Residual ctDNA after treatment predicts early relapse in patients with early-stage non-small cell lung cancer.

BACKGROUND: Identification of residual disease in patients with localized non-small cell lung cancer (NSCLC) following treatment with curative intent holds promise to identify patients at risk of relapse. New methods can detect circulating tumour DNA (ctDNA) in plasma to fractional concentrations as low as a few parts per million, and clinical evidence is required to inform their use. PATIENTS AND METHODS: We analyzed 363 serial plasma samples from 88 patients with early-stage NSCLC (48.9%/28.4%/22.7% at stage I/II/III), predominantly adenocarcinomas (62.5%), treated with curative intent by surgery (n = 61), surgery and adjuvant chemotherapy/radiotherapy (n = 8), or chemoradiotherapy (n = 19). Tumour exome sequencing identified somatic mutations and plasma was analyzed using patient-specific RaDaR™ assays with up to 48 amplicons targeting tumour-specific variants unique to each patient. RESULTS: ctDNA was detected before treatment in 24%, 77% and 87% of patients with stage I, II and III disease, respectively, and in 26% of all longitudinal samples. The median tumour fraction detected was 0.042%, with 63% of samples <0.1% and 36% of samples <0.01%. ctDNA detection had clinical specificity >98.5% and preceded clinical detection of recurrence of the primary tumour by a median of 212.5 days. ctDNA was detected after treatment in 18/28 (64.3%) of patients who had clinical recurrence of their primary tumour. Detection within the landmark timepoint 2 weeks to 4 months after treatment end occurred in 17% of patients, and was associated with shorter recurrence-free survival [hazard ratio (HR): 14.8, P <0.00001] and overall survival (HR: 5.48, P <0.0003). ctDNA was detected 1-3 days after surgery in 25% of patients yet was not associated with disease recurrence. Detection before treatment was associated with shorter overall survival and recurrence-free survival (HR: 2.97 and 3.14, P values 0.01 and 0.003, respectively). CONCLUSIONS: ctDNA detection after initial treatment of patients with early-stage NSCLC using sensitive patient-specific assays has potential to identify patients who may benefit from further therapeutic intervention.

First Direct Detection Constraints on Planck-Scale Mass Dark Matter with Multiple-Scatter Signatures Using the DEAP-3600 Detector.

Dark matter with Planck-scale mass (≃10^{19} GeV/c^{2}) arises in well-motivated theories and could be produced by several cosmological mechanisms. A search for multiscatter signals from supermassive dark matter was performed with a blind analysis of data collected over a 813 d live time with DEAP-3600, a 3.3 t single-phase liquid argon-based detector at SNOLAB. No candidate signals were observed, leading to the first direct detection constraints on Planck-scale mass dark matter. Leading limits constrain dark matter masses between 8.3×10^{6} and 1.2×10^{19} GeV/c^{2}, and ^{40}Ar-scattering cross sections between 1.0×10^{-23} and 2.4×10^{-18} cm^{2}. These results are interpreted as constraints on composite dark matter models with two different nucleon-to-nuclear cross section scalings.

BL-02: a versatile X-ray scattering and diffraction beamline for engineering applications at Indus-2 synchrotron source.

A hard X-ray engineering applications beamline (BL-02) was commissioned recently and started operation in March 2019 at the Indian synchrotron source, Indus-2. This bending-magnet-based beamline is capable of operating in various beam modes, viz. white, pink and monochromatic beam. The beamline utilizes the X-ray diffraction technique in energy-dispersive and angle-dispersive modes to carry out experiments mainly focused on engineering problems, viz. stress measurement, texture measurement and determination of elastic constants in a variety of bulk as well as thin-film samples. An open-cradle six-circle diffractometer with ∼12 kg load capacity allows accommodation of a wide variety of engineering samples and qualifies the beamline as a unique facility at Indus-2. The high-resolution mode of this beamline is suitably designed so as to carry out line profile analysis for characterization of micro- and nano-structures. In the present article the beamline is described starting from the beamline design, layout, optics involved, various operational modes and experimental stations. Experiments executed to validate the beamline design parameters and to demonstrate the capabilities of the beamline are also described. The future facilities to be incorporated to enhance the capabilities of the beamline are also discussed.

Adaptation to life on land at high O2 via transition from ferredoxin-to NADH-dependent redox balance.

Pyruvate : ferredoxin oxidoreductase (PFO) and iron only hydrogenase ([Fe]-HYD) are common enzymes among eukaryotic microbes that inhabit anaerobic niches. Their function is to maintain redox balance by donating electrons from food oxidation via ferredoxin (Fd) to protons, generating H2 as a waste product. Operating in series, they constitute a soluble electron transport chain of one-electron transfers between FeS clusters. They fulfil the same function-redox balance-served by two electron-transfers in the NADH- and O2-dependent respiratory chains of mitochondria. Although they possess O2-sensitive FeS clusters, PFO, Fd and [Fe]-HYD are also present among numerous algae that produce O2. The evolutionary persistence of these enzymes among eukaryotic aerobes is traditionally explained as adaptation to facultative anaerobic growth. Here, we show that algae express enzymes of anaerobic energy metabolism at ambient O2 levels (21% v/v), Chlamydomonas reinhardtii expresses them with diurnal regulation. High O2 environments arose on Earth only approximately 450 million years ago. Gene presence/absence and gene expression data indicate that during the transition to high O2 environments and terrestrialization, diverse algal lineages retained enzymes of Fd-dependent one-electron-based redox balance, while the land plant and land animal lineages underwent irreversible specialization to redox balance involving the O2-insensitive two-electron carrier NADH.

Demodex canis targets TLRs to evade host immunity and induce canine demodicosis.

Widespread incidence of Demodex mites throughout the mammalian class and occasional serious and fatal outcomes in dogs warrant an insight into the host-parasite interface especially. Therefore, this study was aimed to unravel the interplay between innate immune response and canine demodicosis. The dogs diagnosed to have natural clinical demodicosis were allocated into two groups; dogs with localized demodicosis (LD) and with generalized demodicosis (GD). The expression of toll-like receptors (TLRs) 2, 4 and 6 genes in peripheral blood mononuclear cells of these dogs was quantified by real-time PCR. Significantly increased TLR2 gene expression, while significantly diminished TLR4 and TLR6 gene expressions were observed in demodicosed dogs (LD and GD) as compared with the healthy ones. Even the expression of TLR2 gene was found to differ significantly between the dogs with LD and GD. Therefore, it can be inferred that clinical demodicosis in dogs is coupled with an up-regulation of TLR2 and down-regulation of TLR4 and TLR6 gene expressions. Overexpression of TLR2 gene might be responsible for Demodex-induced clinical manifestations, while TLR4 and TLR6 gene down-regulations could be the paramount strategy of Demodex mites to elude the host-immune interface.

Inpatient burden of esophageal cancer and analysis of factors affecting in-hospital mortality and length of stay.

Esophageal cancer (EC) continues to be a major source of morbidity and mortality in the United States. However, there has been a relative dearth of research into hospital utilization in patients with EC. This study examines temporal trends in hospital admissions, length of stay (LOS), mortality, and costs associated with EC. In addition, we also analyzed factors associated with inpatient mortality and LOS. We interrogated National Inpatient Sample (NIS), a large registry of inpatient data, to retrieve information about various demographic and factors associated with hospital stay in patients who were admitted for EC between the years 1998 and 2013 in the United States. After examining trends over time, multivariate analysis was performed to identify factors associated with LOS and mortality. During 1998-2013, 538,776 hospital stays with principal diagnosis of EC were reviewed. Number of hospital stays and inpatient charges increased by 397 per year (±67.8; P < 0.0001) and $3,033 per patient per year (±135; <0.0001) respectively. Mortality and LOS decreased by 0.23% per year (±0.03; P < 0.0001) and 0.07 days per year (±0.006; P < 0.0001) respectively. Multiple factors associated with LOS and mortality were outlined. Despite overall increase in hospital utilization with respect to number of admissions and inpatient charges, inpatient mortality and LOS associated with EC declined. Factors associated with inpatient mortality and LOS may help drive clinical decision-making and influence healthcare or hospital policy.

Power outages and refrigerated medicines: The need for better guidelines, awareness and planning.

WHAT IS KNOWN AND OBJECTIVE: Vaccines and other pharmaceuticals are essential medical supplies that require continuous storage at specific temperatures to maintain viability. Power outages can lead to a break in the cold chain, resulting in the degradation of essential medicines. COMMENT: After a power outage, the stability of vaccines and other medicines can be difficult to ascertain. Many public health guidelines therefore recommend discarding potentially compromised pharmaceuticals unless the cold chain can be guaranteed-a costly endeavour. There are government guidelines aimed at minimizing exposure to high temperatures in the event of a power outage; however, the usefulness of these guidelines is uncertain. WHAT IS NEW AND CONCLUSION: The actual cost of vaccine and pharmaceutical loss due to a break in the cold chain is poorly studied and requires further research. Additional recommendations regarding the stability of specific medicines would also be a valuable resource.

Synthesis of OSL nanophosphor Li3B7O12:Mn and its dosimetric properties.

The present paper reports the structural, morphological and optical properties of nanophosphor Li3B7O12:Mn with an optimised dopant concentration of 0.25 mol% and its surface modification under the irradiation of 250 keV proton beams and gamma photons for ion fluence ranging from 1 × 1013 to 6.25 × 1015 ions cm-2 and doses from 100 mGy-100 Gy, respectively. This nanophosphor has been synthesised by the high temperature solid state reaction method. Its optical properties are characterised by optically stimulated luminescence (OSL) and thermo luminescence (TL) techniques. This nanophosphor is polycrystalline in nature with a grain size of 40-80 nm confirmed by x-ray diffraction (XRD) and transmission electron microscopy (TEM). The OSL decay and TL glow curve response of the proton beam irradiated samples exhibit significant intensity at a fluence of 2.5 × 1014 ions cm-2. Moreover, Li3B7O12:Mn displays a linear response for gamma doses in the range of 100 mGy-50 Gy. We have also investigated the reusability and reproducibility of this material. The above study demonstrates that Li3B7O12:Mn is a robust and promising candidate for medical proton dosimetry.

Isolation of antibacterial protein from Lactobacillus spp. and preparation of probiotic curd.

The study was aimed to isolate antagonistic lactobacilli and the molecules responsible for their antagonistic ability from curd. Preparation of probiotic curd and the ability of the selected lactobacilli to suppress the pathogen therein was also assessed. All the 116 isolates were identified as Lactobacillus spp. based on morphological, biochemical and curdling assays. Five of these lactobacilli (Lb-17, Lb-33, Lb-108, Lb-112, and Lb-N3) were found most promising to inhibit all test pathogens (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Salmonella typhi and Shigella sonnei). The cell-free culture supernatants of these five lactobacilli were recorded as thermo-tolerant when subjected to heat treatment at 100 °C for 20 min. The loss in the activity after protease treatment indicated the proteinaceous nature of the antimicrobial molecule present in the culture supernatants. Active protein (19 kDa) produced by lactobacilli was confirmed by SDS-PAGE followed by agar-overlay method. Antibiotic sensitivity assay revealed that the selected Lactobacillus spp. isolates were resistant to methicillin and vancomycin. Probiotic curd prepared by using Lb-108 and Lb-N3 was found to be superior to rest of the three isolates based on organoleptic tests and shelf-life. Complete inhibition of all the test pathogens in curd was shown by Lb-108 and Lb-N3. Inhibition spectrum, production of thermostable protein and preparation of quality curd suggest Lb-108 and Lb-N3 as promising candidates to prepare probiotic curd.

Demodex canis regulates cholinergic system mediated immunosuppressive pathways in canine demodicosis.

Demodex canis infestation in dogs remains one of the main challenges in veterinary dermatology. The exact pathogenesis of canine demodicosis is unknown but an aberration in immune status is considered very significant. No studies have underpinned the nexus between induction of demodicosis and neural immunosuppressive pathways so far. We have evaluated the involvement of cholinergic pathways in association with cytokines regulation as an insight into the immuno-pathogenesis of canine demodicosis in the present study. Remarkable elevations in circulatory immunosuppressive cytokine interleukin-10 and cholinesterase activity were observed in dogs with demodicosis. Simultaneously, remarkable reduction in circulatory pro-inflammatory cytokine tumour necrosis factor-alpha level was observed in dogs with demodicosis. Findings of the present study evidently suggest that Demodex mites might be affecting the cholinergic pathways to induce immunosuppression in their host and then proliferate incessantly in skin microenvironment to cause demodicosis.

A randomized clinical trial comparing basal insulin peglispro and insulin glargine, in combination with prandial insulin lispro, in patients with type 1 diabetes: IMAGINE 1.

AIMS: The primary objective was to demonstrate that basal insulin peglispro (BIL) was non-inferior compared with insulin glargine (GL) for haemoglobin A1c (HbA1c) at 26 weeks with a non-inferiority margin of 0.4%. MATERIALS AND METHODS: IMAGINE 1 was a Phase 3, open-label, parallel-arm study conducted in nine countries. Adults with type 1 diabetes (n = 455) were randomized (2:1) to bedtime BIL or GL in combination with prandial insulin lispro for 78 weeks, with a primary endpoint of 26 weeks. An electronic diary facilitated data capture and insulin dosing calculations for intensive insulin management. RESULTS: At 26 weeks, mean HbA1c was 7.06% ± 0.04% and 7.43% ± 0.06% for patients assigned to BIL (N = 295) and GL (N = 160), respectively (difference -0.37% [95% CI: -0.50 to -0.23], P < .001); more patients on BIL achieved HbA1c <7% (44.9% vs 27.5%, P < .001). Compared with GL, patients using BIL lost weight, with lower fasting serum glucose and between-day fasting blood glucose variability, and 36% less nocturnal hypoglycemia, 29% more total hypoglycemia and more severe hypoglycemia. Total and prandial insulin doses were lower with BIL; basal insulin doses were higher. Alanine aminotransferase increased with BIL, with more patients having elevations ≥3 × ULN. BIL treatment was associated with more frequent injection site reactions and an increase from baseline in serum triglycerides. CONCLUSIONS: In patients with type 1 diabetes, treatment with BIL compared to GL for 26 weeks was associated with lower HbA1c, less nocturnal hypoglycemia, lower glucose variability and weight loss. Increases in total and severe hypoglycemia, triglycerides, aminotransferases and injection site reactions were also noted.

Similar HbA1c reduction and hypoglycaemia with variable- vs fixed-time dosing of basal insulin peglispro in type 1 diabetes: IMAGINE 7 study.

AIMS: To compare 24-hour fixed-time basal insulin peglispro (BIL) dosing with 8- to 40-hour variable-time BIL dosing for glycaemic control and safety in patients with type 1 diabetes. Primary outcome was non-inferiority of BIL variable-time dosing compared with fixed-time dosing for glycated haemoglobin (HbA1c) change after 12-week treatment (margin = 0.4%). MATERIALS AND METHODS: This Phase 3, open-label, randomized, cross-over study (N = 212) was conducted at 20 centres in the United States. During the 12-week lead-in phase, patients received BIL daily at fixed-times. Two 12-week randomized cross-over treatment phases followed, where patients received BIL dosed at either fixed- or variable-times. During the 4-week safety follow-up, patients received conventional insulins. RESULTS: During the lead-in period, least-squares mean HbA1c decreased from 7.5% to 6.8%. For BIL, variable-time dosing was non-inferior to fixed-time dosing for HbA1c change [least-squares mean difference = 0.06%, 95% confidence interval (-0.01, 0.13)]. In both regimens, HbA1c increased slightly during the cross-over periods, but remained significantly below baseline. Variable- and fixed-time dosing regimens had similar rates of total hypoglycaemia (10.4 ± 0.62 and 10.5 ± 0.67 events/patient/30 days, P = .947) and nocturnal hypoglycaemia (1.3 ± 0.11 and 1.5 ± 0.13 events/patient/30days, P = .060). Comparable proportions of patients achieved HbA1c < 7.0% with variable- [91 (54.5%)] and fixed-time dosing [101 (60.5%)]. CONCLUSIONS: Treatment with BIL allows patients to use flexible dosing intervals from 8 to 40 hours. Glycaemic efficacy (HbA1c), glycaemic variability and hypoglycaemia are similar to fixed-time dosing, suggesting that BIL could potentially provide flexibility in dosing for patients who miss their daily basal insulin.

Effect of home-based light treatment on persons with dementia and their caregivers.

Sleep disorders are problematic for persons with dementia and their family caregivers. This randomized controlled trial with crossover evaluated the effects of an innovative blue-white light therapy on 17 pairs of home-dwelling persons with dementia and their caregivers. Subjects with dementia received blue-white light and control ('red-yellow' light) for six weeks separated by a four-week washout. Neither actigraphic nor most self-reported sleep measures significantly differed for subjects with dementia. For caregivers, both sleep and role strain improved. No evidence of retinal light toxicity was observed. Six weeks of modest doses of blue-white light appear to improve sleep in caregivers but not in persons with dementia. Greater or prolonged circadian stimulation may be needed to determine if light is an effective treatment for persons with dementia.

Correlation of Radiographic Mental Foramen Position and Occulusion in Three Different Indian Populations.

BACKGROUND: The knowledge of the position of the mental foramen (MF) is important for administering local anaesthesia for diagnostic, surgical or operative procedures. AIMS: To determine the shape, position, symmetry of MF and its continuity with the inferior dental canal (IDC) on a digital panoramic view and to find its correlation with Angle's molar relations in three Indian subpopulations. The study also determines the correlation of inter-foramen distance in both genders of three Indian subpopulations. SUBJECTS AND METHODS: One hundred and twenty digital panoramic radiographs were evaluated from three Indian subpopulations (Punjab, Rajasthan and Northeast [NE]). The assessment of occlusion was based on Angle's molar relationships. The data obtained were statistically analysed. RESULTS: The commonest position of the MF in the Rajasthan and NE populations was position 4 bilaterally, while in the Punjab population, it was position 3 on the right and position 4 on the left side. The majority of the MF was round in shape followed by oval. The mean distance between two MF was highest among the Punjab male population and least among the NE female population. The most frequent pattern of MF continuity with IDC was diffuse in Rajasthan population, separated in NE and continuous in Punjab. Correlation between Angle's molar relation with MF position was significant for Classes I and II but not for Class III. Correlation of inter-foramen distance between genders was highly significant in the NE and Punjab populations. CONCLUSION: The commonest MF position was aligned with the 1st premolar and between the 1st and 2nd premolar.

Diabetes and cancer: two diseases with obesity as a common risk factor.

There is a growing body of evidence to support a connection between diabetes (predominantly type 2), obesity and cancer. Multiple meta-analyses of epidemiological data show that people with diabetes are at increased risk of developing many different types of cancers, along with an increased risk of cancer mortality. Several pathophysiological mechanisms for this relationship have been postulated, including insulin resistance and hyperinsulinaemia, enhanced inflammatory processes, dysregulation of sex hormone production and hyperglycaemia. In addition to these potential mechanisms, a number of common risk factors, including obesity, may be behind the association between diabetes and cancer. Indeed, obesity is associated with an increased risk of cancer and diabetes. Abdominal adiposity has been shown to play a role in creating a systemic pro-inflammatory environment, which could result in the development of both diabetes and cancer. Here, we examine the relationship between diabetes, obesity and cancer, and investigate the potential underlying causes of increased cancer risk in individuals with diabetes. Current treatment recommendations for reducing the overall disease burden are also explored and possible areas for future research are considered.

Subcutaneous injection of hyaluronidase with recombinant human insulin compared with insulin lispro in type 1 diabetes.

AIMS: Prandial treatment with human regular insulin for diabetes may result in early postprandial hyperglycaemia and late hypoglycaemia due to its slow onset and long duration of action. This study compared injections of recombinant human insulin (rHI) formulated with recombinant human hyaluronidase [rHuPH20] (INSULIN-PH20) to insulin lispro for prandial treatment in subjects with type 1 diabetes (T1D). METHODS: After a 1-month run-in period using twice-daily insulin glargine (or usual basal insulin therapy for pump users) with prandial lispro, 46 subjects with T1D (42 ± 13 years; body mass index: 26 ± 4 kg/m(2); A1c: 6.8 ± 0.5%) were assigned to INSULIN-PH20 or lispro in a random sequence for two consecutive, 12-week periods as the prandial insulin in an intensive treatment regimen. RESULTS: The mean glycaemic excursion for INSULIN-PH20 (0.96 ± 2.00 mmol/l) was comparable (p = 0.322) to lispro (0.80 ± 1.95 mmol/l). The 8-point self-monitored blood glucose profiles were also comparable in the two groups. Good glycaemic control (A1c) was maintained for both treatments at 12 weeks (INSULIN-PH20: 7.0 ± 0.5%; lispro: 6.9 ± 0.6%). Overall rates of hypoglycaemia (≤ 3.9 mmol/l) were 24 events per patient per 4 weeks for INSULIN-PH20 and 22 events for lispro. There were no significant differences in adverse events or immunogenicity between treatments and both treatments were well tolerated. CONCLUSIONS: Unlike commercially available formulations of regular human insulin, a formulation of rHI with rHuPH20 was comparable to lispro for postprandial glucose excursions in a basal-bolus treatment regimen for T1D patients. Glycaemic control, safety and tolerability profiles were comparable for both treatments.

Impact of medical and behavioural factors on influenza-like illness, healthcare-seeking, and antiviral treatment during the 2009 H1N1 pandemic: USA, 2009-2010.

We analysed a cross-sectional telephone survey of U.S. adults to assess the impact of selected characteristics on healthcare-seeking behaviours and treatment practices of people with influenza-like illness (ILI) from September 2009 to March 2010. Of 216,431 respondents, 8.1% reported ILI. After adjusting for selected characteristics, respondents aged 18-64 years with the following factors were more likely to report ILI: a diagnosis of asthma [adjusted odds ratio (aOR) 1.88, 95% CI 1.67-2.13] or heart disease (aOR 1.41, 95% CI 1.17-1.70), being disabled (aOR 1.75, 95% CI 1.57-1.96), and reporting financial barriers to healthcare access (aOR 1.63, 95% CI 1.45-1.82). Similar associations were seen in respondents aged ≥ 65 years. Forty percent of respondents with ILI sought healthcare, and 14% who sought healthcare reported receiving influenza antiviral treatment. Treatment was not more frequent in patients with high-risk conditions, except those aged 18-64 years with heart disease (aOR 1.90, 95% CI 1.03-3.51). Of patients at high risk for influenza complications, self-reported ILI was greater but receipt of antiviral treatment was not, despite guidelines recommending their use in this population.

N-formylpyrazolines and N-benzoylpyrazolines as novel inhibitors of mammalian cathepsin B and cathepsin H.

Cathepsins, intracellular proteases, are known to be involved in a number of physiological processes ranging from degradation of extracellular proteins, prohormone processing, progressions of atherosclerosis, etc. High levels of cathepsins have been indicated in various pathological conditions like arthritis, cancer and other tissue degenerative disorders. One of the reasons attributed to these high levels is decrease in inhibitor concentration. Therefore, the work on the identification of small molecular weight compounds as inhibitors of cysteine proteases is of great therapeutic significance. Exploring this work in the same direction, we here present the synthesis of substituted N-formylpyrazolines and N-benzoylpyrazolines and study these as inhibitors to cysteine proteases. After a preliminary screening of the compounds as inhibitors to cysteine proteases in general, studies were carried out to study their inhibitory effects on cathepsin B and cathepsin H. SAR studies show that N-formylpyrazolines were better inhibitors than N-benzoylpyrazolines. The most potent inhibitors among the two series were nitro substituted compounds 1i and 2i with Ki values of ∼1.1×10(-9)M and 19.5×10(-8)M for cathepsin B and Ki values of ∼5.19×10(-8)M and 9.8×10(-7)M for cathepsin H, respectively. Docking experiments showing interaction between N-formylpyrazolines and N-benzoylpyrazolines with enzyme active sites structures also provided useful insights.

Clinical & immunological profile of newly diagnosed patients with youth onset diabetes mellitus.

BACKGROUND & OBJECTIVES: There has been a rise in the incidence of diabetes mellitus in the younger population of India. There are limited data available on the immunological profile of youth onset diabetes mellitus (DM) especially in type 2. Therefore, this study was undertaken to evaluate the clinical and immunological profile of youth onset DM in north India. METHODS: Fifty one consecutive patients of 8-35 yr of age with diabetes mellitus attending the Lok Nayak Hospital, Maulana Azad Medical College, New Delhi, and Hormone Care and Research Center at Ghaziabad, Uttar Pradesh, India, were included in the study. All subjects were tested for glutamic acid decarboxylase (GAD), an islet cell antigen ICA512/IA2, and insulin antibodies. GAD and ICA512/IA2 were done by ELISA and insulin autoantibodies were tested by radioimmunoassay (RIA) method. These patients were also screened for hepatitis A to E, cytomegalovirus (CMV) and Epstein-Barr virus (EBV) as trigger factors for onset of type 1 DM. RESULTS: o0 f the total 51 patients, 38 were men and 13 were women. The mean age and BMI of the subjects was 19.7 (±7) years and 21 (± 5) kg/m [2] , respectively. Twenty patients were below the age of 18 yr and their height was more than 75 th percentile of Indian standards. All patients were symptomatic and 12 of these presented with ketoacidosis. Only 48 per cent (n=24) were positive for GAD, 14 per cent (n=7) for ICA512/IA-2, and 28% (n=14) were positive for insulin antibody. Five of these patients had evidence of hepatitis E virus infection. None of the subjects had evidence of active CMV or EBV infection. INTERPRETATION & CONCLUSIONS: About half of the youth onset diabetes mellitus patients from north India had presence of pancreatic autoimmunity in the form of GAD, ICA512/IA2, and insulin antibodies or a combination of antibodies suggestive of having type 1 DM. Further studies need to be done on a large sample size in different parts of the country.

Minimally invasive clinical approach in indirect pulp therapy and healing of deep carious lesions.

Indirect pulp treatment is a conservative vital pulp procedure performed in deep carious lesion approximating the pulp, but without signs or symptoms of pulp degeneration. Removing the carious biomass along with sealing the residual caries from extrinsic substrate and oral bacteria makes residual caries after the first excavation less active. This allows time for pulpo dentinal complex to form tertiary dentine so that at the second excavation, there is less likelihood of pulpal exposure. It has also been suggested that by changing the cavity environment from an active lesion into a more slowly progressing lesion, will be accompanied by more regular tubular tertiary dentin formation. The success of this approach has been demonstrated by various randomized controlled studies comparing conventional treatment of such lesions with stepwise excavation. These results are echoed at clinical, radiographic, macroscopic, microscopic and ultrastructural level during follow up visits. This study reviews promising concepts and rationale of minimally invasive indirect pulp therapy technique where conventional wisdom of caries removal is challenged