Identification of novel homozygous missense and deletion mutations manifesting oligospermia infertility in Kashmiri population.

BACKGROUND: Human male infertility has a lot of known molecular components that have an accurate diagnosis, such as Y chromosome deletion and monogenic causes. Only 4% of all infertile males are diagnosed with genetic causes, while 60-70% of infertile men remain without an accurate diagnosis and are classified as unexplained. Oligospermia is a major cause of human male infertility. Its etiology and pathogenesis are linked to genetic abnormalities. The majority of genetic causes related to human male infertility remain unclear. RESULTS: Generally, we found a significant association between the specific type of disease and gender (p = 0.003), and the regression value (R2 ) for this association was 0.75. Association of the type of disease with body mass index was not significant (p = 0.34). There was no statistically significant difference (p = 0.40) among disease types with patients occupations. All explored mutations are listed for primary and secondary infertility in relation to the oligospermia condition. p.Arg286X is the outcome of a mismatch mutation in which the nucleotide change resulted in the substitution of Arg (arginine) amino acid with X (any amino acid) at position 286 in the Hyal3 gene of primary infertile patients having oligospermia. In primary infertile patients with the p.Arg286X mutation, a frameshift deletion mutation was also found just after the 25 nucleotide sequences of the Hyal3 genes of the second mutated exon. This deletion mutation was only detected in patients with primary infertility and was not found in people with secondary infertility or healthy controls. The other mutations in secondary infertile patients with oligospermia were: p.Lys168Ser, replacement of lysine (Lys) with serine (Ser) at position 168; p.Lys168The, replacement of lysine (Lys) with threonine (The) at position 168; p.His113X, substitution of histidine (His) with an unknown amino acid (X) at position 113; p.Pro162X, substitution of proline (Pro) with an unknown amino acid (X) at position 162; and p.Phe157X, phenylalanine (Phe) substitution with an unknown amino acid (X) at position 157. CONCLUSION: This study clarifies the site of novel mismatch and frameshift deletion mutations in the Hyal3 gene in primary infertile oligospermia patients.

Interactions of Chitosan-coated Green Synthesized Silver Nanoparticles using Mentha spicata and Standard Antibiotics against Bacterial Pathogens.

BACKGROUND: Infectious diseases are caused by various multidrug-resistant pathogenic bacteria and in recent scenarios, nanoparticles have been used as innovative antimicrobial agents. AIMS: This current research aimed to evaluate the bactericidal effect of chitosan-coated green synthesized silver nanoparticles using aqueous extract of Mentha spicata (MSaqu) against bacterial pathogens, i.e., Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus, and Streptococcus pyogenes. METHODS: Synthesis and characterization of silver nanoparticles (MSAgNPs) were carried out via atomic absorption spectrometer and Fourier-transform infrared spectroscopy. Agar well and agar disc diffusion methods were used to assess the antibacterial and synergistic effect of chitosanmediated biogenic silver nanoparticles and standard antibiotics. Three types of interactions, i.e., antagonistic (↓), synergistic (↑), and additive (¥) were observed. RESULTS: Synergistic effect was recorded against Pseudomonas aeruginosa (8.5±0.25 mm↑), Serratia marcescens (19.0±1.0 mm↑), and Klebsiela pneumonia (8.5±0.25 mm↑), an additive effect was exhibited by Escherichia coli (9.0±0.0 mm¥), Streptococcus pyogenes (10.0±0.0 mm¥), and Staphylococcus aureus (7.5±0.25 mm↓) and they showed antagonistic effects when chitosan-coated silver nanoparticles (CLMSAgNPs) were applied compared to chitosan, MSaqu, and MSAgNPs. Interesting antibacterial results were recorded when chitosan-coated Mentha spicata extract and silver nanoparticles were applied along with antibiotics. The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + K were recorded against E. coli (14.5±0.25 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + AML were recorded against E. coli (5.5±0.0 mm), S. pyogenes (10.0±0.0 mm), K. pneumonia (5.5±0.0 mm), and S. aureus (4.0±0.0 mm). The synergistic effects of chitosan-coated silver nanoparticles (CLMSAgNPs) + NOR were recorded against E. coli (16.0±0.0 mm), P. aeruginosa (19.0±0.0 mm), S. marcescens (19.5±0.25 mm), S. pyogenes (11.5.0±0.25 mm), K. pneumonia (23.0±0.0 mm), and S. aureus (8.5±0.25 mm). CONCLUSION: Current findings concluded that chitosan-coated biogenic silver nanoparticles have potential bactericidal effects against infectious pathogens and could be used as forthcoming antibacterial agents.

Retrospective Observational Study of Daytime Add-On Administration of Zopiclone to Difficult-to-Treat Psychiatric Inpatients With Unpredictable Aggressive Behavior, With or Without EEG Dysrhythmia.

Managing violent behavior is a particularly challenging aspect of hospital psychiatric care. Available pharmacological interventions are often unsatisfactory. Aim: To assess the effectiveness and safety of daytime zopiclone add-on administration in violent and difficult-to-treat psychiatric inpatients. Methods: Chart review of inpatients treated with daytime zopiclone, between 2014 and 2018, with up to 12 weeks follow-up. Effectiveness was retrospectively assessed with the Clinical Global Impression rating scale (CGI) and the frequency and severity of aggressive incidents recorded with the Staff Observation Aggression Scale-Revised (SOAS-R). Results: Forty-five (30 male, 15 female) cases, 18-69 years age range, average (SD) baseline CGI-S score of 5.4 (1.0), and a variety of diagnoses. Sixty-nine percent showed CGI-S improvement of any degree. For patients with at least one aggressive incident within 7 days prior to initiation of zopiclone (N = 22), average (SD) SOAS-R-Severity LOCF to baseline change was -3.5 (2.7) P < 0.0001. Most patients reported no side effects; 24% reported one or more side effects, and 11% discontinued zopiclone due to sedation (4), insomnia (1) or slurred speech (1). No SAEs were recorded. Zopiclone maximum daily dose correlated with CGI-S baseline-to-LOCF change (rho = -0.5, P = 0.0003). The ROC AUC of zopiclone maximum daily dose and improvement on CGI-S was 0.84 (95% CI 0.70-0.93, P < 0.0001). The ROC AUC of zopiclone maximum daily dose and SOAS-R-N improvement was 0.80 (95% CI 0.58-0.92; P = 0.0008) and maximum Youden's index value was achieved at a dose of >30 mg. Conclusions: Zopiclone doses >30 mg daily achieved the best anti-aggressive effect.

Identification of a Novel Homozygous Missense (c.443A>T:p.N148I) Mutation in BBS2 in a Kashmiri Family with Bardet-Biedl Syndrome.

BACKGROUND: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive inherited disorder with distinctive clinical feature such as obesity, degeneration of retina, polydactyly, and renal abnormalities. The study was aimed at finding out the disease-causing variant/s in patients exhibiting clinical features of BBS. METHODS: The identification of disease-causing variant was done by using whole exome sequencing on Illumina HiSeq 4000 platform involving the SeqCap EZ Exome v3 kit (Roche NimbleGen). The identified variant was further validated by Sanger sequencing. RESULTS: WES revealed a novel homozygous missense mutation (NM_031885: c.443A>T:p.N148I) in exon 3 of the BBS2 gene. Sanger sequencing confirmed this variant as homozygous in both affected subjects and heterozygous in obligate parents, demonstrating autosomal recessive inheritance pattern. To the best of our knowledge, this variant was not present in literature and all publically available databases. The candidate variant is predicted to be pathogenic by a set of in-silico softwares. CONCLUSION: Clinical and genetic spectrum of BBS and BBS-like disorders is not completely defined in the Pakistani as well as in Kashmiri population. Therefore, more comprehensive genetic studies are required to gain insights into genotype-phenotype associations to facilitate carrier screening and genetic counseling of families with such disorders.

A Comparison of Magnetic Resonance Imaging Methods to Assess Multiple Sclerosis Lesions: Implications for Patient Characterization and Clinical Trial Design.

Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 weighted imaging (T1WI, T2WI), T2 fluid attenuated inversion recovery (FLAIR), magnetization transfer, myelin water fraction, diffusion tensor imaging (DTI), phase-sensitive inversion recovery and susceptibility weighted imaging (SWI), but no study has combined all of these modalities into a single well-controlled investigation. The goals of this study were to: compare different MRI measures for lesion visualization and quantification; evaluate the repeatability of various imaging methods in healthy controls; compare quantitative susceptibility mapping (QSM) with myelin water fraction; measure short-term longitudinal changes in the white matter of MS patients and map out the tissue properties of the white matter hyperintensities using STAGE (strategically acquired gradient echo imaging). Additionally, the outcomes of this study were anticipated to aid in the choice of an efficient imaging protocol reducing redundancy of information and alleviating patient burden. Of all the sequences used, T2 FLAIR and T2WI showed the most lesions. To differentiate the putative demyelinating lesions from inflammatory lesions, the fusion of SWI and T2 FLAIR was used. Our study suggests that a practical and efficient imaging protocol combining T2 FLAIR, T1WI and STAGE (with SWI and QSM) can be used to rapidly image MS patients to both find lesions and study the demyelinating and inflammatory characteristics of the lesions.

Relationship between economic growth and CO2 emissions: does governance matter?

The environmental stress due to massive CO2 emissions is a critical issue for scholars and policymakers. Many studies have discussed various determinants of environmental pollution both from theoretical and empirical perspectives. However, how governance influences the nexus between economic growth and CO2 emissions is rarely studied. Hence this study investigates the relationship between economic growth, governance and CO2 emissions within the framework of the Environmental Kuznets Curve for five high CO2 emission countries over 1996-2017. Empirical results from the panel data estimation methods reflect that measures of governance influence emission levels differently in high CO2 emission countries. Overall, political, economic and institutional governance enhance environmental quality. According to the results, provision of good governance needs to exercise effective measures to enhance and protect environmental quality.

Sequencing and Characterization of Mitochondrial Protein-Coding Genes for Schizothorax niger (Cypriniformes: Cyprinidae) with Phylogenetic Consideration.

The present study was conducted to get more information about the genome and locate the taxonomic position of Schizothorax niger in Schizothoracinae through mitochondrial 13 protein-coding genes (PCGs). These PCGs for S. niger were found to be 11409 bps in length ranging from 165 (ATPase 8) to 1824 bps (NADH dehydrogenase subunit 5) and encode 3801 amino acids. In these PCGs, 4 genes overlap on the similar strands, while one shown on the opposite one: ATPase 6+8 and NADH dehydrogenase subunit 4+4L overlap by 7 nucleotides. Similarly, ND5-ND6 overlap by 4 nucleotides, while ATP6 and COIII overlap by 1 nucleotide. Similarly, four commonly used amino acids in S. niger were Leu (15.6 %), Ile (10.12 %), Thr (8.12 %), and Ala (8.7 %). The results presented that COII, COIII, NDI, ND4L, and Cytb had substantial amino acid conservation as compared to the COI gene. Through phylogenetic analysis, it was observed that S. niger is closely linked with S. progastus, S. labiatus, S. plagiostomus, and S. nepalensis with high bootstrap values. The present study provided more genomic data to know the diversity of the mitochondrial genome and its molecular evolution in Schizothoracinae.

Confirmation of the Role of DHX38 in the Etiology of Early-Onset Retinitis Pigmentosa.

Purpose: Retinitis pigmentosa (RP) is a genetically heterogeneous trait with autosomal-recessive (ar) inheritance underlying 50% of genetic disease cases. Sixty-one arRP genes have been identified, and recently, DHX38 has been reported as a potential candidate gene for arRP with only a single family reported with a variant of unknown significance. We identified a missense variant in DHX38 that co-segregates with the arRP phenotype in two Pakistani families confirming the involvement of DHX38 in the etiology of early-onset RP. Methods: Exome sequencing was performed using two DNA samples from affected members of Pakistani families (MA88 and MA157) with early onset arRP. Sanger sequencing of DNA samples from all family members confirmed the segregation of candidate variant within both families. Results: A novel missense DHX38 variant c.971G>A; p.(Arg324Gln) was identified which segregates with the arRP phenotype and yielded a logarithm of the odds (LOD) score of 5.0 and 4.3 for families MA88 and MA157, respectively. This variant is predicted to be conserved and deleterious by several bioinformatics tools. Conclusions: We identified a second deleterious DHX38 variant that segregates with arRP in two families, providing additional evidence that DHX38 is involved in RP etiology. DHX38 encodes for pre-mRNA splicing factor PRP16, which is important in catalyzing pre-mRNA splicing.

Identification of a novel homozygous TRAPPC9 gene mutation causing non-syndromic intellectual disability, speech disorder, and secondary microcephaly.

TRAPPC9 gene mutations have been linked recently to autosomal recessive mental retardation 13 (MRT13; MIM#613192) with only eight families reported world-wide. We assessed patients from two consanguineous pedigrees of Pakistani descent with non-syndromic intellectual disability and postnatal microcephaly through whole exome sequencing (WES) and cosegregation analysis. Here we report six further patients from two pedigrees with homozygous TRAPPC9 gene mutations, the novel nonsense mutation c.2065G>T (p.E689*) and the previously identified nonsense mutation c.1423C>T (p.R475*). We provide an overview of previously reported clinical features and highlight common symptoms and variability of MRT13. Common findings are intellectual disability and absent speech, and frequently microcephaly, motor delay and pathological findings on MRI including diminished cerebral white matter volume are present. Mutations in TRAPPC9 should be considered in non-syndromic autosomal recessive intellectual disability with severe speech disorder.

Structural Features of Europium(II)-Containing Cryptates That Influence Relaxivity.

EuII -containing complexes were studied with respect to properties relevant to their use as contrast agents for magnetic resonance imaging. The influences of molecular parameters and field strength on relaxivity were studied for a series of EuII -containing cryptates and their adducts with ß-cyclodextrins, poly-ß-cyclodextrins, and human serum albumin. Solid- and solution-phase characterization of EuII -containing complexes is presented that demonstrates the presence of inner-sphere molecules of water. Additionally, relaxivity, water-exchange rate, rotational correlation time, and electronic relaxation times were determined using variable-temperature 17 O NMR, nuclear magnetic relaxation dispersion, and electron paramagnetic resonance spectroscopic techniques. These results are expected to be instrumental in the design of future EuII -based contrast agents.

The Relationship Between Brain MR Spectroscopy and Disability in Multiple Sclerosis: 20-Year Data from the U.S. Glatiramer Acetate Extension Study.

BACKGROUND AND PURPOSE: Conventional MRI techniques do not necessarily provide information about multiple sclerosis (MS) disease pathology or progression. Nonconventional MRI techniques, including proton magnetic resonance spectroscopy (1 H-MRS), are increasingly used to improve the qualitative and quantitative specificity of MR images. This study explores potential correlations between MRI measures of disease and disability progression as measured by the Expanded Disability Status Scale (EDSS), Functional Systems (FS), and ambulation index scores in a unique cohort of MS patients treated with glatiramer acetate that has been closely monitored for over 20 years. METHODS: This was a multicenter, open-label, cross-sectional MRI substudy among participants in the GA-9004 open-label extension of the 36-month, double-blind GA-9001 study, timed to coincide with the prospectively planned 20-year clinical exam. RESULTS: Of 64 patients who participated in the MRI substudy, results are presented for the 39 patients (61%) who had a 1 H-MRS assessment at 20 years of treatment. Both total N-acetylaspartate relative to total creatinine (tNAA/tCr) concentration ratio and T1 lesion volume were found to be robustly associated with disability levels with different statistical approaches. Gray matter (GM) volume was found to be a more consistent parameter than white matter (WM) volume for disability allocation. The elastic net algorithm showed a trade-off between WM and GM volumes for disability estimation when different disability definitions were used. CONCLUSIONS: Among patients with MS receiving long-term glatiramer acetate therapy, consistent effects on disability levels indicated by EDSS and pyramidal FS score thresholds were found for tNAA/tCr concentration ratio and T1 lesion volume.

MR imaging of the yucatan pig head and neck vasculature.

PURPOSE: To evaluate the cerebral venous drainage system of the swine as a probable model to test whether extracranial venous abnormalities may play a role in neurodegenerative diseases as reported recently in multiple sclerosis. MATERIALS AND METHODS: Three Yucatan micropigs, 5 to 7 months old, were scanned with a comprehensive MRI protocol at 3 Tesla. The vascular anatomy of the head and neck was imaged using conventional and angiographic MR sequences. Phase-contrast MR images were collected at multiple levels of the neck and intracranial space to monitor flow. RESULTS: Three large cervical veins were observed; the external jugular vein draining the olfactory and gustatory tissues; the internal jugular vein (IJV) draining the cavernous sinus as well as surrounding soft tissues in the neck; and the ventral vertebral venous plexus (VVVP) surrounding the dural sac and paraspinal region. The majority of the cerebral blood flow in the pig appears to drain through the VVVP. Flow through the IJV comprised a nondominant component. Anastamoses were observed connecting the major veins of the neck bilaterally. CONCLUSION: The dominance of outflow from the brain to the VVVP may be analogous to the typical dominance of the IJVs in humans in the supine position.

Magnetic resonance imaging-based relationships between neck muscle cross-sectional area and neck circumference for adults and children.

BACKGROUND: Computer models and human surrogates used to study the forces and motion of the human neck under various loading conditions are based solely on adult data. Pediatric computer models and dummy surrogates used to improve the safety of children could be improved with the inclusion of previously unavailable pediatric muscle data. METHODS: Measurements of neck circumference and neck muscle cross-sectional area (CSA) were taken from ten 50th percentile adult male and ten 10-year old male volunteer subjects. Muscle cross-sectional areas were calculated from magnetic resonance images of axial cross-sections of the neck. RESULTS: Neck muscle cross-sectional area was calculated for six muscles/muscle groups. A power-law regression analysis was used to describe the relationship between neck circumference and neck muscle cross-sectional area. CONCLUSIONS: The cross-sectional area and the power-law functions determined by the data in this study provide a means of calculating muscle cross-sectional area for young children, where such data are currently unavailable. This will provide an opportunity to develop more representative pediatric neck models.

Mental health legislation in Ireland: a lot done, more to do.

Mental health legislation is necessary to protect the rights of people with mental disorders, a vulnerable section of society. Ireland's new Mental Health Act 2001 was fully implemented in 2006 with the intent of bringing Irish legislation more in line with international standards, such as the European Convention on Human Rights and United Nations Principles for the Protection of Persons with Mental Illness. The new legislation introduced several important reforms in relation to involuntary admission, independent reviews of involuntary detention, consent to treatment, and treatment of children and adolescents. It also presented significant challenges in terms of service delivery and resources within Irish mental health services. Both mental health service users and providers reported a range of difficulties with the new legislation. In this article, we analyze the Irish Mental Health Act focusing on the enhanced protection that it provides for patients, but also highlighting some areas of concern such as the conduct of mental health tribunals, consent and capacity problems, resource allocation, and disruptions in mental health service delivery.

Using magnetic resonance imaging as a means to study chronic cerebral spinal venous insufficiency in multiple sclerosis patients.

The goal of this work is to present a broad magnetic resonance imaging (MRI) protocol for use in the study of chronic cerebrospinal venous insufficiency (CCSVI). The CCSVI MRI protocol includes the following sequences: time-resolved contrast-enhanced 3D MR angiography, 2D time-of-flight MR venography, and 3D volumetric interpolated breath-hold examination to assess venous structural abnormalities; phase-contrast MR imaging at different levels in the neck and thoracic cavity to quantify flow through the veins, arteries, and cerebrospinal fluid; T2-weighted imaging, T2-weighted fluid-attenuated inversion recovery, and pre- and post-contrast T1-weighted imaging of the brain for examinations of parenchymal lesions; and finally, susceptibility-weighted imaging for quantification of iron deposition in the brain. Data from 111 clinically definite multiple sclerosis patients were assessed for potential structural and flow CCSVI risk criteria, including stenosis, atresia, aplasia, dominant to subdominant venous flow ratio (D:sD), and the sum of their flow rates. Of the 111 patients, 50 (45%) were determined to be nonstenotic (NST) with no stenosis or atresia in their internal jugular veins (IJV), and the rest 61 (55%) were stenotic (ST) having at least one internal jugular vein stenosis or atresia. No occurrence of aplasia was observed. A D:sD of greater than 3:1 was observed in 15 (24.6%) patients of the ST group and 2 (4.0%) patients of the NST group. A sum of dominant and subdominant venous flow rate of <8 mL/s was observed in 22 (36.1%) patients of the ST group and 6 (12.0%) patients of the NST group. MRI provides valuable information in the observation of potential CCSVI risk factors. Low total flow in the 2 dominant veins seemed to be the strongest indicator for risk of having stenoses in the multiple sclerosis population.

Aerosol delivery during high frequency jet ventilation: an MRI evaluation.

BACKGROUND: We have previously demonstrated aerosol delivery during conventional and high frequency oscillatory (HFOV) ventilation using magnetic resonance imaging (MRI) in piglets. There are no reports on aerosol delivery during high frequency jet ventilation (HFJV). OBJECTIVE: To compare delivery of aerosolized gadopentetate dimeglumine (Gd-DTPA) in 3 neonatal ventilator circuits: conventional mechanical ventilation, HFOV, and HFJV. METHODS: Aerosols of Gd-DTPA (0.025 mol/L) generated using a jet nebulizer placed in the inspiratory limb of each ventilator were delivered into an in vitro lung model simultaneously. Multi-slice T1-weighted spin-echo sequence scans were obtained prior to and after 10 and 20 min of cumulative aerosol delivery. Gd-DTPA concentration was calculated from signal intensity changes, and the total amount of Gd-DTPA was estimated. RESULTS: Gd-DTPA was visualized in the lung model at 10 and 20 min for all 3 ventilators. Gd-DTPA delivery was highest with conventional mechanical ventilation (1.92 µmol at 10 min, 2.89 µmol at 20 min), followed by HFJV (1.59 µmol at 10 min, 1.98 µmol at 20 min) and HFOV (0.79 µmol at 10 min, 1.00 µmol at 20 min). CONCLUSIONS: This is the first report of effective aerosol delivery in a neonatal HFJV circuit. Future studies are needed for more accurate quantification of aerosol deposition.

Isolation of natural products by preparative high performance liquid chromatography (prep-HPLC).

Preparative HPLC (prep-HPLC) has emerged as a mainstay of natural products isolation and purification. The various modes available to date, e.g. normal phase, reversed-phase, size exclusion, and ion exchange, can be used to purify most classes of natural products. This chapter presents an overview of the different modes along with a practical guide as to how to purify a natural product using the most robust and widely used of the modes, namely reversed-phase prep-HPLC. Instrumentation set-up and detection methods, sample preparation, method development, and sample work up are also discussed.

Patients with multiple sclerosis with structural venous abnormalities on MR imaging exhibit an abnormal flow distribution of the internal jugular veins.

PURPOSE: To evaluate extracranial venous structural and flow characteristics in patients with multiple sclerosis (MS). MATERIALS AND METHODS: Two hundred subjects with MS from two sites (n = 100 each) were evaluated with magnetic resonance (MR) imaging at 3 T. Contrast-enhanced time-resolved MR angiography and time-of-flight MR venography were used to assess vascular anatomy. Two-dimensional phase-contrast MR imaging was used to quantify blood flow. The MS population was divided into two groups: those with evident internal jugular vein (IJV) stenoses (stenotic group) and those without (nonstenotic group). RESULTS: Of the 200 patients, 136 (68%) showed IJV structural abnormalities, including unilateral or bilateral stenoses at different levels in the neck (n = 101; 50.5%) and atresia (n = 35; 17.5%). The total IJV flow normalized to the total arterial flow of the stenotic group (56% ± 22) was significantly lower than that of the nonstenotic group (77% ± 14; P < .001). The arterial/venous flow mismatch in the stenotic group (12% ± 15) was significantly greater than that in the nonstenotic group (6% ± 12; P < .001). The ratio of subdominant venous flow rate (Fsd) to dominant venous flow rate (Fd) for the stenotic group (0.38 ± 0.27) was significantly lower than for the nonstenotic group (0.59 ± 0.23; P < .001). The majority of the stenotic group (67%) also had an Fsd of less than 3 mL/s, a Fd/Fsd ratio greater than 3:1, and/or a total IJV flow rate of less than 8 mL/s. CONCLUSIONS: MR imaging provides a noninvasive means to separate stenotic from nonstenotic MS cases. The former group was more prevalent in the present MS population and carried significantly less flow in the IJVs than the latter.