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("orphan disease" OR "rare disease" OR "orphan diseases" OR "rare diseases")

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Rapid Identification of Klebsiella pneumoniae by Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry and Detection of Meropenem Resistance by Flow Cytometric Assay.

J Clin Lab Anal. 2016 May 30;

Authors: Kilic A, Dogan E, Kaya S, Oren S, Tok D, Ardic N, Baysallar M

Abstract
BACKGROUND: The aim of this study was to develop a rapid detection method of carbapenem-resistant Klebsiella pneumoniae (CRKP) strains both MALDI-TOF MS and flow cytometry (FCM).
METHODS: A total of 174 K. pneumoniae strains were included in this study. Molecular characterization of carbapenemase gene was performed by PCR. Bacterial identification was performed by MALDI-TOF-MS. Meropenem susceptibility was tested at the concentrations of breakpoints described by the Clinical and Laboratory Standards Institute (CLSI) guide by FCM.
RESULTS: Sixty-two CRKP were positive for at least one carbapenemase gene. A total of 174 K. pneumoniae isolates obtained from clinically relevant material were correctly identified by Bruker MALDI-TOF MS with log (score) >2.0. These results were 100% concordant with the Phoenix(™) Automated Microbiology System (BD, MD) and conventional identification results. Based on the analysis of the receiver operating characteristic (ROC) curves, the best validity and sensitivity data were obtained with a cut-off value of 18.88% by FCM. The concordance, sensitivity, and specificity for FCM by the selected cut-off values were 99.4%, 98.9%, and 100%, respectively.
CONCLUSIONS: We conclude that reliable results on bacterial identification and meropenem susceptibility test can be obtained within 2 hr combined by MALDI-TOF-MS and FCM.

PMID: 27239799 [PubMed - as supplied by publisher]

Appendicular mucinous adenocarcinoma associated with pseudomyxoma peritonei, a rare and difficult imaging diagnosis.

Med Ultrason. 2016 Jun;18(2):257-9

Authors: Chira RI, Nistor-Ciurba CC, Mociran A, Mircea PA

Abstract
Pseudomyxoma peritonei (PMP) is a rare disease, caused by primary mucinous tumors that arise most frequently from appendix, ovary, or pancreas. Usually diagnosis is made by computed tomography, but ultrasonography can be a very useful imagistic method, if this diagnosis is taken into account by the observer. We present a case of a PMP caused by an appendiceal mucinous carcinoma, in a 34-year-old male patient, with family history of malignancies, diagnosed in our department. He was thereafter surgically treated - appendiceal resection, peritoneal lavage - followed by chemotherapy. We underline the importance of ultrasonography, even though at first encounter, the diagnosis of PMP being generally difficult.

PMID: 27239665 [PubMed - in process]

Pigment Epithelium-Derived Factor (PEDF) is a Determinant of Stem Cell Fate: Lessons from an Ultra-Rare Disease.

J Dev Biol. 2015 Dec;3(4):112-128

Authors: Sagheer U, Gong J, Chung C

Abstract
PEDF is a secreted glycoprotein that is widely expressed by multiple organs. Numerous functional contributions have been attributed to PEDF with antiangiogenic, antitumor, anti-inflammatory, and neurotrophic properties among the most prominent. The discovery that null mutations in the PEDF gene results in Osteogenesis Imperfecta Type VI, a rare autosomal recessive bone disease characterized by multiple fractures, highlights a critical developmental function for this protein. This ultra-rare orphan disease has provided biological insights into previous studies that noted PEDF's effects on various stem cell populations. In addition to bone development, PEDF modulates resident stem cell populations in the brain, muscle, and eye. Functional effects on human embryonic stem cells have also been demonstrated. An overview of recent advances in our understanding by which PEDF regulates stem cells and their potential clinical applications will be evaluated in this review.

PMID: 27239449 [PubMed - as supplied by publisher]

Validation of the Korean Genome Epidemiology Study Risk Score to Predict Incident Hypertension in a Large Nationwide Korean Cohort.

Circ J. 2016 May 25;

Authors: Lim NK, Lee JW, Park HY

Abstract
BACKGROUND: This study aimed to validate the Korean Genome Epidemiology Study (KoGES) risk score to predict the 4-year risk of hypertension (HT) in a large nationwide sample, and compare its discrimination and calibration with the Framingham and blood pressure (BP)-only models.Methods and Results:This study analyzed 69,918 subjects without HT at baseline from the National Sample Cohort in the National Health Insurance Service database. We compared the Framingham, KoGES, and BP-only models for discrimination using area under the receiver-operating characteristic curves (AROC), calibration using goodness-of-fit tests, and reclassification ability using the continuous net reclassification improvement (NRI) and integrated discrimination improvement. Of 69,918 subjects, 18.6% developed HT during the follow-up. AROC was significantly higher for the KoGES (0.733) than for the Framingham (0.729) or BP-only (0.707) model. Recalibrated Framingham model underestimated HT incidence in all deciles (P<0.001). BP-only model overestimated risk in the lower deciles (P<0.001). KoGES model accurately predicted risk in all except the highest decile (χ(2)=14.85, P=0.062). The KoGES model led to a significant improvement in risk reclassification compared with the Framingham and BP-only models (NRI, 0.354; 95% confidence interval [CI], 0.343-0.365 and 0.542; 95% CI, 0.523-0.561, respectively).
CONCLUSIONS: In this validation study, the KoGES model demonstrated better discrimination, calibration, and reclassification ability than either the Framingham or BP-only model. The KoGES model may help identify Korean individuals at high risk for HT.

PMID: 27238835 [PubMed - as supplied by publisher]

Primary actinomycosis of breast-A diagnosis on cytology.

Diagn Cytopathol. 2016 May 30;

Authors: Gosavi AV, Anvikar AR, Sulhyan KR, Manek DD

Abstract
Primary actinomycosis of breast is a rare disease with only a few cases reported in the literature. We present a case of a 25-year-old lactating woman with primary actinomycosis of breast which was diagnosed on cytology. The patient presented with lump in left breast with dull aching pain. Fine-needle aspiration cytology smears showed acute suppurative inflammation with presence of fluffy basophilic colonies on Hematoxylin and Eosin staining and branched, Gram positive filamentous bacilli on Gram staining. The bacilli were non-acid fast with 1% Zeihl Neelsen stain. A diagnosis of actinomycosis was suggested on cytology. Histopathological examination revealed an abscess with few Gram positive basophilic granules surrounded by eosinophilic Splendore-Hoeppli material thus confirming the diagnosis of actinomycosis. Meticulous search for microorganisms with the aid of special stains should be done on cytology smears before labeling an inflammatory lesion as nonspecific. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

PMID: 27238823 [PubMed - as supplied by publisher]

Association of first-trimester angiogenic factors with placental histological findings in late-onset preeclampsia.

Placenta. 2016 Jun;42:44-50

Authors: Triunfo S, Crovetto F, Crispi F, Rodriguez-Sureda V, Dominguez C, Nadal A, Peguero A, Gratacos E, Figueras F

Abstract
OBJECTIVE: To explore in women with late-onset preeclampsia (PE) the association between maternal levels of angiogenic/antiangiogenic factors in the first trimester of pregnancy and histological findings attributable to placental underperfusion (PUP).
METHODS: A nested case-control cohort study was conducted in 73 women with pregnancies complicated by late-onset PE (>34 weeks at delivery) matched with controls. First trimester uterine artery Doppler (UtA); maternal levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were retrieved. Placentas were histologically evaluated using a hierarchical and standardized classification system. One-way ANOVA with linear polynomial contrast or linear-by-linear association test was performed to test the hypothesis of a linear association across study groups (controls, PE without PUP and PE with PUP).
RESULTS: In 54 (74%) placentas, 89 placental histological findings qualifying for PUP were found. Across study groups, significant values were observed in maternal levels of decreased PlGF (MoM values: 1.53, 1.41 and 1.37; p < 0.001), increased sFlt-1 (MoM values: 3.11, 3.11 and 3.22; p = 0.002), increased sFlt-1/PlGF ratio (MoM values: 2.3, 2.3 and 2.44; p < 0.001), abnormal UtA Doppler (MoM values: 1, 1.26 and 1.32; p < 0.001), and worse perinatal outcomes in terms of gestational age at delivery, cesarean section for not reassuring fetal status, birth weight and neonatal acidosis.
DISCUSSION: In late-onset PE an imbalance of circulating angiogenic and anti-angiogenic factors already present at 8-10 weeks of pregnancy was associated with histological findings reflecting placental insufficiency. An early first trimester screening by angiogenic factors might help to identify patients with placental involvement among late-onset PE cases.
CONCLUSION: In late-onset preeclampsia, first-trimester uterine Doppler and circulating levels of angiogenic/antiangiogenic factors are associated with placental underperfusion.

PMID: 27238713 [PubMed - in process]

A case of DIPNECH presenting as usual interstitial pneumonia.

Pneumonol Alergol Pol. 2016;84(3):174-7

Authors: Chatterjee K, Kamimoto JJ, Dunn A, Mittadodla E, Joshi M

Abstract
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare disease that is classically described as presenting with cough, dyspnea, and wheezing in non-smoker middle aged females. Pulmonary function tests commonly demonstrate an obstructive pattern and CT of chest usually reveals diffuse air trapping with mosaic pattern. We present a case of patient with DIPNECH manifesting with restrictive pattern and as usual interstitial pneumonia on imaging.

PMID: 27238180 [PubMed - in process]

Discovery of a gamma heavy chain disease in a patient followed-up for a lymphoplasma cell proliferative disorder.

Ann Biol Clin (Paris). 2016 Jun 1;74(3):338-340

Authors: Humeau C, Monjanel H, Schellenberg F

Abstract
Gamma-heavy chains disease is a rare disease, with very few cases described in the literature. It is characterized by the presence of a monoclonal gamma-heavy chain without associated light chain. Its prevalence and prognosis are unknown. We report here the accidental discovery of a case of gamma-heavy chain disease during a pancytopenia exploration, performed in the hospital, in a patient known since 2002 for a lymphoplasmacytic type lymphoma first localized in bone marrow.

PMID: 27237805 [PubMed - as supplied by publisher]

The First Reported Case of Erdheim-Chester Disease in Egypt with Bilateral Exophthalmos, Loss of Vision, and Multi-Organ Involvement in a Young Woman.

Am J Case Rep. 2016;17:360-370

Authors: Abdellateef EE, Abdelhai AR, Gawish HH, Abdulmonaem GA, Abdelbary EH, Ahmed AI

Abstract
BACKGROUND Erdheim-Chester disease is a rare non-Langerhans-cell histiocytosis of unknown etiology with multi-organ involvement. CASE REPORT A 19-year-old woman presented with orthopnea, severe fatigue, bilateral exophthalmos, and gradual loss of vision. She had anemia and mild leucocytosis related to chronic illness. Marked left side pleural effusion and massive pericardial effusion with bilateral hydronephrosis were detected by plain X-ray, echocardiography, and computed tomography, respectively. Retro-orbital tissue and bone marrow biopsy revealed histiocytic infiltration, which was CD68-positive and CD1a-negative. CONCLUSIONS This report describes the first case presentation of Erdheim-Chester disease in our country. This case report may advance our understanding of an orphan disease. Our patient's young age and stable clinical status may allow long-term follow-up of treatment results.

PMID: 27237445 [PubMed - as supplied by publisher]

Characteristics of 419 patients with acquired middle ear cholesteatoma.

Braz J Otorhinolaryngol. 2016 May 3;

Authors: Rosito LP, da Silva MN, Selaimen FA, Jung YP, Pauletti MG, Jung LP, Freitas LA, da Costa SS

Abstract
INTRODUCTION: Cholesteatoma is a destructive lesion that can result in life-threatening complications. Typically, it presents with hypoacusis and continuous otorrhea as symptoms. Because it is a rare disease, there are few studies in Brazil describing the characteristics of patients with the disease.
OBJECTIVE: This study aimed to determine the prevalence of cholesteatoma in patients with chronic otitis media and describe clinical, audiological and surgical characteristics of patients with acquired middle ear cholesteatoma treated at a referral hospital in the public health system.
METHODS: Cross-sectional and prospective cohort study, including 1710 patients with chronic otitis media, treated between August 2000 and June 2015, without prior surgery. Detailed clinical history, videotoscopy, and audiometry were performed, in addition to review of medical records to search for surgical data. Cholesteatomas were classified according to their route of formation.
RESULTS: Of the patients with chronic otitis media, 419 (24.5%) had cholesteatoma; mean age of 34.49 years; 53.5% female and 63.8% adults. Bilateral cholesteatoma was observed in 17.1%. Anterior epitympanic cholesteatoma corresponded to 1.9%; posterior epitympanic, 32.9%; posterior mesotympanic, 33.7%; two routes, 14.8%; and indeterminate, 16.7%. The mean air-bone gap was 29.84dB and did not differ between routes of formation. There were no correlations between gap size and patient age or duration of symptoms. Of the surgical cases, 16.8% underwent closed tympanomastoidectomy and 75.2% open tympanomastoidectomy.
CONCLUSION: The prevalence of cholesteatoma in patients with chronic otitis media was 24.5% and it was more common in adults than in children. Posterior mesotympanic cholesteatoma was more frequent, with no difference in mean air-bone gap between the different routes of formation. In patients undergoing surgery, open tympanomastoidectomy was the procedure most frequently chosen.

PMID: 27236633 [PubMed - as supplied by publisher]

Metastatic malignant pleural mesothelioma masquerading as a case of acute abdomen secondary to small bowel perforation.

Ann Saudi Med. 2016 May-Jun;36(3):229-231

Authors: Alkhayal K

Abstract
Metastatic pleural mesothelioma is a rare disease. The present study aimed to report a rare presentation of metastatic malignant mesothelioma (MM). The patient was an elderly man who presented with small bowel (jejunal) perforation secondary to metastatic pleural mesothelioma deposits. This was a rare presentation of a rare disease and the first reported case in the published studies in which MM masqueraded as bowel perforation prior to the primary diagnosis.
SIMILAR CASES PUBLISHED: 1.

PMID: 27236396 [PubMed - as supplied by publisher]

The importance of review articles in making the voice of rare diseases heard: OJRD's 10th anniversary.

Orphanet J Rare Dis. 2016;11(1):71

Authors: Aymé S

PMID: 27234175 [PubMed - as supplied by publisher]

Perirenal Involvement of Mantle Cell Lymphoma: Imaging Features.

Urology. 2016 May 24;

Authors: Ufuk F, Karaman E, Karabulut N

Abstract
Perirenal lymphoma is a rare disease and accouning for less than 10% of all malignant lymphomas. Mantle cell lymphoma (MCL) is the rarest but one of the most aggressive non-Hodgkin's lymphoma (NHL) subtype. The perirenal involvement of MCL has not been reported previously. A 69-year-old male, who had been diagnosed as having mantle cell lymphoma (MCL) one year ago, presented with recent-onset right back pain. Herein we present the key imaging findings of perirenal soft tissue manifestation of MCL.

PMID: 27233934 [PubMed - as supplied by publisher]

GM3 synthase deficiency due to ST3GAL5 variants in two Korean female siblings: Masquerading as Rett syndrome-like phenotype.

Am J Med Genet A. 2016 May 27;

Authors: Lee JS, Yoo Y, Lim BC, Kim KJ, Song J, Choi M, Chae JH

Abstract
There have been a few reports of GM3 synthase deficiency since the disease of the ganglioside biosynthetic pathway was first reported in 2004. It is characterized by infantile-onset epilepsy with severe intellectual disability, blindness, cutaneous dyspigmentation, and choreoathetosis. Here we report the cases of two Korean female siblings with ST3GAL5 variants, who presented with a Rett-like phenotype. They had delayed speech, hand stereotypies with a loss of purposeful hand movements, and choreoathetosis, but no clinical seizures. One of them had microcephaly, while the other had small head circumference less than 10th centile. There were no abnormal laboratory findings with the exception of a high lactate level. MECP2/CDKL5/FOXG1 genetic tests with an array comparative genomic hybridization revealed no molecular defects. Through whole-exome sequencing of the proband, we found compound heterozygous ST3GAL5 variants (p.Gly201Arg and p.Cys195Ser), both of which were novel. The siblings were the same compound heterozygotes and their unaffected parents were heterozygous carriers of each variant. Liquid chromatography-mass spectrometry analysis confirmed a low level of GM3 and its downstream metabolites, indicating GM3 synthase deficiency. These cases expanded the clinical and genetic spectrum of the ultra-rare disease, GM3 synthase deficiency with ST3GAL5 variants. © 2016 Wiley Periodicals, Inc.

PMID: 27232954 [PubMed - as supplied by publisher]

Research advances on medical genetics in China in 2015.

Yi Chuan. 2016 May 20;38(5):363-390

Authors: Yuanfeng L, Yubo H, Pengbo C, Jinfeng M, Haibei L, Geng Q, Feng Z, Guangfu J, Yong Y, Lingqian W, Jie P, Gangqiao Z

Abstract
Steady progress has been achieved in the medical genetics in China in 2015, as numerous original researches were published in the world's leading journals. Chinese scientists have made significant contributions to various fields of medical genetics, such as pathogenicity of rare diseases, predisposition of common diseases, somatic mutations of cancer, new technologies and methods, disease-related microRNAs (miRNAs), disease-related long non-coding RNAs (lncRNAs), disease-related competing endogenous RNAs (ceRNAs), disease-related RNA splicing and molecular evolution. In these fields, Chinese scientists have gradually formed the tendency, from common variants to rare variants, from single omic analyses to multipleomics integration analyses, from genetic discovery to functional confirmation, from basic research to clinical application. Meanwhile, the findings of Chinese scientists have been drawn great attentions of international peers. This review aims to provide an overall picture of the front in Chinese medical genetics, and highlights the important findings and their research strategy.

PMID: 27232486 [PubMed - as supplied by publisher]

Mutations in SLC39A14 disrupt manganese homeostasis and cause childhood-onset parkinsonism-dystonia.

Nat Commun. 2016;7:11601

Authors: Tuschl K, Meyer E, Valdivia LE, Zhao N, Dadswell C, Abdul-Sada A, Hung CY, Simpson MA, Chong WK, Jacques TS, Woltjer RL, Eaton S, Gregory A, Sanford L, Kara E, Houlden H, Cuno SM, Prokisch H, Valletta L, Tiranti V, Younis R, Maher ER, Spencer J, Straatman-Iwanowska A, Gissen P, Selim LA, Pintos-Morell G, Coroleu-Lletget W, Mohammad SS, Yoganathan S, Dale RC, Thomas M, Rihel J, Bodamer OA, Enns CA, Hayflick SJ, Clayton PT, Mills PB, Kurian MA, Wilson SW

Abstract
Although manganese is an essential trace metal, little is known about its transport and homeostatic regulation. Here we have identified a cohort of patients with a novel autosomal recessive manganese transporter defect caused by mutations in SLC39A14. Excessive accumulation of manganese in these patients results in rapidly progressive childhood-onset parkinsonism-dystonia with distinctive brain magnetic resonance imaging appearances and neurodegenerative features on post-mortem examination. We show that mutations in SLC39A14 impair manganese transport in vitro and lead to manganese dyshomeostasis and altered locomotor activity in zebrafish with CRISPR-induced slc39a14 null mutations. Chelation with disodium calcium edetate lowers blood manganese levels in patients and can lead to striking clinical improvement. Our results demonstrate that SLC39A14 functions as a pivotal manganese transporter in vertebrates.

PMID: 27231142 [PubMed - in process]

Intradural synovial cyst of the atlantoaxial joint: a case report.

Acta Neurochir (Wien). 2016 May 27;

Authors: Hartmann S, Tschugg A, Kavakebi P, Thomé C

Abstract
BACKGROUND: Intradural synovial cysts of the cervical spine represent a rare disease entity, causing stenosis of the spinal canal and thereby leading to progressive myelopathy. In particular, at the cranio-cervical junction early intervention is necessary to prevent permanent neurological dysfunction. We present the case of a 74-year-old man who presented with moderate cervicogenic headache, gait disturbance and progressive left-sided weakness. Magnetic resonance imaging (MRI) of the cervical spine confirmed a left-sided cystic mass located anteriorly at the craniovertebral junction compressing the surrounding structures.
METHOD: Surgical decompression was performed by means of a minimal left-sided laminectomy of C1. Postoperatively, the patients symptoms slowly improved, albeit a persistent ataxic gait.
RESULTS: Intraoperatively, a large intradural cyst was removed via a minimal suboccipital craniectomy combined with laminectomy of C1. Histopathological evaluation revealed a synovial cyst without any features of neoplasia. Despite not using craniocervical instrumentation, no clinical or radiological signs of atlantoaxial instability were observed up to 2 years after surgery.
CONCLUSIONS: Cystic lesions located at the atlanto-axial joint are a rare cause of cervical myelopathy. Preoperative imaging of the cervical spine should include not only MRI and computerised tomography (CT) but also dynamic imaging. Dorsal decompression without instrumentation prevents progressive neurological decline and may allow cord function to recover. If there is additional preoperative instability, instrumentation and fusion may be necessary.

PMID: 27230912 [PubMed - as supplied by publisher]

Spatial analysis of gender variation in the prevalence of hypertension among the middle-aged and elderly population in Zhejiang Province, China.

BMC Public Health. 2016;16(1):447

Authors: Xu L, Lai D, Fang Y

Abstract
BACKGROUND: Previous studies have shown that there may be gender disparities in the prevalence of hypertension; however, these studies do not address the spatial information contained in the sample which may limit the analytical results. Our study extends the existing Shared Component Model (SCM) and compares its utility with a logistic regression model to evaluate the significance of spatial information for identifying risk factors for hypertension and other non-rare diseases.
METHODS: A total of 1267 residents aged 45 years of age and over were included in our study, of which 48.1 % were males. The overall prevalence of hypertension was 33.2 %, with females experiencing a higher prevalence than males (35.5 % vs. 30.6 %). The research variables included body mass index (BMI), Waist -to-Height Ratio (WHtR), smoking status, alcohol consumption etc. The extended SCM is employed to investigate regional gender variations in the risk of hypertension and assess the gender variation in the middle-aged and elderly populations of Zhejiang Province in eastern China and then its performance is compared with that of a traditional multiple logistic regression model.
RESULTS: Our SCM analysis determined that the spatial pattern of hypertension risk for the middle-aged and elderly populations of Zhejiang Province in eastern China is quite different for males and females. Furthermore, Waist -to-Height Ratio (WHtR) continues to be a simple and effective predictor of hypertension risk for males at the regional level.
CONCLUSIONS: We believe that the extended SCM spatial model is a useful tool for identifying risk factors at the regional level.

PMID: 27230660 [PubMed - in process]

Feasibility and Success Rate of a Fetal MRI and MR Spectroscopy Research Protocol Performed at Term Using a 3.0-Tesla Scanner.

Fetal Diagn Ther. 2016 May 27;

Authors: Sanz Cortes M, Bargallo N, Arranz A, Simoes R, Figueras F, Gratacos E

Abstract
OBJECTIVES: To report the feasibility and main factors affecting the success of a fetal magnetic resonance imaging (MRI) and MR spectroscopy (MRS) research protocol performed at term using a 3-tesla scanner.
METHODS: Pregnant patients at term underwent an MRI. Specific measures were taken to prevent maternal discomfort and distress, such as detailed counseling and maternal repositioning if needed. MRS data were acquired from the frontal lobe and basal ganglia, and processed applying quality control criteria.
RESULTS: The mean gestational age at MRI was 37.4 ± 0.9 weeks. From a total of 245 patients that showed up for the MRI, 11 referred claustrophobia which prevented the test from starting, and 30 patients started the test but decided to discontinue due to discomfort. Thus, the examination was complete in 204 patients. MRS data could be obtained in 170 cases from the frontal lobe and 165 cases from the basal ganglia, of which 52.4 and 68.6%, respectively, complied with our defined quality criteria. The mean scanning time was 34:16 ± 9:30 min:s after excluding those cases presenting initial intolerance to the test. Minor abnormalities were described in 11 MRI reports.
CONCLUSIONS: The fetal MRI/MRS protocol was feasible and generally well tolerated at term on a 3-tesla scanner, but a significant number of cases were lost to analysis. The rate of patients that eventually provided usable research information was 95.5% for anatomical examination and 52.4-68.6% for MRS. This information should be taken into account in the design of fetal brain MRI studies.

PMID: 27230519 [PubMed - as supplied by publisher]