Emerging Horizons in the Diagnosis of Pancreatic Cancer: The Role of Circulating microRNAs as Early Detection Biomarkers for Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a poor prognosis, primarily due to a late diagnosis. Recent studies have focused on identifying non-invasive biomarkers for early detection, with microRNAs (miRNAs) emerging as promising candidates. This systematic review aims to evaluate the potential of circulating miRNAs as biomarkers for the early detection of PDAC, analyzing their diagnostic accuracy, specificity, and sensitivity. Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a comprehensive search across PubMed, Embase, and the Cochrane Library was conducted. Studies published from January 2013 to October 2023 focusing on miRNA biomarkers for early PDAC detection were included. Data synthesis was performed through a narrative approach due to the heterogeneity of the studies. Nine studies met the inclusion criteria. Key findings include the elevated levels of specific miRNAs, such as miR-18a, miR-106a, and miR-25, in early-stage PDAC patients compared to controls. The integration of miRNA profiles with traditional biomarkers like CA19-9 showed improved diagnostic performance. However, challenges in the standardization of miRNA evaluation methodologies were noted. Circulating miRNAs demonstrate significant potential as non-invasive biomarkers for early PDAC detection. Despite promising results, further research and standardization are necessary for clinical application.

Heavy metals in five commonly consumed fish species from River Swat, Pakistan, and their implications for human health using multiple risk assessment approaches.

This study analyzed the levels of heavy metals bioaccumulation in commonly consumed riverine fish species, including G. cavia, T. macrolepis, G. gotyla, S. plagiostomus, and M. armatus from River Swat in Pakistan, and quantify their potential risk to children and adults in general and fisherfolk communities using multiple pollution and risk assessment approaches. The highest metal detected by inductive coupled plasma mass spectrometry (ICP-MS) was Zn, which ranged from 49.61 to 116.83 mg/kg, followed by Fe (19.25-101.33 mg/kg) > Mn (5.25-40.35 mg/kg) > Cr (3.05-14.59 mg/kg) > Ni (4.26-11.80 mg/kg) > Al (1.59-12.25 mg/kg) > Cu (1.24-8.59 mg/kg) > Pb (0.29-1.95 mg/kg) > Co (0.08-0.46 mg/kg) > Cd (0.01-0.29 mg/kg), demonstrating consistent fluctuation with the safe recommendations of global regulatory bodies. The average bioaccumulation factor (BAF) values in the examined fish species were high (BAF > 5000) for Pb, Zn, Mn, Cu, Cr, Ni, and Cd, bioaccumulate (1000 > BAF < 5000) for Co, and probable accumulative (BAF <1000) for Fe, and Al, while the overall ∑heavy metals pollution index (MPI) values were greater than one (MPI > 1) indicating sever heavy metals toxicity in G. cavia, followed by S. plagiostomus, M. armatus, G. gotyla, and T. macrolepis. The multivariate Pearson's correlation analysis identified the correlation coefficients between heavy metal pairs (NiCr, CuCr, PbCr, AlCo, CuNi, and PbNi), the hierarchical cluster analysis (CA) determined the origin by categorizing heavy metal accumulation into Cluster-A, Cluster-B, and Cluster-C, and the principal component analysis (PCA) discerned nearby weathering, mining, industrial, municipal, and agricultural activities as the potential sources of heavy metals bioaccumulation in riverine fish. As per human risk perspective, S.plagiostomus contributed significantly to the estimated daily intake (EDI) of heavy metals, followed by G.cavia > M.armatus > G.gotyla > T.macrolepis in dependent children and adults of the fisherfolk followed by the general population. The non-carcinogenic target hazard quotient (THQ) and hazard index (HI) values for heavy metal intake through fish exposure were < 1, while the carcinogenic risk (CR) for individual metal intake and the total carcinogenic risk (TCR) for cumulative Cr, Cd, and Pb intake were within the risk threshold of 10-6-10-4, suggesting an acceptable to high non-carcinogenic and carcinogenic risk for both children and adults in the fisherfolk, followed by the general population.

Heavy metal pollution in the soil of a riverine basin: distribution, source, and potential hazards.

Soil pollution with heavy metals (HMs) has become a world environmental problem. This study focuses on surface soil contamination with Cr, Mn, Co, Ni, Cu, Zn, Cd, Hg, Pb, Fe, and Al, their sources, and potential hazards along the basin of River Swat, Pakistan. The average concentrations (mg/kg) of HMs were the most abundant for Al (24,730.19) followed by Fe (22,419.41) > Mn (386.78) > Zn (57.75) > Cr (38.07) > Ni (32.46) > Cu (23.43) > Pb (19.59) > Co (10.77) > Cd (3.18) > Hg (0.12). The concentrations of Cr and Mn in 5.45% each, Co in 10.90%, Zn in 27.27%, Cu in 36.36%, Ni in 41.81%, and Hg in 92.72% of the total soil samples exceeded their respective background values. The geostatistical approaches determined the distribution patterns of HM pollution along the basin, whereas the statistics of principal component analysis exposed the likely sources of HM contamination in the area. Pollution indices evaluated the overall HM distribution and pollution status in the area. Contamination factor showed a high degree of HM contamination in 82% of the total sampling sites, while the geo-accumulation index designated low to moderate contamination with Cr, Mn, Co, Ni, Cu, Zn, Hg, and Pb, and moderate to extreme contamination with Cd, Fe, and Al. The trend of ecological toxicity showed potential ups and downs along with the sites from low to considerable hazard (< 95 < PEHI < 190), whereas the human carcinogenic hazard was within the USEPA acceptable limits (1 × 10-7-1 × 10-4), but the non-carcinogenic hazard was higher than the threshold (HI > 1) for children because they are more exposed than adults.

The COVID-19 Pandemic and Overall Wellbeing: Mediating Role of Virtual Reality Fitness for Physical-Psychological Health and Physical Activity.

Background: Virtual reality applications are made for various objectives such as business, entertainment, education, and healthcare. Anxiety, phobias, distress, disordered eating, drug addiction, panic disorder, post-traumatic stress disorder, schizophrenia, bipolar disorder, psychosis, depression, and autism spectrum disorders may benefit from virtual reality-based approaches. The 2019 coronavirus (COVID-19) pandemic has impacted the way we live, enjoy, study, sport, and socialize significantly. Virtual reality fitness technology gained much attention during the COVID-19 preventive measures time. Objective: The present study explores the role of virtual reality fitness in improving overall wellbeing during the COVID-19 pandemic home isolation period in terms of physical-psychological health and physical activity. Methods: A total of 2300 individuals were recruited using the snowball sampling technique to participate in the study. The primary data were collected using an anonymous web-based survey. SPSS-23 and Smart-PLS 3.2.9 software were used to analyze the data. Results: The direct path coefficient analysis of the study constructs show that virtual reality fitness has (preventive measures -> virtual reality fitness -> overall wellbeing, preventive measures -> virtual reality fitness -> physical exercise, and preventive measures -> virtual reality fitness -> physical health) profound effects on the research participants' mental and physical wellbeing of the study participants while indirect mediation analysis shows that virtual reality fitness has (preventive measures -> virtual reality fitness ->overall wellbeing, preventive measures -> virtual reality fitness -> physical exercise, preventive measures -> virtual reality fitness ->physical health) significant impacts. Conclusion: Our study results concluded that house exercises through virtual reality fitness are a good substitute for public gyms and private group fitness programs during the first pandemic wave for physical-psychological and overall wellbeing. Virtual reality fitness technology can alleviate many of the challenges brought on by the epidemic, resulting in increased utilization.

Heavy metals contamination, potential pathways and risks along the Indus Drainage System of Pakistan.

Riverine water exposed to heavy metals (HMs) pollution is a major concern in the world because of its serious effects on ecosystem and human health. This study assessed the pollution status, sources, diffusion and potential risks of Mn, Co, Cu, Zn, Cr, Ni, Cd, Hg and Pb for the first time along the entire Indus Drainage System of Pakistan. The concentrations of nine HMs in the riverine water ranged from 5.05-101.59 µg/L with a mean value of 41.51 µg/L. The overall metals quantification along the drainage was significantly high (27% of the total) in River Chenab followed by River Indus (26%) > Soan (20%) > Ravi (19%) > Kabul (5%) > Swat (3%). The potential sources of contamination were identified to be the surrounding geogenic activities, industrial/municipal wastewater discharges, agricultural and surface runoffs by using multivariate statistics including metals correlation analysis, hierarchical cluster analysis and principal component analysis. The average mass flux of ∑HMs in the entire drainage was approximately 10.24 tons/year, to which the River Indus contributed 84% of the total, Chenab 11%, Ravi 3%, Kabul 1%, and Soan 1% with more prevalence of biological essential (Zn&Mn) and non-essential (Ni&Cr) metals. In terms of ecological risk, the riverine water metals contamination (1.59 to 57.06) was within the risk threshold (ERI < 110), while the risks of ∑carcinogenic metals for exposed children and adults along the basin were significantly influenced between acceptable to high cancer risk by Cd, Co, Ni, Cr and Pb.

Experience of transcatheter device closure of atrial septal defect in a tertiary care institute.

OBJECTIVE: To share institutional experience of transcatheter device closure of secundum atrial septal defect in children and adults. METHODS: The descriptive cross-sectional study was conducted at the Department of Paediatric Cardiology, Institute of Cardiology, Multan, Pakistan, from February 2011 to September 2019, and comprised patients with moderate to large secundum atrial septal defect without severe pulmonary hypertension. All procedures were performed under general anaesthesia and trans-oesophageal echo guidance. Success and safety of procedure were evaluated. Data was analysed using SPSS 16. RESULTS: Of the 75 patients, 26(34.6%) were males and 49(65.3%) were females. The overall mean age was 25±1.53 years (range: 4 -54 years). Mean defect was 20.38±0.58mm (range: 9-32mm). Large defects >25mm were 17(22.7%). Significant pulmonary stenosis was observed in 3(4%) patients and valvuloplasty was performed. Device size was selected on the basis of trans-oesophageal echo measurement +4-5mm. Balloon sizing was performed in only 3(4%) patients. Amplatzer septal occluder was used in 60(80%) patients. Balloon-assisted technique was used in 9(12%) patients. All the procedures were successful except 2(2.7%) where device was embolised and retrieved by surgery. Transient arrhythmias were observed in 6(8%) patients and small pericardial effusion in 1(1.3%) patient who was managed conservatively. There was no procedure-related mortality. CONCLUSION: Transcatheter closure of moderate to large secundum atrial septal defect in children and adults was found to be a safe procedure.

Bacillus pumilus induced tolerance of Maize (Zea mays L.) against Cadmium (Cd) stress.

Heavy metals contaminate the soil that alters the properties of soil and negatively affect plants growth. Using microorganism and plant can remove these pollutants from soil. The present investigation was designed to evaluate the induced effect of Bacillus pumilus on maize plant in Cadmium (Cd) contaminated soil. Three different concentrations of Cd (i.e. 0.25, 0.50 and 0.75 mg kg-1) were applied in soil under which maize plants were grown. The germination percentage, shoot length, leaf length, number of leaves, root length, fresh weight and nutrient uptake by maize plant were determined. The experiment was conducted by using complete randomized design (CRD) with three replicates. The result indicated that germination percentage, Shoot length, leaf length, root length, number of leaves, and plant fresh weight were reduced by 37, 39, 39, 32 and 59% respectively at 0.75 mg kg-1 of CdSO4 concentration but when maize seeds inoculated with Bacillus pumilus significantly increased the germination percentage, shoot length, leaf length, number of leaves, plant fresh weight at different concentrations of CdSO4. Moreover, the plant protein were significantly increased by 60% in T6 (0.25 mg kg-1 of CdSO4 + inoculated seed) and Peroxidase dismutase (POD) was also significantly higher by 346% in T6 (0.25 mg kg-1 of CdSO4 + inoculated seed), however, the Superoxide dismutase (SOD) was significantly higher in T5 (0.75 mg kg-1 of CdSO4 + uninoculated seed) and was 769% higher as compared to control. The Cd contents in Bacillus pumilus inoculated maize roots and shoots were decreased. The present investigations indicated that the inoculation of maize plant with Bacillus pumilus can help maize plants to withstand Cd stress but higher concentration of Cd can harm the plant. The Bacillus pumilus has good potential to remediate Cd from soil, and also have potential to reduce the phyto availability and toxicity of Cd.

Serologic evidence of Echinococcus granulosus in slaughterhouses in Pakistan: global alarm for butchers in developing countries.

INTRODUCTION: Cystic echinococcosis, caused by Echinococcus granulosus, is a neglected zoonosis that affects humans and livestock. This sero-survey was designed for the first time in Pakistan to assess the exposure of butchers to E. granulosus as there was no previous report in the country for this occupational group. METHODOLOGY: Blood samples were collected from registered butchers (n = 364) in five different slaughterhouses in Faisalabad and Bahawalnagar Districts. Sera were tested for anti-Echinococcus granulosus IgG with a commercially available ELISA kit (specificity, 100%; sensitivity, 97%). RESULTS: Overall, seroprevalence was 9.61% (35/364). Butchers >30 years of age (10.34%), those involved in small ruminants butchery (11.70%), >10 years' experience (10.04%), formal education level up to middle standard (10.28%), contact with dogs (12.71%), improper/unhygienic disposal of dog feces (11.87%), and those unaware of the consequences of eating with unwashed hands (13.80%) were more seropositive with significant statistical differences (p < 0.05). Variables like previous cyst encounter, no knowledge of zoonoses and/or cystic echinococcosis, living in rural areas and the presence of stray/feral dogs in surroundings did not show any significant association (p > 0.05) with seroprevalence in butchers. The binary logistic regression model also showed a statistically significant relationship (p < 0.05) for all risk factors found statistically significant (p < 0.05) in the univariate analysis. CONCLUSIONS: This study shows high prevalence of cystic echinococcosis among butchers in Pakistan and underscores the need for educating native slaughterhouse personnel on cystic echinococcosis. It also serves as a global warning, especially in developing countries.

Green and chemically synthesized zinc oxide nanoparticles: effects on in-vitro seedlings and callus cultures of Silybum marianum and evaluation of their antimicrobial and anticancer potential.

Zinc oxide nanoparticles (ZnO-NPs) have been produced by physical and chemical methods. Here, the comparative evaluation of both chemically-synthesised ZnO-NPs (C-ZNPs) and in-vitro cultured S. marianum mediated green-synthesised ZnO-NPs (G-ZNPs) were investigated on seed germination frequency, root and shoot growth, callus induction and biochemical profile of medicinally important plant Silybum marianum. Of all the treatments, callus-mediated ZnO-NPs gave optimum results for seed germination (65%), plantlet's root length (4.3 cm), shoot length (5.3 cm) and fresh and dry weights (220.4 g L-1 and 21.23 g L-1, respectively). Similarly, the accumulation of phenolic (12.3 µg/mg DW) and flavonoid (2.8 µg/mg DW) contents were also enhanced in callus cultures treated with G-ZNPs. We also observed maximum antioxidant activity (99%) in callus cultures treated with G-ZNPs, however, in case of plantlets, these activities were found highest for in-vitro whole plant-mediated ZnO-NPs. Moreover, G-ZNPs also enhanced total protein content (265.32 BSAE/20g FW) in callus cultures. G-ZNPs were further assessed for their effects on several multidrug resistant bacterial strains and human liver carcinoma (HepG2) cells and our findings revealed that callus extracts treated with G-ZNPs show ameliorated antibacterial (highest zone of inhibition (19 mm) against Klebsiella pneumonia) and anticancer (highest cytotoxicity of 64%) activities.

Outcome Of Open Interlocking Nailing In Closed Fracture Shaft Of Femur.

BACKGROUND: Various treatment modalities have been used in treating femoral shaft fractures, i.e., open intramedullary nailing, plating and external fixators but these does not always produce stable fixation and there is increased risk of infection, closed locked intramedullary nailing technique has being the gold standard and is a routine procedure but it requires proper orthopedic operation table with traction apparatus and the use of image intensifier. The use of open interlocking nailing technique doesn't require any special orthopaedic table nor it requires use of Image intensifier. The objective of this study is to find out and determine the frequency of fracture union and wound infection in open reamed interlocking nailing of close fractures of shaft of femur. METHODS: This study included fifty-eight patients from either gender, above 14 years of age with closed femoral shaft fracture presenting within 2 weeks. Data was collected on Performa about gender, age, address, date of fracture, date of operation and discharge, type of fracture and follow-up visits. RESULTS: Mean age of the patients were 31.24±8.662. According to Winquist & Hansen, femur shaft fractures were divided into four types. Type I were found in the 16(27.6%), Type II in 21 (36.2%), Type III in 12 (20.7%) and Type IV in 9 (15.5%). Total number of fracture union with regard to Winquist & Hensen Classification of fracture shaft femur were, Type I, 14 (24.1%), Type II, 21 (36.2%), Type III, 12 (20.7%), Type IV, 8 (13.8%) respectively while the rest 3 (5.2%) were found in non-union. Total number of fracture union with regard to gender of the patients were, 41 (70.7%) males and 14 (24.1%) were females while the rest 3 (5.2%) patients fracture union has not occurred. Fracture union was found in 55 (94.8%) out of 58 patients; while fracture union had not occurred in 3 (5.2%) out of 58 patients. The total number of patients who developed wound infection following surgery were 5 (8.6%) out of 58 patients; while the non-infected patients were 53 (91.4%) out of 58 patients. CONCLUSIONS: The open interlocking nailing technique for close fractures shaft of femur without the use of image intensifier achieved excellent results in terms of fracture union. Results obtained are mostly similar to the results of close interlocking nailing and it also requires less expertise, recourses and without the use of image intensifier.

Microbial synthesized cadmium oxide nanoparticles induce oxidative stress and protein leakage in bacterial cells.

The bactericidal activity of metal oxide nanoparticles (NPs) offers extensive opportunities in bioengineering and biomedicines. Bioengineered transition metals used in various forms against lethal microbes. In this study, Cadmium Oxide nanoparticles (CdO-NPs) were prepared through the co-precipitation method using fungal strain Penicillium oxalicum and cadmium acetate solution. The structure and elemental composition of the prepared NPs were determined by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), UV-Vis absorption spectroscopy, scanning electron microscope (SEM) and energy dispersive spectroscopy (EDS). Antibacterial activity was assessed through well diffusion method against Staphylococcus aureus (S. aureus), Shigella dysenteriae (S. dysenteriae), and Pseudomonas aeruginosa (P. aeruginosa). In addition, reactive oxygen species (ROS), reducing sugars and protein leakage contribution was examined against selected strains. The XRD analysis proved that the synthesized CdO-NPs possess a crystalline structure with an average crystalline size of 40-80 nm. FTIR confirmed the presence of organic compounds on the particle surface, while UV showed stability of the particles. SEM and EDS confirmed that CdO-NPs were successfully prepared and spherical. The maximum zone of inhibition against S. dysenteriae and P. aeruginosa was found and showed a less optical density of 0.086 after 18 h. ROS, reducing sugar, and protein leakage assay showed a significant difference as compared to control. Based on the present study, it is recommended that microbial mediated synthesized nanoparticles can be used as biomedicines for the treatment of different types of bacterial infections.

LED-enhanced biosynthesis of biologically active ingredients in callus cultures of Ocimum basilicum.

Ocimum basilicum is a medicinal plant with multiple health benefits including cardiovascular, cancer and diabetics. In the present study, the influences of light emitting diodes (LEDs) were investigated on the accumulation of biologically active ingredients in callus cultures of Ocimum basilicum. Among the various tested treatments optimum levels of Total phenolic content (TPC) was noted in callus culture grown under blue lights as compared to control, while maximum accumulation of Total flavonoid content (TFC) was noted in callus culture grown under red light as compared to control. HPLC analyses showed that highest concentrations of Rosmarinic acid (96.0 mg/g DW) and Eugenol (0.273 mg/g DW) were accumulated in blue light which was 2.46 and 2.25 times greater than control (39.0 mg/g DW, 0.171 mg/g DW), respectively. Chicoric acid (81.40 mg/g DW) optimum accumulation was noted in callus grown under the continuous white light, which was almost 4.52 times greater than control. Anthocyanins content were also analyzed, the highest amount of Peonidin (0.127 mg/g DW) and cyanidin (0.1216 mg/g DW) were found in callus culture grown under red light. These findings suggest that application of LED's is a promising strategy for enhancing production of biologically active ingredients in callus cultures Ocimum basilicum.

Mechanistic evaluation of phytochemicals in breast cancer remedy: current understanding and future perspectives.

Breast cancer is one of the most commonly diagnosed cancers around the globe and accounts for a large proportion of fatalities in women. Despite the advancement in therapeutic and diagnostic procedures, breast cancer still represents a major challenge. Current anti-breast cancer approaches include surgical removal, radiotherapy, hormonal therapy and the use of various chemotherapeutic drugs. However, drug resistance, associated serious adverse effects, metastasis and recurrence complications still need to be resolved which demand safe and alternative strategies. In this scenario, phytochemicals have recently gained huge attention due to their safety profile and cost-effectiveness. These phytochemicals modulate various genes, gene products and signalling pathways, thereby inhibiting breast cancer cell proliferation, invasion, angiogenesis and metastasis and inducing apoptosis. Moreover, they also target breast cancer stem cells and overcome drug resistance problems in breast carcinomas. Phytochemicals as adjuvants with chemotherapeutic drugs have greatly enhanced their therapeutic efficacy. This review focuses on the recently recognized molecular mechanisms underlying breast cancer chemoprevention with the use of phytochemicals such as curcumin, resveratrol, silibinin, genistein, epigallocatechin gallate, secoisolariciresinol, thymoquinone, kaempferol, quercetin, parthenolide, sulforaphane, ginsenosides, naringenin, isoliquiritigenin, luteolin, benzyl isothiocyanate, α-mangostin, 3,3'-diindolylmethane, pterostilbene, vinca alkaloids and apigenin.

RISK FACTORS LEADING TO DEVELOPMENTAL COMPLICATIONS AFTER OPEN REDUCTION IN DEVELOPMENTAL DYSPLASIA OF HIP.

BACKGROUND: The developmental dysplasia of the hip (DDH) is regarded as one of the commonest congenital deformities. Its incidence has been estimated to be one in 60 live births according to some estimates. Different forms of treatment modalities have been suggested and their success depends on the age of the patient. The study was done with the objectives to observe the post-operative complications of open reduction in patients with DDH and to determine the possible risk factors associated with these complications. METHODS: A total of 60 patients were enrolled with DDH in this descriptive cross-sectional study from August 2013 to November 2015. After obtaining an informed consent, the patients underwent open reduction and in some cases, subsequent osteotomy. The patients were followed-up at three months intervals for at least 9 months to look for development of complications, if any. RESULTS: The mean age of the patients was 31.32 ± 2.52 months. Majority 45 (75%) of the study population was female. The most common complication observed was osteonecrosis (5 patients; 8.33%) followed by residual dysplasia and re-dislocation in 3 (5%) patients each. Infection was identified as a complication in 2 (3.33%) patients. When stratified with complications of open reduction, female sex and bilateral hip involvement were found to have a significant association with the development of complications. CONCLUSION: Female sex and bilateral hip involvement confer a greater risk of developing a complication following open reduction for DDH.

Accuracy of Anti-Tissue Transglutaminase IgA Antibody in the Diagnosis of Paediatric Celiac Disease.

OBJECTIVE: To determine the accuracy of anti-tissue transglutaminase IgA (TTG) antibody titer in the diagnosis of celiac disease, taking small intestine histopathology as the gold standard. STUDY DESIGN: Cross-sectional analytical study. PLACE AND DURATION OF STUDY: Department of Paediatrics, Benazir Bhutto Hospital, Rawalpindi, from February to July 2013. METHODOLOGY: Sixty patients aged 2 - 13 years, admitted in the Paediatric Department of Benazir Bhutto Hospital, Rawalpindi, having at least 3 features from chronic diarrhea, malnutrition, short stature, anemia, abdominal distension and clubbing, were included. Age, gender, weight and height were recorded. Abdominal distension and clubbing were clinically noted. For hemoglobin, blood complete picture was done. For determination of nutritional status and short stature, standard centile charts were used. TTG titer upper GI endoscopy, duodenal biopsy, and histopathology were done in all cases. RESULTS: There were 60 patients; 32 males, 28 females with mean age of 5.85 &plusmn;3.36 years. Frequency of CD was 63.33% in study population. Sensitivity of TTG was 86.84%, with 81.82% specificity, 89.19% positive predictive value, and 78.26% negative predictive value for diagnosing CD. TTG titre more than 50 iu/ml had a 100% positive predictive value. CONCLUSION: TTG is an excellent screening test for the diagnosis of paediatric CD. TTG value &gt; 50 IU/ml has 100% positive predictive value.

Detection and identification of mouse mammary tumor virus-like DNA sequences in blood and breast tissues of breast cancer patients.

Mouse mammary tumor virus (MMTV) is a well-known cause of mammary tumors in mice transmitted as endogenous proviruses or exogenously as infectious virions. The hypothesis that a retrovirus homologous to MMTV is involved in human breast cancers has resulted in renewed interest in the etiology of human breast cancer. Therefore, the detection of MMTV-like exogenous sequences in 30-40 % of invasive breast cancer has increased attention towards this hypothesis. To detect the prevalence of MMTV in Pakistani population, 666-bp-long MMTV envelop and 630-bp LTR sequences were amplified from breast cancer patient samples (tissue biopsies and peripheral blood) using mouse with mammary tumor as control. MMTV-like virus env and LTR DNA sequences were detected in 20 and 26 % of breast tumor samples, respectively, from the total of 80 breast cancer patients' blood and tissue samples. No significant association was observed between age, grade of disease, and lymph node involvement with the prevalence of MMTV-like sequences. Our data add to the growing number of studies implicating MMTV-like virus in human breast cancer, but still clear causal association of MMTV to breast cancer remains to be reputable.

Detection and genotyping of restriction fragment associated polymorphisms in polyploid crops with a pseudo-reference sequence: a case study in allotetraploid Brassica napus.

BACKGROUND: The presence of homoeologous sequences and absence of a reference genome sequence make discovery and genotyping of single nucleotide polymorphisms (SNPs) more challenging in polyploid crops. RESULTS: To address this challenge, we constructed reduced representation libraries (RRLs) for two Brassica napus inbred lines and their 91 doubled haploid (DH) progenies using a modified ddRADseq technique. A bioinformatics pipeline termed RFAPtools was developed to discover and genotype SNPs and presence/absence variations (PAVs). Using this pipeline, a pseudo-reference sequence (PRF) containing 180,991 sequence tags was constructed. By aligning sequence reads to the pseudo-reference sequence, allelic SNPs as well as PAVs were identified and genotyped with RFAPtools. Two parallel linkage maps, one SNP bin map containing 8,780 SNP loci and one PAV linkage map containing 12,423 dominant loci, were constructed. By aligning marker sequences to B. rapa sequence scaffolds, whose genome is available, we assigned 44 unassembled sequence scaffolds comprising 8.15 Mb onto the B. rapa chromosomes, and also identified 14 instances of misassembly and eight instances of mis-ordering sequence scaffolds. CONCLUSIONS: These results indicate that the modified ddRADseq approach is a cost-effective and simple method to genotype tens of thousands SNPs and PAV markers in a polyploidy plant species. The results also demonstrated that RFAPtools developed in this study are powerful to mine allelic SNPs from homoeologous sequences in polyploids, therefore they are generally applicable in either diploid or polyploid species with or without a reference genome sequence.

Significant correlation of TLR4 expression with the clinicopathological features of invasive ductal carcinoma of the breast.

Toll-like receptor 4 belongs to the family of pattern recognition receptors and is therefore an important part of innate immunity. Since the last decade, Toll-like receptors (TLRs) have gained much interest in cancer research due to their role in tumor progression. However, there is scarcity of data evaluating TLR4 expression in different cell populations of tumor in relation to clinicopathological parameters of invasive ductal carcinoma of the breast. Therefore, we investigated TLR4 expression in 50 primary invasive ductal carcinoma and 17 lymph node sections through immunohistochemistry. Significant association of TLR4 expression with local metastasis and absence of necrosis was observed. The incidence of lymph node metastasis was higher in patients with high TLR4 expression in the tumor cells. We also observed an interesting inverse relationship of TLR4 with necrosis. In endothelial and lymphocytic population constituting breast tumors, a significant association of TLR4 expression was seen with the tumor grade. Therefore, we conclude that TLR4 expression is of biological interest both as a prognostic marker as well as a possible therapeutic target.

Role of serum-ascites albumin gradient in differential diagnosis of ascites.

BACKGROUND: The classification of ascites as 'exudative' and 'transudative' based on ascitic fluid total protein (AFTP) has been challenged in many clinical conditions like cardiac ascites, patients on prolonged diuretic therapy and malignant ascites because it had poor diagnostic efficacy. These drawbacks have led to the development of another approach to classify ascites, which is based on Serum-Ascites Albumin Gradient (SAAG) to differentiate ascitic fluid into two categories: SAAG > or = 11 g/L in ascites due to portal hypertension and SAAG < 11 g/L in ascites unrelated to portal hypertension. Objective of this study was to compare the diagnostic efficacy of serum/ascites fluid albumin gradient and ascitic fluid total protein in patients having ascites. METHODS: This Cross-sectional comparative study was conducted in the Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi from 1st Jun 2007 to 30th May 2008. Ninety-three patients were included in the study by non probability convenience sampling. The patient grouped as: (Group I) 73 cases of liver cirrhosis, (Group II) 14 cases of hepatoma and 6 cases of tuberculous ascites. Ascitic fluid specimen and 3 ml blood were obtained for ascitic fluid estimation of ascitic fluid albumin, total proteins and serum albumin. Diagnostic efficacy of SAAG and AFTP was calculated by comparing the results with clinical, ultrasonographic, histopathological findings, ascitic fluid cell count/acid fast bacilli culture and other relevant investigations. RESULTS: Seventy-three cases had liver cirrhosis (group I), 14 cases had hepatoma and 6 cases had tubercular ascites (group II). Age ranged 25-80 years with mean age 56 years. Diagnostic accuracy, Sensitivity, Specificity, Positive predictive value (PPV) and Negative predictive value (NPV) of SAAG were 96%, 97%, 95%, 98.6%, and 90% respectively, whereas those of AFTP were 56%, 53%,70%, 86%, and 29% respectively. CONCLUSION: Differential diagnosis of ascites should be based on SAAG because diagnostic efficacy of SAAG was significantly higher than AFTP in work-up of ascites.

Feed supplementation prevents post-conception decline in milk progesterone concentrations associated with production stress in dairy buffaloes (Bubalus bubalis).

The onset of pregnancy may be associated with hormonal changes and decline in milk yield of buffaloes. To investigate this, forty lactating buffaloes from 1st to 23rd weeks post-conception were selected. The animals were assigned to three treatments: PRT, PRS, NPRT and three milk yielding groups HMY, 66 to 75 l/week, n = 12; MMY, 56 to 65 l/week, n = 16; LMY, 46 to 55 l/week, n = 12). Milk samples were collected on alternate weeks and analyzed with ultrasonic milk analyzer. EIA was used for milk progesterone concentrations. Group means were compared and correlation analysis was conducted. Progesterone concentrations increased in almost similar pattern with the advancing weeks post-conception. The high and low yielder showed greater progesterone concentrations in the supplemented than the animals on traditional ration (P < 0.001). Progesterone concentrations correlated positively with fat (%), negatively with milk yield, protein (%) and lactose (%). Decline in milk yield became drastic when progesterone concentrations rose above 6.44 ng/ml. The pregnant animals on traditional ration exhibited a sharper decline in milk yield with the increasing progesterone concentrations as compared to pregnant animals with supplemented ration. It is concluded that concentrates supplementation induced a raise in progesterone levels. Progesterone concentrations and milk yield showed an inverse relationship.