Biallelic variants in SLC38A3 encoding a glutamine transporter cause epileptic encephalopathy

The solute carrier (SLC) superfamily encompasses >400 transmembrane transporters involved in the exchange of amino acids, nutrients, ions, metals, neurotransmitters and metabolites across biological membranes. SLCs are highly expressed in the mammalian brain; defects in nearly 100 unique SLC-encoding genes (OMIM: https://www.omim.org) are associated with rare Mendelian disorders including developmental and epileptic encephalopathy (DEE) and severe neurodevelopmental disorders (NDDs). Exome sequencing and family-based rare variant analyses on a cohort with NDD identified two siblings with DEE and a shared deleterious homozygous splicing variant in SLC38A3. The gene encodes SNAT3, a sodium-coupled neutral amino acid transporter and a principal transporter of the amino acids asparagine, histidine, and glutamine, the latter being the precursor for the neurotransmitters GABA and glutamate. Additional subjects with a similar DEE phenotype and biallelic predicted-damaging SLC38A3 variants were ascertained through GeneMatcher and collaborations with research and clinical molecular diagnostic laboratories. Untargeted metabolomic analysis was performed to identify novel metabolic biomarkers. Ten individuals from seven unrelated families from six different countries with deleterious biallelic variants in SLC38A3 were identified. Global developmental delay, intellectual disability, hypotonia, and absent speech were common features while microcephaly, epilepsy, and visual impairment were present in the majority. Epilepsy was drug-resistant in half. Metabolomic analysis revealed perturbations of glutamate, histidine, and nitrogen metabolism in plasma, urine, and cerebrospinal fluid of selected subjects, potentially representing biomarkers of disease. Our data support the contention that SLC38A3 is a novel disease gene for DEE and illuminate the likely pathophysiology of the disease as perturbations in glutamine homeostasis

Hybrid method for selection of the optimal process of leachate treatment in waste treatment and valorization plants or landfills

“The final publication is available at Springer via http://dx.doi.org/10.1007/s10098-014-0834-4”Leachate from waste landfill or treatment plants is a very complex and highly contaminated liquid effluent. In its composition, it is found dissolved organic matter, inorganic salts, heavy metals, and other xenobiotic organic compounds, so it can be toxic, carcinogenic, and capable of inducing a potential risk to biota and humans. European law does not allow such leachate to leave the premises without being depolluted. There are many procedures that enable debugging, always combining different techniques. Choosing the best method to use in each case is a complex decision, as it depends on many tangible and intangible factors that must be weighed to achieve a balance between technical, cost, and environmental sustainability. It is presenting a hybrid method for choosing the optimal combination of techniques to apply in each case, by combining a multicriteria hierarchical analysis based on expert data obtained by the Delphi method with an analysis by the method of VIKOR to reach a consensus solution.Martín Utrillas, MG.; Reyes Medina, M.; Curiel Esparza, J.; Cantó Perelló, J. (2015). Hybrid method for selection of the optimal process of leachate treatment in waste treatment and valorization plants or landfills. Clean Technologies and Environmental Policy. 17(4):873-885. doi:10.1007/s10098-014-0834-4S873885174Abbas AA, Guo J, Ping LZ, Ya PY, Al-Rekabi WS (2009) Review on landfill leachate treatments. AJAS 6(4):672–684Abood AR, Bao J, Abudi Z, Zheng D, Gao C (2013) Pretreatment of nonbiodegradable landfill leachate by air stripping coupled with agitation as ammonia stripping and coagulation–flocculation processes. Clean Technol Environ Policy 15(6):1069–1076Ahn WY, Kang MS, Yim SK, Choi KH (2002) Advanced landfill leachate treatment using an integrated membrane process. Desalination 149(1–3):109–114Al-Subhi Al-Harbi KM (2001) Application of the AHP in project management. Int J Proj Manag 19:19–27Bernasconi M, Choirat C, Seri R (2014) Empirical properties of group preference aggregation methods employed in AHP: theory and evidence. Eur J Oper Res 232(3):584–592Boopathy R, Karthikeyan S, Mandal AB, Sekaran G (2013) Characterization and recovery of sodium chloride from salt-laden solid waste generated from leather industry. Clean Technol Environ Policy 15(1):117–124Brechet T, Tulkens H (2009) Beyond BAT: selecting optimal combinations of available techniques, with an example from the limestone industry. J Environ Manag 90:1790–1801Canto-Perello J, Curiel-Esparza J, Calvo V (2013) Criticality and threat analysis on utility tunnels for planning security policies of utilities in urban underground space. Expert Syst Appl 40(11):4707–4714Chen Y, Liu C, Nie J, Wu S, Wang D (2014) Removal of COD and decolorizing from landfill leachate by Fenton’s reagent advanced oxidation. Clean Technol Environ Policy 16(1):189–193Chiochetta CG, Goetten LC, Almeida SM, Quaranta G, Cotelle S, Radetski CM (2014) Leachates from solid wastes: chemical and eco(geno)toxicological differences between leachates obtained from fresh and stabilized industrial organic sludge. Environ Sci Pollut R 21:1090–1098Chiumenti A, da Borso F, Chiumenti R, Teri F, Segantin P (2013) Treatment of digestate from a co-digestion biogas plant by means of vacuum evaporation: tests for process optimization and environmental sustainability. Waste Manag 33(6):1339–1344Council Directive 1999/31/EC (1999) April 26th 1999, on the landfill of waste. European Union Council, Official Journal L 182, 16/07/1999 P. 0001–0019Curiel-Esparza J, Canto-Perello J (2012) Understanding the major drivers for implementation of municipal sustainable policies in underground space. Int J Sust Dev World 19(6):506–514Curiel-Esparza J, Canto-Perello J (2013) Selecting utilities placement techniques in urban underground engineering. Arch Civ Mech Eng 13(2):276–285Curiel-Esparza J, Canto-Perello J, Calvo MA (2004) Establishing sustainable strategies in urban underground engineering. Sci Eng Ethics 10(3):523–530Dong Y, Zhang G, Hong WC, Xu Y (2010) Consensus models for AHP group decision making under row geometric mean prioritization method. Decis Support Syst 49:281–289Duckstein L, Opricovic S (1980) Multiobjective Optimization in River Basin Development. Water Resour Res 16(1):14–20Ersahin ME, Ozgun H, van Lier JB (2013) Effect of support material properties on dynamic membrane filtration performance. Separ Sci Technol 48(15):2263–2269Gracht HA (2012) Consensus measurement in Delphi studies, review and implications for future quality assurance. Forecast Soc Chang 79(8):1525–1536Grisey E, Laffray X, Contoz O, Cavalli E, Mudry J, Aleya L (2012) The bioaccumulation performance of reeds and cattails in a constructed treatment wetland for removal of heavy metals in landfill leachate treatment (Etueffont, France). Water Air Soil Pollut 223:1723–1741Guoliang Z, Lei Q, Qin M, Zheng F, Dexin W (2013) Aerobic SMBR/reverse osmosis system enhanced by Fenton oxidation for advanced treatment of old municipal landfill leachate. Bioresour Technol 142:261–268Gupta SK, Singh G (2007) Assessment of the Efficiency and Economic Viability of Various Methods of Treatment of Sanitary Landfill Leachate. Environ Monit Assess 135:107–117Heyer KU, Stegmann R (2005) Landfill systems, sanitary landfilling of solid wastes, and long-term problems with leachate. In: Jördening HJ, Winter J (eds) Environmental Biotechnology. Wiley-VCH, Weinheim, p 375Hsu CC, Sandord BA (2007) The Delphi technique: making sense of consensus. PARE 12(10):1–7Kjeldsen P, Barlaz MA, Rooker AP, Baun A, Ledin A, Christensen TH (2002) Present and long-term composition of MSW landfill leachate: a review. Crit Rev Environ Sci Technol 32(4):297–336Lee WS (2013) Merger and acquisition evaluation and decision making model. Serv Ind J 33(15–16):1473–1494Lee GKL, Chan EHW (2008) The analytic hierarchy process (AHP) approach for assessment of urban renewal proposals. Soc Indic Res 89(1):155–168Li G, Wang W, Du Q (2010) Applicability of nanofiltration for the advanced treatment of landfill leachate. J Appl Polym Sci 116(4):2343–2347Mela K, Tiainen T, Heinisuo M (2012) Comparative study of multiple criteria decision making methods for building design. Adv Eng Inform 26:716–726Ozdemir MS, Saaty TL (2006) The unknown in decision making, what to do about it. Eur J Oper Res 174(1):349–359Renou S, Givaudan JG, Poulain S, Dirassouyan F, Moulin P (2008) Landfill leachate treatment: review and opportunity. J Hazard Mater 150(3):468–493Ritzkowski M, Stegmann R (2012) Landfill aeration worldwide: concepts, indications and findings. Waste Manag 32(7):1411–1419Romero C, Ramos P, Costa C, Marquez MC (2013) Raw and digested municipal waste compost leachate as potential fertilizer: comparison with a commercial fertilizer. J Clean Prod 59:73–78Roubelat F (2011) The Delphi method as a ritual: inquiring the Delphi Oracle. Forecast Soc Chang 78(9):1491–1499Saaty TL (1980) The analytic hierarchy process. Mc Graw-Hill, New YorkSaaty TL (2001) Decision making with dependence and feedback: the analytic network process, 2nd edn. RWS Publications, PittsburghSaaty TL (2008) Decision making with the analytic hierarchy process. Int J Serv Sci 1(1):83–98Saaty TL (2012) Decision making for leaders. The analytic hierarchy process for decisions in a complex world, 3rd edn. RWS Publications, PittsburghSan Cristobal J (2012) Contractor selection using multicriteria decision-making methods. J Constr Eng M 138(6):751–758Sayadi MK, Heydari M, Shahanaghi K (2009) Extension of VIKOR method for decision making problem with interval numbers. Appl Math Model 33:2257–2262Statnikova RB, Bordetskya A, Statnikov A (2005) Multi-criteria analysis of real-life engineering optimization problems: statement and solution. Nonlinear Anal 63:685–696Syamsuddin J (2010) The use of AHP in security policy decision making: an open office calc application. JSW 5(10):1162–1169Thapa RB, Murayama Y (2010) Drivers of urban growth in the Kathmandu valley, Nepal: examining the efficacy of the analytic hierarchy process. App Geogr 30(1):70–83van Praagh M, Heerenklage J, Smidt E, Modin H, Stegmann R, Persson KM (2009) Potential emissions from two mechanically–biologically pretreated (MBT) wastes. Waste Manag 29(2):859–868Vedaraman N, Shamshath BS, Srinivasan SV (2013) Response surface methodology for decolourisation of leather dye using ozonation in a packed bed reactor. Clean Technol Environ Policy 15(4):607–616Wang Q, Matsufuji Y, Dong L, Huang Q, Hirano F, Tanaka A (2006) Research on leachate recirculation from different types of landfills. Waste Manag 26:815–824Xing W, Lu W, Zhao Y (2013) Environmental impact assessment of leachate recirculation in landfill of municipal solid waste by comparing with evaporation and discharge (EASEWASTE). Waste Manag 33(2):382–389Yang W, Zhang KN, Chen YG, Zhou XZ, Jin FX (2013) Prediction on contaminant migration in aquifer of fractured granite substrata of landfill. J Cent South Univ 20(11):3193–3201Zavadskas EK, Turskis Z, Tamosaitiene J (2011) Selection of construction enterprises management strategy based on SWOT and multi-criteria analysis. ACME 11(4):1063–108

Variations in the prevalence of point (pre)hypertension in a Nigerian school-going adolescent population living in a semi-urban and an urban area

<p>Abstract</p> <p>Background</p> <p>Hypertension has been shown to start in early life and to track into adulthood. Detecting adolescents with hypertension and prehypertension will aid early intervention and reduce morbidity and mortality from the disorders. This study reports the point-prevalence of the two disorders in a semi-urban and an urban population of school-going adolescents in Nigeria.</p> <p>Methods</p> <p>A total of 843 adolescents from two places of domicile were studied. Their blood pressures and anthropometric indices were measured using standard protocol. Point-hypertension and point-prehypertension were defined with respect to each subject's gender, age and height. The prevalence of the disorders was calculated and reported age-wise and nutritional status-wise.</p> <p>Results</p> <p>The prevalence of point-prehypertension in the semi-urban area was 22.2% (20.7% for girls and 23.1% for boys) while it was 25.0% (21.8% for girls and 29.2% for boys) in the urban area. The prevalence of point-hypertension was 4.6% (4.1% for girls and 4.8% for boys) in the semi-urban area and 17.5% (18.0% for girls and 16.9% for boys) in the urban area. Point-prehypertension was not detected among the thin subjects of both places of domicile. The prevalence of point-prehypertension was similar in both the urban and semi-urban areas among the subjects who had normal BMI-for-age, and over-weight/obese subjects respectively. From the semi-urban to the urban area, the prevalence of point-hypertension increased approximately 3-folds among thin and normal BMI-for-age subjects, and 10-folds among overweight/obese subjects. Systolic hypertension was more preponderant in both the semi-urban and urban areas.</p> <p>Conclusions</p> <p>The prevalence of both disorders is considerably high in the studied populations. Urgent pediatric public health action is needed to address the situation.</p

Identification of a Shared Genetic Susceptibility Locus for Coronary Heart Disease and Periodontitis

Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases. We confirm the known association of two neighboring linkage disequilibrium regions on human chromosome 9p21.3 with CHD and show the additional strong association of these loci with the risk of aggressive periodontitis. For the lead SNP of the main associated linkage disequilibrium region, rs1333048, the odds ratio of the autosomal-recessive mode of inheritance is 1.99 (95% confidence interval 1.33–2.94; P = 6.9×10−4) for generalized aggressive periodontitis, and 1.72 (1.06–2.76; P = 2.6×10−2) for localized aggressive periodontitis. The two associated linkage disequilibrium regions map to the sequence of the large antisense noncoding RNA ANRIL, which partly overlaps regulatory and coding sequences of CDKN2A/CDKN2B. A closely located diabetes-associated variant was independent of the CHD and periodontitis risk haplotypes. Our study demonstrates that CHD and periodontitis are genetically related by at least one susceptibility locus, which is possibly involved in ANRIL activity and independent of diabetes associated risk variants within this region. Elucidation of the interplay of ANRIL transcript variants and their involvement in increased susceptibility to the interactive diseases CHD and periodontitis promises new insight into the underlying shared pathogenic mechanisms of these complex common diseases

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Status and Trends of Physical Activity Surveillance, Policy, and Research in 164 Countries: Findings From the Global Observatory for Physical Activity—GoPA! 2015 and 2020 Surveys

Background: Physical activity (PA) surveillance, policy, and research efforts need to be periodically appraised to gain insight into national and global capacities for PA promotion. The aim of this paper was to assess the status and trends in PA surveillance, policy, and research in 164 countries. Methods: We used data from the Global Observatory for Physical Activity (GoPA!) 2015 and 2020 surveys. Comprehensive searches were performed for each country to determine the level of development of their PA surveillance, policy, and research, and the findings were verified by the GoPA! Country Contacts. Trends were analyzed based on the data available for both survey years. Results: The global 5-year progress in all 3 indicators was modest, with most countries either improving or staying at the same level. PA surveillance, policy, and research improved or remained at a high level in 48.1%, 40.6%, and 42.1% of the countries, respectively. PA surveillance, policy, and research scores decreased or remained at a low level in 8.3%, 15.8%, and 28.6% of the countries, respectively. The highest capacity for PA promotion was found in Europe, the lowest in Africa and low- and lower-middle-income countries. Although a large percentage of the world’s population benefit from at least some PA policy, surveillance, and research efforts in their countries, 49.6 million people are without PA surveillance, 629.4 million people are without PA policy, and 108.7 million live in countries without any PA research output. A total of 6.3 billion people or 88.2% of the world’s population live in countries where PA promotion capacity should be significantly improved. Conclusion: Despite PA is essential for health, there are large inequalities between countries and world regions in their capacity to promote PA. Coordinated efforts are needed to reduce the inequalities and improve the global capacity for PA promotion