Understanding long COVID myocarditis: A comprehensive review.

Infectious diseases are a cause of major concern in this twenty-first century. There have been reports of various outbreaks like severe acute respiratory syndrome (SARS) in 2003, swine flu in 2009, Zika virus disease in 2015, and Middle East Respiratory Syndrome (MERS) in 2012, since the start of this millennium. In addition to these outbreaks, the latest infectious disease to result in an outbreak is the SARS-CoV-2 infection. A viral infection recognized as a respiratory illness at the time of emergence, SARS-CoV-2 has wreaked havoc worldwide because of its long-lasting implications like heart failure, sepsis, organ failure, etc., and its significant impact on the global economy. Besides the acute illness, it also leads to symptoms months later which is called long COVID or post-COVID-19 condition. Due to its ever-increasing prevalence, it has been a significant challenge to treat the affected individuals and manage the complications as well. Myocarditis, a long-term complication of coronavirus disease 2019 (COVID-19) is an inflammatory condition involving the myocardium of the heart, which could even be fatal in the long term in cases of progression to ventricular dysfunction and heart failure. Thus, it is imperative to diagnose early and treat this condition in the affected individuals. At present, there are numerous studies which are in progress, investigating patients with COVID-19-related myocarditis and the treatment strategies. This review focuses primarily on myocarditis, a life-threatening complication of COVID-19 illness, and endeavors to elucidate the pathogenesis, biomarkers, and management of long COVID myocarditis along with pipeline drugs in detail.

Marine biological macromolecules as matrix material for biosensor fabrication.

The ocean covers two-third of our planet and has great biological heterogeneity. Marine organisms like algae, vertebrates, invertebrates, and microbes are known to provide many natural products with biological activities as well as potential sources of biomaterials for therapeutic, biomedical, biosensors, and climate stabilization. Over the years, the field of biosensors has gained huge attention due to their extraordinary ability to provide early disease diagnosis, rapid detection of various molecules and substances along with long-term monitoring. This review aims to focus on the properties and employment of various biomaterials (carbohydrate polymers, proteins, polyacids, etc.) of marine origins such as alginate, chitin, chitosan, fucoidan, carrageenan, chondroitin sulfate, hyaluronic acid, collagen, marine pigments, marine nanoparticles, hydroxyapatite, biosilica, lectins, and marine whole cell in the design and development of biosensors. Furthermore, this review also covers the source of such marine biomaterials and their promising evolution in the fabrication of biosensors that are potent to be employed in the biomedical, environmental science, and agricultural sciences domains. The use of such fabricated biosensors harnesses the system with excellent specificity, selectivity, biocompatibility, thermal stability, and minimal cost advantages.

An automated computer vision based preliminary study for the identification of a heavy metal (Hg) exposed fish-channa punctatus.

Fishes available in the market may be cultured either in fresh or contaminated water bodies. Heavy metals are one of those contaminants which may cause menace to fish health and thereby affect the health of living beings consuming them. The identification of heavy metal residues in fish samples is a challenging task and may require expensive and sophisticated instruments and testing. This paper investigates visual changes which may be used as benchmark for differentiating between fresh water and heavy metal exposed fishes. The proposed method is an automated non-destructive image processing method for identifying visual changes which can be used to differentiate between controlled (untreated) and heavy metals exposed (treated) fishes. The eye of the fish from digital images is considered as focal tissue that was automatically segmented using the Circular Hough Transform and adaptive intensity thresholding. Post segmentation, a potential feature is identified and transformed into mathematical parameters for classification of a fish sample as fresh or heavy metal exposed water fish. The proposed method can identify and translate the potential visual feature for ease of understanding. The accuracy of the proposed method is high, and computation time elapsed indicates the possibility of using such algorithm for real time detection in related field.

Removal of endrin and dieldrin isomeric pesticides through stereoselective adsorption behavior on the graphene oxide-magnetic nanoparticles.

A novel stereoselective removal behavior of isomeric endrin and dieldrin pesticides from sample solution is demonstrated using nanocomposite of graphene oxide (GO) and iron oxide (Fe3O4) magnetic nanoparticles (MNPs). The removal efficiency of endrin and dieldrin was found higher when GO-MNPs was used as a separating probe than the individual use of GO and MNPs. The removal efficiency of both the pesticides was found to be more favorable when the dosage amount of GO-MNPs was 30 mg for 30-min contact time with pH 4.0 at room temperature. The good correlation of determination (R 2) with 0.975 and 0.973 values obtained for endrin and dieldrin, respectively demonstrated a well fitting of Langmuir adsorption isotherm model. The higher removal percentage (86.0%) and higher slope value of Langmuir adsorption isotherm were estimated for endrin compared to dieldrin (74.0%). The reason for higher adsorption percentage of endrin is due to the endo-position of oxygen atom in molecule favors more interaction of molecules with GO-MNPs compared to the exo-position of oxygen present in dieldrin. In addition, the higher value of R 2 for endrin and dieldrin demonstrated better suitability of pseudo-first-order and pseudo-second-order kinetic models, respectively. The advantages of the present method are use of simple UV-vis spectrophotometry for monitoring and low-cost use of GO-MNPs nanomaterial for the removal of pesticides from sample solution.

Synthesis of xanthan gum graft copolymer and its application for controlled release of highly water soluble Levofloxacin drug in aqueous medium.

Graft copolymers (XG-g-PNVP-1 to XG-g-PNVP-5) of xanthan gum (XG) and poly(N-vinyl-2-pyrrolidone) (PNVP) was synthesized by free radical polymerization using peroxymonosulphate/thiourea redox pair. The synthesized graft copolymers were well characterized by 1H NMR, FTIR, XRD, SEM, TGA/DTA and AFM analyses. The optimum conditions for maximum grafting were determined by varying the concentrations of N-vinyl-2-pyrrolidone (NVP) from 10×10-2 to 18×10-2moldm-3; the grafting ratios increases up to 14×10-2moldm-3, while thereafter decreased. Graft copolymer (XG-g-PNVP-D) hybrid was prepared to load levofloxacin drug, about 15mg drug was loaded; and its release was studied in phosphate buffer solution (PBS) at pH 7.4 on 37±0.1°C; About 80% drug was released in 36h.

Solid state thermal degradation behaviour of graft copolymers of carboxymethyl cellulose with vinyl monomers.

The graft copolymer of sodium carboxymethyl cellulose (CMC) with acrylamide (ACM), dimethylacrylamide (DMA), N-vinyl pyrrolidone (NVP), 2-acrylamido-2-methyl-1-propane sulphonic acid (AMPS) and vinyl caprolactum (VCL) were synthesized in nitrogen atmosphere by employing redox initiators. The integral procedural decomposition temperature (IPDT) of CMC and its graft copolymer with ACM, DMA, AMPS, NVP and VCL have been found to be 274°C, 375°C, 421°C, 404°C, 466°C and 331°C, respectively. The higher value of IPDT showed more thermal stability. Among all five graft copolymers, the graft copolymer of CMC with NVP is thermally more stable and VCL grafted copolymer was found least thermally stable. The higher char yield and final decomposition temperature (FDT) were obtained in the case of more thermally stable graft copolymer. All five graft copolymers have shown more than one Tmax, which suggests that degradations were multistep process.

Dose-dependent facilitation of peripheral nerve regeneration by bone marrow-derived mononuclear cells: a randomized controlled study: laboratory investigation.

OBJECT: Bone marrow-derived stem cells enhance the rate of regeneration of neuronal cells leading to clinical improvement in nerve injury, spinal cord injury, and brain infarction. Recent experiments in the local application of bone marrow-derived mononuclear cells (BM-MNCs) in models of sciatic nerve transection in rats have suggested their beneficial role in nerve regeneration, although the effects of variable doses of stem cells on peripheral nerve regeneration have never been specifically evaluated in the literature. In this paper, the authors evaluated the dose-dependent role of BM-MNCs in peripheral nerve regeneration in a model of sciatic nerve transection in rats. METHODS: The right sciatic nerve of 60 adult female Wistar rats (randomized into 2 test groups and 1 control group, 20 rats in each group) underwent transection under an operating microscope. The cut ends of the nerve were approximated using 2 epineural microsutures. The gap was filled with low-dose (5 million BM-MNCs/100 µl phosphate-buffered saline [PBS]) rat BM-MNCs in one group, high-dose (10 million BM-MNCs/100 µl PBS) rat BM-MNCs in another group, and only PBS in the control group, and the approximated nerve ends were sealed using fibrin glue. Histological assessment was performed after 30 days by using semiquantitative and morphometric analyses and was done to assess axonal regeneration, percentage of myelinated fibers, axonal diameter, fiber diameter, and myelin thickness at distal-most sites (10 mm from site of repair), intermediate distal sites (5 mm distal to the repair site), and site of repair. RESULTS: The recovery of nerve cell architecture after nerve anastomosis was far better in the high-dose BM-MNC group than in the low-dose BM-MNC and control groups, and it was most evident (p < 0.02 in the majority of the parameters [3 of 4]) at the distal-most site. Overall, the improvement in myelin thickness was most significant with incremental dosage of BM-MNCs, and was evident at the repair, intermediate distal, and distal-most sites (p = 0.001). CONCLUSIONS: This study emphasizes the role of BM-MNCs, which can be isolated easily from bone marrow aspirates, in peripheral nerve injury and highlights their dose-dependent facilitation of nerve regeneration.

Correlation of diffusion tensor imaging metrics with neurocognitive function in Chiari I malformation.

BACKGROUND: The aim of this study was to examine changes in normal-appearing deep gray and white matter regions of the brain in patients with Chiari I malformation compared with controls using diffusion tensor imaging (DTI) and to correlate these changes with neuropsychological (NP) test scores. METHODS: Conventional magnetic resonance imaging, DTI, and neuropsychological tests were performed on 10 patients (median age 27 years, range 18 to 36 years) with Chiari I malformation and 10 age/sex-matched healthy controls. Diffusion tensor imaging metrics (fractional anisotropy, mean diffusivity [MD], radial diffusivity [RD], and axial diffusivity [AD]) were quantified in different regions of the brain in patients as well as in controls using the region of interest (ROI) method. An independent Student t test was performed to evaluate differences in diffusion tensor imaging metrics from patients and controls. Pearson's correlation coefficient was also used to determine association between NP test scores and DTI metrics in patients. RESULTS: Significantly reduced fractional anisotropy with increased MD was found in genu, splenium, fornix, and putamen in patients compared with controls; however, RD significantly increased in fornix and cingulum, whereas AD significantly increased in putamen, thalamus, and fornix as compared with controls. NP tests were found to be abnormal in patients with Chiari I malformation compared with controls, and some of these tests showed significant correlation with DTI metrics. CONCLUSIONS: We conclude that abnormal changes in the DTI metrics in patients with Chiari I malformation indicate microstructural abnormalities in different brain regions that may be associated with neurocognitive abnormalities.

Loss of heterozygosity on chromosome 10q in glioblastomas, and its association with other genetic alterations and survival in Indian patients.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant central nervous system neoplasm. Loss of heterozygosity (LOH) on chromosome 10q in these tumors has been found to show variable association with prognosis. AIM: To evaluate LOH 10q status in cases of GBM, and to correlate these results with patient characteristics, other genetic alterations, and survival. MATERIAL AND METHODS: Fresh tumor tissue and blood samples were obtained for 25 cases of GBM diagnosed over a 2-year period. LOH 10q assay was performed on blood and tumor DNA by a PCR-based method using four microsatellite markers. TP53 mutation analysis and fluorescence in situ hybridization for epidermal growth factor receptor (EGFR) were performed. Histopathology was reviewed and clinical data were analyzed. RESULTS: LOH 10q was identified in 17 of 25 cases (68%). Losses were frequent with markers D10S1765 (12/20 informative cases; 60%) and D10S587 (12/17 informative cases; 70.5%) in the regions of 10q23.3 and 10q26.1, respectively. D10S540 for 10q25.1 showed LOH in 4/12 informative cases (33.3%) and D10S1770 for 10q26-ter in none of the 25 cases. LOH with D10S1765 at the PTEN gene locus was found to correlate with overall LOH 10q status (P = 0.001). LOH 10q was more common in patients older than 40 years (16/19, 84.2%) than in those below (1/6, 16.7%) (P = 0.006). One of three pediatric patients included demonstrated LOH 10q. Survival rates for patients with LOH were lower than for patients with retained heterozygosity. CONCLUSION: LOH 10q is a frequent genetic abnormality in GBM in Indian patients, is seen more frequently in older adults, and its presence is associated with shorter survival. The single best marker to determine LOH 10q status is D10S1765 at the PTEN region.

Cognitive functions correlate with diffusion tensor imaging metrics in patients with spina bifida cystica.

PURPOSE: Spina bifida cystica (SBC) is a group of neurodevelopmental defects caused by improper neural tube closure, which may be responsible for deficits in cognitive functions. The purpose of this study was to examine changes in normal appearing deep gray and white matter brain regions in SBC patients compared with controls through diffusion tensor imaging (DTI) and correlate these changes with neuropsychometric tests. METHODS: Conventional magnetic resonance imaging and neuropsychometric tests were performed on 13 patients and ten controls. DTI-derived fractional anisotropy (FA) and mean diffusivity (MD) were quantified in different brain regions in controls and patients. RESULTS: Significantly decreased FA was observed in caudate nuclei, putamen, genu, splenium, and increased FA was found in middle cerebellar peduncle (MCP) in patients compared with controls. We observed significantly increased MD in genu and splenium. However, increased MD was found in fornix of patients compared with controls. Majority of neuropsychological tests were found to be significantly impaired and some of these showed significant correlation with DTI metrics in genu, splenium, and MCP in these patients. CONCLUSIONS: We conclude that DTI metrics are significantly abnormal in deep gray matter nuclei, genu, splenium, and MCP in SBC patients and may provide microstructural basis for neuropsychological abnormalities in these patients.

O6-methylguanine DNA methyltransferase gene promoter methylation status in gliomas and its correlation with other molecular alterations: first Indian report with review of challenges for use in customized treatment.

BACKGROUND: O6-methylguanine methyltransferase (MGMT) promoter methylation in adult glioblastomas (glioblastoma multiforme) is considered a promising molecular alteration, predictive of better response to temozolomide therapy and longer overall survival. OBJECTIVE: To look at the frequency of MGMT methylation in glial tumors of all grades and types, and correlate this alteration with loss of heterozygosity 1p/19q, TP53 gene mutations, epidermal growth factor receptor (EGFR) amplification, and isocitrate dehydrogenase 1 (IDH1) mutations. METHODS: One hundred two gliomas of various grades and subtypes were assessed by methylation-specific polymerase chain reaction for MGMT promoter methylation status. The results were correlated with 1p/19q status, EGFR amplification, TP53, and IDH1 mutations. RESULTS: There was an inverse correlation of MGMT promoter methylation frequency with tumor grade, observed in 79.4%, 70.8%, and 56.8% of grade II, grade III, and grade IV gliomas, respectively. The difference was statistically significant in grade II vs IV tumors (P=.036). The majority of cases with 1p/19q loss of heterozygosity also showed MGMT methylation, although the association was not significant. There was no significant correlation of MGMT status with IDH1 mutation. In astrocytic tumors, there was no correlation of MGMT methylation with TP53 mutation or EGFR amplification. CONCLUSION: MGMT promoter methylation was observed in a considerable proportion of all grades and subtypes of gliomas, with no significant correlation with other known genetic alterations. On extensive literature review, in both low- and high-grade gliomas, wide variability of data on the frequency of MGMT methylation and its association with other molecular alterations from various centers was noted, mostly owing to technical causes. This raises questions regarding the capacity of this test for use as an objective and reproducible marker for customized treatment in individual cases.

MGMT gene promoter methylation in pediatric glioblastomas.

PURPOSE: Relatively few studies have been performed on molecular properties of pediatric glioblastoma multiforme (GBM). Methylation of DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT) promoter region has been associated with favorable prognosis and prolonged survival in adult GBM patients treated with temozolomide (TMZ). We explored the frequency of MGMT gene promoter methylation in pediatric glioblastomas and compared it with the known molecular alterations in p53. METHODS: Twenty pediatric GBM cases were selected. MGMT promoter methylation was assessed by methylation specific PCR. p53 expression was determined by immunohistochemistry. RESULTS: MGMT gene promoter methylation was observed in 50% of pediatric glioblastomas. p53 protein expression was detected in 60% of cases. Seventy percent of cases with methylated MGMT promoter were p53 immunopositive. CONCLUSIONS: The frequency of MGMT gene promoter methylation in pediatric GBMs was similar to adult GBM patients. The pediatric GBMs should also be investigated for MGMT promoter methylation to identify a subset of patients likely to benefit from TMZ therapy. p53 protein overexpression was more common in pediatric primary GBMs. To the best of our knowledge this is only the second study on MGMT gene promoter methylation status in pediatric GBMs.

Cerebral oedema in minimal hepatic encephalopathy due to extrahepatic portal venous obstruction.

BACKGROUND: Minimal hepatic encephalopathy (MHE) has recently been reported in patients with extrahepatic portal venous obstruction (EHPVO). AIMS: To evaluate brain changes by magnetic resonance studies in EHPVO patients. METHODS: Blood ammonia level, critical flicker frequency (CFF), brain metabolites on 1H-magnetic resonance (MR) spectroscopy and brain water content on diffusion tensor imaging and magnetization transfer ratio (MTR) were studied in 31 EHPVO patients with and without MHE, as determined by neuropsychological tests. CFF and magnetic resonance imaging studies were also performed in 23 controls. RESULTS: Fourteen patients (14/31, 45%) had MHE. Blood ammonia level was elevated in all, being significantly higher in the MHE than no MHE group. CFF was abnormal in 13% (4/31) with EHPVO and in 21% (3/14) with MHE. On 1H-MR spectroscopy, increased Glx/Cr, decreased mIns/Cr, and no change in Cho/Cr were noted in patients with MHE compared with controls. Significantly increased mean diffusivity (MD) and decreased (MTR) were observed in the MHE group, suggesting presence of interstitial cerebral oedema (ICE). MD correlated positively with blood ammonia level (r=0.65, P=0.003) and Glx (r=0.60, P=0.003). DISCUSSION: MHE was detected in 45% of patients with EHPVO while CFF was abnormal in only 13%. ICE was present in 7/10 brain regions examined, particularly in those with MHE. Hyperammonaemia elevated cerebral Glx levels correlated well with ICE. CONCLUSIONS: MHE was common in EHPVO; CFF could identify it only in a minority. ICE was present in EHPVO, particularly in those with MHE. It correlated with blood ammonia and Glx/Cr levels. Hyperammonaemia seems to contribute to ICE in EHPVO.

Heterozygosity status of 1p and 19q and its correlation with p53 protein expression and EGFR amplification in patients with astrocytic tumors: novel series from India.

There are few reports of loss of heterozygosity (LOH) of 1p and 19q in astrocytic tumors, especially glioblastoma multiforme (GBM). We evaluated 1p and 19q (either or both) heterozygosity status in 71 astrocytomas, including 6 pediatric cases: 20 diffuse astrocytomas (DA), 9 anaplastic astrocytomas (AA), and 42 GBM. In the GBMs, p53 protein expression was assessed by immunohistochemistry and epidermal growth factor receptor (EGFR) gene amplification by fluorescence in situ hybridization; TP53 sequencing was done in 15 of the GBMs. In adults, LOH of 1p or 19q was detected in 16% of DAs and 50% of GBMs; none of the AAs showed this alteration. In GBMs, LOH of 19q was most common (26%), followed by combined 1p and 19q LOH (13%) and 1p LOH (10%). Pediatric GBMs also harbored isolated 1p and 19q LOH (50%). Notably, LOH of 1p or 19q LOH was more frequent in p53 immunopositive secondary GBMs (61%) than in primary GBMs (17%). This suggests that LOH of 1p and 19q may be acquired during progression to secondary GBMs. Thus, 1p and 19q LOH can occur in astrocytic tumors, most commonly in secondary GBMs without morphological correlation with an oligodendroglial histology. The clinical significance of recognition of this subset of GBMs is based on several recent reports of association with better prognosis, although long-term follow-up studies are required.

Brain MR imaging and 1H-MR spectroscopy changes in patients with extrahepatic portal vein obstruction from early childhood to adulthood.

BACKGROUND AND PURPOSE: MR imaging and (1)H-MR spectroscopy changes are well reported in cirrhotic patients, whereas they are inadequately reported in EHPVO. The aim of this study was to investigate age-related changes in brain MR imaging and metabolite profile in EHPVO with and without MHE and to explore any correlation of imaging and (1)H-MR spectroscopy parameters with blood ammonia. MATERIALS AND METHODS: Sixty-three patients with EHPVO (children, 7-12 years [n = 22], adolescents, 13-18 years [n = 15] and adults, 19-41 years [n = 26]) and 47 healthy age/sex-matched volunteers were studied. Neuropsychological tests, MR imaging, (1)H-MR spectroscopy, and blood ammonia estimation were performed in all subjects. RESULTS: Of 63 EHPVO patients, 25 (40%) who had MHE showed significantly increased MD, Glx, and blood ammonia in all 3 age groups; however, myo-inositol was significantly lower only in adults when compared with controls. MD positively correlated with blood ammonia and Glx in all age groups. Brain choline levels were normal in all patients with different age groups. CONCLUSIONS: Increases in brain MD, Glx, and blood ammonia were associated with MHE in all age groups. Normal brain choline in EHPVO signifies healthy liver and may serve as a diagnostic marker for its differentiation from cirrhosis-induced encephalopathy. Significant decrease of myo-inositol in adults is probably due to cellular osmoregulation secondary to long-standing hyperammonemia.

Encephalopathy assessment in children with extra-hepatic portal vein obstruction with MR, psychometry and critical flicker frequency.

BACKGROUND & AIMS: Mild cognitive and psychomotor deficit has been reported in patients with extra-hepatic portal vein obstruction. This prospective study was done to ascertain the presence of minimal hepatic encephalopathy by neuropsychological testing and its correlation with diffusion tensor imaging derived metrics, T1 signal intensity, brain metabolites in (1)H magnetic resonance spectroscopy, blood ammonia and critical flicker frequency in patients with extra-hepatic portal vein obstruction. METHODS: Neuropsychological tests, critical flicker frequency, blood ammonia, diffusion tensor imaging, T1 signal intensity and (1)H magnetic resonance spectroscopy were determined in 22 extra-hepatic portal vein obstruction and 17 healthy children. Bonferroni multiple comparison post hoc analysis was done to compare controls with patient groups. RESULTS: Based on neuropsychological tests, 7/22 patients had minimal hepatic encephalopathy, and significantly increased Glx/Cr ratio, blood ammonia, mean diffusivity and globus pallidus T1 signal intensity with decreased critical flicker frequency in comparison to controls and in those without minimal hepatic encephalopathy. Cho/Cr, mI/Cr ratio and fractional anisotropy were unchanged in patient groups compared to controls. A significant inverse correlation of neuropsychological test with mean diffusivity, Glx/Cr ratio and blood ammonia and a positive correlation among mean diffusivity, blood ammonia and Glx/Cr ratio was seen. CONCLUSIONS: Extra-hepatic portal vein obstruction is a true hyperammonia model with porto-systemic shunting and normal liver functions that results in minimal hepatic encephalopathy in one-third of these children. Hyperammonia results in generalized low grade cerebral edema and cognitive decline as evidenced by increased Glx/Cr ratio, mean diffusivity values and abnormal neuropsychological tests.

Serial changes in diffusion tensor imaging metrics of corpus callosum in moderate traumatic brain injury patients and their correlation with neuropsychometric tests: a 2-year follow-up study.

OBJECTIVE: To assess longitudinally the severity of diffuse axonal injury in the corpus callosum in patients with moderate traumatic brain injury (TBI) through quantitative diffusion tensor imaging and to correlate these changes with neuropsychometric tests (NPT) at 6 and 24 months after injury. DESIGN: Prospective longitudinal study. PARTICIPANTS: Sixteen patients with TBI and 17 age/sex-matched healthy controls. METHODS: Patients underwent magnetic resonance imaging at 3 time points: within 2 weeks (range = 5-14 days), 6 months, and 24 months after injury. NPT could be performed only at 6 and 24 months. RESULTS: In patients with TBI, a significant increase in fractional anisotropy (FA) values in genu as well as an insignificant decrease in radial diffusivity (RD) and mean diffusivity values in genu and splenium were observed over time, respectively. FA, RD, and mean diffusivity values continued to be abnormal in patients compared with controls at the end of 2 years. Although some NPT scores improved over time in these patients, these were still significantly impaired compared with controls. CONCLUSIONS: FA and RD indices appear to be surrogate markers of microstructural alterations in patients over time and correlate significantly with some of the NPT scores. The recovery in these indices associated with recovery in neurocognitive deficits suggests that these indices may be used as an objective marker for residual injury in these patients.

Effect of bone marrow-derived mononuclear cells on nerve regeneration in the transection model of the rat sciatic nerve.

Bone marrow-derived stem cells enhance the rate of regeneration and clinical improvement in nerve injury, spinal cord injury and brain infarction. Recent experiments in rat spinal cord demyelination showed that remyelination was specific to intravenous delivery of the bone marrow-derived mononuclear cell (BM-MNC) fraction, although the specific role of this fraction in peripheral nerve regeneration has not been examined. Therefore we evaluated the role of BM-MNCs in peripheral nerve regeneration in the rat sciatic nerve transection model. After anesthesia, the right sciatic nerve of 20 adult-male Wistar rats was transected under an operating microscope. In the test group, the cut ends of the nerve were approximated with two epineural microsutures, the gap was filled with rat BM-MNCs and the approximated nerve ends were covered with fibrin glue. In the control group, the transected nerve ends were repaired with two epineural microsutures and fibrin sealant only. Histological assessment of the nerve was performed 30 days and 60 days after the operation and regenerative changes were compared between the two groups. The recovery after nerve anastamosis was far better in the test group at both 30 days and 60 days. There was a statistically significant difference in axonal regeneration, remyelination and myelin thickness at sites 5mm and 10mm from the site of repair of the nerve. Schwann cell proliferation and degenerative changes were more prevalent in the controls. This study demonstrates that local delivery of BM-MNCs (which can be isolated easily from bone marrow aspirates) into injured peripheral nerve increases the rate and degree of nerve regeneration. The present study highlights the role of BM-MNCs in peripheral nerve regeneration.

Temporal alterations in brain water diffusivity in neonatal meningitis.

AIM: To compare changes in apparent diffusion coefficient (ADC) in neonatal meningitis using serial diffusion-weighted imaging (DWI). METHOD: Thirty neonates with meningitis and 12 age/sex-matched controls were studied using DWI. ADC was quantified by placing region of interest(s) on periventricular white matter during acute illness and again at 21 days. Three groups of patients were studied: those with normal findings on both conventional MRI and DWI, those with abnormal DWI only and those with abnormal conventional MRI as well as DWI. Neurodevelopment assessment was performed in controls and patients at 3 months using Indian adaptation of Bayley scales of infant development (BSID) kit. RESULTS: Patients with neonatal meningitis with normal imaging (n = 8) showed no significant difference in ADC compared to controls. Patients showing abnormality only on DWI (n = 10) and on both conventional magnetic resonance imaging (MRI) as well as DWI (n = 12) had significantly reduced ADC (p = 0.001) than controls at baseline study. Follow-up study showed no significant differences in ADC in controls compared to any patient group. Significantly reduced neurodevelopmental scores were observed in patient groups compared to controls. CONCLUSION: We conclude that quantitative ADC may detect meningitis-induced hypoxia early in brain parenchyma, which may be associated with abnormal motor and mental development.

Comparative evaluation of corpus callosum DTI metrics in acute mild and moderate traumatic brain injury: its correlation with neuropsychometric tests.

PRIMARY OBJECTIVE: To look for differences in vulnerability of corpus callosum (CC) in patients of mild and moderate traumatic brain injury (TBI) in the acute stage using quantitative diffusion tensor imaging (DTI) and to correlate these with neuropsychometric tests (NPT) done at 6 months post-injury. RESEARCH DESIGN, METHODS AND PROCEDURES: Conventional MRI, DTI and NPT were performed on 83 patients (moderate TBI, n = 57; mild TBI, n = 26) within 5-14 days after TBI. Thirty-three age- and sex-matched healthy controls were also included for comparison. RESULTS: Significantly decreased fractional anisotropy (FA) in genu and splenium; significantly increased radial diffusivity (RD) values in genu, midbody and splenium with significant increase in mean diffusivity (MD) and a decrease in axial diffusivity (AD) only in genu, respectively, in patients with moderate TBI compared to healthy controls were observed. However, in moderate TBI, significantly decreased FA was found only in genu compared to mild TBI. Moderate TBI showed poor NPT scores compared to mild TBI, but this did not reach statistical significance. CONCLUSIONS: It is concluded that DTI abnormalities in the regions of CC were more in patients with moderate TBI compared to mild TBI and this was associated with relatively poor neuropsychological outcome 6 months post-injury.