Peri-operative tobacco cessation interventions: a systematic review and meta-analysis.

Tobacco smoking is associated with a substantially increased risk of postoperative complications. The peri-operative period offers a unique opportunity to support patients to stop tobacco smoking, avoid complications and improve long-term health. This systematic review provides an up-to-date summary of the evidence for tobacco cessation interventions in surgical patients. We conducted a systematic search of randomised controlled trials of tobacco cessation interventions in the peri-operative period. Quantitative synthesis of the abstinence outcomes data was by random-effects meta-analysis. The primary outcome of the meta-analysis was abstinence at the time of surgery, and the secondary outcome was abstinence at 12 months. Thirty-eight studies are included in the review (7310 randomised participants) and 26 studies are included in the meta-analysis (5969 randomised participants). Studies were pooled for subgroup analysis in two ways: by the timing of intervention delivery within the peri-operative period and by the intensity of the intervention protocol. We judged the quality of evidence as moderate, reflecting the degree of heterogeneity and the high risk of bias. Overall, peri-operative tobacco cessation interventions increased successful abstinence both at the time of surgery, risk ratio (95%CI) 1.48 (1.20-1.83), number needed to treat 7; and 12 months after surgery, risk ratio (95%CI) 1.62 (1.29-2.03), number needed to treat 9. More work is needed to inform the design and optimal delivery of interventions that are acceptable to patients and that can be incorporated into contemporary elective and urgent surgical pathways. Future trials should use standardised outcome measures.

Medium optimization for submerged fermentative production of ß-cyclodextrin glucosyltransferase by isolated novel alkalihalophilic Bacillus sp. NCIM 5799 using statistical approach.

ß-cyclodextrin glucosyltransferase (ß-CGTase) is an essential enzyme to catalyse the biotransformation of starch into ß-cyclodextrins (ß-CD). ß-CD has widespread applications in the biomedical, pharmaceutical and food industries. The present study focused on ß-CGTase production using an efficient natural microbial strain and statistical production optimization for enhanced production. The isolated organism Bacillus sp. NCIM 5799 was found to be 5 µm short bacilli under FE-SEM and alkalihalophilic in nature. The ß-CGTase production was optimized using a combination of Plackett-Burman design (PBD) and Central Composite Design-Response Surface Methodology (CCD-RSM). On PBD screening Na2 CO3 , peptone and MgSO4 .7H2 O were found to be significant for optimal ß-CGTase production, whereas the soluble starch and K2 HPO4 concentrations were found to be nonsignificant for ß-CGTase production. The significant factors obtained after PBD were further optimized using CCD-RSM design. Peptone was found to have a significant interaction effect with Na2 CO3 , and MgSO4 ·7H2 O and Na2 CO3 exhibited a significant effect on the production of CGTase. The production of ß-CGTase was enhanced in the presence of peptone (3%) and Na2 CO3 (0·8%). CGTase production obtained was 156·76 U/ml when optimized using CCD-RSM. The final optimized medium (RSM) shows 7·7- and 5·4-fold high productions as compared to un-optimized and one factor at a time production media.

Decontamination of coal mine effluent generated at the Rajrappa coal mine using phytoremediation technology.

Toxicity of the effluent generated at the Rajrappa coal mine complex under the Central Coalfields Limited (CCL, a subsidiary of Coal India Limited) in Jharkhand, India was investigated. The concentrations (mg L-1) of all the toxic metals (Fe, Mn, Ni, Zn, Cu, Pb, Cr, and Cd) in the coal mine effluent were above the safe limit suggested by the Environmental Protection Agency (EPA 2003). Among these, Fe showed the highest concentration (18.21 ± 3.865), while Cr had the lowest effluent concentration (0.15 ± 0.014). Efforts were also made to detoxify the effluent using two species of aquatic macrophytes namely "'Salvinia molesta and Pistia stratiotes." After 10 days of phytoremediation, S. molesta removed Pb (96.96%) > Ni (97.01%) > Cu (96.77%) > Zn (96.38%) > Mn (96.22%) > Fe (94.12%) > Cr (92.85%) > Cd (80.99%), and P. stratiotes removed Pb (96.21%) > Fe (94.34%) > Ni (92.53%) > Mn (85.24%) > Zn (79.51%) > Cr (78.57%) > Cu (74.19%) > Cd (72.72%). The impact of coal mine exposure on chlorophyll content showed a significant decrease of 42.49% and 24.54% from control values in S. molesta and P. stratiotes, respectively, perhaps due to the damage inflicted by the toxic metals, leading to the decay of plant tissues.

Evaluation of pollution of Ganga River water using fish as bioindicator.

Ganga River, life line of millions of people got heavily polluted due to uncontrolled anthropogenic activities. To monitor the effect of pollution of the river on its aquatic life, a field study was conducted by analyzing the different biomarker enzymes and biochemical parameters in the various tissues (muscles, liver, gills, kidney, brain, and skin) of the Indian major carp Labeo rohita collected from the River Ganga from different study sites of Varanasi district. Activities of antioxidant enzymes, e.g., superoxide dismutase, catalase, and level of lipid peroxidation were found to be higher in the fish collected from the river showing pollutant-induced oxidative stress in the fish. Disturbed health status of the river fish was also manifested by increased activities of aspartate amino transferase, alanine amino transferase, and alkaline phosphatase. Concentration of nutritionally important biomolecules (proteins, lipids, and moisture) and energy value were also found to be significantly lower in the tissues of the River fish indicating its decreased nutritional value due to oxidative stress caused by different pollutants.

Electric Field Control of Spin Lifetimes in Nb-SrTiO_{3} by Spin-Orbit Fields.

We show electric field control of the spin accumulation at the interface of the oxide semiconductor Nb-SrTiO_{3} with Co/AlO_{x} spin injection contacts at room temperature. The in-plane spin lifetime τ_{∥}, as well as the ratio of the out-of-plane to in-plane spin lifetime τ_{⊥}/τ_{∥}, is manipulated by the built-in electric field at the semiconductor surface, without any additional gate contact. The origin of this manipulation is attributed to Rashba spin orbit fields (SOFs) at the Nb-SrTiO_{3} surface and shown to be consistent with theoretical model calculations based on SOF spin flip scattering. Additionally, the junction can be set in a high or low resistance state, leading to a nonvolatile control of τ_{⊥}/τ_{∥}, consistent with the manipulation of the Rashba SOF strength. Such room temperature electric field control over the spin state is essential for developing energy-efficient spintronic devices and shows promise for complex oxide based (spin) electronics.

Epidemiology of epilepsy and its burden in Kolkata, India.

BACKGROUND: Disability-adjusted life year (DALY) is a time-based measure of disease burden incorporating both disability and mortality. Our study aimed to determine the DALY lost from epilepsy in an Indian metropolis. METHODS: A population-based prospective study on epilepsy was conducted over 5 years (2003-8) in Kolkata, India, on randomly selected 100,802 subjects (males 53,209, females 47,593) to assess prevalence as well as to capture incident cases of epilepsy and those incident cases that died. Standard case definitions were used. The data were used to estimate years of life lost (YLL) due to premature mortality, years of life lived with disability (YLD), and DALY, utilizing the prevalence-based Global Burden of Disease (GBD) 2010 approach. Age- and gender-specific figures were computed. RESULTS: During 2003-2004, a total of 476 subjects with active epilepsy were detected and the age-adjusted prevalence rate was 4.71 per 1000. Over 5 years, there were 197 incident cases of epilepsy of whom 26 died. The age-adjusted annual incidence rate of epilepsy was 38.3 per 100,000. The all-cause standardized mortality rate (SMR) of epilepsy was 2.4. The burden of epilepsy in the year 2007-8 revealed the overall YLL was 755 per 100,000, and the overall YLD ranged from 14.45 to 31.0 per 100,000 persons depending on the clinical severity of the epilepsy. Both YLL and YLD values were higher in males than in females. The overall DALY lost due to epilepsy in 2007-8 was found to be 846.96 (males 1183.04, females 463.81) per 100,000. CONCLUSIONS: This is the first study in India to determine the DALY of epilepsy using GBD 2010. The results reveal a substantial burden of epilepsy in our setting. Similar such studies are needed in other parts of India in both urban and rural settings.

Epinephrine adjuvant reduced epidural blood vessel penetration incidence in a randomized, double-blinded trial.

BACKGROUND: Accidental intravascular injection is a significant and potentially devastating risk of epidural block, particularly in parturients whose epidural veins are engorged and hence more easily pierced. This prospective randomized, double-blinded study determined whether the addition of epinephrine to epidural ropivacaine administered by gravity before catheter insertion was associated with fewer epidural catheter blood vessel penetrations. METHOD: Four hundred and two parturient patients receiving epidural block for elective C/S were randomly allocated to two groups; group I (n = 201) received only ropivacaine 0.75% with fentanyl 5 µg/mL, whereas group II (n = 200) also received epinephrine 5 µg/mL. Both groups received a total of 21 mL anesthetic solution in four increment doses of 3,5,5,5 mL by gravity into the needle through a 22 inch extension tubing before insertion of the closed-end tip catheter. An additional 3 mL of the anesthetic solution was then administered through the catheter. RESULTS: Epidural epinephrine adjuvant was associated with fewer epidural vessel penetrations (4% vs. 16.5%, P < 0.0001). The addition of epinephrine also significantly reduced catheter insertion problems (12% vs. 23.5%, P-value 0.0024) including the need for catheter readjustment (4.5% vs. 16%, P-value 0.0002) or reinsertion (2.5% vs. 9%, P-value 0.0054). The addition of epinephrine significantly reduced incidence and severity of sedation and had faster onset of surgical block. Sensory level and overall satisfaction did not differ significantly among the groups. CONCLUSION: The addition of epinephrine to ropivacaine improves the safety and quality of epidural anesthesia when administered by gravity flow via the Hustead needle for cesarean sections.

Omega-3 fatty acids enriched chocolate spreads using soybean and coconut oils.

Chocolate spreads were developed by incorporating two different soybean oil margarines, fat phases prepared using 85 % soybean oil (M1) and 1:1 blend of soybean oil and coconut oil (M2) with commercial palm stearin. Eight formulations were tried by varying skim milk powder (SMP)/fluid skimmed milk (FSM), type of fats (M1, M2, a commercial margarine and a table spread), sugar and cocoa powder and their quality characteristics were compared with a commercial hazelnut cocoa spread. The moisture and fat content were 5-6.1 % and 31.4-32.8 % for formulations with SMP and 21.5-24.7 % and 15.6-21.4 % respectively for those with FSM. Rheological studies of FSM spreads showed higher G″ value (loss modulus) than G' (storage modulus) indicating better spreadability. Descriptive sensory analysis revealed that the products had acceptability score of 8.3 to 10.5 (maximum score: 15). Fat extracted from spreads prepared using M1 and M2 was found to contain 43.9 and 22.3 % linoleic acid and 2.1 and 4.4 % linolenic acid respectively, were free from trans fat while the commercial hazelnut spread had 9.8 % linoleic acid but did not contain linolenic acid. Hence, the developed chocolate spreads have the potential to overcome ω-3 deficiency, ω-6/ω-3 imbalance and to enhance the health standard of people.

Contamination of metals in different tissues of rohu (Labeo rohita, Cyprinidae) collected from the Indian River Ganga.

In the present paper, accumulation of zinc (Zn), iron (Fe), copper (Cu), chromium (Cr), nickel (Ni), manganese (Mn) and lead (Pb) was determined in different tissues (skin, muscles, liver, gills, kidney and brain) of rohu (Labeo rohita) collected from the River Ganga in Varanasi, India. Concentrations of Cu (except gills), Fe and Cr (except brain for Cr) in most of the tissues were above the permissible safe limits for human consumption suggested by the Food and Agricultural Organization (FAO 1983). Concentrations of all metals were higher in River Ganga fish than those from the University fish farm. With the exception of Zn in skin, muscle and brain tissue, the studied metals were bioaccumulated in all tissues. The total metal accumulation or metal pollution index was highest in liver (20.8 ± 0.50) followed by kidney (16.8 ± 0.44), gills (15.2 ± 0.15), muscles (12.1 ± 0.08), skin (10.5 ± 0.53) and brain (7.0 ± 0.02).

Non-linear adaptive control inspired by neuromuscular systems.

Current paradigms for neuromorphic computing focus on internal computing mechanisms, for instance using spiking-neuron models. In this study, we propose to exploit what is known about neuro-mechanical control, exploiting the mechanisms of neural ensembles and recruitment, combined with the use of second-order overdamped impulse responses corresponding to the mechanical twitches of muscle-fiber groups. Such systems may be used for controlling any analog process, by realizing three aspects: Timing, output quantity representation and wave-shape approximation. We present an electronic based model implementing a single motor unit for twitch generation. Such units can be used to construct random ensembles, separately for an agonist and antagonist 'muscle'. Adaptivity is realized by assuming a multi-state memristive system for determining time constants in the circuit. Using SPICE-based simulations, several control tasks were implemented which involved timing, amplitude and wave shape: The inverted pendulum task, the 'whack-a-mole' task and a handwriting simulation. The proposed model can be used for both electric-to-electronic as well as electric-to-mechanical tasks. In particular, the ensemble-based approach and local adaptivity may be of use in future multi-fiber polymer or multi-actuator pneumatic artificial muscles, allowing for robust control under varying conditions and fatigue, as is the case in biological muscles.

Angiosarcoma-like presentation of pacemaker-related vascular proliferation.

A 90-year-old man presented with a rapidly growing vascular lesion after a pacemaker generator change. The rapid growth suggested a possible angiosarcoma. A less dramatic presentation of vascular proliferation has been described as reticular telangiectatic erythema, which has been reporting following insertion of pacemakers, implantable cardioverter defibrillators, and drug-delivery devices. The onset of the disorder is described as weeks to years after implantation or generator change. It is a benign condition that generally remains static or regresses over time. The vascular proliferation noted in this case resolved almost completely over a period of 1 year.

Methylglyoxal induces mitochondria-dependent apoptosis in sarcoma.

In the preceding paper (A. Ghosh et al. (2011) Biochemistry (Moscow), 76, 1051-1060), using several comparable tissue materials, it has been convincingly demonstrated that methylglyoxal, a normal metabolite, inhibits mitochondrial complex I of specifically malignant cells. This suggests a distinct alteration of complex I, a highly important enzyme for energy (ATP) production, in malignancy. The present paper shows that as a consequence of this inhibition mitochondrial membrane potential is drastically reduced in sarcoma tissue but not in normal skeletal muscle. This was estimated spectrofluorimetrically using the dye rhodamine 123. As a consequence, cytochrome c was released from the sarcoma mitochondria as evidenced by Western blot analysis. Moreover, on treatment with methylglyoxal membrane potential collapse of sarcoma 180 cells was also indicated by fluorescence-activated cell sorter analysis. Atomic force microscopic study demonstrated gross structural alteration specifically of tumor mitochondria on methylglyoxal treatment. All these studies suggest that methylglyoxal might initiate an apoptotic event in malignant cells.

Association between climate and infectious diseases among children in Varanasi city, India: A prospective cohort study.

The effects of climate on infectious diseases could influence the health impacts, particularly in children in countries with the unfair socioeconomic conditions. In a prospective cohort of 461 children under 16-years-of-age in Varanasi city, India, the association of maximum-temperature (Tmax), relative humidity (RH), absolute humidity (AH), rainfall (RF), wind-speed (WS), and solar radiation (SLR) with prevalent infectious diseases (Diarrhea, Common cold and flu, Pneumonia, Skin-disease and Malaria, and Dengue) was examined using binomial-regression, adjusting for confounders and effect modifiers (socioeconomic-status; SES and child anthropometry), from January 2017 to January 2020. Attributable-fraction (AFx) was calculated due to each climate variable for each infectious disease. The result showed that each unit (1 °C) rise in Tmax was associated with an increase in diarrhea and skin-disease cases by 3.97% (95% CI: 2.92, 5.02) and 3.94% (95% CI: 1.67, 6.22), respectively, whereas, a unit decline in Tmax was associated with an increase in cold and flu cases by 3.87% (95% CI: 2.97, 4.76). Rise in humidity (RH) was associated with increase in cases of cold and flu by 0.73% (95% CI: 0.38, 1.08) and malaria (AH) by 7.19% (95% CI: 1.51, 12.87) while each unit (1 g/m3) decrease in humidity (AH) observed increase in pneumonia cases by 3.02% (95% CI: 0.75, 5.3). WS was positively associated with diarrhea (14.16%; 95% CI: 6.52, 21.80) and negatively with dengue (17.40%; 12.32, 22.48) cases for each unit change (kmph). RF showed marginal association while SLR showed no association at all. The combined AFx due to climatic factors ranged from 9 to 18%. SES and anthropometric parameters modified the climate-morbidity association in children with a high proportion of children found suffering from stunting, wasting, and underweight conditions. Findings from this study draw the attention of government and policymakers to prioritize effective measures for child health as the present association may increase disease burden in the future under climate-change scenarios in already malnourished paediatric population through multiple pathways.

Impact of HAART on survival, weight gain and resting energy expenditure in HIV-1-infected children in India.

BACKGROUND: In resource-limited countries, use of highly active antiretroviral therapy (HAART) in HIV-infected children is still poorly documented in terms of impact on survival, the immune system and growth. Since the availability of HAART, nutrition of HIV-infected children has been neglected. AIM: To evaluate the effect of HAART on survival and immune response in HIV-infected children and to investigate the response to nutritional support. METHODS: In December, 2002 a cohort study was carried out on vertically HIV-1-infected children and was observed longitudinally for CD4(+) T-cell count, antiretroviral treatment and weight until 31 December 2007. Z-scores were calculated for CD4(+) T-cell count to account for age-related differences. Nutritional supplementation was given to all the HIV-infected children and resting energy expenditure (REE) was calculated. Mortality rates were also calculated for the perinatally infected children followed up at the HIV clinic. RESULTS: A total of 180 children were assessed, 100 (56%) of whom were on HAART. Baseline body mass index was lower in the HAART group (p<0.05). Median duration of survival from date of diagnosis was 15.1 years. Those who received HAART survived significantly longer. The average annual mortality rate was 1.2% during 2005-2006. During HAART, a CD4 Z-score increase of 1 SD was associated with a 0.35 increase in body weight Z-score (p<0.001). The increase in daily energy intake owing to nutritional supplementation was associated with increase in weight Z-score in both the no-HAART and HAART group. REE was independently associated with weight change in the models which tested association of changes in CD4(+) T-cell Z-score and daily REE/kg body weight with changes in body weight Z-score in both the HAART and no-HAART group and then separately in the two groups (p<0.001). CONCLUSION: Survival rates of children improved which correlated with an increase in CD4(+) T-cell count concurrent with the expanded use of HAART. HAART had a positive effect on growth in HIV-1-infected children. Nutrition supplementation improved the health of children in both the no-HAART and HAART groups.

Prevalence of essential tremor in the city of Kolkata, India: a house-to-house survey.

BACKGROUND AND PURPOSE: Prevalence of essential tremor (ET), one of the most common movement disorders, has not been properly evaluated amongst heterogeneous population in India. METHODS: We conducted a cross-sectional epidemiological study on the prevalence of ET in a randomly stratified population in the metropolitan city of Kolkata (erstwhile Calcutta), India, by a field team headed by a specialist doctor. A two-stage house-to-house survey was carried out with a validated screening instrument. RESULTS: A population of 52377 was screened and a total of 184 cases of ET were identified as per pre-defined criteria and the prevalence rate adjusted to World Standard Population was 3.95 per 1000 (95% CI: 3.40-4.56). Age-specific prevalence showed increasing prevalence with aging. Sex-specific prevalence did not show significant difference between men and women. Socio-economic factors appeared to influence the prevalence and risk of ET was higher amongst slum dwellers versus non-slum population (odd ratio-2.29). Family history was positive in about one-fifth of the cases. CONCLUSION: This study has documented that the prevalence of ET above 40 years in India is similar to that of many countries globally and common amongst slum dwellers and there are fewer familial cases.

Plasma levels of lipid peroxides in patients with Parkinson's disease.

Oxidative stress is implicated as a major factor for nigral neuronal cell death. Metabolic failure in antioxidant mechanisms could hypothetically facilitate the chemical processes that lead to lipid peroxidation. To elucidate whether elevated lipid peroxidation rates might increase risk of developing Parkinson's disease (PD), the Authors determined plasma levels of malondialdehyde (MDA) in 80 PD patients and 80 controls. There was a significant difference between the plasma MDA levels of PD patients and controls (7.48 +/- 1.55 vs 5.1 +/- 1.26 nmol/ml). Plasma MDA levels were inversely related to the age of the PD patients (r = -0.46; p < 0.01) and age of onset but in the control group, no such correlation was observed between the plasma MDA and age. However, there was no significant correlation between plasma MDA levels and the duration of disease, Hoehn and Yahr stages and the Unified Parkinson's Disease Rating Scale (UPDRS). Thus, the results suggest that high plasma lipid peroxidation rates might contribute as a risk factor for PD in West Bengal.

Haematological presentation of systemic lupus erythematosus.

Haematological manifestations are quite common in systemic lupus erythematosus (SLE) but bone marrow aplasia and secondary myelofibrosis are rare manifestations. We report a case of 45 years old male patient who presented with fever, malaena and anaemia without any clinical features of SLE. He had patches of vitiligo for 25 years for which he was applying psoralen with sunlight exposure. This probably precipitated SLE in this patient. The patient presented with pancytopenia which was due to a combination of Comb's positive haemolytic anaemia and myelofibrosis.

A case report of Blastocystis infection and Steven Johnson's syndrome.

Blastocystis species (spp.) is an emerging pathogen. There are several unsolved issues linked to this parasite ranging from its nomenclature, commensal status, standardization of laboratory diagnostic methods, genotypes and treatment. Recently, there has been an increase in reports of Blastocystis spp. from symptomatic cases which provide enough evidence of its pathogenic potential. A range of signs and symptoms, from gastro-intestinal to cutaneous manifestations have been attributed to Blastocystis infection. Few reports have established an association between intestinal infection with Blastocystis spp. and skin manifestations in form of urticaria, palmoplantar pruritus and allergy with complete resolution of cutaneous lesions with eradication of the parasite. In this report, we describe a case of Steven Johnson's syndrome (SJS) in a 6 years old girl along with infection with Blastocystis spp. marked by diarrhea and abdominal pain. Stool examination revealed the presence of all forms of the parasite with subsequent decrease in parasite burden and diarrhea over a period of time. Interestingly, the clearance of Blastocystis spp. from stool was followed by recovery from skin lesions and other symptoms. In this case, the course of SJS was clearly associated with Blastocystis infection. Though skin manifestation with Blastocystis infection has been previously reported, this is the first report of its association with SJS. This report indicates newer insights of the parasite that are less well studied.

Conversion of clinically isolated syndrome to multiple sclerosis: a prospective multi-center study in Eastern India.

BACKGROUND: In White populations more than 60% of clinically isolated syndrome (CIS) convert to multiple sclerosis (MS) on a long-term follow-up; several predictors for conversion have been identified. OBJECTIVE: This study aimed to determine the conversion rate and the predictors of conversion from CIS to MS (McDonald 2010) among Indians. The other objective was to evaluate the diagnostic accuracy of the new McDonald 2017 criteria in prediction of a second clinical attack. METHODS: Clinical and demographic data of CIS cohorts were collected. Baseline investigations included cerebrospinal magnetic resonance imaging (MRI) with contrast and cerebrospinal fluid (CSF) testing for oligoclonal band (OCB). Follow-up clinical and MRI examinations were performed annually for at least 24 months. RESULTS: Of the 82 subjects (age range 15-58 years), 36 (43.9%) converted to MS; 31/82 (37.8%) converted in 24 months. The predictors for conversion were earlier age of onset, CSF-OCB, cerebral MRI T2 lesion count, and periventricular and juxtacortical location of lesions. Twenty-two (26.83%) CIS fulfilled the McDonald MS 2017 criteria at baseline. CONCLUSION: In this first prospective study of CIS in India, the risk factors for conversion are similar but the conversion rate to MS is lower than that in the western nations.

Structural effects of nogalamycin, an antibiotic antitumour agent, on DNA.

The structural changes of DNA, induced by the antitumour antibiotic nogalamycin, have been studied by atomic force microscopy (AFM). The transformation in the tertiary structure of 4361bp long plasmid pBR322 DNA, after incubation with nogalamycin at 37 degrees C, has been monitored at the single molecule level. The AFM topographs of free DNA and the DNA-nogalamycin complex, incubated for 6, 12, 24, 36 and 48h, reveal a gradual change from the circular supercoiled form having strand crossovers to the more compact plectonemic superhelix. With increasing incubation time, the extent of plectonemic coiling increases, indicating increasing level of drug binding via intercalative mode. Supportive evidences are obtained from the CD and UV-vis spectroscopic studies. To our knowledge, this is the first report on an AFM imaging study of the effects of nogalamycin, an anthracyclin intercalator, on DNA.