Phenomics, genomics of oil palm (Elaeis guineensis Jacq.): way forward for making sustainable and high yielding quality oil palm.

Oil palm (Elaeis guineensis Jacq.) is a heterogeneous, perennial crop having long breeding cycle with a genome size of 1.8 Gb. The demand for vegetable oil is steadily increasing, and expected that nearly 240-250 million tons of vegetable oil may be required by 2050. Genomics and next generation technologies plays crucial role in achieving the sustainable availability of oil palm with good yield and high quality. A successful breeding programme in oil palm depends on the availability of diverse gene pool, ex-situ conservation and their proper utilization for generating elite planting material. The major breeding methods adopted in oil palm are either modified recurrent selection or the modified reciprocal recurrent selection method. The QTLs of yield and related traits are chiefly located on chromosome 4, 10, 12 and 15 which is discussed in the current review. The probable chromosomal regions influencing the less height increment is observed to be on chromosomes 4, 10, 14 and 15. Advanced genomic approaches together with bioinformatics tools were discussed thoroughly for achieving sustainable oil palm where more efforts are needed. Major emphasis is given on oil palm crop improvement using holistic approaches of various genomic tools. Also a road map given on the milestones in the genomics and way forward for making oil palm to high yielding quality oil palm.

Genome-wide association study (GWAS) of major QTLs for bunch and oil yield related traits in Elaeis guineensis L.

Oil palm (Elaeis guineensis Jacq.) is a long breeding cycle perennial crop with a genome size of 1.8 Gb. This is the first report of GWAS on large number of 310 African germplasm using 400 SSR markers till date. Highly significant correlation was found between leaf area (LA) and rachis length (RL) (0.75) followed by bunch weight (BW) and bunch index (BI) (0.65), whereas negative correlation was observed between bunch number (BN) and average bunch weight (ABW). First two principal component analysis (PCA) together explained maximum amount of variation (84.5 %). The PCA1 revealed that group 2 (Guinea Bissau and Cameroon) and group 4 (Zambia and Cameroon) genotypes are best suitable for BN, BI and BW traits. GWAS of six bunch yield and seven bunch oil yield traits with SSRs resulted in the identification 43 significant quantitative trait loci (QTLs) by mixed linear model (MLM) approach. Seven SSR loci were found to be linked to oil to dry mesocarp (ODM) on chromosomes 1,4,7,10,12 and 15. The SSR locus mEgCIR1753 for ODM was significantly linked at a p of ≤0.05 which explained 34.6 % of phenotypic variance. The important parameters like ODM, OWM and OB were located on 4, 10, 11 and 15 chromosomes. The leaf area and ODM were associated with candidate genes representing of low-temperature-induced 65 kDa proteins. The identified markers can be effectively used for marker assisted selection of high yielding oil palm genotypes.

Identification of QTLs in oil palm (Elaeis guineensis Jacq.) using SSR markers through association mapping.

Oil palm (Elaeis guineensis Jacq.) is a perennial vegetable and a high oil-yielding crop (4-6 t/ha). There is a large scope for increasing the oil yield by selecting elite planting material for breeding programme in germplasm evaluation, characterization and utilization. In the present study, a diverse range of 150 oil palm genotypes were characterized using 12 quantitative variables with 54genomic microsatellite markers. A wide variation was observed in the morphological traits among indigenous populations. Highly significantand positive correlations were observed between vegetative dry matter (VDM) and total dry matter (TDM) (0.862), and height and height increment (0.838). The first two principal component analyses explained 67.7% of total variation among morphological traits. The genotypes IC0610001-59 (Pune-2) and IC0610001-60 (Pune-2) were found highly promising based on less height increment, more TDMwith high yield. For the mapping study, general linear model (GLM) approach, quantitative-trait loci (QTL) for annual height increment, number of bunches, bunch yield and bunch index were linked to simple-sequence repeat (SSR) loci mEgCIR3649 with phenotypic variance of 15.08, 10.43, 11.74, 15.39. TDM and VDM were linked to mEgCIR0192 (27.34 and 24.19%), mEgCIR3684 (16.84 and 18.30%), SPSC00163 (18.8 and 15.39%) and mEgCIR0555 (16.47 and 18.81%), with at a significant threshold (P) level of B0.001 and by mixed linear model (MLM) approach. TDM was linked to mEgCIR0555 with phenotypic variance of 20.72%, bunch yield and bunch index were linked to mEgCIR2813 at phenotypic variance of 17.11% and 12.88%, respectively, at a significant threshold (P) level of B0.01.

Genome wide association study (GWAS) and identification of candidate genes for yield and oil yield related traits in oil palm (Eleaeis guineensis) using SNPs by genotyping-based sequencing.

The genotyping-based sequencing (GBS) method used for GWAS of four yield and seven oil yield related traits on highly diverse African oil palm germplasm. GBS generated 325 million-reads covering 50.78Gb of sequence data, with an average of 3.4 million-reads per sample. Finally, 4031 fully informative SNPs with a range between 157 on chromosome 15 to 455 on chromosome 1 were used for GWAS. Association mapping resulted in identification of 40 highly significant loci, where more genetic loci were found to be associated with oil to bunch (OB), followed by average bunch weight (ABW). The loci, SGI|593,593|linked to QTNOB3 explained high amount of phenotypic variance (25.3%). The nucleotide sequences of linked genetic loci for OB were found to be similar to mitogen activated protein kinase-5 (MAPK-5) protein which is an early flowering protein. The significant loci identified can be used to select desirable palms at early stage through marker assisted selection.

Incidence, Risk Factors, and Outcomes of Transition of Acute Kidney Injury to Chronic Kidney Disease in Cirrhosis: A Prospective Cohort Study.

Transition to chronic kidney disease (CKD) after an episode of acute kidney injury (AKI) is known in patients without cirrhosis. We studied the incidence and risk factors for development of CKD in patients with cirrhosis. Competing risk analysis was performed to identify risk factors for CKD development. Of 818 patients with cirrhosis (age, 50.4 ± 11.8 years; 84% males; Model for End-Stage Liver Disease [MELD], 19.9 ± 9.9), 36% had AKI at enrollment, 27% had previous AKI, and 61% developed new episodes of AKI during the follow-up period. CKD developed in 269 (33%) patients. Serum cystatin C (CysC; subdistribution hazard ratio [SHR], 1.58; 1.07-2.33), episodes of previous AKI (SHR, 1.26; 1.02-1.56), and AKI stage at enrollment (no AKI [SHR, 1] vs. stage 1 [SHR, 3.28; 1.30-8.25] vs. stage 2 [SHR, 4.33; 1.76-10.66] vs. stage 3 [SHR, 4.5; 1.59-12.73]) were identified as baseline risk factors for CKD development. On time-varying competing risk analysis, MELD (SHR, 1.01; 1.00-1.03), number of AKI episodes (SHR, 1.25; 1.15-1.37), and CysC (SHR, 1.38; 1.01-1.89) predicted CKD development. Development of CKD was associated with higher risk of death. Reduction in glomerular filtration rate (GFR) not meeting CKD criteria was observed in 66% of patients with cirrhosis, more so in those with previous AKI episodes and a high CysC level and MELD score. Renal histology, available in 55 patients, showed tubulointerstitial injury in 86%, cholemic nephrosis in 29%, and glomerular changes in 38%. Conclusion: Almost two-thirds of patients with cirrhosis develop episodes of AKI and reduction in GFR; one-third progress to CKD, resulting in adverse outcomes. Higher MELD and CysC levels and number of AKI episodes predict development of CKD in patients with cirrhosis.

Genome-wide association study for leaf area, rachis length and total dry weight in oil palm (Eleaeisguineensis) using genotyping by sequencing.

The marker-trait association for complex traits using genotyping by sequencing (GBS) method is being widely spread in plants. The study aimed to identify significant single nucleotide polymorphism (SNP) associations for rachis length (RL), leaf area (LA) and total dry weight (TrDW) in oil palm among diverse African germplasm. The Illumina NextSeq platform has been used for SNP genotyping and retained 4031 fully informative SNPs after applying the filter criterion. These 4031 SNPs were used for genome wide association study for the above three traits. The LD decay rates of the African germplasm using GBS data of SNP is observed to be 25 Kb at 0.45 of average pair wise correlation coefficient (r2). Association mapping led to the identification of seven significant associations for three traits using MLM approach at a P value of ≤ 0.001. Three associations were identified for total dry weight, two each for leaf area index and rachis length. The qtlLA1 was found to be highly significant at a P value of 7.39E-05 (18.4% phenotypic variance) which is located on chromosome 4. Two QTLs (qtlLA2 and qtlRL1) were located on chromosome 1, which explained 11.9% and 12.4% of phenotypic variance respectively. Three QTLs for total dry weight were located on chromosome 2, 14 and 16, all-together explained 40% phenotypic variance. The results showed that the SNP-trait associations identified in the present study could be used in selection of elite oil palm germplasm for higher yields.

Development and validation of whole genome-wide and genic microsatellite markers in oil palm (Elaeis guineensis Jacq.): First microsatellite database (OpSatdb).

The availability of large expressed sequence tag (EST) and whole genome databases of oil palm enabled the development of a data base of microsatellite markers. For this purpose, an EST database consisting of 40,979 EST sequences spanning 27 Mb and a chromosome-wise whole genome databases were downloaded. A total of 3,950 primer pairs were identified and developed from EST sequences. The tri and tetra nucleotide repeat motifs were most prevalent (each 24.75%) followed by di-nucleotide repeat motifs. Whole genome-wide analysis found a total of 245,654 SSR repeats across the 16 chromosomes of oil palm, of which 38,717 were compound microsatellite repeats. A web application, OpSatdb, the first microsatellite database of oil palm, was developed using the PHP and MySQL database ( https://ssr.icar.gov.in/index.php ). It is a simple and systematic web-based search engine for searching SSRs based on repeat motif type, repeat type, and primer details. High synteny was observed between oil palm and rice genomes. The mapping of ESTs having SSRs by Blast2GO resulted in the identification of 19.2% sequences with gene ontology (GO) annotations. Randomly, a set of ten genic SSRs and five genomic SSRs were used for validation and genetic diversity on 100 genotypes belonging to the world oil palm genetic resources. The grouping pattern was observed to be broadly in accordance with the geographical origin of the genotypes. The identified genic and genome-wide SSRs can be effectively useful for various genomic applications of oil palm, such as genetic diversity, linkage map construction, mapping of QTLs, marker-assisted selection, and comparative population studies.

Hydatidiform molar pregnancy following assisted reproduction.

INTRODUCTION: The use of assisted reproduction techniques (ART) is increasing; however, reports of molar pregnancy following ART remain scarce. Currently, the Human Fertility and Embryology Authority (HFEA) collates data on the molar pregnancies that have resulted through the use of ART. Recently, they have indicated that they will no longer collect these data. AIM: This paper aimed to examine the incidence of molar pregnancy amongst patients undergoing assisted reproduction. METHODS: We contacted HFEA and placed a request under the Freedom of Information Act (2000) for the number of molar pregnancies that resulted from fresh/frozen embryo transfer since HFEA started collecting data in 1991 to February 2018. We also asked how many patients who had suffered a molar pregnancy went on to have a normal pregnancy and how many had subsequent molar pregnancies, in subsequent treatment cycles. RESULTS: Between 68 and 76 molar pregnancies occurred within this period using ART (n = 274,655). The incidence of molar pregnancy using fresh intracytoplasmic sperm injection (ICSI) (1/4302) and fresh in vitro fertilisation (IVF) (1/4333) was similar. The risk of recurrence of molar pregnancy following a previous molar was higher following ART compared to spontaneous conceptions. CONCLUSION: The use of ICSI should be protective against triploidy; however, the retrospective data suggests that molar pregnancy is not eliminated with the use of ART. It is pertinent to continue to record this data, through the gestational trophoblastic disease centres, in order to ensure no further increase in incidence, appropriate follow-up, and transparency in communication.

Targeting nucleolin for better survival in diffuse large B-cell lymphoma.

Anthracyclines have been a cornerstone in the cure of diffuse large B-cell lymphoma (DLBCL) and other hematological cancers. The ability of anthracyclines to eliminate DLBCL depends on the presence of topoisomerase-II-alpha (TopIIA), a DNA repair enzyme complex. We identified nucleolin as a novel binding partner of TopIIA. Abrogation of nucleolin sensitized DLBCL cells to TopIIA targeting agents (doxorubicin/etoposide). Silencing nucleolin and challenging DLBCL cells with doxorubicin enhanced the phosphorylation of H2AX (γH2AX-marker of DNA damage) and allowed DNA fragmentation. Reconstitution of nucleolin expression in nucleolin-knockdown DLBCL cells prevented TopIIA targeting agent-induced apoptosis. Nucleolin binding to TopIIA was mapped to RNA-binding domain 3 of nucleolin, and this interaction was essential for blocking DNA damage and apoptosis. Nucleolin silencing decreased TopIIA decatenation activity, but enhanced formation of TopIIA-DNA cleavable complexes in the presence of etoposide. Moreover, combining nucleolin inhibitors: aptamer AS1411 or nucant N6L with doxorubicin reduced DLBCL cell survival. These findings are of clinical importance because low nucleolin levels versus high nucleolin levels in DLBCL predicted 90-month estimated survival of 70% versus 12% (P<0.0001) of patients treated with R-CHOP-based therapy.

Aegle marmelos differentially affects hepatic markers of glycolysis, insulin signalling pathway, hypoxia, and inflammation in HepG2 cells grown in fructose versus glucose-rich environment.

Fructose consumption is responsible for the onset of insulin resistance (IR), and metabolic syndrome. It possesses no functional utility in body and its detrimental effects on hepatic metabolic milieu are beyond those produced by glucose. The need of the hour is to identify fructose-induced IR as an unique pathological state to be managed differentially. The effect of aqueous leaf extract of Aegle marmelos (AM) on hepatic markers of insulin resistance using HepG2 cells cultured in either fructose or glucose-rich environment is investigated. Human hepatocellular carcinoma cells (HepG2) were grown under standard conditions in either-DMEM without glucose (NC), DMEM with high glucose 25 mM (Glu), DMEM-glucose+0.55 mM fructose (FC1), DMEM-glucose+1 mM fructose (FC2) or DMEM-glucose+1 mM fructose+0.1 µM insulin (FC3). The cells were treated with either AM, rutin, quercetin, metformin or pioglitazone and assessed for levels of hexokinase, phosphofructokinase (PFK), aldehyde dehydrogenase, phosphatidylinositol kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3), mitochondrial target of rapamycin (mTOR), hypoxia-induced factor (HIF-1α), vascular endothelial growth factor (VEGF) and tumour necrosis factor (TNF-α). Summarily, when results from fructose- and glucose-rich environment were compared, then (1) IR was more pronounced in former; (2) AM performed better in former; (3) metformin and pioglitazone were equivocal in either; (4) rutin and quercetin showed deviant effects from AM; and lastly (5) effects of rutin were closer to AM than quercetin. We hypothesize that AM ameliorates fructose-induced IR through a mechanism which is distinct from standard drugs and not shared by individual phytoconstituents in toto.

Development, identification and validation of CAPS marker for SHELL trait which governs dura, pisifera and tenera fruit forms in oil palm (Elaeis guineensis Jacq.).

The oil palm fruit forms (dura, pisifera and tenera) governed by the shell thickness gene (Sh) plays a major role in identification of fruit type and also influences palm oil yield. Identification of desired fruit type is a major asset to the breeders and oil palm workers for applications in breeding, seed certification and to reduce time, space and money spent on identification of fruit form. In the present study, we developed Sh gene specific primer pairs and bulk segregant analysis was done using 300 genomic and 8 genic SSR markers. We identified one cleaved amplified polymorphic site (CAPS) marker for differentiation of oil palm fruit type which produced two alleles (280 and 250bp) in dura genotypes, three alleles in tenera genotypes (550, 280, and 250bp) and one allele in pisifera genotypes (550bp). The shell allele sequencing results showed that two SNPs were present, of which SNP2 contributed for variation of fruit forms. The nucleotide 'A' was present in only dura genotypes, where as 'T' was present only in pisifera genotypes, which in turn led to the change of amino acid lysine to aspargine. The identified CAPS marker was validated on 300 dura, 25 pisifera and 80 tenera genotypes, 80 dura/ pisifera cross progenies and 60 lines of tenera/ tenera cross progeny. Association mapping of marker data with phenotypic data of eight oil yield related traits resulted in identification of seven significant QTLs by GLM approach, four by MLM approach at a significant threshold (P) level of 0.001. Significant QTLs were identified for fruit to bunch and oil to bunch traits, which explained R2 of 12.9% and 11.5% respectively. The CAPS marker used in the present study facilitate selection and timely distribution of desirable high yielding tenera sprouts to the farmers instead of waiting for 4-5 years. This saves a lot of land, time and money which will be a major breakthrough to the oil palm community.

Low-level laser therapy as an adjunct to conventional therapy in the treatment of diabetic foot ulcers.

Foot ulcers are serious complications of diabetes mellitus (DM) and are known to be resistant to conventional treatment. This study was conducted to evaluate the efficacy of low-level laser therapy (LLLT) for the treatment of diabetic foot ulcers in a tertiary care centre (Department of Surgery, Mahatma Gandhi Memorial Medical College and Maharaja Yashwantrao Hospital, A.B. Road, Indore). A total of 30 patients with type 2 DM having Meggitt-Wagner grade I foot ulcers of more than 6 weeks duration with negative culture were studied. Patients were randomized into two groups of 15 each. Patients in study group received LLLT (660 ± 20 nm, 3 J/cm2) along with conventional therapy and those in control group were treated with conventional therapy alone. The primary outcome measure was the absolute and relative wound size reduction at 2 weeks compared to the baseline parameter. Percentage ulcer area reduction was 37 ± 9% in the LLLT group and 15 ± 5.4% in the control group (p < 0.001). For ∼75% of wounds of the treatment group, wound area reduction of 30-50% was observed. In contrast, for the control group, ∼80% of wounds showed a wound area reduction of <20% on day 15. Further, the wounds with initial wound area 1000-2000 mm2 seems to have better final outcome than the groups with larger areas. The treated groups showed higher amount of granulation than the control group. The results suggest that LLLT is beneficial as an adjunct to conventional therapy in the treatment of diabetic foot ulcers.

Abnormal feeding behaviour in spinalised rats is mediated by hypothalamus: Restorative effect of exposure to extremely low frequency magnetic field.

STUDY DESIGN: Experimental study. OBJECTIVES: To investigate the role of hypothalamus in abnormal feeding behaviour after spinal cord injury (SCI) and the effect of exposure to extremely low frequency magnetic field (ELF-MF) on it. SETTING: India. METHODS: Male Wistar rats (n=44) were divided into Sham (laminectomy), SCI (complete transection of T13 spinal cord), SCI+MF (ELF-MF exposure to SCI rats), VMHL (lesion of ventromedial hypothalamus; VMH), SCI+VMHL (VMHL after SCI) and SCI+VMHL+MF (ELF-MF exposure to SCI+VMHL rats) groups. Food intake (FI), water intake (WI), calorie intake (CI), body weight (BWT), taste preference and sucrose-induced biphasic (SIB) response to noxious stimulus were studied pre and post surgery. Neuronal activity at VMH was assessed by c-Fos immunohistochemistry. The extent of neuronal degeneration and regeneration in spinal cord was assessed microscopically. RESULTS: Data revealed post-SCI decrease in FI, WI, CI and BWT, preference for sodium chloride and citric acid, prolonged analgesic phase of SIB and increased c-Fos immunoreactivity in VMH of SCI rats vs Sham rats. VMH lesion increased FI, WI, CI, BW, preference for sweet tastants and abolished SIB, whereas in SCI+VMHL rats it abolished the effects of SCI on these parameters indicating probable involvement of VMH in SCI-induced alteration in feeding behaviour. Exposure to MF improved the study parameters in SCI rats and reduced the c-Fos immunoreactivity in VMH besides reduction in lesion volume, greater myelination and neuronal regeneration at SCI site. CONCLUSION: SCI influences VMH, leading to alteration in feeding behaviour, which is improved by exposure to ELF-MF.

Cardiovascular risk factors among patients with schizophrenia, bipolar, depressive, anxiety, and personality disorders.

BACKGROUND: The evidence informing the management of cardiovascular risk in patients with psychiatric disorders is weak. METHODS: This cohort study used data from all patients, aged≥30, registered in 140 primary care practices (n=524,952) in London to estimate the risk of developing diabetes, hypertension, hyperlipidemia, tobacco consumption, obesity, and physical inactivity, between 2005 and 2015, for patients with a previous diagnosis of schizophrenia, depression, anxiety, bipolar or personality disorder. The role of antidepressants, antipsychotics and social deprivation in these associations was also investigated. The age at detection of cardiovascular risk factor was compared between patients with and without psychiatric disorders. Variables, for exposures and outcomes, defined from general practitioners records, were analysed using multivariate regression. RESULTS: Patients with psychiatric disorders had an increased risk for cardiovascular risk factors, especially diabetes, with hazard ratios: 2.42 (2.20-2.67) to 1.31 (1.25-1.37), hyperlipidemia, with hazard ratios: 1.78 (1.60-1.97) to 1.25 (1.23-1.28), and obesity. Antidepressants, antipsychotics and social deprivation did not change these associations, except for smoking and physical inactivity. Antidepressants were associated with higher risk of diabetes, hypertension and hyperlipidemia. Antipsychotics were associated with a higher risk of diabetes. Antidepressants and antipsychotics were associated with lower risk of other risk factors. Patients with psychiatric conditions have later detection of cardiovascular risk factors. The interpretation of these results should acknowledge the lower rates of detection of risk factors in mentally ill patients. CONCLUSIONS: Cardiovascular risk factors require special clinical attention among patients with psychiatric disorders. Further research could study the effect of antidepressants and antipsychotics on cardiovascular risk factors.

Intracellular delivery of antibodies by chimeric Sesbania mosaic virus (SeMV) virus like particles.

The therapeutic potential of antibodies has not been fully exploited as they fail to cross cell membrane. In this article, we have tested the possibility of using plant virus based nanoparticles for intracellular delivery of antibodies. For this purpose, Sesbania mosaic virus coat protein (CP) was genetically engineered with the B domain of Staphylococcus aureus protein A (SpA) at the ßH-ßI loop, to generate SeMV loop B (SLB), which self-assembled to virus like particles (VLPs) with 43 times higher affinity towards antibodies. CP and SLB could internalize into various types of mammalian cells and SLB could efficiently deliver three different monoclonal antibodies-D6F10 (targeting abrin), anti-α-tubulin (targeting intracellular tubulin) and Herclon (against HER2 receptor) inside the cells. Such a mode of delivery was much more effective than antibodies alone treatment. These results highlight the potential of SLB as a universal nanocarrier for intracellular delivery of antibodies.

Comparative evaluation of Bis(thiosemicarbazone)- Biotin and Met-ac-TE3A for tumor imaging.

2,2',2″-(11-(2-((4-mercapto-1-methoxy-1-oxobutan-2-yl)amino)-2-oxoethyl)-1,4,8,11-tetraaza cyclotetradecane-1,4,8-triyl)triacetic acid, Met-ac-TE3A and (E)-N-methyl-2-((E)-3-(2-(2-(5-((3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoyl)hydrazinecarbono-thioyl)hydrazonobutan-2-ylidene)hydrazinecarbothioamide, Bis(thiosemicarbazone)- Biotin were synthesized and evaluated for imaging application. The pharmacokinetics of these ligands were determined by tracer methods. In vitro human serum stability of (99m)Tc Met-ac-TE3A/(99m)Tc Bis(thiosemicarbazone)-Biotin after 24h was found to be 96.5% and 97.0% respectively. Blood kinetics of both ligands in normal rabbits showed biphasic clearance pattern. Ex vivo biodistribution study revealed significant initial tumor uptake and high tumor/muscles ratio which is a pre-requisite condition for a ligand to work as SPECT-radiopharmaceutical for tumor imaging.

AKI in patients with acute on chronic liver failure is different from acute decompensation of cirrhosis.

BACKGROUND AND AIMS: The current definitions of acute kidney injury (AKI) including HRS have been derived from patients with decompensated cirrhosis. No studies have carefully addressed AKI in patients with acute on chronic liver failure (ACLF). We evaluated the prevalence, spectrum, natural history and mortality of AKI at admission and new-onset AKI in hospitalized patients with ACLF and compared the results with patients with acute decompensation of cirrhosis (ADC). PATIENTS AND METHODS: Consecutive patients with ACLF (n = 382) and ADC (n = 451) were prospectively studied. Serial renal and liver functions were recorded and correlated with the disease course and outcome. RESULTS: AKI at admission and new onset AKI in the hospital were not different in patients with ACLF and ADC (p > 0.05). However, a significant difference in the spectrum of AKI was noted; functional volume-responsive AKI was more common (p < 0.05) in ADC, while patients with ACLF more frequently had the structural form of AKI (p < 0.05). Moreover, patients with ADC had significantly less AKI progression (p < 0.05) and prolonged duration (p < 0.05), a lower requirement of RRT (p < 0.05) and also less AKI resolution (p < 0.05) compared to ACLF patients. Patients with ACLF (versus ADC) had a significantly higher mortality on multivariate analysis. CONCLUSIONS: The kidneys are differentially affected in patients with cirrhosis with or without liver failure. Patients with ACLF with AKI have more structural AKI, greater potential for reversibility despite higher progression as well as higher mortality compared to patients with ADC. Prevention and early detection of AKI should be considered in patients with ACLF.

Testicular embryonal cell carcinoma presenting as haemoptysis and skin nodules.

Embryonal cell carcinoma affects young males in the prime of their life with majority of tumours already having metastasised at the time of diagnosis. Subcutaneous metastasis from embryonal carcinoma is rare and is associated with widespread disease and poor prognosis. We report a case of 22-year-old male who presented with haemoptysis and skin nodules. Fine needle aspiration cytology of skin nodules and the lung lesion led to the diognosis of testicular embryonal cell carcinoma.

FAS-antisense 1 lncRNA and production of soluble versus membrane Fas in B-cell lymphoma.

Impaired Fas-mediated apoptosis is associated with poor clinical outcomes and cancer chemoresistance. Soluble Fas receptor (sFas), produced by skipping of exon 6, inhibits apoptosis by sequestering Fas ligand. Serum sFas is associated with poor prognosis of non-Hodgkin's lymphomas. We found that the alternative splicing of Fas in lymphomas is tightly regulated by a long-noncoding RNA corresponding to an antisense transcript of Fas (FAS-AS1). Levels of FAS-AS1 correlate inversely with production of sFas, and FAS-AS1 binding to the RBM5 inhibits RBM5-mediated exon 6 skipping. EZH2, often mutated or overexpressed in lymphomas, hyper-methylates the FAS-AS1 promoter and represses the FAS-AS1 expression. EZH2-mediated repression of FAS-AS1 promoter can be released by DZNeP (3-Deazaneplanocin A) or overcome by ectopic expression of FAS-AS1, both of which increase levels of FAS-AS1 and correspondingly decrease expression of sFas. Treatment with Bruton's tyrosine kinase inhibitor or EZH2 knockdown decreases the levels of EZH2, RBM5 and sFas, thereby enhancing Fas-mediated apoptosis. This is the first report showing functional regulation of Fas repression by its antisense RNA. Our results reveal new therapeutic targets in lymphomas and provide a rationale for the use of EZH2 inhibitors or ibrutinib in combination with chemotherapeutic agents that recruit Fas for effective cell killing.

Role of Alpha Blockers in Hypertension with Benign Prostatic Hyperplasia.

Hypertension and benign prostatic hyperplasia (BPH) are common disorders of aging men. As the world population is aging these two diseases are becoming a significant public health problem worldwide. Approximately 30% of men treated for BPH have coexisting hypertension. The α-Adrenergic Blockers: Prazosin, Terazosin and Doxazosin are established agents in the therapy of hypertension, and are also effective drugs in the treatment of BPH. It is reasonable to use α-Adrenergic Blockers as the treatment of choice for men with hypertension and BPH.