Reformulation of All ONIOM-Type Molecular Fragmentation Approaches and Many-Body Theories Using Graph-Theory-Based Projection Operators: Applications to Dynamics, Molecular Potential Surfaces, Machine Learning, and Quantum Computing.

We present a graph-theory-based reformulation of all ONIOM-based molecular fragmentation methods. We discuss applications to (a) accurate post-Hartree-Fock AIMD that can be conducted at DFT cost for medium-sized systems, (b) hybrid DFT condensed-phase studies at the cost of pure density functionals, (c) reduced cost on-the-fly large basis gas-phase AIMD and condensed-phase studies, (d) post-Hartree-Fock-level potential surfaces at DFT cost to obtain quantum nuclear effects, and (e) novel transfer machine learning protocols derived from these measures. Additionally, in previous work, the unifying strategy discussed here has been used to construct new quantum computing algorithms. Thus, we conclude that this reformulation is robust and accurate.

Rare Events Sampling Methods for Quantum and Classical Ab Initio Molecular Dynamics.

We provide an approach to sample rare events during classical ab initio molecular dynamics and quantum wavepacket dynamics. For classical AIMD, a set of fictitious degrees of freedom are introduced that may harmonically interact with the electronic and nuclear degrees of freedom to steer the dynamics in a conservative fashion toward energetically forbidden regions. A similar approach when introduced for quantum wavepacket dynamics has the effect of biasing the trajectory of the wavepacket centroid toward the regions of the potential surface that are difficult to sample. The approach is demonstrated for a phenol-amine system, which is a prototypical problem for condensed phase-proton transfer, and for model potentials undergoing wavepacket dynamics. In all cases, the approach yields trajectories that conserve energy while sampling rare events.

Human navicular bone: a morphometric and morphological evaluation.

BACKGROUND: The composition of navicular joint complex is crucial to perform surgical interventions for multiple pathological foot aetiologies. The data on human navicular bone and its facets from Indian population remain scarce in literature. AIMS AND OBJECTIVES: To evaluate the morphometry and morphology of navicular bone. METHODOLOGY: A total of 77 (right: 40; left: 37) dried human navicular bones were used. The collected data were entered and analysed in SPSS software. RESULTS: The anteroposterior diameter of navicular bone on right side was 15.19 mm (13.92, 16.77) and on left side was 15.87 mm (13.83, 17.27). The transverse diameter on right and left sides were 34.21 mm (31.74, 36.6) and 33.59 mm (30.23, 35.43), respectively. The vertical diameter measured on the right was 22.31 mm (21.19, 23.94) and on left 22.53 mm (20.8, 24.24). Morphometric evaluation showed no significant difference between right and left navicular bones. The commonest shape for posterior facet was quadrilateral, on the right (62.5%) and left (40.5%). The most common shape of anterior facet for medial cuneiform is quadrilateral, on the right (85%) and left (89.1%). For intermediate cuneiform, triangular facet was common on the right side (72.5%) and on the left (59.5%). The lateral cuneiform facet was bean shaped on right side (72.5%) and quadrilateral on the left side (32.5%). There was a significant difference in shape distribution between right and left (P < 0.05). The median length of the groove for tibialis posterior tendon was 18.01 mm and 16.19 mm on right and left side, respectively. Cuboid facet was observed in 28 (70%) and 26 (65.9%) navicular bones on right and left sides, respectively. CONCLUSION: There is no significant difference between right and left bones with regards to morphometric parameters. Morphological evaluation revealed significant difference in the distribution of shape between right and left bones.

Establishment of Age Specific Reference Interval for Aminoacids and Acylcarnitine in Dried Blood Spot by Tandem Mass Spectrometry.

The Extended Screening for Inborn Errors of Metabolism is done for aminoacidopathies, fatty acid oxidation disorders and organic acid disorders. In a single dried blood spot, the tandem mass spectrometry is capable of measuring multiple analytes like amino acids, acylcarnitines, nucleosides, succinylacetone and lysophosphatidylcholines. This study was proposed to establish age specific reference internal for aminoacids and acylcartinitine in dried blood spot by tandem mass spectrometry. A total of 480 apparently healthy children were enrolled for the study and sub classified into four groups as follows: Group A: 0-1 month, Group B: 1 month-1 year, Group C: 1-5 year and Group D: 5-12 years each having 120 participants. Sample size were calculated as per CLSI approved guidelines. Tables 1 and 2 presents the age-specific percentile distribution of aminoacids and acylcarnitines established from healthy subjects as per rank-based method recommended by the IFCC and CLSI. Tables 3, 4 and 5 presents the cut-off values of primary and secondary marker/ratios for screening of aminoacidopathies, fatty acid oxidation disorders and organic acid disorders respectively. As a general principle, the interpretation of extended newborn screening results should be based on age specific cut-off established by the laboratory for primary analyte concentration and secondary analyte concentration/ ratios. This study was useful in establishing age specific cut-off values for various amino acids and acylcarnitines in South Indian population. [Table: see text] [Table: see text] [Table: see text] [Table: see text] [Table: see text].

Quantum Computing with Dartboards.

We present a physically appealing and elegant picture for quantum computing, using rules constructed for a game of darts. A dartboard is used to represent the state space in quantum mechanics, and the act of throwing the dart is shown to have close similarities to the concept of measurement or collapse of the wave function in quantum mechanics. The analogy is constructed in arbitrary dimensional spaces, that is, using arbitrary dimensional dartboards, and for such arbitrary spaces this also provides us a "visual" description of uncertainty. Finally, connections between qubits and quantum computing algorithms are also made, opening the possibility to construct analogies between quantum algorithms and coupled dart throws.

Graph-|Q⟩⟨C|: A Quantum Algorithm with Reduced Quantum Circuit Depth for Electronic Structure.

The accurate determination of chemical properties is known to have a critical impact on multiple fundamental chemical problems but is deeply hindered by the steep algebraic scaling of electron correlation calculations and the exponential scaling of quantum nuclear dynamics. With the advent of new quantum computing hardware and associated developments in creating new paradigms for quantum software, this avenue has been recognized as perhaps one way to address exponentially complex challenges in quantum chemistry and molecular dynamics. In this paper, we discuss a new approach to drastically reduce the quantum circuit depth (by several orders of magnitude) and help improve the accuracy in the quantum computation of electron correlation energies for large molecular systems. The method is derived from a graph-theoretic approach to molecular fragmentation and enables us to create a family of projection operators that decompose quantum circuits into separate unitary processes. Some of these processes can be treated on quantum hardware and others on classical hardware in a completely asynchronous and parallel fashion. Numerical benchmarks are provided through the computation of unitary coupled-cluster singles and doubles (UCCSD) energies for medium-sized protonated and neutral water clusters using the new quantum algorithms presented here.

Intrathecal pain pumps in pain relief.

Chronic pain is a significant global health issue, described as a bio-psychosocial phenomenon that hampers the integration of body, mind, and social functions. To relieve chronic intractable pain, intrathecal drug-delivery devices (IDDDs) are the last resort after conventional treatment options have been exhausted. This article outlines the indications, pharmacological agents, types, techniques, preparation of the patient, and complications of IDDDs for the management of challenging chronic pain (non-neoplastic and cancer-related pain) conditions in patients who have not responded well to a commonly used conventional line of treatment.

Synchronous COD removal and nitrogen recovery from high concentrated pharmaceutical wastewater by an integrated chemo-biocatalytic reactor systems.

Present report, an investigation of highly concentrated and low bio-degradable pharmaceutical wastewater (HCPWW) treatment; simultaneously ammoniacal nitrogen recovery for struvite fertilizer. The use of multiple solvents and many formulation processes in HCPWW, resulting highly refractory chemicals. Here, in this study focused on evaluation of chemo-biocatalysts for the removal of refractory organics, nitrogen recovery from HCPWW. The initial organics, and nitrogen content in HCPWW was 20,753 ± 4606 mg/L; BOD, 6550 ± 1500 mg/L and NH4+-N, 1057.9 ± 185.8 mg/L. Initially, the biodegradability (BOD5: COD ratio from 0.32 to 0.45) of HCPWW, which was improved by heterogeneous Fenton oxidation (HFO) processes, and porous carbon (PCC, 30 g/L), along with FeSO4.7H2O, 200 mg/L and H2O2 (30% v/v), 0.4 ml/L were used as a catalyst in a weakly acidic medium. For the biocatalytic processes, the microbial culture cultivated from sewage and incorporated into a Fluidized Immobilized Carbon Catalytic Oxidation reactor (FICCO), and dominant species are Pseudomonas Putida sp., Pseudomonas Kilionesis sp., and Pseudomonas Japonica sp., which is identified by using 16 S rDNA sequencing analysis. The COD and BOD5 removal efficiency of 65-93% and 70-82%, and follow the pseudo-second-order kinetic model with the rate constants of 1.0 × 10-4 L COD-1 h-1, 1.5 × 10-3 L COD-1 h-1 and 3.0 × 10-3 L COD-1 h-1 in the HFO-FICCO-CAACO catalytic processes. The optimized hydraulic retention time (HRT) of FICCO reactor was 24 h, and 1 h for the Chemo-Autotrophic Activated Carbon Oxidation (CAACO) reactor for maximum organics removal. MAP (Magnesium Ammonium Phosphate precipitation) process showed 90% of NH4+-N elimination and recovered it as a struvite fertilizer at an optimum molar ratio of 1:1.3:1.3 (NH4+-N: Na2HPO4.2H2O: MgO). FT-IR, UV-visible, and UV-fluorescence data confirm the effective elimination of organics. Hence, this integrated treatment system is appropriate for the management of pharmaceutical wastewater especially elimination of complex organic molecules and the recovery of nitrogen in the wastewater.

Hamiltonian Engineering with Multicolor Drives for Fast Entangling Gates and Quantum Crosstalk Cancellation.

Quantum computers built with superconducting artificial atoms already stretch the limits of their classical counterparts. While the lowest energy states of these artificial atoms serve as the qubit basis, the higher levels are responsible for both a host of attractive gate schemes as well as generating undesired interactions. In particular, when coupling these atoms to generate entanglement, the higher levels cause shifts in the computational levels that lead to unwanted ZZ quantum crosstalk. Here, we present a novel technique to manipulate the energy levels and mitigate this crosstalk with simultaneous off-resonant drives on coupled qubits. This breaks a fundamental deadlock between qubit-qubit coupling and crosstalk. In a fixed-frequency transmon architecture with strong coupling and crosstalk cancellation, additional cross-resonance drives enable a 90 ns CNOT with a gate error of (0.19±0.02)%, while a second set of off-resonant drives enables a novel CZ gate. Furthermore, we show a definitive improvement in circuit performance with crosstalk cancellation over seven qubits, demonstrating the scalability of the technique. This Letter paves the way for superconducting hardware with faster gates and greatly improved multiqubit circuit fidelities.

Alleviation of cadmium phytotoxicity through melatonin modulated physiological functions, antioxidants, and metabolites in tomato (Solanum lycopersicum L.).

The rising concentration of cadmium (Cd) builds a harmful effect on human and plant health associated with food chain contagion. Melatonin (MT) is an indole compound. Hence, the experiment was conducted to understand the physiological and biochemical mechanism of Cd detoxification by exogenous MT in tomato. Pots were filled with 30 ppm of Cd spiked soil and different concentration of exogenous MT was given to the plants through seed treatment (250 ppm), foliar spray viz., 25, 50, and 100 ppm, and both, whereas the foliar spray was given at 30 days after transplanting (DAT) and 46 DAT. When the plants are exposed to Cd stress, it reduces the gas exchange characters. The results revealed that foliar spray of 25 ppm of exogenous MT recorded the highest photosynthetic rate, stomatal conductance, and osmotic potential. MT had a direct interaction with reactive oxygen species scavenging by elevating endogenous antioxidant enzymes as well as the metabolites in plants. The contribution of MT foliar spray of 25 ppm at 30 and 46 DAT can mitigate Cd stress and it has potential implications for ensuring food safety and food security in marginal agriculture.

Response evaluation of locoregional therapies in combined hepatocellular-cholangiocarcinoma and intrahepatic cholangiocarcinoma versus hepatocellular carcinoma: a propensity score matched study.

AIM: To evaluate the response of locoregional therapy (LRT) on combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (IHC) and compare their outcomes with propensity matched hepatocellular carcinoma (HCC) patients. MATERIALS AND METHODS: From January 2011 to July 2020, 13 patients with cHCC-CC (11 men, two women, median age 56 years) and 15 IHC patients (10 men, five women, median age 60 years) were compared with 101 HCC patients (79 men, 22 women, median age 60 years) after LRT. All tumours were proven histologically. Among the 13 cHCC-CC patients, 11 received transarterial chemoembolisation (TACE), one received microwave ablation (MWA) and one received TACE with radiofrequency ablation (RFA). Of 15 IHC patients, eight received TACE, five received RFA, and one received MWA, and one received TACE with RFA. Propensity score matching (PSM) was done with conditional logistic regression adjusted for age, type of LRT, tumour specific features and Child-Pugh score. RESULTS: After LRT, on univariate analysis an objective response was seen in 30% of cHCC-CC and 53% of IHC patients. PSM analysis demonstrated shorter progression-free survival (PFS; cHCC-CC versus HCC: 1.5 versus 7.5 months; IHC versus HCC: 6 versus 14 months, p<0.05), overall survival (OS; cHCC-CC versus HCC: 12 versus 28 months; IHC versus HCC: 18 versus 34 months, p<0.005), and poor objective response (cHCC-CC versus HCC: 25% versus 91%; IHC versus HCC: 58% versus 88%, p<0.05) in cHCC-CC and IHC patients versus HCC patients. Hypovascular tumour, macrovascular invasion, and infiltrative appearance were independent prognostic factors for OS in IHC patients. CONCLUSION: cHCC-CC and IHC are aggressive tumours with a poor objective response, greater distant progression of the disease and shorter PFS and OS post LRT as compared to HCC.

Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis.

Locoregional recurrences following surgery for esophageal cancers represent a significant clinical problem with no standard recommendations for management. We conducted this systematic review and meta-analysis with the objective of studying safety and efficacy of salvage radiotherapy in this setting. All prospective and retrospective cohort studies, which studied patients who developed locoregional recurrence following initial radical surgery for esophageal cancer and subsequently received salvage radiation therapy (RT)/chemoradiation with all relevant information regarding survival outcome and toxicity available, were included. The quality of eligible individual studies was assessed using the Newcastle-Ottawa Scale score for risk of bias. R package MetaSurv was used to obtain a summary survival curve from survival probabilities and numbers of at-risk patients collected at various time points and to test the overall heterogeneity using the I2 statistic. Thirty studies (27 retrospective, 3 prospective) published from 1995 to 2020 with 1553 patients were included. The median interval between surgery and disease recurrence was 12.5 months. The median radiation dose used was 60 Gy and 57% received concurrent chemotherapy. The overall incidence of acute grade 3/4 mucositis and dermatitis were 8 and 4%, respectively; grade 3/4 acute pneumonitis was reported in 5%. The overall median follow-up of all studies included was 27 months. The 1-, 2- and 3-year overall survival (OS) probabilities were 67.9, 35.9 and 30.6%, respectively. Factors which predicted better survival on multivariate analysis were good PS, lower group stage, node negativity at index surgery, longer disease-free interval, nodal recurrence (as compared to anastomotic site recurrence), smaller disease volume, single site of recurrence, RT dose >50 Gy, conformal RT, use of concomitant chemotherapy and good radiological response after radiotherapy. Salvage radiotherapy with or without concomitant chemotherapy for locoregional recurrences after surgery for esophageal cancer is safe and effective. Modern radiotherapy techniques may improve outcomes and reduce treatment-related morbidity.

Development of AI classification model for angiosome-wise interpretive substantiation of plantar feet thermal asymmetry in type 2 diabetic subjects using infrared thermograms.

Diabetic Foot Syndrome (DFS) is the prime impetus for most of the lower extremity complications among the diabetic subjects. DFS is characterized by aberrant variations in plantar foot temperature distribution while healthy subjects exhibit a symmetric thermal pattern between the contralateral and ipsilateral plantar feet. Thus, "asymmetry analysis" of foot thermal distribution is contributory in assessment of overall foot health of diabetic subjects. The study, aims to classify symmetric and asymmetric foot regions angiosome-wise, by comparing minimal number of color image features - color moments and Dissimilarity Index. Further, the asymmetric foot regions are assessed for identifying the hotspots within such angiosomes of the patients that characterize the possibility of onset of diabetic foot ulcer. The color feature based machine learning model developed, achieved an accuracy of 98% for a 10-fold cross validation, test accuracy of 96.07% and 0.96 F1-score thereby convincing that the chosen features are amplest and conducive in the asymmetry analysis. The developed model was validated for generalization by testing on a public benchmark dataset, in which the model achieved 92.5% accuracy and 0.91 F1 score.

Demonstration of a High-Fidelity cnot Gate for Fixed-Frequency Transmons with Engineered ZZ Suppression.

Improving two-qubit gate performance and suppressing cross talk are major, but often competing, challenges to achieving scalable quantum computation. In particular, increasing the coupling to realize faster gates has been intrinsically linked to enhanced cross talk due to unwanted two-qubit terms in the Hamiltonian. Here, we demonstrate a novel coupling architecture for transmon qubits that circumvents the standard relationship between desired and undesired interaction rates. Using two fixed frequency coupling elements to tune the dressed level spacings, we demonstrate an intrinsic suppression of the static ZZ while maintaining large effective coupling rates. Our architecture reveals no observable degradation of qubit coherence (T_{1},T_{2}>100 µs) and, over a factor of 6 improvement in the ratio of desired to undesired coupling. Using the cross-resonance interaction, we demonstrate a 180 ns single-pulse controlled not (cnot) gate, and measure a cnot fidelity of 99.77(2)% from interleaved randomized benchmarking.

Molecular dynamics modeling of lithium ion intercalation induced change in the mechanical properties of LixMn2O4.

The objective of this study is to understand the fracture mechanisms in the lithium manganese oxide (LiMn2O4) electrode at the molecular level by studying mechanical properties of the material at different values of the State of Charge (SOC) using the principles of molecular dynamics (MD). A 2 × 2 × 2 cubic structure of the LiMn2O4 unit cell containing eight lithium ions, eight trivalent manganese ions, eight tetravalent manganese ions, and 32 oxygen ions is studied using a large-scale atomic/molecular massively parallel simulator. As part of the model validation, the lattice parameter and volume changes of LixMn2O4 as a function of SOC (0 < x < 1) have been studied and validated with respect to the experimental data. This validated model has been used for a parametric study involving the SOC value, strain rate (charge and discharge rate), and temperature. The MD simulations suggest that the lattice constant varies from 8.042 Å to 8.235 Å during a full discharging cycle, in agreement with the experimental data. The material at higher SOC shows more ductile behavior compared to low SOC values. Furthermore, yield and ultimate stresses are less at lower SOC values except when SOC values are within 0.125 and 0.375, verifying the phase transformation theory in this range. The strain rate does not affect the fully intercalated material significantly but seems to influence the material properties of the partially charged electrode. Finally, a study of the effect of temperature suggests that diffusion coefficient values for both high and low-temperature zones follow an Arrhenius profile, and the results are successfully explained using the vacancy diffusion mechanism.

Domination of Filamentous Anoxygenic Phototrophic Bacteria and Prediction of Metabolic Pathways in Microbial Mats from the Hot Springs of Al Aridhah.

Microbial mats in hot springs form a dynamic ecosystem and support the growth of diverse communities with broad-ranging metabolic capacity. In this study, we used 16S rRNA gene amplicon sequencing to analyse microbial communities in mat samples from two hot springs in Al Aridhah, Saudi Arabia. Putative metabolic pathways of the microbial communities were identified using phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt). Filamentous anoxygenic phototrophic bacteria associated with phylum Chloroflexi were abundant (> 50 %) in both hot springs at 48 °C. Chloroflexi were mainly represented by taxa Chloroflexus followed by Roseiflexus. Cyanobacteria of genus Arthrospira constituted 3.4 % of microbial mats. Heterotrophic microorganisms were mainly represented by Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes. Archaea were detected at a lower relative abundance (< 1 %). Metabolic pathways associated with membrane transport, carbon fixation, methane metabolism, amino acid biosynthesis, and degradation of aromatic compounds were commonly found in microbial mats of both hot springs. In addition, pathways for production of secondary metabolites and antimicrobial compounds were predicted to be present in microbial mats. In conclusion, microbial communities in the hot springs of Al Aridhah were composed of diverse bacteria, with taxa of Chloroflexus being dominant.

Latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy.

AIM: To assess if latent autoimmune diabetes of adulthood (LADA) is associated with small fibre neuropathy. METHODS: Participants with LADA (n=31), Type 2 diabetes (n=31) and healthy control participants without diabetes (n=31) underwent a detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, skin biopsy and corneal confocal microscopy. RESULTS: The groups were matched for age (healthy control without diabetes: 53.5±9.1 vs. Type 2 diabetes: 58.0±6.5 vs. LADA: 53.2±11.6 years), duration of diabetes (Type 2 diabetes: 10.0±8.3 vs. LADA: 11.0±9.1 years) and blood pressure. However, BMI (P=0.01) and triglycerides (P=0.0008) were lower and HbA1c (P=0.0005), total cholesterol (P=0.01) and HDL (P=0.002) were higher in participants with LADA compared with Type 2 diabetes. Peroneal motor nerve conduction velocity (P=0.04) and sural sensory nerve conduction velocity (P=0.008) were lower in participants with latent autoimmune diabetes in adults compared with Type 2 diabetes. Intra-epidermal nerve fibre density (P=0.008), corneal nerve fibre density (P=0.003) and corneal nerve branch density (P=0.006) were significantly lower in participants with LADA compared with Type 2 diabetes. There were no significant differences in the other neuropathy parameters. CONCLUSIONS: Despite comparable age and duration of diabetes, participants with LADA demonstrate more severe neuropathy and particularly small fibre neuropathy, compared with participants with Type 2 diabetes.

Challenges in constructing accurate methods for hydrogen transfer reactions in large biological assemblies: rare events sampling for mechanistic discovery and tensor networks for quantum nuclear effects.

We present two methods that address the computational complexities arising in hydrogen transfer reactions in enzyme active sites. To address the challenge of reactive rare events, we begin with an ab initio molecular dynamics adaptation of the Caldeira-Leggett system-bath Hamiltonian and apply this approach to the study of the hydrogen transfer rate-determining step in soybean lipoxygenase-1. Through direct application of this method to compute an ensemble of classical trajectories, we discuss the critical role of isoleucine-839 in modulating the primary hydrogen transfer event in SLO-1. Notably, the formation of the hydrogen bond between isoleucine-839 and the acceptor-OH group regulates the electronegativity of the donor and acceptor groups to affect the hydrogen transfer process. Curtailing the formation of this hydrogen bond adversely affects the probability of hydrogen transfer. The second part of this paper deals with complementing the rare event sampled reaction pathways obtained from the aforementioned development through quantum nuclear wavepacket dynamics. Essentially the idea is to construct quantum nuclear dynamics on the potential surfaces obtained along the biased trajectories created as noted above. Here, while we are able to obtain critical insights on the quantum nuclear effects from wavepacket dynamics, we primarily engage in providing an improved computational approach for efficient representation of quantum dynamics data such as potential surfaces and transmission probabilities using tensor networks. We find that utilizing tensor networks yields an accurate and efficient description of time-dependent wavepackets, reduced dimensional nuclear eigenstates and associated potential energy surfaces at much reduced cost.

Impairment of Nrf2- and Nitrergic-Mediated Gastrointestinal Motility in an MPTP Mouse Model of Parkinson's Disease.

BACKGROUND: Gastrointestinal (GI) motility dysfunction is the most common non-motor symptom of Parkinson's disease (PD). Studies have indicated that GI motility functions are impaired before the onset of PD. AIMS: To investigate the underlying mechanism of PD-induced GI dysmotility in MPTP (1-methyl 4-phenyl 1,2,3,6-tetrahydropyridine)-induced animal model. METHODS: C57BL/6 mice were administered with or without a selective dopamine neurotoxin, MPTP, to induce parkinsonian symptoms. In addition to in vivo studies, in vitro experiments were also conducted in colon specimens using l-methyl-4-phenylpyridinium (MPP+), a metabolic product of MPTP. Gastric emptying, colon motility, nitrergic relaxation, and western blot experiments were performed as reported. RESULTS: MPTP-induced PD mice showed decreased expression of nuclear factor erythroid 2-related factor (Nrf2) and its target phase II genes in gastric and colon neuromuscular tissues. Decreased levels of tetrahydrobiopterin (BH4, a critical cofactor for nNOS dimerization) associated with uncoupling of nNOS in gastric and colon tissues exposed to MPTP. Impaired enteric nitrergic system led to delayed gastric emptying and slower colonic motility compared to the control mice. In vitro results in colon specimens confirm that activation of Nrf2 restored MPP+-induced suppression of alpha-synuclein, tyrosine hydroxylase (TH), Nrf2, and heme oxygenase-1. In vitro exposure to L-NAME [N(w)-nitro-L-arginine methyl ester], a NOS synthase inhibitor, reduced protein expression of TH in colon tissue homogenates. CONCLUSIONS: Loss of Nrf2/BH4/nNOS expression in PD impairs antioxidant gene expression, which deregulates NO synthesis, thereby contributing to the development of GI dysmotility and constipation. Nitric oxide appears to be important to maintain dopamine synthesis in the colon.

Measurement of changes in optic nerve sheath diameter using ultrasound and computed tomography scan before and after the ventriculoperitoneal shunt surgery in patients with hydrocephalus - A prospective observational trial.

BACKGROUND: The standard methods for measuring intracranial pressure (ICP) are invasive in nature. Non invasive methods such as ONSD may help circumvent these complications and may serve as a surrogate marker for increased ICP. The primary aim of this study was to assess the ONSD (optic nerve sheath diameter) changes using ultrasonography (USG) and computed tomography (CT) scan in hydrocephalus patients before and after the insertion of VP shunt. MATERIALS AND METHODS: A prospective observational study was conducted among 69 patients undergoing VP shunt surgery between the ages of 2 to 60 years. ONSD variation was measured by USG and CT scan both before and after the surgery. The difference in the pre-operative and post-operative ONSD measurement was analyzed using a paired t-test. Whereas, the measurements of ONSD were compared for agreement between two modalities (USG and CT) using Interclass correlation (ICC) and Bland Altman graph plot. RESULTS: Among 69 patients 38 were males, 31 were females and 12 were under the age of 10 years. In the adult group, average preoperative and postoperative ONSD measurement by USG was 5.80 ± 0.63 mm and 4.52 ± 0.72 (p < 0.001) and by CT was 5.77 ± 0.83 mm and 4.49 ± 0.76 mm (p < 0.001) respectively. Similarly, in the pediatric population, average preoperative and postoperative ONSD measurement by USG was found to be 4.76 ± 1.14 mm and 3.90 ± 1.08 mm and by CT was found to be 4.75+/-1.11 mm and 3.85 ± 1.09 mm respectively (p <0.001). CONCLUSION: In patients with hydrocephalus undergoing VP shunt surgery, we found a significant reduction in ONSD after the shunt insertion in both pediatric and adult population. We also found a good correlation between the USG and CT scan measurements of ONSD.