Goiter prevalence and iodine deficiency disorder among school-age children (6-12 years) in district Ganderbal of Kashmir valley.

BACKGROUND: Iodine deficiency is a major cause of brain damage in childhood which can be prevented. Dietary deficiency of iodine is mainly responsible for iodine deficiency. This study was done to determine the prevalence of goiter among school-aged group of 6-12 years in district Ganderbal. MATERIALS AND METHODS: This was a cross-sectional study done among children of 6-12 years in district Ganderbal. RESULTS: Out of 2700 children examined, Grade 1 goiter was found in 90 (3.3%) children and Grade 2 goiter was found in 6 (0.3%) with a total goiter rate (sum of grade first and grade second) of 3.6%. On analyzing the urine samples, about 19.1% of the children had mild to moderate iodine deficiency. CONCLUSION: The study showed mild goiter prevalence in school-aged children of 6-12 years in the Ganderbal district of Kashmir valley. Continuous periodic surveys to assess the magnitude of the iodine deficiency disorders (IDD) should be undertaken to ensure that we achieve sustainable elimination of IDD in India.

A network meta-analysis of surgical treatments of complete rectal prolapse.

PURPOSE: Surgical treatment of complete rectal prolapse can be undertaken via an abdominal or a perineal approach. The present network meta-analysis aimed to compare the outcomes of different abdominal and perineal procedures for rectal prolapse in terms of recurrence, complications, and improvement in fecal incontinence (FI). METHODS: A PRISMA-compliant systematic review of PubMed, Scopus, and Web of Science was conducted. Randomized clinical trials comparing two or more procedures for the treatment of complete rectal prolapse were included. The risk of bias was assessed using the ROB-2 tool. The main outcomes were recurrence of full-thickness rectal prolapse, complications, operation time, and improvement in FI. RESULTS: Nine randomized controlled trials with 728 patients were included. The follow-up ranged between 12 and 47 months. Posterior mesh rectopexy had significantly lower odds of recurrence than did the Altemeier procedure (logOR, - 12.75; 95% credible intervals, - 40.91, - 1.75), Delorme procedure (- 13.10; - 41.26, - 2.09), resection rectopexy (- 11.98; - 41.36, - 0.19), sponge rectopexy (- 13.19; - 42.87, - 0.54), and sutured rectopexy (- 13.12; - 42.58, - 1.50), but similar odds to ventral mesh rectopexy (- 12.09; - 41.7, 0.03). Differences among the procedures in complications, operation time, and improvement in FI were not significant. CONCLUSIONS: Posterior mesh rectopexy ranked best with the lowest recurrence while perineal procedures ranked worst with the highest recurrence rates.

A systematic review and meta-analysis of the outcome of ileal pouch-anal anastomosis in patients with ulcerative colitis versus patients with familial adenomatous polyposis.

BACKGROUND: Ileal pouch-anal anastomosis (IPAA) is commonly used to restore gastrointestinal continuity after surgical treatment of mucosal ulcerative colitis (MUC) and familial adenomatous polyposis (FAP). The aim of the present systematic review was to compare the outcomes of patients with MUC and patients with FAP who underwent IPAA. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-compliant systematic review was performed. PubMed, Scopus, and Web of Science were searched through December 2021. Cohort and randomized studies were eligible for inclusion if they directly compared patients with MUC and FAP who underwent IPAA. The main outcome measures were pouch failure, complications, and need for pouch excision or revision. ROBINS-I tool was used to assess the risk of bias across the studies. A random-effect meta-analysis was conducted. RESULTS: Twenty-three studies (9200 patients) were included in this meta-analysis. Seven thousand nine hundred fifty (86.4%) had MUC and 1250 (13.6%) had FAP. The median age of patients was 33.1 years. The male to female ratio was 1.4:1. MUC had higher odds of pouchitis (OR 3.9, 95% CI 2.8-5.4, p < 0.001), stricture (OR 1.82, 95% CI 1.25-2.65, p = 0.002), fistula (OR 1.74, 95% CI 1.18-2.54, p = 0.004), and total complications (OR 1.89, 95% CI 1.3-2.77, p < 0.001) as compared to FAP. Both groups had similar odds of pelvic sepsis, leakage, pouch failure, excision, revision, and fecal incontinence. CONCLUSIONS: Although patients with MUC undergoing IPAA may be at a higher risk of developing complications, particularly pouchitis, stricture, and fistula; the ultimate and functional outcome of the pouch is similar to patients with FAP. Pouch failure, excision and revision were similar in the two groups.

A Mixed Methods Population Health Approach to Explore Radon-Induced Lung Cancer Risk Perception in Canada.

BACKGROUND: Radon is a predominant indoor air pollutant and second leading cause of lung cancer in radon-prone areas. Despite the gravity of the health risk, residents in Canada have inadequate perception and taken minimal protective actions. Better perception of a risk motivates people to take preventive measures. Scholarship about radon health risk perception is lacking in Canada. We applied a mixed methods population health approach to explore the determinants shaping perception and actions of a resident population in Canada. METHODS: We conducted mixed surveys (n = 557) and qualitative bilingual interviews (n = 35) with both homeowners and tenants of Ottawa-Gatineau areas. The study explored residents' risk perception and adaptations factors. Descriptive, correlational and regression analyses described and established associations between quantitative variables. Thematic, inductive analyses identified themes in the qualitative data. A mixed methods analysis triangulated both results to draw a holistic perception of the health risk. RESULTS: Residents' quantitative perceptions of radon health risk, smoking at home, synergistic risk perception, social influence and care for family were associated significantly with their intention to test for radon levels in their home, actual testing and mitigation. These results were explained further with the qualitative findings. Residents who had dual cognitive and emotional awareness of the risk were motivated enough to take preventive actions. Caring for family, knowing others who contracted lung cancer and financial capability were enablers, whereas lack of awareness and homeownership, cost of mitigation and stigma were obstacles to preventive actions. We also explored the dual subjective and objective aspects of risk perception that are influenced by micro- and macro-level determinants. CONCLUSIONS: Inducing protective action to reduce risk requires comprehensive population-level interventions considering dual perceptions of the risk that can modify the risk determinants. Future research can explore the dual aspects of risk perception and unequal distribution of the risk factors.

Effectiveness, acceptance and feasibility of home-based intervention model for tuberculosis contact tracing in Kashmir.

BACKGROUND: As long as one case of tuberculosis is replaced by another, elimination of tuberculosis cannot be achieved. Contact tracing is an important strategy for detection of more TB cases early. The present study is concerned with an innovative method of contact tracing. METHODS: A quasi randomized interventional study was conducted in two TB Units of Kashmir for evaluation of newly designed interventional model for its effectiveness, acceptance and feasibility. Data was collected from 1st Jan 2014 to 30th June 2015. RESULTS: In interventional group of 598 eligible household contacts, total 27 (4.51%) contacts were detected as suffering from active pulmonary TB cases. Out these, 21 (3.51%) cases were diagnosed during initial home visit and 6 (1.04%) cases were diagnosed at 6th monthly follow up visit. In controlled group 593 eligible household contacts, total 7 (1.18%) contacts were found suffering from active pulmonary -TB during routine practice under RNTCP for contact screening. In interventional group, during initial home visit by the investigator, 423 (70.74%) of household contacts participated for study and during follow up visit at 6th month, 356 (59.53%) household contacts participated. CONCLUSION: Newly designed "home-based intervention model" for active-case finding among household contacts of index pulmonary-TB case has been found an effective method for contact tracing. This intervention has adequate acceptance by the community and feasible for implementation under existing revised national tuberculosis control programme.

Epidemiology of Cancers in Kashmir, India: An Analysis of Hospital Data.

Cancer is a leading cause of mortality and morbidity in the world. The aim of the present study was to measure the pattern of different cancers in Kashmir, India, a cancer belt with peculiar cancer profile. A hospital based cancer registry was started by the Department of Community Medicine, Government Medical College, Srinagar, in January 2006, wherein information was collected from cancer patients who were diagnosed and treated in the hospital. Data has been analysed for a period extending from January 2006 to December 2012. Descriptive analysis has been done by using statistical software. A total of 1598 cancer patients were admitted during this period. Overall male to female ratio was 1.33 : 1. Stomach cancer was the most commonly reported cancer (25.2%), followed by colorectal cancer (16.4%) and lung cancer (13.2%) among males. For females, colorectal cancer (16.8%), breast cancer (16.1%), and stomach cancer (10.4%) were the most frequently reported cancers in order of frequency. Tobacco related cancers contributed to more than three-fourths of cancers among men and more than half of cancers for women. There is an urgent need to set up a population based cancer registration system to understand the profile of cancers specific to this geographic region.

Bioequivalence of two lansoprazole delayed release capsules 30 mg in healthy male volunteers under fasting, fed and fasting-applesauce conditions: a partial replicate crossover study design to estimate the pharmacokinetics of highly variable drugs.

An open-label, 2-treatment, 3-sequence, 3-period, single-dose, partial replicate crossover studies under fasting (n=48), fed (n=60) and fasting-applesauce (n=48) (sprinkled on one table spoonful of applesauce) modalities were conducted in healthy adult male volunteers to evaluate bioequivalence between 2 formulations of lansoprazole delayed release capsules 30 mg. In all the 3 studies, as per randomization, either test or reference formulations were administered in a crossover manner with a required washout period of at least 7 days. Blood samples were collected adequately (0-24 h) to determine lansoprazole plasma concentrations using a validated LC-MS/MS analytical method. To characterize the pharmacokinetic parameters (Cmax, AUC0-t, AUC0-∞, Tmax, Kel and T1/2) of lansoprazole, non-compartmental analysis and ANOVA was applied on ln-transformed values. The bioequivalence was tested based on within-subject variability of the reference formulation. In fasting and fed studies (within-subject variability>30%) bioequivalence was evaluated with scaled average bioequivalence, hence for the pharmacokinetic parameters Cmax, AUC0-t and AUC0-∞, the 95% upper confidence bound for (µT-µR)2-θσ2 WR was ≤0, and the point estimates (test-to-reference ratio) were within the regulatory acceptance limit 80.00-125.00%. In fasting-applesauce study (within-subject variability<30%) bioequivalence was evaluated with average bioequivalence, the 90% CI of ln-transformed data of Cmax, AUC0-t and AUC0-∞ were within the regulatory acceptance limit 80.00-125.00%. Based on these aforesaid statistical inferences, it was concluded that the test formulation is bioequivalent to reference formulation.

Bioequivalence of fixed dose combination of atorvastatin 10 mg and aspirin 150 mg capsules: a randomized, open-label, single-dose, two-way crossover study in healthy human subjects.

The present study evaluated the bioavailability and bioequivalence of fixed dose combination test formulation (atorvastatin 10 mg and aspirin 150 mg capsule) against marketed reference formulations (Lipitor® tablets 10 mg and Nu-Seals tablets 75 mg). This study was an open label, balanced, randomized, 2-treatment, 2-period, 2-sequence, single dose, crossover trial in 80 healthy adult human volunteers under fasting conditions. Plasma concentrations of atorvastatin, aspirin and salicylic acid were quantified using LC-MS/MS method. Pharmacokinetic parameters were estimated by noncompartmental model and mean pharmacokinetic parameters were comparable between test and reference formulations. The mean pharmacokinetic parameters (AUC0-t, AUC0-∞, Cmax, Cmax /AUC0-t and Cmax/AUC0-∞) for atorvastatin test and reference formulations were (52.69 ng.h/mL, 55.64 ng.h/mL, 9.45 ng/mL, 0.18 1/h and 0.17 1/h) and (52.20 ng.h/mL, 55.38 ng.h/mL, 10.25 ng/mL, 0.20 1/h and 0.19 1/h) respectively; and for aspirin were (1 378.62 ng.h/mL, 1 383.90 ng.h/mL, 1 022.18 ng/mL, 0.75 1/h and 0.75 1/h) and (1 314.17 ng.h/mL, 1 314.50 ng.h/mL, 985.90 ng/mL, 0.75 1/h and 0.75 1/h) respectively. Where as for salicylic acid, above parameters were (42 357.57 ng.h/mL, 44 139.47 ng.h/mL, 9 820.15 ng/mL, 0.24 1/h and 0.23 1/h) and (40 217.08 ng.h/mL, 42 032.44 ng.h/mL, 9 569.18 ng/mL, 0.24 1/h and 0.24 1/h) respectively for test and reference formulations. The 90% confidence intervals of atorvastatin and salicylic acid for AUC0-t, AUC0-∞, Cmax, Cmax /AUC0-t and Cmax/AUC0-∞ parameters were found to be within the acceptable regulatory bioequivalence limits. In conclusion, the new fixed dose combination test formulation was bioequivalent to the reference formulations under fasting conditions.

Axopodial degradation in the heliozoon Raphidiophrys contractilis: a novel bioassay system for detecting heavy metal toxicity in an aquatic environment.

We observed the physiological effects of zinc, lead, mercury, copper, cadmium, and arsenic on the axopodia of the centrohelid heliozoon Raphidiophrys contractilis. In the presence of these heavy metal ions, the axopodial length of the heliozoon decreased in a concentration-dependent manner. When the heavy metal ions were examined at the same concentration, mercury produced the strongest effect on axopodia. At a high concentration (> 10-3 M) of any of the heavy metal ions examined, axopodia disappeared and cells became disrupted. Axopodia were also degraded by the addition of solutions with an acidic (< or = 6) or basic (> or = 8) pH. These observations indicate the toxic effects of heavy metal ions and non-neutral pHs on axopodial length, and also signify that R. contractilis can be used as an effective biological tool for the study of metal poisoning in eukaryotic cells.

Ca2+-dependent in vitro contractility of a precipitate isolated from an extract of the heliozoon Actinophrys sol.

Contraction of axopodia in actinophrid heliozoons (protozoa) is induced by a unique contractile structure, the "contractile tubules structure (CTS)". We have previously shown that a cell homogenate of the heliozoon Actinophrys sol yields a precipitate on addition of Ca2+ that is mainly composed of filamentous structures morphologically identical to the CTS. In this study, to further characterize the nature of the CTS in vitro, biochemical and physiological properties of the precipitate were examined. SDS-PAGE analysis showed that the Ca2+-induced precipitate was composed of many proteins, and that no proteins in the precipitate showed any detectable changes in electrophoretic mobility on addition of Ca2+. Addition of extraneous proteins such as bovine serum albumin to the cell homogenate resulted in cosedimentation of the proteins with the Ca2+-induced precipitate, suggesting that the CTS has a high affinity for other proteins that are not related to precipitate formation. Appearance and disappearance of the precipitate were repeatedly induced by alternating addition of Ca2+ and EGTA, and its protein composition remained unchanged even after repeated cycles. When adhered to a glass surface, the precipitate showed Ca2+-dependent contractility with a threshold of 10-100 nM, and this contractility was not inhibited by colchicine or cytochalasin B. The precipitate repeatedly contracted and relaxed with successive addition and removal of Ca2+, indicating that the contraction was controlled by Ca2+ alone with no need for any other energy supply. From our characterization of the precipitate, we concluded that its Ca2+-dependent formation and contraction are associated with the unique contractile organelle, the "contractile tubules structure".

Ca2+-dependent nuclear contraction in the heliozoon Actinophrys sol.

Ca2+-dependent contractility was found to exist in the nucleus of the heliozoon protozoan Actinophrys sol. Upon addition of Ca2+ ([Ca2+]free = 2.0 x 10(-3) M), diameters of isolated and detergent-extracted nuclei became reduced from 16.5+/-1.7 microm to 11.0+/-1.3 microm. The threshold level of [Ca2+]free for the nuclear contraction was 2.9 x 10(-7) M. The nuclear contraction was not induced by Mg2+, and was not inhibited by colchicine or cytochalasin B. Contracted nuclei became expanded when Ca2+ was removed by EGTA; thus cycles of contraction and expansion could be repeated many times by alternating addition of Ca2+ and EGTA. The Ca2+-dependent nuclear contractility remained even after high salt treatment, suggesting a possible involvement of nucleoskeletal components in the nuclear contraction. Electron microscopy showed that, in the relaxed state, filamentous structures were observed to spread in the nucleus to form a network. After addition of Ca2+, they became aggregated and constructed a mass of thicker filaments, followed by re-distribution of the filaments spread around inside of the nucleus when Ca2+ was removed. These results suggest that the nuclear contraction is induced by Ca2+-dependent transformation of the filamentous structures in the nucleus.

Axopodial contraction in the heliozoon Raphidiophrys contractilis requires extracellular Ca2+.

Axopodial contraction of the centrohelid heliozoon Raphidiophrys contractilis was induced by mechanical or electrical stimulation. For inducing contraction, extracellular Ca(2+) was required. The threshold level of extracellular Ca(2+) was between 10(-6)-10(-7) M. The speed of axopodial contraction was faster than 3.0 mm/sec. Re-elongation of axopodia started just after contraction, and its initial velocity was approximately 0.30 microm/sec. Electron microscopic observations were carried out using an improved fixative that contained 1 mg/ml ruthenium red and 15 microM Taxol. This fixative prevented artificial retraction of axopodia and resulted in better fixation. A bundle of hexagonally-arranged microtubules was observed in each axopodium, but no other filamentous structures were detected, suggesting that the contractile machinery of axopodia in R. contractilis may be different from that in actinophryid heliozoons in which Ca(2+)-dependent contractile filaments are employed for contraction.

Caspase-9 is activated in a cytochrome c-independent manner early during TNFalpha-induced apoptosis in murine cells.

FL5.12 pro-B lymphoma cells utilize the mitochondrial pathway to apoptosis in response to tumor necrosis factor (TNF) receptor occupation, yet high levels of the Bcl-2 family antiapoptotic protein, Bcl-x(L), fail to protect these cells against TNF-receptor-activated death. Bcl-x(L) expression delays, but does not totally block, the release of mitochondrial cytochrome c (cyt c) in these cells in response to TNFalpha-induced apoptosis and caspase-9 is processed prior to mitochondrial cyt c release under these circumstances. Early processing of caspase-9 also occurred in Apaf-1 knockout murine fibroblasts in response to TNF-receptor occupation. A caspase-9-specific inhibitor was more effective in delaying the progression of apoptosis in the FL5.12 Bcl-x(L) cells than was an inhibitor specific to caspase-3. Furthermore, downregulation of caspase-9 levels by RNA interference resulted in partial protection of these cells against TNF-receptor-activated apoptosis, indicating that caspase-9 activation contributed to early amplification of the caspase cascade. Consistent with this, proteolytic processing of caspase-9 was observed prior to processing by caspase-3, suggesting that caspase-3 was not responsible for early caspase-9 activation. We show that murine caspase-9 is efficiently processed by active caspase-8 at SEPD, the motif at which caspase-9 autoprocesses following its recruitment to the apoptosome. Our results suggest that, in addition to processing procaspase-3 and the BH3 protein Bid, active caspase-8 can cleave and activate procaspase-9 in response to TNF receptor crosslinking in murine cells.

Gliding movement in Peranema trichophorum is powered by flagellar surface motility.

A colorless euglenoid flagellate Peranema trichophorum shows unique unidirectional gliding cell locomotion on the substratum at velocities up to 30 micro m/s by an as yet unexplained mechanism. In this study, we found that (1) treatment with NiCl(2) inhibited flagellar beating without any effect on gliding movement; (2) water currents applied to a gliding cell from opposite sides caused detachment of the cell body from the substratum. With only the anterior flagellum adhering to the substratum, gliding movement continued along the direction of the anterior flagellum; (3) gentle pipetting induced flagellar severance into various lengths. In these cells, gliding velocity was proportional to the flagellar length; and (4) Polystyrene beads were translocated along the surface of the anterior flagellum. All of these results indicate that a cell surface motility system is present on the anterior flagellum, which is responsible for cell gliding in P. trichophorum.

Massive lower gastrointestinal bleeding due to Dieulafoy lesion of colon.

A 25-year-old man with massive lower gastrointestinal bleeding underwent emergency mesenteric angiography. An actively bleeding lesion was found in the cecum. Right hemicolectomy was performed. Histology revealed a Dieulafoy lesion of the cecum. This is an extremely rare lesion responsible for massive lower GI bleeding.

Ca2+-dependent contractility of isolated and demembranated macronuclei in the hypotrichous ciliate Euplotes aediculatus.

The hypotrichous ciliated protozoan Euplotes aediculatus possesses a characteristic C-shaped somatic nucleus (macronucleus) within the cytoplasm, which shows dynamic shape change during the cell cycle. It is shown that isolated macronuclei possess Ca(2+)-dependent contractility. Macronuclei were isolated, stuck fast on the glass surface, and subjected to different concentrations of Ca(2+) in a Ca(2+)-EGTA buffer. The nuclei became expanded at [Ca(2+)]<10(-7)M, and they contracted on subsequent addition of higher concentrations of Ca(2+). Cycles of expansion and contraction of the nucleus could be repeated many times by alternate addition of EGTA and Ca(2+), indicating that the size of isolated nuclei can be regulated by [Ca(2+)] alone. The nuclear contraction was observed in all phases of the cell cycle, but contractility was less evident around replication bands in the S phase. In addition to the hypotrichous ciliate Euplotes, similar Ca(2+)-dependent nuclear contractility was found to exist in other cell types, including protozoans of different taxa (a heliozoon Actinophrys sol and a peniculine ciliate Paramecium bursaria), and also mammalian culture cells (HeLa cells). Our findings suggest a possibility that Ca(2+)-dependent nuclear contractility may be shared among diverse eukaryotic organisms.

Small variant STEVOR antigen is uniquely located within Maurer's clefts in Plasmodium falciparum-infected red blood cells.

Malaria parasite antigens encoded by multigene families are important factors in virulence and in disease pathology. In Plasmodium falciparum, the virulence factor PfEMP-1 is encoded by the var multigene family and is exposed at the infected erythrocyte surface. PfEMP-1 is clonally variant, allowing the parasite to evade host immunity. The recently identified P. falciparum stevor multigene family and its products also have the potential to be involved in similar important aspects of host-parasite interactions. Here, we show tightly regulated stage-specific transcription of stevor occurring over just a few hours of the asexual parasite life cycle. Only a subset of stevor genes are transcribed in parasite populations maintained in cultures and in single micromanipulated parasites. Antibodies against STEVOR recognize proteins of the expected size (approximately 37 kDa) and localize STEVOR in Maurer's clefts, unique membranous structures located in the cytoplasm of infected erythrocytes. The fact that the timing of stevor expression and the location of STEVOR are clearly distinct from those of other parasite variant antigens suggests that this gene family may have a novel role in P. falciparum biology.

The 235 kDa rhoptry protein of Plasmodium (yoelii) yoelii: function at the junction.

All malaria parasites are obligate intracellular organisms that must clearly recognise and discriminate between different cells during their life cycle. Invasion into a cell is a multi-step event that is marked by initial attachment proceeding to irreversible junction formation and penetration. A 235 kDa rhoptry protein (Py235) in the rodent malaria, Plasmodium yoelii yoelii has been shown to be involved in red blood cell (rbc) binding and is involved in a new mechanism of clonal phenotypic variation that may be important in adaptation and immune evasion. Immunisation studies using Py235 have also revealed a role for this protein in the virulence phenotype seen with P. y. yoelii in laboratory mice. Interestingly, the genes that encode this protein are present as a multi-gene family. In this paper, we examine Py235 at the level of DNA, transcription and expression, discussing the role of this protein during invasion, in virulence and in immune evasion.