Beyond a Transmission Cable-New Technologies to Reveal the Richness in Axonal Electrophysiology.

The axon is a neuronal structure capable of processing, encoding, and transmitting information. This assessment contrasts with a limiting, but deeply rooted, perspective where the axon functions solely as a transmission cable of somatodendritic activity, sending signals in the form of stereotypical action potentials. This perspective arose, at least partially, because of the technical difficulties in probing axons: their extreme length-to-diameter ratio and intricate growth paths preclude the study of their dynamics through traditional techniques. Recent findings are challenging this view and revealing a much larger repertoire of axonal computations. Axons display complex signaling processes and structure-function relationships, which can be modulated via diverse activity-dependent mechanisms. Additionally, axons can exhibit patterns of activity that are dramatically different from those of their corresponding soma. Not surprisingly, many of these recent discoveries have been driven by novel technology developments, which allow for in vitro axon electrophysiology with unprecedented spatiotemporal resolution and signal-to-noise ratio. In this review, we outline the state-of-the-art in vitro toolset for axonal electrophysiology and summarize the recent discoveries in axon function it has enabled. We also review the increasing repertoire of microtechnologies for controlling axon guidance which, in combination with the available cutting-edge electrophysiology and imaging approaches, have the potential for more controlled and high-throughput in vitro studies. We anticipate that a larger adoption of these new technologies by the neuroscience community will drive a new era of experimental opportunities in the study of axon physiology and consequently, neuronal function.

Morphological aspects and the effectiveness of photodynamic inactivation against Rhizopus oryzae in different life cycles.

Mucormycosis is an extremely aggressive fungal disease with a high mortality rate, especially in people with compromised immune systems. Most cases of mucormycosis are caused by the fungus Rhizopus oryzae. The treatments used are based on high doses of antifungals, associated with surgical resections, when it is possible. However, even with this aggressive treatment, the estimated attributable mortality rate is high. There is therefore a need to develop adjuvant treatments. Photodynamic Inactivation (PDI) may be an auxiliary therapeutic option for mucormycosis. Due to the lack of reports in the literature on the morphology and photodynamic inactivation of R. oryzae, characterization of the fungus using Confocal Microscopy and Transmission Electron Microscopy, and different protocols using Photodithazine® (PDZ), a chlorin e6 compound, as a photosensitizer, were performed. The fungus growth rate under different concentrations and incubation times of the photosensitizer and its association with the surfactant Sodium Dodecyl Sulphate (SDS) was evaluated. For the hyphae, both in the light and dark phases, in the protocols using only PDZ, no effective photodynamic response was observed. Meanwhile with the combination of SDS 0.05% and PDZ, inhibition growth rates of 98% and 72% were achieved for the white and black phase, respectively. In the conidia phase, only a 1.7 log10 reduction of the infective spores was observed. High concentration of melanin and the complex and resistant structures, especially at the black phase, results in a high limitation of the PDI inactivation response. The combined use of the SDS resulted in an improved response, when compared to the one obtained with the amphotericin B treatment.

Fetal 4D flow MRI of the great thoracic vessels at 3 Tesla using Doppler-ultrasound gating: a feasibility study.

OBJECTIVES: To evaluate the feasibility of Doppler-ultrasound (DUS)-gated 4D flow MRI of the fetal great thoracic vessels at 3T in a clinical setting. METHODS: Sixteen consecutive fetuses (range 30+4-38+5 weeks) with (n = 11) and without (n = 5) cardiovascular anomalies underwent 4D flow MRI of the great thoracic vessels at 3T. Direct fetal cardiac gating was obtained using a MR-compatible DUS device. 4D flow MRI-based visualisation and quantification of four target regions (ascending aorta (AAo), descending aorta (DAo), main pulmonary artery (MPA), and ductus arteriosus (DA)) were performed using dedicated software. RESULTS: Fetal 4D flow MRI of the great thoracic vessels was successful in 12/16 fetuses (75%) by adopting clinical 4D flow MR protocols in combination with direct fetal cardiac DUS-gating. Four datasets were excluded due to artefacts by fetal movement or maternal breathing. 4D flow MRI-derived time-velocity curves revealed typical arterial blood flow patterns in the aorta. 4D flow quantification was achieved for the pre-defined target regions. Average velocity and flow volume were 21.1 ± 5.2 cm/s and 6.0 ± 3.1 mL/s in the AAo, 24.3 ± 6.7 cm/s and 8.4 ± 3.7 mL/s in the DAo, 21.9 ± 6.4 cm/s and 7.8 ± 4.2 mL/s in the MPA, and 23.4 ± 4.7 cm/s and 5.9 ± 3.6 mL/s in the DA, respectively. CONCLUSIONS: Combination of DUS-gating of the fetal heart and 4D flow MRI allows comprehensive visualisation and quantification of haemodynamics in the fetal great thoracic vessels. DUS-gated fetal 4D flow MRI may provide a new diagnostic approach for prenatal assessment of blood flow haemodynamics. KEY POINTS: • Fetal cardiac Doppler-ultrasound (DUS) gating and 4D flow MRI can be successfully combined. • DUS-gated fetal 4D flow MRI allowed visualisation and evaluation of streamline directionality, illustration of blood flow variations, and pulsatile arterial waveforms in the target vessels. • 4D flow MRI-based visualisation and quantification of the fetal great thoracic vessels were successful and flow metrics agreed with echocardiographic reference values.

Phytochemicals Against Drug-Resistant Bacterial Biofilms and Use of Green Extraction Solvents to Increase Their Bioactivity.

Antimicrobial resistance has become one of the major global public health issues of the twenty-first century. One of the main factors in the limited action of antimicrobials is related to the ability of microorganisms, particularly bacteria, to form biofilms. These complex and well-organized communities allow the colonizing cells to acquire survival advantages over the same cells in suspension, including antibiotic resistance. A huge percentage of bacterial infections in humans are associated with biofilms, and many of them are chronic. Therefore, there is an urgent need to develop new products effective in controlling or eradicating biofilms. Plant secondary metabolites (phytochemicals) have demonstrated their potential as antibacterials against planktonic cells and sessile communities when used alone or in synergy with other molecules. This chapter covers recent advances in the activity of phytochemicals against biofilms, particularly those formed by drug-resistant bacteria. In addition, taking into account that the extraction step is crucial for the successful development of new bioactive compounds, the use of novel solvents that increase the phytochemical effect, such as natural deep eutectic solvents (NADES), as well as the recent applications of these solvents as antimicrobials are discussed.

Characterization of a DRC1 null variant associated with primary ciliary dyskinesia and female infertility.

PROPOSE: We here present a female case with primary ciliary dyskinesia (PCD) and infertility. In this report, we also present the evaluation of the patient family, including her twin sister, also with PCD and infertility. METHODS: Confirmation of the PCD clinical diagnosis was performed through assessment of cilia motility, by high-speed video microscopy (HSVM), axoneme ultrastructure, by transmission electron microscopy (TEM), and genetic characterization, by whole-exome sequence (WES). Gene expression studies used qPCR for mRNA expression and immunofluorescence to determine cell protein localization. RESULTS: We identified a homozygous nonsense variant in the DRC1 gene (NM 145038.5:c.352C>T (p.Gln118Ter)) in the female patient with PCD and infertility that fit the model of autosomal recessive genetic transmission. This variant eventually results in a dyskinetic ciliary beat with a lower frequency and a partial lack of both dynein arms as revealed by TEM analysis. Moreover, this variant implies a decrease in the expression of DRC1 mRNA and protein. Additionally, expression analysis suggested that DRC1 may interact with other DRC elements. CONCLUSIONS: Our findings suggest that the DRC1 null variant leads to PCD associated with infertility, likely caused by defects in axoneme from Fallopian tube cilia. Overall, our outcomes contribute to a better understanding of the genetic factors involved in the pathophysiology of PCD and infertility, and they highlight the interaction of different genes in the patient phenotype, which should be investigated further because it may explain the high heterogeneity observed in PCD patients.

Allergy to lipid transfer proteins (LTP) in a pediatric population.

Summary: Background. Lipid transfer proteins (LTP) are considered important plant food allergens in the Mediterranean area, but little is known about LTP allergy in pediatric age. Our aim was to characterize LTP allergy in children.Methods. We reviewed the clinical data from all children evaluated in our department with LTP allergy. From the 76 patients with LTP allergy, 26c hildren were included, 50% female, median age 10 years (1-17). Symptoms included urticaria in 58% (n = 15), anaphylaxis in 46% (n = 12) and OAS in 42% (n = 11). Results. Multiple reactions with different foods occurredin 69%. Cofactors were reported in 27% (n = 7). All patients had positive SPT to peach LTP extract and sIgE Pru p 3. No association between the occurrence of severe reactions and sIgE to Pru p 3 (p = 0.462), sIgE to Cor a 8(p = 0.896), SPT to peach LTP extract (p = 0.846) or the number of positive SPT to fruits/tree nuts (p = 0.972; p = 0.676) was found. Ninety-two percent of the patients tolerated fruits from Rosacea family without peel. Twelve percent reported reactions to new LTP containing foods during follow-up. LTP allergy can occur since early childhood. Conclusions. Since anaphylaxisis common and cofactors act as severity enhancers, it is fundamental to recognizeLTP allergy in children. Currently available diagnostic tests (SPT and sIgE) cannot accurately predict food tolerance or anticipate reaction severity.

Relevance of the diagnosis of hypersensitivity reactions to antineoplastic and biological agents: experience with drug provocation test.

Summary: Background. Evidence regarding drug provocation test (DPT) with chemotherapeutic agents is scarce. The aim of our study is to describe the experience of DPT in patients with a history of hypersensitivity reactions (HSRs) to antineoplastic and biological agents. Methods. This was an eight-year retrospective, observational, descriptive study of patients with a history of HSRs to chemotherapy who were submitted to DPT. Anamnesis, skin tests (ST) and DPT were analyzed. Patients with a negative DPT were submitted to at least one regular supervised administration (RSA). Patients with positive DPT or HSR during RSA were offered rapid drug desensitization (RDD). Results. A total of 54 patients were submitted to DPT. The most common suspected drugs were platins (n = 36), followed by taxanes (n = 11). Most initial reactions were classified as grade II (n = 39) according to Brown's grading system. ST with platinum (n = 35), taxanes (n = 10) and biological agents (n = 4) were negative, except for one intradermal test with paclitaxel, which was positive. A total of 64 DPTs were performed. Eleven percent of all DPTs were positive (platins (n = 6), doxorubicin (n = 1)). Of the 57 RSA with the culprit drugs, 2 were positive (platins). The diagnosis of hypersensitivity was confirmed by DPT/RSA in 9 patients. All patients with positive DPT/RSA presented HSRs of equal or less severity than the initial one. Conclusions. DPT followed by RSA allowed to exclude HSRs in 45 patients (55 culprit drugs). DPT before desensitization prevents non-hypersensitivity patients from undergoing RDD. In our study DPT was safe, all reactions were managed by an allergist.

Skin sensitization to fragrance hydroperoxides: interplay between dendritic cells, keratinocytes and free radicals.

BACKGROUND: Skin sensitization to hydroperoxides (R-OOHs) of the commonly used fragrance terpenes limonene, linalool and citronellol is frequently reported. R-OOHs are believed to initiate the process leading to sensitization and allergic contact dermatitis through mechanisms involving radical intermediates. Thus, radical intermediates, keratinocytes and dendritic cells (DCs) may act in concert to initiate the process. OBJECTIVES: To evaluate individual DC activation profiles by R-OOHs in the context of keratinocytes with regard to frequency, specificity and magnitude of upregulation. METHODS: We used 2D and 3D cocultures with keratinocytes/reconstructed human epidermis (RHE) and DCs to evaluate cell surface levels of the costimulatory molecules CD86, CD80 and the adhesion molecule CD54 on cocultured DCs. Analysis of radical formation from limonene hydroperoxides in RHE was performed using electron paramagnetic resonance combined with the spin trapping technique. RESULTS: R-OOHs induce donor-dependent DC activation. Major differences were found between the limonene-OOHs. Limonene-1-OOH was stronger with respect to both frequency and magnitude of response. Using a 3D coculture model, no DC activation was detected after topical application of 0·2% limonene-OOHs (20 µg cm-2 ), while 1·2% limonene-1-OOH or 2% limonene-2-OOH induced DC activation. Furthermore, we demonstrated differences in the carbon and oxygen radicals formed from the limonene-OOHs using RHE, mimicking what may happen in vivo. CONCLUSIONS: We report clear individual differences in DC maturation induced by the most important hydroperoxides. Response rates and magnitude of response both indicate that very small structural alterations in the hydroperoxides are translated into specific DC responses. In addition, we provide more insight into the amounts of hydroperoxides that can activate DCs and induce sensitization.

Pilot approach to analyzing patient and citizen involvement in health technology assessment in four diverse low- and middle-income countries.

BACKGROUND: In low- and middle-income countries (LMICs) striving to achieve universal health coverage, the involvement of different stakeholders in formal or informal ways in health technology assessment (HTA) must be culturally and socially relevant and acceptable. Challenges may be different from those seen in high-income countries. In this article, we aimed to pilot a questionnaire for uncovering the context-related aspects of patient and citizen involvement (PCI) in LMICs, collecting experiences encountered with PCI, and identifying opportunities for patients and citizens toward contributing to local decision- and policy-making processes related to health technologies. METHODS: Through a collaborative, international multi-stakeholder initiative, a questionnaire was developed for describing each LMIC's healthcare system context and the emergence of opportunities for PCI relating to HTA. The questionnaire was piloted in the first set of countries (Brazil, Indonesia, Nigeria, and South Africa). RESULTS: The questionnaire was successfully applied across four diverse LMICs, which are at different stages of using HTA to inform decision making. Only in Brazil, formal ways of PCI have been defined. In the other countries, there is informal influence that is contingent upon the engagement level of patient and citizen advocacy groups (PCAGs), usually strongest in areas such as HIV/AIDS, TB, oncology, or rare diseases. CONCLUSIONS: The questionnaire can be used to analyze the options for patients and citizens to participate in HTA or healthcare decision making. It will be rolled out to more LMICs to describe the requirements and opportunities for PCI in the context of LMICs and to identify possible routes and methodologies for devising a more systematic and formalized PCI in LMICs.

Low-dimensional chaos in the single wave model for self-consistent wave-particle Hamiltonian.

We analyze nonlinear aspects of the self-consistent wave-particle interaction using Hamiltonian dynamics in the single wave model, where the wave is modified due to the particle dynamics. This interaction plays an important role in the emergence of plasma instabilities and turbulence. The simplest case, where one particle (N=1) is coupled with one wave (M=1), is completely integrable, and the nonlinear effects reduce to the wave potential pulsating while the particle either remains trapped or circulates forever. On increasing the number of particles ( N=2, M=1), integrability is lost and chaos develops. Our analyses identify the two standard ways for chaos to appear and grow (the homoclinic tangle born from a separatrix, and the resonance overlap near an elliptic fixed point). Moreover, a strong form of chaos occurs when the energy is high enough for the wave amplitude to vanish occasionally.

Evaluation of the sensitivity of the Express View function in the Mirocam® capsule endoscopy software.

Background: A new computer algorithm called Express-View has recently been introduced by Mirocam, but data concerning its application and efficacy are scarce.Objective: To evaluate the lesion detection rate, per-patient sensitivity and the diagnostic accuracy using Express-View.Methods: All patients who performed CE between January 2018 and June 2019, whose indication was obscure gastrointestinal bleeding (OGIB) and with findings on CE, were included. Lesions identified in conventional reading were selected and considered as reference.Results: Eighty-nine patients were included, 50.6% male, with a mean age of 68.4 years-old (±12.3). The Express-View mode detected 85.5% of lesions previously detected by conventional reading (524 out of 613). There were 89 missed lesions, mainly erosions or ulcers (44.9%) and angioectasias (38.2%). The lesion detection rate was found to be lower in the jejunum and ileum compared to extra-small bowel locations and duodenum (p = .04). Although Express-View had a per-patient sensitivity for all lesions of 56.2% and a per-patient sensitivity for all clinically significant lesions of 83.1%, it achieved a diagnostic accuracy of 91%.Conclusions: The per-patient sensitivity for all lesions was shown to be below expectations, although the lesion detection rate, the per-patient sensitivity for all clinically significant lesions, and the diagnostic accuracy were shown to be higher.

First-trimester intervention in twin reversed arterial perfusion sequence.

OBJECTIVE: To report the outcome of monochorionic twins with twin reversed arterial perfusion (TRAP) sequence following interstitial laser therapy in the first trimester. METHODS: This was a retrospective cohort study of all consecutive cases of TRAP that underwent interstitial laser therapy at ≤ 14 + 3 weeks' gestation between January 2014 and April 2016. Interstitial laser treatment was performed under ultrasound guidance using a 400-nm Nd:YAG laser fiber. Hospital records were reviewed to ascertain perinatal survival and morbidity. RESULTS: Twelve monochorionic twin pregnancies underwent interstitial laser treatment of the umbilical artery of the acardiac fetus, at a median gestational age of 13 + 5 (interquartile range (IQR), 13 + 4 to 14 + 0) weeks. In all cases, one treatment was sufficient to achieve complete interruption of the perfusion of the acardiac twin. There were no procedure-related complications during or within 48 h after the procedure. In one (8.3%) case, intrauterine death of the pump twin occurred 2 weeks after the intervention. All other cases (91.7%) resulted in a live birth at a median gestational age of 39 + 6 (IQR, 37 + 1 to 41 + 2) weeks and with a median birth weight of 3370 (IQR, 2980-3480) g. No neonatal mortality or serious morbidity occurred. CONCLUSIONS: Our results support the use of interstitial laser therapy in the first trimester of pregnancy complicated by TRAP sequence, showing a live birth rate of 92%. The results of a randomized controlled trial, evaluating early vs late intervention in pregnancy with TRAP sequence, are awaited. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

A systematic review of the impact of contemporary treatment modalities for cervical cancer on women's self-reported health-related quality of life.

PURPOSE: Given the high survival rate of cervical cancer patients, understanding women's health-related quality of life (HRQL) during and after treatment is of major clinical importance. We conducted a systematic review to synthesize all available evidence about the effects of each contemporary treatment modality for cervical cancer on all dimensions of women's HRQL, including symptoms, functioning, and global HRQL. METHODS: We searched four electronic databases from January 2000 to September 2019, cross-referenced and searched by author name for studies of patients treated for cervical cancer that reported patient-reported outcomes (PROs) before treatment and with at least one post-treatment measurement. Two independent reviewers applied inclusion and quality criteria and extracted findings. Studies were categorized by treatment to determine specific treatment effects on PROs. Results were narratively summarized. RESULTS: We found twenty-nine papers reporting 23 studies. After treatments with curative intent for early or locally advanced disease, lymphedema, diarrhea, menopausal symptoms, tight and shorter vagina, pain during intercourse, and sexual worries remained long-term problems; however, sexual activity improved over time. HRQL and psychological distress were impacted during treatment with also worsening of global HRQL but improved 3-6 months after treatment. In patients with metastatic or recurrent disease, pain improved during palliative treatment or remained stable, with no differences in global HRQL found over time. CONCLUSION: Whereas most symptoms worsen during treatment and improve in the first 3 months after completing treatment, symptoms like lymphedema, menopausal symptoms, and sexual worries develop gradually and persist after curative treatment. These findings can be used to inform clinical practice and facilitate communication and shared decision-making. More research is needed in very early cervical cancer and the impact of fertility sparing therapy on PROs.

Fetal dynamic phase-contrast MR angiography using ultrasound gating and comparison with Doppler ultrasound measurements.

OBJECTIVES: To investigate the feasibility of fetal phase-contrast (PC)-MR angiography of the descending aorta (AoD) using an MR-compatible Doppler ultrasound sensor (DUS) for fetal cardiac gating and to compare velocimetry with Doppler ultrasound measurements. METHODS: In this prospective study, 2D PC-MR angiography was performed in 12 human fetuses (mean gestational age 32.8 weeks) using an MR-compatible DUS for gating of the fetal heart at 1.5 T. Peak flow velocities in the fetal AoD were compared with Doppler ultrasound measurements performed on the same day. Reproducibility of PC-MR measurements was tested by repeated PC-MR in five fetuses. RESULTS: Dynamic PC-MR angiography in the AoD was successfully performed in all fetuses using the DUS, with an average fetal heart rate of 140 bpm (range 129-163). Time-velocity curves revealed typical arterial blood flow patterns. PC-MR mean flow velocity and mean flux were 21.2 cm/s (range 8.6-36.8) and 8.4 ml/s (range 3.2-14.6), respectively. A positive association between PC-MR mean flux and stroke volume with gestational age was obtained (r = 0.66, p = 0.02 and r = 0.63, p = 0.03). PC-MR and Doppler ultrasound peak velocities revealed a highly significant correlation (r = 0.8, p < 0.002). Peak velocities were lower for PC-MR with 69.1 cm/s (range 39-125) compared with 96.7 cm/s (range 60-142) for Doppler ultrasound (p < 0.001). Reproducibility of PC-MR was high (p > 0.05). CONCLUSION: The MR-compatible DUS for fetal cardiac gating allows for PC-MR angiography in the fetal AoD. Comparison with Doppler ultrasound revealed a highly significant correlation of peak velocities with underestimation of PC-MR velocities. This new technique for direct fetal cardiac gating indicates the potential of PC-MR angiography for assessing fetal hemodynamics. KEY POINTS: • The developed MR-compatible Doppler ultrasound sensor allows direct fetal cardiac gating and can be used for prenatal dynamic cardiovascular MRI. • The MR-compatible Doppler ultrasound sensor was successfully applied to perform intrauterine phase-contrast MR angiography of the fetal aorta, which revealed a highly significant correlation with Doppler ultrasound measurements. • As fetal flow hemodynamics is an important parameter in the diagnosis and management of fetal pathologies, fetal phase-contrast MR angiography may offer an alternative imaging method in addition to Doppler ultrasound and develop as a second line tool in the evaluation of fetal flow hemodynamics.

Role of fetal intertwin difference in middle cerebral artery peak systolic velocity in predicting neonatal twin anemia-polycythemia sequence.

OBJECTIVES: To evaluate the relationship between the fetal intertwin difference in middle cerebral artery peak systolic velocity (MCA-PSV) and intertwin difference in hemoglobin (Hb) concentration at birth in monochorionic diamniotic (MCDA) twin pregnancies in order to assess its potential role in the prediction of twin anemia-polycythemia sequence (TAPS). METHODS: This was a retrospective cohort study of MCDA twin pregnancies delivered between January 2012 and January 2018. All pregnancies with measurements of MCA-PSV within 7 days prior to delivery and in which neonatal Hb concentration was available were included. The correlation between fetal intertwin difference in MCA-PSV, expressed in multiples of the median (MoM), and neonatal intertwin difference in Hb concentration was investigated. Receiver-operating characteristics (ROC) curve analysis was used to assess the performance of fetal intertwin difference in MCA-PSV for predicting intertwin difference in Hb > 90th centile at birth. RESULTS: A total of 154 out of 256 MC twin pregnancies fulfilled the inclusion criteria. Fetal intertwin difference in MCA-PSV MoM correlated positively with neonatal intertwin difference in Hb concentration (r = 0.79; P < 0.001). The 90th centile for intertwin difference in Hb was 7.25 g/dL. There were 15 (9.7%) cases with a Hb difference ≥ 7.25 g/dL at birth. ROC curve analysis showed a high accuracy of fetal intertwin MCA-PSV MoM difference for the prediction of neonatal intertwin Hb difference ≥ 7.25 g/dL at birth (area under the ROC curve, 0.976 (95% CI, 0.935-0.993); P = 0.012). The optimal cut-off for intertwin MCA-PSV MoM difference was 0.373, with a sensitivity of 93.3% (95% CI, 68.1-99.8%) and a specificity of 95.7% (95% CI, 90.8-98.4%). The positive predictive value was 70% (95% CI, 45.7-88.1%) and the negative predictive value was 99.3% (95% CI, 95.9-100%). CONCLUSION: Our findings show that fetal intertwin MCA-PSV MoM difference is a good predictor of neonatal intertwin Hb concentration difference > 90th centile and potentially of TAPS. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Dynamic fetal cardiac magnetic resonance imaging in four-chamber view using Doppler ultrasound gating in normal fetal heart and in congenital heart disease: comparison with fetal echocardiography.

OBJECTIVES: To investigate the diagnostic performance of dynamic fetal cardiac magnetic resonance imaging (MRI), using a MR-compatible Doppler ultrasound (DUS) device for fetal cardiac gating, in differentiating fetuses with congenital heart disease from those with a normal heart, and to compare the technique with fetal echocardiography. METHODS: This was a prospective study of eight fetuses with a normal heart and four with congenital heart disease (CHD), at a median of 34 (range, 28-36) weeks' gestation. Dynamic fetal cardiac MRI was performed using a DUS device for direct cardiac gating. The four-chamber view was evaluated according to qualitative findings. Measurements of the length of the left and right ventricles, diameter of the tricuspid and mitral valves, myocardial wall thickness, transverse cardiac diameter and left ventricular planimetry were performed. Fetal echocardiography and postnatal diagnoses were considered the reference standards. RESULTS: Direct cardiac gating allowed continuous triggering of the fetal heart, showing high temporal and spatial resolution. Both fetal cardiac MRI and echocardiography in the four-chamber view detected pathological findings in three of the 12 fetuses. Qualitative evaluation revealed overall consistency between echocardiography and MRI. On both echocardiography and MRI, quantitative measurements revealed significant differences between fetuses with a normal heart and those with CHD with respect to the length of the right (P < 0.01 for both) and left (P < 0.01 for both) ventricles and transverse cardiac diameter (P < 0.05 and P < 0.01, respectively). Tricuspid valve diameter on cardiac MRI was found to be significantly different in healthy fetuses from in those with CHD (P < 0.05). CONCLUSIONS: For the first time, this study has shown that dynamic fetal cardiac MRI in the four-chamber view, using external cardiac gating, allows evaluation of cardiac anatomy and diagnosis of congenital heart disease in agreement with fetal echocardiography. Dynamic fetal cardiac MRI may be useful as a second-line investigation if conditions for fetal echocardiography are unfavorable. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Dose to the interventional radiologist in CTF-guided procedures.

The aim of this work was to assess the occupational dose received by an interventional radiologist (IR) during computed tomography fluoroscopy (CTF)-guided procedures; to identify the most exposed areas of the body including the hands and fingers; to suggest recommendations for individual monitoring; and to improve radiation safety of the practice. A total of 53 CTF-guided procedures were studied. Twelve whole-body dosimeters were worn by the IR in each procedure for the assessment of the personal dose equivalent, Hp(10), on the chest, waist, and back, both over and under the lead apron, as well as the personal dose equivalent, Hp(0.07), on both arms, knees, and feet. Special gloves with casings to fit extremity dosimeters were prepared to assess Hp(0.07) to the fingers. The measured chest dose values were higher than those on the waist and back; the dominant hand or the left side was the most exposed. In general, the ring, middle, and index fingers of the dominant hand were the most exposed (maximum in the 36-39 mSv range), while wrist dose was negligible compared to finger doses. Based on the results obtained the following recommendations are suggested: protective devices (lead aprons, thyroid shield, and goggles) should be worn; Hp(10) should be assessed at the chest level both above and below the lead apron; finger doses can be measured on the basis of each middle finger; the arm closer to the beam should be monitored; and finally, a wrist dosimeter will not provide useful information.

Characterization of CCDC103 expression profiles: further insights in primary ciliary dyskinesia and in human reproduction.

PROPOSE: To study CCDC103 expression profiles and understand how pathogenic variants in CCDC103 affect its expression profile at mRNA and protein level. METHODS: To increase the knowledge about the CCDC103, we attempted genotype-phenotype correlations in two patients carrying novel homozygous (missense and frameshift) CCDC103 variants. Whole-exome sequencing, quantitative PCR, Western blot, electron microscopy, immunohistochemistry, immunocytochemistry, and immunogold labelling were performed to characterize CCDC103 expression profiles in reproductive and somatic cells. RESULTS: Our data demonstrate that pathogenic variants in CCDC103 gene negatively affect gene and protein expression in both patients who presented absence of DA on their axonemes. Further, we firstly report that CCDC103 is expressed at different levels in reproductive tissues and somatic cells and described that CCDC103 protein forms oligomers with tissue-specific sizes, which suggests that CCDC103 possibly undergoes post-translational modifications. Moreover, we reported that CCDC103 was restricted to the midpiece of sperm and is present at the cytoplasm of the other cells. CONCLUSIONS: Overall, our data support the CCDC103 involvement in PCD and suggest that CCDC103 may have different assemblies and roles in cilia and sperm flagella biology that are still unexplored.

Evolution of the use of antioxidants in anti-ageing cosmetics.

OBJECTIVE: Skin health and beauty are a cornerstone of general well-being in humans. Anti-ageing cosmetics are used to provide a healthy and youthful appearance. Among the different cosmetic actives, antioxidants are incorporated in anti-ageing products due to their beneficial effects in preventing and minimizing the signs of skin ageing. This work aims to understand how anti-ageing formulations changed in the past 7 years regarding pure antioxidants composition. METHODS: Data were collected from anti-ageing formulations commercialized in main stores and pharmacies in the Portuguese market. The study started on 2011 and was updated with products launched or whose composition has been renewed on 2013, 2015 or 2018. RESULTS: Ascorbic acid and tocopherol and their derivatives were consistently the most used antioxidants in anti-ageing formulations; followed by niacinamide and retinyl palmitate. Seven ascorbic acid derivatives are currently used in anti-ageing formulations while only three tocopherol derivatives were identified in this study. Several combinations of antioxidants were routinely found, mainly tocopherol (or tocopherol derivatives) with other antioxidants and tocopherol with tocopherol derivatives. We have not identified emerging antioxidants with great impact in anti-ageing formulations even though niacinamide and retinyl palmitate exhibited over 10% more usage in 2018. CONCLUSION: This insight is relevant to the cosmetic industry providing a better understanding of the scientific-based formulation of modern cosmetics and supports the need for innovative antioxidants in anti-ageing cosmetics.

OBJECTIF: La santé de la peau et la beauté constituent la base du bien-être général chez l'homme. Les cosmétiques anti-âge sont utilisés pour donner une apparence saine et jeune. Parmi les différents principes actifs des cosmétiques, des antioxydants sont incorporées dans les produits anti-âge en raison de leur effet bénéfique sur la prévention et la réduction des signes de vieillissement de la peau. Ce travail vise à comprendre comment les formulations anti-âge ont évolué au cours des 7 dernières années au niveau des antioxydants purs composition. MÉTHODES: Les données ont été recueillies sur des formulations anti-âge commercialisées dans les principaux magasins et pharmacies du marché portugais. Cette étude a commencé en 2011 et a été mise à jour avec des produits mis sur le marché ou dont la composition a été renouvelée en 2013, 2015 ou 2018. RÉSULTATS: L'acide ascorbique et tocophérol et leurs dérivés sont systématiquement les antioxydants les plus utilisés dans les formulations anti-âge; ils sont suivis de la niacinamide et du palmitate de rétinol. Sept dérivés d'acide ascorbique sont actuellement utilisés pour lutter contre le vieillissement, tandis que seulement trois dérivés de tocophérol ont été identifiés dans cette étude. Plusieurs combinaisons d'antioxydants ont été systématiquement observées, principalement le tocophérol ou les dérivés de tocophérol avec d'autres antioxydants, et le tocophérol avec des dérivés de tocophérol. Nous n'avons pas identifié de nouveaux antioxydants présentant un impact majeur dans les formulations anti-âge, même si la niacinamide et le palmitate de rétinol ont vu leur utilisation augmenter de 10% en 2018. CONCLUSION: Cette perspective est pertinente pour le secteur des cosmétiques. Elle permet de mieux comprendre la formulation scientifique des cosmétiques modernes et confirme le besoin d'innover au niveau des antioxydants utilisés dans les produits anti-âge. Les cosmétiques anti-âge sont utilisés pour donner une apparence saine et jeune. Parmi les différents actifs cosmétiques, les antioxydants sont incorporés dans les produits anti-âge en raison de leurs effets bénéfiques dans la prévention et la réduction des signes du vieillissement cutané. Ce travail vise à comprendre comment les formulations anti - vieillissement ont changé au cours des 7 dernières années en ce qui concerne la composition en antioxydants purs.