Ischemia-guided vs routine non-culprit vessel angioplasty for patients with ST segment elevation myocardial infarction and multi-vessel disease: the IAEA SPECT STEMI trial.

BACKGROUND: In patients with multi-vessel disease presenting with ST elevation myocardial infarction (STEMI), the efficacy and safety of ischemia-guided, vs routine non-culprit vessel angioplasty has not been adequately studied. METHODS: We conducted an international, randomized, non-inferiority trial comparing ischemia-guided non-culprit vessel angioplasty to routine non-culprit vessel angioplasty, following primary PCI for STEMI. The primary outcome was the between-group difference in percent ischemic myocardium at follow-up stress MPI. All MPI images were processed and analyzed at a central core lab, blinded to treatment allocation. RESULTS: In all, 109 patients were enrolled from nine countries. In the ischemia-guided arm, 25/48 (47%) patients underwent non-culprit vessel PCI following stress MPI. In the routine non-culprit PCI arm, 43/56 (77%) patients underwent angioplasty (86% within 6 weeks of randomization). The median percentage of ischemic myocardium on follow-up imaging (mean 16.5 months) was low, and identical (2.9%) in both arms (difference 0.13%, 95%CI - 1.3%-1.6%, P < .0001; non-inferiority margin 5%). CONCLUSION: A strategy of ischemia-guided non-culprit PCI resulted in low ischemia burden, and was non-inferior to a strategy of routine non-culprit vessel PCI in reducing ischemia burden. Selective non-culprit PCI following STEMI offers the potential for cost-savings, and may be particularly relevant to low-resource settings. (CTRI/2018/08/015384).

Prevalence of HPV types in HIV-positive and negative females with normal cervical cytology or dysplasia.

The burden of HPV varies by country and HIV status. The study aimed to evaluate HPV types prevalent in HIV-positive females compared with HIV-negative females in the local population of the federal capital territory in Pakistan. METHOD: The selected female population consisted of 65 already diagnosed HIV-positive females and 135 HIV-negative females. Cervical scrap was collected and analyzed for HPV and cytology. RESULTS: The prevalence of HPV in HIV-positive patients was 36.9%, higher than HIV-negative patients (4.4%). 12.30% had cervical cytology interpreted as "LSIL" and 87.69% had cytology interpreted as "NIL." The high-risk type was detected in 15.39% while 21.54% showed low-risk HPV types. Among the high-risk types, HPV18 (6.15%), HPV16 (4.62%), HPV45 (3.07%), HPV33 (1.53%), HPV58 (3.07%), and HPV68 (1.53%) were found. In patients with LSIL, high-risk HPV accounts for 62.5%. Risk factors, such as age, marital status, educational status, residence, parity, other STDs, and contraceptives, were analyzed to find the correlation with HPV infection Age ≤35 years (OR 1.21, 95% CI, 0.44-3.34), illiterate and incomplete secondary education (OR 1.08, 95% CI, 0.37-3.15), and those reported not to use contraceptives (OR: 1.90; 95% CI: 0.67-5.42) have an association for increased risk of HPV infection. CONCLUSION: HPV18, HPV16, HPV58, HPV45, HPV68, and HPV33 were identified among high-risk HPV types. High-risk HPV was detected in 62.5% of low-grade squamous intraepithelial lesions. The data is useful for health policymakers to develop a strategy for HPV screening and prophylactic vaccination to prevent cervical cancer.

Extraosseous soft tissue uptake-in Multiple Myeloma.

Tc-99m Methylene Diphosphonate (MDP) bone scintigraphy has been used for the assessment of benign as well as malignant skeletal conditions. Non-osseous radiotracer uptake on bone scan is an unusual finding. It is usually performed for metastatic bone disease, and is generally not an indication in multiple myeloma, as osteolytic lesions typically show no radiotracer uptake. Despite this, substantial number of multiple myeloma patients undergo bone scintigraphy due to their presentation imitating a metastatic bone disease. We describe a case of multiple myeloma, where extra osseous uptake in lung and diffuse hepatic, has been noted on bone scan.

Comparison of MRI, [18F]FDG PET/CT, and 99mTc-UBI 29-41 scintigraphy for postoperative spondylodiscitis-a prospective multicenter study.

PURPOSE: Postoperative infection still constitutes an important complication of spine surgery, and the optimal imaging modality for diagnosing postoperative spine infection has not yet been established. The aim of this prospective multicenter study was to assess the diagnostic performance of three imaging modalities in patients with suspected postoperative spine infection: MRI, [18F]FDG PET/CT, and SPECT/CT with 99mTc-UBI 29-41. METHODS: Patients had to undergo at least 2 out of the 3 imaging modalities investigated. Sixty-three patients enrolled fulfilled such criteria and were included in the final analysis: 15 patients underwent all 3 imaging modalities, while 48 patients underwent at least 2 imaging modalities (MRI + PET/CT, MRI + SPECT/CT, or PET/CT + SPECT/CT). Final diagnosis of postoperative spinal infection was based either on biopsy or on follow-up for at least 6 months. The MRI, PET/CT, and SPECT/CT scans were read blindly by experts at designated core laboratories. Spine surgery included metallic implants in 46/63 patients (73%); postoperative spine infection was diagnosed in 30/63 patients (48%). RESULTS: Significant discriminants between infection and no infection included fever (P = 0.041), discharge at the wound site (P < 0.0001), and elevated CRP (P = 0.042). There was no difference in the frequency of infection between patients who underwent surgery involving spinal implants versus those who did not. The diagnostic performances of MRI and [18F]FDG PET/CT analyzed as independent groups were equivalent, with values of the area under the ROC curve equal to 0.78 (95% CI: 0.64-0.92) and 0.80 (95% CI: 0.64-0.98), respectively. SPECT/CT with 99mTc-UBI 29-41 yielded either unacceptably low sensitivity (44%) or unacceptably low specificity (41%) when adopting more or less stringent interpretation criteria. The best diagnostic performance was observed when combining the results of MRI with those of [18F]FDG PET/CT, with an area under the ROC curve equal to 0.938 (95% CI: 0.80-1.00). CONCLUSION: [18F]FDG PET/CT and MRI both possess equally satisfactory diagnostic performance in patients with suspected postoperative spine infection, the best diagnostic performance being obtained by combining MRI with [18F]FDG PET/CT. The diagnostic performance of SPECT/CT with 99mTc-UBI 29-41 was suboptimal in the postoperative clinical setting explored with the present study.

Genetic predisposition of SNPs in miRNA-149 (rs2292832) and FOXE1 (rs3758249) in thyroid Cancer.

BACKGROUND: Many efforts have been made in recent years to investigate the alterations in protein-coding genes as well as non-coding RNAs that are playing an emerging role in the development and progression of cancers. These miRNAs are short non-coding functional RNAs that are involved in the regulation of transcriptome. In different studies, it was found that human miRNA-149 is an important microRNA that is functioning either as onco-miRNAs or acting as tumor suppressors, in different conditions. RATIONALE: Many of the miRNAs are regulating different SNPs of FOXE1 in different studies which are causing low-to-moderate penetrance of genes that initiates the development of thyroid cancer. The involvement of SNPs in miRNA-149 gene rs2292832 and FOXE1 rs3758249 with PTC for better disease prognosis and management was determined in this study and the relation between these SNPs at the genotypic level was also evaluated. MATERIALS AND METHODS: PTC patients with age and gender-matched controls were recruited in the present study. Blood samples were collected in EDTA vacutainer followed by DNA extraction by the organic method. Genotyping of rs2292832 and rs3758249 was done by ARMS-PCR and PCR- RFLP respectively. Statistical analyses were carried out by using SPSS software (version 20). RESULTS: The mutation T>C in miRNA-149 rs2292832 was significantly associated with thyroid cancer (p-value 0.0004, < 0.05) while rs3758249 G>C did not show significant association with the disease (p-value 0.124244, > 0.05). Moreover, no correlation of rs2292832 at the genotype level was observed with rs3758249. CONCLUSIONS: miRNA-149 gene SNP rs2292832 was observed in strong association with thyroid cancer. Lack of genetic association of rs3758249 of FOXE1 gene has been ruled for the disease. The statistically significant association of rs2292832 with thyroid cancer depicts its mechanistic involvement at the cellular level in Papillary Thyroid Carcinoma.

Haplotype analysis of XRCC1 gene polymorphisms and the risk of thyroid carcinoma.

PURPOSE: Variants in DNA repair genes may alter the repair mechanisms that make the persons vulnerable to DNA damage. These polymorphic variants in the DNA repair pathway genes, such as XRCC1, have been associated with susceptibility of several types of cancer including thyroid cancer. This study was designed to explore the link between XRCC1 polymorphisms and modulation of thyroid cancer risk. METHODS: Our study consisted of 456 thyroid cancer patients and 400 controls. For XRCC1 polymorphisms analyses, three single nucleotide polymorphisms (SNPs) (rs25489, rs25487 and 1799782) were selected and genotyped by ARMS-PCR. RESULTS: The homozygous mutant (AA) of rs25489 SNP showed highly significant association with thyroid cancer risk (OR=0.17; 95% CI=0.10-0.31; p=0.0001). In the rs25487 polymorphism all genotypes showed no significantly increased risk of thyroid cancer in patients compared to controls (p>0.05). In the rs1799782 of XRCC1 gene, the homozygous mutant (TT) significantly decreased the risk of thyroid cancer (OR=0.71; 95% CI=0.50-1.01; p=0.05). Eight haplotypes were generated for three selected SNPs (rs25489, rs25487 and rs1799782) of XRCC1 gene among thyroid cases and controls. The haplotype GAT (OR=1.69; 95% CI=1.25- 2.30; p=0.0005) and GGC (OR=2.75; 95% CI=2.11-3.58; p=1.29e-014) showed highly significant association with increased risk of thyroid cancer. The haplotypes AAC (OR=0.31; 95% CI=0.17-0.57; p=6.68e-005), AAT (OR= 0.51; 95% CI=0.34-0.78; p=0.001), AGT (OR=0.46; 95%CI=0.29- 0.71; p=0.0003) and GGT (OR=0.80; 95% CI=0.64-0.98; p=0.03) had significant reducing effect in thyroid cancer patients. CONCLUSIONS: XRCC1 Arg280His and Arg194Trp were associated with thyroid cancer in Pakistani population. These genetic markers may provide an insight into the disease pathogenesis and help open novel therapeutic strategies for thyroid cancer.

Zika virus: Global health challenge, threat and current situation.

ZIKV has emerged as grave global health issue in the past few years. ZIKV was firstly isolated in 1947 from a rhesus sentinel monkey in the Zika forest in Uganda. It is usually transmitted by the bite of infected mosquitoes and infects skin fibroblasts, skin keratinocytes, etc. ZIKV until now was under reported because of its clinical similarity with the dengue and chikungunya. It is usually spread through the course of the sylvatic cycle. In this cycle, the virus or pathogen lifespan is spent between the wild animal and vectors. The intrinsic incubation period is not yet fully known but it is observed that the very first symptoms of ZIKV infection can appear or develop within 3-12 days of time period and usually subside within 7 days of time. There is a strong relationship between prenatal Zika virus infection and microcephaly; other serious brain anomalies to the infant or newborn are Guillain-Barré syndrome. To date no vaccines are available for ZIKV prevention hence only symptomatic treatment is recommended in infected patients. Usually ZIKV is detected by serologic (IgM ELISA), plaque reduction neutralization test (PRNT) along with in-house" molecular techniques (RT-PCR). ZIKV infection being imminent global health issue warrants strong protective measures to prevent it from becoming an epidemic. Early detection and prevention is the key to tackle this grave potential health hazard. J. Med. Virol. 89:943-951, 2017. © 2017 Wiley Periodicals, Inc.

(99m)Tc-phytate trans-splenic portal scintigraphy in the diagnosis of cirrhotic portal hypertension and compensatory circulation.

BACKGROUND AND AIM: The trans-splenic portal scintigraphy (TPS) was evaluated as a diagnostic tool in the post viral hepatitis cirrhotic patients of various classes of Child Pugh's (CP) classification. The main aim was to determine the portosystemic shunt index (PSSI) and to compare the results with various clinical grades of disease severity in liver cirrhosis. METHODS: TPS was performed on 72 patients and 10 controls and PSSI was derived. All the 72 patients were categorized according to CP classification into three classes. The cirrhotic patients were categorized as CP A (n = 24),CP B (n = 22), and CP C (n = 26)according to CP criteria. PSSI was compared with different CP classes. RESULTS: In the controlled population, the splenic vein was normal in shape and the mean PSSI was calculated to be 0.178 ± 0.031 (n = 10). For CP classes A, B, and C, the mean PSSI was 0.36 ± 0.04, 0.45 ± 0.05, and 0.54 ± 0.04 (n = 26), respectively. There was statistical significance among groups (p ≤ 0.01).The collateral vessels were mostly uphill or complex. The PSSI index increased as the CP score worsened from A to C. CONCLUSION: PSSI is a useful and minimally invasive tool to detect and quantify the shunt severity, which correlates well with different clinical grades of disease severity.

Gastric Metastasis from Invasive Lobular Breast Cancer, Resembling Primary Gastric Cancer.

Invasive lobular carcinoma (ILC) is the second most common subtype of invasive breast cancer and sometimes presents with an unusual metastatic pattern. Its gastric metastasis is difficult to differentiate from primary adenocarcinoma. This report presents a case of breast ILC for which the initial presentation was gastric metastasis. A 62-y-old woman presented with gastric outlet obstruction secondary to a gastric mass that had been diagnosed on upper gastrointestinal endoscopy and biopsy. The patient had been referred for 18F-FDG PET/CT for staging. The baseline 18F-FDG PET/CT scan demonstrated extensive axillary nodal and gastric metastases with a breast mass, which raised suspicion of a primary breast carcinoma. Distinguishing primary gastric adenocarcinoma from metastatic breast ILC is essential, considering that the 2 diagnoses lead to divergent treatments. Therefore, this entity needs to be considered in the differential diagnosis in clinical practice.

Comparison of absolute renal uptake by using Tc-99m MAG-3 and Tc-99m DMSA.

PURPOSE: The purpose of this study is to compare the value of absolute renal uptake (ARU %) in patients by using Tc-99m MAG-3 and Tc-99m DMSA scan. MATERIAL AND METHODS: Absolute renal uptake is calculated using Tc-99m MAG-3 and Tc-99m DMSA in renal scintigraphy, Itoh and Tauex kidney depth methods used, respectively. n = 40 adult patients of both genders were included. All patients underwent Tc-99m MAG-3 and Tc-99m DMSA, respectively. RESULTS: The values of ARU (%) were calculated separately in selected patients n = 40, (left = 17, right = 23 normal functioning kidneys) by MAG-3 and DMSA. Absolute renal uptake (%) of Tc-99m MAG-3 in left kidneys was found to be 15.2 ±â€…3.4, with spilt renal function 79.2 ±â€…14.7 and ARU (%) in right kidneys 16.2 ±â€…3.4 with spilt renal function 77.5 ±â€…19. Absolute renal uptake of Tc-99m DMSA in left kidneys was 17.5 ±â€…3.2 and in right kidneys 17.9 ±â€…4.5 with spilt renal function 81.8 ±â€…10.7 and 79.3 ±â€…13.8 for left and right kidney, respectively. Statistical analysis showed strong Pearson correlation. CONCLUSION: Absolute renal uptake % was found to be more reliable in cases of bilateral compromised kidneys. ARU (%) calculated by Tc-99m MAG-3 solely can be used as predictor of renal function. The use of Tc-99m MAG-3 has more advantages than Tc-99m DMSA alone in renal scintigraphy as dynamic scintigraphy gives less radiation burden to patient, more information regarding renal function, and shorter stay time at hospital in comparison to static renal imaging. SRF % is less reliable than ARU (%).

Utility of 99mTc-labelled antimicrobial peptide ubiquicidin (29-41) in the diagnosis of diabetic foot infection.

PURPOSE: Detection of osteomyelitis beneath a diabetic foot ulcer is imperative for proper management; however, accurate and noninvasive diagnosis of osteomyelitis remains a challenge. Ubiquicidin 29-41 (UBI 29-41) is a synthetic antimicrobial peptide fragment reported to be highly infection-specific. (99m)Tc-UBI 29-41 has recently been reported to be a promising radiotracer for infection imaging. The aim of this prospective study was to evaluate the utility of (99m)Tc-UBI 29-41 scintigraphy in diabetic patients with suspected osteomyelitis of the foot. METHODS: Included in the study were 65 patients with type 2 diabetes mellitus and foot ulcer and with clinical suspicion of osteomyelitis . Each patient had a three-phase bone scan and a (99m)Tc-UBI scan at 30 and 60 min after injection. The scan was considered to be consistent with osteomyelitis when the (99m)Tc-UBI 29-41 uptake was concordant with the (99m)Tc-MDP uptake. It was considered negative for osteomyelitis if there was no uptake of (99m)Tc-UBI 29-41 or if (99m)Tc-UBI 29-41 accumulated in an area not concordant with the abnormal uptake of (99m)Tc-MDP on the bone scan. In the latter case a diagnosis of soft-tissue infection was made. Bone infection was confirmed by bone biopsy/culture and by clinical and radiological follow-up. RESULTS: Final analysis was done in 55 patients. Osteomyelitis was confirmed in 37 patients, and 18 patients were free of bone infection. (99m)Tc-UBI 29-41 was positive in all 37 patients and with the bone scan as the reference for the bone identified all osteomyelitic foci (68 in total). (99m)Tc-UBI 29-41 was negative for osteomyelitis in all 18 patients, and 17 of these patients were diagnosed with soft-tissue infection ((99m)Tc-UBI 29-41 accumulation without concordant abnormal uptake on bone scintigraphy). The sensitivity, specificity and accuracy of (99m)Tc-UBI 29-41 scan in combination with three-phase bone scan for the diagnosis of osteomyelitis in diabetic foot was 100 %. Accuracy for soft-tissue infection was also 100 %. Maximum accumulation of the (99m)Tc-UBI 29-41 with maximum target to background activity was observed in the infectious foci at 30 min after injection. CONCLUSION: Tc-UBI 29-41 may be a useful agent for the accurate diagnosis of bone infection in diabetic foot because of the high accuracy demonstrated in this pilot study. It was able to differentiate between bone and soft-tissue involvement effectively in combination with a bone scan.

Comparative Evaluation of 99mTc-Octreotide for Diagnostic Accuracy Assessment and Localization of 177Lu-DOTA-TATE in Neuroendocrine Tumors.

INTRODUCTION: Neuroendocrine tumors, due to uncommon and multi-centric origin, pose a clinical challenge for their diagnosis and treatment. Developing countries where Ga-68 DOTA-TOC/NOC PET imaging is very limited and costly, 99mTc based SSR imaging can be used as the key tool for its diagnosis and assessment of therapy response. Hence we used two different 99mTc-radiopharmaceuticals for NET imaging designated as RP-1 and RP-2 for clinical assessment and peptide receptor therapy response of 177Lu-DOTA-TATE by manually synthesized acetate buffer. 99mTc- labeled RP-1 and RP-2 sensitivity, specificity; positive and negative predictive values were calculated and compared by SPECT/CT images for utilization in peptide receptor radionuclide therapy (PRRT). METHOD: Sodium-pertechnetate was used for labeling both radiopharmaceuticals, while 177Lu nca (0.04 N HCl) DOTA-TATE was synthesized by 0.1M ammonium acetate/ascorbic acid. 75 patients of known primary NET imaging with RP-1 and RP-2 were evaluated for SRR avidity and 3 were selected for PRRT. All images were correlated with 68Ga-DOTA-TOC scan, histopathology, CT and/or MRI reports. RESULTS: Out of 75 patients, the somatostatin receptor imaging of 39 patients of neuro-endocrine was performed with RP-1, found 23 as true positive, 7 as true negative with sensitivity, specificity, PPV and NPV of 71.87%, 100%, 100% and 43.75%, whereas 36 images with RP-2 calculated 22 T/P, 6 as T/N, 8 as F/N, with 75.8%, 100%, 100% and 50% respectively. Their 177Lu-DOTA-TATE SPECT/CT revealed specific localization of therapeutic radionuclide. CONCLUSION: 99mTc-imaging of RP-2, as compared to RP-1, had better efficiency and sensitivity and could effectively be used as an alternative to Ga-68 DOTA/TOC PET imaging and Lu-177 DOTA-TATE PRRT therapy response evaluation.

Graphene Based Nanohybrid Aptasensors in Environmental Monitoring: Concepts, Design and Future Outlook.

In view of ever-increasing environmental pollution, there is an immediate requirement to promote cheap, multiplexed, sensitive and fast biosensing systems to monitor these pollutants or contaminants. Aptamers have shown numerous advantages in being used as molecular recognition elements in various biosensing devices. Graphene and graphene-based materials/nanohybrids combined with several detection methods exhibit great potential owing to their exceptional optical, electronic and physicochemical properties which can be employed extensively to monitor environmental contaminants. For environmental monitoring applications, aptamers have been successfully combined with graphene-based nanohybrids to produce a wide range of innovative methodologies. Aptamers are immobilized at the surface of graphene based nanohybrids via covalent and non-covalent strategies. This review highlights the design, working principle, recent developmental advances and applications of graphene based nanohybrid aptasensors (GNH-Apts) (since January 2014 to September 2021) with a special emphasis on two major signal-transduction methods, i.e., optical and electrochemical for the monitoring of pesticides, heavy metals, bacteria, antibiotics, and organic compounds from different environmental samples (e.g., water, soil and related). Lastly, the challenges confronted by scientists and the possible future outlook have also been addressed. It is expected that high-performance graphene-based nanohybrid aptasensors would find broad applications in the field of environmental monitoring.

Antibody Response to SARS-CoV-2 in Relation to the Contributing Factors in COVID-19 Patients.

Human health has always been challenged by variety of viral infections, but severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has surpassed all previous viral diseases and emerged as a major health challenge around the globe. Real-time polymerase chain reaction (PCR) is the gold standard for the diagnosis of SARS-CoV-2 and serological assay provides a compliment to diagnosis after second week of infection. The aim of the study is the characterization of antibody response to SARS-CoV-2 in the blood sample of diagnosed coronavirus disease 2019 (COVID-19) patients, and its potential association with factors such as age, gender, time, and symptoms. Serum from 248 confirmed SARS-CoV-2 patients was investigated for antibodies. Elecsys anti-SARS chemiluminescent immune assay was performed for the detection of nucleocapsid-specific antibodies. Association of antibody response with gender, age, and time after onset of symptoms was analyzed. Among 248 PCR positive SARS-CoV-2 patients, 214 (86.3%) have virus-specific antibody signals. Antibodies positivity rate was higher in male patient patients as compared with female patients (90.8% vs. 79.2%, p = 0.009). Patients aged 30-40 years had the highest antibody positivity rate as compared with other groups (89.10%, p = 0.04). Patients age group >60 years had a lower positivity rate (75%, p = 0.04). The increasing trend in the antibodies detection with time was observed, maximum positive antibodies response rate observed at 8 weeks. Patients were categorized on the basis of clinical symptoms into asymptomatic, mild, and moderate; 17.7% were asymptomatic, 60.5% showed mild symptoms, and 21.8% showed moderate symptoms of the disease. Males were seen to be more asymptomatic as compared with females (i.e., 59.1% to 40.9%). The serological test for SARS-CoV-2 has a high sensitivity at >2 weeks after the positive PCR result or onset of illness. In addition, the serological response differs among patients based on gender, age, as well as time between the onset of symptoms or PCR confirmation and sample collection for the study of antibody response.

Indeterminate Prediction of Hepatitis C Virus Genotype by Commercial Real-Time Polymerase Chain Reaction Assay Resolving by Sequencing to Avoid the Consequence of Inaccurate Typing.

Pakistan is ranked second highest after Egypt in hepatitis C virus (HCV) infection. Accurate typing is mandatory to be compliant with the World Health Organization strategy to eliminate HCV infection in 2030. We characterized the HCV genotypes using Abbott real-time polymerase chain reaction assay and indeterminate samples were sequenced. We also investigated the distribution of HCV genotype among different age groups and gender in chronic HCV patients. One thousand thirteen samples were tested for HCV genotyping using Abbott real-time HCV genotyping assay. RNA extraction from plasma was done using the m2000sp platform. The amplification and detection of genotypes was done on m2000rt instrument. The lower limit of detection assay is 500 IU/mL. The indeterminate genotypes were analyzed by sequencing of the NS5B region. We found genotype 1 in 1.68%, genotype 1b in 0.89%, genotype 1a in 0.79%, genotype 2 in 0.6, genotype 3 in 94.37%, genotype 4 in 0.4%, genotype 5 in 0.09%, and indeterminate genotype result were found in 1.18%. Abbott assay could not identify 12 samples of genotype 3 (1.18%) and gave the indeterminate result. It also fails to assign some of the samples of genotype 1 into 1a and 1b. The indeterminate genotypes were resolved by sequencing followed by phylogenetic analysis. Genotype 3 is the predominant genotype and significantly higher in females as compared with males. Genotype 1a is more common in males than in females. Indeterminate HCV genotypes on sequencing analysis identify as genotype 3a and likewise subtype of genotype1 as 1a.

Fruit Architecture in Polyamine-Rich Tomato Germplasm Is Determined via a Medley of Cell Cycle, Cell Expansion, and Fruit Shape Genes.

Shape and size are important features of fruits. Studies using tomatoes expressing yeast Spermidine Synthase under either a constitutive or a fruit-ripening promoter showed obovoid fruit phenotype compared to spherical fruit in controls, suggesting that polyamines (PAs) have a role in fruit shape. The obovoid fruit pericarp exhibited decreased cell layers and pericarp thickness compared to wild-type fruit. Transgenic floral buds and ovaries accumulated higher levels of free PAs, with the bound form of PAs being predominant. Transcripts of the fruit shape genes, SUN1 and OVATE, and those of CDKB2, CYCB2, KRP1 and WEE1 genes increased significantly in the transgenic ovaries 2 and 5 days after pollination (DAP). The levels of cell expansion genes CCS52A/B increased at 10 and 20 DAP in the transgenic fruits and exhibited negative correlation with free or bound forms of PAs. In addition, the cell layers and pericarp thickness of the transgenic fruits were inversely associated with free or bound PAs in 10 and 20 DAP transgenic ovaries. Collectively, these results provide evidence for a linkage between PA homeostasis and expression patterns of fruit shape, cell division, and cell expansion genes during early fruit development, and suggest role(s) of PAs in tomato fruit architecture.

99m Tc-Ceftizoxime: Synthesis, characterization and its use in diagnosis of diabetic foot osteomyelitis.

INTRODUCTION: The diagnosis of diabetic foot osteomyelitis is crucial and challenging for the proper management of diabetic foot. 99m Tc labelled Ceftizoxime was used as a non-invasive diagnostic agent for diabetic foot osteomyelitis. METHODS: Ceftizoxime [CFT], a third generation cephalosporin, was used in a simple and direct method for the synthesis of 99m TcO4 - labelled infection imaging agent with stannous chloride as reducing agent. Its radiochemical purity was checked by thin Layer chromatography. Partition co-efficient was measured with phosphate buffer and chloroform. The radiochemical complex was injected to control and infected animal model for 3 hours in-vivo localization studied with the help of dual head gamma camera. The labelled complexes were injected to 5 patients of known type II diabetes mellitus suspected of diabetic foot osteomyelitis. All patients underwent dynamic and static 99m Tc-MDP and 99m Tc-CFT scans. RESULTS: The synthesized radio labelled complex was 98.8% pure, with hydrophilic character. When injected to animal model, at 120 minutes, 49.3% was localized in foci of infection with 3.35% in liver and excretion through kidney. Human studies were interpreted as true or false positive and true or false negative based on bone histopathology/culture and clinical follow-up. We found that of 5 patients, 2 were true positive, 2 as true negative with no false positive or negative and 01 patient had soft tissue infection. CONCLUSION: This study showed that 99m Tc-CFT labelled complex could be used for detection of diabetic foot osteomyelitis; however, further confirmation of results with a larger patient population would be optimal.

Human papillomavirus infection in females with normal cervical cytology: Genotyping and phylogenetic analysis among women in Punjab, Pakistan.

BACKGROUND: Globally, cervical cancer is the fourth most common cancer in women and the seventh most common cancer overall, accounting for an estimated 300 000 annual deaths. Human papillomavirus (HPV) is the second most common cause of cervical cancer worldwide. HPV screening is not a common practice in Pakistan. The aim of this study was to determine the prevalence of HPV and HPV types in women with a normal cytology of the cervix living in the upper and lower regions of Punjab, Pakistan, and to analyze the risk factors for HPV in this region. METHODS: PCR analysis was performed for 1011 female patients with a normal cytology of the cervix from various districts of Punjab Province, Pakistan. Risk factors for the acquisition of HPV were studied. High-risk HPV types (HPV16 and HPV18) were detected using the Abbott Real Time HR HPV test. To determine the genotype, partial L1 region sequences of HPV-positive samples were subjected to sequencing using MY/09/MY11 primers, and a phylogenetic tree was constructed using CLC software. RESULTS: The study found a 4.74% prevalence of HPV, with the most frequent HPV type found being the low-risk HPV6 (in 25% of infected individuals), followed by HPV55 (22.9%), HPV11 (20.8%), and high-risk types HPV45 (12.5%), HPV33 (8.33%), HPV18 (6.25%), and HPV16 (4.16%). Phylogenetic analysis of all HPV types in this study showed 80-99% nucleotide identity with types related to the same species. The sequences were clustered with China, India, Mexico, Iran, Slovenia, and Germany, showing the diversity in origin of the various genotypes prevalent in Pakistan. CONCLUSIONS: In this population with a normal cervical cytology, the prevalence of high-risk HPV types was very low. The major prevalent HPV genotype in Punjab Province of Pakistan was the low-risk HPV type 6, followed by HPV type 55. Sequencing of the partial L1 region suggested that the region was highly conserved in all reported sequences. This study highlights the need to conduct robust epidemiological studies in the region and to develop regular HPV screening so that the situation does not reach an alarming stage resulting in cervical cancer.

Sentinel node localization in breast carcinoma.

OBJECTIVE: To determine the success rate of sentinel node dissection and the sensitivity of sentinel node to determine the presence of axillary node metastasis in women with clinically node negative breast cancer. DESIGN: Case series. PLACE AND DURATION OF STUDY: The study was conducted at Department of General Surgery Pakistan Institute of Medical Sciences, Islamabad (PIMS) and Nuclear Oncology and Radiotherapy Institute, Islamabad (NORI) from January 2002 to December 2003. PATIENTS AND METHODS: A total of 15 patients of early carcinoma breast were recruited in the study. Five patients were injected with radiocolloid and later with isosulfan blue in the subareolar region. Ten patients were given isosulfan blue only. All the patients were subjected to standard axillary clearance after sentinel node biopsy through separate incisions. Sentinel node was examined by intra-operative frozen section and all of the dissected lymph nodes were examined histopathologically for tumour deposits. RESULTS: Sentinel lymph node was successfully excised in all the cases 15/15 (100%). In 14 of the patients the sentinel node pathology was truly predictive of axillary nodal status. Sensitivity of the test was 93.33% and the positive predictive value was 100%. CONCLUSION: Sentinel node biopsy should be followed by standard axillary lymph adenectomy until the results of multiple prospective randomized trials define the role of this technique in the management of carcinoma breast.