Natural human IL-1 beta exhibits regulatory actions on human bone-derived cells in vitro.
We have shown that natural homogenous IL-1 beta exhibits regulatory activities on human bone-derived osteoblast-like cells in vitro. IL-1 beta stimulated cellular proliferation and the synthesis of prostaglandin E2 and plasminogen activator activity by the cultured human osteoblast-like cells. In contrast to these stimulatory actions, IL-1 beta antagonised the stimulatory effects of 1.25(OH)2 D3 on the production of alkaline phosphatase and osteocalcin, two markers of the osteoblast phenotype. These studies indicate that this cytokine may therefore have potential physiological and pathological effects on bone metabolism.


Dose-response effects of insulin glargine in type 2 diabetes.
To determine the pharmacokinetic and pharmacodynamic dose-response effects of insulin glargine administered subcutaneously in individuals with type 2 diabetes. Twenty obese type 2 diabetic individuals (10 male and 10 female, aged 50 +/- 3 years, with BMI 36 +/- 2 kg/m(2) and A1C 8.3 +/- 0.6%) were studied in this single-center, placebo-controlled, randomized, double-blind study. Five subcutaneous doses of insulin glargine (0, 0.5, 1.0, 1.5, and 2.0 units/kg) were investigated on separate occasions using the 24-h euglycemic clamp technique. RESULTS Glargine duration of action to reduce glucose, nonessential fatty acid (NEFA), and beta-hydroxybutyrate levels was close to or >24 h for all four doses. Increases in glucose flux revealed no discernible peak and were modest with maximal glucose infusion rates of 9.4, 6.6, 5.5, and 2.8 mumol/kg/min for the 2.0, 1.5, 1.0, and 0.5 units/kg doses, respectively. Glargine exhibited a relatively hepatospecific action with greater suppression (P < 0.05) of endogenous glucose production (EGP) compared with little or no increases in glucose disposal. A single subcutaneous injection of glargine at a dose of >or=0.5 units/kg can acutely reduce glucose, NEFA, and ketone body levels for 24 h in obese insulin-resistant type 2 diabetic individuals. Glargine lowers blood glucose by mainly inhibiting EGP with limited effects on stimulating glucose disposal. Large doses of glargine have minimal effects on glucose flux and retain a relatively hepatospecific action in type 2 diabetes.


isomiRTar: a comprehensive portal of pan-cancer 5'-isomiR targeting.
Inaccurate cleavage of pri- and pre-miRNA hairpins by Drosha and Dicer results in the generation of miRNA isoforms known as isomiRs. isomiRs with 5'-end variations (5'-isomiRs) create a new dimension in miRNA research since they have different seed regions and distinct targetomes. We developed isomiRTar (https://isomirtar.hse.ru)-a comprehensive portal that allows one to analyze expression profiles and targeting activity of 5'-isomiRs in cancer. Using the Cancer Genome Atlas sequencing data, we compiled the list of 1022 5'-isomiRs expressed in 9282 tumor samples across 31 cancer types. Sequences of these isomiRs were used to predict target genes with miRDB and TargetScan. The putative interactions were then subjected to the co-expression analysis in each cancer type to identify isomiR-target pairs supported by significant negative correlations. Downstream analysis of the data deposited in isomiRTar revealed both cancer-specific and cancer-conserved 5'-isomiR expression landscapes. Pairs of isomiRs differing in one nucleotide shift from 5'-end had poorly overlapping targetomes with the median Jaccard index of 0.06. The analysis of colorectal cancer 5'-isomiR-mediated regulatory networks revealed promising candidate tumor suppressor isomiRs: hsa-miR-203a-3p-+1, hsa-miR-192-5p-+1 and hsa-miR-148a-3p-0. In summary, we believe that isomiRTar will help researchers find novel mechanisms of isomiR-mediated gene silencing in different types of cancer.


Synthesis and stability of boratriazaroles.
We describe the synthesis and stability analysis of novel boratriazaroles that can be viewed as bioisosteres of imidazoles or pyrazoles. These heterocycles could conveniently be obtained by condensing a boronic acid and amidrazone 1 in various solvents. A detailed stability analysis of selected compounds at different pH values as a function of time led to the identification of steric hindrance around the boron atom as a key element for stabilization.


Prevalence of Physical Activity and Sedentary Behavior among Chinese Children and Adolescents: Variations, Gaps, and Recommendations.
Physical-activity (PA) and sedentary-behavior (SB) assessment is of particular importance in the promotion of health in young people. However, there is no comprehensive overview of PA and SB from national surveys among Chinese children and adolescents. Following a literature search for Chinese national health surveys, 11 papers from six national surveys were found. Of the included studies, the majority applied self-reported questionnaires to estimate the prevalence of PA and SB. Owing to different definitions of the prevalence of PA and SB and various measures, a large variation in prevalence of PA and SB was observed. Such variations were attributable to methodological and practical issues. This study highlights the current gaps in estimating the national prevalence of PA and SB among Chinese children and adolescents, which should be addressed. To improve the quality of PA and SB surveillance, standardized measurement protocols to estimate the prevalence of PA and SB more accurately among Chinese children and adolescents are urgently required.


Synthesis of less toxic gold nanorods by using dodecylethyldimethylammonium bromide as an alternative growth-directing surfactant.
Gold nanoparticles having a rod-like morphology are regularly investigated as potential nano-therapeutic materials owing to their interesting optical properties, facile surface modification, tunable aspect ratios, and low cytotoxicity. Gold nanorods are historically prepared starting from HAuCl4 in the presence of ascorbic acid, silver nitrate, and the growth directing surfactant, cetyltrimethylammonium bromide (CTAB). While CTAB drives a rod-like morphology, it is known to be cytotoxic. This inherent toxicity is often addressed by removing or masking the native CTAB surfactant present on the nanorod surface. In the current study we have investigated a less toxic alternative surfactant, dodecylethyldimethylammonium bromide (C12EDMAB), as a possible growth-directing agent. Monodisperse gold nanorods having various lengths have been grown in the presence of C12EDMAB. SEM data suggests that the quantity of C12EDMAB on the rod's surface is much higher than that of CTAB. Toxicity assays were performed on HEp-2 and A549 cells showing lower toxicity at select concentrations for C12EDMAB coated rods.


Analytical reduction of combinatorial complexity arising from multiple protein modification sites.
Combinatorial complexity is a major obstacle to ordinary differential equation (ODE) modelling of biochemical networks. For example, a protein with 10 sites that can each be unphosphorylated, phosphorylated or bound to adaptor protein requires 3(10) ODEs. This problem is often dealt with by making ad hoc assumptions which have unclear validity and disallow modelling of site-specific dynamics. Such site-specific dynamics, however, are important in many biological systems. We show here that for a common biological situation where adaptors bind modified sites, binding is slow relative to modification/demodification, and binding to one modified site hinders binding to other sites, for a protein with n modification sites and m adaptor proteins the number of ODEs needed to simulate the site-specific dynamics of biologically relevant, lumped bound adaptor states is independent of the number of modification sites and equal to m + 1, giving a significant reduction in system size. These considerations can be relaxed considerably while retaining reasonably accurate descriptions of the true system dynamics. We apply the theory to model, using only 11 ODEs, the dynamics of ligand-induced phosphorylation of nine tyrosines on epidermal growth factor receptor (EGFR) and primary recruitment of six signalling proteins (Grb2, PI3K, PLCγ1, SHP2, RasA1 and Shc1). The model quantitatively accounts for experimentally determined site-specific phosphorylation and dephosphorylation rates, differential affinities of binding proteins for the phosphorylated sites and binding protein expression levels. Analysis suggests that local concentration of site-specific phosphatases such as SHP2 in membrane subdomains by a factor of approximately 10(7) is critical for effective site-specific regulation. We further show how our framework can be extended with minimal effort to consider binding cooperativity between Grb2 and c-Cbl, which is important for receptor trafficking. Our theory has potentially broad application to reduce combinatorial complexity and allow practical simulation of a variety ODE models relevant to systems biology and pharmacology applications to allow exploration of key aspects of complexity that control signal flux.


[A woman with a painful elbow].
A 24-year-old woman with Ehlers-Danlos syndrome visited the emergency department because of a post-traumatic painful and swollen left elbow with impaired function. A plain radiograph showed chronic luxation of the radial head with impression in the humeral capitellum. The clinical presentation of chronic luxation of the radial head is easily confused with that of an acute dislocation of the radial head, which may wrongly result in subsequent reduction.


Recombinant human thyroid peroxidase generated in eukaryotic cells: a source of specific antigen for the immunological assay of antimicrosomal antibodies in the sera of patients with autoimmune thyroid disease.
Recombinant, enzymatically active human thyroid peroxidase (hTPO) generated in nonthyroidal eukaryotic cells was compared with Graves' thyroid microsomes as a source of antigen for the immunological detection of antimicrosomal/anti-hTPO antibodies. Enzyme-linked immunosorbent assay of 51 sera, selected to produce a balanced distribution of antimicrosomal antibody (anti-MSA) levels, revealed (at 1:100 serum dilution) a moderately good correlation between anti-MSA and anti-hTPO antibody levels (r = 0.668; P less than 0.001). However, a number of sera with high anti-MSA levels yielded markedly discordant values between the two assays. A much lower correlation was observed between antithyroglobulin and anti-hTPO antibody levels (r = 0.315; P less than 0.05). At higher serum dilutions (1:1,000 and 1:10,000), at which low affinity, high capacity binding reactions will be reduced, the correlation between anti-MSA and anti-hTPO antibody values was greatly improved (r = 0.906 and 0.902, respectively; P less than 0.001), and there were no longer widely discrepant values between the two assays. In summary, the present study indicates that recombinant hTPO expressed in nonthyroidal cells provides an unlimited source of human TPO of unvarying quality for anti-hTPO antibody assays. This material offers increased specificity over standard anti-MSA assays that use thyroid cell microsomes as antigen.


New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases.
Brain-derived neurotrophic factor (BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has been reported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.


Factors Associated with Vascular Changes at the Level of Retinal Ganglion Cell Axon versus Soma/Dendrite in Glaucoma Patients.
Superficial and deep macular vessel density (VD) is decreased in eyes with glaucoma. Superficial VD comprises both the retinal nerve fiber layer (RNFL) and ganglion cell/inner plexiform layer (GC/IPL), and various terms have been used previously to describe the layers of macular VD. In our study, we readjusted the macular segmentation. We obtained RNFL and GC/IPL VDs separately to evaluate VD changes of axon versus soma/dendrite of the retinal ganglion cells (RGCs) in detail. We included 66 eyes of normal tension glaucoma patients with inferior localized RNFL defects solely impacting the inferior hemiretina. Macular VD was measured as RNFL VD and GC/IPL VD. VD ratio was calculated by dividing the VD from the affected hemiretina by the VD from the unaffected hemiretina. RNFL VD ratio was related to RNFL and GC/IPL thicknesses (p = 0.005, p = 0.001), whereas GC/IPL VD ratio was not (p = 0.596, p = 0.783). A lower GC/IPL VD ratio was associated with lower RNFL VD (p = 0.017) and systemic hypertension (p = 0.03) in multivariate analysis. Patients with a reduced GC/IPL VD ratio were more prone to poor visual field defects (p = 0.022) and paracentral scotoma (p = 0.046) and more likely to be on treatment for systemic hypertension (p = 0.024). Therefore, glaucoma patients on systemic hypertension treatment and reduced GC/IPL VD require cautious management.


Seasonal depression.
Seasonal affective disorders are mood disturbances that occur with a change in season. The most common form is winter depression, marked by sadness, anxiety, decreased physical activity, increased appetite, carbohydrate craving, weight gain, hypersomnia, decreased libido, worsening of premenstrual symptoms, impaired work performance and interpersonal conflict. This syndrome often responds to daily exposure to bright artificial light.


Pneumothorax following cytotoxic chemotherapy in malignant lymphoma.
Pneumothorax occurring as a complication of the antitumor effect of cytotoxic chemotherapy has been reported in occasional cases of a variety of tumors. Its occurrence in malignant lymphoma has not been reported heretofore. In this report, we describe two cases of this complication in patients with malignant lymphoma and discuss the possible pathophysiologic mechanisms involved. Because pulmonary involvement with the tumor was found in both cases, pneumothorax could be attributed to the anti-tumor effect of cytotoxic agents on underlying lung involvement in patients with malignant lymphoma.


Can Diffusion Weighted Imaging Aid in Differentiating Benign from Malignant Sinonasal Masses?: A Useful Adjunct.
To evaluate the role of diffusion weighted imaging (DWI) and apparent diffusion coefficient (ADC) values at 3 Tesla in characterizing sinonasal masses. After ethical clearance, 79 treatment naive patients with head and neck masses underwent magnetic resonance imaging (MRI), including DWI at 3 Tesla using the following b values - 0, 500 and 1000 s/mm2. Thirty-one patients were found to have sinonasal tumours and were subsequently analysed. Image analysis consisted of a morphological evaluation of conventional MR images, qualitative evaluation of DW trace images and quantitative assessment of mean ADC values. Receiver operating characteristic (ROC) curve was drawn to determine a cut-off ADC value for the differentiation between benign and malignant masses. Sinonasal masses showed an overlapping growth pattern on conventional imaging, irrespective of their biological nature. The mean ADC value of benign lesions was 1.948±0.459×10-3 mm2/s, while that of malignant lesions was 1.046±0.711×10-3 mm2/s, and the difference was statistically significant (p=0.004). When a cut-off ADC value of 1.791×10-3 mm2/s was used, sensitivity of 80% and specificity of 83.3% were obtained for characterization of malignant lesions, which was statistically significant. Juvenile nasopharyngeal angiofibroma (JNA) showed distinctly high ADC values, while meningioma was the only benign lesion with restricted diffusion. Atypical entities with unexpected diffusion characteristics included: adenocarcinoma, adenoid cystic carcinoma, meningioma, chondrosarcoma and fibromyxoid sarcoma. DWI in conjunction with conventional imaging can potentially enhance the diagnostic accuracy in characterizing sinonasal masses as benign or malignant. Some specific entities such as JNA and meningioma showed distinctive diffusion characteristics.


Minority ethnic groups in dementia care: a review of service needs, service provision and models of good practice.
Sixty-seven English language articles were obtained for the review, the majority of which (44, 65.7%) had US origins. Broadly, the main issues covered in the literature were the under-utilization of services by minority ethnic groups; the prevalence of dementia in different ethnic groups; the experience of care giving in different racial groups and language as a factor in cognitive assessment. Although it has been argued that the instruments used to assess cognitive function are culturally biased, the available published evidence would seem to suggest that the fundamental issue is language ability, rather than minority group membership per se. Studies into the care giving experience amongst different ethnic or racial groups suffer from theoretical and methodological weaknesses. Studies of help-seeking among various ethnic groups in the US have found that many do not prioritize dementia as a health problem in the face of more pressing concerns. There was little consensus amongst the articles about whether services should be provided specifically for different ethnic groups, reflecting a lack of evidence concerning the efficacy of different models of service provision.


Cytochrome pigments in Mycobacterium leprae isolated from armadillos (Dasypus novemcinctus L.).
The bacilli were isolated from granulomata harvested from armadillos. Cytochrome systems in whole cell suspensions as well as in cell-free extracts were examined spectrophotometrically. The intact cells contained cytochromes of the a+b3, b and c type which were found to be present mainly in the reduced form. The cytochrome systems in cell-free extracts of M. leprae were in the oxidized form but contained the same type of cytochromes as the intact bacteria. The presence of cytochromes was easily detectable in the anaerobically-reduced (no substrate added) as well as in the dithionite- or succinate-reduced minus O2-oxidized difference spectra. The dithionite-reduced plus CO minus reduced difference spectra exhibited cytochromes a3 and o monoxide binding pigments.


The 50 Most Cited Papers in Craniofacial Anomalies and Craniofacial Surgery.
Citation analysis is a recognized scientometric method of classifying cited articles according to the frequency of which they have been referenced. The total number of citations an article receives is considered to reflect it's significance among it's peers. Until now, a bibliometric analysis has never been performed in the specialty of craniofacial anomalies and craniofacial surgery. This citation analysis generates an extensive list of the 50 most influential papers in this developing field. Journals specializing in craniofacial surgery, maxillofacial surgery, plastic surgery, neurosurgery, genetics and pediatrics were searched to demonstrate which articles have cultivated the specialty within the past 55 years. The results show an intriguing compilation of papers which outline the fundamental knowledge of craniofacial anomalies and the developments of surgical techniques to manage these patients. This citation analysis provides a summation of the current most popular trends in craniofacial literature. These esteemed papers aid to direct our decision making today within this specialty.


Cloning of macromomycin apoprotein gene from Streptomyces macromomyceticus by use of 50-mer deoxynucleotide probes.
A mixed probe consisting of two synthetic deoxynucleotides (52 and 54 mers referred to as 50-mer) with arbitrarily chosen C or G for the third letters was prepared based on the amino acid sequences No. 31-48 and No. 72-90 of macromomycin (MCM) apoprotein and successfully used to clone the MCM apoprotein gene. Digestion with Sph I of total DNA of MCM-producing Streptomyces macromomyceticus M480-M1 yielded a 2.6-kb fragment that hybridized strongly to the probes. The hybridized probe was stable to washing with 3 x SSC at 75 degrees C. Radioactivity derived from the hybridized probe was comparable to that expected theoretically from hybridization between the probe and the true target sequence. The 2.6-kb fragment was cloned into Escherichia coli RR1 with pBR322 and subsequently subcloned into Streptomyces lividans TK21 with pIJ702. Nucleotide sequence analysis of the cloned fragment verified the existence of the sequence corresponding to the amino acid sequence of MCM apoprotein and about 90% homologies with the probes. Thus, the use of relatively long deoxynucleotide probes with arbitrarily chosen C or G for the third letters will be advantageous in cloning Streptomyces protein genes where more than 90% of the third letters have been known to be C or G. In addition, theoretical diagnosis of hybridization should be a great help to distinguish true positives from false ones.


Effect of silicon on wheat seedlings (Triticum turgidum L.) grown in hydroponics and exposed to 0 to 30 µM Cu.
Aqueous Si limits Cu uptake by a Si-accumulating plant via physicochemical mechanisms occurring at the root level. Sufficient Si supply may alleviate Cu toxicity in Cu-contaminated soils. Little information is available on the role of silicon (Si) in copper (Cu) tolerance while Cu toxicity is widespread in crops grown on Cu-contaminated soils. A hydroponic study was set up to investigate the influence of Si on Cu tolerance in durum wheat (Triticum turgidum L.) grown in 0, 0.7, 7.0 and 30 µM Cu without and with 1.0 mM Si, and to identify the mechanisms involved in mitigation of Cu toxicity. Si supply alleviated Cu toxicity in durum wheat at 30 µM Cu, while Cu significantly increased Si concentration in roots. Root length, photosynthetic pigments concentrations, macroelements, and organic anions (malate, acetate and aconitate) in roots, were also increased. Desorption experiments, XPS analysis of the outer thin root surface (≤100 Å) and µXRF analyses showed that Si increased adsorption of Cu at the root surface as well as Cu accumulation in the epidermis while Cu was localised in the central cylinder when Si was not applied. Copper was not detected in phytoliths. This study provides evidences for Si-mediated alleviation of Cu toxicity in durum wheat. It also shows that Si supplementation to plants exposed to increasing levels of Cu in solution induces non-simultaneous changes in physiological parameters. We propose a three-step mechanism occurring mainly at the root level and limiting Cu uptake and translocation to shoots: (i) increased Cu adsorption onto the outer thin layer root surface and immobilisation in the vicinity of root epidermis, (ii) increased Cu complexation by both inorganic and organic anions such as aconitate and, (iii) limitation of translocation through an enhanced thickening of a Si-loaded endodermis.


Chronic glomerulonephritis: inflammatory mediators stimulate the collagen synthesis in glomerular epithelial cells.
C5b-9 membrane attack complexes of complement (MAC) stimulate the production of type IV collagen in cultures of human glomerular epithelial cells. Together with other known effects of MAC interaction with glomerular cells, the complex is ascribed a role in the progress of acute glomerulitis into the chronic nephritic state.


Controlling the vector of distraction osteogenesis in the management of obstructive sleep apnea.
Obstructive sleep apnea (OSA) in individuals with craniofacial anomalies can compromise airway and is a serious life-threatening condition. In many cases, tracheostomy is carried out as the treatment of choice. Distraction osteogenesis of the mandible as a treatment modality for OSA is very useful and may spare the need for tracheostomy or allow decannulation, yet controlling the vector of distraction is still a major challenge. We present a method for controlling the vector of distraction. Eight patients with severe respiratory distress secondary to a micrognathic mandible were treated by mandibular distraction osteogenesis using either external or internal devices. Temporary anchorage devices (TADs) and orthodontic elastics were used to control the vector of distraction. Cephalometric X-rays, computed tomography, and polysomnographic sleep studies were used to analyze the results. A mean distraction of 22 mm using the internal devices and a mean of 30 mm using the external devices were achieved. Increase in the pharyngeal airway and hyoid bone advancement was also observed. Anterior-posterior advancement of the mandible was noted with no clockwise rotation. Most importantly, clinical improvement in symptoms of OSA, respiratory distress, and feeding was noted. We describe a method for controlling the vector of distraction used as a treatment for OSA. In these cases, TADs were used as an anchorage unit to control the vector of distraction. Our results show excellent clinical and radiographical results. TADs are a simple and nonexpensive method to control the vector of distraction.


Two perplexing skin tumors: microcystic adnexal carcinoma and keratoacanthoma.
Microcystic adnexal carcinoma and keratoacanthoma have a marked predilection for the skin of the head and neck. The adnexal carcinoma continues to be underrecognized, and the consequences for the patient are locally aggressive recurrences. The keratoacanthoma, on the other hand, may be inappropriately overdiagnosed, causing squamous cell carcinoma of the skin to be missed. In the instance of the solitary keratoacanthoma a conservative complete excision is recommended.


Effect of hemorrhagic shock on endotoxin-induced pulmonary hypertension and increased vascular permeability in unanesthetized sheep.
The lung is very susceptible to sepsis or endotoxin injury in the trauma patient. We studied the effect of an episode of hemorrhagic shock and resuscitation on the prostaglandin-induced pulmonary hypertension and leukocyte-induced increased permeability phase of endotoxin lung injury. Eight unanesthetized sheep with chronic lung lymph fistula were bled 50% of blood volume for 2 hr, then resuscitated. Thromboxane, TxA2, levels increased from 0.1 to 0.6 ng/ml during shock, while blood white cell count decreased. Both parameters returned to baseline while lung lymph flow increased twofold during resuscitation with lymph being protein-poor, indicating no increase in permeability. Lung water was not increased but some pulmonary leukostasis was evident histologically after resuscitation. We then studied the effect of this process on all immediate endotoxin insult. Seven unanesthetized sheep were given 0.7 microgram/kg E. coli endotoxin alone, and again after shock and resuscitation, in paired studies performed 3 days apart. There was no difference in either the early pulmonary hypertension or the later increased permeability phase of endotoxin lung injury when comparing the paired studies, as measured by lymph flow and protein flux. Hemorrhagic shock, despite producing a transient increase in thromboxane and pulmonary leukocyte sequestration, does not accentuate the lung injury of endotoxin if the shock state is adequately resuscitated.


Colorectal cancer-susceptibility single-nucleotide polymorphisms in Korean population.
Considering the significant racial and ethnic diversity in genetic variation, it is unclear whether the genome-wide association studies-identified colorectal cancer (CRC)-susceptibility single-nucleotide polymorphisms (SNPs) discovered in European populations are also relevant to the Korean population. However, studies on CRC-susceptibility SNPs in Koreans are limited. To investigate the racial and ethnic diversity of CRC-susceptibility genetic variants, we genotyped for the established European CRC-susceptibility SNPs in 198 CRC cases and 329 controls in Korea. To identify novel genetic variants using genome-wide screening in Korea, Illumina HumanHap 370K/610K BeadChips were performed on 105 CRC patients, and candidate CRC-susceptibility SNPs were selected. Subsequently, genotyping for replication was done in 189 CRC cases and 190 controls. Among the European CRC-susceptibility SNPs, rs4939827 in SMAD7 was associated with a significant decreased risk of Korean CRC (age-/gender-adjusted odds ratio [95% confidence interval]: additive model, 0.67 [95% CI, 0.47-0.95]; dominant model, 0.59 [95% CI, 0.39-0.91]). rs4779584 and rs10795668 were associated with CRC risk in females and males, respectively. Among candidate CRC-susceptibility SNPs selected from genome-wide screening, novel SNP, rs17051076, was found to be associated with a significantly increased risk of microsatellite instability-high CRC (age-/gender-adjusted odds ratio [95% confidence interval]: additive model, 4.25 [95% CI, 1.51-11.98]; dominant model, 3.52 [95% CI, 1.13-10.94]) in the replication study. rs4939827, rs4779584, and rs10795668 may contribute to the risk of CRC in the Korean population as well as in European populations. Novel rs17051076 could be associated with microsatellite instability-high CRC in Koreans. These associations support the ethnic diversity of CRC-susceptibility SNPs and should be taken into account in large-scale studies.


Colon cancer screening and surveillance in inflammatory bowel disease.
Patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer (CRC). Accordingly, the duration and anatomic extent of the disease have been known to affect the development of IBD-related CRC. When CRC occurs in patients with IBD, unlike in sporadic CRC, it is difficult to detect the lesions because of mucosal changes caused by inflammation. In addition, the tumor types vary with ill-circumscribed lesions, and the cancer is difficult to diagnose and remedy at an early stage. For the diagnosis of CRC in patients with IBD, screening endoscopy is recommended 8 to 10 years after the IBD diagnosis, and surveillance colonoscopy is recommended every 1 to 2 years thereafter. The recent development of targeted biopsies using chromoendoscopy and relatively newer endoscopic techniques helps in the early diagnosis of CRC in patients with IBD. A total proctocolectomy is advisable when high-grade dysplasia or multifocal low-grade dysplasia is confirmed by screening endoscopy or surveillance colonoscopy or if a nonadenoma-like dysplasia-associated lesion or mass is detected. Currently, pharmacotherapies are being extensively studied as a way to prevent IBD-related CRC.


Searching for Objects in Everyday Scenes: Measuring Performance in People With Dry Age-Related Macular Degeneration.
Treatment success in clinical trials for AMD would ideally be aligned to measurable performance in visual tasks rather than imperceptible changes on clinical charts. We test the hypothesis that patients with dry AMD perform worse than visually healthy peers on computer-based surrogates of "real-world" visual search tasks. A prospective case-control study was conducted in which patients with dry AMD performed a computer-based "real-world" visual search task. Participants searched for targets within images of everyday scenes while eye movements were recorded. Average search times across the images were recorded as a primary outcome measure. Comparisons were made against a 90% normative limit established in peers with healthy vision (controls). Eye movement parameters were examined as a secondary outcome measure. Thirty-one patients and 33 controls with median (interquartile range) age of 75 (70-79) and 71 (66-75) years and logMAR binocular visual acuity 0.2 (0.18-0.31) and -0.06 (-0.12 to 0), respectively, were examined. Four, 18, and 9 patients were categorized as having early, intermediate, and late AMD, respectively. Nineteen (61%) patients exceeded the 90% normative limits for average search time; this was statistically significant (Fisher's exact test, P < 0.0001). On average, patients made smaller saccades than controls (P < 0.001). People with dry AMD, certainly those with advanced disease, are likely to have measurable difficulties beyond those observed in visually healthy peers on "real-world" search tasks. Further work might establish this type of task as a useful outcome measure for clinical trials.


Slow dynamics in gelation phenomena: from chemical gels to colloidal glasses.
We here discuss the results of three-dimensional Monte Carlo simulations of a minimal lattice model for gelling systems. We focus on the dynamics investigated by means of the time autocorrelation function of the density fluctuations and the particle mean-square displacement. We start from the case of chemical gelation, i.e., with permanent bonds, and characterize the critical dynamics as determined by the formation of the percolating cluster, as actually observed in polymer gels. By opportunely introducing a finite bond lifetime tau(b), the dynamics displays relevant changes and eventually the onset of a glassy regime. This has been interpreted in terms of a crossover to dynamics more typical of colloidal systems and a connection between classical gelation and recent results on colloidal systems is suggested. By systematically comparing the results in the case of permanent bonds to finite bond lifetime, the crossover and the glassy regime can be understood in terms of effective clusters.


[Steroid receptors in brain tumors].
Recently the presence of steroid hormone receptors (SHR) have been reported in a series of nervous system human tumors, mainly in meningiomas. The possibility of characterizing brain tumors deserves attention because of the poor knowledge of endocrine-related behaviour of such tumors. The reliability of biochemical characterization of various receptor types should allow for better understanding of biological profile of primary and metastatic brain tumor, together with new avenues for combined modality treatment. In the future the highest priority might be assigned to the definition of the cut-off value of positivity for single receptors and to the receptor-endocrine modulation complex relationship for individual patients. A clear definition of the role of SHR in human brain tumors might improve our therapeutic potentials.


Experimental studies on human health effects of air pollutants. II. Four-hour exposure to ozone alone and in combination with other pollutant gases.
Eight adult male volunteers were exposed to ozone (O3) alone and then in combination with nitrogen dioxide and carbon monoxide under conditions simulating ambient air pollution exposures. Four "normal" men showed few or no effects from repeated exposures. Four male volunteers with a history of "hyperreactive" airways, but with normal base line pulmonary function spirometric studies, after O3 exposure developed definite symptoms and decrement in pulmonary function.


The Effect of Four Commonly used Root Canal Irrigants on the Removal of Smear Layer: An In-vitro Scanning Electron Microscope Study.
The objective of this study was to compare the efficiency of four commonly used chemicals in their ability to remove smear layer after instrumentation using scanning electron microscope (SEM). Seventy-five extracted single canaled teeth of roots ranging 10-12 mm in length were used for the study. Teeth were divided into 4 study groups and 1 control group of 15 teeth each. Standard access to the pulp chambers were performed with diamond burs. The lengths of the teeth were determined by the introduction of a size 15 K-file into the root canal until the tip reached the apical foramen. The working length for preparation of the canal is set 0.5 mm shorter than the measurement. Irrigation was performed using 2 ml of irrigant for every instrument change and finally rinsed using 5 ml of the respective solutions. The roots were then split with a chisel and hammer. One-half of each tooth was selected and prepared for SEM examination. After assembly on coded stubs, the specimens were placed in a vacuum chamber and sputter-coated with a 300 Å gold layer. The specimens were then analyzed using a Philips SEM XL 30. The dentinal wall of the cervical, middle and apical thirds was observed at magnifications of up to ×1000 for the presence/absence of smear layer and visualization of the entrance to dentinal tubules. Photomicrographs (×1000) of these areas on each of the coronal, middle and apical thirds were made Data were analyzed using Kruskal-Wallis test and Mann-Whitney U test. SEM study done on these prepared teeth with the popularly used four chemicals, namely, 3% NaOCl (Group A), 3% NaOCl followed by 17% ethylene diamine-tetra-acetic acid (Group B), 0.2% chlorhexidine (Group C) and 3% NaOCl followed by MTAD (Group D), with distilled water (Group E) which is used as control, revealed that NaOCl showed statistically significant, better cleansing effect than distilled water. Chlorhexidine and NaOCl showed equal kind of efficacy but were statistically significant, with lower efficacy than MTAD. It may be concluded that MTAD appears to be the most effective solution compared to the rest. The study demonstrated that MTAD as a final rinse after the entire instrumentation with 3% NaOCl as irrigant provided the best cleansing in all parts of the root canal system. The smear layer has been shown to hinder the penetration of intracanal disinfectants and sealers into dentinal tubules and has the potential of compromising the seal of the root filling. Degradation of the smear layer after treatment may contribute to leakage and reinfection of the root canal space. Removal of the smear layer reduced the penetration of bacteria through the root canal system after root filling.


IGF-1R inhibition sensitizes breast cancer cells to ATM-related kinase (ATR) inhibitor and cisplatin.
The complexity of the IGF-1 signalling axis is clearly a roadblock in targeting this receptor in cancer therapy. Here, we sought to identify mediators of resistance, and potential co-targets for IGF-1R inhibition. By using an siRNA functional screen with the IGF-1R tyrosine kinase inhibitor (TKI) BMS-754807 in MCF-7 cells we identified several genes encoding components of the DNA damage response (DDR) pathways as mediators of resistance to IGF-1R kinase inhibition. These included ATM and Ataxia Telangiectasia and RAD3-related kinase (ATR). We also observed a clear induction of DDR in cells that were exposed to IGF-1R TKIs (BMS-754807 and OSI-906) as indicated by accumulation of γ-H2AX, and phosphorylated Chk1. Combination of the IGF-1R/IR TKIs with an ATR kinase inhibitor VE-821 resulted in additive to synergistic cytotoxicity compared to either drug alone. In MCF-7 cells with stably acquired resistance to the IGF-1R TKI (MCF-7-R), DNA damage was also observed, and again, dual inhibition of the ATR kinase and IGF-1R/IR kinase resulted in synergistic cytotoxicity. Interestingly, dual inhibition of ATR and IGF-1R was more effective in MCF-7-R cells than parental cells. IGF-1R TKIs also potentiated the effects of cisplatin in a panel of breast cancer cell lines. Overall, our findings identify induction of DDR by IGF-1R kinase inhibition as a rationale for co-targeting the IGF-1R with ATR kinase inhibitors or cisplatin, particularly in cells with acquired resistance to TKIs.


Apical root resorption due to mandibular first molar mesialization: A split-mouth study.
Our aim was to evaluate the risk of external apical root resorption (EARR) in mesialized mandibular molars due to space closure in patients with unilateral second premolar agenesis. The contralateral side served as the control. After application of eligibility criteria, 25 retrospectively selected subjects (median age, 14.9 years; range, 12.0-31.9 years) were analyzed. Space closure (approximately 10 mm) was performed using skeletal anchorage. EARR was measured at the mandibular permanent canines, first premolars, and first molars in the pretreatment and posttreatment orthopantomograms. Measurements were performed by 2 examiners independently and were corrected for distortion and magnification of radiographs, which were assessed in a pilot study. Multivariate analysis of covariance and pairwise comparisons were performed. The mean enlargement factor of the panoramic machine was 29% ± 0.3%. Distortion exceeded 5% only in cases of large positioning errors (>20°). Intraclass correlation coefficients showed strong to almost perfect agreement (mean, 0.80 mm; 95% CI, 0.75-0.85) of the two examiners. Multivariate analysis of covariance resulted in no difference in EARR between the canines and premolars of the space closure and control sides. On the contrary, there was a statistically significant difference between mesialized and nonmezialized molars (0.73 mm; 95% confidence interval, 0.19-1.27). The mean total EARR in each tooth type did not exceed 1 mm. Space closure through extensive tooth movement in the mandible was identified as a risk factor for EARR. However, the amount of EARR attributed to space closure and the total EARR were not considered clinically significant.


Genetic testing for single gene disorders.
Genetic testing for single gene disorders is becoming available in Sri Lanka. While it offers many benefits, there are concerns about psychological and social problems that can be a consequence of such tests. This article aims to review the potential benefits and disadvantages of genetic testing, and recommends mechanisms that would help minimise problems associated with the inappropriate use of genetic tests.


[Fine structure of the vegetative and spore-forming hyphae of Micropolyspora fascifera].
Changes in the fine structure of the hyphae were studied in the course of spore formation by Micropolyspora fascifera. Sporulating hyphae differ from vegetative hyphae by a less dense cytoplasm, a large zone of the nucleoid with distinctly fibrillar structure, and a thin layerless cell wall. Spore formation is accompanied with autolysis of the vegetative hyphae, which consists in vacuolization of the hyphae and appearance of a large number of tubular membrane structures within them. Spores are formed, like in Actinomyces spp., by simultaneous division of the hyphae with septa; the structure of sporulating septa is similar to that of the fragmenting mycelium in Nocardia; the structure of mature spores is similar to that in some Actinomyces spp. Therefore, M. fascifera differs from other Micropolyspora spp. not only by the chemical composition of the cells (the presence of nocardiomicolic acids) but also by their structure. Taxonomic position of the species is discussed.


Context reinforcement degrades discriminative control: a memory approach.
This study measured effects of context reinforcement on a visual discrimination. Five pigeons responded to 1 key in the presence of 6 shorter wavelengths and to another key for 6 longer wavelengths. Psychometric functions provided measures of discriminative sensitivity (d') and overall stimulus control. Sensitivity and control were slightly but significantly better when 20% of correct choices yielded reinforcement than when 5% did. Reinforcement of pecks to the sample stimulus reduced control substantially and sensitivity slightly; noncontingent reinforcement during intertrial intervals also reduced control, whether such reinforcement was signaled or not. Accuracy was excellent during an extinction session, but it fell substantially when reinforcement for sample pecks was added during choice extinction. Simulations based on a memory model of the discrimination process reproduced most of the experimental findings.


Human Anthrax Transmission at the Urban-Rural Interface, Georgia.
Human anthrax has increased dramatically in Georgia and was recently linked to the sale of meat in an urban market. We assessed epidemiological trends and risk factors for human anthrax at the urban-rural interface. We reviewed epidemiologic records (2000-2012) that included the place of residence (classified as urban, peri-urban, or rural), age, gender, and self-reported source of infection (handling or processing animal by-products and slaughtering or butchering livestock). To estimate risk, we used a negative binomial regression. The average incidence per 1 million population in peri-urban areas (24.5 cases) was > 2-fold higher compared with rural areas and > 3-fold higher compared with urban area. Risk from handling or purchasing meat was nearly 2-fold higher in urban areas and > 4-fold higher in peri-urban areas compared with rural area. Our findings suggest a high risk of anthrax in urban and peri-urban areas likely as a result of spillover from contaminated meat and animal by-products. Consumers should be warned to purchase meat only from licensed merchants.


Pelvic floor exercises versus vaginal weight cones in genuine stress incontinence.
To compare pelvic floor exercises and vaginal weight cones in the treatment of genuine stress incontinence. Randomised controlled trial. Sixty ambulatory and fit white women (mean age 56 years) with urinary stress incontinence, treated by a single physiotherapist as outpatients during twelve weeks. Thirty women were allocated to a weekly session of pelvic floor exercises. Thirty were allocated to using cones, they were seen every two weeks. Objective: stress test, vaginal squeezing capacity. Subjective: urinary diary, visual analogue scales. Characteristics of both study groups were comparable. Unfortunately, there was an early withdrawal of fourteen (47%) women in the group treated with cones, and none in the other group. Therefore the pelvic floor exercise group was compared not only with the group intended to be treated with cones, but also with the selected group that only received cone therapy. No statistically significantly differences in outcome measures were found between the groups: 53% in the group assigned to pelvic floor exercises and 57% into the group assigned to cones, of which 50% in the group actually treated with cones, considered themselves as cured or improved to a significant degree. Long-term follow-up was not possible as all cone users refused continued exercises with cones once the twelve weeks had ended. Pelvic floor exercises and cones are equally effective in the treatment of genuine stress incontinence. Cones are cost and time saving. However, the low patient compliance with the cones importantly limits its clinical applicability, especially in the long run. Therefore, we do not recommend the use of cones.


Uptake of Pharmaceuticals Influences Plant Development and Affects Nutrient and Hormone Homeostases.
The detection of a range of active pharmaceutical ingredients (APIs) in the soil environment has led to a number of publications demonstrating uptake by crops, however very few studies have explored the potential for impacts on plant development as a result of API uptake. This study investigated the effect of carbamazepine and verapamil (0.005-10 mg/kg) on a range of plant responses in zucchini (Cucurbita pepo). Uptake increased in a dose-dependent manner, with maximum leaf concentrations of 821.9 and 2.2 mg/kg for carbamazepine and verapamil, respectively. Increased carbamazepine uptake by zucchini resulted in a decrease in above (<60%) and below (<30%) ground biomass compared to the controls (p < 0.05). At soil concentrations >4 mg/kg the mature leaves suffered from burnt edges and white spots as well as a reduction in photosynthetic pigments but no such effects were seen for verapamil. For both APIs, further investigations revealed significant differences in the concentrations of selected plant hormones (auxins, cytokinins, abscisic acid and jasmonates), and in the nutrient composition of the leaves in comparison to the controls (p < 0.05). This is some of the first research to demonstrate that the exposure of plants to APIs is likely to cause impacts on plant development with unknown implications.


Parenteral immunization with Shigella ribosomal vaccine elicits local IgA response and primes for mucosal memory.
The parenteral Shigella ribosomal vaccine (SRV), which previously was shown to protect guinea pigs and monkeys, has been compared with lypopolysaccharide (LPS) for its ability to induce a systemic and a local immune response. Injection of SRV caused a significant rise of the serum O antibodies of different classes and the appearance of IgA O antibodies in tears of guinea pigs and saliva and bile of monkeys. In guinea pigs, the local IgA response to parenteral SRV was much more intensive than that to feeding of high doses of LPS, while in monkeys it was nearly as high as that to challenge with a high dose of live pathogen. These data provide an immunological basis for the protective effect of SRV and are in disagreement with the widely accepted view of the inefficiency of parenteral antigens in stimulating mucosal immunity. The results are interpreted from the viewpoint of the role of ribosomes as a delivery system for the Shigella O antigen which provides high potency of SRV in stimulating local lymphoid tissue and makes it a good vaccine candidate.


VEGF Manipulation in Glioblastoma.
Glioblastoma is the most common malignant primary brain tumor that is universally lethal, despite optimized treatment including surgery, radiation, and chemotherapy. Targeting angiogenesis has been and continues to be an attractive therapeutic modality in both newly diagnosed and recurrent glioblastoma patients. Vascular endothelial growth factor (VEGF) is the most abundant and important mediator of angiogenesis in glioblastoma. Multiple strategies have been developed to target VEGF/VEGF receptor (VEGFR)-mediated angiogenesis, including VEGF blockade, VEGF Trap, and suppression of VEGFR signaling via receptor tyrosine kinase inhibitors (TKIs). These strategies have been explored in a spectrum of clinical trials, yielding findings that have all contributed to furthering our overall understanding of antiangiogenic therapy. The role of these agents and how to best incorporate them into the treatment paradigm for glioblastoma continues to evolve as understanding of resistance mechanisms improves. Although the excitement surrounding antiangiogenic therapy has waned over the years due to the lack of durable responses and survival benefit, there continues to be hope that combining antiangiogenic therapies with radiation therapy, cytotoxic drugs, immunotherapy, and targeted molecular agents may greatly enhance treatment strategies for high-grade gliomas.


Aberrant Wnt signalling and cellular over-proliferation in a novel mouse model of Meckel-Gruber syndrome.
Meckel-Gruber syndrome (MKS) is an embryonic lethal ciliopathy resulting from mutations in genes encoding proteins localising to the primary cilium. Mutations in the basal body protein MKS1 account for 7% of cases of MKS. The condition affects the development of multiple organs, including brain, kidney and skeleton. Here we present a novel Mks1(tm1a(EUCOMM)Wtsi) knockout mouse which accurately recapitulates the human condition, consistently developing pre-axial polydactyly, complex posterior fossa defects (including the Dandy-Walker malformation), and renal cystic dysplasia. TOPFlash Wnt reporter assays in mouse embryonic fibroblasts (MEFs) showed general de-regulated high levels of canonical Wnt/β-catenin signalling in Mks1(-/-) cells. In addition to these signalling defects, we also observed ectopic high proliferation in the brain and kidney of mutant animals at mid- to late-gestation. The specific role of Mks1 in regulating cell proliferation was confirmed in Mks1 siRNA knockdown experiments which showed increased levels of proliferation after knockdown, an effect not seen after knockdown of other ciliopathy genes. We suggest that this is a result of the de-regulation of multiple signalling pathways (Wnt, mTOR and Hh) in the absence of functional Mks1. This novel model system offers insights into the role of MKS1 in Wnt signalling and proliferation, and the impact of deregulation of these processes on brain and kidney development in MKS, as well as expanding our understanding of the role of Mks1 in multiple signalling pathways.


Elaboration of new formulations to remove micropollutants in MSWI flue gas.
This study consists in identifying and testing potential inorganic substitutes to carbon based materials commonly used as adsorbents for the removal of organic pollutants such as dioxins and furans released from Municipal Solid Waste Incinerators (MSWI). Although carbon materials enable to reach the current regulation in terms of dioxins and furans emissions, they exhibit a potential auto ignition risk when present in hot flue gases. Here, the adsorption potential of carbon based products is compared to the one of some inorganic materials. Chlorobenzene was chosen as a reference molecule to compare the removal performance of the different adsorbents. This comparison was based on the determination of the adsorption energies derived from temperature programmed desorption (TPD) experiments. In the first part of this study, five inorganic materials were selected according to their chlorobenzene adsorption performance compared to those of carbon based products currently used to remove micropollutants from MSWI flue gases. In the second part of the study, the influence of the inlet concentration of adsorbate on the adsorption potential of sorbents is investigated. Actually, the organic compound concentration was decreased in order to be closer to those met in MSWI. Furthermore, the adsorption experiments were performed with other adsorbates whose molecular mass or chlorine content are higher. Thanks to these adsorption results a new organic free formulation has been proposed for the removal of micropollutants. Tests carried out on an industrial scale, demonstrated that this product enables to reach the current norm concerning dioxins and furans emissions.


Food allergy: cause or consequence of pediatric eosinophilic esophagitis? Potential implications of ultraprocessed foods in prevention and management.
Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disease characterized by eosinophilic infiltration, leading to esophageal dysfunction, inflammation, and fibrotic remodeling. In the last few decades, there has been an increased prevalence of EoE at an alarming rate in the pediatric age. The pathogenesis of EoE is still largely undefined, and this limits the definition of effective strategies for the prevention and management of this condition. EoE is considered a multifactorial disease arising from a negative interaction between environmental factors and genetic background, causing an impaired esophageal epithelial barrier with subsequent abnormal allergen exposure activating type 2 (Th2) inflammation. Food antigens have been suggested as key players in Th2 inflammation in pediatric patients with EoE, but emerging evidence suggests a potential role of other dietary factors, including ultraprocessed foods, as possible triggers for the occurrence of EoE. In this paper, we discuss the potential role of these dietary factors in the development of the disease, and we propose a new approach for the management of pediatric patients with EoE.


Microsatellite in Aeschynomene falcata (Leguminosae): diversity, cross-amplification, and chromosome localization.
Aeschynomene falcata is an important forage species; however, because of low seed production, it is underutilized as forage species. Aeschynomene is a polyphyletic genus with a challenging taxonomic position. Two subgenera have been proposed, and it is suggested that Aeschynomene can be split in 2 genera. Thus, new markers, such as microsatellite sequences, are desirable for improving breeding programs for A. falcata. Based on transferability and in situ localization, these microsatellite sequences can be applied as chromosome markers in the genus Aeschynomene and closely related genera. Here, we report the first microsatellite library developed for this genus; 11 microsatellites were characterized, with observed and expected heterozygosities ranging from 0.0000 to 0.7143 and from 0.1287 to 0.8360, respectively. Polymorphic information content varied from 0.1167 to 0.7786. The departure from Hardy-Weinberg equilibrium may have resulted from frequent autogamy, which is characteristic of A. falcata. Of the 11 microsatellites, 9 loci were cross-amplified in A. brevipes and A. paniculata and 7 in Dalbergia nigra and Machaerium vestitum. Five of these 7 cross-amplified microsatellites were applied as probes during the in situ hybridization assay and 2 showed clear signals on A. falcata chromosomes, ensuring their viability as chromosome markers.


Maternal mental health and infant neurodevelopment at 6 months in a low-income South African cohort.
Maternal mental health disorders and the adverse consequences for infant neurodevelopment have received substantial research attention in high-income countries over the past five decades. In Africa, where relatively little work has been done on this topic, researchers have largely focused on infant physical health outcomes. This longitudinal study investigated the neurodevelopment of infants at 6 months post-term with exposure to mothers with a clinical diagnosis of persistent mental health disorders residing in low-income communities in Cape Town, South Africa. Adjusted models revealed no significant differences on the Bayley Scales of Infant and Toddler Development (BSID-III) domains (cognitive, motor, language, socio-emotional, and adaptive behavior) between infants exposed to maternal mental health disorders (n = 62) and the comparison group (n = 35) at 3 and 6 months. Subgroup analyses found no significant differences on the BSID-III domains between infants with exposure to mood disorders (n = 31), as well as infants with exposure to comorbid (i.e., a combination of two or three) mental health disorders (n = 14) and the comparison group. However, infants with exposure to psychotic disorders (n = 14) scored significantly lower on the cognitive and the motor domains and the fine motor subscale. These novel data provide an important contribution to the scientific literature especially in the field of maternal psychotic disorders in Africa.


Relationship among the variables of kinematic and tilt angle of whole body according to the foot trip during gait.
The aim of this study was to analyze the relation between incline angle of whole body and kinematic variables at tripping during gait. The participants consisted of healthy adult female (n=6). The three-dimensional (3D) motion analysis of posture restoring after inducing tripping of right foot at supporting phase of left foot was performed. As a result, supporting time elapsed of one stride and one foot at tripping showed longer than that of normal gait. The length of one stride showed longer at tripping than that of normal gait, and velocity of center of gravity (COG) showed faster at tripping than that of normal gait. Anteriorposterior incline angle of whole body showed more forwarded incline at tripping than that of normal gait. As a result of correlation among variables, one stride and supporting time elapsed showed positive relation r=0.973 (R2 =0.947, P<0.001), also r=0.920 (R2 =0.846, P<0.001) relative to velocity of COG, r=0.970 (R2 =0.941, P<0.001) of 1-stride time elapsed relative to velocity of COG and r=0.833 (R2 =0.613, P<0.05) of velocity of COG relative to anteriorposterior incline angle respectively. Therefore instantaneous stoppage of gait posture when tripped at supporting phase of one leg during gait may be impossible and rather may cause a recovery of gait pattern when secured the faster velocity of COG and the longer of supporting time elapsed of one leg.


A GPR18-based signalling system regulates IOP in murine eye.
GPR18 is a recently deorphaned lipid receptor that is activated by the endogenous lipid N-arachidonoyl glycine (NAGly) as well the behaviourally inactive atypical cannabinoid, abnormal cannabidiol (Abn-CBD). The presence and/or function of any GPR18-based ocular signalling system remain essentially unstudied. The objectives of this research are: (i) to determine the disposition of GPR18 receptors and ligands in anterior murine eye, (ii) examine the effect of GPR18 activation on intraocular pressure (IOP) in a murine model, including knockout mice for CB₁, CB₂ and GPR55. IOP was measured in mice following topical application of Abn-CBD, NAGly or the GPR55/GPR18 agonist O-1602, alone or with injection of the GPR18 antagonist, O-1918. GPR18 protein localization was assessed with immunohistochemistry. Endocannabinoids were measured using LC/MS-MS. GPR18 protein was expressed most prominently in the ciliary epithelium and the corneal epithelium and, interestingly, in the trabecular meshwork. The GPR18 ligand, NAGly, was also detected in mouse eye at a level comparable to that seen in the brain. Abn-CBD and NAGly, but not O-1602, significantly reduced IOP in all mice tested. The antagonist, O-1918, blocked the effects of Abn-CBD and NAGly. We present evidence for a functional GPR18-based signalling system in the murine anterior eye, including receptors and ligands. GPR18 agonists, Abn-CBD and NAGly, reduce IOP independently of CB₁, CB₂ or GPR55. These findings suggest that GPR18 may serve as a desirable target for the development of novel ocular hypotensive medications.


Impact of 24 weeks of supervised endurance versus resistance exercise training on left ventricular mechanics in healthy untrained humans.
In addition to the well-known cardiac structural adaptation to exercise training, little work has examined changes in left ventricle (LV) mechanics. With new regional and global indexes available we sought to determine the effect of 24-wk endurance versus resistance training on LV mechanics. Twenty-three male subjects were randomly allocated to a 24-wk endurance or resistance training program. Pre- and posttraining two-dimensional echocardiographic images were acquired. Global LV mechanics [strain (ε)] were recorded in longitudinal, circumferential, and radial planes. Rotation was assessed at apical and basal levels. In addition, longitudinal ε-volume loops, across the cardiac cycle, were constructed from simultaneous LV ε (longitudinal and transverse strain) and volume measurements across the cardiac cycle as a novel measure of LV mechanics. Marginal differences in ε and rotation data were found between groups. After training, we found no change in global peak ε data. Peak basal rotation significantly increased after training, with changes in the endurance group (-2.2 ± 1.9° to -4.5 ± 3.3°) and the resistance group (-2.9 ± 3.0° to -3.4 ± 2.9°). LV ε-volume loops revealed a modest rightward shift in both groups. Although most global and regional indexes of LV mechanics were not significantly altered, 24 wk of intense supervised exercise training increased basal rotation. Further studies that assess LV mechanics in larger cohorts of subjects and those with cardiovascular disease and risk factors may reveal important training impacts. NEW & NOTEWORTHY This study builds on previous work by our group and presents a comprehensive assessment of cardiac mechanics after dichotomous exercise training programs. We highlight novel findings in addition to the inclusion of strain-volume loops, which shed light on subtle differences in longitudinal and transverse contribution to volume change throughout the cardiac cycle. Our findings suggest that training has an impact on basal rotation and possibly strain-volume loops.


In Immunopeptidomics We Need a Sniper Instead of a Shotgun.
Immunopeptidomics employs the use of mass spectrometry to identify and quantify peptides presented on the surface of cells by major histocompatibility complex (MHC; human leukocyte antigen [HLA], in humans) molecules, an essential component of adaptive immunity. Currently, immunopeptidomics follows the same or similar workflows as the more established field of shotgun proteomics, yet inherent differences between these two fields create significant drawbacks for the former. In this viewpoint, we would like to highlight such technical issues and provide suggestions for novel workflows that would increase peptide sequencing coverage, depth, and confidence, collectively enhancing the capabilities of the field of immunopeptidomics.


Mechanisms for biopolymer accumulation in immobilized Acinetobacter calcoaceticus system.
The gram-positive bacteria, Acinetobacter calcoaceticus, is capable of accumulating biopolymer in the carrier matrix of an immobilized cell system. Several possible mechanisms for the biopolymer accumulation are evaluated. It appears that direct solid surface polymer adsorption and polymer diffusion limitation within the pore space are minor factors in biopolymer accumulation. Calculations demonstrate that the cell bound polymer to dry cell weight ratio is much higher for immobilized cells than for free cells. The higher cell-bound polymer to dry-cell-weight ratio for immobilized cells as well as the accumulation of the immobilized cells in the Celite matrix are believed to be the main factors for biopolymer accumulation in the Carrier matrix. Further studies reveal that the cell-bound polymer to dry-cell-weight ratio is strongly affected by shear forces. At zero shear stress, such as would be present in the carrier matrix, cell bound polymer to dry cell weight ratio can be as high as 1.6. As the shear stress increases, this ratio decreases. When shear stress increases above 5 dyn/cm(2), a level equivalent to the shear experienced by free cells in a stirred tank fermentation, cell-bound polymer decreases to less than 20% of dry cell weight. A macroscopic model is developed to describe the effect of shear stress on the cell-bound polymer to dry-cell-weight ratio.


Disruption of estrogen receptor beta's DNA binding domain impairs its tumor suppressive effects in triple negative breast cancer.
Triple negative breast cancer (TNBC) is an aggressive sub-type of the disease which accounts for a disproportionately high percentage of breast cancer morbidities and mortalities. For these reasons, a better understanding of TNBC biology is required and the development of novel therapeutic approaches are critically needed. Estrogen receptor beta (ERβ) is a reported tumor suppressor that is expressed in approximately 20% of primary TNBC tumors, where it is associated with favorable prognostic features and patient outcomes. Previous studies have shown that ERβ mediates the assembly of co-repressor complexes on DNA to inhibit the expression of multiple growth promoting genes and to suppress the ability of oncogenic transcription factors to drive cancer progression. To further elucidate the molecular mechanisms by which ERβ elicits its anti-cancer effects, we developed MDA-MB-231 cells that inducibly express a mutant form of ERβ incapable of directly binding DNA. We demonstrate that disruption of ERβ's direct interaction with DNA abolishes its ability to regulate the expression of well characterized immediate response genes and renders it unable to suppress TNBC cell proliferation. Loss of DNA binding also diminishes the ability of ERβ to suppress oncogenic NFκB signaling even though it still physically associates with NFκB and other critical co-factors. These findings enhance our understanding of how ERβ functions in this disease and provide a model system that can be utilized to further investigate the mechanistic processes by which ERβ elicits its anti-cancer effects.


An Interesting Case of Ingrowing Hair.
Cutaneous pili migrans is a rare condition caused by embedded hair shafts or fragments which presents as a mobile black linear rash and is easily confused with cutaneous larva migrans. "Ingrowing hair", in which the hair shaft grows inside the skin and burrows into the uppermost dermis rather than exiting the skin, is much rarer, and only 8 cases have been reported thus far, all in Asian men. We report a case of a 22-year-old Chinese male with a 4 cm-long black linear rash that migrated from the anterior abdomen to the left lower abdomen. The black lines represented hair shafts with follicular structures. The lesion disappeared immediately after hair removal. No recurrence occurred in 4 weeks of follow-up. To our knowledge, this is the first description of ingrowing hair occurring in the abdomen.


Nicotine dependence and psychosis in Bipolar disorder and Schizoaffective disorder, Bipolar type.
Patients with Bipolar disorder smoke more than the general population. Smoking negatively impacts mortality and clinical course in Bipolar disorder patients. Prior studies have shown contradictory results regarding the impact of psychosis on smoking behavior in Bipolar disorder. We analyzed a large sample of Bipolar disorder and Schizoaffective disorder, Bipolar Type patients and predicted those with a history of psychosis would be more likely to be nicotine dependent. Data from subjects and controls were collected from the Genomic Psychiatry Cohort (GPC). Subjects were diagnosed with Bipolar disorder without psychosis (N = 610), Bipolar disorder with psychosis (N = 1544). Participants were classified with or without nicotine dependence. Diagnostic groups were compared to controls (N = 10065) using logistic regression. Among smokers (N = 6157), those with Bipolar disorder had an increased risk of nicotine dependence (OR = 2.5; P < 0.0001). Patients with Bipolar disorder with psychosis were more likely to be dependent than Bipolar disorder patients without psychosis (OR = 1.3; P = 0.03). Schizoaffective disorder, Bipolar Type patients had more risk of nicotine dependence when compared to Bipolar disorder patients with or without psychosis (OR = 1.2; P = 0.02). Bipolar disorder patients experiencing more severity of psychosis have more risk of nicotine dependence. © 2015 Wiley Periodicals, Inc.


The self as mediator in the psychopathology of female children of alcoholics.
Theoreticians long have argued for the centrality of strength or poverty of self-definitions in the prediction and understanding of psychopathology. In this research an empirical measure of strength of self-definition was developed based on the work of Hazel Markus. Consistency of self-description and resistance to challenge for this self-description were found to be related to reported alcoholism, trust, and life satisfaction/depression in children of alcoholics. In fact, nearly all variance in life satisfaction and alcoholism differentiating children of alcoholics (COA) from non-COA groups was controlled by the self variables. Clinical and theoretical implications of the significant findings were discussed.


THE DISTRIBUTION OF PHENOTYPIC VARIANCE WITH INBREEDING.
Fifty-two inbred populations of Drosophila melanogaster, each founded from a single pair, and a large number of control, outbred flies were measured for fitness and a set of six traits. A survey of the literature on the effects of inbreeding and population bottlenecks demonstrates that the commonly observed pattern of an apparent variance among characters and among species in changes of phenotypic variance may in fact be largely the result of sampling error, given the pattern of change that we demonstrate within a species for the same character. In our study, population bottlenecks on average decrease the amount of phenotypic variance for a suite of wing characteristics and size, but there is large and significant variation among lines in the amount of phenotypic variance. As a result, several lines increased in variance in spite of the average decrease. Interestingly, the changes in phenotypic variance for fitness are in sharp contrast to those seen for phenotypic variance for morphological traits. The amount of phenotypic variance for fitness varies highly significantly among lines but, on average, is increased by bottlenecks. The changes in phenotypic variance as a result of population bottlenecks are large enough to significantly affect the probability of peak shifts by the variance-induced peak shift model.


Consumer-driven health plans: implications for providers.
By shifting more healthcare costs to workers, employers are hoping to slow the rise in company costs. It is too early to tell whether these consumer-driven health plans will address the issue of soaring costs. However, one thing is certain: They will have ramifications for healthcare providers.


Facilitating trypanosome imaging.
Research on trypanosomes as a model organism has provided a substantial contribution to a detailed understanding of basic cellular processes within the last few years. At the same time, major advances in super-resolution microscopy have been achieved, facilitating the resolution of biological structures in living cells at a scale of a few nm. However, the motility of trypanosomes has prevented access to high resolution microscopy of live cells. Here, we present a hydrogel based on poly(ethylene glycol) functionalized with either norbornene or thiol moieties for UV induced thiol-ene crosslinking for the embedding and imaging of live trypanosomes. The resulting gel exhibits low autofluorescence properties, immobilizes the cells efficiently on the nanometer scale and is compatible with cell viability for up to one hour at 24 °C. We applied super-resolution imaging to the inner plasma membrane leaflet using lipid-anchored eYFP as a probe. We find specific domains within the membrane where the fluorescence either accumulates or appears diluted rather than being homogenously distributed. Based on a Ripley's analysis, the size of the domains was determined to be raccumulated=170±5 nm and rdilute>115±15 nm. We hypothesize that this structuring of the membrane is associated with the underlying cytoskeleton.


Effect of cetirizine on histamine-induced bronchoconstriction and bronchoalveolar cells.
The effect of the histamine H1 receptor antagonist (cetirizine) on histamine-induced bronchoconstriction and inflammatory cells in bronchoalveolar lavage fluid was studied in 12 healthy volunteers. In previous studies we have observed an increased number of inflammatory cells, albumin and hyaluronan in the bronchoalveolar lavage (BAL) fluid 24 h after an inhalation challenge test with histamine-chloride. In the present study certirizine blocked the histamine-induced bronchoconstriction but did not influence the cell counts in the bronchoalveolar lavage fluid. Our result suggests that the histamine-induced bronchoconstriction but not the recruitment of inflammatory cells in the BAL fluid is mediated by histamine H1 receptors.


Field evaluation of a tailor-made new passive sampler for the determination of NO2 levels in ambient air.
This study describes the field evaluation of a tailor-made new glass passive sampler developed for the determination of NO(2), based on the collection on triethanolemine (TEA)-coated fibre filter paper. The sampler has been derived from a Palmes design. The overall uncertainty of the sampler was determined by using Griess-Saltzman ASTM D 1607 standard test method as a reference method. The agreement between the results of the passive sampler and the reference method was +/-7.90% with the correlation coefficient of 0.90. Method precision in terms of coefficient of variance (CV) for three simultaneously applied passive samplers was 8.80%. The uptake rate of NO(2) was found to be 2.49 ml/min in a very good agreement with the value calculated from theory (2.63 ml/min). Sampler detection limit was 1.99 microg/m(3) for an exposure period of 1 week and the sampler can be stored safely for a period of up to 6 weeks before exposure. A comparison of the sampler performance was conducted against a commercially available diffusion tube (Gradko diffusion tube). The results from the applied statistical paired t test indicated that there was no significant difference between the performances of two passive samplers (R (2) > 0.90). Also, another statistical comparison was carried out between the dark and transparent glass passive samplers. The results from the dark-colour sampler were higher than that from the transparent sampler (approximately 25%) during the summer season because of the possible photodegradation of NO(2)-TEA complex.


Comparative effectiveness of inhaled corticosteroids for paediatric asthma: protocol for a systematic review and Bayesian network meta-analysis.
Use of inhaled corticosteroid (ICS) is the mainstream maintenance therapy for paediatric asthma. Several forms of ICS are available, but the relative effectiveness among ICS has not been well investigated in published, randomised, controlled trials. The paucity of direct comparisons between ICS may have resulted in insufficient estimation in former systematic reviews/meta-analyses. To supplement the information on the comparative effectiveness of ICS for paediatric asthma, we plan to conduct a network meta-analysis that will enable summary of direct and indirect evidence. We will retrieve randomised, controlled trials that examined the effectiveness of ICS for paediatric asthma from the PubMed and Cochrane Central Register of Controlled Trials. After one author scans the title and abstract for eligible studies, two authors will independently review study data and assess the quality of the study. Studies of children (≤18 years old) with chronic asthma or recurrent wheezing episodes will be included if they used ICS for ≥4 weeks. We will define a priori core outcomes and supplemental outcomes of paediatric asthma, including exacerbation, healthcare use and pulmonary function. Studies reporting a minimum of one core outcome will be entered into the systematic review. After the systematic review is performed, extracted data of relevant studies will be synthesised in the Bayesian framework using a random-effects model. The results will be disseminated through peer-reviewed publications and conference presentations. UMIN (000016724) and PROSPERO (CRD42015025889).


A multi-biomarker disease activity score can predict sustained remission in rheumatoid arthritis.
Reliable assessment of remission is important for the optimal management of rheumatoid arthritis (RA) patients. In this study, we used the multi-biomarker disease activity (MBDA) test to explore the role of biomarkers in predicting point remission and sustained remission. RA patients on > 6 months stable therapy in stable low disease activity (DAS28-ESR ≤ 3.2) were assessed every 3 months for 1 year. Baseline, intermittent (IR) and sustained (SR) remission were defined by DAS28-ESR, DAS28-CRP, simple disease activity index (SDAI), clinical disease activity index (CDAI) and ACR/EULAR Boolean criteria. Patients not fulfilling any remission criteria at baseline were classified as 'low disease activity state' (LDAS). Patients not fulfilling any remission criteria over 1 year were classified as 'persistent disease activity' (PDA). MBDA score was measured at baseline/3/6 months. The baseline MBDA score, the 6-month time-integrated MBDA score and MBDA biomarkers were used for analyses. The area under the receiver operating characteristic curve (AUROC) assessed the ability of the MBDA score to discriminate between remission and non-remission. Biomarkers were analysed at baseline using the Mann-Whitney test and over time using the Jonckheere-Terpstra trend test. Of 148 patients, 27% were in the LDAS, 65% DAS28-ESR remission, 51% DAS28-CRP remission, 40% SDAI remission, 43% CDAI remission and 25% ACR/EULAR Boolean remission at baseline. Over 1 year, 9% of patients were classified as PDA. IR and SR were achieved in 42%/47% by DAS28-ESR, 46%/29% by DAS28-CRP, 45%/20% by SDAI, 44%/21% by CDAI and 35%/9% by ACR/EULAR Boolean criteria, respectively. By all remission criteria, baseline MBDA score discriminated baseline remission (AUROCs 0.68-0.75) and IR/SR (AUROCs 0.65-0.74). The 6-month time-integrated MBDA score discriminated IR/SR (AUROCs 0.65-0.79). Baseline MBDA score and concentrations of IL-6, leptin, SAA and CRP were significantly lower in all baseline remission criteria groups vs LDAS. They and the 6-month time-integrated values were lower among patients who achieved IR/SR vs PDA over 1 year. This study demonstrated that the MBDA score and its biomarkers IL-6, leptin, SAA and CRP differentiated between small differences in disease activity (i.e. between low disease activity and remission states). They were also predictors of remission over 1 year.


New Insight into Mechanisms of Protein Adaptation to High Temperatures: A Comparative Molecular Dynamics Simulation Study of Thermophilic and Mesophilic Subtilisin-Like Serine Proteases.
In high-temperature environments, thermophilic proteins must possess enhanced thermal stability in order to maintain their normal biological functions. However, the physicochemical basis of the structural stability of thermophilic proteins at high temperatures remains elusive. In this study, we performed comparative molecular dynamics simulations on thermophilic serine protease (THM) and its homologous mesophilic counterpart (PRK). The comparative analyses of dynamic structural and geometrical properties suggested that THM adopted a more compact conformation and exhibited more intramolecular interactions and lower global flexibility than PRK, which could be in favor of its thermal stability in high-temperature environments. Comparison between protein solvent interactions and the hydrophobicity of these two forms of serine proteases showed that THM had more burial of nonpolar areas, and less protein solvent hydrogen bonds (HBs), indicating that solvent entropy maximization and mobility may play a significant role in THM's adaption to high temperature environments. The constructed funnel-like free energy landscape (FEL) revealed that, in comparison to PRK, THM had a relatively flat and narrow free energy surface, and a lower minimum free energy level, suggesting that the thermophilic form had lower conformational diversity and flexibility. Combining the FEL theory and our simulation results, we conclude that the solvent (entropy force) plays a significant role in protein adaption at high temperatures.


Automatic recognition of pertrochanteric bone fractures in femur using level sets.
Femur fracture is one of the common diseases in the elderly. In this paper, an automatic and efficient classification method of femoral pertrochanteric fractures is proposed based on image segmentation techniques. The types of femoral pertrochanteric fracture are defined firstly according to the difference of fracture parts. To reduce the computational complexity, only four directions images are used in each 3D femur, i.e. the anterior, the anterolateral, the posterior and the posterolateral images of a femur. And then those fracture images are segmented from background using level set method. Considering the numerical errors and the instability of evolution in conventional level set formulations, a distance regularization term and an external energy constraint term are used, which are able to maintain a desired shape of the level set function and speed up the motion of the zero level contour in evolution process. After segmentation, the Canny edge detector is used to extract the fracture edges on femur. The types of femoral pertrochanteric fracture are classified by comparing the difference of edges between reference normal images and the testing images. Except the given four directions of 3D image, the classification is processed automatically. Experimental results illustrated the effectiveness of the proposed method.


Reduced efficiency of influenza vaccine in prevention of influenza-like illness in working adults: a 7 month prospective survey in EDF Gaz de France employees, in Rhône-Alpes, 1996-1997.
The efficiency of influenza vaccine was evaluated in the working population by comparing the percentage of people presenting with an influenza-like illness (ILI) according to their influenza immunization status, drug expenses and workdays lost. A self-completed questionnaire about the vaccination was sent to 5785 people randomly chosen among 18 249 workers. When any sick leave was incurred amongst the respondents (63.3%), of whom 301 were vaccinated and 3362 unvaccinated, a clinical form was completed by the private physician and the medical adviser of the firm (Electricité de France and Gaz de France). A final self-completed questionnaire was sent to people whose sick leave was not documented by a physician's reported diagnosis. In total, we obtained complete data for 90.9% of the sampling. The vaccine coverage rate of 8.2% [95% confidence interval (95% CI) = 7.4-9.0%] was higher in men than in women, increasing with age and professional category. Among the 775 subjects with a medical diagnosis, the vaccine effectiveness was not significant: 27.3% (95% CI = -13.8 to 53.5%). In the unvaccinated group, 9.6% had days absent from work, versus 7.0% in the vaccinated group; the two populations were comparable in terms of clinical symptoms, smoking habits, exposure to respiratory risk factors and chronic pathology. The average duration of sick leave for ILI was not significantly different between vaccinated (0.5 days) and unvaccinated workers (0.6 days). Despite the large size of the population and the occurrence of an epidemic due to a virus closely related to the vaccine strain (A/Wuhan/359/95), the vaccine did not effectively protect the small vaccine group nor result in an economic benefit, whatever the professional group.


Switch from biphasic human insulin 30 to biphasic insulin aspart 30 in Pakistani subjects.
To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in type 2 diabetes subjects switched from biphasic human insulin 30 (BHI 30) in the Pakistani subgroup of the multinational, prospective, non-interventional A1chieve study. Subjects who switched therapy from BHI 30 to BIAsp 30 were included in this analysis. Serious adverse drug reactions (SADRs, including major hypoglycaemia) and effectiveness parameters (glycated haemoglobin [HbA1c], fasting plasma glucose [FPG], postprandial plasma glucose [PPPG], systolic blood pressure [SBP]) and body weight were evaluated at the end of 24 weeks. A total of 152 subjects (79 males, 73 females; mean age, 53.4 +/- 10.3 years; BMI, 28.4 +/- 5.8 kg/m2) with an average diabetes duration of 11.2 +/- 4.8 years switched therapy from BHI 30 to BIAsp 30. The mean pre-study BHI 30 dose was 0.66 +/- 0.25 IU/kg and the mean starting BIAsp 30 dose was 0.65 +/- 0.23 U/kg, titrated up to 0.77 +/- 0.22 U/kg after 24 weeks. No SADRs were reported. From baseline to Week 24, overall hypoglycaemia did not change and no major hypoglycaemia was reported at Week 24. HbA1c levels decreased significantly from 9.1 +/- 1.1% at baseline to 7.4 +/- 0.7% (57 +/- 8 mmol/mol) at Week 24 (p < 0.001). Significant improvements in FPG, post-breakfast PPPG and SBP were reported (p < 0.001). Switching from BHI 30 to BIAsp 30 was well tolerated and improved glucose control without an increased incidence of hypoglycaemia in this Pakistani cohort.


Formulation development of paracetamol instant jelly for pediatric use.
Paracetamol is a common antipyretic and analgesic medicine used in childhood illness by parents and physicians worldwide. Paracetamol has a bitter taste that is considered as a significant barrier for drug administration. This study aimed to develop an oral dosage form that is palatable and easy to swallow by pediatric patients as well as to overcome the shortcomings of liquid formulations. The paracetamol was encapsulated in beads, which were prepared mainly from alginate and chitosan through electrospray technique. The paracetamol beads were sprinkled on the instant jelly prepared from glycine, ι-carrageenan and calcium lactate gluconate. The paracetamol instant jelly characteristics, in terms of physical appearance, texture, rheology, in vitro drug release and palatability were assessed on a human volunteer. The paracetamol instant jelly was easily reconstituted in 20 mL of water within 2 min to form jelly with acceptable consistency and texture. The jelly must be ingested within 30 min after reconstitution to avoid the bitter taste. The palatability assessment carried out on 12 human subjects established the similar palatability and texture of the paracetamol instant jelly dosage comparable to the commercial paracetamol suspension and was found to be even better in overcoming the aftertaste of paracetamol. Such findings indicate that paracetamol instant jelly will compensate for the use of sweetening and flavoring agents as well as develop pediatric dosage forms with limited undesired excipients.


Neonatal Skin Emergencies.
Although the majority of neonatal skin rashes can be safely monitored without intervention, there are a significant few that are dermatologic emergencies. When called to assess a neonate, it is important to distinguish what requires immediate diagnosis and treatment from those that represent benign etiologies. The skin may be the first clue to certain infections such as herpes simplex virus, syphilis, varicella, cytomegalovirus, fungal infections, and staphylococcal scalded skin syndrome, all of which require immediate testing and some of which may lead to severe sequelae. Cutaneous findings in neonates may also indicate the need for further evaluation. Purpura fulminans, sclerema neonatorum, neonatal lupus, and blueberry muffin rash can be indications of other underlying disorders and are reviewed as well. This article outlines these potential neonatal dermatologic emergencies and highlights the important clinical clues to each. [Pediatr Ann. 2019;48(1):e36-e42.].


Cell identification using single beam lensless imaging with pseudo-random phase encoding.
In this Letter, we propose a novel compact optical system for automated cell identification. Our system employs pseudo-random encoding of the light modulated by the cells under inspection to capture the unique opto-biological signature of the micro-organisms by an image sensor and without using a microscope objective lens to magnify the object beam. The proposed instrument can be fabricated using a compact light source, a thin diffuser, and an image sensor connected to computational hardware; thus, it can be compact and cost effective. Experiments are presented using the proposed system to identify and classify various micro-objects and demonstrate proof of concept. The captured opto-biological signature pattern can be attributed to the micro-object's morphology, size, sub-cellular complex structure, index of refraction, internal material composition, etc. Using the captured signature of the micro-object, we extract statistical features such as mean, variance, skewness, kurtosis, entropy, and correlation coefficients for cell identification using the random forest classifier. For comparison, similar identification experiments were repeated with a digital shearing interferometer. To the best of our knowledge, this is the first report on automated cell identification using the proposed approach.


Primary anastomosis vs nonrestorative resection for perforated diverticulitis with peritonitis: a prematurely terminated randomized controlled trial.
This randomized controlled trial (RCT) was performed to test the hypothesis that adverse event rates following primary anastomosis (PRA) are not inferior to those following nonrestorative colon resection for perforated diverticulitis with peritonitis. Patients admitted for perforated diverticulitis with peritonitis were randomly assigned to PRA (left colon resection with PRA and loop ileostomy) or nonrestorative colon resection (left colon resection with end colostomy). The endpoint was adverse events defined as mortality and morbidity following PRA or nonrestorative colon resection and stoma reversal. The estimated sample size was 300 patients in each study arm (alpha 0.10; 90% power). During a 9-year period, 90 patients were randomly assigned to undergo PRA or nonrestorative colon resection in 14 centres in eight countries. Thirty-four PRA patients were comparable to 56 nonrestorative colon resection patients for age (P = 0.481), gender (P = 0.190), APACHE III (P = 0.281), Hinchey stage III vs IV (P = 0.394) and Mannheim Peritonitis Index (P = 0.145). There were no differences in operating time (P = 0.231), surgeries performed at night (P = 0.083), open vs laparoscopic approach (P = 0.419) and litres of peritoneal irrigation (P = 0.096). There was no significant difference in mortality (2.9 vs 10.7%; P = 0.247) and morbidity (35.3 vs 46.4%; P = 0.38) following PRA or nonrestorative colon resection. After a similar lag time (P = 0.43), 64.7% of PRA patients and 60% of nonrestorative colon resection patients underwent stoma reversal (P = 0.659). Adverse event rates following stoma reversal differed significantly after PRA and reversal of nonrestorative resection (4.5 vs 23.5%; P = 0.0589). No conclusions may be drawn on preference of one treatment over another from this RCT because it was prematurely terminated following accrual of 15% of its sample size.


Clean-contaminated neck surgery: risk of infection by intrinsic and extrinsic factors.
To evaluate the risk of surgical wound infection (the most common complication in neoplastic clean-contaminated neck surgery) due to 10 intrinsic risk factors and 5 extrinsic risk factors. Retrospective clinical study. Academic tertiary referral medical center. The study group included 115 patients with laryngeal carcinomas referred to our department from January 1, 1996, to August 31, 2002. Fifty-seven patients underwent total laryngectomy and 58 underwent subtotal laryngectomy. The association between surgical wound infection due to 10 intrinsic risk factors and 5 extrinsic risk factors was evaluated with multivariate models. Surgical wound infection occurred in 27 patients (23.5%). There was no significant increase in the incidence of infection in patients with extensive tumors (P>.20) and in patients undergoing total laryngectomy and subtotal laryngectomy (P>.20). The incidence of infection was significantly higher in patients with stage IV disease (P<.01), in patients who underwent neck dissections (P<.05), and in those presenting with lymph node metastases (P<.001). Multivariate analysis showed that the presence of higher tumor stage is the best predictor of infection because it is the only significant factor (P<.03) even when adjusting for others. The association between infection and the other factors considered in this study (age [P>1.0], underweight [P = .26], anemia [P = .84], lymphocytopenia [P = .79 by Fisher exact test], number of preoperative hospitalizations [P<1.0], preoperative radiotherapy [P = .57 by Fisher exact test], diabetes mellitus [P = .70 by Fisher exact test], cirrhosis, resection margins infiltrated by the tumor [P = .57 by Fisher exact test], and myocutaneous flap reconstructions [P = .82]) was not significant. The risk of surgical wound infection is correlated with a higher tumor stage and lymph node metastases; it is not associated with the extent of surgery or other factors considered.


Heterotopic gastric mucosa in the cervical esophagus (inlet patch): endoscopic prevalence, histological and clinical characteristics.
Heterotopic gastric mucosal patch, which has a 0.1-10% frequency, is encountered when the cervical esophagus is examined carefully during endoscopy. In this study, we aimed to determine the prevalence of the patch in the cervical esophagus, to identify its macroscopic and histological characteristics and to evaluate demographic and clinical features. Six hundred and sixty patients (317 male, 343 female; mean age 50.28 years, range 14-90) with upper gastrointestinal symptoms had elective esophagogastroduodenoscopy and the cervical esophagus was examined for the patch during withdrawal of the endoscope. Biopsies were obtained from the antrum and the patch. Helicobacter pylori was assessed using an immunohistochemical method. The patch was found in 11 patients of 660, with a prevalence of 1.67%. Patch size ranged between 5 and 30 mm, appeared as a single patch in nine patients and as twin patches in two patients. Mean age and male : female ratio were not significantly different from the patient population without patches, but the female sex was predominant (three men, eight women; mean age 43.6 years, range 32-64). In five of 11 patients, the upper esophageal and laryngopharyngeal symptoms were remarkable. Eight patients in whom histological confirmation was carried out showed three fundic and five antral-type mucosa. Two of five patients with antral H. pylori also had the bacteria in the patch. H. pylori prevalence in the patch was 25%. Heterotopic gastric mucosal patches in the proximal esophagus should not be overlooked during endoscopy because they may lead to important complications in relation to their acid secretion, which may vary according to their parietal cell mass.


Genes in S. cerevisiae encoding proteins with domains homologous to the mammalian ras proteins.
The ras genes, which were first identified by their presence in RNA tumor viruses and which belong to a highly conserved gene family in vertebrates, have two close homologs in yeast, detectable by Southern blotting. We have cloned both genes (RAS1 and RAS2) from plasmid libraries and determined the complete nucleotide sequence of their coding regions. They encode proteins with nearly 90% homology to the first 80 positions of the mammalian ras proteins, and nearly 50% homology to the next 80 amino acids. Yeast RAS1 and RAS2 proteins are more homologous to each other, with about 90% homology for the first 180 positions. After this, at nearly the same position that the mammalian ras proteins begin to diverge from each other, the two yeast ras proteins diverge radically. The yeast ras proteins, like the proteins encoded by the mammalian genes, terminate with the sequence cysAAX, where A is an aliphatic amino acid. Thus the yeast ras proteins have the same overall structure and interrelationship as the family of mammalian ras proteins. The domains of divergence may correspond to functional domains of the ras proteins. Monoclonal antibody directed against mammalian ras proteins immunoprecipitates protein in yeast cells containing high copy numbers of the yeast RAS2 gene.