Assessment of nitrification process in a sequencing batch reactor: Modelling and genomic approach.

Nitrification of ammoniacal nitrogen (N-NH4+) to nitrate (N-NO3-) was investigated in a lab-scale sequencing batch reactor (SBR) to evaluate its efficiency. During the nitrification process the removal of N-NH4+ reached 96%, resulting in 73% formation of N-NO3-. A lineal correlation (r2 = 0.9978) was obtained between the concentration of volatile suspended solids (VSS) and the maximal N-NO3- concentration at the end of each batch cycle under stationary state. The bacterial taxons in the initial inoculum were identified, revealing a complex diverse community mainly in the two major bacterial phyla Proteobacteria and Actinobacteria. The FAPROTAX algorithm predicted the presence in the inoculum of taxa involved in relevant processes of the nitrogen metabolism, highlighting the bacterial genera Nitrospira and Nitrosomonas that are both involved in the nitrification process. A kinetic model was formulated for predicting and validating the transformation of N-NH4+, N-NO2- and N-NO3- and the removal of organic and inorganic carbon (TOC and IC, respectively). The results showed how the increase in biomass concentration slowed down the transformation to oxidised forms of nitrogen and increased denitrification in the settling and filling stages under free aeration conditions.

Short-term impact of air pollution, noise and temperature on emergency hospital admissions in Madrid (Spain) due to liver and gallbladder diseases.

BACKGROUND: Very few epidemiological studies have explored the environmental and meteorological risk factors that influence liver diseases and gallbladder disorders, and no studies have addressed the specific case of Spain. METHODS: This is a retrospective ecological study conducted during 2013-2018. We analysed emergency admissions in the central area of the Region of Madrid for the following causes: Liver and gallbladder diseases (L&GB) (ICD-10: K70-K81); disorders of gallbladder (DGB) (ICD 10: K80-K81); liver disease (LD) (ICD 10: K70-K77); alcoholic liver disease (ALD) (ICD-10: K70); viral hepatitis (VH) (ICD10:B15-B19); and hepatic failure, not elsewhere classified (HFNS) (ICD-10: K72). Independent variables used: meteorological (maximum daily temperature (Tmax in °C), minimum daily temperature (Tmin in °C), and relative humidity (RH in %)); chemical air pollution (8-hO3, NO2, PM10, PM2.5 in µg/m3); and noise pollution (equivalent level of daily noise (Ld in dB(A)). Transformed variables: extreme heat in degrees (Theat); wet cold (WC); and high ozone. We fitted Poisson models, negative binomials and zero-inflated Poisson controlled for seasonality, day of the week, holidays, trend, and autoregressive trend. Based on these models, the percentage of cases attributable to statistically significant risk factors was then estimated. RESULTS: In L&GB emergency admissions daily noise is related to 4.4% (CI95%: 0.8 7.9) of admissions; NO2 to 2.9% (CI95%: 0.1 5.7) and wet cold to 0.2% (CI95%: 0.8 7.9). Heat wave temperature was only related to ALD. In addition, the wet cold association with L&GB is also related to HFNS attributing 1.0% (CI95%: 0.3 1.8) of admissions for this cause. CONCLUSIONS: Daily noise and NO2 are associated with more than 7% of urgent L&GB admissions. Both pollutants, are mainly emitted by road traffic. A reduction of traffic in cities would result in a reduction of emergency admissions due to this cause.

Integral evaluation of effective conversion of sewage sludge from WWTP into highly porous activated carbon.

Urban sewage sludge (SL) is a major concern due to the number of environmental problems it causes. Its application for different purposes is strictly regulated, limiting the possibilities of recycling and reusing this material. Thus, in this work, a complete study of a simple method to convert SL into activated carbon (AC) was carried out. The comprehensive study involves an evaluation of the main process parameters, such as the activating agent (AA) content (25 %, 33 %, 50 %), using the lowest amount of AA as novelty, different pyrolysis temperatures (600 and 800 °C), and purification conditions (6 M HCl:AC ratio, v:w). Under controlled and optimised conditions and through a single combined activation and pyrolysis step followed by acid purification, ACs with well-developed porosity can be obtained. Surface area values of around 870 m2/g and over 60 % carbon content were achieved, demonstrating that the prepared ACs could have applications in a wide variety of fields as high-value products. As an innovative aspect in this research, the gases streams and liquid effluents generated during the global process were analysed, achieving elimination of over 63 % of the concentration of the chemical elements contained in the SL during the chemical purification stage. Finally, mass, energy, and economic balances were carried out to estimate the production cost of AC derived from SL (<€ 8/kg AC).

CHECK - multilevel real-world pediatric asthma care coordination: results and lessons learned.

OBJECTIVE: Because asthma health disparities in children remain common, innovative approaches to obtain asthma health equity are essential. Comprehensive care coordination programs may address the social determinants of health that influence these disparities. This analysis aims to ascertain if receipt of Coordination of Healthcare for Complex Kids (CHECK) program services was associated with changes in school absence, cost, healthcare utilization, and controller prescription in children with asthma. METHODS: The CHECK program ran from December 1, 2014 through August 31, 2017. Engagement with community health workers was rolling and targeted based on risk level (low, medium, or high determined by healthcare utilization). This analysis included school-aged children with asthma (n = 2,629) and sufficient Chicago Public Schools attendance data (n = 430). RESULTS: Children engaged in CHECK were more likely to be female (p = .046) and to identify as Black and/or Hispanic/Latino than enrolled-only children. School absence was not different between the groups. Average total cost for engaged children was 21.3% more than enrolled-only children the first year (p = .027) but did not differ by the second year (p = .948). At baseline, 68.1% of the cohort had at least one ED visit 12 months prior to CHECK, this reduced to 49.5% post-1 and 41.9% post-2. Engaged children were 21% more likely to visit an ED (p = .010) and 40% more likely to have a controller. CONCLUSIONS: CHECK program receipt was associated with improved healthcare utilization and controller prescriptions. School attendance did not change. The CHECK model offers potential pathways to support low-income children with asthma.

Odor emission assessment of different WWTPs with Extended Aeration Activated Sludge and Rotating Biological Contactor technologies in the province of Cordoba (Spain).

In this study, five urban WWTPs (Wastewater Treatment Plant) with different biological treatment (Extended Aeration Activated Sludge - EAAS; Rotating Biological Contactor - RBC), wastewater type (Urban; Industrial) and size, were jointly evaluated. The aim was twofold: (1) to analyze and compare their odor emissions, and (2) to identify the main causes of its generation from the relationships between physico-chemical, respirometric and olfactometric variables. The results showed that facilities with EAAS technology were more efficient than RBC, with elimination yields of organic matter higher than 90%. In olfactometric terms, sludge managements facilities (SMFs) were found to be the critical odor source in all WWTPs compared to the Inlet point (I) or Post primary treatment (PP), and for seasonal periods with ambient temperature higher than 25 °C. Moreover, the global odor emissions quantified in all SMFs revealed that facilities with EAAS (C-WWTP, V-WWTP and Z-WWTP) had a lower odor contribution (19,345, 14,800 and 11,029 ouE/s·m2, respectively) than for those with RBC technology (P-WWTP and NC-WWTP) which accounted for 19,747 ouE/s·m2 and 80,061 ouE/s·m2, respectively. In addition, chemometric analysis helped to find groupings and differences between the WWTPs considering the wastewater (71.27% of total variance explained) and sludge management (64.52% of total variance explained) lines independently. Finally, odor emissions were adequately predicted from the physico-chemical and respirometric variables in the wastewater (r2 = 0.8738) and sludge (r2 = 0.9373) lines, being pH, volatile acidity and temperature (wastewater line), and pH, moisture, temperature, SOUR (Specific Oxygen Uptake Rate) and OD20 (Cumulative Oxygen Demand at 20 h) (sludge line) the most influential variables.

Analysis of vulnerability to heat in rural and urban areas in Spain: What factors explain Heat's geographic behavior?

INTRODUCTION: There is currently little knowledge and few published works on the subject of vulnerability to heat in rural environments at the country level. Therefore, the objective of this study was to determine whether rural areas are more vulnerable to extreme heat than urban areas in Spain. This study aimed to analyze whether a pattern of vulnerability depends on contextual, environmental, demographic, economic and housing variables. METHODS: An ecological, longitudinal and retrospective study was carried out based on time series data between January 01, 2000 and December 31, 2013 in 42 geographic areas in 10 provinces in Spain. We first analyzed the functional relationship between the mortality rate per million inhabitants and maximum daily temperature (Tmax). We then determined the summer temperature threshold (Pthreshold) (June-September) at which increases in mortality are produced that are attributable to heat. In a second phase, based on Pthreshold, a vulnerability variable was calculated, and its distribution was analyzed using mixed linear models from the Poisson family (link = log). In these models, the dependent variable was vulnerability, and the independent variables were exposure to high temperatures, aridity of the climate, deprivation index, percentage of people over age 65, rurality index, percentage of housing built prior to 1980 and condition of dwellings. RESULTS: Rurality was a protective factor, and vulnerability in urban areas was six times greater. In contrast, risk factors included aridity (RR = 5.89 (2.26 15.36)), living in cool summer zones (2.69 (1.23, 5.91)), poverty (4.05 (1.91 8.59)) and the percentage of dysfunctional housing (1.13 (1.04 1.24)). CONCLUSIONS: Rural areas are less vulnerable to extreme heat than the urban areas analyzed. Also, population groups with worse working conditions and higher percentages of dwellings in poor conditions are more vulnerable.

Gender differences in adaptation to heat in Spain (1983-2018).

In Spain the average temperature has increased by 1.7 °C since pre-industrial times. There has been an increase in heat waves both in terms of frequency and intensity, with a clear impact in terms of population health. The effect of heat waves on daily mortality presents important territorial differences. Gender also affects these impacts, as a determinant that conditions social inequalities in health. There is evidence that women may be more susceptible to extreme heat than men, although there are relatively few studies that analyze differences in the vulnerability and adaptation to heat by sex. This could be related to physiological causes. On the other hand, one of the indicators used to measure vulnerability to heat in a population and its adaptation is the minimum mortality temperature (MMT) and its temporal evolution. The aim of this study was to analyze the values of MMT in men and women and its temporal evolution during the 1983-2018 period in Spain's provinces. An ecological, longitudinal retrospective study was carried out of time series data, based on maximum daily temperature and daily mortality data corresponding to the study period. Using cubic and quadratic fits between daily mortality rates and the temperature, the minimum values of these functions were determined, which allowed for determining MMT values. Furthermore, we used an improved methodology that provided for the estimation of missing MMT values when polynomial fits were inexistent. This analysis was carried out for each year. Later, based on the annual values of MMT, a linear fit was carried out to determine the rate of evolution of MMT for men and for women at the province level. Average MMT for all of Spain's provinces was 29.4 °C in the case of men and 28.7 °C in the case of women. The MMT for men was greater than that of women in 86 percent of the total provinces analyzed, which indicates greater vulnerability among women. In terms of the rate of variation in MMT during the period analyzed, that of men was 0.39 °C/decade, compared to 0.53 °C/decade for women, indicating greater adaptation to heat among women, compared to men. The differences found between men and women were statistically significant. At the province level, the results show great heterogeneity. Studies carried out at the local level are needed to provide knowledge about those factors that can explain these differences at the province level, and to allow for incorporating a gender perspective in the implementation of measures for adaptation to high temperatures.

Analysis of the impact of heat waves on daily mortality in urban and rural areas in Madrid.

The objective of this study was to analyze and compare the effect of high temperatures on daily mortality in the urban and rural populations in Madrid. Data were analyzed from municipalities in Madrid with a population of over 10,000 inhabitants during the period from January 1, 2000 to December 31, 2020. Four groups were generated: Urban Metropolitan Center, Rural Northern Mountains, Rural Center, and Southern Rural. The dependent variable used was the rate of daily mortality due to natural causes per million inhabitants (CIE-X: A00-R99) between the months of June and September for the period. The primary independent variable was maximum daily temperature. Social and demographic "context variables" were included: population >64 years of age (%), deprivation index and housing indicators. The analysis was carried out in three phases: 1) determination of the threshold definition temperature of a heat wave (Tumbral) for each study group; 2) determination of relative risks (RR) attributable to heat for each group using Poisson linear regression (GLM), and 3) calculation of odds ratios (OR) using binomial family GLM for the frequency of the appearance of heat waves associated with context variables. The resulting percentiles (for the series of maximum daily temperatures for the summer months) corresponding to Tthreshold were: 74th percentile for Urban Metropolitan Center, 76th percentile for Southern Rural, 83rd for Rural Northern Mountains and 98th percentile for Center Rural (98). Greater vulnerability was found for the first two. In terms of context variables that explained the appearance of heat waves, deprivation index level, population >64 years of age and living in the metropolitan area were found to be risk factors. Rural and urban areas behaved differently, and socioeconomic inequality and the composition of the population over age 64 were found to best explain the vulnerability of the Rural Center and Southern Rural zones.

Influence of packing material on the biofiltration of butyric acid: A comparative study from a physico-chemical, olfactometric and microbiological perspective.

The influence of bed material on the odor removal performance of a biofilter was studied. A compost-wood biofilter and a wood biofilter were treated with a gaseous stream contaminated with butyric acid and comparatively evaluated at pilot scale using olfactometric, physico-chemical and microbiological approaches. The variables analyzed in both biofilters were correlated with specific families of their microbiota composition. In addition to a higher nutrients content (nitrogen and phosphorus), the compost-wood biofilter registered maximum values in number of aerobic microorganisms (3.6·108 CFU/g) and in aerobic microbiological activity (≈40 mg O2/g VS of cumulative oxygen demand at 20 h). This may explain the higher performance of this biofilter compared to the wood biofilter, withstanding odor loads of up to 1450 ouE/m2·s with odor removal efficiencies close to 100%. The analysis of the microbial community showed that Actinobacteria, particularly the mostly aerobic Microbacteriaceae family, might play an important role in butyric acid degradation and hence reduce odor impact. The multidisciplinary analysis carried out in this work could be a very useful strategy for the optimal design of biofiltration operations.

Enhancement of nonlinear functionality of step-index silica fibers combining thermal poling and 2D materials deposition.

This work proposes a new route to overcome the limits of the thermal poling technique for the creation of second order nonlinearity in conventional silica optical fibers. We prove that it is possible to enhance the nonlinear behavior of periodically poled fibers merging the effects of poling with the nonlinear intrinsic properties of some materials, such as MoS2, which are deposited inside the cladding holes of a twin-hole silica fiber. The optical waves involved in a second harmonic generation process partially overlap inside the thin film of the nonlinear material and exploit its higher third order susceptibility to produce an enhanced SHG.

Biofiltration of butyric acid: Monitoring odor abatement and microbial communities.

The objective of this study is to evaluate comparatively the odor removal efficacy of two biofilters operated under different conditions and to identify taxonomically the microbial communities responsible for butyric acid degradation. Both biofiltration systems, which were filled with non-inoculated wood chips and exposed to gas streams containing butyric acid, were evaluated under different operational conditions (gas airflow and temperature) from the physical-chemical, microbiological and olfactometric points of view. The physical-chemical characterization showed the acidification of the packing material and the accumulation of butyric acid during the biofiltration process (<60 days). The removal efficacy was found to be 98-100% during the first 20 days of operation, even at high odor concentration. Changes in the operational temperature increased the odor load factor from 400 to 1400 ouE/m2·s, which led to the reduction of microbiota in the packing material, and a drastic drop of the odor removal efficacy. However, the progressive increase in gas airflow improved the biodegradation efficacy of butyric acid up to 88% with odor loadings as high as 33,000 ouE/m3, while a linear relationship between odor inlet load and removal capacity was also found. The analysis of the microbial community showed that Proteobacteria was the most abundant phylum along the biofiltration time (58-92%) and regardless of the operational conditions. Finally, principal component analysis applied to the physical-chemical and microbiological data set revealed significant differences between the two biofilters under study.

Environmental performance of an industrial biofilter: Relationship between photochemical oxidation and odorous impacts.

Biological techniques are widely used to treat gaseous streams derived from waste treatment plants. The generation of volatile organic compounds (VOCs) is one of the principal pollution sources in composting facilities from which nuisance odours are released. In addition, the generation of photochemical smog with other gases such as NOX can produce ozone at ground level due to their photochemical ozone creation potential (POCP). In this work, the performance of an industrial biofilter was evaluated from an environmental point of view. Specifically, this study evaluated the potential impact in terms of photochemical oxidation and odour emission derived from composting in a vessel under four different aeration conditions. Gas chromatography-time-of-flight mass spectrometry (GC-TOFMS) was used to perform the chemical characterisation of the gaseous streams, while dynamic olfactometry was used to carry out the sensorial analysis. A total of 95 compounds belonging to 12 different families of VOCs were selected. Principal component analysis revealed the influence of each VOC family on each impact category and explained 88% of the total variance. Multivariate regression was used to study the correlation between photochemical oxidation and odour impact, which has never been reported before. The correlations obtained (r ≥ 0.97) evidenced the direct relationship between these two impacts. Photochemical oxidation and odour emission were proven to be important environmental impacts derived from composting facilities, whose abatement might be carried out by biofiltration systems.

Sewage sludge composting under semi-permeable film at full-scale: Evaluation of odour emissions and relationships between microbiological activities and physico-chemical variables.

In the present study, physico-chemical characteristics, heavy metals content, odour emissions, microbial enumeration and enzymatic activities were analysed during industrial scale composting of sewage sludge partially pre-treated to evaluate the effect of a combined system of semi-permeable film and aeration on these parameters. The results related to physico-chemical parameters showed a decrease in total organic carbon (TOC), organic matter (OM), total carbon (TC) along the process. Volatile solids (VS) were also reduced, reaching 36% at 120 days, which is above the limit according to the current legislation. Similarly, metal content was found to be an important variable in the evolution of enzymatic activity, while lead (Pb), zinc (Zn), and nickel (Ni) were the most influential. Moreover, heavy metals were found below the limit of type B compost quality or European class 2 at the end of the process, which is suitable for agriculture soil. The odorous impact generated during the hydrolytic stage was reduced to an average value of 4 ouE/s. This suggests that, covered stage with the semi-permeable film, could be a viable solution to mitigate odour emissions. The highest temperature was reached at 10 days and it was favoured by semi-permeable film. Temperature promoted the presence of thermophilic bacteria and fungi and indicated an early biodegradation process mediated by microorganisms. Statistical analyses revealed a high correlation of physico-chemical variables with microbial activity. Thus, samples from the first 14 days were highly correlated with enzymatic activities such as ß-glucosidase (Ac-ßGlu), protease (Ac-Pr), and dehydrogenase (Ac-De), which have usually been involved in the hydrolysis of organic matter.

Co-composting of sewage sludge and eggplant waste at full scale: Feasibility study to valorize eggplant waste and minimize the odoriferous impact of sewage sludge.

Sewage sludge and bulking agent with small proportions of eggplant waste (EP) (4.7 and 8.6%) were co-composted at full scale to evaluate the feasibility of their joint valorization and to reduce the odorous impact during composting. In this sense, physico-chemical, respirometric and olfactometric variables were monitored throughout the co-composting process. The physico-chemical variables studied were related to each other to evaluate their effect on the quality of the final product and the odoriferous impact. It was observed that the reduction in nitrogen concentration was not parallel to the removal of organic matter, which influenced the odor concentration emitted. Furthermore, during the hydrolytic stage of the co-composting process, the odor concentration was lower when the agricultural waste content was highest (8.6% EP: 6317 and 8192 ouE/m3) in comparison with the lowest concentration of EP (4.7% EP: 9214 and 14720 ouE/m3) or without the addition of EP (reference composting pile: 10200 and 22500 ouE/m3). Although sewage sludge is more biodegradable than eggplant waste, the co-composting process was carried out under suitable conditions. Approximately 90 days were required to obtain a stabilized compost. Consequently, co-composting might be a suitable alternative to valorize EP and reduce the odoriferous impact of sewage sludge, with the consequent economic, social and environmental benefits.

Non-osteogenic muscle hypertrophy in children with McArdle disease.

INTRODUCTION: McArdle disease is an inborn disorder of muscle glycogen metabolism that produces exercise intolerance, and has been recently associated with low values ​​of lean mass (LM) and bone mineral content (BMC) and density (BMD) in affected adults. Here we aimed to study whether this bone health problem begins in childhood. METHODS: Forty children and adolescents were evaluated: 10 McArdle disease and 30 control children (mean age of both groups, 13 ± 2y). Body composition was evaluated by dual-energy X-ray absorptiometry and creatine kinase (CK) levels were determined in the patients as an estimate of muscle damage. RESULTS: Legs bone mass was significantly lower in patients than in controls (-36% for BMC and -22% for BMD). Moreover, patients had significantly higher LM values in the legs than controls, whereas no difference was found for fat mass. CK levels were positively associated with LM in McArdle patients. A correlation was found between LM and BMD variables in the control group but not in McArdle patients. CONCLUSION: We have identified a 'non-osteogenic muscle hypertrophy' in children with McArdle disease. This phenomenon warrants special attention since low osteogenesis at an early age predicts a high risk for osteoporosis later in life.

Increased future ice discharge from Antarctica owing to higher snowfall.

Anthropogenic climate change is likely to cause continuing global sea level rise, but some processes within the Earth system may mitigate the magnitude of the projected effect. Regional and global climate models simulate enhanced snowfall over Antarctica, which would provide a direct offset of the future contribution to global sea level rise from cryospheric mass loss and ocean expansion. Uncertainties exist in modelled snowfall, but even larger uncertainties exist in the potential changes of dynamic ice discharge from Antarctica and thus in the ultimate fate of the precipitation-deposited ice mass. Here we show that snowfall and discharge are not independent, but that future ice discharge will increase by up to three times as a result of additional snowfall under global warming. Our results, based on an ice-sheet model forced by climate simulations through to the end of 2500 (ref. 8), show that the enhanced discharge effect exceeds the effect of surface warming as well as that of basal ice-shelf melting, and is due to the difference in surface elevation change caused by snowfall on grounded versus floating ice. Although different underlying forcings drive ice loss from basal melting versus increased snowfall, similar ice dynamical processes are nonetheless at work in both; therefore results are relatively independent of the specific representation of the transition zone. In an ensemble of simulations designed to capture ice-physics uncertainty, the additional dynamic ice loss along the coastline compensates between 30 and 65 per cent of the ice gain due to enhanced snowfall over the entire continent. This results in a dynamic ice loss of up to 1.25 metres in the year 2500 for the strongest warming scenario. The reported effect thus strongly counters a potential negative contribution to global sea level by the Antarctic Ice Sheet.

Full-scale composting of sewage sludge and market waste: Stability monitoring and odor dispersion modeling.

The aim of this study was to assess the odor immission derived from full-scale composting of different abundant and highly pollutant organic waste: sewage sludge with bulking agent (SL), sewage sludge pretreated through anaerobic digestion and supplemented with bulking agent (SL-AD), and market waste with olive leaves (MW-OL). The combination of dynamic olfactometry and Gaussian dispersion modeling allowed both the quantification of odor emissions from each waste and the evaluation of their global odorous impact in nearby urban areas. Wind speed, summer and winter seasons, and atmospheric conditions were considered in the dispersion model. The results revealed that high wind speed (2.6 m/s) increases the global odor immission in summer season, independently of atmospheric stability. However, the maximum odor immission concentration recommended for composting process was not exceeded in any case, which depends on each country/region. The experimental results also enable to evaluate the influence of several physico-chemical variables on odor emissions derived from composting. The removal of nitrogen and volatile solids was the main cause for odor generation. Moreover, the microbiological activity of each substrate was monitored throughout the process and different percentages of biodegradability were quantified depending on the type of substrate and pretreatment applied.

Application of ATAD technology for digesting sewage sludge in small towns: Operation and costs.

In an economic context marked by increasing energy costs and stricter legislation regarding the landfill disposal of wastewater treatment plant (WWTP) sewage sludge, and where biomethanization is difficult to implement in small WWTPs, an efficient alternative is required to manage this polluting waste. This study shows that autothermal thermophilic aerobic digestion (ATAD) is a feasible technique for treating sewage sludge in small- and medium-sized towns. The experiments were carried out at pilot scale on a cyclical basis and in continuous mode for nine months. The main results showed an optimal hydraulic retention time of 7 days, which led to an organic matter removal of 34%. The sanitized sludge meets the microbial quality standards for agronomic application set out in the proposed European sewage sludge directive. An economic assessment for the operation of ATAD technology was carried out, showing a treatment cost of €6.5/ton for dewatered sludge.

The homozygous R504C mutation in MTO1 gene is responsible for ONCE syndrome.

We report clinical and biochemical finding from three unrelated patients presenting ONCE (Optic Neuropathy, Cardiomyopathy and Encephalopathy with lactic acidosis and combined oxidative phosphorylation deficiency) syndrome. Whole-exome sequencing (WES) of the three patients and the healthy sister of one of them was used to identify the carry gene. Clinical and biochemical findings were used to filter variants, and molecular, in silico and genetic studies were performed to characterize the candidate variants. Mitochondrial DNA (mtDNA) defects involving mutations, deletions or depletion were discarded, whereas WES uncovered a double homozygous mutation in the MTO1 gene (NM_001123226:c.1510C>T, p.R504C, and c.1669G>A, p.V557M) in two of the patients and the homozygous mutation p.R504C in the other. Therefore, our data confirm p.R504C as pathogenic mutation responsible of ONCE syndrome, and p.V557M as a rare polymorphic variant.

Cyclosporine A for severe atopic dermatitis in children. efficacy and safety in a retrospective study of 63 patients.

BACKGROUND: Cyclosporine A (CSA) is an immunosuppressant agent widely used in severe atopic dermatitis (AD). However, experience in children is limited. OBJECTIVES: To assess the efficacy and adverse events of CSA therapy in children. METHODS: Retrospective study of children with severe AD treated with CSA between January 2009 and December 2015. RESULTS: Data from 63 patients were collected. Mean age at the beginning of treatment was 8.4 years (±3.6). The median starting dose was 4.27 (±0.61) mg/kg/day. After 4 weeks of treatment, the outcome was excellent in 35% of cases, good in 29% and poor in 36% of the patients. The response was better in patients without eosinophilia (P < 0.05). The median duration of treatment was 4.6 months (range 1.5-21.6). Side-effects were frequent but mild, being more common in patients after longer treatment periods (P < 0.05). Mean time of follow-up was 19.4 months (±12.7). Prolonged remission (>6 months) was observed in 13 patients (20%). LIMITS: This is a retrospective review. The follow-up period is limited. CONCLUSIONS: Our data confirm that CSA is efficacious and acts rapidly in the majority of children with severe AD. CSA therapy can provide sustained remission in some patients. CSA seems to be well tolerated in children, but strict monitoring is mandatory.