Application of near infra-red laser light increases current threshold in optic nerve consistent with increased Na+-dependent transport.

Increases in the current threshold occur in optic nerve axons with the application of infra-red laser light, whose mechanism is only partly understood. In isolated rat optic nerve, laser light was applied near the site of electrical stimulation, via a flexible fibre optic. Paired applications of light produced increases in threshold that were reduced on the second application, the response recovering with increasing delays, with a time constant of 24 s. 3-min duration single applications of laser light gave rise to a rapid increase in threshold followed by a fade, whose time-constant was between 40 and 50 s. After-effects were sometimes apparent following the light application, where the resting threshold was reduced. The increase in threshold was partially blocked by 38.6 mM Li+ in combination with 5  µ M bumetanide, a manoeuvre increasing refractoriness and consistent with axonal depolarization. Assessing the effect of laser light on the nerve input resistance ruled out a previously suggested fall in myelin resistance as contributing to threshold changes. These data appear consistent with an axonal membrane potential that partly relies on temperature-dependent electroneutral Na+ influx, and where fade in the response to the laser may be caused by a gradually diminishing Na+ pump-induced hyperpolarization, in response to falling intracellular [Na+].

Digitization in Skin Shade Matching for Maxillofacial Prostheses: A Systematic Review.

Color matching of maxillofacial prostheses for the restoration of maxillofacial defects is an important factor for esthetic results. Various methods have been introduced for the accurate and reliable color matching of prostheses with the skin color of patients. A systematic review was conducted to search the existing literature on color-matching digital techniques for maxillofacial prostheses. An electronic literature search was conducted in PubMed/Medline, Scopus, and Web of Science from January 2000 to December 2022 using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Two independent reviewers conducted the search. Eight articles that fulfilled the inclusion criteria after a full-text evaluation were included in this review. Most of these studies were published in prosthodontics journals and conducted in various countries around the world. A computerized color formulation system was used in three studies; a non-contact spectroradiometer (PR 705; Photo Research Inc., Chatsworth, CA) with a Xenon arc lamp was used in two studies; a mobile phone colorimeter was used in one study; additive manufacturing of 3D facial skin with a spectrophotometer was used in one study; and a recently introduced computerized method known as e-skin (Spectromatch, Bath, UK) was used in two studies. Most of these methods were accurate in color matching, except for the additive manufacturing system, which showed less accuracy, but good repeatability. Owing to a lack of sufficient studies, no method can be labeled as the best method for color-matching maxillofacial prostheses. The latest computerized method, the e-skin, can be used to achieve better accuracy and good color matching. However, further studies are required to validate the use of e-skin for precise color matching.

Engineering benefits of replacing natural sand with manufactured sand in landfill construction.

Translational sliding failures in landfills are often triggered by inadequate shear strength of interfaces in liners and covers. Geosynthetic Clay Liners (GCL) are used in different components of landfills to contain the leachate. GCLs are usually placed above a compacted sand subgrade to develop higher shear resistance. In the context of depleting natural sand resources, the present study explores the feasibility of replacing natural sand with manufactured sand (Msand) in landfill construction. Interface shear tests were performed on GCL in contact with river sand and Msand of similar gradation to evaluate the shear strength at different normal stresses and hydration conditions. It is found that Msand provides higher interface shear strength with GCL compared to river sand. Digital image analysis of tested specimens of GCL showed that variation in particle morphology of the two sands has direct influence on the microlevel interaction mechanisms governing the shear strength. Quantification of morphological parameters showed that Msand particles are angular and rough compared to natural sand particles, leading to higher particle interlocking. Hydration of the GCL reduced the interface shear strength, the effect being less in case of Msand. The study highlights that replacement of natural sand with Msand has added benefits.

Impact of Autoantibodies to Complement Components on the Disease Activity in SLE.

INTRODUCTION: Systemic Lupus Erythematosus (SLE) is a chronic multi-system autoimmune disease with varied clinical presentations. Complement components are the major players in disease pathogenesis. This retrospective cross-sectional study was aimed at assessing the role of autoantibodies to these complement components and their association disease activity in newly diagnosed SLE patients from India. METHOD: Clinically diagnosed SLE patients (n=57) classified as per 2015 ACR/SLICC revised criteria were enrolled between November 2016 to April 2017. Patients' sera were tested for C3 and C4 by nephelometry, while serum levels of factor H, factor P (properdin) as well as autoantibodies to C3, C4, factor H and factor P were detected by ELISA. GraphPad Prism Version 6.01 was used for statistical analysis. Mean, SD, SEM were calculated. Mann Whittney U-test, ANOVA, Chi-square test, Odd's Ratio were calculated. Pearson's correlation was used to study relativeness of the study parameters. RESULTS: Among the 57 SLE patients, low C3 were seen in 51% patients, low C4 in 49%, low factor H in 19% and low factor P in 49% patients. Positivity for autoantibodies against complement components, anti-C3 were seen in 42% patients, anti-C4 in 7%, anti-factor H in 19% and anti-factor P in 28% patients. Serum levels of C3 (p=0.0009), C4 (p=0.0031) and anti-C3 autoantibodies (p=0.0029) were significantly associated with ACR/SLICC 2015 scores. CONCLUSION: Hypocomplementemia was found to be associated with higher disease damage score in newly diagnosed SLE patients. This study adds novel arguments for the importance of the anti-C3 autoantibodies as a marker of SLE.

Role of MMP-2 and its inhibitor TIMP-2 as biomarkers for susceptibility to systemic lupus erythematosus.

Aim: To investigate the possible association between MMP-2 (-1575 G/A, -1306 C/T) and its inhibitor TIMP-2 (-418 G/C) functional polymorphisms with development of severity in systemic lupus erythematosus (SLE) patients. Materials & methods: 150 SLE patients and matched healthy controls were recruited. Polymorphisms were detected by PCR-RFLP and serum levels by ELISA. Results: Mean MMP-2 and TIMP-2 serum level and mRNA expression were significantly increased in SLE cases as compared with controls (p < 0.0001). The concomitant presence of both MMP-2 1575A and its inhibitor TIMP-2 418C alleles synergistically increased the risk of SLE by 3.25-fold (CI: 1.44-7.34, p = 0.003). Conclusion: MMP-2, TIMP-2 and MMP-2/TIMP-2 ratios may act as biomarkers for susceptibility to SLE.

Infections in Systemic Lupus Erythematosus.

OBJECTIVES: Infections are a major cause of morbidity and mortality in patients of Systemic Lupus erythematosus (SLE). We therefore aimed to determine the spectrum of infections in patients of SLE, find a correlation between various disease parameters and the severity and outcome of infections and to compare the outcome between different modalities of immunosuppressive therapy. METHODS: A cross-sectional study was carried out by including all the diagnosed patients of Systemic lupus erythematosus (based on SLICC criteria[1]) aged 12 years and above who developed infections during the study period of 18 months. Immunocompromised patients because of coexisting diseases like diabetes, retroviral disease and cancer patients on immunosuppression were excluded. 139 cases of infections were identified in 104 patients of SLE during the study period. RESULTS: 92 patients had one episode of infection, 19 patients had two episodes and 3 patients contracted infections thrice during the study period. The mean age of the sample population was 29.45 ± 7.9 years. 21-30 years age group constituted 51.75% (59/114) of the patients. 61/139 infections (44%) were bacterial, 22/139 (16%) fungal, 20/139 (14%) viral and 4/139 (3%) parasitic. Tuberculosis was the most common infection (40/139, 28.78%). Lower respiratory tract was the most common site of infections found in the study (37/139, 26.62%). 75/139 (54%) were major infections. 50% tuberculous infections were extrapulmonary. The mean duration of SLE until the time of infection was 35.84 ± 53.80 months. SLE Disease Activity Index (SLEDAI) was ≥ 5 in 92.09% of cases. End organ damage was found in 82.7% (115 cases) and amongst them, renal lupus was found in 110/115 cases. No association was found between end organ damage and severity or outcome of infections. In 89 cases patients were on prednisolone alone, in 29 cases patients were additionally on Cyclophosphamide or had received it in the past, and in 15 cases Mycophenolate mofetil (MMF) with prednisolone while in 6 cases all the three drugs had been given at some point of time. Tuberculosis was the most common infection amongst all the groups. The mean daily dose of prednisolone was 19.62 ± 16.04 mg/day. The mean cumulative steroid dose in patients of our study was 9165.76 ± 7833.72 mg. Central nervous system infections occurred more in patients who had received Cyclophosphamide (p = 0.01). Five deaths occurred due to life threatening infections and all of them were either on high dose prednisolone or on cytotoxic drugs (Cyclophosphamide/Mycophenolate mofetil [MMF]). There was no association between treatment modality and severity and outcome of infection. CONCLUSION: SLE patients are predisposed to various minor as well as lifethreatening infections. It is essential to prevent infections by screening, reducing exposure to sources or contacts of infection and minimizing the exposure to immunosuppressive agents while controlling disease activity.

Vault packaged enzyme mediated degradation of amino-aromatic energetic compounds.

Amino-aromatic compounds, 2-amino-4-nitrotoluene (ANT), and 2,4-diaminotoluene (DAT) are carcinogens and environmentally persistent pollutants. In this study, we investigated their degradation by natural manganese peroxidase (nMnP) derived from Phanerochaete chrysosporium and recombinant manganese peroxidase packaged in vaults (vMnP). Encapsulation of manganese peroxidase (MnP) in ribonucleoprotein nanoparticle cages, called vaults, was achieved by creating recombinant vaults in yeast Pichia pastoris. Vault packaging increased the stability of MnP by locally sequestering multiple copies of the enzyme. Within 96  h, both vMnP and nMnP catalyzed over 72% removal of ANT in-vitro, which indicates that vault packaging did not limit substrate diffusion. It was observed that vMnP was more efficient than nMnP and P. chrysosporium for the catalysis of target contaminants. Only 57% of ANT was degraded by P. chrysosporium even when MnP activity reached about 480 U L-1 in cultures. At 1.5 U L-1 initial activity, vMnP achieved 38% of ANT and 51% of DAT degradation, whereas even 2.7 times higher activity of nMnP showed insignificant biodegradation of both compounds. These results imply that due to protection by vault cages, vMnP has lower inactivation rates. Thus, it works effectively at lower dosage for a longer duration compared to nMnP without requiring frequent replenishment. Collectively, these results indicate that fungal enzymes packaged in vault nanoparticles are more stable and active, and they would be effective in biodegradation of energetic compounds in industrial processes, waste treatment, and contaminated environments.

Fibrotic Cytokine Interplay in Evaluation of Disease Activity in Treatment Naïve Systemic Sclerosis Patients from Western India.

BACKGROUND: : Systemic sclerosis (SSc) is a demyelinating disease of skin, subcutaneous tissue, muscles and internal organs, with fibrosis as an important pathological event. AIM: : To understand cytokine interplay of IL-1ß, IL-4 and IL-6 and their association with disease activity in treatment naïve active cases of systemic sclerosis from Western India. METHODS: Twenty-five SSc patients as per ACR-EULAR 2013 criteria (classified based on pulmonary fibrosis and generalized fibrosis) and 25 age-sex matched controls were enrolled. Serum cytokine levels of IL-1ß, IL-4 and IL-6 were assessed by multiplex bead based immunoassay. RESULTS: Ten patients had Interstitial lung disease (ILD), whereas, 16 patients had generalized fibrosis. Anti-nuclear antibodies were seen in 22 patients (88%); antiScl70 in 15 patients (60%) and anti-Centromere antibodies in 5 patients (20%). Serum levels of IL-1ß in patients were significantly higher than healthy controls (p=0.0006). IL-4 levels in all SSc patients were marginally raised (p=0.0102), while IL-6 levels were significantly raised (p<0.0001). IL-4 was found to be significantly raised in SSc patients with ILD (p=0.021) as compared to patients without ILD. IL-1ß (p=0.0293) and IL-4 (p<0.0001) were significantly higher in SSc patients with fibrosis. On the contrary, IL-6 levels in patients with fibrosis were found to be lower than in patients without fibrosis. CONCLUSION: Significantly raised cytokine levels among treatment naïve systemic sclerosis patients were found to be associated with higher disease severity in our study. Higher levels of IL-1ß and IL-6 indicated an active inflammatory status, whereas significantly raised IL-4 levels indicated at higher fibrotic activity.

Association between genetic polymorphisms of CYP2C9 and VKORC1 and safety and efficacy of warfarin: Results of a 5 years audit.

OBJECTIVE: Genetic polymorphisms of CYP2C9 and VKORC1 play major role in pharmacokinetics and pharmacodynamics of warfarin, respectively. Purpose of our study was to assess the utility of pretesting patients for the above mutations in predicting tendency for bleeding and achieving target INR. METHODS: This was an audit of data collected between July 2011 and December 2016. For safety and efficacy, patients were divided into two subgroups: those with or without bleeding and those who achieved target INR or not. Chi square test was applied to compare the between group differences and crude Odds Ratio (cOR) calculated. RESULTS: Among 521 patients evaluated, most common indication for warfarin therapy was valvular heart disease (210/521 = 40%); 36% (187/521) had at least one bleeding episode; 56% (269/479) had below target INR. 26% (136/521) had polymorphic alleles of CYP2C9 and 69% (358/521) had the GG haplotype of VKORC1. Polymorphic alleles of CYP2C9 or AG/AA haplotype had twice the odds of bleeding (cOR = 2.14 and 2.44 respectively) relative to those with wild CYP2C9 allele or GG haplotype. Combined CYP2C9 mutant alleles and/or AG/AA haplotypes had thrice the odds of bleeding (cOR = 3.12) relative to those with wild CYP2C9 alleles and GG haplotype. Those with GG haplotype had twice the odds (cOR = 1.81) and those with GG haplotype along with wild CYP2C9 allele had four times the odds (cOR = 4.27) of not achieving the target INR relative to those with other haplotype/alleles. All these associations were statistically significant (p < 0.05). CONCLUSIONS: Pretesting patients for genetic polymorphisms could aid in individualizing warfarin therapy.

A functional SNP MCP-1 (-2518A/G) predispose to renal disorder in Indian Systemic Lupus Erythematosus patients.

Systemic Lupus Erythematosus (SLE) is a clinically heterogeneous chronic, inflammatory autoimmune disorder that affects multiple organs where exact etiology of the disease is not yet clearly understood. Various evidences suggest that genetic polymorphisms in inflammatory mediators like cytokines and chemokines may influence development of the disease. Here, we investigated whether functional polymorphism at the Monocyte Chemoattractant Protein-1 (MCP-1) regulatory region associates with disease phenotype in Indian SLE patients. This case control study included 200 SLE patients and 201 ethnically matched healthy controls. Genotyping of MCP-1 (-2518 A/G) polymorphism was performed using PCR-RFLP method. Serum MCP-1 levels were detected by bead-based multiplex immunoassay. Serum MCP-1 levels were found to be higher in patients compared with healthy individuals (p<0.0001). A significant difference for MCP-1G allele frequency (OR=1.9, 95%CI=1.4-2.6, p<0.0001) was observed among SLE patients against healthy individuals. A significant difference in the distribution of MCP-1 -2518GG (OR=3.0, 95%CI=1.4-6.7, p=0.0041) and AG+GG genotypes (OR=2.0, 95%CI=1.4-3.0, p=0.0005) was also noted among SLE patients when compared with healthy individuals. A significant association was observed between A/G and G/G versus A/A genotypes with renal manifestations (p<0.0001, Pc<0.001). Serum MCP-1 levels in active LN patients were found to be significantly higher than inactive LN (p=0.0059), mild LN (p=0.0061) as well as non-LN patients (p=0.0001). These findings suggest that -2518G allele of MCP-1 -2518 A/G polymorphism is associated with renal disorders and may influence MCP-1 gene expression among Indian SLE patients.

Development of model for prediction of Leachate Pollution Index (LPI) in absence of leachate parameters.

Leachate pollution index (LPI) is an environmental index which quantifies the pollution potential of leachate generated in landfill site. Calculation of Leachate pollution index (LPI) is based on concentration of 18 parameters present in leachate. However, in case of non-availability of all 18 parameters evaluation of actual values of LPI becomes difficult. In this study, a model has been developed to predict the actual values of LPI in case of partial availability of parameters. This model generates eleven equations that helps in determination of upper and lower limit of LPI. The geometric mean of these two values results in LPI value. Application of this model to three landfill site results in LPI value with an error of ±20% for ∑inwi⩾0.6.

Impact of TNF-α and LTα gene polymorphisms on genetic susceptibility in Indian SLE patients.

The promoter polymorphisms of tumour necrosis factor-α (TNF-α) and intronic Lymphotoxin-α (LTα) have been implicated as genetic risk factors for systemic lupus erythematosus (SLE) in various ethnic groups. The aim of this study was to investigate an impact of TNF-α (-308G/A; 238G/A) and LTα (+252A/G) gene polymorphisms in disease susceptibility among Indian 200 SLE patients along with 201 healthy controls. The gene polymorphisms were studied by using direct DNA sequencing and Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) methods. Serum levels were measured by multiplex assay. Allelic frequencies of TNF-α -308A (OR=2.3, p=0.0001, Pc=0.0003) and LTα +252G (OR=2.1, p<0.0001, Pc<0.001) were significantly higher in SLE patients. Frequency of haplotype-AGG was found to be higher in patients than controls (OR=12.2, p=0.0050). Serum levels of TNF-α and LTα also were found to be significantly higher in patients showing variant alleles. TNF-α -308G/A+A/A genotypes (p<0.01) and LTα +252 A/G+G/G genotypes (p<0.02) were significantly associated with renal disorders and haematological manifestations. SLE patients with -308G/A+A/A genotypes showed higher prevalence of anti-dsDNA antibodies (OR=3.9, p=0.0014, Pc=0.0098) and anti-Sm antibodies (OR=4.1, p=0.0002, Pc=0.0014). The present study suggests TNF-α -308A and LTα +252G as risk alleles for disease susceptibility associated with higher serum levels of TNF-α and LTα and concomitant discrete clinical features among Indian SLE patients.

Testing the Feasibility of Remote Patient Monitoring in Prenatal Care Using a Mobile App and Connected Devices: A Prospective Observational Trial.

BACKGROUND: Excessive weight gain and elevated blood pressure are significant risk factors for adverse pregnancy outcomes such as gestational diabetes, premature birth, and preeclampsia. More effective strategies to facilitate adherence to gestational weight gain goals and monitor blood pressure may have a positive health benefit for pregnant women and their babies. The impact of utilizing a remote patient monitoring system to monitor blood pressure and weight gain as a component of prenatal care has not been previously assessed. OBJECTIVE: The objective of this study is to determine the feasibility of monitoring patients remotely in prenatal care using a mobile phone app and connected digital devices. METHODS: In this prospective observational study, 8 women with low risk pregnancy in the first trimester were recruited at an urban academic medical center. Participants received a mobile phone app with a connected digital weight scale and blood pressure cuff for at-home data collection for the duration of pregnancy. At-home data was assessed for abnormal values of blood pressure or weight to generate clinical alerts to the patient and provider. As measures of the feasibility of the system, participants were studied for engagement with the app, accuracy of remote data, efficacy of alert system, and patient satisfaction. RESULTS: Patient engagement with the mobile app averaged 5.5 times per week over the 6-month study period. Weight data collection and blood pressure data collection averaged 1.5 times and 1.1 times per week, respectively. At-home measurements of weight and blood pressure were highly accurate compared to in-office measurements. Automatic clinical alerts identified two episodes of abnormal weight gain with no false triggers. Patients demonstrated high satisfaction with the system. CONCLUSIONS: In this pilot study, we demonstrated that a system using a mobile phone app coupled to remote monitoring devices is feasible for prenatal care.

Data in support of FSH induction of IRS-2 in human granulosa cells: Mapping the transcription factor binding sites in human IRS-2 promoter.

Insulin receptor substrate-2 (IRS-2) plays critical role in the regulation of various metabolic processes by insulin and IGF-1. The defects in its expression and/or function are linked to diseases like polycystic ovary syndrome (PCOS), insulin resistance and cancer. To predict the transcription factors (TFs) responsible for the regulation of human IRS-2 gene expression, the transcription factor binding sites (TFBS) and the corresponding TFs were investigated by analysis of IRS-2 promoter sequence using MatInspector Genomatix software (Cartharius et al., 2005 [1]). The ibid data is part of author׳s publication (Anjali et al., 2015 [2]) that explains Follicle stimulating hormone (FSH) mediated IRS-2 promoter activation in human granulosa cells and its importance in the pathophysiology of PCOS. Further analysis was carried out for binary interactions of TF regulatory genes in IRS-2 network using Cytoscape software tool and R-code. In this manuscript, we describe the methodology used for the identification of TFBSs in human IRS-2 promoter region and provide details on experimental procedures, analysis method, validation of data and also the raw files. The purpose of this article is to provide the data on all TFBSs in the promoter region of human IRS-2 gene as it has the potential for prediction of the regulation of IRS-2 gene in normal or diseased cells from patients with metabolic disorders and cancer.

FSH stimulates IRS-2 expression in human granulosa cells through cAMP/SP1, an inoperative FSH action in PCOS patients.

Follicle stimulating hormone (FSH) plays a central role in growth and differentiation of ovarian follicles. A plethora of information exists on molecular aspects of FSH responses but little is known about the mechanisms involved in its cross-talk with insulin/IGF-1 pathways implicated in the coordination of energy homeostasis in preovulatory granulosa cells (GCs). In this study, we hypothesized that FSH may regulate IRS-2 expression and thereby maintain the energy balance in GCs. We demonstrate here that FSH specifically increases IRS-2 expression in human and rat GCs. FSH-stimulated IRS-2 expression was inhibited by actinomycin D or cycloheximide. Furthermore, FSH decreases IRS-2 mRNA degradation indicating post-transcriptional stabilization. Herein, we demonstrate a role of cAMP pathway in the activation of IRS-2 expression by FSH. Scan and activity analysis of IRS-2 promoter demonstrated that FSH regulates IRS-2 expression through SP1 binding sites. FSH stimulates SP1 translocation into nucleus and its binding to IRS-2 promoter. These results are corroborated by the fact that siRNA mediated knockdown of IRS-2 decreased the FSH-stimulated PI3K activity, p-Akt levels, GLUT4 translocation and glucose uptake. However, FSH was not able to increase IRS-2 expression in GCs from PCOS women undergoing IVF. Interestingly, IRS-2 mRNA expression was downregulated in GCs from the PCOS rat model. Taken together, our findings establish that FSH induces IRS-2 expression and thereby activates PI3K, Akt and glucose uptake. Crucially, our data confirms a molecular defect in FSH action in PCOS GCs which may cause deceleration of metabolism and follicular growth leading to infertility. These results lend support for a therapeutic potential of IRS-2 in the management of PCOS.

Recombination in the human Pseudoautosomal region PAR1.

The pseudoautosomal region (PAR) is a short region of homology between the mammalian X and Y chromosomes, which has undergone rapid evolution. A crossover in the PAR is essential for the proper disjunction of X and Y chromosomes in male meiosis, and PAR deletion results in male sterility. This leads the human PAR with the obligatory crossover, PAR1, to having an exceptionally high male crossover rate, which is 17-fold higher than the genome-wide average. However, the mechanism by which this obligatory crossover occurs remains unknown, as does the fine-scale positioning of crossovers across this region. Recent research in mice has suggested that crossovers in PAR may be mediated independently of the protein PRDM9, which localises virtually all crossovers in the autosomes. To investigate recombination in this region, we construct the most fine-scale genetic map containing directly observed crossovers to date using African-American pedigrees. We leverage recombination rates inferred from the breakdown of linkage disequilibrium in human populations and investigate the signatures of DNA evolution due to recombination. Further, we identify direct PRDM9 binding sites using ChIP-seq in human cells. Using these independent lines of evidence, we show that, in contrast with mouse, PRDM9 does localise peaks of recombination in the human PAR1. We find that recombination is a far more rapid and intense driver of sequence evolution in PAR1 than it is on the autosomes. We also show that PAR1 hotspot activities differ significantly among human populations. Finally, we find evidence that PAR1 hotspot positions have changed between human and chimpanzee, with no evidence of sharing among the hottest hotspots. We anticipate that the genetic maps built and validated in this work will aid research on this vital and fascinating region of the genome.

Unprecedented development of anammox in presence of organic carbon using seed biomass from a tannery Common Effluent Treatment Plant (CETP).

This work describes development of a microbial consortium dominant in anammox in presence of organic carbon (available through cell lyses) by employing simple sequencing batch operation in 23 cycles exceeding 400days. Seed biomass from a tannery Common Effluent Treatment Plant (CETP) was enriched for anammox and attained maximum removals of NH4-N (95%) and NO2-N (98%). The anammox was confirmed by nitrogen mass balance in a controlled batch experiment and by DNA extraction-PCR-agarose gel electrophoresis. The effective anammox followed first order reaction kinetics with rate constant of 0.0141/h and half-saturation constant of 10.6mg/L. Evidence for coexistence of denitrification (99% NO2-N removal) and anammox (57.8% NH4-N removal) was demonstrated. This study opens-up possible application of microbial consortium dominant in anammox for simultaneous removal of ammonia and organic carbon from wastewaters.

Transmylohoid/Submental Endotracheal Intubation in Pan-facial Trauma: A Paradigm Shift in Airway Management with Prospective Study of 35 Cases.

The present study was planned to assess the efficacy, utility and complications of transmylohoid intubation in facial polytrauma patients, by setting and design: prospective study. This study was conducted between May 2008 and May 2011 and 35 patients of facial polytrauma were included irrespective of sex, caste and religion. All the selected 35 patients were male and the age of patients ranged between 15 to 45 years (mean age 31 years). All the patients were intubated with transmylohoid, orotracheal intubation using an armoured endotracheal tube (ETT). Average time to perform transmylohoid intubation was 15.51 + 1.85 min (mean + standarad deviation). Average time for drawing the ETT transmylohoid from the submental incision was 49.7 + 24.8 s. Mean duration for which the ETT was kept indwelling was 0.37 + 1.03 days. Accidental extubation of ETT was noted in two patients. Minor post operative complications like swelling in the submental area (2 patient), dehiscence of the submental incision (2 patient) and minor infection at the site of submental incision (3 patients) were noticed, which were found to be statistically insignificant. The transmylohoid intubation allowed simultaneous reduction and fixation of all the facial fractures and intraoperative control of dental occlusion without interference from the tube during the surgery without interfering in the maintenance of the anesthesia and air way.

Biologics in SLE: the current status.

Systemic lupus erythematosus (SLE) can be a severe and potentially life-threatening disease that often represents a therapeutic challenge because of its heterogeneous organ manifestations. Only glucocorticoids, hydroxychloroquine, mycophenolate mofetil, azathioprine, cyclophosphamide, and very recently belimumab have been approved for SLE therapy. Dependence on glucocorticoids and resistance to the approved therapeutic agents, as well as substantial toxicity, are frequent. B-cells abnormalities leading to autoantibody production play a central role in Systemic Lupus Erythematosus (SLE) pathogenesis. The targets of these biological therapies are directed toward the B cell depletion, interference in the co-stimulation signals and the blockade of cytokines. Biologic agents targeting specific pathways (i.e. T-B lymphocyte interaction, cytokines and complement) have been also proposed as new tools for SLE treatment. B-cell targeted therapies, including anti-B lymphocyte stimulator (BLyS) and anti-CD20 monoclonal antibodies are at forefront of new SLE treatment. Results from randomized trials in systemic lupus erythematosus (SLE) have been very disappointing, with lack of efficacy for some drugs and development of severe side-effects such as infections for others. Fortunately, as more and more trials of biologics in the treatment of lupus are being performed, the first promising results have been achieved. Today, belimumab is expected to become the first approved drug for use in lupus in several decades. In this review we will focus on biological drugs whose potential efficacy have been evaluated in open-label and randomized clinical trials. Biologics provide encouraging results that represent a possible option in the treatment of refractory lupus. Thus we review recent clinical trials in patients with systemic lupus erythematosus (SLE), with emphasis on outcomes and on mechanisms by which the biological agents suppress autoimmunity.

The landscape of recombination in African Americans.

Recombination, together with mutation, gives rise to genetic variation in populations. Here we leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P value < 10(-245)). We identify a 17-base-pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of PRDM9 alleles common in West Africans and rare in Europeans. Sites of this motif are predicted to be risk loci for disease-causing genomic rearrangements in individuals carrying these alleles. More generally, this map provides a resource for research in human genetic variation and evolution.