Potential contribution of monoamine oxidase a gene variants in ADHD and behavioral co-morbidities: scenario in eastern Indian probands.

Attention deficit hyperactivity disorder (ADHD) is the most frequently diagnosed behavioral disorder in children with a high frequency of co-morbid conditions like conduct disorder (CD) and oppositional defiant disorder (ODD). These traits are controlled by neurotransmitters like dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA), a mitochondrial enzyme involved in the degradation of amines, has been reported to be associated with aggression, impulsivity, depression, and mood changes. We hypothesized that MAOA can have a potential role in ADHD associated CD/ODD and analyzed 24 markers in a group of Indo-Caucasoid subjects. ADHD probands and controls (N = 150 each) matched for ethnicity and gender were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV. Appropriate scales were used for measuring CD and ODD traits. Markers were genotyped by PCR-based methods and data obtained analyzed using the Cocaphase program under UNPHASED. Only eight markers were found to be polymorphic. rs6323 "G" allele showed higher frequencies in ADHD (P = 0.0023), ADHD + CD (P = 0.03) and ADHD + ODD (P = 0.01) as compared to controls. Haplotype analysis revealed statistically significant difference for three haplotypes in ADHD cases (P < 0.02). Statistically significant differences were also noticed for haplotypes in ADHD + CD and ADHD + ODD cases (P < 0.01). LD analysis showed significant variation in different groups. Multidimensionality reduction analysis showed independent as well as interactive effects of markers. Genotypes showed correlation with behavioral problems in ADHD and ADHD + CD. We interpret that MAOA gene variants may contribute to the etiology of ADHD as well as associated co-morbid CD and ODD in this ethnic group.

Association between Vitamin D Receptor Gene Polymorphism (Fok 1), Vitamin D Status and Autoimmune Thyroiditis.

Autoimmune thyroiditis gradually destroys the thyroid gland leading to hypothyroidism and may even lead to papillary thyroid carcinoma. Deficiency of Vitamin D has been linked to development of autoimmunity. Single nucleotide polymorphisms of the Vitamin D receptor gene have associated with autoimmune diseases in several studies. In this hospital based non interventional cross-sectional study Vitamin D receptor gene was studied for FokI (rs2228570) polymorphism from purified DNA in forty-eight adult cases and fifty age and sex matched healthy controls. This study was conducted in the department of Biochemistry, Calcutta National Medical College, Kolkata, West Bengal, India from January 2021 to July 2022. Their DNA was isolated using phenol chloroform method and were analysed for the related single nucleotide polymorphism by restriction digestion using appropriate restriction enzymes after amplification by PCR. Differences in allele frequencies between two groups were estimated by chi square and odds ratio test. Any potential association between the vitamin D anti TPO antibody and thyroid hormone status with polymorphic variations were assessed by post hoc ANOVA among the three genotypes. The distribution of FF genotype was significantly higher among the case group (Χ²=10.2788, p=0.006). The odds ratio for the allele F was significantly higher in case group for a range of 1.97 to 5.94 for 95 percent confidence interval (Χ²=13.9678, p=<0.001). The genotype FF group had significantly lowest Vitamin D (p=0.008) and highest Anti TPO ab (p=0.031) compared to Ff and ff genotypes. Thus, significant association was revealed between the VDR gene Fok1(rs2228570) polymorphism and autoimmune thyroiditis with the predominance of FF genotype being a strong susceptibility factor for autoimmune thyroiditis and Vitamin D deficiency in the studied population of Eastern India.

Right trace wrong place: a normal capnography trace despite the tip of the tracheal tube existing outside the airway.

Head and neck trauma can result in difficult airway management. A 25-year-old male required emergency tracheal intubation on arrival to the emergency department following a motorbike accident. Despite the presence of a normal capnography a computed tomography scan demonstrated a tracheal opening, an extra-tracheal position of the distal end of the tracheal tube, and extensive subcutaneous emphysema. The tube was re-directed into the trachea and the tracheal injury was surgically repaired. This case highlights that the presence of a normal capnograph does not necessarily mean that the distal end of the tracheal tube resides within the airway.

Observation of gigawatt-class THz pulses from a compact laser-driven particle accelerator.

We report the observation of subpicosecond terahertz (T-ray) pulses with energies ≥460 µJ from a laser-driven ion accelerator, thus rendering the peak power of the source higher even than that of state-of-the-art synchrotrons. Experiments were performed with intense laser pulses (up to 5×10(19) W/cm(2)) to irradiate thin metal foil targets. Ion spectra measured simultaneously showed a square law dependence of the T-ray yield on particle number. Two-dimensional particle-in-cell simulations show the presence of transient currents at the target rear surface which could be responsible for the strong T-ray emission.

Carbon nanotubes enhance the internalization of drugs by cancer cells and decrease their chemoresistance to cytostatics.

Etoposide is a semisynthetic, chemotherapeutic drug widely recommended to treat an extensive range of human cancers. Our studies indicate that, while etoposide is capable of killing human cancer cells, exposure to single-walled carbon nanotubes (SWCNTs) and etoposide results in enhanced cell death that appears to be synergistic and not merely additive. In this study, we used high pressure liquid chromatography and mass spectrometry to quantify the internal effective dose of etoposide when the human pancreatic cancer cell (PANC-1) was exposed to the combination of these agents. Our results unequivocally indicate that SWCNTs improve etoposide uptake and increase its capacity to kill cancer cells. We suggest that a combination of SWCNTs and etoposide may prove to be a more efficient chemotherapeutic protocol, especially because of the potential to lower toxic drug doses to levels that may be useful in decreasing adverse side effects, as well as in lowering the probability of inducing chemoresistance in exposed cancer cells.

A new unstable hemoglobin variant Hb Acharnes or [ß53(D4) Ala - Thr]: a case report.

Hb Acharnes or [ß53(D4) Ala - Thr] is a newly discovered unstable hemoglobin variant. It has been reported in very few literatures across the world and no cases have been reported from India till date. Hb Acharnes is known to interact with ß°-thalassemia to produce thalassemia intermedia and heterozygotes may present with borderline HbA2 levels. Here we report a rare case discovered during routine screening of thalassemia and hemoglobinopathies in a 19 year old pregnant lady. To emphasize the diagnostic difficulties and importance of detection of a rare hemoglobin variant Hb Acharnes [ß53(D4) Ala - Thr] in an asymptomatic patient in West Bengal, India. The 19 year old asymptomatic pregnant lady P1+0, LMP - 21.01.2011 reported in antenatal OPD of Burdwan Medical College & Hospital, Burdwan, West Bengal, India for routine follow up. After proper antenatal check up her blood was collected as a routine screening for Thalassemia, EDTA blood was taken on 5th April 2011 and was subjected to Hemoglobin estimation by Cyanmethemoglobin method, Cell parameters in automated cell counter (SYSMEX KX21) and Hemoglobin analysis by HPLC in BIORAD VARIANT system. The patient was normal with respect to clinical examination and urinalysis. Routine blood counts revealed mild microcytic hypochromic anemia and on HPLC an unknown band (retention time 2.2 minutes, 21.2%, appearing as a shoulder of HbA0 band) of hemoglobin variant was discovered with normal level of HbF and HbA2. Hemoglobin analysis of her mother showed similar pattern while her father and her husband had normal Hb-HPLC pattern. The unknown hemoglobin variant was identified as Hemoglobin Acharnes or [ß53 (D4) Ala - Thr] by the Biorad laboratories upon consulting the standard chromatogram patterns for this particular hemoglobin variant. Only Haemoglobin Electrophoresis by conventional gel technique may miss the case and the HPLC pattern may be used as a standard control for identification.

Radiation-pressure acceleration of ion beams from nanofoil targets: the leaky light-sail regime.

A new ion radiation-pressure acceleration regime, the "leaky light sail," is proposed which uses sub-skin-depth nanometer foils irradiated by circularly polarized laser pulses. In the regime, the foil is partially transparent, continuously leaking electrons out along with the transmitted laser field. This feature can be exploited by a multispecies nanofoil configuration to stabilize the acceleration of the light ion component, supplementing the latter with an excess of electrons leaked from those associated with the heavy ions to avoid Coulomb explosion. It is shown by 2D particle-in-cell simulations that a monoenergetic proton beam with energy 18 MeV is produced by circularly polarized lasers at intensities of just 10¹9 W/cm². 100 MeV proton beams are obtained by increasing the intensities to 2 × 10²° W/cm².

Molecular epidemiology of goat pox viruses.

Goat pox disease outbreaks were observed in different places affecting Black Bengal Goats in West Bengal (WB) and Tellicherry, Vembur and non-descriptive breeds in Tamil Nadu (TN) causing severe lesions and mortality up to 30%. Clinical specimens from all the outbreaks were screened by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and confirmed the diseases as Goat Pox. Virus isolation in Vero cell line was done with randomly selected ten samples, cytopathic effects (CPE) characterized by syncytia and intracytoplasmic inclusion bodies were observed after several blind passages. Nucleotide sequence of complete p32 gene using randomly selected two isolates and three clinical specimens revealed presence of Goat pox virus (GTPV)-specific signature residues in all the sequences. Phylogenetic analysis using the present five sequences along with GenBank data of GTPV complete p32 gene sequences showed all the GTPV sequences cluster together except Pellor strain (NC004003) and FZ Chinese strain (KC951854). The five sequences either from WB or TN cluster more closely with GTPV isolates of Maharashtra state that were responsible for cross species outbreak of pox disease in both sheep (KF468759) and goats (KF468762) in India during the year 2010. All the Indian goat pox viruses, including the Mukteswar strain, isolated in 1946 and sequence reported in 2004 clustered together with the GTPVs causing the recent outbreaks. It was observed that GTPVs caused similar clinical manifestation irrespective of their geographical locations and breed characteristics, no variation observed among the Indian isolates based on p32 gene over the period of seventy years and disease outbreaks could not be observed or reported in vaccinated goats.

High prevalence of mutations of the p53 gene in poorly differentiated human thyroid carcinomas.

The development and progression of thyroid tumors is signaled by phenotype-specific mutations of genes involved in growth control. Molecular events associated with undifferentiated thyroid cancer are not known. We examined normal, benign, and malignant thyroid tissue for structural abnormalities of the p53 tumor suppressor gene. Mutations were detected by single-strand conformation polymorphisms of PCR-amplified DNA, using primers bracketing the known hot spots on either exons 5, 6, 7, or 8. The prevalence of mutations was as follows: normal thyroid 0/6; follicular adenomas 0/31; papillary carcinomas 0/37; medullary carcinomas 0/2; follicular carcinomas 1/11; anaplastic carcinomas 5/6; thyroid carcinoma cell lines 3/4. Positive cases were confirmed by direct sequencing of the PCR products. All five anaplastic carcinoma tissues and the anaplastic carcinoma cell line ARO had G:C to A:T transitions leading to an Arg to His substitution at codon 273. In both tumors and cell lines, examples of heterozygous and homozygous p53 mutations were identified. The only thyroid carcinoma cell line in which p53 mutations were not detected in exons 5-8 had markedly decreased p53 mRNA levels, suggesting the presence of a structural abnormality of either p53 itself or of some factor controlling its expression. The presence of p53 mutations almost exclusively in poorly differentiated thyroid tumors and thyroid cancer cell lines suggests that inactivation of p53 may confer these neoplasms with aggressive properties, and further loss of differentiated function.

Machine vision based evaluation of impact of light emitting diodes (LEDs) on shoot regeneration and the effect of spectral quality on phenolic content and antioxidant capacity in Swertia chirata.

The present study demonstrates the influence of LED irradiance of various wavelengths on shoot regeneration, biomass accumulation, photosynthetic pigment contents, and antioxidant potentials of Swertia chirata - a critically endangered medicinal plant. Mixed treatment of blue (BL) and red LEDs (RL) in equal proportion (1:1) significantly improved the shoot regeneration response. A machine vision system was developed to assess the shoot regeneration potential under different lighting treatments. Regenerated shoots exposed under BL:RL (1:1) exhibited higher biomass accumulation and canopy development compared to other lighting treatments. Improved canopy growth was evident from the increase in the area, major axis, minor axis, convex area, equivalent diameter and perimeter of regenerated shoot clusters. A higher correlation of dry weight (DW) was noted with the image feature, weighted density (WD) than the fresh weight (FW) in all the LED treated cultures. The significant correlation between DW and WD implies that the image feature WD can be adopted as a non-invasive approach for measuring biomass accumulation as well as detecting hyperhydricity. The developed machine vision approach provides a new direction in the evaluation of shoot organogenesis that displayed features including both shoot multiplication and canopy development. Chlorophyll and carotenoid contents of the regenerated shoots were found to be higher under BL:RL (1:1) than the other treatments. Supplementation of RL led to a reduction in the pigment contents. Spectral quality of lights also significantly influenced the accumulation of total phenolics, flavonoids and flavonols. Cultures exposed under BL exhibited the maximum accumulation of polyphenols. A similar effect of spectral quality was observed with the antioxidant capacity and reducing power potential of leaf extract. The findings demonstrate the ability of LEDs in inducing shoot regeneration as well as accumulation of phenolic antioxidants and suggest that the proportion of blue and red LEDs is an important factor in achieving the optimum response.

Laser-plasma-based Space Radiation Reproduction in the Laboratory.

Space radiation is a great danger to electronics and astronauts onboard space vessels. The spectral flux of space electrons, protons and ions for example in the radiation belts is inherently broadband, but this is a feature hard to mimic with conventional radiation sources. Using laser-plasma-accelerators, we reproduced relativistic, broadband radiation belt flux in the laboratory, and used this man-made space radiation to test the radiation hardness of space electronics. Such close mimicking of space radiation in the lab builds on the inherent ability of laser-plasma-accelerators to directly produce broadband Maxwellian-type particle flux, akin to conditions in space. In combination with the established sources, utilisation of the growing number of ever more potent laser-plasma-accelerator facilities worldwide as complementary space radiation sources can help alleviate the shortage of available beamtime and may allow for development of advanced test procedures, paving the way towards higher reliability of space missions.

Nanodelivery of Parthenolide Using Functionalized Nanographene Enhances its Anticancer Activity.

Advances in anticancer chemotherapy have been hindered by the lack of biocompatibility of new prospective drugs. One significant challenge concerns water insolubility, which compromises the bioavailability of the drugs leading to increased dosage and higher systemic toxicity. To overcome these problems, nanodelivery has been established as a promising approach for increasing the efficacy and lowering the required dosage of chemotherapeutics. The naturally derived compound, parthenolide (PTL), is known for its anti-inflammatory and anticancer activity, but its poor water solubility limits its clinical value. In the present study, we have used carboxyl-functionalized nanographene (fGn) delivery to overcome the extreme hydrophobicity of this drug. A water-soluble PTL analog, dimethylamino parthenolide (DMAPT), was also examined for comparison with the anticancer efficacy of our PTL-fGn complex. Delivery by fGn was found to increase the anticancer/apoptotic effects of PTL (but not DMAPT) when delivered to the human pancreatic cancer cell line, Panc-1. The IC50 value for PTL decreased from 39 µM to 9.5 µM when delivered as a mixture with fGn. The IC50 of DMAPT did not decrease when delivered as DMAPT-fGn and was significantly higher than that for PTL-fGn. There were significant increases in ROS formation and in mitochondrial membrane disruption in Panc-1 cells after PTL-fGn treatment as compared to PTL treatment, alone. Increases in toxicity were also seen with apoptosis detection assays using flow cytometry, ethidium bromide/acridine orange/DAPI staining, and TUNEL. Thus, fGn delivery was successfully used to overcome the poor water solubility of PTL, providing a strategy for improving the effectiveness of this anticancer agent.

Effect of Liverubin™ on hepatic biochemical profile in patients of alcoholic liver disease: a retrospective study.

Liverubin™ is an available drug in the Indian market that contains silymarin, the major active complex extracted from the medicinal plant milk thistle (Silybum marianum L.). The study retrospectively tracked and analyzed the data of 602 patients, out of which 230 were alcohol induced; 131 with alcohol-induced liver damage (ALD), 13 with liver cirrhosis, and 86 with fatty liver; to assess the effects of water soluble Silymarin (Liverubin™) on important hepatic biochemical parameters. The data was collected from 32 major cities treated by 72 physicians across India who were observed for the specified treatment duration of 11 months. Data was analyzed by using descriptive statistics. At the end of the treatment the hepatic biochemical profile was appreciably improved: the mean % of change in the levels of important hepatic biochemical parameters was observed as follows: total bilirubin 63.48% (direct bilirubin: 64.96%; indirect bilirubin: 61.63%). The serum SGOT and SGPT changed at a mean % of 65.43 and 69.31 respectively while serum alkaline phosphatase was changed at a mean % rate of 39.81. Liverubin™ proved to be safe & well-tolerated among the studied population and no significant treatment related adverse events were reported during the study. Liverubin™ treatment is found to bring about effective lowering of abnormally elevated hepatic biochemical parameters. Liverubin™, water soluble active Silymarin, in the popularly prescribed doses of 140-mg tid is observed to be a promising safe and effective drug in cases of alcoholic liver disease.

A Griffiths-like phase in antiferromagnetic R0.5Eu0.5MnO3 (R = Pr, Nd, Sm).

We report a Griffiths-like phase in isovalent doped rare-earth manganites R(0.5)Eu(0.5)MnO(3) (R = Pr, Nd, Sm). Rietveld refinement of the structural data reveals strong orthorhombic and Jahn-Teller distortions. The dc and ac magnetic studies nicely demonstrate aspects of Griffiths phase-like behaviour. The presence of short range ferromagnetically correlated spin clusters is observed above the antiferromagnetic transition temperature. A disorder driven phase inhomogeneity arising from strong structural distortion is the possible origin of this behaviour.

Nonlinearity exponent of ac conductivity in disordered systems.

We measured the real part of ac conductance Σ(x,f) or Σ(T,f) of iron-doped mixed-valent polycrystalline manganite oxides LaMn(1-x)Fe(x)O(3) as a function of frequency f by varying initial conductance Σ(0) by quenched disorder x at a fixed temperature T (room) and by temperature T at a fixed quenched disorder x. At a fixed temperature T, Σ(x,f) of a sample with fixed x remains almost constant at its zero-frequency dc value Σ(0) at lower frequency. With increase in f, Σ(x,f) increases slowly from Σ(0) and finally increases rapidly following a power law with an exponent s at high frequency. Scaled appropriately, the data for Σ(T,f) and Σ(x,f) fall on the same universal curve, indicating the existence of a general scaling formalism for the ac conductivity in disordered systems. The characteristic frequency f(c) at which Σ(x,f) or Σ(T,f) increases for the first time from Σ(0) scales with initial conductance Σ(0) as f(c) ~ Σ(0)(x(f)), where x(f) is the onset exponent. The value of x(f) is nearly equal to one and is found to be independent of x and T. Further, an inverse relationship between x(f) and s provides a self-consistency check of the systematic description of Σ(x,f) or Σ(T,f). This apparent universal value of x(f) is discussed within the framework of existing theoretical models and scaling theories. The relevance to other similar disordered systems is also highlighted.

Observation of Griffiths phase in antiferromagnetic La(0.32)Eu(0.68)MnO3.

We report the Griffiths phase (GP) scenario for isovalent doping in antiferromagnetic La(0.32)Eu(0.68)MnO(3). Rietveld refinement of structural data displays strong crystal structural distortion. The dc and ac magnetic studies nicely demonstrate unambiguous aspects of robust GP. The presence of ferromagnetically correlated spin clusters is found above the transition temperature, T(N). The disorder-driven phase inhomogeneity is correlated to strong structural distortion, giving rise to the GP. This is an unique example in manganite where double exchange interaction does not play any role for the observed phenomenon.

Charge carrier dynamics and relaxation in (polyethylene oxide-lithium-salt)-based polymer electrolyte containing 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide as ionic liquid.

In this paper we report the dynamics of charge carriers and relaxation in polymer electrolytes based on polyethylene oxide (PEO), lithium bis(trifluoromethylsulfonyl)imide (LiTFSI) and 1-butyl-1-methylpyrrolidinium bis(trifluoromethylsulfonyl)imide (BMPTFSI) ionic liquid prepared by solution cast technique. It has been observed that the incorporation of BMPTFSI into PEO-LiTFSI electrolyte is an effective way for increasing the amorphous phase to a large extent. It has also been observed that both the glass transition and melting temperatures decrease with the increase of BMPTFSI concentration. The ionic conductivity of these polymer electrolytes increases with the increase of BMPTFSI concentration. The highest ionic conductivity obtained at 25 °C is ~3×10(-4) S cm(-1) for the electrolyte containing 60 wt % BMPTFSI and ethylene oxide (EO)/Li ratio of 20. The temperature dependence of the dc conductivity and the hopping frequency show Vogel-Tamman-Fulcher type behavior indicating a strong coupling between the ionic and the polymer chain segmental motions. The frequency dependence of the ac conductivity exhibits a power law with an exponent n which decreases with the increase of temperature. The scaling of the ac conductivity indicates that relaxation dynamics of charge carriers follows a common mechanism for all temperatures and BMPTFSI concentrations. We have also presented the electric modulus data which have been analyzed in the framework of a Havriliak-Negami equation and the shape parameters obtained by the analysis show slight temperature dependence, but change sharply with BMPTFSI concentration. The stretched exponent ß obtained from Kohlrausch-Williams-Watts fit to the modulus data is much lower than unity signifying that the relaxation is highly nonexponential. The decay function obtained from analysis of experimental modulus data is highly asymmetric with time.

Tuning A-site ionic size in R(0.5)Ca(0.5)MnO3 (R = Pr, Nd and Sm): robust modulation in dc and ac transport behavior.

Structural investigations on Pr(0.5)Ca(0.5)MnO(3), Nd(0.5)Ca(0.5)MnO(3) and Sm(0.5)Ca(0.5)MnO(3) display a systematic tuning in orthorhombic distortion which appears due to a change in A-site ionic size. Comprehensive investigations on dc conduction using various models indicate strong correlation with structural changes. Careful analysis of the ac conductivity mechanism as a function of frequency and temperature brings out a pronounced effect of structural modifications on the polaron conduction mechanism. Contrary to typical manifestations, dc conductivity and relaxation of charge carriers reveal non-Arrhenius behavior. This work provides a detailed and systematic addition to the phase diagram of electronic transport in the rare-earth manganite system doped with a divalent alkali atom.

Structural and magnetic properties of spontaneously phase-separated Eu0.5Sm0.5MnO3.

We have studied structural and magnetic properties of Eu(0.5)Sm(0.5)MnO(3). The system shows strong orthorhombic distortion. The static Jahn-Teller effect modifies the low temperature magnetic properties, creating a complicated anisotropic magnetic ground state. A low temperature magnetic phase separation has also been realized that builds magnetic interfaces exhibiting strong exchange bias. Careful analysis of the magnetic behaviour indicates the origin of the exchange bias to be a phase separation between an A-type antiferromagnetic phase and a low temperature highly anisotropic phase originating from another ordering at the rare-earth sublattice.