remodeling including neointimal lesions. In congenital heart disease, increased pulmonary blood flow has appeared to be a key mediator in the development of these characteristic lesions, but the molecular mechanisms underlying the pulmonary vascular lesions are largely unknown. We employed a rat model of flow-associated PAH, which induced specific pulmonary neointimal lesions. We identified gene expression profiles in rats specifically related to the addition of increased pulmonary blood flow to monocrotaline and the associated occurrence of neointimal lesions. Increased pulmonary blood flow induced the expression of the transcription factors activating transcription factor-3 (ATF3) and early growth response factor-1 (EGR-1), for which presence was confirmed in neointimal lesions. Monocrotaline alone induced increased numbers of activated mast cells and their products. We further identified molecular pathways that may be involved in treatment with the prostacyclin analog iloprost, a vasoactive compound with clinically beneficial effects in patients with PAH, which were similar to pathways described in samples from patient studies. These pathways, associated with the development of angioproliferative lesions as well as with the response to therapy in PAH, may provide new therapeutic targets.


Vecuronium-induced depression of phrenic nerve activity during hypoxia in the rabbit.
We investigated the effects of a close carotid injection of vecuronium on changes in phrenic nerve activity during different states of oxygenation. Experiments were performed on normothermic and mechanically ventilated adult New Zealand White rabbits with a tracheostomy under continuous thiopental infusion. Carotid arteries and carotid bodies were identified bilaterally followed by glomectomy on the contralateral side and positioning of a lingual artery catheter with its tip located in the carotid bifurcation on the ipsilateral side. From the dissected ipsilateral C-4 nerve root, changes in integrated phrenic nerve activity (IPA) were recorded after isocapnic step reductions from hyperoxia to normoxia (fraction of inspired oxygen [FIO2] 0.21, normoxic challenge) and from hyperoxia to moderate hypoxia (FIO2 0.15, hypoxic challenge) immediately after a close carotid bolus injection of either normal saline or 1 or 10 microgram of vecuronium. Arterial blood gases were analyzed during each ventilatory state. Phrenic nerve response to hypoxia expressed as chemosensitivity (Sch) was computed as the relative change in phrenic nerve activity per unit decrease in arterial oxygen saturation (Sao2), that is: Sch = (IPA challenge/IPA hyperoxia) - 1/Sao2 hyperoxia - Sao2 challenge. Hypoxic challenges were associated with reduced phrenic nerve response (Sch) after injection of 1 and 10 micrograms of vecuronium compared with normal saline. During normoxic challenges, no change occurred after 1 microgram, but reduced chemosensitivity was seen after 10 micrograms of vecuronium. We conclude that vecuronium depresses phrenic nerve activity during hypoxia.


Neuropathology of Psoriasis.
The histopathology of nervous, tissue, elements was studied with three different stains in the lesions and the uninvolved skin of psoriasis vulgaris patient. No abnormal change, was detected.


Fracture dislocation of the lumbar spine without paraplegia. A case report.
A 17-year-old boy sustained a complete fracture-dislocation of the lumbar spine. Immediately after the injury there was motor paralysis of the lower limbs; 17 hours post-injury, operative reduction and fixation were carried out. Nearly full neurological recovery was obtained.


Beyond quitting: predictors of teen smoking cessation, reduction and acceleration following a school-based intervention.
There remains a great need for effective, cost-efficient, and acceptable youth smoking cessation interventions. Unfortunately, only a few interventions have been demonstrated to increase quit rates among youth smokers, and little is known about how elements of cessation interventions and participants' psychosocial characteristics and smoking histories interact to influence program outcomes. Additionally, few studies have examined how these variables lead to complete smoking abstinence, reduction or acceleration over the course of a structured cessation intervention. Data for the present investigation were drawn from a sample of teen smokers (n=5892) who voluntarily participated in either a controlled study or field study (i.e., no control group) of the American Lung Association's Not On Tobacco (N-O-T) program between 1998 and 2006 in five states. Results suggest that those who reduce smoking (but do not achieve full abstinence) are similar to those who quit on most measures except stage of change. Furthermore, it was found that those who increased smoking were heavier smokers at baseline, more addicted, were more likely to have parents, siblings, and significant others who smoked and reported less confidence in and less motivation for quitting than did those who quit or reduced smoking. Finally, a path model demonstrated how peers, siblings and romantic partners affected tobacco use and cessation outcomes differently for males and females. Implications for interventions are discussed.


Review of six cases of maxillary ameloblastoma from the West Indies: re-entry cryosurgery as prophylactic surgical intervention.
Maxillary ameloblastoma is a rare histopathological entity. A total of six cases of histologically confirmed maxillary ameloblastoma from the West Indies is reviewed. Three of the cases were taken from a total of 47 histologically confirmed ameloblastoma over a 15-year period (1980-1995) from two major maxillofacial units in Jamaica. Two other cases were from documentation in Jamaica between 2000 and 2002, one of which occurred in a 13-year-old girl (these two patients have been followed-up periodically to 2006). The sixth case was from the records of the maxillofacial department of the University of the West Indies in Trinidad and Tobago. This last patient, at a recent review, has inoperable recurrence. These cases were reviewed with respect to demographics (patient's age and gender), location and extent of tumour, radiological features, concurrent involvement of the mandible, treatment with special emphasis on current treatment modality and follow-up. The findings do not differ from what has been documented by other authors from other parts of the world. Because of the radiographic anatomy of the maxilla, recurrence may be detected late despite such occurring earlier following initial surgical management. It is for this reason that we suggest re-entry cryosurgery for prevention of recurrence for maxillary ameloblastoma. The only case of maxillary ameloblastoma that had re-entry cryosurgery continues to benefit from absence of recurrence at periodic follow-ups at four years post-primary surgical management (which was enucleation).


Reconstruction of Total Bone Defects following Resection of Malignant Tumors of the Upper Extremity with 3D Printed Prostheses: Presentation of Two Patients with a Follow-Up of Three Years.
Wide tumor resection is the local treatment of choice for patients with primary malignant bone tumors and a prerequisite for long-term survival. We present two patients that underwent total bone resection in the upper limb because of primary malignant bone tumors. The defects were then reconstructed by a 3D printed prosthesis, a procedure that, to our knowledge, has not been reported for bone defects of the upper extremity so far. Complete resection of the affected bone was required in a five-year-old girl with a high-grade osteoblastic osteosarcoma of the humerus and a 53-year-old man with a dedifferentiated leiomyosarcoma of the radius, due to the tumor's extent. Following neoadjuvant chemotherapy, resection of the entire affected humerus including the axillary nerve took place in the first case and the entire affected radius including parts of the radial nerve in the second case. Approximately three years after surgery, both patients are alive and pain-free. Despite a postoperative drop hand that affected the now 56-year-old man, he is able to carry out everyday activities such as brushing his teeth, writing, and eating. The now eight-year-old girl is also able to engage in normal activities with her left arm such as eating and carrying lightweight objects. Both patients are tumor-free to date.


Jules Bordet (1870-1961): a bridge between early and modern immunology.
Jules Bordet, a pioneering immunologist, lived until the dawn of molecular immunology. He was born in Belgium in 1870, obtained a medical degree in 1892, worked at l'Institut Pasteur in Paris from 1894 to 1901 and then established the Pasteur Institute of Brabant in Brussels. Before World War I, Bordet found that complement binds to antibody-antigen complexes regardless of the antigen or antibodies involved. Subsequently he developed the complement fixation test that was of diagnostic importance for several decades. For his research concerning complement he was awarded the 1919 Nobel Prize in Physiology or Medicine. During that period he also discovered anaphylatoxin, conglutinin, and the cause of whooping cough (Bordetella pertussis). After World War I he found how thrombin forms, how platelets participate in clotting, lysozyme in human milk and much of the biology of bacteriophages. In addition, Bordet worked fervently to limit weapons of mass destruction and promote peace until his death in 1961.


Uterine environment and pregnancy rate of heifers with elevated plasma urea nitrogen.
Diets high in protein are associated with lower reproductive performance and changes in the uterine environment. The objective of this study was to determine the effect of elevated systemic concentrations of urea nitrogen on the uterine environment and pregnancy success in beef heifers. Heifers (n=150) were matched by breed, age, and body weight then randomly assigned to one of two dietary treatments: 1) Control (10% CP) or 2) High protein (14% CP) over three replicates (n=40/replicate). Estrus was synchronized with an injection of PGF2α. Uterine pH, plasma urea nitrogen (PUN), ammonia, and glucose concentrations were determined on d 7 of the estrous cycle. Pregnancy status was determined by ultrasonography 30 d following the breeding season. In vitro fertilization was performed on heifers precluded from uterine analysis (n=15/diet) to determine the effect of a High Protein diet on oocyte quality. Plasma urea concentrations were greater in the High Protein diet compared to Control (P<0.001). There was no effect of diet on plasma ammonia (P=0.12), plasma glucose (P=0.40), uterine pH (P=0.67), interval to estrus (P=0.54), duration of estrus (P=0.38), or pregnancy rate (P=0.83). There was no effect of diet (P>0.40) on the number of oocytes collected, number of oocytes cleaved, amount of blastocysts, percentage of oocytes cleaved and percentage of blastocysts present. In summary, high nitrogen diets increased PUN concentrations in heifers; however, there were no deleterious effects on reproduction.


Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1.
Osteoradionecrosis (ORN) of the mandible is a serious complication of head and neck radiotherapy. This study aims to investigate the effect of hyperbaric oxygen (HBO) treatment on ORN in two randomized, controlled multicentre trials. Patients with ORN with indication for surgical treatment were randomised to either group 1: surgical removal of necrotic mandibular bone supplemented by 30 pre- and 10 postoperative HBO exposures at 243 kPa for 90 min each, or group 2: surgical removal of necrotic bone only. Primary outcome was healing of ORN one year after surgery evaluated by a clinically adjusted version of the Common Toxicity Criteria of Adverse Events (CTCAE) v 3.0. Secondary outcomes included xerostomia, unstimulated and stimulated whole salivation rates, trismus, dysphagia, pain, Activities of Daily Living (ADL) and quality of life according to EORTC. Data were combined from two separate trials. Ninety-seven were enrolled and 65 were eligible for the intent-to-treat analysis. The 33% drop-out was equally distributed between groups. In group 1, 70% (21/30) healed compared to 51% (18/35) in group 2. HBO was associated with an increased chance of healing independent of baseline ORN grade or smoking status as well as improved xerostomia, unstimulated whole salivary flow rate, and dysphagia. Due to insufficient recruitment, none of the endpoints reached a statistically significant difference between groups. ADL data could only be obtained from 50 patients. Hyperbaric oxygen did not significantly improve the healing outcome of osteoradionecrosis after surgical removal of necrotic bone as compared to standard care (70% vs. 51%). This effect is not statistically significant due to the fact that the study was underpowered and is therefore prone to type II error.


[A study on immunohistochemical detection of estrogen receptor in the breast cancer tissue--a comparison between routinely paraffin-embedded and frozen sections].
On immunohistochemical detection of estrogen receptor in the breast cancer tissue, we examined whether ER1D5 [Anti-estrogen receptor monoclonal antibody, clone ER1D5(MBL)] using routinely fixed paraffin-embedded section may take the place of ERICA [Estrogen receptor immunocytochemical assay kit (DAINABOT)] using frozen one or not. With 63 breast cancer cases, estrogen receptor was positive in 63.4% of the cases by ERICA, while in 25.4% and 28.6% by ER1D5 in which enhancement of the antigen with microwave heating (high frequency power 500W 5 minutes) and autoclave heating (121 degrees C, 20 minutes) had been carried out. At present, it is unreasonable for ER1D5 to take the place of ERICA. However, it is noteworthy that estrogen receptor is detectable with paraffin-embedded section although the rate of positivity is low. It is desirable that further development of the antibody for estrogen receptor in the breast cancer tissue with paraffin-embedded section will be continued.


Biomechanical evaluation of the pedicle screw insertion depth effect on screw stability under cyclic loading and subsequent pullout.
A biomechanical ex vivo study of the human lumbar spine. To evaluate the effects of transpedicular screw insertion depth on overall screw stability and pullout strength following cyclic loading in the osteoporotic lumbar spine. Although much is known about the clinical outcomes of spinal fusion, questions remain in our understanding of the biomechanical strength of lumbar pedicle screw fixation as it relates to screw sizing and placement. Biomechanical analyses examining ideal pedicle screw depth with current pedicle screw technology are limited. In the osteoporotic spine, optimized pedicle screw insertion depth may improve construct strength, decreasing the risk of loosening or pullout. A total of 100 pedicles from 10 osteoporotic lumbar spines were randomly instrumented with pedicle screws in mid-body, pericortical, and bicortical depths. Instrumented specimens underwent cyclic loading (5000 cycles of ±2 N m pure flexion moment) and subsequent pullout. Screw loosening, failure loads, and energy absorption were calculated. Cyclic loading significantly (P<0.001) reduced screw-bone angular stiffness between prefatigue and postfatigue conditions by 25.6%±17.9% (mid-body), 20.8%±14.4% (pericortical), and 14.0%±13.0% (bicortical). Increased insertion depth resulted in lower levels of reduction in angular stiffness, which was only significant between mid-body and bicortical screws (P=0.009). Pullout force and energy of 583±306 N and 1.75±1.98 N m (mid-body), 713±321 N and 2.40±1.79 N m (pericortical), and 797±285 N and 2.97±2.33 N m (bicortical) were observed, respectively. Increased insertion depth resulted in higher magnitudes of both pullout force and energy, which was significant only for pullout force between mid-body and bicortical screws (P=0.005). Although increased screw depth led to increased fixation and decreased loosening, additional purchase of the stiff anterior cortex is essential to reach superior screw-bone construct stability and stiffness.


Apoptosis is inhibited early in the dysplasia-carcinoma sequence of Barrett esophagus.
To evaluate the alteration of apoptosis in the esophageal epithelium during the esophagitis-Barrett esophagus-adenocarcinoma sequence. Archival tissue samples of 85 lesions in 58 cases were used. The lesions represented 7 groups: normal esophagus (n = 10), reflux esophagitis (n = 12), Barrett metaplasia (n = 21), Barrett low-grade dysplasia (n = 17), Barrett high-grade dysplasia (n = 5), well- or moderately differentiated adenocarcinoma (n = 10), and poorly differentiated adenocarcinoma (n = 10). Apoptotic cells with fragmented DNA were detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP)-biotin nick end labeling (TUNEL) method. Monoclonal antibodies against bcl-2 protein were applied using the avidin-biotin complex immunoperoxidase method. The esophagitis group showed many apoptotic cells on the epithelial surface; in the other groups, few apoptotic cells were seen. Weak bcl-2 expression was seen in the basal cells in normal subjects and those with esophagitis. There was overexpression of bcl-2 in 72% of Barrett metaplasia, 100% of Barrett low-grade dysplasia, 25% of Barrett high-grade dysplasia, 40% of well- or moderately differentiated adenocarcinoma, and 20% of poorly differentiated adenocarcinoma. Increased apoptosis in reflux esophagitis may be a protective mechanism counteracting increased proliferation. Inhibition of apoptosis by overexpression of bcl-2 protein occurs early in the dysplasia-carcinoma sequence of Barrett esophagus. The resulting prolongation of cell survival may promote neoplastic progression. Despite the absence of apoptosis, bcl-2 was not widely overexpressed in Barrett high-grade dysplasia and adenocarcinoma, suggesting that cells acquire other ways of avoiding apoptosis as malignancy appears.


Optimal designs for 2-color microarray experiments.
Statisticians can play a crucial role in the design of gene expression studies to ensure the most effective allocation of available resources. This paper considers Pareto optimal designs for gene expression studies involving 2-color microarrays. Pareto optimality enables the recommendation of designs that are particularly efficient for the effects of most interest to biologists. This is relevant in the microarray context where analysis is typically carried out separately for those effects. Our approach will allow for effects of interest that correspond to contrasts rather than solely considering parameters of the linear model. We further develop the approach to cater for additional experimental considerations such as contrasts that are of equal scientific interest. This amounts to partitioning all relevant contrasts into subsets of effects that are of equal importance. Based on the partitions, a penalty is employed in order to recommend designs for complex and varied microarray experiments. Finally, we address the issue of gene-specific dye bias. We illustrate using studies of leukemia and breast cancer.


Public health financial management competencies.
The absence of appropriate financial management competencies has impeded progress in advancing the field of public health finance. It also inhibits the ability to professionalize this sector of the workforce. Financial managers should play a critical role by providing information relevant to decision making. The lack of fundamental financial management knowledge and skills is a barrier to fulfilling this role. A national expert committee was convened to examine this issue. The committee reviewed standards related to financial and business management practices within public health and closely related areas. Alignments were made with national standards such as those established for government chief financial officers. On the basis of this analysis, a comprehensive set of public health financial management competencies was identified and examined further by a review panel. At a minimum, the competencies can be used to define job descriptions, assess job performance, identify critical gaps in financial analysis, create career paths, and design educational programs.


Unraveling the Mysteries of Restless Leg Syndrome.
Restless leg syndrome (RLS) or Willis-Ekbom disease (WED) is an under-diagnosed, chronic, and progressive primary sensory-motor disorder. It is characterized by an uncontrollable urge to move the legs due to uncomfortable and sometimes painful sensations, with a diurnal variation. RLS can lead to severe sleep disturbances, a usual cause of consultation. The pathophysiology is known partially, and it is believed that there is an association between the different variants of genetic mutations combined with dopaminergic and brain iron dysregulation, which plays an important role. The data used for this study were extracted from the articles found in the PubMed database that discuss different gene variants, pathophysiology, and various methods of treatment. They also highlight the role of iron in the pathogenesis of RLS as it is required for the synthesis of tyrosine hydroxylase, which is the rate-limiting step for dopamine synthesis. This review article provides a clinically useful overview of RLS in terms of pathophysiological findings, its genetic associations, and therapeutic options by using the currently available literature. Because RLS presents with vague symptoms and shares similarities with many other diseases, it might be overlooked by many physicians resulting in underdiagnosis and under-treatment. While these discoveries provide a breakthrough in understanding the details of RLS, further studies are recommended as these studies are limited to animal models and provide a limited representation of the general population.


Interfacial aggregation of Janus rods in binary polymer blends and their effect on phase separation.
Janus particles interfacially self-assemble into different structures when incorporated into multiphase systems. Dissipative particle dynamics simulations are employed herein to investigate the interplay between aggregation mechanisms and phase separation in polymer blends. Shorter rods with a standing configuration become increasingly "caged" or trapped in larger aggregates as weight fraction increases, which is reflected in the way that their diffusion is coupled to their aggregation rates. Janus rods of higher aspect ratios that are tilted at the interface aggregate side-by-side and are able to hinder phase separation kinetics. This is due to a combination of individual Janus rod conformations at the interface, their intrinsic aggregation mechanisms, aggregate fractal dimension, and aggregation rates, and can also be traced back to the scaling of the diffusion coefficient of aggregates with their size. Findings presented provide insight into the mechanisms governing two dimensionally growing colloidal aggregates at fluid interfaces, more specifically, those associated with Janus particles, and shed light on the potential of these systems in paving the way for designing new functional materials.


[Effect of the 5-HT3 receptor antagonist granisetron on estramustine phosphate sodium (Estracyt)-induced emesis in ferrets].
Estracyt(R) is an antimitotic drug used for the treatment of prostate cancer, and its most common adverse effects are nausea and vomiting. In this study, we investigated the effect of a 5-HT3 receptor antagonist, granisetron, on emesis induced in ferrets by estramustine phosphate sodium (EMP), the active ingredient of Estracyt. To clarify the mechanism of action of EMP-induced emesis, we also investigated the effect of EMP on the release of serotonin (5-HT) in the isolated rat ileum. EMP (3 mg/kg, per os) induced 75.3+/-10.2 retching episodes and 7.5+/-1.3 vomiting episodes during a 2-h observation period. The latency to the first emetic response was 58.0+/-13.5 min. Granisetron (0.1 mg/kg, per os) administered 1 h before the administration of EMP reduced the number of EMP-induced retching and vomiting episodes to 1.3+/-1.3 and 1.0+/-1.0, respectively, and prolonged the latency by a factor of almost two. EMP (10-5 and 10-4 M) increased 5-HT release from isolated rat ileum, and 10 -7 M granisetron almost completely inhibited the increase induced by 10-4 M EMP. These results suggest that EMP induces nausea and vomiting via 5-HT release from the ileum, and that 5-HT3 receptor antagonists may be useful to prevent gastrointestinal adverse effects that occur during treatment with Estracyt.


Long non-coding RNA MNX1-AS1 promotes hepatocellular carcinoma proliferation and invasion through targeting miR-218-5p/COMMD8 axis.
Long noncoding RNAs (lncRNAs) are involved in tumorigenesis. Previously, lncRNA MNX1-AS1 was reported to increase the malignancy of ovarian cancer, cervical cancer and lung cancer. However, the potential function of MNX1-AS1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we found that MNX1-AS1 was remarkably upregulated in HCC tissues and cell lines. Furthermore, MNX1-AS1 overexpression was related to advanced stage and metastasis, and predicted poor prognosis. Loss-of-function assays showed that MNX1-AS1 knockdown suppressed the proliferation, migration and invasion of HCC cells in vitro. Further investigation indicated that MNX1-AS1 silencing delayed HCC growth in vivo. Mechanistically, we identified that MNX1-AS1 was a competing endogenous RNA (ceRNA) for miR-218-5p. We demonstrated that MNX1-AS1 promoted COMMD8 expression through sponging miR-218-5p, and then contributed to HCC progression. Restoration of COMMD8 significantly reversed the effects of MNX1-AS1 knockdown. Taken together, our findings demonstrated that MNX1-AS1 promoted the malignant properties of HCC through targeting miR-218-5p/COMMD8 pathway.


Dementia.
Dementia is a clinical diagnosis requiring new functional dependence on the basis of progressive cognitive decline. It is estimated that 1.3% of the entire UK population, or 7.1% of those aged 65 or over, have dementia. Applying these to 2013 population estimates gives an estimated number of 19,765 people living with dementia in Northern Ireland. The clinical syndrome of dementia can be due to a variety of underlying pathophysiological processes. The most common of these is Alzheimer's disease (50-75%) followed by vascular dementia (20%), dementia with Lewy bodies (5%) and frontotemporal lobar dementia (5%). The clinical symptoms and pathophysiological processes of these diseases overlap significantly. Biomarkers to aid diagnosis and prognosis are emerging. Acetylcholinesterase inhibitors and memantine are the only medications currently licensed for the treatment of dementia. The nature of symptoms mean people with dementia are more dependent and vulnerable, both socially and in terms of physical and mental health, presenting evolving challenges to society and to our healthcare systems.


Late-life (migrainous) scintillating zigzags without headache: one person's 27-year experience.
Episodes of typical scintillating zigzags similar to the visual aura of migraine may occur without headache, especially after the age of 50. There is no record of one individual's long-term experience. This paper is a personal account of all 41 episodes of scintillating zigzags that occurred between the ages of 59 and 85. Observations were made on several aspects of the visual event itself--evolution, pattern, scotoma, coloration, duration, lateralization, etc. The chronological distribution of spells, circumstances of occurrence, time of day, the season, etc were noted. The study was observational in nature. Documentation of this experience could be of value clinically and scientifically. The spells occurred irregularly, unrelated to season, time of day, activity at onset, diet, and temperamental state. The characteristic appearance was a flickering zigzag line that began centrally and migrated to the periphery. The display, which was stereotyped, was achromatic. The average duration was 15 minutes. Both visual fields were equally involved, never at the same time. The details of the scintillating zigzag line are actually complex and an account of the observations of others and of the author is included here.


Serum transferrin receptors: Distribution and diagnostic performance in pre-school children.
Soluble transferrin receptors have gained interest in the field of diagnosing anemias. Reference ranges differ according to the method used for the quantification of sTfR. We aim to explore the distributional properties and diagnostic performance of sTfR in pre-school healthy children as well as in children with beta-thalassemia carriers, iron deficiency with normal hematological phenotype (ID) and iron deficiency anemia (IDA). Circulating sTfR as well as biochemical and hematological indices were determined in 521 pre-school children and four groups (normal children, beta-thalassemia traits, ID and IDA) were formed. Diagnostic performance and distribution of sTfR according to age and in relation to several parameters were evaluated in every group. Three hundred eighty one children (261 normal, 60 beta-thalassemia traits, 44 ID and 16 IDA) aged 1-6 years were included. We found that distribution of sTfR differed significantly among the four groups (Kruskal Wallis p<0.001) with children in the normal group exhibiting lower concentrations compared to all other. A negative correlation between sTfR and age occurred in the normal (beta=-0.12, p<0.001) and the ID groups (beta=-0.13, p=0.035). In the beta-thal and IDA groups sTfR is correlated to HbA(2) (beta=0.34, p=0.001) and ferritin (Spearman's rho=-0.6, p=0.014) respectively. An area under the curve equal to 0.63 was achieved by sTfR in distinguishing between normal and ID children. Sensitivity and specificity were 70.5% and 50% respectively at a cut-off of 2.5 mg/l. Levels of sTfR are negatively correlated to age in pre-school children while dyserythropoietic procedures like beta-thal, ID, and IDA significantly affect them. These findings indicated that the accuracy of sTfR in diagnosing ID from normal children is limited. Standardization will allow the use of formulas that combine sTfR and ferritin which are of greater diagnostic value than sTfR alone.


Global gene expression profiles reveal pathways related to the pathogenesis of chronic obstructive pulmonary disease.
Extract: Chronic obstructive pulmonary disease (COPD) is a slowly progressive, and irreversible disorder characterized by airway obstruction, which is a significant cause of morbidity, mortality and health care costs. COPD is a collective term describing two separate chronic lung diseases: emphysema and chronic bronchitis, which have a common culprit -- the cigarette. Cigarette smoke has been generally accepted as the primary factor in the development of COPD; cigarette use accounts for about 80% to 90% of COPD cases in the United States. However, only 15 to 20% of smokers develop clinically significant symptoms of COPD, which suggests there may be a genetic susceptibility to the development of the disease. The genes that determine this genetic susceptibility to cigarette smoking and disease progression to COPD are poorly understood. Individual genes or groups of genes that are expressed differently in smokers with and without COPD can be determined by comparing their corresponding global gene expression profiles. Two approaches, microarray and serial analysis of gene expression (SAGE), are currently used for simultaneous and rapid analysis of the expression levels of thousands of genes in a given cell population. Microarray, involving the binding of labeled nucleic acids targets to immobilized probes, is a relatively rapid and widely used technique. However, microarray is a closed method, meaning that it only measures expression levels of already collected nucleic acids sequences.


Evolution of caudal fin ray development and caudal fin hypural diastema complex in spotted gar, teleosts, and other neopterygian fishes.
The caudal fin of actinopterygians transitioned from a heterocercal dorsoventrally asymmetrical fin to a homocercal externally symmetrical fin in teleosts through poorly understood evolutionary developmental mechanisms. We studied the caudal skeleton of major living actinopterygian lineages, including polypteriformes, acipenseriformes, Holostei (gars and bowfin), and teleosts, compared with reports of extinct neopterygians and basal teleosteans. We focused on the hypural diastema complex, which includes (1) a gap between hypurals 2 and 3, that (2) separates two plates of connective tissue at (3) the branching of caudal vasculature; these features had been considered as a shared, derived trait of teleosts, a synapomorphy. These studies revealed that gars and teleosts share all three features of the hypural diastema complex. Absence of a complex with these features from bowfin, fossil Holostei, and stem Teleostei argues in favor of repetitive, independent emergence in several neopterygian and basal Teleostei lineages, or less likely, many independent losses. We further observed that, in gars and teleosts, the earliest developing lepidotrichia align with the horizontal adult body axis, thus participating in external symmetry. These results suggest that the hypural diastema complex in teleosts and gars represents a homoplasy among neopterygians and that it emerged repeatedly by parallel evolution due to shared inherited underlying genetic and developmental programs (latent homology). Because the hypural diastema complex exists in gars with heterocercal tails, this complex is independent of homocercality. Developmental Dynamics 247:832-853, 2018. © 2018 Wiley Periodicals, Inc.


Percutaneous absorption of gold sodium thiosulfate used for patch testing.
Contact allergy to gold has been shown to be correlated to wearing of golden jewellery as well as to the presence of dental gold. The prerequisite for sensitization and elicitation of an allergic contact dermatitis to gold is ionization and percutaneous absorption of the allergen. The present study was undertaken with the aim to demonstrate gold in blood after an occlusive patch testing with gold sodium thiosulfate (GSTS). Patients were patch tested with GSTS 0.5, 2.0 and 5.0% in petrolatum. Venous blood was sampled before testing as well as on day 3 (D3) or day 7 (D7). Blood gold levels were analysed by inductively coupled plasma mass spectrometry. In all 66 patients, the blood level of gold was significantly higher in the 2nd blood sample than in the 1st (median 0.34 versus 0.03 micro g/l). The increase was similar in patients allergic and not allergic to gold. There was no difference between gold levels on D3 and on D7 after epicutaneous application. Presumably, other allergens may also be taken up in blood during patch testing.


The effect of ulnar variance on scapholunate and capitolunate angles.
Background Ulnar variance (UV), which is measured using anteroposterior (AP) X-rays, is associated with the development of multiple wrist pathologies. The scapholunate angle (SLA) and capitolunate angle (CLA) are measured using lateral X-rays, and these can be used in the diagnosis of intercalated segmental instability. Purpose To determine the effect of UV on SLA and CLA. Material and Methods A total of 140 patients (73 women, 67 men; mean age, 37.8 ± 14.6 years; 95% confidence interval [CI], 35.4-40.3) were included in the study. Participants were excluded if they presented with fractures or malunions, any arthritic conditions, avascular necrosis, congenital deformities, or bone and soft tissue tumors. UV, SLA, and CLA were measured using AP and lateral wrist X-rays. Results Patients were grouped as positive, neutral, and negative UV. There was no statistically significant difference in mean ages, sex, and sides (left or right) between the UV groups ( P > 0.05). In addition, there was no statistically significant difference in the mean values of SLA and CLA between the UV groups ( P > 0.05). UV showed no statistically significant association with SLA and CLA (r = -0.064; P = 0.455, and r = 0.059; P = 0.485, respectively). However, there was a statistically significant association between SLA and CLA (r = -0.482; P < 0.001). Conclusion There is higher prevalence of neutral UV and no correlation between UV with respect to age and sex of patients in the local Turkish population. SLA and CLA are not affected by UV. There is a negative correlation between SLA and CLA.


Sources of job satisfaction and psychological distress in GPs and medical house officers.
The psychological health and job satisfaction of 285 GPs and 89 medical house officers from Leeds was compared using standardized self-report measures. Forty-eight per cent of the GPs and 20% of the house officers scored as 'cases' of psychiatric disorder. The GPs were less satisfied with the recognition they received for their work and their hours of work, but more satisfied with their job variety and job autonomy. Further research examining the sources of work-related distress in different medical settings could help inform future organizational changes.


Hass avocado composition and potential health effects.
Hass avocados, the most common commercial avocado cultivars in the world, contain a variety of essential nutrients and important phytochemicals. Although the official avocado serving is one-fifth of a fruit (30 g), according to NHANES analysis the average consumption is one-half an avocado (68 g), which provides a nutrient and phytochemical dense food consisting of the following: dietary fiber (4.6 g), total sugar (0.2 g), potassium (345 mg), sodium (5.5 mg), magnesium (19.5 mg), vitamin A (43 μg), vitamin C (6.0 mg), vitamin E (1.3 mg), vitamin K1 (14 μg), folate (60 mg), vitamin B-6 (0.2 mg), niacin (1.3 mg), pantothenic acid (1.0 mg), riboflavin (0.1 mg), choline (10 mg), lutein/zeaxanthin (185 μg), phytosterols (57 mg), and high-monounsaturated fatty acids (6.7 g) and 114 kcals or 1.7 kcal/g. The avocado oil consists of 71% monounsaturated fatty acids (MUFA), 13% polyunsaturated fatty acids (PUFA), and 16% saturated fatty acids (SFA), which helps to promote healthy blood lipid profiles and enhance the bioavailability of fat soluble vitamins and phytochemicals from the avocado or other fruits and vegetables, naturally low in fat, which are consumed with avocados. There are eight preliminary clinical studies showing that avocado consumption helps support cardiovascular health. Exploratory studies suggest that avocados may support weight management and healthy aging.


The prevalence of retinal vein occlusion: pooled data from population studies from the United States, Europe, Asia, and Australia.
To summarize the prevalence of retinal vein occlusion (RVO) from studies in the United States, Europe, Asia, and Australia. Pooled analysis using individual population-based data. Individual participant data from population-based studies around the world that had ascertained RVO from fundus photographs. Each study provided data on branch RVO and central RVO by age, sex, and ethnicity. Prevalence rates were directly age and sex standardized to the 2008 world population aged 30 years and older. Estimates were calculated by study and, after pooling, by ethnicity. Summary estimates included studies in which RVO was assessed from fundus photographs on >or=2 fields of both eyes. Any RVO, CRVO, or BRVO. The combined pooled data contained 68,751 individuals from 15 studies, with participants' ages ranging from 30 to 101 years. In analyses of 11 studies that assessed >or=2 fundus fields of both eyes (n=49,869), the age- and sex-standardized prevalence was 5.20 per 1000 (confidence interval [CI], 4.40-5.99) for any RVO, 4.42 per 1000 (CI, 3.65-5.19) for BRVO, and 0.80 per 1000 (CI, 0.61-0.99) for CRVO. Prevalence varied by race/ethnicity and increased with age, but did not differ by gender. The age- and sex-standardized prevalence of any RVO was 3.7 per 1000 (CI, 2.8-4.6) in whites (5 studies), 3.9 per 1000 (CI, 1.8-6.0) in blacks (1 study), 5.7 per 1000 (CI, 4.5-6.8) in Asians (6 studies), and 6.9 per 1000 (CI, 5.7-8.3) in Hispanics (3 studies). Prevalence for CRVO was lower than BRVO in all ethnic populations. On the basis of these data, an estimated 16.4 million (CI, 13.9-18.9) adults are affected by RVO, with 2.5 million (CI, 1.9-3.1) affected by CRVO and 13.9 million (CI, 11.5-16.4) affected by BRVO. Study limitations include non-uniform sampling frames in identifying study participants and in acquisition and grading of RVO data. Our study provides summary data on the prevalence of RVO and suggests that approximately 16 million people may have this condition. Research on preventive and treatment strategies for this sight-threatening eye disease is needed.


Magnetic anisotropy of a cyclic octanuclear Fe(III) cluster and magneto-structural correlations in molecular ferric wheels.
The magnetic anisotropy of the cyclic octanuclear Fe(III) cluster [Cs subsetFe(8)[N(CH(2)CH(2)O)(3)](8)]Cl was investigated. Based on a spin Hamiltonian formalism and the consequent use of all symmetries, the magnetic anisotropy could be calculated exactly to first order, i.e., in the strong exchange limit. Experimentally, the magnetic anisotropy was investigated by magnetic susceptibility and high-field torque magnetometry of single crystals. The field and angle dependence of the torque at 1.7 K could be accurately reproduced by the calculations with one single parameter set, providing accurate results for the coupling constant and single-ion zero-field-splitting. These magnetic parameters are compared to those of several related hexanuclear ferric wheels and are discussed with respect to magneto-structural correlations for both coupling constant and single-ion anisotropy.


Inferior Vena Cava Resection and Reconstruction for Tumoral Recurrence after Right Nephrectomy.
We report a 60 years old patient who was admitted for a local recurrence after a right nephrectomy performed 2 years ago (papillary renal carcinoma with areas of sarcomatoid differentiation - pT3a). CT scan showed a retroperitoneal mass with invasion of the inferior vena cava. We performed a complete en-bloque excision of the tumor with the infrarenal portion of the inferior vena cava and lympha-denectomy. The vascular reconstruction was performed by the interposition of a 20 mm diameter Dacron prosthesis. The postoperative course was complicated due to an episode of digestive bleeding (duodenal ulcer) which stopped after conservative treatment (antisecretory and hemostatics, including rFVIIa), but eventually favourable. At 6 months follow-up the patient presents no sign of tumoral relapse and a functional vascular prosthesis. The case is interesting due to the rarity of the surgical procedure and the indication. The surgical approach of the retroperitoneal tumors with vascular involvement is possible in centers with adequate technical endownment and human expertise.


Determination of Integral Depth Dose in Proton Pencil Beam Using Plane-parallel Ionization Chambers.
This study aimed to determine the integral depth-dose curves and assess the geometric collection efficiency of different detector diameters in proton pencil beam scanning. The Varian ProBeam Compact spot scanning system was used for this study. The integral depth-dose curves with a proton energy range of 130 to 220 MeV were acquired with 2 types of Bragg peak chambers: 34070 with 8-cm diameter and 34089 with 15-cm diameter (PTW), multi-layer ionization chamber with 12-cm diameter (Giraffe, IBA Dosimetry), and PeakFinder with 8-cm diameter (PTW). To assess geometric collection efficiency, the integral depth-dose curves of 8- and 12-cm chamber diameters were compared to a 15-cm chamber diameter as the largest detector. At intermediate depths of 130, 150, 190, and 220 MeV, PTW Bragg peak chamber type 34089 provided the highest integral depth-dose curves followed by IBA Giraffe, PTW Bragg peak chamber type 34070, and PTW PeakFinder. Moreover, PTW Bragg peak chamber type 34089 had increased geometric collection efficiency up to 3.8%, 6.1%, and 3.1% when compared to PTW Bragg peak chamber type 34070, PTW PeakFinder, and IBA Giraffe, respectively. A larger plane-parallel ionization chamber could increase the geometric collection efficiency of the detector, especially at intermediate depths and high-energy proton beams.


A new program for highly reproducible automatic evaluation of the substantia nigra from transcranial sonographic images.
Recent studies report increased echogenicity of the substantia nigra (SN) in patients with Parkinson's disease (PD) using transcranial sonography (TCS). However, the main limitation to TCS is its dependence on the sonographer's experience. Experimental software for quantitative evaluation of the echogenic SN area was thus developed by us. The aim of this study was to test the reliability of the data using developed B-Mode Assist software in patients with parkinsonism and in healthy volunteers. The SN was imaged from the right temporal bone window in mesencephalic plane using TCS. DICOM images of SN were saved, converted into JPEG format, encoded and processed. Two observers performed 3 automatic evaluations of the SN area (measurements of SN area in each gray scale intensity inside the region of interest) by counting the standard deviation of all 6 measurements using developed software. The average value of all 3 measurements of each observer was used for computing Cohen's kappa coefficient to determine inter-observer correlations. Cohen's kappa coefficients as an intra-observer correlation for observer 1 and observer 2 were counted from the first 2 measurements of both observers. In total, 92 images were evaluated using this software. The mean of the standard deviations was 3.87; Cohen's kappa for intra-observer agreement of two observers were 0.947, and 0.943, resp.; Cohen's kappa for inter-observers agreement was 0.880. The agreement between visual and automatic detection of SN pathology was in 97.8% images. The sensitivity, specificity, positive and negative predictive values of automatic measurement were 100, 96.2, 95.1, 100%, resp. The results show very reliable measurement of SN features using designed application with "almost perfect" inter-observer and intra-observer agreements.


Immune enhancement and anti-tumour activity of IL-23.
Immunotherapy, including the use of cytokines and/or modified tumour cells immune stimulatory cytokines, can enhance the host anti-tumour immune responses. Interleukin-23 (IL-23) is a relative novel cytokine, which consists of a heterodimer of the IL-12p40 subunit and a novel p19 subunit. IL-23 has biological activities similar to but distinct from IL-12. IL-23 can enhance the proliferation of memory T cells and the production of IFN-gamma, IL-12 and TNF-alpha from activated T cells. IL-23 activates macrophages to produce TNF-alpha and nitric oxide. IL-23 can also act directly on dendritic cells and possesses potent anti-tumour and anti-metastatic activity in murine models of cancer. IL-23 can also induce a lower level of IFN-gamma production compared with that induced by IL-12. This may make IL-23 an alternative and safer therapeutic agent for cancer, as IL-12 administration can lead to severe toxic side effects because of the extremely high levels of IFN-gamma it induces.


Direct carbon-carbon bond formation via chemoselective soft enolization of thioesters: a remarkably simple and versatile crossed-Claisen reaction applied to the synthesis of LY294002.
Thioesters undergo chemoselective soft enolization and acylation by N-acylbenzotriazoles on treatment with MgBr2 x OEt2 and i-Pr2NEt to give beta-keto thioesters. Prior enolate formation is not required, and the reaction is conducted using untreated CH2Cl2 open to the air. The coupled products are stable synthetic equivalents of beta-keto acids and can be converted directly into beta-keto esters, beta-keto amides, and beta-diketones under mild conditions. The utility of this carbon-carbon bond-forming method is shown through the synthesis of the PI3-K inhibitor LY294002.


[A case of amyotrophic lateral sclerosis with SIADH and throbbing headache induced by selective serotonin reuptake inhibitor].
A 57-year-old man with amyotrophic lateral sclerosis (ALS) was admitted because of depressive state. Selective serotonin reuptake inhibitor (SSRI), an antidepressant, was started on the admission day. The throbbing headache in the right temporal region appeared on day 3, and an analgesic drug was not completely effective. Serum sodium value on admission was 131 mEq/l. After SSRI was started the hyponatremia rapidly progressed, and it became 112 mEq/l on day 4. SSRI was discontinued, and headache disappeared; serum sodium was improved to 129 mEq/l. It has been reported that syndrome of inappropriate secretion of antidiuretic hormone (SIADH) may be associated with ALS. We consider that subclinical SIADH was manifested by SSRI in this case. SSRI seems to be a cause of headache, since headache disappeared completely by discontinuation of SSRI.


[Causes, diagnosis and treatment strategies for dental pulp calcification].
Dental pulp calcification can lead to root canal stenosis or obliteration. It is usually difficult to negotiate the root canal if the affected tooth needs to be treated and intraoperative complications are easily brought about during the root canal treatment. The etiologies of dental pulp calcification are complicated and careful considerations should be given to the diagnosis and treatment. Only by weighing the advantages and disadvantages can appropriate treatment plan be chosen. Based on the literature and authors' clinical experiences, the present article summarizes the causes, pathogenesis, diagnosis and treatment strategies of dental pulp calcification, in order to provide some references in diagnosis and treatment for the dental clinicians.


Redox control by dithiol-disulfide exchange in plants: I. The chloroplastic systems.
In plants, the photons of light are absorbed at the level of the photosystems in the chloroplasts. The functioning of the photosynthetic electron transfer chain linked to this process is required to generate NADPH and ATP. In addition, the light signal promotes a regulatory cascade, situated in the stroma, that involves ferredoxin, ferredoxin-thioredoxin reductase, and thioredoxins. This redox-based signal transduction chain allows fine regulation of stromal enzymes and tight control of the photosynthetic process. The molecular properties and the functioning of this redox regulatory chain will be described in this review.


[Evaluation of results of a series of 58 breast reconstruction after cancer].
The evaluation of 58 breast reconstructions operated in Boucicaut Hospital demonstrated positive result. The authors review the techniques used for contralateral breast symmetrization. The policy generally adapted has been to perform two sequential operations: 1st step: implantation of a prefilled prosthesis and contralateral breast symmetrization; 2d step: reconstruction of areolo-nipple complex and refinement of contralateral breast. Radiotherapy seems to be a problem in reconstruction. A 12% recurrence rate has been quoted in this group. Tram flap has been exceptionaly used by our team, as we tend to prefer the latissimus dorsi myocutaneous flap. Very few expanders have been implanted.


[Formation Mechanism of a Serious Pollution Event in January 2013 in Beijing].
The weather conditions, atmospheric environmental background and formation mechanism of a heavy air pollution episode in Beijing City from January 9th to 15th, 2013 was preliminarily investigated by combining observed data and the WRF meteorology model. The results showed that the average concentration of PM2.5 was 323 μg x m(-3) from January 10th to 14th; the heavy pollution episode was closely related to the local meteorological conditions; the stable atmospheric circulation pattern provided favorable environmental field for the lasting of this heavy air pollution; small wind speed, high humidity, low PBL, and lasting temperature inversion were the main reasons for this heavy air pollution incident; further analysis showed that contributions of regional transmission to the receptor sites in Beijing were between 53% - 69% and there were obvious secondary conversions and transformations; overall regional transportation played a more important role during this serious air pollution incident; the meteorological conditions played a key role in the formation and destruction of the heavy air pollution, therefore we need to strengthen the study on early warning of heavy air pollution, in order to prevent and control the air heavy pollution effectively.


Life-threatening hemorrhage from a vulvar hemangioma.
Capillary hemangioma, the most common tumor of infancy, usually does not require any treatment, but in a minority of cases it may cause morphologic, functional, or life-threatening complications. The authors report a case of a vulvar emangioma complicated by life-threatening hemorrhage not responsive to corticosteroids therapy, which showed no signs of spontaneous involution. The therapeutic approach consisted of 3 steps of selective arterial embolizations followed 5 months later by surgical excision and reconstruction of the vulva. Selective embolization rarely is used in the treatment of hemangiomas but may be required in cases of intractable bleeding, severe heart failure, large and poorly involuting hemangiomas, and as preparation for surgery. The results of the combined approach in this case are reported, and the indications discussed.


Fast Curing Bio-Based Phenolic Resins via Lignin Demethylated under Mild Reaction Condition.
Demethylation technique has been used to enhance lignin reactivity for preparation of phenolic resins. However, the demethylation efficiency and the demethylated lignin (DL) reactivity were still unsatisfactory. To improve the demethylation efficiency, alkali lignin was demethylated under different mild conditions using sodium sulfite as a catalyst. Lignin and DL were characterized by ¹H-NMR (nuclear magnetic resonance) and Fourier transform infrared (FT-IR) spectroscopy to determine the demethylation mechanism. With the demethylation of lignin, the methoxyl group content decreased from 1.93 m mol/g to 1.09 m mol/g, and the phenolic hydroxyl group content increased from 0.56 m mol/g to 0.82 m mol/g. These results revealed that methoxyl groups were attacked by SO₃²-, and some methoxyl groups were converted to phenolic hydroxyl groups by a nucleophilic substitution reaction, generating DL with high reactivity. The chemical properties of lignin-based phenolic resins were studied by 13C-NMR and FT-IR spectroscopy, and their physical properties were also investigated. The results indicated that lignin-based phenolic resins exhibited faster curing rate and shorter gel time. In addition, the bonding strength increased from 0.92 MPa to 1.07 MPa, and the formaldehyde emission decreased from 0.58 mg/L to 0.22 mg/L after lignin demethylated at the optimum condition.


Silicon cellular morphology.
We describe a design technique for neuromorphic engineering that exploits both Mead's notion of physical equivalence between transistors and ion channels and the intrinsic properties of the materials of which transistors are composed. This is in contrast to the "algorithmic" design technique in common use. A "physical" design technique allows us to emphasise the morphology of cells. We hope to use this in an exploration of the effect of cell morphology upon function.


Role of endosulfan in mediating stress responses in Sorghum bicolor (L.) Moench.
Present study revealed the importance of endosulfan in mediating stress responses in Sorghum bicolor L. Moench (variety JP-1-1). The seeds treated with different concentrations (0.2, 0.4 and 0.6%) of endosulfan showed a significant decrease in percent germination over control. As the concentration increased, the shoot length, root length and biomass decreased. The amount of chlorophyll-a and protein decreased gradually with the increase in endosulfan concentration, whereas phenol and proline contents increased from 1.08 to 1.57 mg g(-1) and 0.18 to 0.98 mg g(-1), respectively. Chlorophyll-b decreased in 0.2% (0.97 mg g(-1)) as compared to control and revealed a gradual increase in 0.4% (1.11 mg g(-1)) and 0.6% (1.13 mg g(-1)). Endosulfan treatment suppressed the catalase and protease activity, but significantly increased the level of peroxidase, polyphenol oxidase, SOD and amylase enzymes. Lowerdose (0.2%) of endosulfan stimulated the activity of amylases.


Comparison of left atrial volumes and function by real-time three-dimensional echocardiography in patients having catheter ablation for atrial fibrillation with persistence of sinus rhythm versus recurrent atrial fibrillation three months later.
Real-time 3-dimensional echocardiography (RT3DE) can provide a unique combination of accurate left atrial (LA) volume quantification and rapid, automatic assessment of LA function. The aim of the study was to evaluate the changes in LA volumes and function in patients with atrial fibrillation (AF) undergoing radiofrequency catheter ablation (RFCA) using RT3DE; 57 consecutive patients referred for RFCA were studied. Paroxysmal AF was present in 43 patients (75%) and persistent AF in 14 (25%). After a mean follow-up of 7.9 +/- 2.7 months, patients were divided into 2 groups: successful RFCA (SR group) and recurrence of AF (AF group). RT3DE was performed before, within 3 days, and 3 months after RFCA to assess LA volumes (maximum, minimum, and preA) and LA functions (passive, active, and reservoir). A total of 38 patients (67%) had successful RFCA (SR group). Immediately after RFCA, no significant changes in LA volumes and function were observed. After 3 months, a significant reduction in LA volumes (maximum: 26 +/- 8 to 23 +/- 7 ml/m(2), p <0.01) was noted only in the SR group, with a significant improvement in LA active (22 +/- 8% to 33 +/- 9%, p <0.01) and reservoir functions (116 +/- 45% to 152 +/- 54%, p <0.01). Conversely, the AF group showed a trend towards a deterioration of LA volumes and function. In conclusion, in patients who maintain sinus rhythm after RFCA, a significant reverse remodeling and functional improvement of the left atrium is observed using RT3DE.


The origin of the term plasticity in the neurosciences: Ernesto Lugaro and chemical synaptic transmission.
The Italian psychiatrist Ernesto Lugaro can be regarded as responsible for introducing the term plasticity into the neurosciences as early as 1906. By this term he meant that throughout life the anatomo-functional relations between neurons can change in an adaptive fashion to enable psychic maturation, learning, and even functional recovery after brain damage. Lugaro's concept of plasticity was strongly inspired by a neural hypothesis of learning and memory put forward in 1893 by his teacher Eugenio Tanzi. Tanzi postulated that practice and experience promote neuronal growth and shorten the minute spatial gaps between functionally associated neurons, thus facilitating their interactions. In addition to discovering the cerebellar cells known by his name and advancing profound speculations about the functions of the glia, Lugaro lucidly foresaw the chemical nature of synaptic transmission in the central nervous system, and was the first to propose the usage of the terms "nervous conduction" and "nervous transmission" in their currently accepted meaning.


Presenting symptoms and onset-to-arrival time in patients with acute stroke and transient ischemic attack.
Delayed arrival to the emergency department (ED) precludes most stroke patients from receiving thrombolytic treatment. Our objective in this study was to examine the association between presenting symptoms and onset-to-arrival time (ie, time between onset of symptoms to arrival at the ED) in a statewide stroke registry. Demographics, clinical data, and presenting symptoms were collected for patients with acute stroke or symptomatic transient ischemic attack (TIA) admitted to 15 Michigan hospitals (n = 1922). Polytomous logistic regression models were developed to test the association between presenting symptoms and onset-to-arrival time (classified as <2 hours, 2-6 hours, or >6 hours/unknown). Onset-to-arrival time was <2 hours in 19% of the patients, 2-6 hours in 22%, and >6 hours/unknown in 59%. Unilateral symptoms (reported by 40%) and speech difficulties (reported by 22%) were associated with increased likelihood of arriving within 2 hours (unilateral: adjusted odds ratio [aOR], 1.5; 95% confidence interval [CI], 1.1-1.9; speech: aOR, 1.6; 95% CI, 1.2-2.2). Difficulty with walking, balance, or dizziness (12%), confusion (9%), loss of consciousness (6.7%) and falls (3.4%) were associated with lower likelihood of arriving within 2 hours (walking: aOR, 0.7; 95% CI, 0.4-1.0; confusion: aOR, 0.5; 95% CI, 0.3-0.8; consciousness: aOR, 0.5; 95% CI, 0.1-0.9; falls: aOR, 0.4; 95% CI, 0.3-0.9). Presenting symptoms were strongly associated with time of arrival; patients with unilateral symptoms and speech difficulties were more likely to seek care early. Future studies should consider including more specific patient-level data to identify psychosocial and behavioral aspects of recognition and action to stroke symptoms.


Distribution and Frequency of ABO and Rhesus (D) Blood Groups in Somalia: A Retrospective Study on Students of Jazeera University, Mogadishu-Somalia.
There are differences in the distribution and frequency of ABO and D blood groups in different populations of the world. Relatively very little information is available about blood group distributions in the Somali population. Objectives: To identify the distribution and frequency of ABO and D blood groups among the Somali people. A retrospective cross-sectional study of 1811 enrolled students of Jazeera University was conducted in Jazeera University diagnosis and research center, Mogadishu-Somalia from December 2017 to December 2020. The result was presented as the frequency of each blood group with percentage. A Fisher's exact test was carried out to test the significant association of the ABO blood group with sex and D antigen with sex. Blood group O was the most prevalent (61%), followed by A (27%), B (10%), and AB (2%). The D-antigen was present in 97% of participants and 3% were D-negative. The distribution of O+, A+, B+, AB+ among D-positive subjects were 62%, 27%, 9% and 2.0% while that of O-, A-, B- and AB- among D-negative subjects were 57%, 27%, 12% and 3%, respectively. The frequencies of ABO and D-antigens in both male and female subjects were O > A > B > AB. However, this study found no significant difference of ABO with Sex and D-antigens with sex (P-value>0.05). The frequency of ABO and D blood groups among the Somalia population was found to be O > A > B > AB which was similar to those reported from most East African populations.


Kabuki Syndrome and Anorectal Malformations: Implications for Diagnosis and Treatment.
Kabuki syndrome (KS) is a rare genetic condition characterized by a distinctive facies, intellectual disability, growth delay, and a variety of skeletal, visceral, and other anomalies, including anorectal malformations (ARMs). We present two cases of female patients with KS, diagnosed and successfully managed at our institution, one with a perineal fistula and one with a rectovestibular fistula. Our report, along with a literature review, shows that the syndrome is usually associated with "low" anomalies, with a potential for a good prognosis. Management of the anorectal anomaly in patients with KS is not essentially different from that in other nonsyndromic patients, taking into account the frequent association of the syndrome with serious congenital heart disease, which might affect the decision-making and timing of the stages of anorectal reconstruction. The frequent occurrence of learning and feeding difficulties makes establishment of toilet training and bowel management rather more challenging, requiring the expertise of a multidisciplinary team. The finding of ARMs in female patients with other characteristics of KS, although inconstant, could support the clinical suspicion for the syndrome until genetic confirmation is available, and should alert the physician for the potential of severe cardiac defects.


Binocularity in accommodative esotropia.
One hundred twenty-seven medical records of patients with accommodative esotropia met our inclusion criteria and were analyzed. All included patients were within 10 prism diopters of orthophoria and had stereopsis and other binocular sensory test results recorded at their latest visit. Bifixation, defined as stereopsis of 50 arc seconds or better, was present in 31 patients (24%) with an average follow up of 89 months. Monofixation (peripheral fusion) was present in the remaining 96 patients (76%) with an average follow up of 84 months. Patients with bifixation were less likely to have presented with constant esotropia (19% vs 39% [P = .04]) and were more likely to be aligned within 8 delta of orthophoria in their first glasses (84% vs 21% [P < .0001]). No patient with bifixation had constant esotropia longer than 4 months. In addition, patients with bifixation were less likely to have worn bifocals (39% vs 59% [P = .09]), or undergone esotropia surgery (23% vs 62% [P < .0001]). These data suggest that maintenance of bifixation is possible in accommodative esotropia if the eyes are straightened before or shortly after the esodeviation becomes constant. With this early therapy, amblyopia and deterioration of ocular alignment are also less likely.


Atomic structure of a tryptophan-zipper pentamer.
Coiled-coil motifs are ubiquitous mediators of specific protein-protein interactions through the formation of interlocking hydrophobic seams between alpha-helical chains. Residues that form these seams occur at the first (a) and fourth (d) positions of a characteristic 7-aa repeat and are primarily aliphatic. The potential of aromatic residues to promote helix association in a coiled coil was explored by engineering a "Trp-zipper" protein with Trp residues at all 14 a and d positions. The protein forms a discrete, stable, alpha-helical pentamer in water at physiological pH. Its 1.45-A crystal structure reveals a parallel, five-stranded coiled coil, a previously uncharacterized type of "knobs-into-holes" packing interaction between interfacial Trp side chains, and an unusual approximately 8-A-diameter axial channel lined with indole rings that is filled with polyethylene glycol 400 and water and sulfate ion molecules. The engineered Trp-zipper pentamer enlarges current views of coiled-coil assembly, molecular recognition, and protein engineering, and may serve as a soluble model for membrane ion channels.


Plasma FGF-19 Levels are Increased in Patients with Post-Bariatric Hypoglycemia.
Hypoglycemia is an increasingly recognized complication of bariatric surgery. Mechanisms contributing to glucose lowering remain incompletely understood. We aimed to identify differentially abundant plasma proteins in patients with post-bariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB), compared to asymptomatic post-RYGB. Proteomic analysis of blood samples collected after overnight fast and mixed meal challenge in individuals with PBH, asymptomatic RYGB, severe obesity, or overweight recruited from outpatient hypoglycemia or bariatric clinics. The top-ranking differentially abundant protein at 120 min after mixed meal was fibroblast growth factor 19 (FGF-19), an intestinally derived hormone regulated by bile acid-FXR signaling; levels were 2.4-fold higher in PBH vs. asymptomatic post-RYGB (mean + SEM, 1094 ± 141 vs. 428 ± 45, P < 0.001, FDR < 0.01). FGF-19 ELISA confirmed 3.5-fold higher concentrations in PBH versus asymptomatic (360 ± 70 vs. 103 ± 18, P = 0.025). To explore potential links between increased FGF-19 and GLP-1, residual samples from other human studies in which GLP-1 was modulated were assayed. FGF-19 levels did not change in response to infusion of GLP-1 and PYY in overweight/obese individuals. Infusion of the GLP-1 receptor antagonist exendin 9-39 in recently operated asymptomatic post-RYGB did not alter FGF-19 levels after mixed meal. By contrast, GLP-1 receptor antagonist infusion yielded a significant increase in FGF-19 levels after oral glucose in individuals with PBH. While plasma bile acids did not differ between PBH and asymptomatic post-RYGB, these data suggest unique interrelationships between GLP-1 and FGF-19 in PBH. Taken together, these data support FGF-19 as a potential contributor to insulin-independent pathways driving postprandial hypoglycemia in PBH.


The influence of hearing aid cost on perceived benefit in older adults.
Self-report hearing handicap scales are gaining widespread acceptance among clinicians as a technique for quantifying hearing aid benefit. Both auditory and nonauditory (e.g., personality, health, motivation) factors contribute to an individual's response to hearing loss and ultimately to perceived hearing aid benefit. Among the recognized extra-audiological variables, financial concerns may influence a hearing aid user's expectations regarding hearing aid benefit. The present study compared self-perceived benefit in 26 insured and 26 uninsured new hearing aid wearers using the Hearing Handicap Inventory for the Elderly (HHIE). HHIE scores at 3 weeks and 6 mo postfitting were equivalent between groups. The findings suggest that the HHIE may be used as an index of hearing aid benefit without concern that the source of funds required to purchase amplification may act as an uncontrolled variable.


Parental consanguinity and nonsyndromic orofacial clefts in children: a systematic review and meta-analyses.
To assess whether individuals born to consanguineous parents had a higher frequency of nonsyndromic orofacial clefts compared with those with no parental consanguinity. A prespecified plan for a search strategy, inclusion/exclusion criteria, and data extraction from studies reporting consanguinity in relation to nonsyndromic orofacial clefts (NSOFC) was carried out. Papers reporting observational studies with control populations were included, without language restrictions, and these reports were assessed for quality. Sensitivity analyses using subgroups, homogeneity evaluation, and assessment of publication bias were carried out, and meta-analyses of extracted data were performed. Sixteen studies fulfilled the selection criteria and were included in the meta-analyses. There were statistically significant relationships between consanguinity and NSOFC for all 16 studies combined (P = .0003), with odds ratio (OR) = 1.83 and 95% confidence interval (CI) = (1.31, 2.54); 10 case-control studies (P = .006), with OR = 2.06 and 95% CI = (1.23, 3.46); six cross-sectional studies (P = .03), with OR = 1.34 and 95% CI = (1.02, 1.76); first cousins consanguineous marriages (P = .04), with OR = 1.40 and 95% CI = (1.01, 1.93); cleft palate alone (P = .01), with OR = 1.89 and 95% CI = (1.14, 3.13); and cleft lip with or without cleft palate cases (P = .002), with OR = 1.56 and 95% CI = (1.18, 2.07). Although there was a high level of study heterogeneity, the evidence is consistent in suggesting that consanguinity is a risk factor for NSOFC, with an overall OR of 1.83 (95% CI, 1.31 to 2.54), implying that there was almost twice the risk of a child with NSOFC being born if there was parental consanguinity.


[Dermatofibrosarcoma in children. Report of 7 Tunisian cases].
Dermatofibrosarcoma (DFS) protuberans is a rare mesenchyma tumor in childhood characterised by slow growth. We report the result of a retrospective study of 7 childhood (4 males) cases of through a fifteen year period. The mean age was 13 years. 4 Tumors were (DFS) located on the limbs: 2 on the trunk: and on the scalp. Clinical types were multinodular and infiltrated in 3 cases, nodular in two cases and ulcerated with budding also in two cases. The mean delay between diagnostic and the appearance of the tumor was about 24 months for 4 initial tumors. Histological features were typical in all cases. We report 3 recurrences of dermatofibrosarcoma arising few months after surgical excision of an initial tumor, in one case the tumor was diagnosed histocytofibroma. Six patient underwent surgical excision with wide margins, and in one case the margins were considered borderline. No recurrences were reported, the follow-up was between 17 months to 9 years. It's a rare tumor in childhood, 160 cases were reported. The clinical and evolutive mode were entirely comparable to the adult cases. However the initial appearance as benign atrophic or indurated plaque is more frequent in childhood, but this appearance wasn't noted in our series.


Timing stroke: A review on stroke pathophysiology and its influence over time on diffusion measures.
Diffusion imaging (DWI) is considered an optimal technique to detect hyperacute cerebral ischemia and has thus enriched the clinical management of patients with suspected stroke. Researchers have taken this technique beyond with Diffusion Tensor Imaging (DTI)-extracted measures, which have been proposed as biomarkers of stroke progression. A large body of literature report on the correlates between pathophysiological events, such as cytotoxic and vasogenic edema, and diffusion changes in the brain. However, a unified picture of these changes, and their exploration as stroke pathology progression biomarkers, remains to be done. We present here a narrative review on the different pathophysiological events underlying stroke from onset until late subacute stages and its relation to different brain edema forms. Studies included in this review used either DWI and/or DTI analysis in hyperacute (<24 h), acute (1-7 days), early subacute (7-30 days) and/or late subacute (1-6 months) phase of stroke, including human and animal models. Our conclusions are that diffusion measures should be considered as a potential proxy measure for stroke neuroinflammation status, specially in early stages of the disease. Furthermore, we suggest that the choice of diffusion measures and the interpretation of their changes, in both research and clinical settings, need to be linked to the different stroke phases to account correctly for the progression, and eventual resolution, of neuroinflammation.


Quantitative comparison of cerebral artery development in human embryos with other eutherians.
The embryonic and early fetal human brain is known to undergo extraordinary expansion of its cellular population during embryonic and early fetal life, and is critically dependant on a steady supply of nutrients and oxygen for proper brain development. Quantitative analysis of the internal radius of the aorta and cerebral arteries in a range of eutherian mammals has been used to compare arterial flow to the developing human brain with that to the brains of non-human eutherians. Human embryos showed a much steeper rise of internal radius of the aorta with increasing body size than the embryos of non-human eutherians, but the thickness of the aorta rose at the same pace relative to body size in both humans and non-humans, suggesting that aortic pressure is similar in all eutherian embryos of a similar size. The sums of internal radii of both the internal carotids and vertebral arteries of human embryos raised to the fourth power were much lower at embryonic stages (less than 22 mm body length) than in non-human eutherians, were similar between humans and non-humans at 22-30 mm body length, and exceeded the non-humans at body lengths of more than 30 mm. The relative size of the internal calibre of the cerebral feeder arteries (internal carotid and vertebral) to the aorta did not change between embryonic and fetal sizes in either humans or non-humans. The findings suggest that the developing human brain may actually receive less blood flow at embryonic sizes (less than 22 mm body length) than do other mammalian embryos of a similar body size, but that internal carotid and vertebral flow is higher in human fetuses (body length greater than 30 mm) than in developing non-humans of the same body size. Increased flow to the developing human brain relative to non-humans is achieved by simultaneous increases in both aortic and cerebral feeder artery internal calibre.


Optimality of Gaussian discord.
In this Letter we exploit the recently solved conjecture on the bosonic minimum output entropy to show the optimality of Gaussian discord, so that the computation of quantum discord for bipartite Gaussian states can be restricted to local Gaussian measurements. We prove such optimality for a large family of Gaussian states, including all two-mode squeezed thermal states, which are the most typical Gaussian states realized in experiments. Our family also includes other types of Gaussian states and spans their entire set in a suitable limit where they become Choi matrices of Gaussian channels. As a result, we completely characterize the quantum correlations possessed by some of the most important bosonic states in quantum optics and quantum information.


Bladder neck mobility and urethral closure pressure as predictors of genuine stress incontinence.
Two hundred and seventy-five consecutive patients with symptoms of lower urinary tract dysfunction underwent urodynamic evaluation, including multichannel urodynamics, urethral pressure profilometry, X-ray and ultrasound imaging. After women with previous incontinence or prolapse surgery or pelvic radiotherapy and those with evidence of urethral kinking on ultrasound had been excluded, 179 datasets were analyzed. Both bladder neck descent ( P<0.0001) and maximum urethral closure pressure ( P<0.0001) were strongly associated with a fluoroscopic diagnosis of GSI. Only weak correlations between bladder neck mobility and urethral pressure parameters (highest r = -0.17) were observed. Regression analysis yielded a mathematical model that demonstrated a wide spread of odds ratios for GSI for the measured values (from <0.2 to >100). Bladder neck descent explained 29% and urethral closure pressure 12% of overall variability. Both bladder neck mobility and maximum urethral closure pressure are strong predictors of the diagnosis of GSI, provided major confounders are excluded. Bladder neck mobility appears to be the stronger predictor.


The adolescent years: an academic-community partnership in Harlem comes of age.
Much has been written about the potential benefits in health promotion that are possible through partnerships between academic institutions and community-based organizations, but little practical advice has been provided on how to sustain these relationships when the original grant funds have been exhausted. Here we document our experiences in Harlem, New York City, a community with grave social, structural, and physical environmental inequities, and describe the successes and failings of a partnership now in its "adolescence" between researchers at the Joseph L. Mailman School of Public Health of Columbia University and community activists at West Harlem Environmental Action (WE ACT).


[Sentinel lymph node biopsy and low axillary node sampling for breast cancer].
Since sentinel lymph node(SLN) biopsy has a higher negative predictive value than that of four-node sampling, SLN biopsy might become the new acknowledged standard of clinical care for patients with early breast cancer. SLN biopsy is widely used in Western countries despite the lack of data from randomized trials. Clinical practice guidelines document that SLN biopsy should be performed with prudent informed consent and thorough surgical technique. Before surgeons replace axillary dissection with SLN biopsy as the staging procedure at their institution, they should perform backup axillary dissection until a detection rate of more than 90% and a false-negative rate of less than 5% are achieved. Recently, SLN biopsy has more often been indicated for multicentric breast cancer, larger tumors, prior excisions, and noninvasive carcinoma. While SLN biopsy is widely used in Western countries, there is little experience in Japan. If randomized studies, clinical practice guidelines, and the coverage of lymphoscintigraphy under health insurance were introduced, SLN biopsy would be used more widely in Japan.


Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus: A Model of International Cooperation for Highly Specialized Treatments.
Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.


Effects of High-Forage Diets Containing Raw Flaxseeds or Soybean on In Vitro Ruminal Fermentation, Gas Emission, and Microbial Profile.
Lipid metabolism plays an important role in the energy economy of ruminants. However, its interactions of fat, rumen fermentation, gas emission, and microorganisms are not yet clear. This study evaluated the effect of adding raw oilseeds to high-forage diets on in vitro ruminal fermentation, gas composition, and microbial profile. Three isoenergetic and isoproteic experimental diets were designed and used as fermentation substrate: control treatment (CON group) was the basal diet lacking oilseeds, the other two treatments were the basal diet supplemented by 100 g/kg dry matter (DM) raw whole soybean (S group) and 50 g/kg DM raw flaxseed (F group), respectively. Data showed that the acetate, butyrate, and total VFA concentration of culture fluids in the S group were lower (p < 0.05) than in the F group. There was a tendency to a higher level (p = 0.094) of propionate concentration in the F group compared with the other two groups. The gas production in the F group was higher (p < 0.05) than in the control group. There was a lower abundance of Sutterella (p < 0.05) and a greater abundance of Butyrivibrio (p < 0.05) in both of the two oilseed treatments. Methanobrevibacter (p = 0.078) in the F group was the lowest. Our results suggested that CH4 emission could be inhibited with flaxseed supplementation by propionate production metabolism, biohydrogenation of unsaturated fatty acid (FA), and toxicity to Methanobrevibacter, while regarding soybean seed supplementation, the emission of CH4 was more likely to be reduced through biohydrogenation of unsaturated FA modulated by Butyrivibrio.


Pigmentary retinopathy due to Bardet-Biedl syndrome: case report and literature review.
Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder with clinical and genetic heterogeneity. This syndrome was first described by Laurence and Moon in 1866 and additional cases were described by Bardet and Biedl between 1920 and 1922. The main features are obesity, polydactyly, pigmentary retinopathy, learning disabilities, various degrees of intellectual impairment, hypogonadism, and renal abnormalities. Bardet-Biedl syndrome is both phenotypically and genetically heterogeneous. Clinical diagnosis is based on the presence of 4 of the 5 cardinal features. The authors present a typical case of pigmentary retinopathy due to Bardet-Biedl syndrome and made a brief commentary about the disease's cardinal manifestations.


Hereditary cancer syndromes of the gastrointestinal system.
Gastrointestinal (GI) malignancies account for a large percentage of the cancer burden in the United States. Although the majority of cancer cases are sporadic, approximately 5% to 10% of cancer results from inherited genetic mutations. There are several hereditary cancer syndromes of the GI tract that have been identified. To date, the genetics of colorectal cancer and its associated hereditary cancer syndromes have been characterized in detail, and effective screening modalities and recommendations have been incorporated into standards of care. Today, scientists are beginning to understand the genetic basis of pancreatic and gastric cancer, and in some cases have identified a number of their associated inherited cancer syndromes. Information about cancer genetics and hereditary cancer syndromes not only will provide advanced practice nurses with knowledge of these diseases but also, more importantly, will provide opportunities to improve patient care by providing patients with treatment options and opportunities for the early detection and prevention of cancer.


Causes and prevalence of traumatic injuries to the permanent incisors of school children aged 10-14 years in Maseru, Lesotho.
Traumatic dental injuries are widespread in the population and the prevalence of traumatic dental injuries among school children in different parts of the world varies from about 3% to 45%. Most injuries involve the anterior teeth, which may lead to eating restrictions, changes in physical appearance, speech defects and psychological impacts that affect the child's quality of life. A cross-sectional survey was carried out to investigate the prevalence, aetiology and types of injuries to permanent incisors among schoolchildren aged 10-14 years from Maseru, Lesotho. Upper and lower permanent incisors were examined for dental injuries. The prevalence of traumatic injuries to the permanent incisor teeth was 9.3% (13.3% boys and 6.3% girls). Significantly more boys than girls suffered injury. The most common type of injury was enamel fractures and most common cause was falls. Health promotion policies should aim to create an appropriate and safe environment for children. Soft playground surfaces, school-crossing patrols, marked zebra crossings and bicycle lanes would help create a safe environment. Speed limits for cars and the use of seat belts, air bags, special car seats for children and bicycle helmets should be enforced. Mouth guards should be used when playing sport, in particular contact sports. Education regarding the epidemiology of dental injuries and their prevention through health promotion may play a major role in reducing the prevalence of dental injury and avoiding the financial costs of treatment, especially in developing countries.


Mesenchymal stromal cells equipped by IFNα empower T cells with potent anti-tumor immunity.
Cancer treatments have been revolutionized by the emergence of immune checkpoint blockade therapies. However, only a minority of patients with various tumor types have benefited from such treatments. New strategies focusing on the immune contexture of the tumor tissue microenvironment hold great promises. Here, we created IFNα-overexpressing mesenchymal stromal cells (IFNα-MSCs). Upon direct injection into tumors, we found that these cells are powerful in eliminating several types of tumors. Interestingly, the intra-tumoral injection of IFNα-MSCs could also induce specific anti-tumor effects on distant tumors. These IFNα-MSCs promoted tumor cells to produce CXCL10, which in turn potentiates the infiltration of CD8+ T cells in the tumor site. Furthermore, IFNα-MSCs enhanced the expression of granzyme B (GZMB) in CD8+ T cells and invigorated their cytotoxicity in a Stat3-dependent manner. Genetic ablation of Stat3 in CD8+ T cells impaired the effect of IFNα-MSCs on GZMB expression. Importantly, the combination of IFNα-MSCs and PD-L1 blockade induced an even stronger anti-tumor immunity. Therefore, IFNα-MSCs represent a novel tumor immunotherapy strategy, especially when combined with PD-L1 blockade.


[Correlation between increased incidence of pulmonary tuberculosis and AIDS].
There is an interaction between pulmonary TB abd AIDS, so it is necessary for these patients to take up HIV testing. Therefore, the young are especially considered for this and also those risk groups (homosexuals, drug abusers--i.v. injections, persons from specific geographic areas, haemophilics and persons who were often blood recipients. Pulmonary TB is sometimes the first sign of HIV infection; HIV positive and by TB infected persons are 30 times more likely to develop active tuberculosis than HIV negative; One third of increased incidence od TB in the last five years may be attributed to HIV; AIDS and pulmonary TB are both fatal--each of them accelerate the progress of the other; TB is the leading cause of death among HIV positive persons; The effective implementation DOTS strategy recommended by the World Health Organisation for the detecting and treatment of TB may ensure the longer life to the HIV positive patients: The treatment of TB to the HIV positive patients with antituberculotic drugs may be as effective as the cure with antituberculotic drugs for HIV negative persons. Finally, it is important to mention that doctors must think about tuberculosis infection among patients with AIDS, so they must give immediately sputum and tissue samples, for BK control the patients, but consider to make HIV test also especially young people and risk groups.


[Renal abscess in childhood: a case report].
We describe the case of a previously healthy six-year-old boy with a right renal abscess due to a methicillin-resistant Staphylococcus aureus, which necessitated a radical nephrectomy. Although renal ultrasonography is often the initial tool to identify fluid collection, in our case the diagnosis was obtained only after performing an abdominal CT with intravenous contrast. It is therefore necessary to combine these different imaging techniques in all children with fever and abdominal/lumbar pain without any apparent cause in order to obtain an early diagnosis and minimise organ damage.


Periodontal Maintenance Therapy in a Public University: A Six-Year Prospective Study.
Few prospective studies have reported results of periodontal status and tooth loss in public/academic periodontal maintenance therapy (PMT) programs. This prospective study aimed to evaluate the periodontal retreatment needs and progression of periodontitis, as well as tooth loss, in individuals under PMT in a public/academic environment. From a PMT program at a public university, 39 individuals determined to be regular compliers (RC) and 52 irregular compliers (IC) were monitored over the course of 78 months [mean interval between visits of 6.2 ± 0.6 and 13.1 ± 1.9 months, respectively]. Complete periodontal examinations were conducted to evaluate probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) at baseline and final examinations. Biological, demographic, and behavioral predictive risk variables were collected. Univariate and multivariate logistic regressions were performed when appropriate. At final examination, periodontal retreatment needs and progression of periodontitis, as well as tooth loss, were signifi cantly higher among IC when compared to RC (p less than 0.05). Multivariate logistic regression analysis showed that: 1) age and greater than 30% of sites with CAL ≥ 4 mm were associated with the progression of periodontitis; 2) smoking, co-habitation status, family income, and greater than 30% of sites with BOP were associated with periodontal retreatment needs; 3) age, family income, low frequency of tooth brushing, and diabetes were associated with tooth loss. RC individuals in public or academic PMT programs presented with lower periodontal retreatment needs and progression of periodontitis, as well as tooth loss when compared to IC individuals.


Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.
Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80+CD206+ macrophages and activated T cells (CD4+CD69+) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms.


Childhood obesity: results of a multicenter study of obesity treatment in Italy.
The prevalence of pediatric obesity is increasing and many patients are followed by specialized centers or private doctors. The aim of this study was to verify short- and medium term results of a therapeutic approach based on nutritional intervention in a large pediatric population: 1383 subjects (695 females, 688 males) aged 10.1 +/- 2.7 yr, followed in 11 pediatric departments in Italy. No difference was found between centers in age, height, weight, BMI and IBW. The drop-out rate after the first visit was 30.2% (58.1% IBW > 140%) in females and 34.2% (70.7% IBW > 140%) in males. After two years of follow-up only 9.7% of females and 6.4% of males remained on treatment. Of these patients only 7.3% of females and 6.4% of males had IBW < 120%. These data show that an approach based on nutritional intervention alone is not sufficient for long-term treatment of pediatric obesity. Only an approach started early and involving the family can produce permanent results.


Targeting WNT Signaling for Multifaceted Glioblastoma Therapy.
The WNT signaling pathway has been of great interest to developmental biologists for decades and has more recently become a central topic for study in cancer biology. It is vital for cell growth and regulation of embryogenesis in many organ systems, particularly the CNS and its associated vasculature. We summarize the role of WNT in CNS development and describe how WNT signaling makes key contributions to malignant glioma stemness, invasiveness, therapeutic resistance, and angiogenesis. The role of WNT in these mechanisms, along with creation and maintainance of the blood-brain barrier (BBB), points to the potential of WNT as a multi-faceted target in malignant glioma therapy.


[Polymeric forms of the influenza virus nucleoprotein].
Two high-molecular-weight types of in vivo formed nucleoproteins (NP) capable of reacting with anti-NP monoclonal antibodies were detected in continuous MDCK cells and primary CEFs, along with the monomeric virus NP. High-molecular NP were stable at 37 degrees C, despite the presence of dodecyl sulfate and B-mercaptoethanol, but were converted to monomeric NP at 37 degrees C in the presence of 6 M urea, 1 M NaCl, and at acid pH. Hence, high-molecular-weight NP may be the polymeric forms of NP, which are probably stabilized by noncovalent bonds. The kinetics of NP-polymers formation suggests that NP-monomers are their precursors and NP-polymers are formed rapidly after monomeric NP molecules synthesis. Both forms of NP-polymers are detected in the sedimented and soluble fractions of not only cell lysate, but in the extracellular maintenance medium as well. NP-polymers are resistant to RNAse and are more resistant to protease than NP-monomers.