Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Exposure To Effluent From Pharmaceutical Industry Induced Cytogenotoxicity, Hematological And Histopathological Alterations In Clarias Gariepinus (Burchell, 1822)

Pharmaceutical effluents contain toxic xenobiotics capable of contaminating aquatic environments. Untreated effluents are illegally discharged into aquatic environment in most developing countries. Pharmaceutical effluent induced alterations in biomarkers of genetic and systemic damage on rodents. However, information is relatively scarce on the possible cytogenotoxicity and systemic toxicity of this effluent on aquatic vertebrates. The study herein assessed the cytogenotoxic, hematological and histopathological alterations induced by pharmaceutical effluent in Clarias gariepinus. 96 h acute toxicity of the effluent was determined after C. gariepinus was exposed to six different concentrations (10 - 60 %) of the effluent. Subsequently, fish was exposed to sub-lethal concen-trations (2.18 - 17.41 %) obtained from the 96 h LC50 for 7 and 14 days after which micronucleus (MN) and nu-clear abnormalities (NAs) in peripheral erythrocytes were assessed as cytogenotoxic biomarkers, alterations in hematological indices and histopathological lesions were also examined. Fish, concurrently exposed to dechlo-rinated tap water and benzene (0.01 mL/L), served as negative and positive controls respectively. The derived 96 h LC50 of 17.41 % which was 1.89 times more toxic than the 24 h LC50 (32.95 %) showed that the effluent induced concentration-dependent mortality according to exposure duration. The effluent caused significant (p<0.05) time-dependent increase in the frequency of MN and abnormal nuclear erythrocytes compared to the negative control. Also, there was decrease in total erythrocyte counts, hemoglobin and hematocrit concentrations and increase in leucocyte and lymphocyte counts. The effluent induced pathological lesions on gills, liver and kidneys of treated fish. Higher physicochemical parameters than standard permissible limits in the effluent are capable of inducing genomic instability and systemic damage in fish. Pharmaceutical effluent can increase micropollutants in aquatic environmental and health risks to aquatic biota. There is need to promulgate stringent laws against illegal discharge of effluents into aquatic environment

Exposure to effluent from pharmaceutical industry induced cytogenotoxicity, hematological and histopathological alterations in Clarias gariepinus (Burchell, 1822)

Pharmaceutical effluents contain toxic xenobiotics capable of contaminating aquatic environments. Untreated effluents are illegally discharged into aquatic environment in most developing countries. Pharmaceutical effluent induced alterations in biomarkers of genetic and systemic damage on rodents. However, information is relatively scarce on the possible cytogenotoxicity and systemic toxicity of this effluent on aquatic ertebrates. The study herein assessed the cytogenotoxic, hematological and histopathological alterations induced by pharmaceutical effluent in Clarias gariepinus. 96 h acute toxicity of the effluent was determined after C. gariepinus was exposed to six different concentrations (10 - 60 %) of the effluent. Subsequently, fish was exposed to sub-lethal concentrations (2.18 - 17.41 %) obtained from the 96 h LC50 for 7 and 14 days after which micronucleus (MN) and nuclear abnormalities (NAs) in peripheral erythrocytes were assessed as cytogenotoxic biomarkers, alterations in hematological indices and histopathological lesions were also examined. Fish, concurrently exposed to dechlorinated tap water and benzene (0.01 mL/L), served as negative and positive controls respectively. The derived 96 h LC50 of 17.41 % which was 1.89 times more toxic than the 24 h LC50 (32.95 %) showed that the effluent induced concentration-dependent mortality according to exposure duration. The effluent caused significant (p<0.05) time-dependent increase in the frequency of MN and abnormal nuclear erythrocytes compared to the negative control. Also, there was decrease in total erythrocyte counts, hemoglobin and hematocrit concentrations and increase in leucocyte and lymphocyte counts. The effluent induced pathological lesions on gills, liver and kidneys of treated fish. Higher physicochemical parameters than standard permissible limits in the effluent are capable of inducing genomic instability and systemic damage in fish. Pharmaceutical effluent can increase micropollutants in aquatic environmental and health risks to aquatic biota. There is need to promulgate stringent laws against illegal discharge of effluents into aquatic environment

Modulatory Effect of Baphia Nitida Dye in Toluene Induced Cytogenotoxicity, Hematotoxicity and Histopathology in Dermal Exposed Wistar Rats

Background: There is unprecedented increase in the processing and packaging of many plant materials into food supplements, herbal medicine, skincare and cosmetic products for human needs. Baphia nitida is used for topical skincare products. Toluene, a toxic aromatic solvent, is increasingly being used in the production of these skincare and cosmetic products in many industries. This study assessed toluene toxicological profile and the ability of Baphia nitida dye to ameliorate toluene induced cytogenotoxicity, hematotoxicity and histopathological effects in rats. Methods: Rats were treated with various concentrations; 0, 1000, 2000 and 5000 mg of the aqueous, ethanol and toluene processed B. nitida dye via dermal exposure for acute and sub-lethal toxicity. 96 h acute toxicity was assessed for the solvents. Micronuclei induction, alterations in hematological indices and erythrocyte morphology and skin histology were assessed after sub-lethal treatment. Results: 96 h LD50 of B. nitida processed dye for the three solvents were indeterminate. There was insignificant (p>0.05) alterations in the hematological indices and erythrocyte morphology, induction of micronucleated polychromatic erythrocyte and polychromatic and normochromatic erythrocyte ratio in the aqueous and ethanol processed B. nitida treated rats compared to their corresponding controls. Toluene induced significant (p<0.05) decrease in erythrocytes count, hematocrit and leucocytes, increased micronucleated PCE, decreased PCE/NCE ratio and induced necrosis, thick dermal layer and dispersed areolar tissues in treated rats. But, these effects were ameliorated by the B. nitida dye. Conclusion: Camwood dye protects against toluene induced toxicity in rats. This suggests its relative safety in topical cosmetic and skincare production

Association of adiponectin gene (ADIPOQ) polymorphisms with measures of obesity in Nigerian young adults

Background: The association of obesity with adiponectin gene has been reported in different populations with various inconsistencies. Data from Nigeria is very scanty on the association. Aim: We investigated possible associations of adiponectin gene (ADIPOQ) single nucleotide polymorphisms (SNPs) rs2241766 (+45T>G in exon 2), rs266729 (−11377C>G in promoter) and rs1501299 (+276G>T in intron 2) with body mass index (BMI), waist circumference (WC) and hip circumference (HC), in our cross-sectional study. Subjects and methods: SNPs in ADIPOQ were genotyped in 107 subjects (81 females, 26 males; mean age 22.2 years) by Sequenom MassARRAY. Notably, rs2241766 was removed for not reaching Hardy-Weinberg equilibrium. BMI was calculated (kg/m2) while WC and HC were measured using standard procedures Results: Linear regression showed that variant rs1501299 was not associated with BMI, WC or HC but rs266729 was associated with increased measures of obesity involving BMI (recessive model; beta coefficient [β], 12.85; 95% confidence interval [CI], 6.47, 19.24, codominant model; GG, β, 13.08; 95% CI, 6.71, 19.46, GC, β, 1.04; 95% CI, −0.60, 2.68 and log-additive model; β, 2.117; 95% CI, 0.55, 3.68), WC (recessive model; β, 22.17; 95% CI, 7.11, 37.23 and codominant model; GG, β, 21.857; 95% CI, 6.74, 36.98, GC, β, −1.459; 95% CI, −5.34, 2.43) and HC (recessive model; β, 33.56; 95% CI, 15.41, 51.70, codominant model; GG, β, 34.171; 95% CI, 16.04, 52.30, GC, β, 2.771; 95% CI, −1.79, 7.34 and log-additive model; β, 5.466; 95% CI, 1.14, 9.80). Conclusion: This study in young Nigerian adults confirmed previously reported association of SNP −11377C>G with obesity measures in other populations. Keywords: Obesity, rs2241766, rs1501299, rs266729, Nigeri

Management and Outcomes Following Surgery for Gastrointestinal Typhoid: An International, Prospective, Multicentre Cohort Study

Background: Gastrointestinal perforation is the most serious complication of typhoid fever, with a high disease burden in low-income countries. Reliable, prospective, contemporary surgical outcome data are scarce in these settings. This study aimed to investigate surgical outcomes following surgery for intestinal typhoid. Methods: Two multicentre, international prospective cohort studies of consecutive patients undergoing surgery for gastrointestinal typhoid perforation were conducted. Outcomes were measured at 30 days and included mortality, surgical site infection, organ space infection and reintervention rate. Multilevel logistic regression models were used to adjust for clinically plausible explanatory variables. Effect estimates are expressed as odds ratios (ORs) alongside their corresponding 95% confidence intervals. Results: A total of 88 patients across the GlobalSurg 1 and GlobalSurg 2 studies were included, from 11 countries. Children comprised 38.6% (34/88) of included patients. Most patients (87/88) had intestinal perforation. The 30-day mortality rate was 9.1% (8/88), which was higher in children (14.7 vs. 5.6%). Surgical site infection was common, at 67.0% (59/88). Organ site infection was common, with 10.2% of patients affected. An ASA grade of III and above was a strong predictor of 30-day post-operative mortality, at the univariable level and following adjustment for explanatory variables (OR 15.82, 95% CI 1.53–163.57, p = 0.021). Conclusions: With high mortality and complication rates, outcomes from surgery for intestinal typhoid remain poor. Future studies in this area should focus on sustainable interventions which can reduce perioperative morbidity. At a policy level, improving these outcomes will require both surgical and public health system advances

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Global economic burden of unmet surgical need for appendicitis

Background There is a substantial gap in provision of adequate surgical care in many low- and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially