Identification of novel potential genetic predictors of urothelial bladder carcinoma susceptibility in Pakistani population

Urothelial bladder carcinoma (UBC) is the most common among urinary bladder neoplasms. We carried out a preliminary study to determine the genetic etiology of UBC in Pakistani population, for this 25 sequence variants from 17 candidate genes were studied in 400 individuals by using polymerase chain reaction-based techniques. Multivariate logistic regression analysis was performed for association analysis of the overall data as well as the data stratified by smoking status, tumor grade and tumor stage. Variants of GSTM1, IGFBP3, LEPR and ACE were found to be associated with altered UBC risk in the overall comparison. CYP1B1 and CDKN1A variants displayed a risk modulation among smokers; IGFBP3 and LEPR variants among non­smokers while GSTM1 polymorphism exhibited association with both. GSTM1 and LEPR variants conferred an altered susceptibility to low grade UBC; GSTT1, IGFBP3 and PPARG variants to high grade UBC while ACE polymorphism to both grades. GSTM1 and LEPR variants exhibited risk modulation for non-muscle-invasive bladder cancer (NMIBC); GSTT1 and PPARG variants for muscle-invasive bladder cancer (MIBC), and ACE variant for NMIBC as well as MIBC. In general, the susceptibility markers were common for low grade and NMIBC; and distinct from those for high grade and MIBC indicating the distinct pathologies of both groups. In brief, our results conform to reports of previously associated variants in addition to identifying novel potential genetic predictors of UBC susceptibility.     

Assessment of pelvic floor dysfunctions using dynamic magnetic resonance imaging

Purpose

The purpose of this study was to assess pelvic floor dysfunction using dynamic MRI.

Material and methods

A prospective study was carried out on 21 consecutive patients presented during February 2013 to June 2013 with pelvic pain, difficulty in defecation, constipation or organ prolapse. Pelvic floor was imaged using T2-weighted and fast imaging employing steady-state acquisition sequences. Pubococcygeal line was used as the line of reference which further allowed measurement of width and vertical descent of levator hiatus. Anorectal angle was measured to assess relaxation and contraction of puborectalis muscle. Grading of prolapse was classified as mild, moderate and severe. All data were recorded both in resting and during straining phase.

Results

A total of 21 patients were studied, with a mean age of 37.3 (9.4) years with 15 (71.4%) females and 6 (21%) males. Dynamic MR revealed cystocele and rectocele in 7 (33.3%) patients, each. Three (14.28%) patients had enteroceles and spastic pelvic syndrome, each. Only one patient (4.76%) had descending perineal syndrome. Intussusception was observed in 10 (47.6%) patients with commonest type being intra rectal seen in 7 (33.3%) patients.

Conclusion

Dynamic MRI is an ideal, non invasive technique which does not require patient preparation for evaluation of pelvic floor. It acts as one stop shop for diagnosing single or multiple pelvic compartment involvement in patients with pelvic floor dysfunction.     

Effect of khat,its constituents and restraint stress on free radical metabolism of rats

The leaves of khat (Catha edulis) are found to have stimulating and pleasurable effect and are chewed habitually by people of East Africa and Arabian Peninsula. Due to various toxic and psychostimulative effect of khat the present study was undertaken to evaluate the effect of intragastric khat alone or its major constituents flavonoids/alkaloids administration and before and after 4 h of immobilization stress in terms of alteration of free radical scavenging/metabolizing enzymes, uric acid and glucose in rats. Oral khat, alkaloid administration or 4 h restraint stress resulted in the decrease of the circulating levels of superoxide dismutase, catalase, glutathione-S-transferase and glucose with enhanced uric acid concentrations as compared with control rats. Oral treatment with flavonoid fraction of khat was found to enhance the activities of GST and catalase but showed no effect on SOD while the level of glucose was decreased and uric acid increased. The levels of these biochemical parameters were more altered in post stress khat/alkaloid treated rats than pre stress khat/alkaloid treated rats. The alteration in the levels of SOD, GST, catalase and uric acid in the pre stress khat treated rats were comparable with that of khat alone, except the level of glucose which was further decreased in pre stress khat treated rats. The flavonoid fraction of khat reduced the stress induced oxidative stress in terms of above mentioned biochemical parameters. The present study suggests that khat alone or khat/alkaloid consumption preceding stress may significantly decrease the levels of free radical metabolizing/scavenging enzymes and glucose leading to enhanced free radical concentration and toxicity of khat, which could be due to its alkaloid fraction as flavonoids were found to show antioxidant properties for oxidative stress generated during restraint stress.     

Association of ABO blood groups with glaucoma in the Pakistani population

Objective: To study the association of blood groups with different types of glaucoma including primary open-angle glaucoma (POAG), primary closed-angle glaucoma (PCAG), and pseudoexfoliative glaucoma (PEXG) in the Pakistani population.Study Design: The present study was a prospective case control study.Participants: ABO and Rh blood groups were analyzed in 2046 controls and 477 glaucoma patients (220 POAG, 146 PCAG, and 111 PEXG).Methods: Hemagglutination patterns were used to determine the prevalence of the ABO and Rh blood groups in all the subjects. Logistic regression analysis was carried out to evaluate any association of the different blood groups with glaucoma.Results: In the present study, the percentage of blood groups A, B, AB, and O in patients was found to be 19%, 41%, 10%, and 30%, and in the control group, the values were 26%, 31%, 12%, and 31%, respectively. A significant positive association was found between the B blood group and glaucoma (p value < 0.05, odds ratio [OR] 1.5, and χ² 15.8). Logistic regression analysis revealed that the blood group B was associated with all types of glaucoma with OR of 1.35 (95% CI 1.01-1.80; p = 0.04) for POAG, 1.71 (95% CI 1.21-2.40; p = 0.002) for PCAG, and 1.61 (95% CI 1.09-2.36; p = 0.016) for PEXG. POAG was also found to be associated with the Rh- allele (p < 0.05) with an OR of 4.05 (95% CI 2.98-5.51), as compared with controls.Conclusions: In the Pakistani patient cohort, blood group B is associated with all types of glaucoma and the Rh-allele is associated only with POAG.     

Anti fi larial potential of the fruits and leaves extracts of Pongamia pinnata on cattle filarial parasite Setaria cervi

The effect of aqueous and alcohol extracts of the fruits and leaves of Pongamia pinnata (Linn.) Merr. (Syn. Pongamia glabra Vent, leguminosae) on the spontaneous movements of both the whole worm and the nerve-muscle preparation of Setaria cervi and on the survival of micro fi lariae in vitro was studied. The aqueous and alcohol extracts of fruits and the alcohol extract of leaves caused an inhibition of spontaneous movements of the whole worm and the nerve-muscle preparation of S. cervi. The initial stimulatory effect was not observed with the aqueous extract of fruits on the nerve-muscle preparation. The concentration required to inhibit the movements of the whole worm preparation was 250 micro g/mL for aqueous, 120 micro g/mL for alcohol extract of fruits and 270 microgram/mL for alcohol extracts of the leaves. The concentrations of P. pinnata extracts required to produce an equivalent effect on the nerve-muscle preparation were 25 micro g/mL, 5 micro g/mL and 20 micro g/mL, respectively, suggesting a cuticular permeability barrier.     

10-Year Experience with the Modified Pectoralis Major Flap: The Use of the Deltopectoral Flap to Reduce Skin Tension

Purpose: Pectoralis major myocutaneous flap has been the work horse flap for head and neck reconstruction. However, due to the bulky nature of the pedicle it is not uncommon to struggle to achieve tension free closure of the neck skin incision. This case series presents a modified pectoralis major flap technique to overcome the difficulty of tight closure or the need to graft the residual cutaneous defect. Method: This 10-year study includes 73 patients who underwent modified pectoralis major flap reconstruction for complex laryngo-pharyngeal defects following resection of tumours involving larynx, hypopharynx oropharynx and cervical oesophagus. The modified technique involves accommodating a deltopectoral fasciocutaneous flap which rotates over the pedicle to insert into the neck incision providing extra tissue to achieve a tension free closure. Results: 73 patients underwent the procedure, 80% were male. Mean age of patients was 62.8years. Larynx was the most common site and the average size of the tumour was 34.8 mm. 13 patients developed minor complications such as wound dehiscence out of which 10 were managed conservatively, 3 patients required additional reconstructive procedures. 13 patients developed pharyngocutaneous fistula and 6 developed Neopharyngeal stenosis. 51 patients achieved good swallowing and 55 developed intelligible speech following recovery. Conclusion: We recommend the use of this technique as an effective method to achieve tension free neck incision closure and improved cosmetic results especially in centres which do not have free flap facility readily available.     

Quantitative T1ρ MRI of the Head and Neck Discriminates Carcinoma and Benign Hyperplasia in the Nasopharynx

BACKGROUND AND PURPOSE:T1ρ imaging is a new quantitative MR imaging pulse sequence with the potential to discriminate between malignant and benign tissue. In this study, we evaluated the capability of T1ρ imaging to characterize tissue by applying T1ρ imaging to malignant and benign tissue in the nasopharynx and to normal tissue in the head and neck.MATERIALS AND METHODS:Participants with undifferentiated nasopharyngeal carcinoma and benign hyperplasia of the nasopharynx prospectively underwent T1ρ imaging. T1ρ measurements obtained from the histogram analysis for nasopharyngeal carcinoma in 43 participants were compared with those for benign hyperplasia and for normal tissue (brain, muscle, and parotid glands) in 41 participants using the Mann-Whitney U test. The area under the curve of significant T1ρ measurements was calculated and compared using receiver operating characteristic analysis and the Delong test, respectively. A P < . 05 indicated statistical significance.RESULTS:There were significant differences in T1ρ measurements between nasopharyngeal carcinoma and benign hyperplasia and between nasopharyngeal carcinoma and normal tissue (all, P < . 05). Compared with benign hyperplasia, nasopharyngeal carcinoma showed a lower T1ρ mean (62.14 versus 65.45 × ms), SD (12.60 versus 17.73 × ms), and skewness (0.61 versus 0.76) (all P < .05), but no difference in kurtosis (P = . 18). The T1ρ SD showed the highest area under the curve of 0.95 compared with the T1ρ mean (area under the curve  = 0.72) and T1ρ skewness (area under the curve  = 0.72) for discriminating nasopharyngeal carcinoma and benign hyperplasia (all, P < .05).CONCLUSIONS:Quantitative T1ρ imaging has the potential to discriminate malignant from benign and normal tissue in the head and neck.

The spin-lattice relaxation time in the rotating frame known as T1ρ is sensitive to biologic processes associated with alterations in the macromolecular content of tissue. Quantitative T1ρ imaging has been used to study normal tissue and nonmalignant diseases in cartilage, discs, and ligaments,^1-3 brain,^4-7 liver,^8,9 heart,¹⁰ muscles,¹¹ and parotid glands.^11-13 However, T1ρ imaging also has the potential to characterize benign and malignant processes, but only a few studies have preliminarily evaluated T1ρ for human cancer imaging. These studies showed differences of T1ρ values between high- and low-grade gliomas¹⁴ and between benign and malignant tissue in the brain,^15,16 breast,¹⁷ and prostate.¹⁸We are interested in quantitative MR imaging sequences that can be used to discriminate nasopharyngeal carcinoma (NPC) from benign hyperplasia in the nasopharynx because these entities may overlap on anatomic MR imaging sequences.^19,20 Our hypothesis is that the T1ρ value of malignancy is different from that of benign tissue and can be used to discriminate these 2 entities. In this preliminary study, we also applied T1ρ imaging to a range of normal tissue in the head and neck (brain, pterygoid muscle, and parotid gland) to compare the T1ρ values of normal tissue with those of NPC.     

Theoretical underpinnings of state institutionalisation of inclusion and struggles in collective health in Latin America

ABSTRACT

Community participation as a strategy in health aims to increase the role of citizens in health decision-making which are contextualised within the institutions of democracy. Electoral representation as the dominant model of democracy globally is based on the elite theory of democracy that sees political decision-making a prerogative of political elites. Such political elitism is counter to the idea of democratic participation. Neoliberalism together with elitism in political sphere have worsened social inequities by undermining working class interests. Latin America has seen adverse consequences of these social inequities. In response, social movements representing collective struggles of organised citizens arose in the region. This paper explores the theoretical underpinnings of democratic participation in contemporary Latin American context at the nexus of emerging social movement activism and policy responses. The paper will use empirical examples to highlight how such democratic practices at the societal level evolved while demanding political inclusion. These societal democratic practices in Latin America are redefining democracy, which continues to be seen in the political sphere only. Health reforms promoting participatory democracy in several Latin American countries have demonstrated that establishing institutions and mechanisms of democratic participation facilitate collective participation by the organised citizenry in state affairs.     

The Status of Polychlorinated Biphenyls (PCBs) Extract from Zhanjiang Mangrove Sediments and the Effects on Tissue Structure and Inflammatory Cytokines in Zebrafish Liver

Bulletin of Environmental Contamination and Toxicology - Polychlorinated biphenyls (PCBs) are released into the environment from a wide range of sources. The aim of the present study was to...     

In silico CD4+ T-cell epitope prediction and HLA distribution analysis for the potential proteins of Neisseria meningitidis Serogroup B—A clue for vaccine development

Neisseria meningitidis, an exclusive human pathogen, is a major cause of mortality due to meningococcal meningitis and sepsis in many developing countries. Three meningococcal serogroup B proteins, i.e. T-cell stimulating protein A (TspA), autotransporter A (AutA), and IgA-specific serine endopeptidase (IGA1) elicits CD4+ T-cell response and may enhance the effectiveness of meningococcal vaccines by acting as protective immunogens. A very limited data on T-helper cell epitopes in MenB proteins is available. Hence, in silico prediction of peptide sequences which may act as helper T lymphocyte epitopes in MenB proteins was carried out by NetMHCIIpan web server. HLA distribution analysis was done by using the population coverage tool of Immune Epitope Database to determine the fraction of individuals in various populations expected to respond to a given set of predicted T-cell epitopes based on HLA genotype frequencies. Six epitopic core sequences, two from each MenB proteins, i.e. AutA, TspA and IgA1 protease were predicted to associate with a large number of HLA-DR alleles. These six peptides may act as T-cell epitope in more than 95% of populations in 8 out of 12 populations considered. The T-cell stimulation potential of these predicted peptides containing the core epitopic sequences is to be validated by using laboratory experiments for their efficient use as peptide vaccine candidates against N. meningitidis serogroup B.