Insights from in silico study of receptor energetics of SARS-CoV-2 variants.

The emergence of new variants of the novel coronavirus SARS-CoV-2 with increased infectivity, superior virulence, high transmissibility, and unmatched immune escape has demonstrated the adaptability and evolutionary fitness of the virus. The subject of relative order of the binding affinity of SARS-CoV-2 variants with the human ACE2 (hACE2) receptor is hotly debated and its resolution has implications for drug design and development. In this work, we have investigated the energetics of the binding of receptor binding domain (RBD) of SARS-CoV-2 variants of concern (VOCs): Beta (B.1.351), Delta (B.1.617.2), Omicron (B.1.1.529), variant of interest (VOI): Kappa (B.1.617.1), and Delta Plus (B.1.617.2.1) variant with the human ACE2 receptor by using the umbrella sampling (US) method. Our work indicates that Delta and Delta Plus variants have greater values of the US binding free energy than Wild-type (WT), whereas Beta, Kappa, and Omicron variants have lower values. Further analysis of hydrogen bonding, salt bridges, non-bonded interaction energy, and contact surface area at the RBD-hACE2 interface establish Delta as the variant with the highest binding affinity among these variants.

Base flipping mechanism and binding strength of methyl-damaged DNA during the interaction with AGT.

Methyl damage to DNA bases is common in the cell nucleus. O6-alkylguanine-DNA alkyl transferase (AGT) may be a promising candidate for direct damage reversal in methylated DNA (mDNA) at the O6 point of the guanine. Indeed, atomic-level investigations in the contact region of AGT-DNA complex can provide an in-depth understanding of their binding mechanism, allowing to evaluate the silico-drug nature of AGT and its utility in removing methyl damage in DNA. In this study, molecular dynamics (MD) simulation was utilized to examine the flipping of methylated nucleotide, the binding mechanism between mDNA and AGT, and the comparison of binding strength prior and post methyl transfer to AGT. The study reveals that methylation at the O6 atom of guanine weakens the hydrogen bond (H-bond) between guanine and cytosine, permitting for the flipping of such nucleotide. The formation of a H-bond between the base pair of methylated nucleotide (i.e., cytosine) and the intercalated arginine of AGT also forces the nucleotide to rotate. Following that, electrostatics and van der Waals contacts as well as hydrogen bonding contribute to form the complex of DNA and protein. The stronger binding of AGT with DNA before methyl transfer creates the suitable condition to transfer methyl adduct from DNA to AGT.

A 5'-Flanking C/G Pair at the Core Region Enhances the Recognition and Binding of Kaiso to Methylated DNA.

Methyl CpG binding proteins (MBPs) are transcription factors that recognize the methylated CpG sites in DNA and mediate the DNA methylation signal into various downstream cellular processes. The C2H2 zinc finger (ZF) protein, Kaiso, also an MBP, preferentially binds to two symmetrically methylated CpG sites in DNA sequences via C-terminal C2H2 ZF domains and mediates the transcription regulation process. Investigation of the molecular mechanism of the recognition of methylated DNA (meDNA) by Kaiso is important to understand how this protein reads and translates this methylation signal into downstream transcription outcomes. Despite previous studies in Kaiso-meDNA interactions, detailed structural investigations on the sequence-specific interaction of Kaiso with the meDNA sequence are still lacking. In this work, we used molecular modeling and molecular dynamics (MD) simulation-based computational approaches to investigate the recognition of various methylated DNA sequences by Kaiso. Our MD simulation results show that the Kaiso-meDNA interaction is sequence specific. The recognition of meDNA by Kaiso is enhanced in the MeECad sequence compared to the MeCG2 sequence. Compared to the 5'-flanking T/A pair in MeCG2, both MeCG2_mutCG and MeECad sequences show that a C/G base pair allows GLU535 of Kaiso to preferably recognize and bind the core mCpG site. The core mCGmCG site is crucial for the recognition process and formation of a stable complex. Our results reveal that the 5'-flanking nucleotides are also important for the enhanced binding and recognition of methylated sites.

Structural stability of R-state conformation of carbonmonoxyl sickle and normal hemoglobin dimer.

A mutation at the sixth residue, glutamic acid to valine, in beta chain of hemoglobin distorts the entire shape of hemoglobin into a sickle shape. The investigation of the binding mechanisms of different chains of hemoglobin under the mutated condition can give an understanding of the molecular distortion. In this work, we have studied the binding mechanism between two chains in the dimer structure of the R-state conformation of carbonmonoxyl sickle hemoglobin and is compared with that of normal hemoglobin by using molecular dynamics simulations. The binding strength between α-chain (PROA) and ß-chain (PROB) in hemoglobin dimer has been analyzed by estimating hydrogen bonds, salt bridges, hydrophobic interactions and non-bonded interactions (electrostatics and van der Waals). The quantitative estimation of aforementioned interactions depicts that the structural stability of normal hemoglobin dimer is found to be greater than that of sickle one. The outcomes of such interactions are also supported by the estimated free energy between the chains in R-state conformation of the dimers. The difference of binding free energy, calculated by utilizing the umbrella sampling technique, is found to be ≈ (0.67 ± 0.06) kcal/mol.Communicated by Ramaswamy H. Sarma.

Microsatellite instability in colon cancer: A single center experience from North India.

Background: Due to the defects of mismatch repair (MMR) genes MLH1, PMS2, MSH2, and MSH6, the mutations which occur in microsatellite region are not repaired during deoxyribonucleic acid synthesis, leading to microsatellite instability (MSI). MSI is one of the major molecular changes that occur in colorectal carcinoma (CRC). Studies have shown that MMR deficient CRC has different clinicopathological characteristics and a better stage adjusted survival when compared to microsatellite stable tumors. Materials and Methods: We have retrospectively analyzed the cases of colon cancers treated in our institute for 3 years from 2017 to 2019. Most of the patients underwent surgery and received adjuvant chemotherapy. MSI testing was done in surgical specimen with immunohistochemistry. The clinical details of the patients were tabulated in Microsoft Excel, and statistical analysis was done using IBM SPSS Statistics for Windows, version 21 (IBM Corp., Armonk, NY, USA). Results: A total of 52 patients who were treated in our institution from 2017 to 2019 were analyzed. The mean age was 46.8 ± 13.5 (19-72) years. The male-to-female ratio was 8:5. No significant association in patient demographics and clinicopathological parameters was observed between MSI stable and unstable disease. However, lymphovascular invasion showed a significantly higher trend in MSI unstable patients (P = 0.052). The median progression-free survival (PFS) of the entire cohort was 27.8 months (95% confidence interval = 22.7-32.9) and the median overall survival (OS) is not reached. The median PFS is 21.3 months in MSI stable patients whereas it is not reached in MSI unstable patients (P = 0.049). The median OS is 27.1 months in MSI stable patients, but it is not reached in MSI unstable patients and the difference shows a trend towards statistical significance (P = 0.061). Conclusion: MSI unstable tumors were found to have higher PFS and higher OS in our study. It needs prospective validation in larger studies in Indian scenario.

Adsorption of water on C sites vacancy defected graphene/h-BN: First-principles study.

Heterostructures (HS), vacancy defects in HS, and molecular adsorption on defected HS of 2D materials are fervently inspected for a profusion of applications because of their aptness to form stacked layers that confer approach to an amalgamation of favorable electronic and magnetic properties. In this context, graphene (Gr), hexagonal boron nitride (h-BN), HS of graphene/h-BN (Gr/h-BN), and molecular adsorption on Gr/h-BN offer promising prospects for electronic, spintonic, and optoelectronic devices. In this study, we investigated the structural, electronic, and magnetic properties of C sites vacancy defects in Gr/h-BN HS and adsorption of water molecule on defected Gr/h-BN HS materials by using first-principles calculations based on spin-polarized density functional theory method within van der Waals (vdW) corrections DFT-D2 approach. We found that these considered materials are stable 2D vdW HS. Based on band structure calculations, they are semimetallic, and on density of states and partial density of states analysis, they are magnetic materials. The magnetic moment developed in these defected systems is due to the unpaired up-spin and down-spin states in the orbitals of atoms present in the materials created by the vacancy defects.

Structural insights into the repair mechanism of AGT for methyl-induced DNA damage.

Methylation induced DNA base-pairing damage is one of the major causes of cancer. O6-alkylguanine-DNA alkyltransferase (AGT) is considered a demethylation agent of the methylated DNA. Structural investigations with thermodynamic properties of the AGT-DNA complex are still lacking. In this report, we modeled two catalytic states of AGT-DNA interactions and an AGT-DNA covalent complex and explored structural features using molecular dynamics (MD) simulations. We utilized the umbrella sampling method to investigate the changes in the free energy of the interactions in two different AGT-DNA catalytic states, one with methylated GUA in DNA and the other with methylated CYS145 in AGT. These non-covalent complexes represent the pre- and post-repair complexes. Therefore, our study encompasses the process of recognition, complex formation, and separation of the AGT and the damaged (methylated) DNA base. We believe that the use of parameters for the amino acid and nucleotide modifications and for the protein-DNA covalent bond will allow investigations of the DNA repair mechanism as well as the exploration of cancer therapeutics targeting the AGT-DNA complexes at various functional states as well as explorations via stabilization of the complex.

"Christie Regimen" palliative radiotherapy in advanced head-and-neck cancer: A single-center experience.

BACKGROUND: Relevance of aggressive treatment in advanced head neck squamous cell cancers(HNSCC) is debatable in view of expected poor outcome. Long treatment duration only adds up to the cost of treatment without any improvements in outcomes. AIMS AND OBJECTIVES: To assess the outcomes of hypofractionated "Christie" palliative radiotherapy regimen in advanced HNSCC. MATERIALS AND METHODS: Patients of advanced HNSCC registered from June 2015 to June 2019 were treated by parallel pair field technique on Cobalt60 machine (Theatron 780E) to total dose of 50 Gray/16 fractions over 3.2 weeks. Toxicity was scored using Radiation Therapy Oncology Group (RTOG) criteria and response was evaluated as per WHO criteria. RESULTS: Records of 110 patients of HNSCC with mean age of 56.19 years were analysed. Evaluation at 4-8 weeks after radiotherapy resulted in a complete response (CR) in 19.1%, partial response (PR) in 32.7%, stable disease (SD) in 29.1% and progressive disease (PD) in 3.6%, while 15.5% patients did not report for post treatment evaluation. Median progression free survival was 9.52 months (95% CI 5.9 - 13.1 months). The median overall survival was 12.7 ± 2.2 months (95% CI 8.2 - 17.2). Median time to progression after completion of radiotherapy was 84 days. Grade IV dermatitis and mucositis was encountered in 2.7% and 1.8% cases respectively, requiring hospitalization. CONCLUSION: Christie regimen for advanced HNSCC is a clinically viable option with acceptable outcomes in a resource constrained setting.

First-principles study of structure, electronic, and magnetic properties of C sites vacancy defects in water adsorbed graphene/MoS2 van der Waals heterostructures.

We have studied structure, electronic, and magnetic properties of water adsorbed vdW heterostructure graphene/MoS2 (w-(HS)G/MoS2) and its C sites vacancy defects materials (w-Catoms-vacancy-(HS)G/MoS2) by using a spin polarized density functional theory (DFT) method of calculations within DFT-D2 approach to take in to account of vdW interactions. All the structures are optimized and relaxed by BFGS method using computational tool Quantum ESPRESSO package. By structural analysis, we found that both w-(HS)G/MoS2 and w-Catoms-vacancy-(HS)G/MoS2 are stable materials. The stability and compactness of these materials decrease with an increase in their defects concentrations. From band structure calculations, our findings show that w-(HS)G/MoS2 has a metallic nature, and there is formation of n-type Schottky contact of barrier height 0.42 eV. Also, the left 1C atom vacancy defects in w-(HS)G/MoS2 (L1C-w-(HS)G/MoS2) and center 1C atom vacancy defects in w-(HS)G/MoS2 (C1C-w-(HS)G/MoS2) materials have no band gap for up and down spin electronic states, indicating that they have also a metallic nature. On the other hand, 2C atom vacancy defects in w-(HS)G/MoS2 (2C-w-(HS)G/MoS2) has a small band gap for up spins states and no band gap for down spin electronic states which means that the band structure resembles with half metallic nature. Thus, the endowment of metallic nature decreased with increase in the concentrations of defects in structures. To study the magnetic properties in materials, DOS and PDOS calculations are used, and we found that non-magnetic w-(HS)G/MoS2 material changes to magnetic in all the three different L1C-w-(HS)G/MoS2, C1C-w-(HS)G/MoS2, and 2C-w-(HS)G/MoS2 materials with vacancy. L1C-w-(HS)G/MoS2, C1C-w-(HS)G/MoS2, and 2C-w-(HS)G/MoS2 have magnetic moments of + 0.21 µB/cell, + 0.26 µB/cell, and - 2.00 µB/cell, respectively. The spins of electrons in 2s and 2p orbitals of C atoms give a principal effect of magnetism in w-Catoms-vacancy-(HS)G/MoS2 materials.

Prevalence of Hypertension in a Community.

INTRODUCTION: Hypertension is one of the leading risk factors for the global burden of disease and is of rising public health concerns in the developing world including Nepal. However, few studies have focused on awareness, treatment, and control of hypertension among people living with this condition. In this scenario, this study aimed to find out the prevalence of hypertension and its awareness, treatment, and control among hypertensive patients residing in different parts of Kaski district, Nepal. METHODS: A descriptive cross-sectional study was performed among 977 family members of 290 households from August to December 2017. Ethical approval was taken from the Institutional Review Committee (reference number:73/074/75) of the Pokhara University Research Center. Simple random sampling was done. Hypertension screening was performed through averaging three values obtained by standardized aneroid sphygmomanometer in three observations. Primary data was collected through self-administered questionnaires and face-to-face interviews based on the participant's preferences. Collected data were analyzed using Statistical Package for the Social Sciences version 20. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Out Of total 997 family members screened, 294 (29.49%) (26.66-32.32 at 95% confidence interval) had hypertension whereas only 127 (43.2%) were completely aware of their disease condition. 279 (94.9%) were taking antihypertensive medication and 201 (68.4%) had their blood pressure controlled. CONCLUSIONS: We found that almost one-fourth of the adult population in the community suffered from hypertension but less than half of the hypertensive patients are aware of their conditions.

Primary CNS Lymphoma in India: A 17-Year Experience From the All India Institute of Medical Sciences.

PURPOSE: The information about the outcome of primary CNS lymphoma (PCNSL) in India is scarce, because there is no population-based or large hospital-based data. MATERIALS AND METHODS: This is a retrospective study that spanned 17 years (2001 to 2017) to study the outcome of PCNSL at the All India Institute of Medical Sciences (AIIMS), which is a tertiary care center in Northern India. RESULTS: Only one of 99 patients was positive for HIV serology. Diffuse large B-cell lymphoma was the most common histology (97.7%). The median patient age was 50 years (range, 13 to 70 years), and the ratio of men to women was 1.9. The median duration of symptoms before diagnosis was 3.5 months (range, 0.5 to 48 months), and 58.5% had a performance status (PS) of 3 or more. Multiple intracranial lesions were present in 81.8% of patients. Surgical resection was performed in 45%, and approximately 22% of patients were ineligible for treatment. Most patients (n = 73) were treated with high-dose methotrexate (HDMTX)-based regimens (ie, methotrexate, vincristine, and procarbazine with or without rituximab). Pharmacokinetic monitoring of methotrexate was not available at our center. HDMTX-related mortality was 3.9%. The median follow-up duration, event-free survival (EFS), and overall survival (OS) were 34 months, 20.4 months, and 31.7 months, respectively. Addition of rituximab (n = 27) to MVP resulted in a higher objective response rate (88.9% v 73.9% without rituximab; P = .12), complete remission (81.5% v 56.5%; P = .03), 2-year EFS (57.3% v 40.4%; P = .02), and 2-year OS (61.6% v 53.4%; P = .056). CONCLUSION: This is the largest study of PCNSL from India. The patients were immunocompetent and young but presented with a high-burden disease that precluded treatment in approximately 22%. The treatment with HDMTX appears safe without pharmacokinetic monitoring. The outcome is comparable to those observed in the West, and rituximab use showed additional benefit. There are notable barriers with respect to management of PCNSL in the real world, and efforts are required to improve the outcome more.

A Rare Case of Primary Central Nervous System Lymphoma in an Adolescent Female Treated with High-Dose Methotrexate and Rituximab-Based Chemoimmunotherapy and Consolidation Whole Brain Radiotherapy.

Primary central nervous system lymphoma (PCNSL) is a rare pediatric brain tumor. A 16-year-old female patient presented to the clinic with complaints of multiple episodes of generalized tonic clonic seizures, nystagmus, and weakness on the left side of the body for 3 weeks. She had similar symptoms, waxing and waning for the last 2 years, responding to corticosteroids. Repeat magnetic resonance imaging (MRI) of the brain showed multiple areas of signal abnormalities involving the left temporal lobe, the basal ganglion, the thalamus, and the right frontal and occipital lobes with contrast enhancement in bitemporal lesions. With a clinico- radiological diagnosis of demyelinating disorder, she underwent an image-guided right frontal lobe biopsy, which revealed sheets of atypical lymphoid cells diffusely immunopositive for CD20 but negative for CD3, CD10, BCL-6, and MUM-1, suggesting diffuse large B-cell lymphoma, germinal center B-cell subtype. The systemic lymphoma workup was essentially normal. She received 5 cycles of chemoimmunotherapy with rituximab, high-dose methotrexate (HDMTX), vincristine, and procarbazine and had a complete radiological response (CR). This was followed by whole brain radiotherapy (WBRT) to a dose of 36 Gy in 20 fractions over 4 weeks. Subsequently she received 2 cycles of consolidation chemoimmunotherapy with rituximab and high-dose cytarabine. Serial brain MRI done 1, 4, and 8 months after completion of treatment showed persistence of the CR. At the last follow-up visit, 15 months from the date of diagnosis, she was disease free and asymptomatic. This report underlines the fact that PCNSL in adolescents may be effectively treated with a combination of HDMTX- and rituximab-based chemoimmunotherapy followed by consolidation with WBRT.

A rare case of paediatric primary central nervous system lymphoma treated with high-dose methotrexate and rituximab-based chemoimmunotherapy and whole brain radiotherapy followed by tumour bed boost with three-dimensional conformal radiation technique.

BACKGROUND: Primary central nervous system lymphomas (PCNSL) are rare in the paediatric population. CLINICAL CASE: A 12-year-old boy presented to our clinic with complaints of multiple episodes of generalised tonic-clonic seizures for 1 year and gradual loss of vision in both eyes for 3 months. Baseline magnetic resonance imaging (MRI) of the brain showed a large (7.2 × 7 cm) enhancing soft tissue lesion in the right frontal lobe causing mass effect and midline shift. With a radiological diagnosis of supratentorial primitive neuroectodermal tumour, he underwent subtotal resection of tumour. The post-operative histopathology revealed diffuse large B cell lymphoma (DLBCL). Systemic lymphoma workup was essentially normal. He received five cycles of chemoimmunotherapy with rituximab, high-dose methotrexate (HDMTX), vincristine and procarbazine and had complete radiological response (CR). This was followed by whole brain radiotherapy (WBRT) to a dose of 36 Gy in 20 fractions and sequential tumour bed boost to a dose of 9 Gy in 5 fractions by three-dimensional conformal technique. Subsequently, he received two cycles of consolidation chemotherapy with high-dose cytarabine. At completion of treatment, 3 and 6 months thereafter, MRI brain showed CR. At last follow-up visit, 13 months from the date of diagnosis, he was disease-free and asymptomatic with the exception of dimness of vision in both eyes due to long-standing bilateral optic atrophy. CONCLUSION: This report highlights the fact that paediatric PCNSL may be effectively treated by a combination of HDMTX and rituximab-based chemoimmunotherapy followed by consolidation with conformal WBRT and tumour bed boost. Lack of awareness of this rare entity may lead to diagnostic delay and potential ramifications as exemplified by chronic atrophic papilloedema and visual loss in the illustrative case.

A prospective phase II trial of response adapted whole brain radiotherapy after high dose methotrexate based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma-analysis of acute toxicity profile and early clinical outcome.

BACKGROUND: The treatment of primary CNS lymphoma (PCNSL) comprises high dose methotrexate (HDMTX) based chemotherapy followed by whole brain radiotherapy (WBRT), the major drawback of which is long term neurotoxicity. We intended to assess the feasibility of response adapted WBRT in PCNSL in the Indian setting. METHODS: We screened 32 patients and enrolled 22 eligible patients with PCNSL from 2015 to 2017 in a prospective phase II trial. The patients underwent five 2-weekly cycles of induction chemotherapy with rituximab, methotrexate, vincristine, procarbazine. Patients with complete response(CR) to induction chemotherapy were given reduced dose WBRT 23.4 Gy/13 fractions/2.5 weeks while those with partial response (PR), stable or progressive disease (SD or PD) were given standard dose WBRT 45 Gy/25 fractions/5 weeks. Thereafter two cycles of consolidation chemotherapy with cytarabine were given. The primary endpoints of the study were assessment of response rate (RR) and progression free survival (PFS). The secondary endpoints of the study were assessment of overall survival (OS), toxicity profile of treatment and serial changes in quality of life and neuropsychological parameters. RESULTS: Out of 19 patients who completed HDMTX based chemotherapy, 10 (52.63%) patients achieved CR, 8 (42.11%) patients had PR and 1 patient had PD. After a median follow-up period of 11.25 months, the estimated median OS was 19 months. The actuarial rates of PFS and OS were respectively 94.1 and 68.2% at 1 year and 50.2 and 48.5% at 2 years. Three patients in reduced dose WBRT arm had recurrence and two of them died of progressive disease, whereas there was no recurrence or disease related death in standard dose WBRT arm. On univariate analysis of PFS, age ≤ 50 years and use of standard dose WBRT (45 Gy) led to significantly improved outcome (p value 0.03 and 0.02 respectively). CONCLUSION: In patients with PCNSL, reduced dose WBRT after CR to HDMTX based chemotherapy may lead to suboptimal clinical outcome due to higher risk of recurrence, progression and early death. Trial Registration No CTRI/2015/10/006268.

NUT Midline Carcinoma: A Series of Five Cases, Including One with Unusual Clinical Course.

NUT midline carcinomas (NMCs) are rare, poorly differentiated tumors with aggressive biological behavior and a characteristic molecular signature. Availability of NUT antibody has facilitated diagnosis of NMC without molecular testing. We report a series of head and neck NMCs diagnosed using NUT IHC at our institute, including one case with an unusual course. Immunohistochemistry for NUT was performed in nasal and sinonasal tumors with diagnoses of undifferentiated carcinoma, poorly differentiated squamous cell carcinoma and malignant neoplasm, not otherwise specified, to identify cases of NMC. Clinicopathological features were reviewed. Five cases of NMC were identified, accounting for 9.6% of poorly differentiated/undifferentiated carcinomas of the sinonasal region. These patients had a sex ratio of 2:3, and ranged in age from of 10 to 31 years (mean: 25.2 years). Patient 4 had previously been diagnosed with basal cell carcinoma arising in left nasolacrimal duct, and inverted papilloma of nasal cavity. She presented to us with a left lacrimal fossa mass extending into nasal cavity, which was diagnosed as NMC. NMC is a rare neoplasm, the awareness of which is imperative for pathologists to identify cases in which NUT IHC should be ordered. NUT IHC should be performed in all cases of a poorly differentiated carcinoma, particularly those with foci of squamous differentiation, irrespective of patient age and unusual tumor location, as seen in one of our cases. Although considered a highly aggressive and lethal neoplasm, NMC can have a more prolonged clinical course on occasion.

Current Trends in Management of Oral Mucositis in Cancer Treatment

Oral Mucositis (OM) is among the most common and dreaded toxicities of cancer therapy. It occurs in almost all patients who receive radiation therapy in which areas of oral and oropharyngeal mucosa are included in the treatment field. With the advent of chemotherapy in 1940 and its extended clinical legacy, it is only within the past two decade or so that mucositis' complex pathobiology has become fully appreciated. There are still many unanswered questions about the risk factors for developing OM, but historically, risk factors have been attributed to both therapy and patient m characteristics. One thing that has been consistent from the initial descriptions of its clinical manifestations has been the frustration on the part of clinicians and patients with the scarcity of therapeutic options to prevent or treat the condition, or effectively ameliorate the symptoms. Clinicians, researchers and those involved in oral and periodontal medicine should join hand in hand in persuit of understanding and developing treatment strategies for treatment of inflammatory conditions like OM in oncology. This will lead to development of effective treatments and reducing the burden of OM and other inflammatory conditions in oncology.

Study of structural and transport properties of argon, krypton, and their binary mixtures at different temperatures.

Molecular dynamics simulation of argon, krypton, and their binary mixtures were performed at different temperatures and constant pressure (P = 1.013 bar) using GROMACS - Groningen Machine for Chemical Simulations. The gases are modeled by Lennard-Jones pair potential, with parameters taken from the literature. The study of radial distribution functions (RDFs) shows a single peak which indicates that there is no packing effect in gaseous state for argon, krypton, and their binary mixtures. The self-diffusion coefficients of argon and krypton is determined by using mean-square displacement(MSD) method and the mutual diffusion coefficients of binary mixtures are determined using Darken's relation. The values of simulated diffusion coefficients are compared with their corresponding theoretical values, numerical estimation, and experimental data. A good agreement between these sets of data is found. The diffusion coefficients obey Arrhenius behavior to a good extent for both pure components and binary mixtures. The values of simulated diffusion coefficient are used to estimate viscosities and thermal conductivities which agree with theoretical values, numerical estimation, and experimental data within 10 %. These results support that the LJ potential is sufficient for description of molecular interactions in argon and krypton.

Metabolic toxicities in patients undergoing treatment for nonhematological malignancy: A cross-sectional study.

OBJECTIVES: The objective of this study was to evaluate the prevalence of metabolic toxicities in patients with different nonhematological malignancies admitted in oncology ward of a tertiary cancer care center while on treatment. METHODS: We did this cross-sectional study over a period of 7 months (January-July 2013) for all adult patients (n = 280) who, while undergoing anti-cancer therapy at our center, got admitted to our oncology inpatient ward with metabolic toxicity. Grading of toxicity was done using National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0. RESULTS: A total of 46 events of metabolic toxicities were noted in 31 patients over this period. The most common of them was hyperglycemia (n = 10). The others were hypokalemia (n = 9), hyponatremia (n = 9), hypernatremia (n = 5), hyperkalemia (n = 5), tumor lysis syndrome (n = 4), hypercalcemia (n = 2), and grade ≤2 hypomagnesemia (n = 2). Majority of the patients were asymptomatic (n = 26). However, death occurred in five patients. Treatment interruptions took place in 19 patients. Age ≤40 years (P = 0.03), Eastern Cooperative Oncology Group performance status ≥2 (P = 0.023), history of addiction (P = 0.02), comorbidities (P = 0.037) were associated with increased risk of having metabolic toxicities on univariate analysis. While on multivariate analysis, only age, performance status, and history of addiction retained their statistical significance. Age ≤40 years (P = 0.02), use of more than one modality of treatment (P = 0.013), and hyperglycemia (P = 0.037) were associated with higher risk of death. CONCLUSION: Metabolic toxicities are common phenomena among cancer patients, especially those with young age, comorbidities, and having history of addictions. In young age, they might even be fatal, especially when they are treated with combined modality of treatment.