Modeling Glutaric Aciduria Type I in human neuroblastoma cells recapitulates neuronal damage that can be rescued by gene replacement.

Glutaric Aciduria type I (GA1) is a rare neurometabolic disorder caused by mutations in the GDCH gene encoding for glutaryl-CoA dehydrogenase (GCDH) in the catabolic pathway of lysine, hydroxylysine and tryptophan. GCDH deficiency leads to increased concentrations of glutaric acid (GA) and 3-hydroxyglutaric acid (3-OHGA) in body fluids and tissues. These metabolites are the main triggers of brain damage. Mechanistic studies supporting neurotoxicity in mouse models have been conducted. However, the different vulnerability to some stressors between mouse and human brain cells reveals the need to have a reliable human neuronal model to study GA1 pathogenesis. In the present work we generated a GCDH knockout (KO) in the human neuroblastoma cell line SH-SY5Y by CRISPR/Cas9 technology. SH-SY5Y-GCDH KO cells accumulate GA, 3-OHGA, and glutarylcarnitine when exposed to lysine overload. GA or lysine treatment triggered neuronal damage in GCDH deficient cells. SH-SY5Y-GCDH KO cells also displayed features of GA1 pathogenesis such as increased oxidative stress vulnerability. Restoration of the GCDH activity by gene replacement rescued neuronal alterations. Thus, our findings provide a human neuronal cellular model of GA1 to study this disease and show the potential of gene therapy to rescue GCDH deficiency.

Treatment of COVID-19 pneumonia with low-dose radiotherapy plus standard of care versus standard of care alone in frail patients : The SEOR-GICOR IPACOVID comparative cohort trial.

PURPOSE: To assess the efficacy of lung low-dose radiotherapy (LD-RT) in the treatment of patients with COVID-19 pneumonia. MATERIALS AND METHODS: Ambispective study with two cohorts to compare treatment with standard of care (SoC) plus a single dose of 0.5 Gy to the whole thorax (experimental prospective cohort) with SoC alone (control retrospective cohort) for patients with COVID-19 pneumonia not candidates for admission to the intensive care unit (ICU) for mechanical ventilation. RESULTS: Fifty patients treated with LD-RT were compared with 50 matched controls. Mean age was 85 years in both groups. An increase in arterial oxygen partial pressure (PaO2)/fraction of inspired oxygen (PAFI) in the experimental LD-RT-treated group compared to the control group could not be found at 48 h after LD-RT, which was the primary endpoint of the study. However, PAFI values significantly improved after 1 month (473 vs. 302 mm Hg; p < 0.0001). Pulse oxymetric saturation/fraction of inspired oxygen (SAFI) values were also significantly higher in LD-RT-treated patients than in control patients at 1 week (405 vs. 334 mm Hg; p = 0.0157) and 1 month after LD-RT (462 vs. 326 mm Hg; p < 0.0001). All other timepoint measurements of the respiratory parameters were similar across groups. Patients in the experimental group were discharged from the hospital significantly earlier (23 vs. 31 days; p = 0.047). Fifteen and 26 patients died due to COVID-19 pneumonia in the experimental and control cohorts, respectively (30% vs. 48%; p = 0.1). LD-RT was associated with a decreased odds ratio (OR) for 1­month COVID-19 mortality (OR = 0.302 [0.106-0.859]; p = 0.025) when adjusted for potentially confounding factors. Overall survival was significantly prolonged in the LD-RT group compared to the control group (log-rank p = 0.027). No adverse events related to radiation treatment were observed. CONCLUSION: Treatment of frail patients with COVID-19 pneumonia with SoC plus single-dose LD-RT of 0.5 Gy improved respiratory parameters, reduced the period of hospitalization, decreased the rate of 1­month mortality, and prolonged actuarial overall survival compared to SoC alone.

Incidental appendectomy in surgical treatment of ileocolic intussusception in children. Is it safe to perform? / Apendicectomía incidental en el tratamiento quirúrgico de la intususcepción ileocólica en niños. ¿Es segura?

BACKGROUND: Surgical treatment of ileo-colic intussusception (ICI) has been reported as the second cause of emergency laparotomy in children. The performance of incidental appendectomy after surgical reduction is currently controversial. The aim is to analyse the outcomes of performing incidental appendectomy after surgical ICI reduction with or without associated bowel resection. MATERIALS AND METHODS: A retrospective study was performed in patients with ICI episodes, who underwent surgical treatment in our institution between 2005-2019. Patients were divided in two groups according to the performance of associated appendectomy (AA group) or not (NA group). Subsequently, a stratified analysis was performed according to the need for bowel resection in both groups. Demographic variables, intraoperative findings, surgical time, hospital stay, postoperative complications and recurrences were analysed. RESULTS: A total of 101 patients (77 AA group; 24 NA group) were included, without differences in demographics or intraoperative findings. A total of 36 bowel resections were performed (24 group AA; 10 group NA), with no differences in surgical time (55.7 min in group AA vs. 61.2 min in group NA; p = 0.587) or hospital stay (median 5 days in both groups). There were also no differences in postoperative complications or recurrences between the two groups. Stratified analysis showed that bowel resection increases operative time, hospital stay and postoperative complications, regardless of whether associated appendectomy was performed or not. CONCLUSIONS: Incidental appendectomy during surgical treatment of ICI in children is a safe procedure that does not increase operative time, hospital stay, postoperative complications or recurrence.

OBJETIVO: El tratamiento quirúrgico de la intususcepción ileocólica (IIC) es la segunda causa más frecuente de laparotomía de urgencia en niños. La realización de una apendicectomía incidental tras la reducción quirúrgica sigue siendo motivo de controversia. El objetivo de este trabajo es analizar los resultados obtenidos al llevar a cabo una apendicectomía incidental tras la reducción quirúrgica de una IIC con o sin resección intestinal asociada. MATERIAL Y METODO: Se realizó un estudio retrospectivo en pacientes con episodios de IIC sometidos a tratamiento quirúrgico en nuestro centro entre 2005 y 2019. Los pacientes se dividieron en dos grupos según se llevara a cabo apendicectomía asociada (grupo AA) o no (grupo NA). Posteriormente, se elaboró un análisis estratificado según la necesidad de practicar resección intestinal en ambos grupos. Se analizaron las variables demográficas, los hallazgos intraoperatorios, el tiempo quirúrgico, la estancia hospitalaria, las complicaciones posoperatorias y las recidivas. RESULTADOS: Se incluyeron un total de 101 pacientes (77 en el grupo AA, y 24 en el grupo NA), sin diferencias en las características demográficas ni en los hallazgos intraoperatorios. Se practicaron un total de 36 resecciones intestinales (24 en el grupo AA; 10 en el grupo NA), sin diferencias en el tiempo quirúrgico (55,7 min en el grupo AA frente a 61,2 min en el grupo NA; p = 0,587) ni en la estancia hospitalaria (mediana de 5 días en ambos grupos). Tampoco se registraron diferencias en términos de complicaciones posoperatorias o recidivas entre los dos grupos. El análisis estratificado mostró que la resección intestinal incrementa el tiempo quirúrgico, la estancia hospitalaria y las complicaciones posoperatorias, con independencia de si se lleva a cabo apendicectomía asociada o no. CONCLUSION: La apendicectomía incidental durante el tratamiento quirúrgico de la IIC en niños es un procedimiento seguro que no aumenta el tiempo quirúrgico, la estancia hospitalaria, las complicaciones posoperatorias ni las posibilidades de recidiva.

Apendicectomía incidental en el tratamiento quirúrgico de la intususcepción ileocólica en niños. ¿Es segura? / Incidental appendectomy in surgical treatment of ileocolic intussusception in children. Is it safe to perform?

Objetivo: El tratamiento quirúrgico de la intususcepción ileocólica(IIC) es la segunda causa más frecuente de laparotomía de urgencia enniños. La realización de una apendicectomía incidental tras la reduc-ción quirúrgica sigue siendo motivo de controversia. El objetivo deeste trabajo es analizar los resultados obtenidos al llevar a cabo unaapendicectomía incidental tras la reducción quirúrgica de una IIC cono sin resección intestinal asociada. Material y método: Se realizó un estudio retrospectivo en pacientescon episodios de IIC sometidos a tratamiento quirúrgico en nuestro centroentre 2005 y 2019. Los pacientes se dividieron en dos grupos según sellevara a cabo apendicectomía asociada (grupo AA) o no (grupo NA). Posteriormente, se elaboró un análisis estratificado según la necesidad depracticar resección intestinal en ambos grupos. Se analizaron las variablesdemográficas, los hallazgos intraoperatorios, el tiempo quirúrgico, laestancia hospitalaria, las complicaciones posoperatorias y las recidivas. Resultados: Se incluyeron un total de 101 pacientes (77 en el gru-po AA, y 24 en el grupo NA), sin diferencias en las características demográficas ni en los hallazgos intraoperatorios. Se practicaron untotal de 36 resecciones intestinales (24 en el grupo AA; 10 en el grupoNA), sin diferencias en el tiempo quirúrgico (55,7 min en el grupo AAfrente a 61,2 min en el grupo NA; p = 0,587) ni en la estancia hospi-talaria (mediana de 5 días en ambos grupos). Tampoco se registrarondiferencias en términos de complicaciones posoperatorias o recidivasentre los dos grupos. El análisis estratificado mostró que la resecciónintestinal incrementa el tiempo quirúrgico, la estancia hospitalaria y las complicaciones posoperatorias, con independencia de si se lleva a caboapendicectomía asociada o no.(AU)

Background: Surgical treatment of ileo-colic intussusception (ICI)has been reported as the second cause of emergency laparotomy inchildren. The performance of incidental appendectomy after surgicalreduction is currently controversial. The aim is to analyse the outcomesof performing incidental appendectomy after surgical ICI reduction withor without associated bowel resection. Materials and methods: A retrospective study was performed inpatients with ICI episodes, who underwent surgical treatment in ourinstitution between 2005-2019. Patients were divided in two groupsaccording to the performance of associated appendectomy (AA group)or not (NA group). Subsequently, a stratified analysis was performedaccording to the need for bowel resection in both groups. Demographicvariables, intraoperative findings, surgical time, hospital stay, postopera-tive complications and recurrences were analysed.Results. A total of 101 patients (77 AA group; 24 NA group) wereincluded, without differences in demographics or intraoperative findings. A total of 36 bowel resections were performed (24 group AA; 10 groupNA), with no differences in surgical time (55.7 min in group AA vs.61.2 min in group NA; p = 0.587) or hospital stay (median 5 days in bothgroups). There were also no differences in postoperative complicationsor recurrences between the two groups. Stratified analysis showed thatbowel resection increases operative time, hospital stay and postopera-tive complications, regardless of whether associated appendectomy wasperformed or not.(AU)

Near-range atmospheric dispersion of an anomalous selenium-75 emission.

On May 15th of 2019, an anomalous emission of selenium-75 was detected at the stack of the Belgian Reactor 2 (BR2) in Mol. Although the release exceeded the prescribed limits for BR2, there was no harm to the population or food chain and so the event was classified as INES 1. However, it was very interesting from the perspective of near-range atmospheric dispersion. This publication brings together all available information at the near range - stack-monitored source term data, on-site meteorological data, ambient dose equivalent rates, deposition and concentration measurements - in one dataset that covers the initial puff release on May 15th, 2019 as well as a residual release through early November 2019. To demonstrate the consistency of this dataset, supporting atmospheric transport and dispersion calculations are performed using a Gaussian plume model. These calculations, in turn, are supported by near-range Flexpart calculations in the context of the residual release.

Role of modelling in monitoring soil and food during different stages of a nuclear emergency.

In case of a nuclear accident, adequate protection of the public and the environment requires timely assessment of the short- and long-term radiological exposure. Measurements of the radiation dose and the radioactive contamination in the environment are essential for the optimization of radiation protection and the decision making process. In the early phase, however, such measurements are rarely available or sufficient.To compensate for the lack of monitoring data during nuclear emergencies, especially in the early phase of the emergency, mathematical models are frequently used to assess the temporal and spatial distribution of radioactive contamination. During the transition and recovery phase, models are typically used to optimise remediation strategies by assessing the cost-effectiveness of different countermeasures. A prerequisite of course is that these models are fit for purpose. Different models may be needed during different phases of the accident. In this paper, we discuss the role of radioecological models during a nuclear emergency, and give an outlook on the scientific challenges which need to be addressed to further improve our predictions of human and wildlife exposure.

Publisher Correction: Feasibility and effects of enhanced recovery vs. conventional care after emergency colon surgery for patients with left colon perforation.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Feasibility and effects of enhanced recovery vs. conventional care after emergency colon surgery for patients with left colon perforation.

The impact of an enhanced recovery after surgery (ERAS) programme in emergency colorectal surgery has not yet been reported. The objective of this study was to evaluate the feasibility and the results of patients included in an ERAS protocol following emergency colon surgery for left colon perforation. For this purpose, patients with a low to moderate risk of mortality, according to a Peritonitis Severity Score (PSS), and treated with an ERAS protocol (ERAS group) after emergency surgery for left colon perforation were compared for a period of 40 months (March 2014-June 2017) with a control group of patients treated with conventional care (CC group) during the 38 months prior to implementation of the new ERAS protocol (January 2011-February 2014). The main endpoint was 90-day postoperative morbidity according to the Clavien-Dindo classification. Secondary endpoints included length of postoperative hospital stay, 90-day readmission rate, protocol compliance and mortality. Fifty patients were included in the study, 29 in the ERAS group and 21 in the CC group. There were no significant differences between the groups in the demographic data or in the operative characteristics. A reduction in the incidence of postoperative complications (20.7% vs. 38%; p > 0.05) and in the postoperative hospital stay (7.7 + /- 3.85 vs. 10.9 + /- 5.6 days; p = 0.009) were observed in the ERAS group. The 90-day readmission rate did not differ significantly between the two groups (2 vs. 1). No 90-day mortality was observed in either group. The ERAS group showed better results than the CC group in protocol compliance. We conclude that ERAS protocols are feasible and help to reduce morbidity and length of hospital stay without adversely affecting the rate of readmission or mortality.

Effects of radiotherapy on plasma energy metabolites in patients with breast cancer who received neoadjuvant chemotherapy.

PURPOSE: Neoadjuvant chemotherapy (NACT) is employed in patients with breast cancer (BC) with the aim of reducing tumor burden and improving surgical outcomes. We evaluated the levels of energy metabolites pre- and post-radiotherapy (RT) in breast cancer (BC) patients who previously received NACT and investigated the alterations of these metabolites in relation to the patient achieving a pathologic complete response to NACT. MATERIALS AND METHODS: We included 37 BC patients who were treated with NACT following surgery and analyzed the concentrations of energy balance-related metabolites using targeted metabolomics before and one month after the end of RT. The control group was composed of 44 healthy women. RESULTS: Pre-radiotherapy, patients had significant decreases in the plasma levels of 12 metabolites. RT corrected these alterations and the improvement was superior in patients with a pathologic complete response. CONCLUSION: Our results highlight the importance of metabolism in the outcomes of patients with BC.

Circumventing Magnetostatic Reciprocity: A Diode for Magnetic Fields.

Lorentz reciprocity establishes a stringent relation between electromagnetic fields and their sources. For static magnetic fields, a relation between magnetic sources and fields can be drawn in analogy to the Green's reciprocity principle for electrostatics. So far, the magnetostatic reciprocity principle remains unchallenged and the magnetostatic interaction is assumed to be symmetric (reciprocal). Here, we theoretically and experimentally show that a linear and isotropic electrically conductive material moving with constant velocity is able to circumvent the magnetostatic reciprocity principle and realize a diode for magnetic fields. This result is demonstrated by measuring an extremely asymmetric magnetic coupling between two coils that are located near a moving conductor. The possibility to generate controlled unidirectional magnetic couplings implies that the mutual inductances between magnetic elements or circuits can be made extremely asymmetric. We anticipate that this result will provide novel possibilities for applications and technologies based on magnetically coupled elements and might open fundamentally new avenues in artificial magnetic spin systems.

X-ray structural, functional and computational studies of the O2-sensitive E. coli hydrogenase-1 C19G variant reveal an unusual [4Fe-4S] cluster.

The crystal structure of the Escherichia coli O2-sensitive C19G [NiFe]-hydrogenase-1 variant shows that the mutation results in a novel FeS cluster, proximal to the Ni-Fe active site. While the proximal cluster of the native O2-tolerant enzyme can transfer two electrons to that site, EPR spectroscopy shows that the modified cluster can transfer only one electron, this shortfall coinciding with O2 sensitivity. Computational studies on electron transfer help to explain how the structural and redox properties of the novel FeS cluster modulate the observed phenotype.

Paraoxonase-1 activity in patients with cancer: A systematic review and meta-analysis.

PURPOSE: Paraoxonase-1 (PON1) is a lipolactonase implicated in the elimination of carcinogenic free radicals and in the scavenging mechanisms to maintain oxidative balance. The objective of the present systematic review and meta-analysis was to evaluate possible alterations in serum PON1 activity in patients with cancer. METHODS: A systematic search of the observational studies in humans published in the last 15 years was performed through Medline databases following the PRISMA and STARLITE statements. Further, a keyword-based computerized search with restrictions on publication date, and a meta-analysis of case-control studies was performed. RESULTS: In total, 23 studies were included most of which reported decreased PON1 activity in patients with cancer. This could indicate impaired defense ability against oxidative stress with potential implications in cell proliferation, promotion of genetic instability, and alterations in cellular sensitivity to chemotherapy. CONCLUSION: This systematic review and meta-analysis confirms a consistent association between cancer and decreased serum PON1 activities. These findings may open fruitful lines of research with clinical relevance, and an understanding of molecular alterations underlying carcinogenesis.

The work programme of NERIS in post-accident recovery.

NERIS is the European platform on preparedness for nuclear and radiological emergency response and recovery. Created in 2010 with 57 organisations from 28 different countries, the objectives of the platform are to: improve the effectiveness and coherency of current approaches to preparedness; identify further development needs; improve 'know how' and technical expertise; and establish a forum for dialogue and methodological development. The NERIS Strategic Research Agenda is now structured with three main challenges: (i) radiological impact assessments during all phases of nuclear and radiological events; (ii) countermeasures and countermeasure strategies in emergency and recovery, decision support, and disaster informatics; and (iii) setting up a multi-faceted framework for preparedness for emergency response and recovery. The Fukushima accident has highlighted some key issues for further consideration in NERIS research activities, including: the importance of transparency of decision-making processes at local, regional, and national levels; the key role of access to environmental monitoring; the importance of dealing with uncertainties in assessment and management of the different phases of the accident; the use of modern social media in the exchange of information; the role of stakeholder involvement processes in both emergency and recovery situations; considerations of societal, ethical, and economic aspects; and the reinforcement of education and training for various actors. This paper emphasises the main issues at stake for NERIS for post-accident management.

Ultrafocused Electromagnetic Field Pulses with a Hollow Cylindrical Waveguide.

We theoretically show that a dipole externally driven by a pulse with a lower-bounded temporal width, and placed inside a cylindrical hollow waveguide, can generate a train of arbitrarily short and focused electromagnetic pulses. The waveguide encloses vacuum with perfect electric conducting walls. A dipole driven by a single short pulse, which is properly engineered to exploit the linear spectral filtering of the cylindrical hollow waveguide, excites longitudinal waveguide modes that are coherently refocused at some particular instances of time, thereby producing arbitrarily short and focused electromagnetic pulses. We numerically show that such ultrafocused pulses persist outside the cylindrical waveguide at distances comparable to its radius.

Preliminary study on serum paraoxonase-1 status and chemokine (C-C motif) ligand 2 in hospitalized elderly patients with catheter-associated asymptomatic bacteriuria.

Urinary tract infections (UTI) are common among elderly patients in residential care facilities, as well as in the hospital setting. Identifying new biochemical markers of UTI is an active line of research since UTI management is resource intensive. Paraoxonase-1 (PON1) forms part of the patient's immune system, the response-to-injury and inflammation. Our study sought to evaluate alterations in inflammation-related paraoxonase-1 (PON1) and chemokine (C-C motif) ligand 2 (CCL2) in patients with an indwelling catheter to assess their potential usefulness as biomarkers of infection. Patients (n = 142) who had had the urinary catheter removed and 100 healthy volunteers were recruited. In all participants we measured serum PON1 activity, PON1 concentration, CCL2, procalcitonin and C-reactive protein (CRP). Results indicated that patients had higher CCL2, CRP and procalcitonin concentrations than the control group, and lower paraoxonase activity. There were no significant differences in PON1 concentrations. When comparing the diagnostic accuracy of CRP, procalcitonin, CCL2 and the PON1-related variables in discriminating between patients with and those without UTI, we found a considerable degree of overlap between groups, i.e., a low diagnostic accuracy. However, there were significant inverse logarithmic correlations between serum paraoxonase activity and the number of days the urinary catheter had been in situ. Our results suggest that measurement of these biochemical variables may be useful in investigating complications of long-term use of these devices and help to improve the economic and clinical investment required in the management of the often-associated infection.

A preliminary study of a new endodontic irrigation system: Clean Jet Endo.

The purpose of the present study was to assess the irrigant penetration and cleaning ability of a new irrigation system, the Clean Jet Endo (Produits Dentaires SA, Switzerland) in comparison to conventional irrigation followed or not by sonic activation. Irrigant penetration was evaluated on resin blocks simulators by measuring the methylene blue absorbance thanks to a UV/visible spectrophotometer and cleaning ability was assessed in an ex vivo experiment according to the debris score in an artificial canal extension before and after the final irrigation protocol. A statistical analysis was carried out in order to highlight the significant differences between the irrigation techniques. Clean Jet Endo permitted to better eliminate the methylene blue into the simulated canals. A significant difference between the 2 techniques was observed in the middle third (p = 0.005) as well as in the apical third (p < 0.2). An additional microscope observation (16X) confirmed that Clean Jet Endo@ usage led to a better penetration of irrigant within the lateral canals of the simulators. Likewise, this irrigating system permitted to better eliminate the debris in the lateral groove than the other techniques. In conclusion, our findings implied the potential of this new irrigation system to enhance root canal debridement and disinfection.