Evolution of NLR genes in genus Arachis reveals asymmetric expansion of NLRome in wild and domesticated tetraploid species.

Arachis hypogaea is an allotetraploid crop widely grown in the world. Wild relatives of genus Arachis are the rich source of genetic diversity and high levels of resistance to combat pathogens and climate change. The accurate identification and characterization of plant resistance gene, nucleotide binding site leucine rich repeat receptor (NLRs) substantially contribute to the repertoire of resistances and improve production. In the current study, we have studied the evolution of NLR genes in genus Arachis and performed their comparative genomics among four diploids (A. duranensis, A. ipaensis, A. cardenasii, A. stenosperma) and two tetraploid (wild: A. monticola and domesticated: A. hypogaea) species. In total 521, 354, 284, 794, 654, 290 NLR genes were identified from A. cardenasii, A. stenosperma and A. duranensis, A. hypogaea, A. monticola and A. ipaensis respectively. Phylogenetic analysis and classification of NLRs revealed that they belong to 7 subgroups and specific subgroups have expanded in each genome leading towards divergent evolution. Gene gain and loss, duplication assay reveals that wild and domesticated tetraploids species have shown asymmetric expansion of NLRome in both sub-genome (AA and BB). A-subgenome of A. monticola exhibited significant contraction of NLRome while B-subgenome shows expansion and vice versa in case of A. hypogaea probably due to distinct natural and artificial selection pressure. In addition, diploid species A. cardenasii revealed the largest repertoire of NLR genes due to higher frequency of gene duplication and selection pressure. A. cardenasii and A. monticola can be regarded as putative resistance resources for peanut breeding program for introgression of novel resistance genes. Findings of this study also emphasize the application neo-diploids and polyploids due to higher quantitative expression of NLR genes. To the best of our knowledge, this is the first study that studied the effect of domestication and polyploidy on the evolution of NLR genes in genus Arachis to identify genomic resources for improving resistance of polyploid crop with global importance on economy and food security.

Understanding health service quality in emergency department through the length of stay and its determinants.

Objectives: To identify and analyse the determinants of emergency department length of stay. METHODS: The cross-sectional study was conducted from December 20 to 31, 2017, at the Centre of Referral Hospital after approval from the ethics review committee of Dr Soetomo General Hospital, Surabaya, Indonesia, and comprised patients of either gender aged 18 years or above who visited the emergency department who required follow-up after triage, such as diagnostics or hospitalisation. Emergency department length of stay, assessment time, review and consultation, and disposition or decision were the variables noted. Data was analysed using SPSS 18. RESULTS: Of the 172 patients, 95(57%) were men and 74(43%) were women. The largest age group was of those aged 45-59 years 61(34.4%). There were 48(27%) cases of surgery and 124(73%) of medicine. Mean emergency department length of stay was 575.94±306.402 minutes (range: 100-2215 minutes), and it was significantly associated with assessment time (p=0.001), review and consultation time (p=0.001) and disposition or decision time (p=0.002). CONCLUSIONS: The emergency department length of stay was found to be rather prolonged and needed to be improved.

A Novel Homozygous Nonsense Variant in the DYM Underlies Dyggve-Melchior-Clausen Syndrome in Large Consanguineous Family.

(1) Background: Dyggve-Melchior-Clausen Syndrome is a skeletal dysplasia caused by a defect in the DYM gene (OMIM number 607461). Pathogenic variants in the gene have been reported to cause Dyggve-Melchior-Clausen (DMC; OMIM 223800) dysplasia and Smith-McCort (SMC; OMIM 607326) dysplasia. (2) Methods: In the present study, large consanguineous families with five affected individuals with osteochondrodysplasia phenotypes were recruited. The family members were analyzed by polymerase chain reaction for homozygosity mapping using highly polymorphic microsatellite markers. Subsequent to linkage analysis, the coding exons and exon intron border of the DYM gene were amplified. The amplified products were then sent for Sanger sequencing. The structural effect of the pathogenic variant was analyzed by different bioinformatics tools. (3) Results: Homozygosity mapping revealed a 9 Mb homozygous region on chromosome 18q21.1 harboring DYM shared by all available affected individuals. Sanger sequencing of the coding exons and exon intron borders of the DYM gene revealed a novel homozygous nonsense variant [DYM (NM_017653.6):c.1205T>A, p.(Leu402Ter)] in affected individuals. All the available unaffected individuals were either heterozygous or wild type for the identified variant. The identified mutation results in loss of protein stability and weekend interactions with other proteins making them pathogenic (4) Conclusions: This is the second nonsense mutation reported in a Pakistani population causing DMC. The study presented would be helpful in prenatal screening, genetic counseling, and carrier testing of other members in the Pakistani community.

A novel homozygous variant in the GLI1 underlies postaxial polydactyly in a large consanguineous family with intra familial variable phenotypes.

Polydactyly is a human inherited disorder caused by to anomalies in the genes involved in autopod development. The disorder segregates in both autosomal recessive and autosomal dominant form. Up till now, eleven genes causing non-syndromic polydactyly, have been identified. This includes ZNF141, GLI3, ZRS in LMBR1, MIPOL1, PITX1, IQCE, GLI1, FMA92A1, KIAA0825, STKLD1, and DACH1. In the present study, we have investigated a large consanguineous family of Pakistani origin segregating polydactyly in autosomal recessive pattern. Clinical examination of affected individuals revealed a non-syndromic form of the disorder. Genetic study based on homozygosity mapping and Sanger sequencing using DNA of the normal and affected individuals found a novel homozygous missense sequence variant [NM_005269.3: c.1133C > T, p.(Ser378Leu)] in the GLI1 located on human chromosome 12q13.3. In silico analysis of the identified variant showed a significant change in the secondary structure of the mutant protein that affects its function. Findings of the present study expand the mutation spectrum of the GLI1. In addition, the study will help in prevention of the disorder through carrier testing and bringing awareness among families affected with polydactyly.

Beneficial Biological Activities of Cinnamomum osmophloeum and its Potential Use in the Alleviation of Oral Mucositis: A Systematic Review.

The aim of this review was to provide an updated overview of studies on the medical-biological activities of Cinnamomum osmophloeum (C. osmophloeum) in vitro and in vivo and the potential therapeutic use of natural agents prepared from this plant for the alleviation of oral mucositis (OM). Reported articles were collected using web search engine tools. The systematic review was organized according to the preferred reporting items for reviews and meta-analyses (PRISMA) statement. Additional sources were identified through cross-referencing to identify the potential use of C. osmophloeum in the alleviation of OM. The results disclosed that C. osmophloeum is comprised of bioactive ingredients that could act diversely as a reagent in anti-inflammation, antibacterial, antioxidant, anti-hyperglycemic, antidyslipidemia, anti-cancer, renal disease therapy and anti-hyperuricemia capacities. Recent studies revealed that the overall effects on anti-inflammation, wound repair, and the antibacterial and antioxidant activities of its constituents would act as a potential remedy for oral mucositis. Up-to-date in vitro and in vivo studies on the medical-biological activities of C. osmophloeum suggested that C. osmophloeum and its constituents could be promising remedies as adjuvants in OM therapy and warrant further investigation.

Left Renal Vein Compression Syndrome: Cracking the Nut of Clinical Dilemmas - Three Cases and Review of Literature.

BACKGROUND The term nutcracker phenomenon (NCP) elucidates anatomical structure and hemodynamics, whereas nutcracker syndrome (NCS) refers to clinical manifestations. We present three cases of similar clinical features of hematuria and flank pain with different clinical outcomes. CASE REPORT Case 1: A 36-year-old Caucasian female with a past medical history (PMH) of HIV infection presented for evaluation of hematuria. Computed tomography (CT) without contrast showed pelvic venous congestion and narrowing of the extra-renal left renal vein (LRV). After the failure of conservative management, renal auto-transplantation was attempted but failed because of extensive venous collateral; the patient subsequently required a total hysterectomy due to recurrence of symptoms. Case 2: A 41-year-old Caucasian female with extensive PMH presented with chronic abdominal pain. A CT scan of the abdomen and pelvis showed pelvic venous congestion. The patient underwent angioplasty and stent placement of the LRV. Subsequently, a left ovarian vein embolization was performed. On follow-up visits, her symptoms improved. Case 3: A 36-year-old female with PMH of HIV infection, gastroesophageal reflux disease, and hypertension presented with hematuria and flank pain. Her venogram revealed 1 mm Hg pressure gradient across stenosis, suggestive of LRV hypertension. Over the months of her follow-up after discharge, her hematuria gradually decreased from daily to intermittent non-daily frequency, without any intervention. CONCLUSIONS The treatment of NCS includes observation, percutaneous angioplasty, open or endovascular surgery, or nephrectomy. In patients younger than 18 years of age, the best option is a conservative approach with observation for at least two years, as approximately 75% of patients have complete resolution of hematuria.