Comparison of quality and interpretation of newborn ultrasound screening examinations for developmental dysplasia of the hip by basically trained nurses and junior physicians with no previous ultrasound experience.

BACKGROUND: We are obliged to give babies the chance to profit from a nationwide screening of developmental dysplasia of the hip in very rural areas of Mongolia, where trained physicians are scarce. This study aimed to compare the quality and interpretation of hip ultrasound screening examinations performed by nurses and junior physicians. METHODS: A group of 6 nurses and 6 junior physician volunteers with no previous ultrasound experience underwent Graf's standard training in hands-on practice. Newborns were examined before discharge from the hospital, according to the national guideline. Two standard documentation images of each hip were saved digitally. The groups were compared on the proportion of good quality of sonograms and correct interpretation. Two Swiss supervisors' agreed diagnosis according to Graf was considered the final reference for the study purposes. RESULTS: A total of 201 newborns (402 hips or 804 sonograms) were examined in the study, with a mean age of 1.3±0.8 days at examination. Junior physicians examined 100 newborns (200 hips or 400 sonograms), while nurses examined 101 newborns (202 hips or 404 sonograms). The study subjects of the two groups were well balanced for the distribution of baseline characteristics. The study observed no statistically significant difference in the quality of Graf's standard plane images between the providers. Eventually, 92.0% (92) of the physician group and 89.1% (90) of the nurse group were correctly diagnosed as "Group A" (Graf's Type 1 hip) or "Non-Group A" hips (p = 0.484). The most common errors among the groups were a missing lower limb, wrong measurement lines, and technical problems. CONCLUSION: Our study provides evidence that while there might be a trend of slightly more technical mistakes in the nurse group, the overall diagnosis accuracy is similar to junior physicians after receiving standard training in Graf's hip ultrasound method. However, after basic training, regular quality control is a must and all participants should receive refresher trainings. More specifically, nurses need training in the identification of anatomical structures.

Harmonic radiation contribution and X-ray transmission at the Small Quantum Systems instrument of European XFEL.

Transmission measurements of the soft X-ray beamline to the Small Quantum Systems (SQS) scientific instrument at the SASE3 undulator of European XFEL are presented. Measurements are reported for a wide range of photon energies (650 eV to 2400 eV), using X-ray gas monitors as well as a bolometric radiometer. The results are in good agreement with simulations for the beam transport and show a transmission of up to 80% over the whole photon energy range. The contribution of second- and third-harmonic radiation of the soft X-ray undulator is determined at selected photon energies by performing transmission measurements using a gas absorber to provide variable attenuation of the incoming photon flux. A comparison of the results with semi-analytic calculations for the generation of free-electron laser pulses in the SASE3 undulator reveals an influence of apertures along the beam transport on the exact harmonic content to be accounted for at the experiment. The second-harmonic content is measured to be in the range of 0.1% to 0.3%, while the third-harmonic contributed a few percent to the SASE3 emission. For experiments at the SQS instrument, these numbers can be reduced through specific selections of the mirror reflection angles.

Accuracy of Trained Physicians is Inferior to Deep Learning-Based Algorithm for Determining Angles in Ultrasound of the Newborn Hip.

PURPOSE: Sonographic diagnosis of developmental dysplasia of the hip allows treatment with a flexion-abduction orthosis preventing hip luxation. Accurate determination of alpha and beta angles according to Graf is crucial for correct diagnosis. It is unclear if algorithms could predict the angles. We aimed to compare the accuracy for users and automation reporting root mean squared errors (RMSE). MATERIALS AND METHODS: We used 303 306 ultrasound images of newborn hips collected between 2009 and 2016 in screening consultations. Trained physicians labelled every second image with alpha and beta angles during the consultations. A random subset of images was labeled with time and precision under lab conditions as ground truth. Automation predicted the two angles using a convolutional neural network (CNN). The analysis was focused on the alpha angle. RESULTS: Three methods were implemented, each with a different abstraction of the problem: (1) CNNs that directly learn the angles without any post-processing steps; (2) CNNs that return the relevant landmarks in the image to identify the angles; (3) CNNs that return the base line, bony roof line, and the cartilage roof line which are necessary to calculate the angles. The RMSE between physicians and ground truth were found to be 7.1° for alpha. The best CNN architecture was (2) landmark detection. The RMSE between landmark detection and ground truth was 3.9° for alpha. CONCLUSION: The accuracy of physicians in their daily routine is inferior to deep learning-based algorithms for determining angles in ultrasound of the newborn hip. Similar methods could be used to support physicians.

Traditional Mongolian swaddling and developmental dysplasia of the hip: a randomized controlled trial.

BACKGROUND: Mongolian traditional swaddling of infants, where arms and legs are extended with a tight wrapping and hips are in adduction position, may lead to abnormal maturation and formation of the hip joint; and is a contributing factor for developmental dysplasia of the hip (DDH). This hypothesis was tested in this randomized controlled trial. METHODS: Eighty newborns with one or two hips at risk of worsening to DDH (Graf Type 2a; physiologically immature hips) at birth were randomized into 2 groups at a tertiary hospital in Ulaanbaatar. The "swaddling" group (n = 40) was swaddled in the common traditional Mongolian method for a month while the "non-swaddling" group (n = 40) was instructed not to swaddle at all. All enrollees were followed up on monthly basis by hip ultrasound and treated with an abduction-flexion splint if necessary. The groups were compared on the rate of Graf's "non-Type 1" hips at follow-up controls as the primary outcome. Secondary outcomes were rate of DDH and time to discharge (Graf Type 1; healthy hips). In addition, correlation between the primary outcome and swaddling length in days and frequency of swaddling in hours per day were calculated. RESULTS: Recruitment continued from September 2019 to March 2020 and follow-up data were completed in June 2020. We collected final outcome data in all 80 enrollees. Percentages of cases with non-Type 1 hip at any follow-up examination were 7.5% (3/40) in the non-swaddling group and 40% (16/40) in the swaddling group (p = 0.001). There was no DDH case in the non-swaddling group while there were 8 cases of DDH in the swaddling group. The mean time to discharge was 5.1 ± 0.3 weeks in the non-swaddling group and 8.4 ± 0.89 weeks in the swaddling group (p = 0.001). There is a correlation between the primary outcome and the swaddling frequency in hours per day (r = 0.81) and swaddling length in days (r = 0.43). CONCLUSIONS: Mongolian traditional swaddling where legs are extended and hips are in extension and adduction position increases the risk for DDH. TRIAL REGISTRATION: Retrospectively registered, ISRCTN11228572 .

Ne-22 Ion-Beam Radiation Damage to DNA: From Initial Free Radical Formation to Resulting DNA-Base Damage.

We report on the physicochemical processes and the products of DNA damage involved in Ne-22 ion-beam radiation of hydrated (12 ± 3 H2O/nucleotide) salmon testes DNA at 77 K. Free radicals trapped at 77 K were identified using electron spin resonance (ESR) spectroscopy. The measurement of DNA damage using two different techniques of mass spectrometry revealed the formation of numerous DNA products. Results obtained by ESR spectroscopy showed that as the linear energy transfer (LET) of the ion-beam radiation increases along the beam track, the production of DNA radicals correspondingly increases until just before the Bragg peak is reached. Yields of DNA products along the ion-beam track were in excellent agreement with the radical production. This work is the first to use the combination of ESR spectroscopy and mass spectrometric techniques enabling a better understanding of mechanisms of radiation damage to DNA by heavy ion beams detailing the formation of DNA free radicals and their subsequent products.

Implementation of a nationwide universal ultrasound screening programme for developmental dysplasia of the neonatal hip in Mongolia.

PURPOSE: Mongolia is the first Asian country to launch universal ultrasound screening for newborns with developmental dysplasia of the hip (DDH). The aims of this study were to determine the coverage and treatment rate of this programme. METHODS: Data from birth statistics and ultrasound hip screening from 29 hospitals were retrospectively reviewed (2010 to 2016, pre-nationwide phase; and 2017 to 2019, nationwide programme). DDH was diagnosed using the Graf-technique and treated according to 'ABCD', a modified Graf classification (Group A: Graf Type 1, mature; B: 2a, physiologically immature; C: 2c to 3, early DDH; D: 4, dislocated). Group B children were followed with monthly ultrasound. Group C and D children were treated with a flexion and abduction orthosis (Tübingen). Screeners used a web-based platform to upload images for quality surveillance. RESULTS: Between 2017 and 2019, 230 079 live births were registered and 176 388 newborns screened. The nationwide screening coverage rate in newborns increased from 73.6% in 2017 to 82.1% in 2019. Group A (148 510 children, 84.2%) was discharged, while Group B (25 820, 14.6%) was followed. Among children in Group B, 284 cases worsened to Group C and were, therefore, treated with a Tübingen orthosis. The remaining 2058 (1.2%) of newborns with DDH were treated with a Tübingen orthosis, including 1999 newborns in Group C and 59 in Group D. Since 2017, a total of 142 860 (81.0%) hip sonograms were uploaded to the platform. CONCLUSION: A simplified diagnostic and therapeutic framework for ultrasound DDH screening for newborns was successfully deployed in Mongolia, a developing country, providing high surveillance coverage and appropriate treatment.Level of evidence: IV.

International Interdisciplinary Consensus Meeting on the Evaluation of Developmental Dysplasia of the Hip.

In September 2018, an international meeting of doctors of various disciplines, with expertise in the detection and treatment of DDH, was held in Csolyospalos, Hungary. The aim was to achieve consensus on the detection and early treatment of the condition and to develop a standardized system of teaching and training for hip ultrasound. There was strong agreement that US screening is essential. Specifically the Graf technique was selected as the technique of choice. Universal US screening was strongly favored. Screening should be carried out as soon as possible, but not later than the sixth week of age. US screening is cost-effective, does not result in overtreatment, and contributes to a reduction of long-term consequences. The essential principle of treatment is timely application of a device to achieve reduction, retention and maturation, by holding the hips in flexion, and a safe degree of abduction. It was agreed that the effectiveness of any screening policy depends on the correct scanning technique. Therefore, standardization of teaching and training of the Graf technique is mandatory. A unified teaching policy and materials should be developed for this purpose. Certification, re-certification and audit were discussed. The group, which has been formalized as the International Interdisciplinary Consensus Committee On DDH Evaluation (ICODE), will continue to meet and work towards establishing international consensus on DDH, standardizing and developing teaching and training of the Graf technique for hip US, and maintaining standards for detection and management.

Treatment of dizziness: an interdisciplinary update.

This review provides an update on interdisciplinary treatment for dizziness. Dizziness can have various causes and the treatment offered should depend on the cause. After reading this article, the clinician will have an overview of current treatment recommendations. Recommendations are made for the most prevalent causes of dizziness including acute and chronic vestibular syndromes, vestibular neuritis, benign paroxysmal positional vertigo, endolymphatic hydrops and Menière's disease, vestibular paroxysmia and vestibular migraine, cardiac causes, transient ischaemic attacks and strokes, episodic ataxia type 2, persistent postural-perceptual dizziness, bilateral vestibulopathy, degenerative, autoimmune and neoplastic diseases, upbeat- and downbeat nystagmus. Recommendations include clinical approaches (repositioning manoeuvres), medication (adding, removing or changing current medication depending on aetiology), vestibular physiotherapy, ergotherapy and rehabilitation, treatment of chest pain or stroke units and surgical interventions. If symptoms are acute and severe, medication with antivertigo agents is recommended as a first step, for a maximum period of 3 days. Following initial symptom control, treatment is tailored depending on aetiology. To assist the clinician in obtaining a useful overview, the level of evidence and number needed to treat are reported whenever possible based on study characteristics. In addition, warnings about possible arrhythmias due to medication are issued, and precautions to enable these to be avoided are discussed.

Incidence and treatment of developmental hip dysplasia in Mongolia: a prospective cohort study.

BACKGROUND: In Mongolia, adequate early diagnosis and treatment of developmental hip dysplasia (DDH) have been unavailable and its incidence was unknown. We determined the incidence of ultrasonographic DDH in newborns and established adequate procedures for diagnosis and treatment of DDH at the largest maternity hospital in Ulaanbaatar, Mongolia. METHODOLOGY/PRINCIPAL FINDINGS: During one year (Sept 2010 - Aug 2011) we assessed the hips newborns using ultrasound and Graf's classification of DDH. 8,356 newborns were screened; median age at screening was 1 day. We identified 14,873 Type 1 (89.0%), 1715 Type 2a (10.3%), 36 Type 2c (0.2%), 70 Type D (0.4%), 14 Type 3 (0.08%), and 4 Type 4 hips (0.02%). Children with Type 1 hips (normal) were discharged. Children with Type 2a hips (physiologically immature) received follow-up ultrasounds at monthly intervals. Children with Type 2c to 4 (DDH; deformed or misaligned hip joint) hips were treated with a Tubingen hip flexion splint and also followed up. The hip abnormalities resolved to mature hips in all children who were followed up. There was no evidence for severe treatment related complications. CONCLUSION/SIGNIFICANCE: This study suggests that the incidence of DDH in Mongolian neonates is comparable to that in neonates in Europe. Early ultrasound-based assessment and splinting treatment of DDH led to mature hips in all children followed up. Procedures are feasible and will be continued.

RAD51 plays a crucial role in halting cell death program induced by ionizing radiation in bovine oocytes.

Reproductive health of humans and animals exposed to daily irradiants from solar/cosmic particles remains largely understudied. We evaluated the sensitivities of bovine and mouse oocytes to bombardment by krypton-78 (1 Gy) or ultraviolet B (UV-B; 100 microjoules). Mouse oocytes responded to irradiation by undergoing massive activation of caspases, rapid loss of energy without cytochrome-c release, and subsequent necrotic death. In contrast, bovine oocytes became positive for annexin-V, exhibited cytochrome-c release, and displayed mild activation of caspases and downstream DNAses but with the absence of a complete cell death program; therefore, cytoplasmic fragmentation was never observed. However, massive cytoplasmic fragmentation and increased DNA damage were induced experimentally by both inhibiting RAD51 and increasing caspase 3 activity before irradiation. Microinjection of recombinant human RAD51 prior to irradiation markedly decreased both cytoplasmic fragmentation and DNA damage in both bovine and mouse oocytes. RAD51 response to damaged DNA occurred faster in bovine oocytes than in mouse oocytes. Therefore, we conclude that upon exposure to irradiation, bovine oocytes create a physiologically indeterminate state of partial cell death, attributed to rapid induction of DNA repair and low activation of caspases. The persistence of these damaged cells may represent an adaptive mechanism with potential implications for livestock productivity and long-term health risks associated with human activity in space.

Characterization of Tusc5, an adipocyte gene co-expressed in peripheral neurons.

Tumor suppressor candidate 5 (Tusc5, also termed brain endothelial cell derived gene-1 or BEC-1), a CD225 domain-containing, cold-repressed gene identified during brown adipose tissue (BAT) transcriptome analyses was found to be robustly-expressed in mouse white adipose tissue (WAT) and BAT, with similarly high expression in human adipocytes. Tusc5 mRNA was markedly increased from trace levels in pre-adipocytes to significant levels in developing 3T3-L1 adipocytes, coincident with several mature adipocyte markers (phosphoenolpyruvate carboxykinase 1, GLUT4, adipsin, leptin). The Tusc5 transcript levels were increased by the peroxisome proliferator activated receptor-gamma (PPARgamma) agonist GW1929 (1microg/mL, 18h) by >10-fold (pre-adipocytes) to approximately 1.5-fold (mature adipocytes) versus controls (p<0.0001). Taken together, these results suggest an important role for Tusc5 in maturing adipocytes. Intriguingly, we discovered robust co-expression of the gene in peripheral nerves (primary somatosensory neurons). In light of the marked repression of the gene observed after cold exposure, these findings may point to participation of Tusc5 in shared adipose-nervous system functions linking environmental cues, CNS signals, and WAT-BAT physiology. Characterization of such links is important for clarifying the molecular basis for adipocyte proliferation and could have implications for understanding the biology of metabolic disease-related neuropathies.

Expression of VPAC2 receptor and PAC1 receptor splice variants in the trigeminal ganglion of the adult rat.

PACAP and VIP are members of the VIP/secretin/glucagon family of peptides with neurotransmitter, neuroprotective, and neurotrophic functions. PACAP and VIP are known to be upregulated in primary sensory neurons following nerve injury, implying that these neuropeptides could be mediators of sensory transmission in neuropathic pain states. Nerve injury at the level of the trigeminal root is thought to be the prime cause of trigeminal neuralgia. Since cross-excitation (a chemically-mediated form of nonsynaptic transmission) within the TG is postulated to play a central role in trigeminal neuralgia, we studied the expression of PACAP and VIP receptors in the TG by RT PCR and immunocytochemistry. Of the three known receptors (PAC1, VPAC1 and VPAC2), RT PCR revealed the presence of mRNA for VPAC2 and several splice variants of the PAC1 receptor. Immunocytochemistry showed PAC1 and VPAC2 to be present in small-diameter TG neurons. Thus, PACAP and VIP are potential mediators of cross-excitation in the TG.

Responses of adult human dorsal root ganglion neurons in culture to capsaicin and low pH.

This study examined the responses of cultured adult human dorsal root ganglion (hDRG) neurons to protons and capsaicin, two substances known to produce pain and hyperalgesia in humans. Both substances were applied to each neuron and responses were examined under both voltage- and current-clamp recording conditions. Sensitivity to protons was tested with rapid acidification of the extracellular fluid from pH 7.35 to 6.0. In neurons nominally clamped near -60 mV, low pH evoked a transient inward current which, in all 40 hDRG neurons tested, was followed by a more sustained inward current. The sustained current was associated with an increase in membrane conductance in 10 neurons, a decrease in 27 neurons, and no overt change in conductance (< 10%) in 3 neurons. Current-clamp recordings in the same neurons showed that the proton-induced sustained net inward current caused a prolonged depolarization of the membrane potential in all 40 hDRG neurons. The prolonged depolarization was associated with action potential discharge in 5 neurons. Unlike low pH, capsaicin evoked a sustained net inward current in only a subset of neurons tested (10 nM: 1/4, 30 nM: 4/8, 100 nM: 11/18, and 10 microM: 10/10 neurons tested). The capsaicin-evoked currents were accompanied by an increase in membrane conductance in 15 neurons, a decrease in 2, and no overt change in conductance in 9 neurons. Capsaicin currents, like proton-induced currents, resulted in prolonged depolarizations (10 nM: 0/4, 30 nM: 5/8, 100 nM: 8/18, and 10 microM: 10/10 neurons tested). The depolarization resulted in the discharge of action potentials in 14 neurons. It is concluded that, while both protons and capsaicin exert excitatory effects on human sensory neurons, multiple membrane mechanisms lead to the depolarization of cultured hDRG neurons by low pH. Inhibition of resting membrane conductances contributes to the responses to low pH in some hDRG neurons.