Post-Myocardial Infarction Remodeling and Hyperkinetic Remote Myocardium in Sheep Measured by Cardiac MRI Feature Tracking.

BACKGROUND: Cardiac MRI feature tracking (FT) allows objective assessment of segmental left ventricular (LV) function following a myocardial infarction (MI), but its utilization in sheep, where interventions can be tested, is lacking. PURPOSE: To apply and validate FT in a sheep model of MI and describe post-MI LV remodeling. STUDY TYPE: Animal model, longitudinal. ANIMAL MODEL: Eighteen lambs (6 months, male, n = 14; female, n = 4; 25.2 ± 4.5 kg). FIELD STRENGTH/SEQUENCE: Two-dimensional balanced steady-state free precession (bSSFP) and 3D inversion recovery fast low angle shot (IR-FLASH) sequences at 3 T. ASSESSMENT: Seven lambs underwent test-retest imaging to assess FT interstudy reproducibility. MI was induced in the remaining 11 by coronary ligation with MRI being undertaken before and 15 days post-MI. Injury size was measured by late gadolinium enhancement (LGE) and LV volumes, LV mass, ejection fraction (LVEF), and wall thickness (LVWT) were measured, with FT measures of global and segmental radial, circumferential, and longitudinal strain. STATISTICAL TESTS: Sampling variability, inter-study, intra and interobserver reproducibility were assessed using Pearson's correlation, Bland-Altman analyses, and intra-class correlation coefficients (ICC). Diagnostic performance of segmental strain to predict LGE was assessed using receiver operating characteristic curve analysis. Significant differences were considered P < 0.05. RESULTS: Inter-study reproducibility of FT was overall good to excellent, with global strain being more reproducible than segmental strain (ICC = 0.89-0.98 vs. 0.77-0.96). MI (4.0 ± 3.7% LV mass) led to LV remodeling, as evident by significantly increased LV volumes and LV mass, and significantly decreased LVWT in injured regions, while LVEF was preserved (54.9 ± 6.9% vs. 55.6 ± 5.7%; P = 0.778). Segmental circumferential strain (CS) correlated most strongly with LGE. Basal and mid- CS increased significantly, while apical CS significantly decreased post-MI. DATA CONCLUSION: FT is reproducible and compensation by hyperkinetic remote myocardium may manifest as overall preserved global LV function. EVIDENCE LEVEL: N/A TECHNICAL EFFICACY: Stage 2.

Radical Cascade Cyclization of Unactivated Alkene-Tethered Indoles with Aryldiazonium Salt and Sodium Metabisulfite to Access Azo- and Sulfonylated-2,3-Dihyro-1H-pyrrolo[1,2-a]indoles.

A method for the construction of heterocyclic scaffold 2,3-dihyro-1H-pyrrolo[1,2-a]indoles via arylsulfonyl radical-triggered cascade cyclization of unactivated alkene-tethered indoles in the absence of any external photocatalyst has been developed. This protocol features easily accessible starting materials such as sodium metabisulfite and aryldiazonium tetrafluoroborates at room temperature and offers good functional group compatibility, enabling the introduction of various functionalized sulfonyl and azo groups into pyrrolo[1,2-a]indoles.

Assessment of liver fibrosis using a 3-dimensional high-resolution late gadolinium enhancement sequence in children and adolescents with Fontan circulation.

OBJECTIVES: To assess abnormal liver enhancement on 15-20 min delayed 3D high-resolution late gadolinium enhancement (3D HR LGE) sequence in patients with Fontan circulation. METHODS: Retrospective study of pediatric Fontan patients (< 18 years old) with combined cardiac-liver MRI from January 2018 to August 2021. Abnormal hepatic enhancement was graded (0-3) for each lobe, summed for a total liver enhancement score (0-6), and compared to repaired tetralogy of Fallot (rTOF) patients. Correlations with other hepatic imaging biomarkers were performed. Temporal relationships of enhancement compared to traditional early portal venous and 5-7-min delayed phase liver imaging were analyzed. RESULTS: The Fontan group (n = 35, 13 ± 3.4 years old, median time from Fontan 10 (9-12) years) had 23/35 (66%) with delayed 3D HR LGE total liver enhancement score > 0 (range 0-5), with greater involvement of the right lobe (1 (0-1) vs 0 (0-1), p < 0.01). The rTOF group (n = 35, 14 ± 2.6 years old) had no abnormal enhancement. In the Fontan group, total liver enhancement was 3 (2-4) in the early portal venous phase, lower at 1 (1-2) in the 5-7-min delayed phase (p < 0.01), and lowest at 1 (0-2) in the 15-20-min delayed phase (p = 0.03). 3D HR LGE enhancement correlated inversely with portal vein flow (rs = - 0.42, p = 0.01) and positively with left lobe stiffness (rs = 0.51, p < 0.01). The enhancement score decreased in 13/35 (37%) between the 5-7- and 15-20-min delayed phases. CONCLUSIONS: Liver fibrosis can be assessed on 3D HR LGE sequences in patients with Fontan circulation, correlates with other imaging biomarkers of Fontan liver disease, and may add information for hepatic surveillance in this population. KEY POINTS: • Abnormal liver enhancement on 3D HR LGE sequences in Fontan patients likely represents liver fibrosis and is seen in up to 66% of children and adolescents with variable distribution and severity. • The degree of 3D HR LGE liver enhancement correlates with decreased portal vein flow and increased left hepatic lobe stiffness.

Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing.

Microcephaly is a frequent feature of neurodevelopmental disorders (NDDs). Our study presents the heterogeneous spectrum of genetic disorders in patients with microcephaly either in isolated form or in association with other neurological and extra-neural abnormalities. We present data of 91 patients from 87 unrelated families referred to our clinic during 2016-2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP, MINPP1, PNPLA8, AIMP2, ANKLE2, NCAPD2 and TRIT1.

Partial Trisomy of Chromosome 8q and Partial Monosomy of Chromosome 6p with Robinow Syndrome-Like Phenotype.

Genetic disorders can be monogenic or chromosomal. Deletions, duplications, and cryptic imbalances due to rearrangements of the telomeres are seen in a number of patients with psychomotor and language delay. Here, the authors report a case of 1-y-old boy born to nonconsanguineous couple who was evaluated for global developmental delay with phenotypic resemblance to a monogenic disorder namely Robinow syndrome. Cytogenetic microarray showed a double segment imbalance involving chromosome 6p25.3p25.2 and chromosome 8q23.3q24.3. Robinow syndrome also known as fetal face syndrome is a rare disorder with characteristic facial phenotype resembling fetal face with macrocephaly, low-set ears, broad great toes, gum hypertrophy, micropenis, and rhizomelia. Facial features include hypertelorism, wide mouth and short nose with upturned tip. It can have dominant or recessive mode of inheritance. The chromosomal abnormality in this case may provide clue to some novel gene for Robinow syndrome etiology.

Cost benefit analysis of portable chest radiography through glass: Initial experience at a tertiary care centre during COVID-19 pandemic.

INTRODUCTION: Portable chest radiography through glass (TG-CXR) is a novel technique, particularly useful during the COVID-19 (Coronavirus disease 2019) pandemic. The purpose of this study was to understand the cost and benefit of adopting TG-CXR in quantifiable terms. METHODS: Portable or bedside radiographs are typically performed by a team of two technologists. The TG-CXR method has the benefit of allowing one technologist to stay outside of the patient room while operating the portable radiography machine, reducing PPE use, decreasing the frequency of radiography machine sanitization and decreasing technologists' exposures to potentially infectious patients. The cost of implementing this technique during the current COVID-19 pandemic was obtained from our department's operational database. The direct cost of routinely used PPE and sanitization materials and the cost of the time taken by the technologists to clean the machine was used to form a quantitative picture of the benefit associated with TG-CXR technique. RESULTS: Technologists were trained on the TG-CXR method during a 15 min shift change briefing. This translated to a one-time cost of $424.88 USD. There was an average reduction of portable radiography machine downtime of 4 min and 48 s per study. The benefit of adopting the TG-CXR technique was $9.87 USD per patient imaged. This will result in a projected net cost savings of $51,451.84 USD per annum. CONCLUSION: Adoption of the TG-CXR technique during the COVID-19 pandemic involved minimal one-time cost, but is projected to result in a net-benefit of over $51,000 USD per annum in our emergency department.

Homozygosity stretches around homozygous mutations in autosomal recessive disorders: patients from nonconsanguineous Indian families.

India has a large heterogeneous population with its unique social and genetic characteristics. Tradition of marriage between specific caste groups have produced unique characteristics to the mutation spectrum of genetic disorders and may be a higher prevalence of autosomal recessive (AR) disorders in some communities. We observed that in many nonconsanguineous families with rare autosomal disorders, maternally and paternally inherited mutations are same, indicating common ancestor. In this era of genomic techniques, finding homozygous regions have become easy. It was seen that the patients with AR disorders, who were homozygous for the disease causing pathogenic / likely pathogenic variations, have large stretches (0.6-188 Mb) of homozygosity around the causative sequence variations. SNP microarray data of patients from consanguineous and nonconsanguineous families also showed that even patients from nonconsanguineous families had 3-49 Mb size regions of homozygosity. Long stretches of homozygosity around homozygous rare pathogenic variants in nonconsanguineous families with rare AR disorders supports the notion that these couples may have a common ancestor for more than six generations and the system of marriages between same groups. Hence, using the strategy of homozygosity by descent even in nonconsanguineous families can be fruitful in identifying the novel pathogenic variations and novel genes.

Clinical and molecular characterization of four patients with Robinow syndrome from different families.

Robinow syndrome (RS) is a rare heterogeneous disorder characterized by short stature, short-limbs, craniofacial, oro-dental abnormalities, vertebral segmentation defects, and frequently genital hypoplasia. Both autosomal dominant and recessive patterns of inheritance are observed with many causative genes. Here, we present the phenotypes and genotypes of four children with RS from different Indian families. Sequence variants were identified in genes ROR2, DVL1, and DVL3. Our results expand the mutational spectrum of RS and we also highlight the radiological changes in the radius and ulna in patients with ROR2 sequence variants which are primarily characteristic for ROR2 related RS but have been reported in WNT5A related RS.

Portable Chest Radiography Through Glass During COVID-19 Pandemic-Initial Experience in a Tertiary Care Center.

BACKGROUND: Portable chest radiograph for COVID-19 positive patients and persons under investigation can be acquired through glass doors or walls of isolation rooms to limit exposure to the pathogen and conserve resources. PURPOSE: To report our initial experience with acquiring portable chest radiographs through glass doors of isolation rooms. METHODS: Only 1 of 2 radiology technologist team members donned personal protective equipment and stayed inside the isolation room, while the second technologist and the radiography unit remained outside during the procedure. First hundred radiographs acquired through glass at the emergency department of our institute formed the "through glass radiograph" group. Hundred consecutive portable chest radiographs performed in a conventional manner formed the "conventional radiograph" group for comparison. Imaging database and feedback from operations leader were used to identify occurrences of a failed procedure. Suggestion of repeating the study and comments related to quality of the study were recorded from the reports of the staff radiologist. RESULTS: There was no instance of failed acquisition, nondiagnostic examination, or suggestion of repetition in both groups. No significant difference in the number of reports with quality related remarks (P > .05) was found between the 2 groups. Radiography through glass doors was associated with increased suboptimal positioning related remarks in radiology reports (P < .05). No significant association was identified among other comments about image quality. CONCLUSION: Our initial clinical experience suggests that the acquisition of portable chest radiographs through the glass doors of isolation rooms is technically feasible and results in diagnostic quality studies.

Proof of Concept: Phantom Study to Ensure Quality and Safety of Portable Chest Radiography Through Glass During the COVID-19 Pandemic.

BACKGROUND: Chest radiography is often used to detect lung involvement in patients with suspected pneumonia. Chest radiography through glass walls of an isolation room is a technique that could be immensely useful in the current COVID-19 pandemic. PURPOSE: The purpose of this study was to ensure quality and radiation safety while acquiring portable chest radiographs through the glass doors of isolation rooms using an adult anthropomorphic thorax phantom. MATERIALS AND METHODS: Sixteen chest radiographs were acquired utilizing different exposure factors without glass, through the smart glass, and through regular glass. Images were scored independently by 2 radiologists for quantum mottle and sharpness of anatomical structures using a 5-point Likert scale. Statistically significant differences in Likert scale scores and entrance surface dose (ESD) between images acquired without glass and through the smart and regular glass were tested. Interreader reliability was also evaluated. RESULTS: Compared with conventional radiography, equal or higher mean image quality scores (mottle and anatomical structures) were observed with the smart glass using 100 kVp at 12 mAs and 20 mAs and 125 kVp at 6.3 mAs (100 kVp at 2 mAs and 125 kVp at 3.2 mAs were used for conventional radiography observations). There was no statistically significant difference in the Likert scale scores for image quality and the entrance surface dose for radiographs acquired without glass, through the smart glass, and through regular glass. Backscatter from the smart glass was minimal at a distance of 3 m and was recorded as zero at a distance of 4 m from the x-ray tube outside an isolation room. CONCLUSIONS: Good-quality portable chest radiographs can be obtained safely through the smart glass doors of the isolation room. However, this technique does result in minor backscatter radiation. Modifications in the exposure factors (such as increasing milliampere seconds) may be required to optimize image quality while using this technique.

A potential seedling-stage evaluation method for heat tolerance in Indian mustard (Brassica juncea L. Czern and Coss).

Heat stress is one of the major limitations to crop productivity. In the present study, an efficient method of screening was adopted for identification of heat tolerant Indian Mustard genotypes by applying 4-day cycle of heat stress to seedlings. Thirty-four genotypes were screened based upon lipid peroxidation and survival percentage and classified them into five different classes according to membership function value (MFV) for response against high temperature. The maximum and minimum value of mean MFV were 0.89 (highly heat tolerant, TPM1) and 0.12 (highly heat sensitive, JM2), respectively. The coefficient of determination (R 2) between the mean MFV and the heat tolerance index (HTI) of MDA content, survival percentage was 0.914 and 0.808 suggesting that these parameters are reliable traits to evaluate the heat tolerance of Brassica juncea genotypes. The evaluation method was further validated using identified contrasting genotypes and assessment of heat stress associated biochemical parameters. Results showed efficient recovery of tolerant genotype as compared to sensitive genotype. Expression profiling of heat stress-related genes (HSP21 and HSFA7A) showed significant upregulation in the tolerant genotype (TPM1) (9.73- and 4.87-fold, respectively) as compared to the sensitive genotype (JM2) (4.18- and 1.73-fold, respectively) under heat stress condition. The results imply development of an efficient screening method which is useful for evaluation and breeding of thermo-tolerant B. juncea.

Assessing Changes in Characteristics of Hot Extremes Over India in a Warming Environment and their Driving Mechanisms.

Change in hot extremes is one of the accepted evidence and also a global indicator of an anthropogenic climate change, which has serious environmental and economic impacts. In the present study, the India Meteorological Department gridded temperature data is used to characterize hot extremes over India in terms of frequency and intensity. Results provide compelling evidence that large parts of India, except the Indo-Gangetic plains, have experienced more occurrences of hot days (upsurge by 24.7%) having higher temperatures in the recent period (1976-2018), compared to the past (1951-1975), which suggests a shift in climate. Strong positive geopotential height anomalies at 500 hPa over the northern parts of India, which dynamically produces subsidence and clear sky conditions along with reduced precipitable water and depleted soil moisture are identified to be the crucial factors responsible for an increase of hot extremes in recent decades. Furthermore, the preceding December-February Niño-3.4 sea surface temperature (SST) anomalies are strongly connected with hot days frequency and the mechanism for the lag of several months is related to 3-4 months delayed response of Indian Ocean SSTs to El Niño/Southern Oscillation. Thus, post-Niño hot extremes over India can be potentially anticipated in advance and this will help society to prepare for such extremes.

A mild phenotype of LGI4-Related arthrogryposis multiplex congenita with intrafamilial variability.

Arthrogryposis multiplex congenita (AMC) is a heterogeneous group of congenital disorders characterized by multiple joint contractures. We report a family with two children affected with AMC. First child had a severe AMC phenotype and died in infancy. Second child, currently 4-years-old, was ascertained at the age of 30 months with mild AMC phenotype with cognitive and speech delay. On whole exome sequencing, a novel biallelic sequence variant in initiation codon of LGI4 (leucine-rich glioma-inactivated 4) gene was identified in her. Real-Time PCR revealed 50% reduction in mRNA transcript levels in subject as compared to control which explains the milder phenotype. Till date, only four families with nine affected individuals with LGI4-related AMC have been reported. Except for one child surviving up to 6 years, all others were either terminated after prenatal diagnosis or succumbed in neonatal period. This study adds to mutation spectrum of LGI4 and reports the second case of mild AMC with extended phenotype. We review the existing phenotypic and genotypic information for the individuals with this condition and highlight the intrafamilial and interfamilial variability in these individuals.

Cytogenetic microarray in structurally normal and abnormal foetuses: a five year experience elucidating increasing acceptance and clinical utility.

The aim of the present study was to evaluate the diagnostic yield of prenatal cytogenetic microarray (CMA) in structurally normal and abnormal foetuses and record the acceptance rate of CMA for prenatal diagnosis over a course of five year. In 128 structurally normal and abnormal foetuses, CMA was performed along with foetal karyotype, after exclusion of aneuploidy by quantitative fluorescence polymerase chain reaction. The microarray was able to detect the pathogenic variants in 5.5% cases; the diagnostic yield in structurally abnormal foetuses was 8.8% and 4.7% in foetuses with a high aneuploidy risk. Balanced and unbalanced translocations, and low level mosaicism were detected. Reanalysis of variants of uncertain significance identified pathogenic variant. The study shows higher diagnostic yield in structurally abnormal cases, the importance of foetal karyotype and reanalysis in microarray. The acceptance rate of prenatal CMA increased five-fold over a period of five year.

Deletion 7q21.2-q22.1 in a case with split hand-split foot malformation, sensorineural hearing loss and intellectual disability: Phenotype subtypes and the correlation with genotypes.

The split hand/split foot malformation (SHFM) or ectrodactyly is a rare congenital heterogeneous limb developmental disorder with at least 6 associated loci. It is characterized by absence of central rays of hands and feet and fusion of remaining digits. It can present as an isolated malformation or in combination with additional anomalies (non-syndromic or syndromic ectrodactyly). This is a report of a 4 year old male child with SHFM with facial dysmorphism, profound sensorineural hearing loss, microcephaly and developmental delay associated with a large deletion of 7.242 MB on chromosome 7q21.2-q22.1. This is the region of SHFM1 (OMIM No. 183600) and deletions of varying sizes have been reported. We have reviewed the phenotypes and genotypes of this locus. The deletions with this severe phenotype are large and some of them detected on traditional karyotyping. The cases with submicroscopic deletions are few but show some correlation of genotype with phenotype which will help in counseling the families with prenatally or neonatally detected deletion at this locus.

Malan syndrome: Extension of genotype and phenotype spectrum.

Malan syndrome and Marshall-Smith syndrome (MSS) are allelic disorders caused by mutation in NFIX gene. We report a 3-year- 6 months- old female with clinical features suggestive of Malan syndrome with mutation in exon 2 of NFIX gene. NFIX gene, where most of the mutations in Malan syndrome are located. She did not have advanced bone age. The radiographs of long bones showed metaphyseal changes which were not reported previously. This study reports the first mutation proven case from India and highlights the overlap between MSS and Malan syndrome.