First isolation and characterization of SARS-CoV-2 from COVID-19 patient of North East India.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) responsible for the current pandemic has resulted in over 5 million deaths globally. More than a year has passed, still SARS-CoV-2 panic the public life. Virus isolation is of paramount importance for development of vaccines, in-vitro screening of antiviral compounds, pathogenesis studies, etc., Many cell lines were studied for amplification and replication of SARS-CoV-2 and Vero cells were found to be ideal cell lines for isolation. In May 2020, ICMR-Regional Medical Research Centre, NE region, India, successfully established the SARS-CoV-2 culture system in Vero CCL-81 cell lines. Phylogenetic analyses of the whole genome sequences of the SARS-CoV-2 isolate (EPI_ISL_2501532 | 2020-05-19) showed monophyletic clade G and lineage B.1.1.

Modifying the ICP pulse wave: effects on parenchymal blood flow pulsatility.

Pulsation of the cerebral blood flow (CBF) produces intercranial pressure (ICP) waves. The aim of this study is to determine whether externally modifying ICP pulsatility alters parenchymal blood flow pulsatility. A cardiac-gated inflatable device was inserted in the lateral epidural space of 12 anesthetized canines (canis familiaris) and used to cause reduction, inversion, and augmentation of the ICP pulse. CBF in each hemisphere was measured using laser Doppler velocimetry. A significant increase in both mean CBF and its amplitude was observed for reduction as well as inversion of the ICP pulse, with larger changes observed for the inversion protocol. Significant increases in the mean CBF were also observed ipsilaterally for the augmentation protocol together with indications of reduced CBF amplitude contralaterally. External alteration of the ICP pulse thus caused significant changes in parenchymal blood flow pulsatility. The inverse relationship between the ICP and CBF amplitude suggests that the changes did not occur via modification of the intracranial Windkessel mechanism. Thus, the effects likely occurred in the low-pressure vessels, i.e., capillaries and/or venules, rather than the high-pressure arteries. Future MRI studies are however required to map and quantify the effects on global cerebral blood flow.NEW & NOTEWORTHY This study demonstrated that external modification of ICP pulsatility, using a cardiac-gated inflatable device implanted epidurally in canines, alters brain tissue blood flow pulsatility. Specifically, decreasing systolic ICP increased blood flow pulsatility in brain tissue. The results suggest that the altered CBF pulsatility is unlikely to depend on modification of the Windkessel effect on the feeding arterial system but was rather an effect directly on tissue and the lower pressure distal vessels.

Impact of Blood Rheology on Transition to Turbulence and Wall Vibration Downstream of a Stenosis.

Previous experimental flow studies have demonstrated a delay (∼20%) in transition to turbulence for whole blood compared to a Newtonian analog fluid in both a straight pipe and eccentric stenosis model with ridged walls. The impact of wall compliance on the transition to turbulence of blood compared to Newtonian analog and on wall vibration is unknown. The present study employed flexible walls downstream of an eccentric stenosis model and examined the wall vibration during the transition to turbulence with whole blood and a Newtonian analog. Measurements of tube wall vibration velocity (WVV) were used as an indicator of the turbulence level within the flexible tube. WVV was measured at 5, 10, and 15 diameters downstream of the stenosis using a laser Doppler vibrometer at Reynolds numbers 0, 200, 300, 350, 400, 450, 500, 550, 600, 650, 700, and 750. The root mean squares (RMS) of the measured WVV were utilized as an indirect measure of fluid velocity fluctuations present at that location, and hence, an indicator of transition to turbulence. WVV RMS was near-constant until approximately Reynolds number 400. It increased monotonically with Reynolds number for both whole blood and the Newtonian fluid. No differences in the transition to turbulence were observed between whole blood and the Newtonian fluid, as the WVV RMS curves were remarkably similar in shape. This result suggests that rheology had minimal impact on the WVV downstream of a stenosis for transition to turbulence since the fluids had a similar level of vibration.

Facilitators and barriers to the uptake of COVID-19 vaccine precaution dose among adult population: qualitative analysis across six different states of India.

Introduction: India launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues. Methods: An exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach. Results: It was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation. Discussion: The study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies.

Fouling of mammalian hair fibres exposed to a titanium dioxide colloidal suspension.

Fouling of surfaces in prolonged contact with liquid often leads to detrimental alteration of material properties and performance. A wide range of factors which include mass transport, surface properties and surface interactions dictate whether foulants are able to adhere to a surface. Passive means of foulant rejection, such as the microscopic patterns, have been known to develop in nature. In this work, we investigate the anti-fouling behaviour of animal fur and its apparent passive resistance to fouling. We compare the fouling performance of several categories of natural and manufactured fibres, and present correlations between contamination susceptibility and physio-mechanical properties of the fibre and its environment. Lastly, we present a correlation between the fouling intensity of a fibre and the cumulative impact of multiple interacting factors declared in the form of a dimensionless group. Artificial and natural hair strands exhibit comparable anti-fouling behaviour in flow, however, the absence of flow improves the performance of some artificial fibres. Among the plethora of factors affecting the fouling of fur hair, the dimensionless groups we present herein provide the best demarcation between fibres of different origin.

Multisite surveillance for influenza and other respiratory viruses in India: 2016-2018.

There is limited surveillance and laboratory capacity for non-influenza respiratory viruses in India. We leveraged the influenza sentinel surveillance of India to detect other respiratory viruses among patients with acute respiratory infection. Six centers representing different geographic areas of India weekly enrolled a convenience sample of 5-10 patients with acute respiratory infection (ARI) and severe acute respiratory infection (SARI) between September 2016-December 2018. Staff collected nasal and throat specimens in viral transport medium and tested for influenza virus, respiratory syncytial virus (RSV), parainfluenza virus (PIV), human meta-pneumovirus (HMPV), adenovirus (AdV) and human rhinovirus (HRV) by reverse transcription polymerase chain reaction (RT-PCR). Phylogenetic analysis of influenza and RSV was done. We enrolled 16,338 including 8,947 ARI and 7,391 SARI cases during the study period. Median age was 14.6 years (IQR:4-32) in ARI cases and 13 years (IQR:1.3-55) in SARI cases. We detected respiratory viruses in 33.3% (2,981) of ARI and 33.4% (2,468) of SARI cases. Multiple viruses were co-detected in 2.8% (458/16,338) specimens. Among ARI cases influenza (15.4%) were the most frequently detected viruses followed by HRV (6.2%), RSV (5%), HMPV (3.4%), PIV (3.3%) and AdV (3.1%),. Similarly among SARI cases, influenza (12.7%) were most frequently detected followed by RSV (8.2%), HRV (6.1%), PIV (4%), HMPV (2.6%) and AdV (2.1%). Our study demonstrated the feasibility of expanding influenza surveillance systems for surveillance of other respiratory viruses in India. Influenza was the most detected virus among ARI and SARI cases.

Transition to Turbulence Downstream of a Stenosis for Whole Blood and a Newtonian Analog Under Steady Flow Conditions.

Blood, a multiphase fluid comprised of plasma, blood cells, and platelets, is known to exhibit a shear-thinning behavior at low shear rates and near-Newtonian behavior at higher shear rates. However, less is known about the impact of its multiphase nature on the transition to turbulence. In this study, we experimentally determined the critical Reynolds number at which the flow began to transition to turbulence downstream of eccentric stenosis for whole porcine blood and a Newtonian blood analog (water-glycerin mixture). Velocity profiles for both fluids were measured under steady-state flow conditions using an ultrasound Doppler probe placed 12 diameters downstream of eccentric stenosis. Velocity was recorded at 21 locations along the diameter at 11 different flow rates. Normalized turbulent kinetic energy was used to determine the critical Reynolds number for each fluid. Blood rheology was measured before and after each experiment. Tests were conducted on five samples of each fluid inside a temperature-controlled in vitro flow system. The viscosity at a shear rate of 1000 s-1 was used to define the Reynolds number for each fluid. The mean critical Reynolds numbers for blood and water-glycerin were 470 ± 27.5 and 395 ± 10, respectively, indicating a ∼19% delay in transition to turbulence for whole blood compared to the Newtonian fluid. This finding is consistent with a previous report for steady flow in a straight pipe, suggesting some aspect of blood rheology may serve to suppress, or at least delay, the onset of turbulence in vivo.

Evaluation of the equivalence of different intakes of Fruitflow in affecting platelet aggregation and thrombin generation capacity in a randomized, double-blinded pilot study in male subjects.

BACKGROUND: The water-soluble tomato extract, Fruitflow® is a dietary antiplatelet which can be used to lower platelet aggregability in primary preventative settings. We carried out a pilot study to investigate the range of intakes linked to efficacy and to make an initial assessment of variability in response to Fruitflow®. METHODS: Platelet response to adenosine diphosphate (ADP) agonist and thrombin generation capacity were monitored at baseline and 24 h after consuming 0, 30, 75, 150 or 300 mg of Fruitflow® in a randomized, double-blinded crossover study in male subjects 30-65 years of age (N = 12). Results were evaluated for equivalence to the standard 150 mg dose. RESULTS: Results showed that the changes from baseline aggregation and thrombin generation observed after the 75 mg, 150 mg, and 300 mg supplements were equivalent. Aggregation was reduced from baseline by - 12.9 ± 17.7%, - 12.0 ± 13.9% and - 17.7 ± 15.7% respectively, while thrombin generation capacity fell by - 8.6 ± 4.1%, - 9.2 ± 3.1% and - 11.3 ± 2.3% respectively. Effects observed for 0 mg and 30 mg supplements were non-equivalent to 150 mg and not different from baseline (aggregation changed by 3.0 ± 5.0% and - 0.7 ± 10.2% respectively, while thrombin generation changed by 0.8 ± 3.0% and 0.8 ± 3.1% respectively). CONCLUSIONS: The data suggest that the efficacious range for Fruitflow® lies between 75 mg and 300 mg, depending on the individual. It may be pertinent to personalize the daily intake of Fruitflow® depending on individual platelet response. TRIAL REGISTRATION: ISRCTN53447583 , 24/02/2021.

T cell responses in symptomatic moderate patients with pandemic 2009 H1N1 influenza A virus infection.

The response of the host immune system should be appropriate to fight against pandemic 2009 H1N1 (pH1N1) influenza A virus without causing damage to its self. T cells play an indispensable role in the fight against the virus, but have the potential to cause host immunopathological changes. A better understanding of the immunoregulation that occurs during pH1N1 infection is necessary for preventing severity of the disease. In this study, we found that a significantly higher percentage of Vδ1+ T cells and increased expression of activation markers in total T cells in patients with moderate pH1N1 infection could lead to its efficient fight against the virus. On the other hand, the percentages of total and CD4+ T cells were decreased along with an increased expression of exhaustion marker-Tim-3 on T cells that might suppress excessive T cell responses in the host. This tuning of T cell responses might be necessary in efficient combat against pH1N1 virus, without aggravating T cell mediated immunopathology in patients with moderate pH1N1-infection. Keywords: pH1N1; T cells; activation; exhaustion; Tim-3.

Characteristics of Circulatory γδ T cells in Patients with Symptomatic Chronic Hepatitis B Infection.

Hepatitis B is a viral infection that can cause serious liver disease. Chronic hepatitis B (CHB) infection places individuals at higher risk of developing cirrhosis of the liver and hepatocellular cancer. Immune dysfunction, including altered distribution and functional status of T cell immunity, is a contributor to hepatitis B virus (HBV) pathogenesis. In this study, we examined the distribution of circulating γδ T cell subpopulations and levels of cell surface expression of suppressive markers on γδ T cells in individuals with CHB infection and clinical liver disease. A significantly higher proportion of terminally differentiated (TEMRA) (CD27-CD45RA+) γδ T cells along with significantly lower percentages of central memory (CD27+CD45RA-) and effector memory (CD27-CD45RA-) γδ T cells were observed in peripheral blood of these individuals. The expression of exhaustion markers-Tim-3 and Lag-3 was elevated in γδ T cells from CHB-infected individuals compared with healthy controls (HC) and blockade of these exhaustion markers resulted in restoration of interferon gamma (IFN-γ) secretion by γδ T cells. In addition, γδ T cells from CHB patients expressed increased levels of CD69, another important regulator of immune responses. Together, these results suggest that CHB patients with clinical sign of liver disease have TEMRA γδ T cells with a potentially exhausted phenotype that may in turn impair their immunoregulatory role and facilitate pathogenesis of CHB disease.

Hydrodynamics and surface properties influence biofilm proliferation.

A biofilm is an interface-associated colloidal dispersion of bacterial cells and excreted polymers in which microorganisms find protection from their environment. Successful colonization of a surface by a bacterial community is typically a detriment to human health and property. Insight into the biofilm life-cycle provides clues on how their proliferation can be suppressed. In this review, we follow a cell through the cycle of attachment, growth, and departure from a colony. Among the abundance of factors that guide the three phases, we focus on hydrodynamics and stratum properties due to the synergistic effect such properties have on bacteria rejection and removal. Cell motion, whether facilitated by the environment via medium flow or self-actuated by use of an appendage, drastically improves the survivability of a bacterium. Once in the vicinity of a stratum, a single cell is exposed to near-surface interactions, such as van der Waals, electrostatic and specific interactions, similarly to any other colloidal particle. The success of the attachment and the potential for detachment is heavily influenced by surface properties such as material type and topography. The growth of the colony is similarly guided by mainstream flow and the convective transport throughout the biofilm. Beyond the growth phase, hydrodynamic traction forces on a biofilm can elicit strongly non-linear viscoelastic responses from the biofilm soft matter. As the colony exhausts the means of survival at a particular location, a set of trigger signals activates mechanisms of bacterial release, a life-cycle phase also facilitated by fluid flow. A review of biofilm-relevant hydrodynamics and startum properties provides insight into future research avenues.

Accuracy of cardiac-induced brain motion measurement using displacement-encoding with stimulated echoes (DENSE) magnetic resonance imaging (MRI): A phantom study.

PURPOSE: The goal of this study was to determine the accuracy of displacement-encoding with stimulated echoes (DENSE) MRI in a tissue motion phantom with displacements representative of those observed in human brain tissue. METHODS: The phantom was comprised of a plastic shaft rotated at a constant speed. The rotational motion was converted to a vertical displacement through a camshaft. The phantom generated repeatable cyclical displacement waveforms with a peak displacement ranging from 92 µm to 1.04 mm at 1-Hz frequency. The surface displacement of the tissue was obtained using a laser Doppler vibrometer (LDV) before and after the DENSE MRI scans to check for repeatability. The accuracy of DENSE MRI displacement was assessed by comparing the laser Doppler vibrometer and DENSE MRI waveforms. RESULTS: Laser Doppler vibrometer measurements of the tissue motion demonstrated excellent cycle-to-cycle repeatability with a maximum root mean square error of 9 µm between the ensemble-averaged displacement waveform and the individual waveforms over 180 cycles. The maximum difference between DENSE MRI and the laser Doppler vibrometer waveforms ranged from 15 to 50 µm. Additionally, the peak-to-peak difference between the 2 waveforms ranged from 1 to 18 µm. CONCLUSION: Using a tissue phantom undergoing cyclical motion, we demonstrated the percent accuracy of DENSE MRI to measure displacement similar to that observed for in vivo cardiac-induced brain tissue.

Prevalence of campylobacter enteritis in children under 5 years hospitalised for diarrhoea in two cities of Northeast India.

Background: Campylobacter enteritis is the major cause of bacterial gastroenteritis worldwide. In recent years, there has been a rise in global incidence of campylobacteriosis. There are no available data on prevalence of Campylobacter diarrhoea from Northeast India. Materials and Methods: The study investigated archival stool samples collected between 2014 and 2016 from two hospitals of Northeast India. A total of 407 archival stool samples from cases of diarrhoea under 5 years of age were screened for Campylobacter spp. using commercial probe-based real-time polymerase chain reaction assay. Results: Campylobacter spp. was detected in overall 10.1% (41/407; 95% confidence interval: 7.4%-13.3%) in children under 5 years hospitalised for diarrhoea. The prevalence was significantly higher from Dibrugarh, Assam, compared to Dimapur, i.e., 13.4% (27/201) versus 6.8% (14/206), respectively (P = 0.02). Campylobacter detection was highest in the month of June and July compared to December and January (20%-18.8% vs. 8.9%-6.2%, respectively). Further, Campylobacter infection was higher in the age group below 24 months (11.7%) compared to above 24 months (7.0%). Campylobacter jejuni was detected in 80.5% of the positive cases. Conclusion: The present study reveals that Campylobacter infection is endemic in the studied regions of Northeast India and microbiological laboratories of the region should actively pursue the isolation or detection of Campylobacter spp. in cases of diarrhoea in routine stool cultures.

Clivus length distinguishes between asymptomatic healthy controls and symptomatic adult women with Chiari malformation type I.

PURPOSE: While the presence of cerebellar tonsillar descent in radiological images has been used as evidence of Chiari malformation type I (CMI), tonsillar ectopia alone is insufficient to identify individuals with symptomatic CMI. This study sought to identify differences in brain morphology between symptomatic CMI and healthy controls in adult females. METHODS: Two hundred and ten adult females with symptomatic CMI and 90 age- and body mass index-matched asymptomatic female controls were compared using seven brain morphometric measures visible on magnetic resonance images. The CMI and control groups were divided into four subgroups based on the tonsillar position (TP) relative to the foramen magnum: group 1 was made up of healthy controls with normal TP (TP < 0 mm); group 2 was comprised of control individuals with low-lying TP (1-5 mm); group 3 was comprised of symptomatic CMI patients with low-lying TP (1-5 mm); group 4 contained symptomatic CMI patients with severe tonsillar descent (6-13 mm). RESULTS: All morphometrics for symptomatic CMI with severe tonsillar descent were significantly different than those for both control groups. The CMI group with low-lying TP was significantly different for four measures when compared to controls with normal TP. However, only clivus length was statistically different between the CMI and healthy control groups with low-lying TP. CONCLUSION: This study demonstrates that clivus length distinguishes adult female healthy individuals with low-lying tonsils from those with symptomatic CMI. Further investigation is required to understand the importance of a shorter clivus length on CMI symptomatology and pathophysiology.

Genetic characterisation of influenza A(H1N1)pdm09 viruses circulating in Assam, Northeast India during 2009-2015.

Introduction: Influenza A(H1N1)pdm09 virus, since its identification in April 2009, has continued to cause significant outbreaks of respiratory tract infections including pandemics in humans. In the course of its evolution, the virus has acquired many mutations with an ability to cause increased disease severity. A regular molecular surveillance of the virus is essential to mark the evolutionary changes that may cause a shift to the viral behavior. Materials and Methods: Samples of Throat/Nasal swabs were collected from a total of 3715 influenza-like illness cases and screened by Real-time Reverse Transcription-Polymerase Chain Reaction for influenza viruses. Nucleotide sequence analysis was done to identify changes in antigenicity of the virus strains. Results: The present study describes the molecular characteristics of influenza A(H1N1)pdm09 viruses detected in Assam of Northeast India during 2009-2015. Influenza A viruses were detected in 11.4% (425/3715), of which influenza A(H1N1)pdm09 viruses were detected in 41.4% (176/425). The nucleotide sequencing of influenza A(H1N1)pdm09 viruses revealed a total of 17 and 22 amino acid substitutions in haemagglutinin (HA) and neuraminidase (NA) genes of the virus, respectively, compared to contemporary vaccine strain A/California/07/2009. The important mutations detected in HA genes of A/Assam(H1N1)pdm09 strains included E391K, K180Q and S202T. Mutation 'N248D' which has an ability to develop oseltamivir resistance was also detected in NA gene of A/Assam(H1N1)pdm09 strains. Conclusions: Regular molecular surveillance of influenza A(H1N1)pdm09 is important to monitor the viral behavior in terms of increase virulence, drug resistance pattern and emergence of novel strains.

Evidence for sex differences in morphological abnormalities in type I Chiari malformation.

BACKGROUND AND PURPOSE: Relatively little is known about the influence of individual difference variables on the presentation of macro-level brain morphology in type I Chiari malformation (CMI). The goal of the present study is to examine how case-control differences in Chiari are affected by patient sex. MATERIALS AND METHODS: Patient-provided magnetic resonance images were acquired through the Chiari 1000 database. Twenty-four morphometric measurements were taken using mid-sagittal images of 104 participants (26 male CMI, 26 female CMI, 26 male controls, and 26 female controls) using internally developed and validated custom software, Morphpro. Case-control comparisons were conducted separately by sex using healthy controls matched by age and body mass index. Probability-based t-tests, effect sizes (Cohen's d), and confidence intervals were used to compare case-control differences separately by sex. RESULTS: Male and female case-control comparisons yielded largely the same trends of CMI-related morphometric abnormalities. Both groups yielded reductions in posterior cranial fossa (PCF) structure heights. However, there was evidence for greater PCF structure height reductions in male CMI patients as measured by Cohen's d. CONCLUSIONS: Case-control differences indicated strong consistency in the morphometric abnormalities of CMI malformation in males and females. However, despite the higher prevalence rates of CMI in females, the results from the present study suggest that male morphometric abnormalities may be greater in magnitude. These findings also provide insight into the inconsistent findings from previous morphometric studies of CMI and emphasize the importance of controlling for individual differences when conducting case-control comparisons in CMI.

Three-Dimensional CT Morphometric Image Analysis of the Clivus and Sphenoid Sinus in Chiari Malformation Type I.

This study evaluated three-dimensional (3D) volumetric image reconstructions to identify morphological differences of the clivus and sphenoid sinus on computed tomography (CT) scans of Chiari malformation type I (CMI) and control subjects. Axial CT images of adult females for 30 CMI subjects and 30 age and body mass index (BMI) matched controls were used for this retrospective study. 3D volumetric reconstructions were created from the bone windows of axial data following image registration for position and orientation correction of the head. The volume, surface area, linear dimensions and spatial position in the x, y, and z-axes were computed separately for the clivus and the sphenoid sinus for each subject. Eleven parameters were found to be significantly different between CMI subjects compared to controls. Most notably, clivus volume was reduced by 31% on average in CMI subjects. In contrast, we found that the sphenoid sinus volume was 38% greater on average in CMI subjects. Moreover, clivus length, height, width, and thickness were 3.7, 2.8, 3.0 and 9.4 mm reduced, respectively, in CMI subjects. This is the first study to demonstrate cephalometric differences in the 3D morphology of the clivus and sphenoid sinus between CMI subjects and controls.