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Background: Watermelon [Citrullus lanatus (Thunb.) Matsum. & Nakai] is an economically important crop with an attractive ripe fruit that has colorful flesh. Fruit ripening is a complex, genetically programmed process., Results: In this study, a comparative transcriptome analysis was performed to identify the regulators and pathways that are involved in the fruit ripening of pale-yellow-flesh cultivated watermelon (COS) and red-flesh cultivated watermelon (LSW177). We first identified 797 novel genes to extend the available reference gene set. Second, 3958 genes in COS and 3503 genes in LSW177 showed at least two-fold variation in expression, and a large number of these differentially expressed genes (DEGs) during fruit ripening were related to carotenoid biosynthesis, plant hormone pathways, and sugar and cell wall metabolism. Third, we noted a correlation between ripening-associated transcripts and metabolites and the key function of these metabolic pathways during fruit ripening., Conclusion: The results revealed several ripening-associated actions and provide novel insights into the molecular mechanisms underlying the regulation of watermelon fruit ripening.

A variety of melons are cultivated worldwide, and their specific biological properties make them an attractive model for molecular studies. This study aimed to investigate the single nucleotide polymorphisms (SNPs) from the mitochondrial, chloroplast, and nuclear genomes of seven melon accessions ( Cucumis melo L.) to identify the phylogenetic relationships among melon cultivars with the Illumina HiSeq 2000 platform and bioinformatical analyses. The data showed that there were a total of 658 mitochondrial SNPs (207-295 in each), while there were 0-60 chloroplast SNPs among these seven melon cultivars, compared to the reference genome. Bioinformatical analysis showed that the mitochondrial tree topology was unable to separate the melon features, whereas the maximum parsimony/neighbor joining (MP/NJ) tree of the chloroplast SNPs could define melon features such as seed length, width, thickness, 100-seed weight, and type. SNPs of the nuclear genome were better than the mitochondrial and chloroplast SNPs in the identification of melon features. The data demonstrated the usefulness of mitochondrial, chloroplast, and nuclear SNPs in identification of phylogenetic associations among these seven melon cultivars.

Mechanistic insights into pain pathways are essential for a rational approach to treating this vast and increasing clinical problem. Sensory neurons that respond to tissue damage (nociceptors) may evoke pain sensations and are typically classified on the basis of action potential velocity. Electrophysiological studies have suggested that most of the C-fiber nociceptors are polymodal, responding to a variety of insults. In contrast, gene deletion studies in the sensory neurons of transgenic mice have frequently resulted in modality-specific deficits. We have used an in vivo imaging approach using the genetically encoded fluorescent calcium indicator GCaMP to study the activity of dorsal root ganglion sensory neurons in live animals challenged with painful stimuli. Using this approach, we can visualize spatially distinct neuronal responses and find that >85% of responsive dorsal root ganglion neurons are modality-specific, responding to either noxious mechanical, cold, or heat stimuli. These observations are mirrored in behavioral studies of transgenic mice. For example, deleting sodium channel Nav1.8 silences mechanical- but not heat-sensing sensory neurons, consistent with behavioral deficits. In contrast, primary cultures of axotomized sensory neurons show high levels of polymodality. After intraplantar treatment with prostaglandin E 2 , neurons in vivo respond more intensely to noxious thermal and mechanical stimuli, and additional neurons (silent nociceptors) are unmasked. Together, these studies define polymodality as an infrequent feature of nociceptive neurons in normal animals.

Xeroderma pigmentosum group A (XPA)-binding protein 2 (XAB2) is a multi-functional protein that plays critical role in processes including transcription, transcription-coupled DNA repair, pre-mRNA splicing, homologous recombination and mRNA export. Microarray analysis on gene expression in XAB2 knockdown cells reveals that many genes with significant change in expression function in mitotic cell cycle regulation. Fluorescence-activated cell scanner analysis confirmed XAB2 depletion led to cell arrest in G2/M phase, mostly at prophase or prometaphase. Live cell imaging further disclosed that XAB2 knockdown induced severe mitotic defects including chromosome misalignment and defects in segregation, leading to mitotic arrest, mitotic catastrophe and subsequent cell death. Among top genes down-regulated by XAB2 depletion is mitotic motor protein centrosome-associated protein E (CENPE). Knockdown CENPE showed similar phenotypes to loss of XAB2, but CENPE knockdown followed by XAB2 depletion did not further enhance cell cycle arrest. Luciferase assay on CENPE promoter showed that overexpression of XAB2 increased luciferase activity, whereas XAB2 depletion resulted in striking reduction of luciferase activity. Further mapping revealed a region in CENPE promoter that is required for the transcriptional regulation by XAB2. Moreover, ChIP assay showed that XAB2 interacted with CENPE promoter. Together, these results support a novel function of XAB2 in mitotic cell cycle regulation, which is partially mediated by transcription regulation on CENPE.

We address the problem of 3D pose estimation of multiple humans from multiple views. The transition from single to multiple human pose estimation and from the 2D to 3D space is challenging due to a much larger state space, occlusions and across-view ambiguities when not knowing the identity of the humans in advance. To address these problems, we first create a reduced state space by triangulation of corresponding pairs of body parts obtained by part detectors for each camera view. In order to resolve ambiguities of wrong and mixed parts of multiple humans after triangulation and also those coming from false positive detections, we introduce a 3D pictorial structures (3DPS) model. Our model builds on multi-view unary potentials, while a prior model is integrated into pairwise and ternary potential functions. To balance the potentials' influence, the model parameters are learnt using a Structured SVM (SSVM). The model is generic and applicable to both single and multiple human pose estimation. To evaluate our model on single and multiple human pose estimation, we rely on four different datasets. We first analyse the contribution of the potentials and then compare our results with related work where we demonstrate superior performance.

A simple and cost effective RPLC-UV bio-analytical method was developed and used for tenoxicam quantification on ODS Hypersil C-18 column using classical liquid-liquid extraction technique for sample preparation. Acetonitrile was used as precipitating agent for plasma proteins and supernatant was taken for injection without any further modification. The bio-analytical method depends upon isocratic elution using binary mixture of aqueous 0.1 M potassium dihydrogen phosphate and acetonitrile in 6 : 4 ratio. The pH of mobile phase was adjusted to 2.8 which favor tenoxicam to remain undissociated throughout the analysis. The optimized flow rate of 1.0 mL/min provided proper separation of peaks and column clean up within 5 min. The UV detection was achieved at 381 nm and 4.29 min. Reproducible calibration curve gave 0.325 μg/mL LOQ, linear dynamic range from 0.325 to 20 μg/mL and recovery from plasma was 98.5% with %CV 0.2314 achieved. After validation, the method was applied in pharmacokinetic study in healthy human volunteers (n = 8). The pharmacokinetic parameters were evaluated using kinetica version 4.1.1. The values of C. and area under curve for current study were 1.776 ± 0.003 pg/mL and 179.97 ± 0.0681 (mean ± SEM) pg x h/mL. The values of t, and volume of distribution for tenoxicam in current study were 74.103 0.167 h (mean ± SEM) and 11.962 ± 0.0677 L/kg (mean ± SEM), respectively. This method was simple, sensitive and successfully applied in pharmacokinetic studies. It can be extended to bioequivalence studies and evaluation of tenoxicam in different clinical situations.

Garlic has the charisma of a potent remedy and holds its repute of a therapeutic panacea since the dawn of civilization. An integrated approach was adopted to evaluate the genetic diversity among Chinese garlic cultivars for their antifungal potency as well as allicin content distribution and, furthermore; a bioassay was performed to study the bio-stimulation mechanism of aqueous garlic extracts (AGE) in the growth and physiology of cucumber (Cucumis sativus). Initially, 28 garlic cultivars were evaluated against four kinds of phytopathogenic fungi; Fusarium oxysporum, Botrytis cinerea, Verticillium dahliae and Phytophthora capsici, respectively. A capricious antifungal potential among the selected garlic cultivars was observed. HPLC fingerprinting and quantification confirmed diversity in allicin abundance among the selected cultivars. Cultivar G025, G064, and G074 had the highest allicin content of 3.98, 3.7, and 3.66 mg g(-1), respectively, whereas G110 was found to have lowest allicin content of 0.66 mg g(-1). Cluster analysis revealed three groups on the basis of antifungal activity and allicin content among the garlic cultivars. Cultivar G025, G2011-4, and G110 were further evaluated to authenticate the findings through different solvents and shelf life duration and G025 had the strongest antifungal activity in all conditions. minimum inhibitory concentration and minimum fungicidal concentration of Allicin aqueous standard (AAS) and AGE showed significant role of allicin as primary antifungal substance of AGE. Leaf disk bioassay against P. capsici and V. dahliae to comparatively study direct action of AGE and AAS during infection process employing eggplant and pepper leaves showed a significant reduction in infection percentage. To study the bioactivity of AGE, a bioassay was performed using cucumber seedlings and results revealed that AGE is biologically active inside cucumber seedlings and alters the defense mechanism of the plant probably activating reactive oxygen species at mild concentrations. However, at higher concentrations, it might cause lipid peroxidation and membrane damage which temper the growth of cucumber seedlings. At the outcome of the study, an argument is advanced that current research findings provide bases for cultivar selection in antifungal effectivity as well as genetic variability of the cultivars. Allicin containing AGE can be used in specialized horticultural situations such as plastic tunnel and organic farming as a bio-stimulant to enhance cucumber growth and attenuate fungal degradation of agricultural produce.

Increasing evidence suggests that botulinum neurotoxins (BoNTs) delivered into the skin and muscle in certain human and animal pain states may exert antinociceptive efficacy though their uptake and transport to central afferent terminals. Cleavage of soluble N-methylaleimide-sensitive attachment protein receptor by BoNTs can impede vesicular mediated neurotransmitter release as well as transport/insertion of channel/receptor subunits into plasma membranes, an effect that can reduce activity-evoked facilitation. Here, we explored the effects of intraplantar botulinum toxin- B (BoNT-B) on peripheral inflammation and spinal nociceptive processing in an inflammatory model of pain. C57BL/6 mice (male) received unilateral intraplantar BoNT (1 U, 30 μL) or saline prior to intraplantar carrageenan (20 μL, 2%) or intrathecal N-methyl-D-aspartate (NMDA), substance P or saline (5 μL). Intraplantar carrageenan resulted in edema and mechanical allodynia in the injected paw and increased phosphorylation of a glutamate subunit (pGluA1ser845) and a serine/threonine-specific protein kinase (pAktser473) in spinal dorsal horn along with an increased incidence of spinal c-Fos positive cells. Pre-treatment with intraplantar BoNT-B reduced carrageenan evoked: (i) allodynia, but not edema; (ii) pGluA1 and pAkt and (iii) c-Fos expression. Further, intrathecal NMDA and substance P each increased dorsal horn levels of pGluA1 and pAkt. Intraplantar BoNT-B inhibited NMDA, but not substance P evoked phosphorylation of GluA1 and Akt. These results suggest that intraplantar toxin is transported centrally to block spinal activation and prevent phosphorylation of a glutamate receptor subunit and a kinase, which otherwise contribute to facilitated states., (© 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Cirrhosis, the twelfth leading cause of death, accounts for 1.1% of all deaths in the United States. Although there are multiple pulmonary complications associated with liver disease, the most important complications that cause significant morbidity and mortality are hepatopulmonary syndrome, hepatic hydrothorax, and portopulmonary hypertension. Patients with cirrhosis who complain of dyspnea should be evaluated for these complications. This article reviews these complications., (Copyright © 2016 Elsevier Inc. All rights reserved.)

A hydroponic co-culture system was adopted to determine the allelopathic potential of garlic on the growth of pepper plants. Different numbers of garlic plants (0, 2, 4, 8 and 12) were hydroponically co-cultured with two pepper plants to investigate allelopathic effects on the growth attributes and antioxidative defense system of the test pepper plants. The responses of the pepper plants depended on the number of garlic plants included in the co-culture system, indicating an association of pepper growth with the garlic root exudate concentration. When grown at a pepper/garlic ratio of 1:1 or 1:2, the pepper plant height, chlorophyll content, and peroxidase (POD), catalase (CAT) and phenylalanine ammonia-lyase (PAL) activities were significantly increased after 30 days of co-culture; in contrast, reduction in methane dicarboxylic aldehyde (MDA) content was observed. However, when the pepper/garlic ratio was 1:4 or higher, these morphological indices and protective enzyme activities were significantly inhibited, whereas MDA levels in the pepper leaves were significantly increased due to severe membrane lipid peroxidation. The results indicate that although low concentrations of garlic root exudates appear to induce protective enzyme systems and promote pepper growth, high concentrations have deleterious effects. These findings suggest that further investigations should optimize the co-culture pepper/garlic ratio to reduce continuous cropping obstacles in pepper production., (© 2016. Published by The Company of Biologists Ltd.)

Although most pain research focuses on skin, muscles, joints and viscerae are major sources of pain. We discuss the mechanisms of deep pains arising from somatic and visceral structures and how this can lead to widespread manifestations and chronification. We include how both altered peripheral and central sensory neurotransmission lead to deep pain states and comment on key areas such as top-down modulation where little is known. It is vital that the clinical characterization of deep pain in patients is improved to allow for back translation to preclinical models so that the missing links can be ascertained. The contribution of deeper somatic and visceral tissues to various chronic pain syndromes is common but there is much we need to know.

Aims: Though impaired cognition in Parkinson's disease (PD) is well known, data in early PD is sparse. This study was designed to assess the cognitive profile in patients with early PD (motor symptoms <5 years and Hoehn and Yahr stage <2), and to compare the cognitive profile between these patients with right versus left side onset of motor symptoms., Materials and Methods: National Institute of National Health and Neurosciences (NIMHANS) neuropsychological battery was used to assess the cognitive profile in 50 patients with early PD and compared with 50 age-, education-, and gender-matched healthy controls. Within the PD group, the cognitive profile was also compared between patients with right side onset motor symptoms (RPD) versus those with left side onset (LPD). The neuropsychological tests assessed the executive functions, memory, attention, visuospatial functions, and psychomotor speed., Results: Among the 50 patients, 25 each were RPD and LPD. The two subgroups were matched for age, gender, education, age at disease onset, disease duration, and degree of motor disability. There was no significant difference between the groups on Hoehn and Yahr staging or Unified Parkinson Disease Rating Scale (UPDRS) motor score. Patients with early PD performed significantly worse in the tasks involving memory, executive functions, and attention compared to controls. However, there was no difference in the cognitive profile between RPD and LPD subgroups., Conclusions: Patients with early PD have cognitive dysfunction with predominant involvement of frontal and temporal lobes. Side of onset of motor symptoms probably does not have significant role in future development or profile of cognitive dysfunction in PD.

Loss-of-function mutations in the SCN9A gene encoding voltage-gated sodium channel Nav1.7 cause congenital insensitivity to pain in humans and mice. Surprisingly, many potent selective antagonists of Nav1.7 are weak analgesics. We investigated whether Nav1.7, as well as contributing to electrical signalling, may have additional functions. Here we report that Nav1.7 deletion has profound effects on gene expression, leading to an upregulation of enkephalin precursor Penk mRNA and met-enkephalin protein in sensory neurons. In contrast, Nav1.8-null mutant sensory neurons show no upregulated Penk mRNA expression. Application of the opioid antagonist naloxone potentiates noxious peripheral input into the spinal cord and dramatically reduces analgesia in both female and male Nav1.7-null mutant mice, as well as in a human Nav1.7-null mutant. These data suggest that Nav1.7 channel blockers alone may not replicate the analgesic phenotype of null mutant humans and mice, but may be potentiated with exogenous opioids.

Unfortunately Pakistan carries one of the world's highest burdens of chronic hepatitis along with mortality due to liver failure and hepatocellular carcinoma. Scientists after extensive research have come up with this outcome that host genetics play a vital role in dictating the type of treatment response produced by the patients. In 2009, a genome wide association study (GWAS) revealed that genetic variants in close proximity to the IL28B (IFNL3) gene predicted greater likelihood of achieving sustained virological response (SVR) following treatment with pegylated IFN-alpha (peg INF-α) and ribavirin. IL28B (rs12979860 and rs8099917) single nucleotide polymorphisms (SNPs) have been recently found among the Pakistani population associated with response to chronic HCV infection INF-α + ribavirin therapy. Therefore, this study was aimed to investigate the IL-28B protein levels in the HCV infected patients. The findings showed that the serum IL28B protein level was higher in HCV infected patients as compared to healthy controls (7.743 ± 1.519 pg/mL versus 1.600 ± 0.06054 [mean ± SEM], p < 0.05). When the chronic hepatitis C (CHC) patients were further categorized into SVR and NR (non-responders) on the basis of treatment outcomes, the mean IL28B protein level was higher in NRs (15.54 ± 3.609) than SVRs (4.259 ± 0.3405). Thus, there was a significant correlation between IL28B protein level in varied treatment response (p < 0.05). However, the findings can lead us to propose that IL28B could be used as a prognostic marker. It can help the clinicians to take better pre-informed decisions whether to take combinational therapy of peg IFN ± ribavirin or not. This will in turn prove beneficial for the patient by saving patients' health, treatment cost and undesirable treatment side effects., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

Translational research is key to bridging the gaps between preclinical findings and the patients, and a translational model of inflammatory pain will ideally induce both peripheral and central sensitisation, more effectively mimicking clinical pathophysiology in some chronic inflammatory conditions. We conducted a parallel investigation of two models of inflammatory pain, using ultraviolet B (UVB) irradiation alone and UVB irradiation with heat rekindling. We used rodent electrophysiology and human quantitative sensory testing to characterise nociceptive processing in the peripheral and central nervous systems in both models. In both species, UVB irradiation produces peripheral sensitisation measured as augmented evoked activity of rat dorsal horn neurones and increased perceptual responses of human subjects to mechanical and thermal stimuli. In both species, UVB with heat rekindling produces central sensitisation. UVB irradiation alone and UVB with heat rekindling are translational models of inflammation that produce peripheral and central sensitisation, respectively. The predictive value of laboratory models for human pain processing is crucial for improving translational research. The discrepancy between peripheral and central mechanisms of pain is an important consideration for drug targets, and here we describe two models of inflammatory pain that involve ultraviolet B (UVB) irradiation, which can employ peripheral and central sensitisation to produce mechanical and thermal hyperalgesia in rats and humans. We use electrophysiology in rats to measure the mechanically- and thermally-evoked activity of rat spinal neurones and quantitative sensory testing to assess human psychophysical responses to mechanical and thermal stimulation in a model of UVB irradiation and in a model of UVB irradiation with heat rekindling. Our results demonstrate peripheral sensitisation in both species driven by UVB irradiation, with a clear mechanical and thermal hypersensitivity of rat dorsal horn neurones and enhanced perceptual responses of human subjects to both mechanical and thermal stimulation. Additional heat rekindling produces markers of central sensitisation in both species, including enhanced receptive field sizes. Importantly, we also showed a correlation in the evoked activity of rat spinal neurones to human thermal pain thresholds. The parallel results in rats and humans validate the translational use of both models and the potential for such models for preclinical assessment of prospective analgesics in inflammatory pain states., (© 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.)

Hepatitis C virus (HCV) pathogenesis and treatment outcomes are multifactorial phenomena involving both viral and host factors. This study was designed to determine the role of tumor necrosis factor-related apoptosis-inducing ligand receptor 1(TRAIL-R1) and interferon gamma (IFN-γ) genetic mutations in susceptibility and response to interferon-based therapy of hepatitis C virus (HCV) infection. The detection of TRAIL-R1 rs4242392 and IFN-γ rs2069707 single nucleotide polymorphisms was completed in 118 chronic HCV patients and 96 healthy controls by allele-specific polymerase chain reaction and restriction fragment length polymorphisms polymerase chain reaction. Patients were further categorized into sustained virological responder (SVR) and nonresponder (NR) groups on the basis of their response to interferon-based therapy for HCV infection. Real-time PCR was used for HCV quantification. HCV genotyping was performed by Ohno's method. The results demonstrated that the distribution of the TRAIL-R1 rs4242392TT genotype was significantly higher in the SVR group (78%) compared to the NR group (36%). It showed that chronic HCV patients possessing the TRAIL-R1 rs4242392TT genotype are better responders to interferon-based therapy (p<0.05). The prevalence of the TRAIL-R1 rs4242392TT genotype in healthy controls and chronic HCV patients was 56% and 65% respectively. It indicated that there is the TRAIL-R1 rs4242392 genetic variation plays no role in the spontaneous clearance of HCV infection (p>0.05). The distribution of IFN-γ rs2069707 was the opposite to TRAIL-R1 rs4242392 prevalence, that is, there was high distribution of the IFN-γ rs2069707GG genotype in patients and healthy controls (p<0.05), while the prevalence of IFN-γ rs2069707GG in SVR and NR groups was comparable (p>0.05). In conclusion, genetic variation of TRAIL-R1 rs4242392 is linked with response to interferon-based therapy for HCV infection, and genetic variation IFN-γ rs2069707 is associated with natural clearance of HCV infection.

Background: High risk deliveries are usually associated with increased neonatal mortality and morbidity. Neonatal resuscitation can appreciably affect the outcome in these types of deliveries. Presence of personnel trained in basic neonatal resuscitation at the time of delivery can play an important role in reducing perinatal complications in neonates at risk. The study was carried out to evaluate the effects of newborn resuscitation on neonatal outcome in high risk deliveries., Methods: This descriptive case series was carried out at the Department of Obstetrics and Gynecology, Jinnah Hospital, Lahore. Ninety consecutive high risk deliveries were included and attended by paediatricians trained in newborn resuscitation. Babies delivered by elective Caesarean section, normal spontaneous vaginal deliveries and still births were excluded. Neonatal resuscitation was performed in babies who failed to initiate breathing in the first minute after birth. Data was analyzed using SPSS-16.0., Results: A total of 90 high risk deliveries were included in the study. Emergency. caesarean section was the mode of delivery in 94.4% (n=85) cases and spontaneous vaginal delivery in 5.6% (n=5). Preterm pregnancy was the major high risk factor. Newborn resuscitation was required in 37.8% (n=34) of all high risk deliveries (p=0.013). All the new-borns who required resuscitation survived., Conclusion: New-born resuscitation is required in high risk pregnancies and personnel trained in newborn resuscitation should be available at the time of delivery.

Hepatitis C virus (HCV) genotypes and genetic variants of interleukin 28B (IL28B) are significantly associated with interferon plus ribavirin treatment of HCV infection. We investigated the distribution of HCV genotypes and single-nucleotide polymorphisms (SNPs) of IL28B (rs12979860 and rs8099917) in Pakistani population. IL28B genotyping was performed by allele-specific PCR and restriction fragment length polymorphism PCR in 140 chronic hepatitis C patients (CHC) and 120 healthy controls. HCV genotype 3 (HCVG3) was the most prevalent genotype, 71.4% (n = 100/140) and with the highest treatment response of 90% (n = 90/100). The overall treatment response of all the HCV genotypes was 82% (n = 115/140). The distribution of IL28B rs12979860CC genotype in treatment responder and non-responder groups was 40.8% (n = 47/115) and 16% (n = 4/25) respectively. IL28B rs12979860CC genotype demonstrated a significant correlation (p = 0.019) with interferon-based therapy of HCV infection. However, there was no observed association of IL28B rs8099917 polymorphism with treatment response in CHC patients (p = 0.264). In conclusion, HCV genotypes and IL28B rs12979860 are predictive markers for the efficiency of interferon plus ribavirin combinational therapy of HCV infection. We recommend the inclusion of testing for these markers in the clinical criteria for decision making for HCV therapy in Pakistani population., (© 2015 APMIS. Published by John Wiley & Sons Ltd.)

To estimate genetic and forensic parameters, the entire mitochondrial DNA control region of 100 unrelated Makrani individuals (males, n=96; females, n=4) living in Pakistan (Turbat, Panjgur, Awaran, Kharan, Nasirabad, Gwadar, Buleda, Karachi and Burewala) was sequenced. We observed a total of 70 different haplotypes of which 54 were unique and 16 were shared by more than one individual. The Makrani population showed a high genetic diversity (0.9688) and, consequently, a high power of discrimination (0.9592). Our results revealed a strongly admixed mtDNA pool composed of African haplogroups (28%), West Eurasian haplogroups (26%), South Asian haplogroups (24%), and East Asian haplogroups (2%), while the origin of the remaining individuals (20%) could not be confidently assigned. The results of this study are a valuable contribution to build a database of mtDNA variation in Pakistan., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The analysis of mitochondrial DNA (mtDNA) control region was carried in 85 unrelated Sariki individuals living in the different provinces of Pakistan. DNA was extracted from blood preserved in EDTA vacutainers. Hypervariable regions (HV1, HV2 & HV3) were PCR amplified and sequenced. Sequencing results were aligned and compared with revised Cambridge reference sequence (rCRS). The sequencing results showed presence of total 63 different haplotypes, 58 of them are unique and 05 are common haplotypes shared by more than one individual. The most common haplotype observed was (W6) with a frequency 12.9% of population sample. The Saraiki population was detected with genetic diversity (0.9570) and power of discrimination (0.9458). This study will be beneficial for forensic casework., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

WT1 + KTS and -KTS isoforms only differ in 3 amino acids in protein sequence but show significant functional difference. The +/-KTS isoforms were generated by alternative usage of 2 adjacent 5' splice sites at RNA level, however, how these 2 isoforms are regulated is still elusive. Here we report the identification of an intronic pyrimidine-rich sequence that is critical for the ratio of +/-KTS isoforms, deletion or partial replacement of the sequence led to full/significant shift to -KTS isoform. To identify trans-factors that can regulate +/-KTS isoforms via the binding to the element, we performed RNP assembly using in vitro transcribed RNA with or without the pyrimidine-rich sequence. Mass spectrometry analysis of purified RNPs showed that the element associated with many splicing factors. Co-transfection of these factors with WT1 reporter revealed that HuR promoted the production of -KTS isoform at the reporter level. RNA immuno-precipitation experiment indicated that HuR interacted with the pyrimidine-rich element in WT1 intron 9. We further presented evidence that transient or stable over-expression of HuR led to enhanced expression of endogenous -KTS isoform. Moreover, knockdown of HuR resulted in decreased expression of endogenous -KTS isoform in 293T, SW620, SNU-387 and AGS cell lines. Together, these data indicate that HuR binds to the pyrimidine-rich sequence and antagonize its effect in regulating WT1 +/-KTS isoforms.

Objectives: The aim of this study was to determine frequency of thyroid incidentalomas (TI) through ultrasound (US) and its association with age, gender and ethnicities., Methods: It was a cross-sectional study. Total 269 adults who were asymptomatic for thyroid disease aged 21 years and above underwent ultrasound examination of their thyroid., Results: Frequency of TI found was 21%. TI was detected in 25% of females and 16% males (P= 0.078). 61% had thyroid nodules (TNs) in one lobe (right, left or isthmus) and 39% had TNs in more than one location. About 55% had single TN and 45% had multiple TNs. 38% had TNs greater than 1cm while 57% had TNs smaller than 1 cm. 5% had TNs greater and smaller than 1 cm. TI was equally common in individuals of different ethinicities (P= 0.758)., Conclusion: Frequency of thyroid incidentalomas found in our study was higher than most of the other iodine sufficient states. Unlike other studies, incidentalomas were equally common in both the genders of our study. This may be due to the previous iodine deficient status of Pakistan which was prevalent. However further studies on the same topic will help us in identifying the correct status of thyroid incidentalomas if Pakistan retains it's status as an iodine sufficient state.

Hepatitis C virus (HCV) infection is the most important problem across the world. It causes acute and chronic liver infection. Different approaches are in use to inhibit HCV infection, including small organic compounds, siRNA, shRNA and peptide inhibitors. This review article summarizes the current and future therapies for HCV infection. PubMed and Google Scholar were searched for articles published in English to give an insight into the current inhibitors against this life-threatening virus. HCV NS3/4A protease inhibitors and nucleoside/nucleotide inhibitors of NS5B polymerase are presently in the most progressive stage of clinical development, but they are linked with the development of resistance and viral breakthrough. Boceprevir and telaprevir are the two most important protease inhibitors that have been approved recently for the treatment of HCV infection. These two drugs are now the part of standard-of-care treatment (SOC). There are also many other drugs in phase III of clinical development. When exploring the various host-cell-targeting compounds, the most hopeful results have been demonstrated by cyclophilin inhibitors. The current SOC treatment of HCV infection is Peg-interferon, ribavirin and protease inhibitors (boceprevir or telaprevir). The future treatment of this life-threatening disease must involve combinations of therapies hitting multiple targets of HCV and host factors. It is strongly expected that the near future, treatment of HCV infection will be a combination of direct-acting agents (DAA) without the involvement of interferon to eliminate its side effects.

Objective: To determine the frequency, severity and risk indicators of diabetic retinopathy (DR) in patients with diabetes attending a primary care diabetes centre., Methods: This observational study was conducted at Diabetic Association of Pakistan - a World Health Organization collaborating center in Karachi, from March 2009 to December 2011. Registered patients with diabetes were screened by two field fundus photographs. Retina specialists graded the signs of retinopathy according to diabetic retinopathy disease severity scale., Results: Of total registered diabetic patients (n=11,158), 10,768 (96.5 %) were screened for DR. Overall DR was found in 2661 (24.7%) patients. DR was found in decreasing order of frequency in patients with type 2 (n= 2555, 23.7%) followed by patients with type 1 diabetes (n=101, 0.93% ) and patients with gestational diabetes mellitus (GDM) (n=5, 0.46%). Among patients with DR, signs of non-sight threatening retinopathy was dominant. Females and patients of working age group predominantly had retinopathy. Type 1 patients >16 years and type 2 patients < 5 years of history of diabetes had sign of retinopathy in increased frequency., Conclusion: Every forth patient with diabetes in this large cohort had signs of diabetic retinopathy. Females and patients in working age group predominantly had retinopathy. Type 2 patients with short while type 1 patients with long history of diabetes most frequently had DR. Dissemination of the present study findings may help in increasing the awareness of this serious complication of diabetes.

Pam18/Tim14 and Pam16/Tim16, highly conserved proteins among eukaryotes, are two essential subunits of protein import motors localized in the inner mitochondrial membrane. The heterodimer formed by Pam18 and Pam16 via their J-type domains serves a regulatory function in protein translocation. Here, we report that thirty-one Pam18 and twenty-six Pam16 putative orthologues in twelve plant species were identified and analyzed through bioinformatics strategy. Results data revealed that Pam18 and Pam16 were also highly conserved among plants including their J-type domains within the hydrophilic region. Key amino acid residues and an HPD motif of Pam18 were identical among the orthologues except OsPam18L5. N-myristoylation sites of Pam18 and casein kinase II phosphorylation sites of Pam 16 were more abundant, which might be important functional sites. Some Pam18 and Pam16 proteins contained a transmembrane region at the N-terminal region. Sub-cellular prediction results indicated that many orthologues localized at mitochondria. Gene expression analyses revealed that Pam18 and Pam16 in Arabidopsis might play roles in senescence and abiotic stress responses. Our detailed study provides a better understanding of Pam18 and Pam16 in plant kingdom.

The current standard of care (SOC) for hepatitis C virus (HCV) infection is the combination of pegylated interferon (PEG-IFN), Ribavirin and protease inhibitor for HCV genotype 1. Nevertheless, this treatment is successful only in 70-80% of the patients. In addition, the treatment is not economical and is of immense physical burden for the subject. It has been established now, that virus-host interactions play a significant role in determining treatment outcomes. Therefore identifying biological markers that may predict the treatment response and hence treatment outcome would be useful. Both IFN and Ribavirin mainly act by modulating the immune system of the patient. Therefore, the treatment response is influenced by genetic variations of the human as well as the HCV genome. The goal of this review article is to summarize the impact of recent scientific advances in this area regarding the understanding of human and HCV genetic variations and their effect on treatment outcomes. Google scholar and PubMed have been used for literature research. Among the host factors, the most prominent associations are polymorphisms within the region of the interleukin 28B (IL28B) gene, but variations in other cytokine genes have also been linked with the treatment outcome. Among the viral factors, HCV genotypes are noteworthy. Moreover, for sustained virological responses (SVR), variations in core, p7, non-structural 2 (NS2), NS3 and NS5A genes are also important. However, all considered single nucleotide polymorphisms (SNPs) of IL28B and viral genotypes are the most important predictors for interferon based therapy of HCV infection.

Down's syndrome results from full or partial trisomy of chromosome 21. However, the consequences of the underlying gene-dosage imbalance on adult tissues remain poorly understood. Here we show that in Ts65Dn mice, which are trisomic for 132 genes homologous to genes on human chromosome 21, triplication of Usp16 reduces the self-renewal of haematopoietic stem cells and the expansion of mammary epithelial cells, neural progenitors and fibroblasts. In addition, Usp16 is associated with decreased ubiquitination of Cdkn2a and accelerated senescence in Ts65Dn fibroblasts. Usp16 can remove ubiquitin from histone H2A on lysine 119, a critical mark for the maintenance of multiple somatic tissues. Downregulation of Usp16, either by mutation of a single normal Usp16 allele or by short interfering RNAs, largely rescues all of these defects. Furthermore, in human tissues overexpression of USP16 reduces the expansion of normal fibroblasts and postnatal neural progenitors, whereas downregulation of USP16 partially rescues the proliferation defects of Down's syndrome fibroblasts. Taken together, these results suggest that USP16 has an important role in antagonizing the self-renewal and/or senescence pathways in Down's syndrome and could serve as an attractive target to ameliorate some of the associated pathologies.

This review selectively explores some areas of pain research that, until recently, have been poorly understood. We have chosen four topics that relate to clinical pain and we discuss the underlying mechanisms and related pathophysiologies contributing to these pain states. A key issue in pain medicine involves crucial events and mediators that contribute to normal and abnormal pain signaling, but remain unseen without genetic, biomarker or imaging analysis. Here we consider how the altered genetic make-up of familial pains reveals the human importance of channels discovered by preclinical research, followed by the contribution of receptors as stimulus transducers in cold sensing and cold pain. Finally we review recent data on the neuro-immune interactions in chronic pain and the potential targets for treatment in cancer-induced bone pain., (© 2013 Elsevier B.V. All rights reserved.)

Translational studies are key to furthering our understanding of nociceptive signalling and bridging the gaps between molecules and pathways to the patients. This requires use of appropriate preclinical models that accurately depict outcome measures used in humans. Whereas behavioural animal studies classically involve reports related to nociceptive thresholds of, for example, withdrawal, electrophysiological recordings of spinal neurones that receive convergent input from primary afferents permits investigation of suprathreshold events and exploration of the full-range coding of different stimuli. We explored the central processing of nociceptive inputs in a novel parallel investigation between rats and humans. Using radiant laser pulses, we first compared the electrophysiological responses of deep wide dynamic range and superficial nociceptive-specific neurones in the rat dorsal horn with human psychophysics and cortical responses. Secondly, we explored the effects of spatial summation using laser pulses of identical energy and different size. We observed 3 main findings. Firstly, both rodent and human data confirmed that neodymium-yttrium aluminium perovskite laser stimulation is a nociceptive-selective stimulus that never activates Aβ afferents. Secondly, graded laser stimulation elicited similarly graded electrophysiological and behavioural responses in both species. Thirdly, there was a significant degree of spatial summation of laser nociceptive input. The remarkable similarity in rodent and human coding indicates that responses of rat dorsal horn neurones can translate to human nociceptive processing. These findings suggest that recordings of spinal neuronal activity elicited by laser stimuli could be a valuable predictive measure of human pain perception., (Copyright © 2013. Published by Elsevier B.V.)

Background and Purpose: Lack of information is a major hurdle in combating stroke mortality and morbidity in India. This survey was undertaken in a slum area in Dharavi, Mumbai, to study the prevalence of stroke and post-stroke cognitive impairment in the elderly aged 60 years and above., Methods: Participants selected using systematic random sampling of households, were interviewed using a modified version of the World Health Organization Protocol for Screening of Neurological Diseases. Stroke was confirmed through clinical examination, medical records review and interviews with caregivers. Cognitive impairment was assessed using Addenbrooke's scale and Mini mental status examination., Results: Participants comprised 730 men and 996 women. Confirmed stroke in 66 individuals yielded a crude prevalence rate of 3.82% (95% CI 3.01 - 4.84); the prevalence standardized to WHO world population was 4.87% (95% CI 3.76 - 6.23). Prevalence rates increased with age and were higher in men than in women. Out of 27 stroke survivors evaluated for cognitive dysfunction, 18 (66.66%) had MMSE scores of less than 24., Conclusion: Stroke prevalence in slum-dwellers is comparable to that of other sections of society. Prevalence rates in this study are higher than rates seen in previous Indian studies, possibly due to the combined effects of population ageing with increased incidence of hypertension and diabetes mellitus, which also affect cognitive functions in stroke survivors.

Pro-nociceptive ON-cells in the rostral ventromedial medulla (RVM) facilitate nociceptive processing and contribute to descending serotonergic controls. We use RVM injections of neurotoxic dermorphin-saporin (Derm-SAP) in rats to evaluate the role of putative ON-cells, or μ-opioid receptor-expressing (MOR) neurones, in visceral pain processing. Our immunohistochemistry shows that intra-RVM Derm-SAP locally ablates a substantial proportion of MOR and serotonergic cells. Given the co-localization of these neuronal markers, some RVM ON-cells are serotonergic. We measure visceromotor responses in the colorectal distension (CRD) model in control and Derm-SAP rats, and using the 5-HT(3) receptor antagonist ondansetron, we demonstrate pro-nociceptive serotonergic modulation of visceral nociception and a facilitatory drive from RVM MOR cells. The α(2)δ calcium channel ligand pregabalin produces state-dependent analgesia in neuropathy and osteoarthritis models relating to injury-specific interactions with serotonergic facilitations from RVM MOR cells. Although RVM MOR cells mediate noxious mechanical visceral input, we show that their presence is not a permissive factor for pregabalin analgesia in acute visceral pain., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Purpose of Review: Visceral pain represents a major clinical problem, yet far less is known about its mechanisms compared with somatic pains, for example, from cutaneous and muscular structures., Recent Findings: In this review, we describe the neuroanatomical bases of visceral pain signalling in the peripheral and central nervous system, comparing to somatic pains and also the channels and receptors involved in these events. We include an overview of potential new targets in the context of mechanisms of visceral pain and hypersensitivity., Summary: This review should inform on the recognition of what occurs in patients with visceral pain, why comorbidities are common and how analgesic treatments work.

Objective: To determine the presence of Babesia bovis (B. bovis) in large ruminants in southern Punjab and its effect on hematological and serum biochemical profile of host animals., Methods: Blood samples were collected from 144 large ruminants, including 105 cattle and 39 buffaloes, from six districts in southern Punjab including Multan, Layyah, Muzaffar Garh, Bhakar, Bahawalnagar and Vehari. Data on the characteristics of animals and herds were collected through questionnaires. Different blood (hemoglobin, glucose) and serum (ALT, AST, LDH, cholesterol) parameters of calves and cattle were measured and compared between parasite positive and negative samples to demonstrate the effect of B. bovis on the blood and serological profile of infected animals., Results: 27 out of 144 animals, from 5 out of 6 sampling districts, produced the 541-bp fragment specific for B. bovis. Age of animals (P=0.02), presence of ticks on animals (P=0.04) and presence of ticks on dogs associated with herds (P=0.5) were among the major risk factors involved in the spread of bovine babesiosis in the study area. ALT concentrations were the only serum biochemical values that significantly varied between parasite positive and negative cattle., Conclusions: : This study has reported for the first time the presence of B. bovis in large ruminant and the results can lead to the prevention of babesiosis in the region to increase the livestock output.

Objective: Congestive heart failure (CHF) is a highly prevalent comorbidity among patients with symptomatic peripheral arterial disease. The effect of CHF on the procedural success of endovascular treatment, however, remains unknown. Theoretically, poor inflow secondary to systolic dysfunction and peripheral vascular alterations may predispose endovascular interventions to failure., Methods: A retrospective review of a prospectively maintained database was performed to identify CHF patients undergoing endovascular peripheral arterial intervention from 2004 to 2009. Demographics, comorbidities, procedural details, and outcomes were analyzed. Patients underwent duplex ultrasound imaging and clinical follow-up at scheduled intervals. Kaplan-Meier and Cox proportional hazards models were used to evaluate risk factors for loss of primary patency, secondary patency, and limb salvage., Results: Of 1220 patients undergoing intervention, 271 (22%) with documented congestive heart failure (CHF) underwent an intervention for claudication (22.5%) or critical limb ischemia (77.5%). Primary patency at 1 year was 51.9% ± 2.5% among those with CHF vs 64.6% ± 1.3% in those without CHF (P < .001); this disparity continued throughout follow-up (P < .001). Patients with CHF also had reduced secondary patency throughout follow-up. Multivariate analysis showed CHF was an independent predictor of reduced primary patency (hazard ratio [HR], 1.2; 95% confidence interval [CI] 1.0-1.4; P = .038) and secondary patency (HR, 1.5; 95% CI, 1.2-1.8; P < .001). In the setting of CHF, 1-year patency was 56.6% ± 4.1% if the ejection fraction (EF) was >40% (n = 147) vs 43.2% ± 3.5% if the EF was <40% (n = 124; P < .001). Secondary patency was also significantly reduced in patients with EF <40% throughout follow-up compared with patients without CHF (n = 949) as well as those with CHF and EF >40% (P < .001). CHF with EF <40% was an independent predictor of reduced primary patency (HR, 1.4; 95% CI, 1.2-1.8; P < .01) and secondary patency (HR, 1.8; 95% CI, 1.3-2.3; P < .001). Limb salvage was also worse in patients with EF <40% (P = .038)., Conclusions: CHF is associated with reduced patency after peripheral endovascular intervention and is an independent risk factor for patency loss. Specifically, CHF and reduced EF (<40%) is a strong independent risk factor for patency loss., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Current-generating (exoelectrogenic) bacteria in bioelectrochemical systems (BESs) may not be culturable using standard in vitro agar-plating techniques, making isolation of new microbes a challenge. More in vivo like conditions are needed where bacteria can be grown and directly isolated on an electrode. While colonies can be developed from single cells on an electrode, the cells must be immobilized after being placed on the surface. Here we present a proof-of-concept immobilization approach that allows exoelectrogenic activity of cells on an electrode based on applying a layer of latex to hold bacteria on surfaces. The effectiveness of this procedure to immobilize particles was first demonstrated using fluorescent microspheres as bacterial analogs. The latex coating was then shown to not substantially affect the exoelectrogenic activity of well-developed anode biofilms in two different systems. A single layer of airbrushed coating did not reduce the voltage produced by a biofilm in a microbial fuel cell (MFC), and more easily applied dip-and-blot coating reduced voltage by only 11% in a microbial electrolysis cell (MEC). This latex immobilization procedure will enable future testing of single cells for exoelectrogenic activity on electrodes in BESs.

Brainstem and spinal mechanisms mediating visceral nociception are investigated here using electrophysiology and immunohistochemistry techniques in a model of acute visceral pain. Colorectal distension (CRD) produced graded visceromotor responses (VMR) in normal rats, and these were facilitated by intracolonic mustard oil (MO) that generated acute visceral hyperalgesia. The neuropathic pain drug pregabalin (PGB) is thought to have state-dependent effects in attenuating neuropathic, but not acute somatic pain, likely by impairing calcium-channel trafficking. We found that systemic PGB produced antinociceptive effects on CRD-evoked VMRs in naïve rats lacking pathophysiology and in MO-pretreated rats. Systemic PGB also significantly reduced Fos labelling in lumbosacral spinal cords of rats given noxious repetitive CRD; however, PGB did not alter this measure of neural activity in the brainstem. Differential brainstem processing of noxious somatic and visceral stimuli may underlie the unique lack of state-dependent actions of PGB in this visceral pain model. Single-unit recordings in the rostral ventromedial medulla (RVM) verify that brainstem processing of somatic and visceral stimuli differs. The effects of CRD on RVM cells classed as ON, OFF, or NEUTRAL were independent of their somatic responses, with surprising changes in RVM cell activity to innocuous visceral stimulation. PGB also markedly reduced the visceral responses of RVM ON-cells to noxious CRD. These results illustrate clear differences in the central processing of visceral and somatic stimuli, yet a common role for descending modulation by brainstem activity in mediating evoked pain measures., (Copyright © 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background: Opioid-induced hyperalgesia is recognized in the laboratory and the clinic, generating central hyperexcitability in the absence of peripheral pathology. We investigated pregabalin, indicated for neuropathic pain, and ondansetron, a drug that disrupts descending serotonergic processing in the central nervous system, on spinal neuronal hyperexcitability and visceral hypersensitivity in a rat model of opioid-induced hyperalgesia., Methods: Male Sprague-Dawley rats (180-200 g) were implanted with osmotic mini-pumps filled with morphine (90 μg · μl⁻¹ · h⁻¹) or saline (0.9% w/v). On days 7-10 in isoflurane anesthetized animals, we evaluated the effects of (1) systemic pregabalin on spinal neuronal and visceromotor responses, and (2) spinal ondansetron on dorsal horn neuronal response. Messenger ribonucleic acid concentrations of α2δ-1, 5HT3A, and μ-opioid receptor in the dorsal root ganglia of all animals were analyzed., Results: In morphine-treated animals, evoked spinal neuronal responses were enhanced to a subset of thermal and mechanical stimuli. This activity was attenuated by pregabalin (by at least 71%) and ondansetron (37%); the visceromotor response to a subset of colorectal distension pressures was attenuated by pregabalin (52.8%; n = 8 for all measures, P < 0.05). Messenger ribonucleic acid concentrations were unchanged., Conclusions: The inhibitory action of pregabalin in opioid-induced hyperalgesia animals is neither neuropathy-dependent nor reliant on up-regulation of the α₂δ-1 subunit of voltage-gated calcium channels-mechanisms proposed as being essential for pregabalin's efficacy in neuropathy. In opioid-induced hyperalgesia, which extends to colonic distension, a serotonergic facilitatory system may be up-regulated, creating an environment that is permissive for pregabalin-mediated analgesia without peripheral pathology.

Background: The differences in implantable pressure sensor aneurysm sac readings were compared following endovascular aneurysm repair (EVAR) among three different stent grafts., Methods: From January 2006 to March 2009, 51 aortic stent grafts were implanted along with the Endosure sensor. Grafts used were Zenith, Talent, and Excluder. In the present retrospective study, pulse ratios were measured intraoperatively before and after aneurysm sac exclusion and in follow-up (within 30 days). Analysis of variance was used to determine significance., Results: The average aneurysm size that was repaired was 5.75 cm (range: 4-8.5 cm); 41 patients (80.4%) being male with an average age of 76.3 years (range: 58-90 years). Thirty-four grafts were Zenith, 9 were Talent, and 8 were Excluder. The average pre-aneurysm exclusion pulse ratios for the Zenith, Talent, and Excluder were 1.00, 1.08, and 0.95 (p = 0.18), respectively. The average post-aneurysm exclusion pulse ratios were 0.34, 0.67, and 0.35, respectively (p = 0.003). Pulse ratios at the time of follow-up (within 30 days) were 0.17, 0.22, and 0.11, respectively (p = 0.44). Nine of 51 (17.6%) patients had a reduction of pulse ratio of less than 30% after endograft implantation. Five of those 9 patients (55.5%) had the Talent endograft, although there was no angiographic evidence of endoleak., Conclusions: The Talent graft has significantly higher pulse ratios following endograft implantation despite having no angiographic evidence of endoleak when compared to the Zenith and Excluder grafts. However, the pulse ratios decreased to levels similar to Zenith and Excluder within 30 days of endograft implantation. This suggests that the Talent endograft may have increased porosity initially. If pulse ratios do not appropriately decrease immediately after device implantation, further angiographic imaging may not be necessary if no obvious endoleak is seen.

Colorectal cancer metastatic recurrence and chemoresistance are major causes of morbidity and mortality. Colon cancer initiating cells (CCIC) are thought to contribute to both these processes. To identify drugs with anti-CCIC activity we screened a number of FDA approved and investigational compounds. We found that the class I selective histone deacetylase inhibitor (HDACi) MGCD0103 has significant activity against CCIC, and also significantly inhibits non-CCIC CRC cell xenograft formation. Both MGCD0103 and the pan-HDAC inhibitor Trichostatin impairs CCIC clonogenicity and cause cell cycle arrest and cell death. Gene expression profiling revealed that the canonical WNT ligand DKK-1 is a highly upregulated target of HDAC inhibitors. Despite the presence of APC mutations and constitutive WNT signaling in CCIC, both transfected and recombinant DKK-1 dramatically inhibit CCIC proliferation and clonogenicity. Overall, these data show that inhibition of class I HDACs is a promising novel approach to target both CCIC and non-CCIC CRC cells. Our studies also provide novel insights into roles for DKK1 in addition to canonical WNT signaling and the mechanism of CCIC tumor formation.

Authors describe diagnostic dilemma of differentiating pyelonephritis with lymphomatous involvement of kidney in a known case of lymphoma. FDG uptake pattern was non-discriminatory and pyelonephritis diagnosed retrospectively on follow up study. Authors emphasize the importance of recognition of features and subtle clues of infection evident on CT component of PET-CT.

Background: Cholera is a major public health problem in developing countries of the world. Bacterial resistance, lack of surveillance data and proper microbiological facilities are major problems regarding diagnosis of cholera. The spread of microbial drug resistance is a global public health challenge that results in increased illness and death rate. Newer antimicrobials or agents are urgently required to overcome this problem. This work was therefore done to investigate the antimicrobial potential of onion against thirty-three clinical isolates of Vibrio cholerae., Methods: The extract was prepared by reflux extraction method. Antibacterial screening of clinical isolates of V. cholerae was done by agar well diffusion method. Agar dilution method was used to assess the Minimum Inhibitory Concentration (MIC)., Results: All tested strains of V. cholerae were sensitive to onion (Allium cepa) extracts of two types (purple and yellow). Purple type of extract had MIC range of 19.2-21.6 mg/ml. The extract of yellow type onion had an MIC range of 66-68.4 mg/ml., Conclusion: The results indicated that onion (Allium cepa) has an inhibitory effect on V. cholerae. Keeping in view the anti-bacterial activity of this compound can be exploited as a therapeutic agent in an animal model. This finding is a positive point for further investigation of this herb of traditional medicine.

Background: Vascular cognitive impairment, being the only treatable cause of dementia in the early stages, and having a diverse etiology, requires sensitive criteria for definition., Aim: This study aimed to study cognitive functions at 3 months post-stroke, utilising the Mini mental scale examination (MMSE) and the Frontal assessment battery (FAB), and to correlate the same with subgroups of ischemic stroke., Results: 164 patients were studied, 108 of these having multiple infarcts. Pure cortical infarcts were seen in 41 patients. At 3 months, 112/164 patients had MMSE more than 24, with no frontal executive dysfunction. MMSE score less than 24 was seen in 24 patients, all of them having FAB score below 10. Normal MMSE with impaired FAB was seen in 28 patients., Conclusions: Impairment on either the MMSE or the FAB was thus seen in 31.7% patients (52/164), at 3 months after stroke. FAB impairment alone, with MMSE in normal range, was seen in 28/52 (53.8%) patients. Memory was significantly more commonly affected in muti-infarct strokes as compared to single infarcts. Frontal executive dysfunction was not significantly different when single and multiple infarcts, or cortical and subcortical infarcts, were compared.

E. coli AlkB has been intensively studied since 1983, but the in vivo roles of its mammalian homologue Alkbh1 are unknown. We, therefore, created null mice for Alkbh1. Alkbh1 mRNA is expressed at highest levels in the trophoblast lineages of the developing placenta. Alkbh1(-/-) placentas have decreased expression of differentiated trophoblast markers including Tpbp, Gcm1, and Pl-1, and increased expression of the trophoblast stem cell marker Eomes. Alkbh1 localizes to nuclear euchromatin, and interacts strongly with Mrj, an essential placental gene that mediates gene repression by recruitment of class II histone deacetylases (HDACs). Competition experiments show Alkbh1 and HDAC4 binding to Mrj are mutually exclusive, which causes decreased HDAC activity and increased target gene expression. Our study demonstrates Alkbh1 performs important functions in placental trophoblast lineage differentiation and participates in mechanisms of transcriptional regulation.

Lamina 1 projection neurones which express the NK1 receptor (NK1R+) drive a descending serotonergic pathway from the brainstem that enhances spinal dorsal horn neuronal activity via the facilitatory spinal 5-HT3 receptor. Selective destruction of these cells via lumbar injection of substance P-saporin (SP-SAP) attenuates pain behaviours, including mechanical and thermal hypersensitivity, which are mirrored by deficits in the evoked responses of lamina V-VI wide dynamic range (WDR) neurones to noxious stimuli. To assess whether removing the origin of this facilitatory spino-bulbo-spinal loop results in alterations in GABAergic spinal inhibitory systems, the effects of spinal bicuculline, a selective GABA(A) receptor antagonist, on the evoked neuronal responses to electrical (Abeta-, Adelta-, C-fibre, post-discharge and Input) and mechanical (brush, prod and von Frey (vF) 8 and 26 g) stimuli were measured in SAP and SP-SAP groups. In the SAP control group, bicuculline produced a significant dose related facilitation of the electrically evoked Adelta-, C-fibre, post-discharge and input neuronal responses. The evoked mechanical (prod, vF8 g and 26 g) responses were also significantly increased. Brush evoked neuronal responses in these animals were enhanced but did not reach significance. This facilitatory effect of bicuculline, however, was lost in the SP-SAP treated group. The generation of intrinsic GABAergic transmission in the spinal cord appears dependent on NK1 bearing neurons, yet despite the loss of GABAergic inhibitory controls after SP-SAP treatment, the net effect is a decrease in spinal cord excitability. Thus activation of these cells predominantly drives facilitation.

From a large collection of families with autosomal recessive non-syndromic hearing impairment (NSHI) from Pakistan, linkage has been established for two unrelated consanguineous families to 19p13.2. This new locus was assigned the name DFNB68. A 10 cM genome scan and additional fine mapping were carried out using microsatellite marker loci. Linkage was established for both families to DFNB68 with maximum multipoint LOD scores of 4.8 and 4.6. The overlap of the homozygous regions between the two families was bounded by D19S586 and D19S584, which limits the locus interval to 1.9 cM and contains 1.4 Mb. The genes CTL2, KEAP1 and CDKN2D were screened but were negative for functional sequence variants.