The human-wildlife conflict in Musk Deer National Park, Neelum Gureze Valley, Azad Jammu & Kashmir, Pakistan.

Growing human population is a solemn risk to biodiversity at a global level. Massive anthropogenic pressure and invasion in the natural habitats initiated the human-wildlife conflict in rural areas. Present study aimed to assess human-wildlife conflict in Musk Deer National Park (MDNP) from 2013 to 2018. Results revealed an estimated 241784 nomadic and 5589 residential livestock heads grazed in different areas of MDNP during the summer season. A total of 126 heads were depredated by carnivores during the study period. Majority (n=39) of livestock heads were killed in May (n=29). Livestock depredation resulted in economic losses worth 3.115 million PKRs (25744 US$) to the herder community while farmers received 1.629 million PKRs (13466 US$) losses due to crop raiding. Most (64%) of the respondents believed human-wildlife conflict heightened due to scarcity of food or prey in the natural habitats of carnivores. Majority (92%) of the respondents did not like the presence of predators in MDNP. Loss compensation schemes could turn this negative attitude into the positive one and increase tolerance about the presence of carnivores in their vicinity. This study provides an insight into the human-wildlife conflict in MDNP and paves a way for understanding the conflict and conservation of carnivore species in the study area.

Insilco identification and characterization of superoxide dismutase gene family in Brassica rapa.

Superoxide Dismutase SODs are defense associated proteins that detoxify ROS and primarily serve as scavengers. They have been described in numerous plant species, but their in-depth characterization in Brassica rapa has not been reported. Therefore, the present investigation on genome wide study of SOD gene family was conducted to identify BrSOD genes, their domain-based organization, gene structure analysis, phylogenetic analysis, intron-exon structure of genes and expression analysis. The sequence characterization of Super oxide dismutase gene family in Brassica rapa, their syntenic associateship of conserved motifs and phylogenetic correlationship, prediction of cis-elements and determing the expression analysis in distinct tissues namely plant callus, root, stem, leaf, flower, and silique under abiotic conditions have been analysed using different software's. The study on SOD gene family identified 17 BrSOD genes which were grouped into eight BrCu-ZnSODs and nine BrFe-MnSODs domain-based organization. Furthermore, the conserved character of BrSODs were confirmed by intron-exon organisation, motif arrangements and domain architectural investigations. Expression analysis using RNA Sequence data of different developmental stages proclaimed that genes were manifested in all six tissues with an exception of BrCu-ZnSOD3, which was not manifested in roots; however, whose transcript was detected in all other tested tissues. The study has genome wide insight into the occurrence and functional specifications of BrSOD gene family in Brassica rapa that can be potentially utilized in breeding program for resilience to climate change and abiotic stresses tolerance Brassica variety.

International cancer seminars: a focus on esophageal squamous cell carcinoma.

The International Agency for Research on Cancer (IARC) and the US National Cancer Institute (NCI) have initiated a series of cancer-focused seminars [Scelo G, Hofmann JN, Banks RE et al. International cancer seminars: a focus on kidney cancer. Ann Oncol 2016; 27(8): 1382-1385]. In this, the second seminar, IARC and NCI convened a workshop in order to examine the state of the current science on esophageal squamous cell carcinoma etiology, genetics, early detection, treatment, and palliation, was reviewed to identify the most critical open research questions. The results of these discussions were summarized by formulating a series of 'difficult questions', which should inform and prioritize future research efforts.

Response to angiotensin blockade with irbesartan in a patient with metastatic colorectal cancer.

BACKGROUND: A patient suffering from metastatic colorectal cancer, treatment-related toxicity and resistance to standard chemotherapy and radiation was assessed as part of a personalized oncogenomics initiative to derive potential alternative therapeutic strategies. PATIENTS AND METHODS: Whole-genome and transcriptome sequencing was used to interrogate a metastatic tumor refractory to standard treatments of a patient with mismatch repair-deficient metastatic colorectal cancer. RESULTS: Integrative genomic analysis indicated overexpression of the AP-1 transcriptional complex suggesting experimental therapeutic rationales, including blockade of the renin-angiotensin system. This led to the repurposing of the angiotensin II receptor antagonist, irbesartan, as an anticancer therapy, resulting in the patient experiencing a dramatic and durable response. CONCLUSIONS: This case highlights the utility of comprehensive integrative genomic profiling and bioinformatics analysis to provide hypothetical rationales for personalized treatment options.

Genotypes of CYP1A1,†SULT1A1 and SULT1A2 and risk of squamous cell carcinoma of esophagus: outcome of a case-control study from Kashmir, India.

Studies on associations of various polymorphism in xenobiotic metabolizing genes with different cancers including esophageal squamous cell carcinoma (ESCC) are mixed and inconclusive. To evaluate the association of CYP1A1*4, SULT1A1*2 and SULT1A2*2 genotypes with ESCC risk and their modifying effects on different risk factors of ESCC, we conducted a case-control study in Kashmir, India, an area with relative high incidence of ESCC. We recruited 404 histopathologically confirmed ESCC cases, and equal number of controls, individually matched for sex, age and district of residence to respective case. Information was obtained on various dietary, lifestyle and environmental factors in face-to-face interviews, using a structured questionnaire, from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and direct sequencing. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A higher risk was observed in the subjects who harbored variant genotype of CYP1A1*4 (OR = 2.06; 95% CI: 1.28-3.32); and the risk was further enhanced in ever smokers (OR = 3.47; 95% CI: 1.62-7.42), adobe dwellers (OR = 6.71; 95% CI: 3.02-14.89), and biomass fuel users (OR = 5.11; 95% CI: 1.34-19.50). We did not find any significant differences in the polymorphic variants of SULT1A1*2 and SULT1A2*2 between cases and controls. The study indicates that, unlike SULT1A1*2 and SULT1A2*2, the polymorphism of CYP1A1*4 is associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate our findings.

Family history of cancer and the risk of squamous cell carcinoma of oesophagus: a case-control study in Kashmir, India.

BACKGROUND: Only a few studies have examined the association between family history of cancer (FHC) and the risk of oesophageal squamous cell carcinoma (ESCC) in high incidence areas of ESCC. We conducted a case-control study to evaluate the relationship between FHC and ESCC risk in Kashmir, India, with analysis of detailed epidemiological data and information on multiple gene polymorphisms. METHODS: We collected detailed information on FHC and a number of socio-demographic and lifestyle factors, and also obtained blood samples for genetic analysis from 703 histopathologically confirmed ESCC cases and 1664 individually matched controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Participants who had FHC showed a strong association with ESCC risk, and the risk was stronger when first-degree relatives (FDRs) had FHC (OR=6.8; 95% CI=4.6-9.9). Having a sibling with a cancer showed the strongest association (OR=10.8; 95% CI=6.0-19.3), but having a child with a cancer was not associated with ESCC risk. A history of any cancer in the spouse was also associated with ESCC risk (OR=4.1; 95% CI=1.6-10.2). Those with two or more relatives with FHC were at a higher risk of ESCC. After restricting FHC to familial ESCC only, the above associations were strengthened, except when spouses were affected with ESCC (OR=2.5; 95% CI=0.7-8.9). When we examined the associations between several single-nucleotide polymorphisms and ESCC in those with and without FHC, the associations of variant genotypes in cytochrome P450 (CYP) 2C19 and CYP2D6 and the wild genotype of CYP2E1 with ESCC were much stronger in those with FHC. The FHC had an additive interaction with several risk factors of ESCC in this population. CONCLUSION: Our results showed that FHC was strongly associated with ESCC risk in Kashmir. It seems both genetic factors and shared environment are involved in this association.

Poor oral hygiene and risk of esophageal squamous cell carcinoma in Kashmir.

BACKGROUND: Several studies have suggested an association between poor oral health and esophageal squamous cell carcinoma (ESCC). We conducted a case-control study in Kashmir, a region with relatively high incidence of ESCC in north India, to investigate the association between oral hygiene and ESCC risk. METHODS: We recruited 703 histologically confirmed ESCC cases, and 1664 controls individually matched to the cases for age, sex, and district of residence. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found an inverse association between teeth cleaning and ESCC risk. As compared with never cleaning teeth, the OR (95% CI) was 0.41 (0.28-0.62) for cleaning less than daily and 0.44 (0.25-0.77) for cleaning at least once a day (P for trend=0.026) in models adjusted for multiple potential confounders, including several indicators of socioeconomic status. This association persisted after we limited our analyses to never tobacco users. The inverse association between cleaning teeth and ESCC was stronger with using brushes than with using sticks/fingers. We also found an association between the number of decayed, filled, and missing teeth and ESCC risk, but the trend of the associations was not statistically significant. Avoiding solid food and cold beverages because of teeth and oral problems were also associated with ESCC risk. CONCLUSION: We found an association between poor oral hygiene indicators and ESCC risk, supporting the previous studies that showed the same associations.

Purification, characterization and preparation immunomatrixes of S-layer proteins of Thermobifida fusca.

AIM: S-layer proteins are considered as a good nanocarrier due to their binding and self-assembled properties. These can be used to prepare the immunomatrixes for the removal of toxins from the samples. METHODS AND RESULTS: Two S-layer proteins 70 and 40 kDa of thermophilic Thermobifida fusca were extracted with guanidine hydrochloride and purified. Antibodies against S-layer proteins were developed, and their monospecificity was checked. Immunogold labelling indicated that these are surface proteins. Immunomatrixes (70-SLIM, 40 SLIM) were prepared by covalently immobilizing S-layer proteins in microwell and further conjugated with anti- Staphylococcus aureus enterotoxin B (SEB) antibodies. The binding of 70 and 40 kDa proteins was observed nearly 7·0 µg cm(-1) to binding area, and the conjugation with anti-SEB antibodies was found 1·22 µg µg(-1) of 70 kDa and 0·875 µg µg(-1) of 40 kDa. The average binding and elution of pure SEB toxin on 70-SLIM and 40-SLIM was 5·0 µg SEB toxin. The SEB toxin in milk samples was also removed on immunomatrixes successfully. CONCLUSION: It is the first report, and this study shows that the thermophilic S-layer proteins can be used to prepare the immunomatrixes. SIGNIFICANCE AND IMPACT OF STUDY: Information in this study can be used to design the strategies for the removal of biologically important materials or toxins from samples.

Hookah smoking, nass chewing, and oesophageal squamous cell carcinoma in Kashmir, India.

BACKGROUND: Although cigarette smoking is an established risk factor for oesophageal squamous cell carcinoma (ESCC), there is little information about the association between other smoking and smokeless tobacco products, including hookah and nass, and ESCC risk. We conducted a case-control study in Kashmir Valley, India, where hookah smoking, nass chewing, and ESCC are common, to investigate the association of hookah smoking, nass use, and several other habits with ESCC. METHODS: We recruited 702 histologically confirmed ESCC cases and 1663 hospital-based controls, individually matched to the cases for age, sex, and district of residence from September 2008 to January 2012. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Ever-hookah smoking (OR=1.85; 95% CI, 1.41-2.44) and nass chewing (OR=2.88; 95% CI, 2.06-4.04) were associated with ESCC risk. These associations were consistent across different measures of use, including intensity, duration, and cumulative amount of use, and after excluding ever users of the other product and cigarette smokers. Our results also suggest an increased risk of ESCC associated with ever-gutka chewing and -bidi smoking. However, the latter associations were based on small number of participants. CONCLUSION: This study shows that hookah and nass use are associated with ESCC risk. As prevalence of hookah use seems to be increasing among young people worldwide, these results may have relevance not only for the regions in which hookah use has been a traditional habit, but also for other regions, including western countries.

Asymmetrical periflexural exanthem exhibiting pseudoisomorphic Köebner response in an adult.

Asymmetrical periflexural exanthem is a rare clinical condition, seen almost exclusively in children. Very few adult cases have been reported in the literature. We report a case of this rare eruption in an adult man showing characteristic clinical and histological features. Interestingly, this patient also exhibited a pseudoisomorphic Köebner response. Although an infective aetiology of viral origin has been suggested for this localized eruption, the aetiology remains unknown. We are of the opinion that the pseudoisomorphic Köebner response in this patient may support the inoculation hypothesis in the pathogenesis of this disorder.

Transcriptional activation of cyclooxygenase-2 by tumor suppressor p53 requires nuclear factor-kappaB.

Overexpression of cyclooxygenase-2 (Cox-2) is thought to exert antiapoptotic effects in cancer. Here we show that the tumor suppressor p53 upregulated Cox-2 in esophageal and colon cancer cell lines by inducing the binding of nuclear factor-kappaB (NF-kappaB) to its response element in the COX-2 promoter. Inhibition of NF-kappaB prevented p53 induction of Cox-2 expression. Cooperation between p53 and NF-kappaB was required for activation of COX-2 promoter in response to daunomycin, a DNA-damaging agent. Pharmacological inhibition of Cox-2 enhanced apoptosis in response to daunomycin, in particular in cells containing active p53. In esophageal cancer, there was a correlation between Cox-2 expression and wild-type TP53 in Barrett's esophagus (BE) and in adenocarcinoma, but not in squamous cell carcinoma (P<0.01). These results suggest that p53 and NF-kappaB cooperate in upregulating Cox-2 expression, promoting cell survival in inflammatory precursor lesions such as BE.

Efficacy of concomitant use of PUVA and methotrexate in disease clearance time in plaque type psoriasis.

OBJECTIVE: To document the efficacy of concomitant use of PUVA and methotrexate in disease clearance time in plaque type psoriasis. METHOD: Sixty male patients between 18 to 50 years of age suffering from plaque type of psoriasis with PASI score more than 10 were enrolled in the study between March 2001 to November 2001. They were divided into three groups of 20 patients each. Group A received only PUVA, Group B received only Methotrexate and group C received both PUVA and Methotrexate concomitantly. PUVA was given four times a week according to11011 schedule. The end point for clearance of psoriasis was taken as 75% reduction in PASI score from the baseline. RESULTS: Group A: The minimum number of PUVA sessions needed for clearance was 20 and the maximum number was 25 (mean - 22.5). The mean clearance time was 5.5 weeks. The cumulative dose of UVA radiation ranged from 150-250 J/cm2 (mean -200 J/cm2). Group B: The time required for clearance was 7 weeks at the minimum and 9 weeks at the maximum (mean - 8 weeks). Group C: The minimum number of PUVA sessions needed for clearance was 8 and maximum was 12 (mean 10). The mean time for clearance was 2.5 weeks. The cumulative dose of UVA radiation ranged from 56-108 J/cm2 (mean-82 J/cm2). No significant side effects were seen in the three treatment groups. CONCLUSION: The results suggest that combination of PUVA and methotrexate is an effective and safe modality for clearance of psoriasis.

Ossifying fibroma of nose in a two year old child.

We report a cast of ossifying fibroma of the nose, arising from the bony septum and extending into the nasophaynx in a 2 yrs. old child presenting with features of obstructed nose.

An unique case of organic foreign body (bone) in the hard palate.

A unique report of impacted organic foreign body (animal bone) in the hard palate is presented. A patient with vague palatal discomfort for two years reported to the ENT OPD, work-up revealed the above foreign body, subsequently proven to be bone by histology.