Clinicopathological presentation and management outcome of appendicitis in Gombe, north-east Nigeria: A 7-year retrospective audit

Background: Acute appendicitis is a common cause of acute abdomen and right iliac fossa pain in the study centre with attendant negative appendicectomies.Aim: To study the demographic pattern,aetiology,clinical presentation and management outcome of appendicitis.Methods: This is a retrospective study carried out on patients, who had appendicectomies between January 2007 and December 2014.A total of two hundred and thirteen (213) cases were operated during the study period. Only one hundred and forty one (141) folders retrieved. Relevant clinical information were entered in to a proforma designed for the study. Statistical analysis was done using Epi info (version 3.5.1). Quantitative data were presented in frequencies and percentages,mean and standard deviations were calculated.Result: Out of the 141 patients, 55(39.0%) were males while 86(61.0%) were females giving a M:F= 1: 1.6 .Their ages range from 8 to 65 years .The peak age group was 21-30 years.Acute inflammation was seen in 69 (48.9%) patients,lymphoid hyperplasia in 39 (27.7%) patients while parasitic appendicitis was seen in one (0.7%) patient. Post-operative complications observed include surgical site infection in 7 (5.0%) patients, delayed wound healing in 11( 7.8%) patients and enterocutaneous fistula in one( 0.7%) patient.Conclusion: The diagnosis of appendicitis still rests on the pillars of thorough clinical evaluation.The judicious use of modern diagnostic equipment will reduce the rate of negative appendicectomies.Keywords: Appendicitis,demography,aetiology,management outcom

Prevalence and associated risk factors of ante‑partum hemorrhage among Arab women in an economically fast growing society

Objective: The aim of this study was to determine the prevalence and associated risk factors of antepartum hemorrhage (APH) in the third trimester of Arab women residing in Qatar and their neonatal outcome.Design and Setting: A prospective hospital‑based study was conducted in the Women’s Hospital and Maternity Clinics.Materials and Methods: The study was based on pregnant women in the third trimester from the first week of January 2010 to April 2011. A total of 2,056 pregnant women, who had any kind of maternal complications, were approached and 1,608 women (78.2%) expressed their consent to participate in the study. The questionnaire covered variables related to socio‑demographic factors, family history, medical history, maternal complications and neonatal outcome. Multiple logistic regressions were used to describe the association between socio‑demographic factors and APH.Results: The overall prevalence of APH among Arab women residing in Qatar was 15.3% with 6.7% among Qatari’s and 8.6% among non‑Qatari Arab women; the difference in ethnicities was not significant. Among maternal socio‑demographic characteristics, lower education (primary or below AOR 1.72; 95%CI 1.22‑2.43, and intermediate education AOR 1.41; 95%CI 0.88‑2.26; P=0.005) compared to university education was significantly associated with APH. As for maternal biological characteristics, family history of G6PD (AOR 1.87; 95% CI 1.18‑2.95; P=0.007) and family history of Down’s Syndrome (AOR 1.88; 95%CI 1.35‑2.62; P=<0.001) were significantly associated with APH at the multivariable level; family history of hypertension (OR 1.78; 95%CI 1.30‑2.44; P<0.001) was significant at the univariate level. Neonatal outcomes as a result of APH included increased risk of Apgar score at 1 minutes <7 (AOR 1.44; 95%CI 1.12‑2.02; P=0.04) and minor congenital anomaly (AOR 2.82; 95%CI 1.39‑5.71; P=0.004).Conclusion: Qatar has a high prevalence of APH. Poor education, family history of hypertension, G6PD and Down’s syndrome were found to be significantly associated with increased risk of APH in Qatar. Neonates of APH are at significantly increased risk of adverse outcome. Thus it is essential that obstetricians are alerted to these risk factors for early detection and to decrease the negative effects of APH

In vitro multiplication of the rare and endangered slipper orchid, Paphiopedilum rothschildianum (Orchidaceae)

Paphiopedilum rothschildianum is an endangered orchid species endemic to Mount Kinabalu, Sabah, and Malaysia. The vegetative propagation of this plant has always been restricted due to its slow growth and maturation rates. Thus, an in vitro tissue culture technique was explored in order to overcome this limitation. In this study, clonal propagation of P. rothschildianum was achieved through in vitro formation of multiple shoots from stem nodal and single shoot explants cultured onto halfstrength Murashige and Skoog medium. The responses of the explants to the presence of different types of organic nitrogen additives viz. casein hydrolysate, peptone and tryptone-peptone (in amount of 0.5, 1.0 and 2.0 g/l) in the culture medium were also evaluated. The addition of these organic nitrogen additives into the basal medium slightly enhanced the number of multiple shoots formed on both types of explants when compared to additive-free MS medium. After 16 weeks of culture, an average of 2.9 shoots per stem nodal explant and 2.8 shoots per single shoot explant were obtained on half-strength MS medium supplemented with 1.0 g/l peptone and 2.0 g/l tryptone-peptone, respectively. All the newly-formed shoots were divided into single plantlets and subcultured onto similar respective medium. After an additional 12 weeks of culture on the same medium, plantlets with 3 - 4 roots were acclimatized and transferred to a glass house where they showed 90% survival rate. Thus, the method presented in this study had provided a promising strategy for the production of large numbers of phenotypically stable P. rothschildianum

Transcriptomic analyses of myeloid-derived suppressor cell subsets in the circulation of colorectal cancer patients

Myeloid-derived suppressor cells (MDSCs) promote tumor immune evasion and favor tumorigenesis by activating various tumor-promoting downstream signals. MDSC expansion is evident in the circulation and tumor microenvironment of many solid tumors including colorectal cancer (CRC). We have recently reported the transcriptomic profiles of tumor-infiltrating MDSCs in CRC patients and uncovered pathways, which could potentially assist tumor progression. In this study, we sorted different subsets of circulating MDSCs in CRC patients and investigated their transcriptomic profiles in order to disclose pathways, which could potentially contribute to disease progression. The sorted subsets included polymorphonuclear/granulocytic MDSCs (PMN-MDSCs), immature MDSCs (I-MDSCs), and monocytic MDSCs (M-MDSCs). Our functional annotation analyses revealed that multiple pathways including DNA damage-, chemotaxis-, apoptosis-, mitogen-activated protein kinase-, transforming growth factor β-, and myeloid differentiation–related transcripts were higher in PMN-MDSCs, compared with monocytic antigen-presenting cells (APCs) or I-MDSCs. Furthermore, genes related to Janus kinase (JAK)–signal transducer and activator of transcription (STAT) were also elevated in PMN-MDSCs. These data suggest that upregulation of JAK-STAT pathway could trigger multiple downstream targets in PMN-MDSCs, which favor tumor progression. Additionally, we found that pathways including phosphatidyl inositol 3-kinase (PI3K), interleukin 6, and TGF-β in M-MDSCs and cell cycle–related pathways in I-MDSCs were upregulated, compared with monocytic APCs. Moreover, acetylation-related genes were upregulated in both PMN-MDSCs and M-MDSCs. This latter finding implicates that epigenetic modifications could also play a role in the regulation of multiple tumor-promoting genes in PMN-MDSCs and M-MDSCs. Taken together, this study reveals various signaling pathways, which regulate the function of MDSC subsets in the circulation of CRC patients. However, functional studies are warranted to support these findings

Transcriptomic profiling disclosed the role of DNA methylation and histone modifications in tumor-infiltrating myeloid-derived suppressor cell subsets in colorectal cancer

Increased numbers of myeloid-derived suppressor cells (MDSCs) are positively correlated with poor prognosis and reduced survivals of cancer patients. They play central roles in tumor immune evasion and tumor metastasis. However, limited data are available on phenotypic/transcriptomic characteristics of the different MDSCs subsets in cancer. These cells include immature (I-MDSCs), monocytic (M-MDSCs), and polymorphonuclear/granulocytic (PMN-MDSCs). Phenotypic characterization of myeloid subsets from 27 colorectal cancer (CRC) patients was assessed by flow cytometric analyses. RNA-sequencing of sorted I-MDSCs, PMN-MDSCs, and antigen-presenting cells (APCs) was also performed. We found that the levels of I-MDSCs and PMN-MDSCs were increased in tumor tissues (TT), compared with normal tissues (NT) in colorectal cancer. Our functional annotation analyses showed that genes associated with histone deacetylase (HDAC) activation- and DNA methylation-mediated transcriptional silencing were upregulated, and histone acetyl transferase (HAT)-related genes were downregulated in tumor-infiltrating I-MDSCs. Moreover, pathways implicated in cell trafficking and immune suppression, including Wnt, interleukin-6 (IL-6), and mitogen-activated protein kinase (MAPK) signaling, were upregulated in I-MDSCs. Notably, PMN-MDSCs showed downregulation in genes related to DNA methylation and HDAC binding. Using an ex vivo model, we found that inhibition of HDAC activation or neutralization of IL-6 in CRC tumor tissues downregulates the expression of genes associated with immunosuppression and myeloid cell chemotaxis, confirming the importance of HDAC activation and IL-6 signaling pathway in MDSC function and chemotaxis. This study provides novel insights into the epigenetic regulations and other molecular pathways in different myeloid cell subsets within the CRC tumor microenvironment (TME), giving opportunities to potential targets for therapeutic benefits

Analysis of expressed sequence tags derived from inflorescence shoot of ,i>Tectona grandis (teak)

Teak Inflorescence Shoot Stage 4 (TIS4) shoots bearing the floral meristems were used to construct a cDNA librariy with insert size range of 1500 - 5000 bp. The titer of the library was 7.5 x 105 pfu/ml(primary) and 4.5 x 109 pfu/ml (amplified). EST generation and analysis were performed using the cDNA library where a total of 1384 plaques were randomly picked and their inserts PCR-amplified using T3and T7 universal primers. Only 1125 plaques generated single amplified fragments, each which were purified and sequenced using the SK universal primer. The generated raw 5’ ESTs were filtered and clustered. A total of 674 nonredundants (69 consensus sequences and 605 singletons) were generated and their identities searched through BLASTX. Of the 674 nonredundants, 107 of them (15.9%) showed no hits or no identity. All the 567 nonredundants identified through BLASTX were categorized into theirfunctional categories and were further analysed using InterProScan to detect their protein signatures and to assign their GO numbers. From all the sequences analysed, only 186 (32.8%) sequences were given the GO numbers and grouped into the three GO main categories namely biological process, cellular component and molecular function. Several important ESTs were highlighted based on their functional categories. There were five sequences found to be related to flowering and light induction

Effect of Bone Marrow-derived Mesenchymal Stem Cells and Umbilical Cord Blood-CD34+ cells on Experimental Rat liver Fibrosis

Background and Objective: Liver disease is one of the major causes of death in many countries. Hence, the development of effective therapies for liver fibrosis is a major aim of medical research. So this study was designed to investigate the therapeutical role of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) transplantation in the experimental rat liver fibrosis. Design and Method: Bone marrow-derived MSCs were isolated from femoral and tibial bones of male albino rats, then were grown and propagated in culture for 2 weeks and were characterized morphologically and by detection of CD29 by real time-PCR. Human umbilical cord blood cells were obtained after full-term caesarean delivery from healthy donors after written informed consent. Low-density mononuclear cells were separated over Ficoll- Paque (Gibco-Invitrogen, Grand Island, NY), and then CD34+ HSC was isolated using a magnetic cell sorter (MiniMACS; Miltenyi Biotec, Bergisch Gladbach, Germany). The cells were then infused intraperitoneally in rats that received CCl4 injection to induce liver fibrosis. Rats were divided into 4 groups: control, CCl4, CCl4 plus MSC, and CCl4 plus CD34+. Liver tissue was examined histopathologically for all groups. The expression of collagen I and metalloproteinase-2 genes as a marker of liver fibrosis was measured by real time RT- PCR. Results: The results of the present study showed that both MSCs and CD34+ have a significant antifibrotic effect as evidenced by the significant decrease in liver collagen gene expression as well as the decrease in MMP-2 (p < 0.05) compared to the CCl4 group

RNA-seq analysis of colorectal tumor-infiltrating myeloid-derived suppressor cell subsets revealed gene signatures of poor prognosis

Elevated levels of myeloid-derived suppressor cells (MDSCs), including polymorphonuclear MDSCs (PMN-MDSCs) and immature MDSCs (I-MDSCs), are usually associated with disease progression in cancer patients, including colorectal cancer (CRC). However, biological mechanisms and molecular pathways regulated by MDSC subpopulations in the CRC tumor microenvironment (TME) have not been fully investigated. In this study, we performed transcriptomic analysis of tumor-infiltrating I-MDSCs and PMN-MDSCs isolated from tumor tissues of six CRC patients, compared to antigen-presenting cells (APCs). We also compared the transcriptomic profiles of tumor-infiltrating PMN-MDSCs to I-MDSCs. Our results showed different molecular pathways regulated by each MDSC subset, potentially reflecting their phenotypical/molecular/functional characteristics in the CRC TME. Moreover, we identified gene signatures in PMN-MDSC and I-MDSC of poor overall survival (OS) and disease-free survival (DFS) using the Cancer Genome Atlas (TCGA) dataset from patients with colon adenocarcinoma (COAD). However, functional studies are required to validate these findings

Polymorphisms in Cyclooxygenase, Lipoxygenase and TP53 genes predict colorectal polyp risk reduction by aspirin in the seAFOod polyp prevention trial

Aspirin and eicosapentaenoic acid (EPA) reduce colorectal adenomatous polyp risk and affect synthesis of oxylipins including prostaglandin E2. We investigated whether 35 single nucleotide polymorphisms (SNPs) in oxylipin metabolism genes such as cyclooxygenase [PTGS] and lipoxygenase [ALOX], as well as 7 SNPs already associated with colorectal cancer (CRC) risk reduction by aspirin (eg. TP53; rs104522), modified the effects of aspirin and EPA on colorectal polyp recurrence in the randomised 2x2 factorial seAFOod trial. Treatment effects were reported as the incidence rate ratio (IRR) and 95% confidence interval (CI) by stratifying negative binomial and Poisson regression analyses of colorectal polyp risk on SNP genotype. Statistical significance was reported with adjustment for the false discovery rate as the P and q value. Five hundred and forty-two (of 707) trial participants had both genotype and colonoscopy outcome data. Reduction in colorectal polyp risk in aspirin users compared with non-aspirin users was restricted to rs4837960 (PTGS1) common homozygotes (IRR 0.69 [95%CI 0.53,0.90]; q=0.06), rs2745557 (PTGS2) compound heterozygote-rare homozygotes (IRR 0.60 [0.41,0.88]; q=0.06), rs7090328 (ALOX5) rare homozygotes (IRR 0.27 [0.11,0.64]; q=0.05), rs2073438 (ALOX12) common homozygotes (IRR 0.57 [0.41,0.80]; q=0.05), and rs104522 (TP53) rare homozygotes (IRR 0.37 [0.17,0.79]; q=0.06). No modification of colorectal polyp risk in EPA users was observed. In conclusion, genetic variants relevant to the proposed mechanism of action on oxylipins are associated with differential colorectal polyp risk reduction by aspirin in individuals who develop multiple colorectal polyps. SNP genotypes should be considered during development of personalised, predictive models of CRC chemoprevention by aspirin

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation