Developing a framework for arts in health programs targeting individuals with chronic pain: a mixed-methods study of practitioners.

OBJECTIVES: Chronic pain is a leading cause of morbidity and disability across the world. Cultural engagement may be a valuable tool in addressing the social disconnection that often accompanies chronic pain. This study sought to develop a framework for arts in health programs targeting individuals with chronic pain. STUDY DESIGN: Sequential explanatory mixed-methods study. METHODS: Web-based, cross-sectional survey sent to arts and cultural professionals to assess their experience with arts in health programming. Semi-structured interviews conducted with a sample of survey respondents to explore their perspectives on targeted arts in health programming for individuals with chronic pain. RESULTS: Between October 2019 and January 2020, 208 surveys were completed by arts and cultural professionals. One hundred and twenty (58%) of the respondents indicated that they currently run an arts in health or museums in health program. Among these 120 respondents, 52 (43%) targeted older adults, 50 (42%) targeted individuals with mental health concerns, and 18 (15%) targeted individuals living with pain. Improving well-being (101 [84%]) and reducing social isolation (90 [75%]) were the most common intended program outcomes, while improving pain was the least common outcome (26 [22%]). Fifteen survey respondents were interviewed. Interviewees identified four interdependent themes regarding best practices for arts in health programs pertaining to (1) program content and structure, (2) program facilitation, (3) partnerships, and (4) programs for individuals with chronic pain. CONCLUSIONS: The cultural sector can support chronic pain prevention and treatment efforts through the development of specialized programs. This study provides a framework for developing arts in health programs that support individuals living with chronic pain.

Phenolic compounds, antioxidant capacity and antimutagenic activity in different growth stages of in vitro raised plants of Origanum vulgare L.

Efficient micropropagation procedure was developed for Origanum vulgare, a high-value culinary herb, and the phytochemicals, phenolic content, antioxidant and antimutagenic activity of leaf and stem, derived from different growing stages were analyzed. The agar solidified Murashige and Skoog (MS) medium supplemented with a combination of 6-benzylaminopurine and α-naphthaleneacetic acid was optimized as best shoot-multiplication-medium. Shoots were rooted best on 1/2 strength MS medium supplemented with 50 µM indole-3-butyric acid (IBA). The plantlets were successfully acclimatized ex vitro in a soil, sand and farmyard manure mixture (2:1:1 v/v/v) with 100% survival rate in greenhouse. The total anthocyanin and total phenolic content were observed significantly higher in leaves of in vitro-raised plants. However, total tannin, flavonoid and antioxidant activity remained higher in leaves of mother plant maintained under ployhouse condition. All the plant extracts have shown significant antimutagenic activity except in vitro-growing plants. A total of 13 polyphenolic compounds were detected in different extracts using high performance liquid chromatography. Among these, catechin was detected maximum in in vitro-growing cultures and chlorogenic acid in leaves of mother plant. These findings will help the farmers, medicinal plant growers, and industries for mass multiplication and effective extraction of phytochemicals from O. vulgare.

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N=18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values=1.6 × 10(-11) and 2.7 × 10(-11)), which were also in strong linkage disequilibrium (r(2)=0.7) with each other, lie in the 23-kb long commonly shared 5' flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value=3.9 × 10(-09)) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 10(-09))-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value=2.2 × 10(-05)) and Parkinson's disease pathways (P-value=3.6 × 10(-05)).

Structure based designing of thiazolidinone-pyrimidine derivatives as ERK2 inhibitors: Synthesis and in vitro evaluation.

Breast cancer has been associated with an overexpression of various molecular targets; accordingly, various target-specific chemotherapeutic agents have been developed. Inhibition of ERK2, a member of MAPK pathway, is an important target involved in the treatment of both oestrogen receptor-positive and triple-negative breast cancer. Thus, in continuation of our previous work on the ERK2 target, we here report novel inhibitors of this kinase. Out of three lead molecules reported in our previous study, we selected the thiazolidinone-pyrimidine scaffold for further development of small molecule inhibitors of ERK2. Analogues of the lead molecule were docked in the target kinase, followed by molecular dynamic simulations and MM-GBSA calculations. Analogues maintaining key interactions with amino acid residues in the ATP-binding domain of ERK2 were selected and duly synthesized. In vitro biochemical evaluation of these molecules against ERK2 kinase disclosed that two molecules possess significant kinase inhibitory potential with IC50 values ≤ 0.5 µM.

Exploring RdRp-remdesivir interactions to screen RdRp inhibitors for the management of novel coronavirus 2019-nCoV.

A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has resulted in an increasing number of patients globally, and has become a highly lethal pathogenic member of the coronavirus family affecting humans. 2019-nCoV has established itself as one of the most threatening pandemics that human beings have faced, and therefore analysis and evaluation of all possible responses against infection is required. One such strategy includes utilizing the knowledge gained from the SARS and MERS outbreaks regarding existing antivirals. Indicating a potential for success, one of the drugs, remdesivir, under repurposing studies, has shown positive results in initial clinical studies. Therefore, in the current work, the authors have attempted to utilize the remdesivir-RdRp complex - RdRp (RNA-dependent RNA polymerase) being the putative target for remdesivir - to screen a library of the already reported RdRp inhibitor database. Further clustering on the basis of structural features and scoring refinement was performed to filter out false positive hits. Finally, molecular dynamics simulation was carried out to validate the identification of hits as RdRp inhibitors against novel coronavirus 2019-nCoV. The results yielded two putative hits which can inhibit RdRp with better potency than remdesivir, subject to further biological evaluation.

Topological descriptors in modeling the HIV inhibitory activity of 2-aryl-3-pyridyl-thiazolidin-4-ones.

The HIV-1 RT inhibitory activity of 2-(2,6-dihalophenyl)-3-(substituted pyridin-2-yl)-thiazolidin-4-ones has been analyzed with different topological descriptors obtained from DRAGON software. Here, simple topological descriptors (TOPO), Galvez topological charge indices (GVZ) and 2D autocorrelation descriptors (2DAUTO) have been found to yield good predictive models for the activity of these compounds. The correlations obtained from the TOPO class descriptors suggest that less extended or compact saturated structural templates would be better for the activity. The participating GVZ class descriptors suggest that they have same degree of influence on the activity. In 2DAUTO class, the large participation of descriptors of lags seven and three indicate the association of activity information with the seven and three centered structural fragments of these compounds. The physicochemical weighting components of these descriptors suggest homogeneous influence of mass, volume, electronegativity and/ or polarizability on the activity.

Mechanism of Adefovir, Tenofovir and Entecavir Resistance: Molecular Modeling Studies of How A Novel Anti-HBV Agent (FMCA) Can Overcome the Drug Resistance.

Regardless of significant improvement in the area of anti-HBV therapy, resistance and cross-resistance against available therapeutic agents are the major consideration in drug discovery of new agents. The present study is to obtain the insight of the molecular basis of drug resistance conferred by the B and C domain mutations of HBV-polymerase on the binding affinity of four anti-HBV agents [Adefovir (ADV), Tenofovir (TNF), Entecavir (ETV) & 2'-Fluoro-6'-methylene-carbocyclic adenosine (FMCA)]. In this regard, homology modeled structure of HBV polymerase was used for minimization, conformational search and Glide XP docking followed by binding energy calculation on wild-type as well as on mutant HBV-polymerases (N236T, L180M+M204V+S202G & A194T). Our studies suggest a significant correlation between the fold resistances and the binding affinity of anti-HBV nucleosides. The domain B residue, L180 is indirectly associated with other active-site hydrophobic residues such as A87, F88 and M204, whereas the domain C residue, M204 is closely associated with sugar/pseudosugar ring positioning in the active site. These hydrophobic residues can directly influence the interaction of the incoming nucleoside triphosphates and change the binding efficacy. The carbohydrate ring part of natural substrate dATP, dGTP, FMCA and ETV, are occupied in similar passion in the grooves of HBV polymerase active site. The exocyclic double bond of Entecavir and FMCA occupies in the backside hydrophobic pocket (made by residues A87, F88, L180and M204), which enhances the overall binding affinity. Additional hydrogen bonding interaction of 2'-fluorine of FMCA with R41 residue of polymerase promotes a positive binding in wild-type as well as in ADVr, ETVr and TNFr with respect to that of entecavir.

Assessing benefits of combining biochemical and immunological markers in patients with lung carcinoma.

Establishment of a simple biochemical index for diagnosis of cancer and management of patients with neoplastic diseases remains one of the important goals to be achieved in cancer research. The current investigation determined serum levels of carcinoembryonic antigen (CEA), total sialic acid (TSA) and lipid bound sialic acid (LSA) in 192 untreated lung cancer patients and compared with 80 age- and sex-matched controls (44 non-smokers and 36 smokers). The levels of all the markers were significantly elevated (P < 0.001) in lung cancer patients compared to the controls. CEA and LSA values were significantly raised (P < 0.001 and P < 0.01, respectively) in smokers compared to non-smokers. TSA and LSA values were more sensitive than CEA for diagnosis of lung cancer. Mean values of the three markers were higher in non-responders (n = 5) compared to the responders (n = 10). The results suggest that along with CEA, TSA and LSA might be included as routine parameters in lung cancer patients.

Effects of positive end-expiratory pressure on dead space and its partitions in acute lung injury.

OBJECTIVE: A large tidal volume (VT) and lung collapse and re-expansion may cause ventilator-induced lung injury (VILI) in acute lung injury (ALI). A low VT and a positive end-expiratory pressure (PEEP) can prevent VILI, but the more VT is reduced, the more dead space (VD) compromises gas exchange. We investigated how physiological, airway and alveolar VD varied with PEEP and analysed possible links to respiratory mechanics. SETTING: Medical and surgical intensive care unit (ICU) in a university hospital. DESIGN: Prospective, non-randomised comparative trial. PATIENTS. Ten consecutive ALI patients. INTERVENTION: Stepwise increases in PEEP from zero to 15 cm H2O. MEASUREMENTS AND RESULTS: Lung mechanics and VD were measured at each PEEP level. Physiological VD was 41-64% of VT at zero PEEP and increased slightly with PEEP due to a rise in airway VD. Alveolar VD was 11-38% of VT and did not vary systematically with PEEP. However, in individual patients a decrease and increase of alveolar VD paralleled a positive or negative response to PEEP with respect to oxygenation (shunt), respectively. VD fractions were independent of respiratory resistance and compliance. CONCLUSIONS: Alveolar VD is large and does not vary systematically with PEEP in patients with various degrees of ALI. Individual measurements show a diverse response to PEEP. Respiratory mechanics were of no help in optimising PEEP with regard to gas exchange.

Long-term effects of perinatal asphyxia on basal ganglia neurotransmitter systems studied with microdialysis in rat.

Asphyxia was induced in pups delivered by caesarean section on pregnant Sprague-Dawley rats. Rats within the last day of gestation were anaesthetised and hysterectomized. The uterus horns including the foetuses were placed in a water bath for various periods of time. Following asphyxia the uterus horns were opened. The pups were removed, stimulated to breathe, left to recover and given to surrogate mothers. Control and asphyctic pups were obtained from each mother. Rats surviving asphyctic periods longer than 20 min at 37 degrees C showed chronic deficits in the release of neurotransmitters monitored with microdialysis in the basal ganglia. The main change observed in 6-month-old male rats that underwent severe perinatal asphyxia was a marked decrease in striatal dopamine release, monitored under basal and D-amphetamine stimulated conditions, as compared with control (normal- or caesarean-delivered) rats. Striatal glutamate and aspartate levels were also decreased following asphyxia. In the substantia nigra, the main effect of asphyxia was a decrease of both gamma-aminobutyric acid (GABA) and aspartate levels. Thus, this study provides evidence that perinatal asphyxia leads to chronic deficits in neurotransmission in the basal ganglia.

Evaluation of telomerase activation in head and neck cancer.

During replication of the linear chromosomes, telomeres, i.e. the ends of the chromosomes, are not replicated completely by the conventional DNA polymerases. Therefore, normal somatic cells senesce after certain number of cell divisions. Telomerase is a special reverse transcriptase used by most eukaryotes to achieve immortalization. Telomerase activity has been determined in a variety of cancers. However, there are few reports on telomerase activity in head and neck cancer. The etiology of the disease in India is completely different from Western countries. Tobacco consumption is more prevalent in India and the mode of tobacco consumption (e.g. chewing, snuffing, bidi smoking, reverse smoking) is also different. The present study determined telomerase activity in 32 malignant tumour samples of head and neck cancer patients, 11 samples from patients with precancerous/benign lesions and 30 samples of adjacent normal tissues. Telomerase was found to be activated in 80% of the patients with head and neck cancer, 100% of the patients with precancerous/benign lesions and 74% of the adjacent normal tissues. According to the theory of field cancerization, carcinogenic insults (e.g. tobacco) may result into multiple malignant foci. This fact may explain the reason for high telomerase positivity in adjacent normal as well as precancerous/benign tissues. Telomerase activation and the clinical or histopathological characteristics of the head and neck cancer patients were observed to be independent features. This is a preliminary report which has generated a greater interest for in-depth elucidation of the role of telomerase and telomeres in head and neck carcinogenesis in India.

Role of sialic acid and alkaline DNase in breast cancer.

Serum levels of sialic acid and alkaline DNase (ADA) were analysed in 495 blood samples collected from 170 breast cancer patients before and during/after anticancer treatment. Fifty-six healthy females were included in the study to define the cutoff values. The markers were analysed by highly sensitive spectrophotometric methods. Statistical evaluation of the data was done using Student's 't' test, paired 't' test and ROC curve analysis. The total sialic acid (TSA), lipid bound sialic acid (LSA) and ADA in sera of untreated breast cancer patients were significantly higher than in controls. ROC curve analysis revealed TSA and LSA to be useful markers for diagnosis of breast cancer. Serum levels of TSA and LSA were significantly decreased in complete responders as compared to their pretreatment values. The pretreatment ADA values showed much individual variation. However, responders showed higher levels of ADA than untreated patients. In nonresponders the values of the biomarkers were comparable with pretreatment levels. The study suggested that TSA and LSA can be helpful in the diagnosis of breast cancer. All three markers can be used for assessment of response to anticancer treatment in breast cancer patients.

Role of pretherapeutic biomarkers in predicting postoperative radiotherapy response in patients with advanced squamous cell carcinoma.

PURPOSE: To assess the role of biomarker levels in predicting radiotherapy (RT) response in patients with squamous cell carcinoma of buccal mucosa treated with postoperative RT. MATERIALS AND METHODS: Thirty-one patients with squamous cell carcinoma of buccal mucosa who received postoperative RT were enrolled for the study. Glutathione S-transferase (GST), glutathione reductase (GR), superoxide dismutase (SOD) and catalase activity were analysed from primary tumour and adjacent normal mucosa of the same patients before RT. p53 and p21ras were localized immunohistochemically. RESULTS: Enzyme activation was predicted by comparing the levels of these enzymes in tumour and adjacent normal mucosa. Deactivation of GST, activation of GR, SOD and catalase were associated with poor response to RT. p53 immunoreactivity was associated with failure to respond to RT. CONCLUSIONS: These markers may be useful in predicting treatment outcome in patients receiving postoperative RT, although this conclusion requires confirmation in a larger group of patients.

Seromucoid fraction: a useful biomarker for patients with breast cancer.

Seromucoid fraction was measured in terms of mucoid proteins (MP) and hexose content from sera of 1) 47 healthy women, 2) 48 women who had benign breast diseases, 3) 151 untreated patients with breast cancer, and 4) 245 follow-up samples collected from the same breast cancer patients. Mucoid proteins and hexose levels were found to be significantly elevated in untreated patients with breast cancer when compared with the healthy participants (p < 0.001) and patients who had benign breast diseases (p < 0.02 and p < 0.05, respectively). Receiver operating characteristic (ROC) curve analysis revealed potential diagnostic application of both markers for breast cancer. A good correlation was observed between favorable treatment response and decline in serum-marker levels. The markers in patients who did not respond to anticancer therapy remained stable or increased during follow-up. These data indicate that seromucoid fraction can be an useful biochemical marker for breast cancer patients.

Comparison between serum levels of carcinoembryonic antigen, sialic acid and phosphohexose isomerase in lung cancer.

The identification and application of quantifiable tumor markers as adjuncts to clinical care is a story of both success and failure. The present study compared serum levels of carcinoembryonic antigen (CEA) with total sialic acid/total protein (TSA/TP) ratio and phosphohexose isomerase (PHI) in 192 untreated lung cancer patients as well as 80 age and sex matched controls (44 non-smokers and 36 smokers). CEA values were significantly raised (p < 0.001) in smokers as compared to the non-smokers; whereas, TSA/TP and PHI values were comparable between the two groups of the controls. All the biomarkers were significantly elevated (p < 0.001) in untreated lung cancer patients as compared to the controls. Receiver operating characteristic curve analysis revealed higher sensitivities of TSA/TP and PHI as compared to CEA at different specificity levels between 60% and 95%. Mean values of CEA, TSA/TP and PHI were higher in non-responders compared to the responders. The results indicate that TSA/TP and PHI are superior tumor markers than CEA for lung cancer patients.

Serum glutathione-S-transferase and glutathione reductase activity in head and neck cancer patients.

Glutathione, an antioxidant plays an important role in phase-II detoxification of carcinogens. The levels of reduced glutathione are maintained by glutathione-depleting as well as replenishing enzymes such as glutathione-s-transferase (GST) and glutathione reductase (GR), respectively. Pre and post treatment changes in GST and GR activities in head and neck cancer patients were analysed. Serum GST and GR were analysed from untreated head and neck cancer patients (PT) (n=146), controls with habit of tobacco (VHT) (n=25) as well as without (no) habit of tobacco (NHT) (n=25) and patients with oral precancerous conditions (OPC) (n=50). The cancer patients were followed-up after initiation of anticancer therapy. Follow-up blood samples were collected. Serum GST and GR activities were estimated by highly sensitive and specific spectrophotometric methods. Untreated cancer patients showed elevated mean serum GST and GR activities as compared to NHT. Patients with OPC had declined mean GST activity as compared to WHT and untreated cancer patients. Paired t-test revealed that complete responders (CR) showed significantly elevated GST levels and declined GR activities (p < 0.001) as compared to those in PT. No correlation was found between stage of the disease and GST, GR activity. Paired t-test showed significant decreased in GR activity in nonresponders (NR) treated with radiotherapy (p=0.01). The study suggested that analysis of glutathione and glutathione-depleting enzymes can be helpful for treatment monitoring of head and neck cancer patients.

Glycoprotein electrophoretic pattern in sera of patients with oral precancerous conditions and upper aerodigestive tract cancer.

Cancer of the upper aerodigestive tract is one of the leading sites of human malignancies in India. Various glycoproteins have been claimed to be specifically associated with cancer. Serum glycoprotein electrophoresis was carried out in sera obtained from 23 healthy individuals [10 without habit of tobacco consumption (NHT) 13 with habit of tobacco consumption (WHT)], 46 patients with oral precancerous conditions (OPC) and 110 untreated patients with upper aerodigestive tract cancer. Eighty-six samples from the cancer patients were also collected after initiation of anticancer therapy. The albumin, alpha, beta and gamma region glycoproteins were quantitated by densitometric scanning after separation by polyacrylamide disc gel (PADG) electrophoresis. Mean values of albumin and alpha region glycoproteins were significantly lower in WHT and patients with OPC as compared to NHT. The gamma region glycoproteins were significantly elevated in WHT, patients with OPC and untreated cancer patients as compared to the NHT. The albumin region glycoproteins were significantly low, whereas, gamma region glycoproteins were significantly elevated in nonresponders as compared to their pretreatment levels. The glycoprotein values in complete responders were comparable with NHT. An extra glycoprotein band was found in the post beta region, in most of the individuals (>50%) with habit of tobacco consumption in all the groups. There was a decrease in the albumin/gamma, alpha/gamma and beta/gamma values in patients with OPC as well as untreated cancer patients as compared to NHT. Albumin/gamma, alpha/gamma and beta/gamma values were lower in nonresponders as compared to their pretreatment value. The results indicate that the alterations in glycoprotein electrophoresis pattern may be useful for early detection of cancer of the upper aerodigestive tract. It may also be helpful in treatment monitoring of cancer patients.

Alterations in plasma lipid profile patterns in head and neck cancer and oral precancerous conditions.

BACKGROUND: The changes in lipid profile have long been associated with cancer because lipids play a key role in maintenance of cell integrity. AIMS: The present study evaluated alterations in plasma lipid profile in untreated head and neck cancer patients as well as patients with oral precancerous conditions (OPC) and its association with habit of tobacco consumption. MATERIAL AND METHODS: This hospital-based case control study included 184 head and neck cancer patients, 153 patients with OPC and 52 controls. Plasma lipids including: (i) Total cholesterol, (ii) LDL cholesterol (LDLC), (iii) HDL cholesterol (HDLC) (iv) VLDL cholesterol (VLDLC) and (v) triglycerides were analysed by spectrophotometric kits. STATISTICAL ANALYSIS USED: Student's t-test was performed to compare mean values of the parameters. RESULTS: A significant decrease in plasma total cholesterol and HDLC was observed in cancer patients (P=0.008 and P=0.000 respectively) as well as in patients with OPC (P=0.014 and P=0.000, respectively) as compared to the controls. The plasma VLDL and triglycerides levels were significantly lower in cancer patients as compared to the patients with OPC (P=0.04) and controls (P=0.059). The tobacco habituates showed lower plasma lipid levels than the non-habituates. Our data strengthen the evidence of an inverse relationship between plasma lipid levels and head and neck malignancies as well as OPC. CONCLUSION: The lower levels of plasma cholesterol and other lipid constituents in patients might be due to their increased utilization by neoplastic cells for new membrane biogenesis. The findings strongly warrant an in-depth study of alterations in plasma lipid profile in head neck cancer patients.

A clinical study of eye complications in leprosy.

A study was conducted to find out the incidence of ocular complications in leprosy. The ocular lesions were found in 6.6% of lepromatous leprosy and 1.6% in nonlepromatous leprosy. Out of 150 patients with eye lesions 74% were males and 80% belonged to lepromatous leprosy. The age group in all the patients varied from 3rd to 6th decade. Mean duration of leprosy ln lepromatous leprosy was 6.2 years. The important eye complication observed were lagophthalmos (8.1%), corneal ulcers (10%) and iridocyclitis (24%). The loss of eye-brows (76%) was found to be most frequent in this study followed by corneal lesion (62%). It is concluded that examination of eyes are essential in all types of leprosy.