Corrosion Resistance of 3D-Printed Titanium Alloy Ti64-ELI Parts for Dental Application.

Corrosion in the human body can cause materials to change structurally and release undesirable products that may bring about complications such as toxicity and inflammation. These may jeopardize the mechanical stability of prostheses. The purpose of this study was to evaluate the effect of solutions (Ringer's and table salt [NaCl]) and immersion periods on 3D-printed titanium alloy Ti64-ELI samples and the changes in mechanical properties before and after corrosion testing. The microstructure of prepared samples was analyzed, and the formation of α- and ß-phases was studied. During testing, the ß-phases showed up as white, and the α-phases presented as dark. In both, corrosion by pitting was observed after corrosion analysis. The results show that, by comparing NaCl and Ringer's, the E corr of the solutions increased by 0.8 V and the I corr decreased by an order of magnitude. It was observed that the weight loss in the solutions will lead to dental implant instability and will cause failure.

Short term response of plankton community to nutrient enrichment in central eastern Arabian Sea: Elucidation through mesocosm experiments.

Oligotrophic waters (OW), generally favour longer food chain facilitated by the microbial loop. In such ecosystems, physical mixing (e.g. upwelling, and winter convection) inject nutrients and propagules from subsurface to the photic zone. Such events are expected to alter the food chain through shifts in the plankton community. Mesocosm experiments were carried out to evaluate the influence of nutrient enrichment from the deep (100-150 m) on the surface plankton community for the first time in the Arabian Sea, through custom-designed enclosures in OW of the central-eastern Arabian Sea (CEAS). Surface water was characterized by low nutrients and phytoplankton biomass (chlorophyll-a of <0.2 µg m-3) and upon nutrient enrichment yielded differing response. Higher abundance of picophytoplankton, bacteria and protists was noticed at a depth of ~100 m than at surface. The inoculation of such a population to the surface, resulted in a significant enhancement of autotrophic (picophytoplankton) and heterotrophic (bacteria and protists) populations. However, significant changes in the abundance of larger plankton was not evident till three days of incubation. Even though autotrophic picophytoplankton responded positively, a distinct increase in chlorophyll-a was not evident. This study points out that the lack of sufficient viable microphytoplankton propagules, neither at the surface nor at the depth (inoculum) are the possible reasons for the lack of their distinct positive response. These experiments suggest the dominance of microbial community response to physical mixing in the OW regions of the Arabian Sea and the importance of propagule diversity. The insights from this experiment will serve as a precursor for appropriate modifications in ocean modelling and forecasting studies and help in building global environmental management tools.

Perinatal and infant outcome of fetuses with prenatally diagnosed hyperechogenic kidneys.

OBJECTIVE: Hyperechogenic kidneys are a relatively rare antenatal finding, which can generate significant parental anxiety due to uncertain prognosis. We report on the perinatal and infant outcomes of a large cohort of fetuses with antenatally diagnosed hyperechogenic kidneys. METHODS: This was a retrospective analysis of all cases diagnosed prenatally with hyperechogenic kidneys between 2002 and 2017 in a large tertiary fetal medicine unit. Hyperechogenicity was defined as kidney parenchyma with greater echogenicity than that of the liver. Pregnancy, pathological and postnatal outcomes were collected from hospital and general practitioner records up to 1 year of age. Abnormal renal outcome was defined as elevated creatinine beyond 6 months of age, hypertension requiring medication or major kidney surgery, such as nephrectomy. Severe abnormal renal outcome was defined as the need for dialysis or kidney transplant at any stage. RESULTS: Three-hundred and sixteen fetuses with hyperechogenic kidneys were identified at a mean gestational age of 21 (range, 13-37) weeks. The majority of cases (97%) had bilateral hyperechogenic kidneys. In the 265 cases with available follow-up data, other associated renal tract abnormalities were identified prenatally in 36%, concomitant extrarenal structural abnormalities in 39% and abnormal karyotype in 15% of cases. Of the 316 included cases, 139 did not survive, including 105 terminations of pregnancy, five intrauterine deaths and 29 early neonatal deaths. Only 4.3% (6/139) of these fetuses had isolated hyperechogenic kidneys while 28.1% (39/139) had associated multiple renal tract abnormalities alongside hyperechogenic kidneys and over two-thirds (67.6%; 94/139) had concomitant extrarenal abnormalities. Of the 177 cases that survived beyond 1 month of age, outcome data were available in 126. Of these, based on the antenatal findings, 60 (47.6%) cases had isolated hyperechogenic kidneys, 56 (44.4%) had associated renal structural abnormalities and 10 (7.9%) had additional extrarenal abnormalities. Considering renal outcome alone, kidney function was abnormal in 13 (21.7%), 10 (17.9%) and 0 (0%) infants in these three groups, respectively, although concurrent pathology clearly affected global outcome in the more complex cases. Neonatal mortality of 1.6% was observed in the isolated renal hyperechogenicity group. The presence of oligohydramnios or abnormal renal volume was not associated significantly with abnormal renal function (odds ratio (OR), 2.32 (99% CI, 0.54-10.02) and OR, 0.74 (99% CI, 0.21-2.59), respectively) in this group. CONCLUSIONS: Hyperechogenic kidneys are often complicated by associated renal tract and extrarenal abnormalities, aberrant karyotype and genetic disease, and these factors have a greater effect on overall outcome than does kidney echogenicity. The renal outcome of fetuses with isolated hyperechogenic kidneys is good generally, with over 70% of cases having normal renal function postpartum. Importantly, for prognostic counseling, all of the fetuses in this non-selected series with isolated hyperechogenic kidneys and normal amniotic fluid levels had normal renal outcome in infancy. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Multiscale analysis and experimental validation of the effective elastic modulus of epoxy-dioctahedral phyllosilicate clay composite.

In this research, developed finite element codes were used to study the effective elastic modulus and stress-strain distribution profiles of epoxy resin filled with 6 wt. % microparticles of kaolinite. The random distribution of the particles was microstructurally regenerated with Digimat MSC software and random sequential algorithm codes in epoxy matrix. Stochastic representative volume element models of the composites were developed and analyzed under periodic boundary conditions. For validation, the predicted result by finite element analysis was compared with that of Mori-Tanaka's mean field homogenization scheme, selected micromechanical models and experiment. All the results indicated that 6 wt. % of kaolinite microparticles can improve the elastic modulus and load-bearing capacity of epoxy resin with <5 % error between predicted and actual results. The microstructure, phase identification and chemical characterization of the composite were also studied with scanning electron microscopy, x-ray diffraction spectroscopy and energy-dispersive x-ray spectroscopy, respectively. In addition, the particle size and distribution of the kaolinite in the epoxy matrix were experimentally investigated.

Nanoparticles carrying fingolimod and methotrexate enables targeted induction of apoptosis and immobilization of invasive thyroid cancer.

Metastatic tumors are the main cause of cancer-related death, as the invading cancer cells disrupt normal functions of distant organs and are nearly impossible to eradicate by traditional cancer therapeutics. This is of special concern when the cancer has created multiple metastases and extensive surgery would be too dangerous to execute. Therefore, combination chemotherapy is often the selected treatment form. However, drug cocktails often have severe adverse effects on healthy cells, whereby the development of targeted drug delivery could minimize side-effects of drugs and increase the efficacy of the combination therapy. In this study, we utilized the folate antagonist methotrexate (MTX) as targeting ligand conjugated onto mesoporous silica nanoparticles (MSNs) for selective eradication of folate receptor-expressing invasive thyroid cancer cells. The MSNs was subsequently loaded with the drug fingolimod (FTY720), which has previously been shown to efficiently inhibit proliferation and invasion of aggressive thyroid cancer cells. To assess the efficiency of our carrier system, comprehensive in vitro methods were employed; including flow cytometry, confocal microscopy, viability assays, invasion assay, and label-free imaging techniques. The in vitro results show that MTX-conjugated and FTY720-loaded MSNs potently attenuated both the proliferation and invasion of the cancerous thyroid cells while keeping the off-target effects in normal thyroid cells reasonably low. For a more physiologically relevant in vivo approach we utilized the chick chorioallantoic membrane (CAM) assay, showing decreased invasive behavior of the thyroid derived xenografts and an increased necrotic phenotype compared to tumors that received the free drug cocktail. Thus, the developed multidrug-loaded MSNs effectively induced apoptosis and immobilization of invasive thyroid cancer cells, and could potentially be used as a carrier system for targeted drug delivery for the treatment of diverse forms of aggressive cancers that expresses folate receptors.

Bioactivities and molecular networking-based elucidation of metabolites of potent actinobacterial strains isolated from the Unkeshwar geothermal springs in India.

The bioactive potential of Actinobacteria endemic to hot springs has rarely been investigated. This study highlights the cultivable diversity and bioactivities of Actinobacteria associated with the Unkeshwar hot springs, India. Potent strains were evaluated for their biosynthetic potentials and metabolite analysis was performed using effective dereplication molecular networking tools. A total of 86 actinobacterial strains were isolated and grouped into 21 distinct genera, based on 16S rRNA gene sequence analysis. These strains included rare members such as Micromonospora, Marmoricola, Actinomadura, Cellulomonas, Cellulosimicrobium, Janibacter, Rothia, Barrentisimonas, Dietzia and Glycomyces. In antimicrobial screening, Micromonospora sp. strain GH99 and Streptomyces sp. strain GH176 were found to be potent antimicrobial strains. The metabolic extracts of these strains exhibited strong antimicrobial activity against Staphylococcus epidermidis (NCIM 2493), Shigella flexneri (NCIM 5265), Klebsiella pneumonia (NCIM 2098), and Salmonella abony (NCIM 2257). The extracts also displayed strong anti-biofilm and anticancer activities against Pseudomonas aeruginosa (NCIM 5029), Acinetobacter junii (NCIM 5188) and breast cancer cell line MCF7, respectively. Both strains also tested positive for the presence of the PKS biosynthetic gene cluster in their genomes. To effectively delineate the secondary metabolites, the extracts were subjected to MS/MS-guided molecular networking analysis. Structurally diverse compounds including the polyketides 22-dehydroxymethyl-kijanolide (GH99 strain) and Abyssomicin I (GH176 strain) were detected in the extracts. Interestingly, Brevianamide F was detected in the extract of Micromonospora, which has previously been mostly found in fungal species. Other compounds such as cyclic tripeptides, Cyclo(l-Pro-d-Ile) and Cyclo(d-Pro-l-Phe), were also identified in this strain. In summary, for the first time, we explored the diversity of Actinobacteria and evaluated their bioactive potential from the Unkeshwar hot springs. The potent strains isolated in the study could be useful in drug discovery programs.

Evaluation of antiviral activity of Ocimum sanctum and Acacia arabica leaves extracts against H9N2 virus using embryonated chicken egg model.

BACKGROUND: In the view of endemic avian influenza H9N2 infection in poultry, its zoonotic potential and emergence of antiviral resistance, two herbal plants, Ocimum sanctum and Acacia arabica, which are easily available throughout various geographical locations in India were taken up to study their antiviral activity against H9N2 virus. We evaluated antiviral efficacy of three different extracts each from leaves of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) against H9N2 virus using in ovo model. METHODS: The antiviral efficacy of different leaves extracts was systematically studied in three experimental protocols viz. virucidal (dose-dependent), therapeutic (time-dependent) and prophylactic (dose-dependent) activity employing in ovo model. The maximum non-toxic concentration of each herbal extracts of O. sanctum and A. arabica in the specific pathogen free embryonated chicken eggs was estimated and their antiviral efficacy was determined in terms of reduction in viral titres, measured by Haemagglutination (HA) and real time quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays. RESULTS: All the extracts of O. sanctum (crude extract, terpenoid and polyphenol) and A. arabica (crude extract, flavonoid and polyphenol) showed significant virucidal activity, however, crude extract ocimum and terpenoid ocimum showed highly significant to significant (p < 0.001-0.01) decrease in virus genome copy numbers with lowest dose tested. Similarly, therapeutic effect was observed in all three extracts of O. sanctum in comparison to the virus control, nevertheless, crude extract ocimum and terpenoid ocimum maintained this effect for longer period of time (up to 72 h post-incubation). None of the leaves extracts of A. arabica had therapeutic effect at 24 and 48 h post-incubation, however, only the crude extract acacia and polyphenol acacia showed delayed therapeutic effect (72 h post-inoculation). Prophylactic potential was observed in polyphenol acacia with highly significant antiviral activity compared to virus control (p < 0.001). CONCLUSIONS: The crude extract and terpenoid isolated from the leaves of O. sanctum and polyphenol from A. arabica has shown promising antiviral properties against H9N2 virus. Future investigations are necessary to formulate combinations of these compounds for the broader antiviral activity against H9N2 viruses and evaluate them in chickens.

Two-stage hypospadias repair with a free graft for severe primary and revision hypospadias: A single surgeon's experience with long-term follow-up.

INTRODUCTION: Repair of severe primary and revision hypospadias is a demanding procedure. Debate continues as to whether a two-stage approach or single-stage technique is superior. The two-stage procedure with a free graft involves penile straightening followed by application of a graft for the neourethral plate at stage one; with tubularization at stage two after graft maturation. OBJECTIVE: To report the outcomes of a single surgeon's experience with the two-stage repair using a free graft for both severe primary and revision hypospadias with long-term follow-up. MATERIALS AND METHODS: Between July 1998 and January 2010, 301 boys underwent a two-stage reconstruction. The surgical technique is described in the manuscript. Primary repairs (n = 208): indications for a two-stage approach with a free graft included meatal position, presence of corporal chordee, and poor glans development. Median follow-up from completion of the second stage was 75 months. Revision repairs (n = 93): indications included urethral fistula, excessive scarring/meatal stenosis, balanitis xerotica obliterans (BXO), and residual or untreated chordee. Median follow-up from completion of the second stage was 85 months. RESULTS: For the primary repairs (n = 208), the graft took well in all but one case. Second-stage complications included fistula (7), meatal stenosis (3), partial glans dehiscence (3), and all were re-operated (13). For the revision repairs (n = 93), the graft took well in all but four cases. Second-stage complications included fistula (5), meatal stenosis (3), breakdown (1) and reoperation (8). DISCUSSION: In a systematic review of 20 years of publications on the repair of primary severe hypospadias, the two-stage procedure with a free graft demonstrated an overall complication rate of 22%; this was a distinct overall benefit when compared with the single-stage procedures in terms of lower complication rates (Castagnetti and El-Ghoneimi, 2010). Our results for the severe primary repairs revealed significantly lower complication rates than those in the literature, with an overall re-operation rate of 6.3%, a fistula rate of 3.4%, and meatal stenosis and partial glans dehiscence at 1.4% each. Several papers have documented outcomes following the single-stage tubularized incised plate urethroplasty for re-operative hypospadias, giving overall complication rates ranging from 15.4 to 30%. Our data show a re-operative rate of 8.6%, a fistula rate of 5.3%, breakdown in 1.1%, and meatal stenosis in 3.2%. CONCLUSION: The two-stage repair with a free graft for correction of both severe primary and failed primary hypospadias is a safe, viable, and durable procedure offering low morbidity and excellent cosmetic results. The authors advocate the two-stage repair with a free graft as the technique of choice for treatment of both of these challenging groups of the deformity.

Pain and Opioid Addiction: A Systematic Review and Evaluation of Pain Measurement in Patients with Opioid Dependence on Methadone Maintenance Treatment.

BACKGROUND: While chronic pain has been said to impact patient's response to methadone maintenance treatment for opioid dependence, the reported findings are inconsistent. These discrepancies may be a direct result of variations in the measurement of chronic pain or definitions of response to methadone treatment. The goal of this study is to evaluate the association between pain and substance use behaviour to determine the real impact of comorbid pain in the methadone population. We also aim to examine sources of variation across the literature with a specific focus on the measurement of pain. METHODS/DESIGN: We performed a systematic review using an electronic search strategy across CINAHL, MEDLINE, Web of Science, PsychINFO, EMBASE, and the Cochrane Library including Cochrane Reviews and the Cochrane Central Register of Controlled Trials databases. Title, abstract, as well as full text screening and extraction were performed in duplicate. Studies evaluating the association between chronic pain and methadone maintenance treatment response were eligible for inclusion in this review. Using a sample of 297 methadone patients from the Genetics of Opioid Addiction (GENOA) research collaborative, we assessed the reliability of patient self-reported pain and the validated Brief Pain Inventory (BPI) assessment tool. RESULTS: After screening 826 articles we identified five studies eligible for full text extraction, of which three showed a significant relationship between the presence of pain and the increase in substance abuse among patients on methadone for the treatment of opioid dependence. Studies varied largely in the definitions and measurement of both pain and response to treatment. Results from our validation of pain measurement in the GENOA sample (n=297) showed the use of a simple self-reported pain question is highly correlated to the use of the BPI. Simply asking patients whether they have pain showed a 44.2% sensitivity, 88.8% specificity, 84.4% PPV and 53.6% NPV to the BPI. The area under the ROC curve was 0.67 and the Pearson χ(2) was 37.3; (p<0.0001). DISCUSSION: The field of addiction medicine is at a lack of consensus as to the real effect of chronic pain on treatment response among opioid dependent patients. Whether it be the lack of a single "gold standard" measurement of response, or a lack of consistent measurement of pain, it is difficult to summarize and compare the results of these relatively small investigations. In comparison to the BPI, use of the simple self-reported pain has lower sensitivity for identifying patients with pain, suggesting the inconsistencies in these studies may result from differences in pain measurement. Future validation studies of pain measurement are required to address the predictive value of self-reported pain.

Mathematical Model-Based Accelerated Development of Extended-release Metformin Hydrochloride Tablet Formulation.

A computational fluid dynamic (CFD) model was developed to predict metformin release from a hydroxypropylmethylcellulose (HPMC) matrix-based extended-release formulation that took into consideration the physical and chemical properties of the drug substance, composition, as well as size and shape of the tablet. New high dose strength (1000 mg) tablet geometry was selected based on the surface area/volume (SA/V) approach advocated by Lapidus/Lordi/Reynold to obtain the desired equivalent metformin release kinetics. Maintaining a similar SA/V ratio across all extended-release metformin hydrochloride (Met XR) tablet strengths that had different geometries provided similar simulations of dissolution behavior. Experimental dissolution profiles of three lots of high-strength tablets agreed with the simulated release kinetics. Additionally, a pharmacokinetic absorption model was developed using GastroPlus™ software and known physicochemical, pharmacokinetic, and in vitro dissolution properties of metformin to predict the clinical exposure of the new high strength (1000 mg) tablet prior to conducting a human clinical bioequivalence study. In vitro metformin release kinetics were utilized in the absorption model to predict exposures in humans for new 1000-mg Met XR tablets, and the absorption model correctly projected equivalent in vivo exposure across all dose strengths. A clinical bioequivalence study was pursued based on the combined modeling results and demonstrated equivalent exposure as predicted by the simulations.

Shape engineering boosts antibacterial activity of chitosan coated mesoporous silica nanoparticle doped with silver: a mechanistic investigation.

In this study, mesoporous silica nanoparticles (MSPs) of different size and shape were developed, and their surface coatings were utilized to study their differential effects in enhancing antibacterial activity. In brief, MSPs with three different aspect ratios (1, 2 and 4) were prepared, doped with silver ions and finally coated with the polymer chitosan. Both Gram-positive and Gram-negative bacteria were treated with the MSPs. Results indicate that silver ion doped and chitosan coated MSPs with the aspect ratio of 4 (Cht/MSP4:Ag+) have the highest antimicrobial activity among the prepared series. Further studies revealed that Cht/MSP4:Ag+ was most effective against Escherichia coli (E.coli) and least effective against Vibrio cholerae (V. cholerae). To investigate the detailed inhibition mechanism of the MSPs, the interaction of the nanoparticles with E.coli membranes and its intracellular DNA was assessed using various spectroscopic and imaging-based techniques. Furthermore, to increase the efficiency of the MSPs, a combinatorial antibacterial strategy was also explored, where nanoparticles, in combination with kanamycin (antibiotic), were used against Vibrio Cholerae (V. cholerae). Toxicity screening of these on MSPs was conducted on Caco-2 cells, and the results show that the dose used for antibacterial screening is below the limit of the toxicity threshold. Our findings show that both shape and surface engineering contribute positively towards killing bacteria, and the newly developed silver ion-doped and chitosan-coated MSPs have good potential as antimicrobial nanomaterials.

What accounts for ethnic differences in newborn skinfold thickness comparing South Asians and White Caucasians? Findings from the START and FAMILY Birth Cohorts.

OBJECTIVE: South Asians are a high-risk group for type 2 diabetes and coronary heart disease. We sought to determine ethnic differences in newborn adiposity comparing South Asians (SA) to White Caucasians (Whites). METHODS: Seven hundred ninety pregnant women (401 SA, 389 Whites) and their full-term offspring from two birth cohorts in Canada were analyzed. Pregnant women completed a health assessment including a 75-g oral glucose tolerance test to assess for dysglycemia. Birthweight, length, waist and hip circumference, and triceps and subscapular skinfold thickness (a surrogate measure of body adiposity) were measured in all newborns. Multivariate regression was used to identify maternal factors associated with newborn skinfold measurements. RESULTS: South Asian women were younger (30.1 vs 31.8 years, P<0.001), their prepregnancy body mass index was lower (23.7 vs 26.2, P<0.0001) and gestational diabetes was substantially higher (21% vs 13%, P=0.005) compared with Whites. Among full-term newborns, South Asians had lower birthweight (3283 vs 3517 g, P=0.0001), had greater skinfold thickness (11.7 vs 10.6 mm; P=0.0001) and higher waist circumference (31.1 vs 29.9 cm, P=0.0001) compared with Whites. Risk factors for newborn skinfold thickness included South Asian ethnicity (standardized estimate (s.e.): 0.24; P<0.0001), maternal glucose (s.e.: 0.079; P=0.04) and maternal body fat (s.e.: 0.14; P=0.0002). CONCLUSIONS: South Asian newborns are lower birthweight and have greater skinfold thickness, compared with White newborns, and this is influenced by maternal body fat and glucose. Interventions aimed at reducing body fat prior to pregnancy and gestational diabetes during pregnancy in South Asians may favorably alter newborn body composition and require evaluation.

Accuracy of conventional digital palpation and ultrasound of the cricothyroid membrane in obese women in labour.

Success of cricothyroidotomy depends on accurate identification of anatomical neck landmarks. Anaesthetists palpated the cricothyroid membrane of 28 obese and 28 non-obese women in labour (cut-off BMI 30 kg.m(-2) ) and marked the entry point for device insertion with an ultraviolet invisible pen. Ultrasonography was used to mark the midpoint of the cricothyroid membrane and the distance between the two marks was measured. The median (IQR [range]) distance between the two marks was significantly greater in the obese than the non-obese patients (5 (2-9.5 [0-34]) mm vs 1.8 (0.1-6 [0-15]) mm, respectively; p = 0.02). The cricothyroid membrane was accurately identified with digital palpation in only 39% (11/28) of obese compared with 71% (20/28) of non-obese patients (p = 0.03). Increased neck circumference in obese patients was significantly associated with inaccuracy in locating the cricothyroid membrane. Percutaneous identification of the cricothyroid membrane in obese women in labour was poor. Pre-procedural ultrasound may help improved the identification of neck landmarks for cricothyroidotomy.

A field study of lignite as a drying aid in the superheated steam drying of anaerobically digested sludge.

Dried sludge is preferred when the sludge is either to be incinerated or used as a soil amendment. This paper focuses on superheated steam drying which has many benefits, because the system is totally enclosed, thereby minimising odours and particulate emissions. This work reports on field trials at a wastewater treatment plant where anaerobically digested sludge is dried immediately after being dewatered by belt press. The trials showed that unlike previous off-site tests, the sludge could be dried without the addition of a filter aid at a low production rate. However, the trials also confirmed that the addition of the lignite (brown coal) into the anaerobically digested sludge led to a more productive drying process, improved product quality and a greater fraction of the product being in the desired product size range. It is concluded that these results were achieved because the lignite helped to control the granule size in the dryer. Furthermore neither Salmonella spp or E coli were detected in the dried samples. Tests on spontaneous combustion show that this risk is increased in proportion to the amount of lignite used as a drying aid.

Immunohistochemical assessment of proliferating cell nuclear antigen protein expression in plaque, reticular and erosive types of oral lichen planus.

BACKGROUND: Proliferating cell nuclear antigen (PCNA) is a nuclear protein synthesized in the late G1 and S-phase of the cell cycle. Immunodetection of this protein represents a useful marker of the proliferation status of lesions. AIMS: The aim of this study is to evaluate the immunohistochemical expression of PCNA in oral lichen planus (OLP) and to assess the PCNA expression in a different layer of epithelium in different types of OLP. SUBJECTS AND METHODS: A total of 96 cases of histologically proven OLP, 32 cases each of erosive, reticular and plaque type were selected. Two sections were taken from each one for H and E. Other sections were stained according to super sensitive polymer horseradish peroxidase method for identifying PCNA expression. RESULTS: Of the three types of OLP, erosive type showed higher expression of PCNA (average 66.8%, minimum of 55% and maximum of 80.3%) followed by reticular (average 37.7%, minimum of 26% and maximum of 47%) and plaque type (average 17%, minimum of 5% and maximum of 25%) indicating increased proliferative activity. The erosive type also showed higher expression of PCNA in all the layers of epithelium followed by reticular and plaque type. CONCLUSION: PCNA is a good marker to indicate proliferation status of disease. Out of three types, erosive type possess more proliferative ratio, chances of malignant changes is more in this type.

CCL2 release by airway smooth muscle is increased in asthma and promotes fibrocyte migration.

BACKGROUND: Asthma is characterized by variable airflow obstruction, airway inflammation, airway hyper-responsiveness and airway remodelling. Airway smooth muscle (ASM) hyperplasia is a feature of airway remodelling and contributes to bronchial wall thickening. We sought to investigate the expression levels of chemokines in primary cultures of ASM cells from asthmatics vs healthy controls and to assess whether differentially expressed chemokines (i) promote fibrocyte (FC) migration towards ASM and (ii) are increased in blood from subjects with asthma and in sputum samples from those asthmatics with bronchial wall thickening. METHODS: Chemokine concentrations released by primary ASM were measured by MesoScale Discovery platform. The chemokine most highly expressed by ASM from asthmatics compared with healthy controls was confirmed by ELISA, and expression of its cognate chemokine receptor by FCs was examined by immunofluorescence and flow cytometry. The role of this chemokine in FC migration towards ASM was investigated by chemotaxis assays. RESULTS: Chemokine (C-C motif) ligand 2 (CCL2) levels were increased in primary ASM supernatants from asthmatics compared with healthy controls. CCR2 was expressed on FCs. Fibrocytes migrated towards recombinant CCL2 and ASM supernatants. These effects were inhibited by CCL2 neutralization. CCL2 levels were increased in blood from asthmatics compared with healthy controls, and sputum CCL2 was increased in asthmatics with bronchial wall thickening. CONCLUSIONS: Airway smooth muscle-derived CCL2 mediates FC migration and potentially contributes to the development of ASM hyperplasia in asthma.

Clinical significance of small airway obstruction markers in patients with asthma.

BACKGROUND: The role of small airway obstruction in the clinical expression of asthma is incompletely understood. OBJECTIVE: We tested the hypotheses that markers of small airway obstruction are associated with (i) increased asthma severity, (ii) impaired asthma control and quality of life and (iii) frequent exacerbations. METHODS: Seventy-four adults with asthma and 18 healthy control subjects underwent impulse oscillometry (IOS), multiple breath inert gas washout (MBW), body plethysmography, single-breath determination of carbon monoxide uptake and spirometry. Patients completed the six-point Asthma Control Questionnaire (ACQ-6) and standardized Asthma Quality of Life Questionnaire [AQLQ(S)]. Asthma severity was classified according to the Global Initiative for Asthma (GINA) treatment steps. RESULTS: The putative small airway obstruction markers Sacin , resistance at 5 Hz minus resistance at 20 Hz (R5-R20) and reactance area (AX) were not independently associated with asthma severity, control, quality of life or exacerbations. In contrast, markers of total (R5) and mean airway resistance of large and small airways (R20) were significantly higher in the severe asthma group compared with the mild-moderate group (0.47 vs. 0.37, P < 0.05 for R5; 0.39 vs. 0.31, P < 0.01 for R20). The strongest independent contributors to ACQ-6 score were R20 and forced expiratory volume in one second (% pred.), and the strongest independent contributors to AQLQ(S) score were R20 and forced vital capacity (% pred.). A history of one or more exacerbations within the previous year was independently associated with R20. CONCLUSIONS AND CLINICAL RELEVANCE: Previously reported markers of small airway obstruction do not appear to be independently associated with asthma disease expression. In contrast, the IOS parameter R20, a marker of mean airway resistance of both large and small airways, appears to have independent clinical significance. These observations require confirmation in prospective longitudinal studies.

Primary bladder exstrophy closure in neonates: challenging the traditions.

PURPOSE: We describe a novel approach to neonatal bladder exstrophy closure that challenges the role of postoperative immobilization and pelvic osteotomy. MATERIALS AND METHODS: We reviewed the primary management of bladder exstrophy at our institutions between 2007 and 2011. In particular we compared postoperative management in the surgical ward using epidural analgesia to muscle paralysis and ventilation in the intensive care unit. Clinical outcome measures were time to full feed, length of stay, postoperative complications and redo closure. Cost-effectiveness was also evaluated using hospital financial data. Data are expressed as median (range). Significance was explored by Fisher exact test and unpaired t-test. RESULTS: A total of 74 patients underwent primary closure without osteotomy. Successful closure was achieved in 70 patients (95%). A total of 48 cases (65%) were managed on the ward (group A) and 26 (35%) were transferred to the intensive care unit (group B). The 2 groups were homogeneous for gestational age (median 39 weeks, range 27 to 41) and age at closure (3 days, 1 to 152). Complications requiring surgical treatment were noted in 4 patients (8.3%) in group A and 3 (11.5%) in group B (p = 0.609). Length of stay was significantly shorter for the group managed on the ward (11 vs 18 days, p <0.0001). Median costs were $42,732 for patients admitted to the intensive care unit and $16,214 for those admitted directly to the surgical ward (p <0.0001). CONCLUSIONS: Primary closure of bladder exstrophy without lower limb immobilization and osteotomy is feasible. Postoperative care on the surgical ward using epidural analgesia results in shorter hospitalization.

Difficulties in obtaining representative samples for compliance with the Ballast Water Management Convention.

As implementation of the Ballast Water Convention draws nearer a major challenge is the development of protocols which accurately assess compliance with the D-2 Standard. Many factors affect the accuracy of assessment: e.g. large volume of ballast water, the shape, size and number of ballast tanks and the heterogeneous distribution of organisms within tanks. These factors hinder efforts to obtain samples that truly represent the total ballast water onboard a vessel. A known cell density of Tetraselmis suecica was added to a storage tank and sampled at discharge. The factors holding period, initial cell density and sampling interval affected representativeness. Most samples underestimated cell density, and some tanks with an initial cell density of 100 cells ml(-1) showed <10 cells ml(-1) at discharge, i.e. met the D-2 standard. This highlights difficulties in achieving sample representativeness and when applied to a real ballast tank this will be much harder to achieve.