Laronidase-loaded liposomes reach the brain and other hard-to-treat organs after noninvasive nasal administration.

Mucopolysaccharidosis type I (MPS I) is caused by a lack of the lysosomal enzyme α-L-iduronidase (IDUA), responsible for the degradation of the glycosaminoglycans (GAGs) dermatan and heparan sulfate, leading to multisystemic signs and symptoms. Enzyme replacement therapy (ERT) is a treatment that consists of weekly intravenous administrations of laronidase, a recombinant version of IDUA. However, ERT has limited access to certain tissues, such as bone, cartilage, and brain, and laronidase fails to trespass the BBB. In this sense, this study reports the development and characterization of laronidase-loaded liposomes for the treatment of MPS I mice. Liposomal complexes were obtained by the thin film formation method followed by microfluidization. The main characterization results showed mean vesicle size of 103.0 ± 3.3 nm, monodisperse populations of vesicles, zeta potential around + 30.0 ± 2.1 mV, and mucoadhesion strength of 5.69 ± 0.14 mN. Treatment of MPS I mice fibroblasts showed significant increase in enzyme activity. Nasal administration of complexes to MPS I mice resulted in significant increase in laronidase activity in the brain cortex, heart, lungs, kidneys, eyes, and serum. The overall results demonstrate the feasibility of nasal administration of laronidase-loaded liposomes to deliver enzyme in difficult-to-reach tissues, circumventing ERT issues and bringing hope as a potential treatment for MPS I.

Medical staff dose estimation during pediatric cardiac interventional procedures.

The purpose of this study is to evaluate the occupational doses (eye lens, extremities and whole body) in paediatric cardiac interventional and diagnostic catheterization procedures performed in a paediatric reference hospital located in Recife, Pernambuco. For eye lens dosimetry, the results show that the left eye receives a higher dose than the right eye, and there is a small difference between the doses received during diagnostic (D) and therapeutic (T) procedures. The extrapolated annual values for the most exposed eye are close to the annual limit. For doses to the hands, it was observed that in a significant number of procedures (37 out of 45 therapeutic procedures, or 82%) at least one hand of the physician was exposed to the primary beam. During diagnostic procedures, the physician's hand was in the radiation field in 11 of the 17 catheterization procedures (65%). This resulted in a 10-fold increase in dose to the hands. The results underscore the need for optimization of radiation safety and continued efforts to engage staff in a radiation safety culture.

Detection of metallo-beta-lactamase-producing genes blaSPM and blaNDM in Pseudomonas aeruginosa isolated from wastewater in Southern Brazil.

Pseudomonas aeruginosa is commonly associated with the ability to acquire antimicrobial resistance. The surveillance of resistance genes in various environmental matrices has gained prominence in recent years, being seen as a potential threat to public health. The objective of this study was to investigate genes encoding metallo-beta-lactamases (MBLs), which confer resistance to carbapenems, in wastewater. Fifteen isolates of P. aeruginosa were collected for five months from samples obtained from a municipal wastewater treatment plant in Rio Grande do Sul. These isolates were subjected to disk diffusion testing using 10 different antimicrobials. Phenotypic enzymatic tests for MBLs were conducted, and positive isolates underwent DNA extraction and gene detection using the polymerase chain reaction. The resistance rate to ceftazidime was 100%, cefepime 73.3%, piperacillin-tazobactam 66.67%, imipenem 53.30%, levofloxacin 46.67%, tobramycin 40%, and ciprofloxacin and amikacin 13.33%. Both meropenem and aztreonam resistances were rare accounting for 6.60% of the tested isolates. Among these isolates, 20% were classified as multidrug-resistant and were found to carry the blaNDM and blaSPM genes. The results suggest that evaluating resistance genes in bacteria from urban raw sewage can provide data that assist in surveillance, as this environment can stimulate increased bacterial resistance.

Development of ring radiation dosemeters using 3D printing.

Extremity radiation monitoring is an important tool for the assessment of occupational exposures to staff at a variety of workplaces where ionising radiation is used. This work shows the feasibility of applying 3D printing for the development of customisable ring dosemeters. The rings were developed using two types of resin, hard and flexible and has the possibility of sterilisation using different techniques. The printed ring dosemeter was associated with BeO optically stimulated dosemeters. The energy and angular response were found within ±20% in the energy range from 24 to 662 keV and from 0° to 60° angle of incidence. This contributes to the reduction of measurement uncertainty when compared with currently used thermoluminescent detectors dosemeters. The new ring dosemeter showed a satisfactory response with respect to the performance criteria of the IEC 62387 Standard, in addition to providing improved ergonomics in relation to the commercial ring dosemeter.

Results and analysis of an intercomparisons study for individual monitoring services of Latin American and Caribbean regions.

The aim of this paper is to present the results obtained by the Latin-American and Caribbean personal dosimetry services that participated, with the support of IAEA, in the 2020-Eurados whole-body dosemeter intercomparison for photon radiation. All participant services in this study use thermoluminescent dosimetry (TLD) systems except one that uses optically stimulated luminescence (OSL) dosemeters. Data analysis shows that 93.4% of the results are within the acceptance range, according to International ISO Standard ISO 14146: 2018. The evaluation of the trumpet curves shows that only three laboratories presented a few dosemeters results outside the limits of acceptability. Participation in this Eurados intercomparison exercise gave the Latin American and Caribbean laboratories the opportunity to show compliance with their own quality management system, to compare results with other participants and to develop plans for improving their dosimetry systems. It also gave the assurance that occupational doses are being measured properly and following the international standards in the regions.

Determination of Ethyl Glucuronide and Ethyl Sulfate in Dried Blood Spots by UHPLC-MS-MS: Method Validation and Assessment of Ethanol Exposure in Postmortem Samples from Road Traffic Victims.

The determination of ethyl glucuronide (EtG) and ethyl sulfate (EtS) in blood has been proposed in clinical and forensic applications to identify recent alcohol consumption. Also, there is a growing interest on the use of dried blood spots (DBS) in toxicological analysis, allowing increased stability of the analytes and simplifying sample transportation and storage. This study presents the development and validation of a method for quantifying EtG and EtS in DBS using ultra-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS-MS). The DBS samples were extracted with a mixture of methanol and acetonitrile (80:20 v/v) and analyzed using UHPLC-MS-MS with electrospray source in negative mode, after separation with a fluoro-phenyl stationary phase. Validation was performed according to the Scientific Working Group for Forensic Toxicology (SWGTOX) guidelines, with calibrations ranging from 0.10 to 18 µg/mL for EtG and 0.02 to 6 µg/mL for EtS. The analytes were stable in DBS stored from -20 to 45°C for 21 days. The method was successfully applied to capillary and venous DBS samples from 20 volunteers after ethanol ingestion and to DBS samples from 99 fatal victims of road traffic injuries. Capillary DBS was comparable to venous DBS and fresh whole blood in Passing-Bablok and Bland-Altman analysis, with correlation coefficients >0.91 (P < 0.001) for all comparisons. In postmortem application, the DBS EtG and EtS analysis indicated positive exposure to ethanol in 72.7% of the cases (EtG: 0.10-24.0 µg/mL and EtS: 0.03-4.11 µg/mL). The identification of ethanol consumption from blood alcohol concentrations (BACs) and EtG/EtS in DBS was in agreement in 98.6% of positive and 96.3% of negative cases (kappa 0.877, P < 0.001), indicating a high level of concordance with BAC in assessing alcohol use in postmortem samples.

The Differential Effect of Schooling and Physical Activity on Dementia in Older Women and Men from Brazil: Implications for Policymaking.

BACKGROUND: Modifiable risk factors exert crucial impact on dementia. OBJECTIVE: We sought to answer the question: do two modifiable risk factors, schooling level and physical activity (PA), affect cognitive function similarly in each sex? METHODS: This cross-sectional study was conducted in 2019 and 2021, and the survey was applied to the residents of the metropolitan area of Santos, a seashore of Sao Paulo State. Four hundred and twenty-two participants (women = 254 and men = 168) were eligible. Baecke questionnaire for the elderly was applied for the classification as physically inactive (PI) or active (PA). Cognitive function was assessed by the Mini-Mental State Examination (MMSE) and the Clinical Dementia Rating (CDR). Participants were also stratified by schooling status for both sexes. RESULTS: Higher education had a sex-independent positive influence on MMSE and CDR (p < 0.001). PA influences positively MMSE in older women (PI: 25±5 and PA: 27±3, p < 0.03), but has no effect in older men (26±5 and 25±5, p > 0.05). Concordantly, older women who were PA (1.7 and 0 %) showed a lower prevalence of dementia compared with PI (6.2 and 2.1%), for mild and moderate respectively. Active older women had higher odds of improving the MMSE score (OR: 1.093; 95% CI: 1.008-1.186) than men (OR: 0.97 (95% CI: 0.896-1.051). CONCLUSION: Education affects cognitive function equally in Brazilian elderly whereas older women are more responsive to the beneficial effects of PA for dementia than men.

Masking Level Difference: Performance of School Children Aged 7-12 Years.

BACKGROUND AND OBJECTIVES: In masking level difference (MLD), the masked detection threshold for a signal is determined as a function of the relative interaural differences between the signal and the masker. Study 1 analyzed the results of school-aged children with good school performance in the MLD test, and study 2 compared their results with those of a group of children with poor academic performance. SUBJECTS AND METHODS: Study 1 was conducted with 47 school-aged children with good academic performance (GI) and study 2 was carried out with 32 school-aged children with poor academic performance (GII). The inclusion criteria adopted for both studies were hearing thresholds within normal limits in basic audiological evaluation. Study 1 also considered normal performance in the central auditory processing test battery and absence of auditory complaints and/or of attention, language or speech issues. The MLD test was administered with a pure pulsatile tone of 500 Hz, in a binaural mode and intensity of 50 dBSL, using a CD player and audiometer. RESULTS: In study 1, no significant correlation was observed, considering the influence of the variables age and sex in relation to the results obtained in homophase (SoNo), antiphase (SπNo) and MLD threshold conditions. The final mean MLD threshold was 13.66 dB. In study 2, the variables did not influence the test performance either. There was a significant difference between test results in SπNo conditions of the two groups, while no differences were found both in SoNo conditions and the final result of MLD. CONCLUSIONS: In study 1, the cut-off criterion of school-aged children in the MLD test was 9.3 dB. The variables (sex and age) did not interfere with the MLD results. In study 2, school performance did not differ in the MLD results. GII group showed inferior results than GI group, only in SπNo condition.

Dosimetric evaluation of X-ray examinations of paranasal sinuses in pediatric patients.

OBJECTIVE: To estimate the entrance surface air kerma (Ka,e) and air kerma in the region of radiosensitive organs in radiographs of pediatric paranasal sinuses. MATERIALS AND METHODS: Patient data and irradiation parameters were collected in examinations of the paranasal sinuses in children from 0 to 15 years of age at two children's hospitals in the city of Recife, PE, Brazil. We estimated the Ka,e using the X-ray tube outputs and selected parameters. To estimate the air kerma values in the regions of the eyes and thyroid, we used thermoluminescent dosimeters. RESULTS: The Ka,e values ranged from 0.065 to 1.446 mGy in cavum radiographs, from 0.104 to 7.298 mGy in Caldwell views, and from 0.113 to 7.824 mGy in Waters views. Air kerma values in the region of the eyes ranged from 0.001 to 0.968 mGy in cavum radiographs and from 0.011 to 0.422 mGy in Caldwell and Waters views . In the thyroid region, air kerma values ranged from 0.005 to 0.932 mGy in cavum radiographs and from 0.002 to 0.972 mGy in Caldwell and Waters views. CONCLUSION: The radiation levels used at the institutions under study were higher than those recommended in international protocols. We recommend that interventions be initiated in order to reduce patient exposure to radiation and therefore the risks associated with radiological examination of the paranasal sinuses.

OBJETIVO: Estimar o kerma no ar na superfície de entrada (Ka,e) e o kerma no ar na região de órgãos radiossensíveis em radiografias pediátricas dos seios paranasais. MATERIAIS E MÉTODOS: Foram coletados os dados dos pacientes e parâmetros de irradiação em exames de seios paranasais de crianças com 0 a 15 anos, em dois hospitais infantis na cidade do Recife, PE. O Ka,e foi estimado utilizando os rendimentos dos tubos de raios X e os parâmetros selecionados. Os valores de kerma no ar nas regiões dos olhos e tireoide foram estimados utilizando dosímetros termoluminescentes. RESULTADOS: Os valores de Ka,e variaram de 0,065 a 1,446 mGy para radiografias cavum, 0,104 a 7,298 mGy para Caldwell e 0,113 a 7,824 mGy para Waters. Os valores de kerma no ar na região dos olhos variaram de 0,001 a 0,968 mGy para cavum e 0,011 a 0,422 mGy para Caldwell e Waters. Na região tireóidea, os valores de kerma no ar variaram de 0,005 a 0,932 mGy para cavum e 0,002 a 0,972 mGy para Caldwell e Waters. CONCLUSÃO: Os parâmetros de irradiação utilizados pelas instituições foram mais elevados do que os recomendados em protocolos britânicos. Ações de otimização são recomendadas de modo a contribuir para a redução da radiação nos pacientes e, portanto, os riscos.