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Background and Objectives: Cancer is one of the leading causes of death in the world affecting millions of people. The commercially available anticancer drugs lack the selectivity and show several undue side effects during the biologically targeted therapy, thus calling for the exploration of wider chemical space to furnish new structural leads with promising anticancer potential. In this endeavor, we synthesized a series of coumarinyl thiazolotriazoles with diverse functional group tolerance and will be tested for their anticancer properties against cancer cell lines (HeLa and MCF-7) and a normal cell line (BHK-21). Materials and Methods: To overcome such complications, in the current study, we evaluated the cytotoxic effects of coumarinyl thiazolotriazole hybrids on human breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) cells and normal cells i.e., Baby Hamster Kidney cells (BHK-21) using MTT (dimethyl-2-thiazolyl- 2,5-diphenyl-2H-tetrazolium bromide) assay. DNA binding studies of compound 6c was performed on Herring- Sperm DNA (HS-DNA) and docking studies were also carried out. The mechanistic studies were performed on potent compounds by fluorescent microscopic studies, release of Lactate Dehydrogenase (LDH) and mitochondrial membrane potential, activation of caspase-9 and -3 and flow cytometric analysis. Results: As revealed by MTT assay, compounds 6m and 6c were identified as the most potent derivatives among the tested series with IC50 values of 5.64 and 29.1 μM against HeLa and MCF cells, respectively as compared to cisplatin which gave IC50 values of 11.3 and 6.20 μM, respectively. DNA binding studies of compound 6c showed the binding of compound in DNA with Gibbs free energy of ‒17 KJ/mol and docking studies validated the DNA binding studies. Fluorescent microscopic studies using 4′,6-diamidino-2-phenylindole (DAPI) and Propidium Iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active compound 6m. Moreover, compounds 6m and 6c also triggered the release of Lactate Dehydrogenase (LDH) in treated HeLa and MCF-7 cells while a luminescence assay displayed a remarkable increase in the activity of caspase-9 and -3. Moreover, flow cytometric results revealed that compound 6m caused G0 /G1 arrest in the treated HeLa cells. Conclusion: Our results suggested that the compound possesses chemotherapeutic properties against breast cancer and cervical adenocarcinoma cells, thus warranting further research to test the anticancer efficacy of this compound at clinical level.

Background and Objectives: Despite various technological advances for the treatment of cancer, the identification of new chemical entities with potent anticancer effects remain an indispensable requirement of the time due to multi-drug resistance exhibited by previously developed anticancer drugs. Particularly, the hybrid drugs incorporating two individual bioactive pharmacophores present medicinally important structural leads, thus improving the pharmacodynamic profile of the drug molecules. The antiproliferative and pro-apoptotic activity of the carbazole-chalcone hybrids on human breast and cervical cancer cells will be examined. Materials and Methods: To overcome such complications, in the current study, we evaluated the cytotoxic effects of carbazole-chalcone hybrids on human breast adenocarcinoma (MCF-7), cervical adenocarcinoma (HeLa) cells and normal cells i.e., baby hamster kidney cells (BHK-21) using MTT (dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) assay. The mechanistic studies were performed on potent compound 4g by fluorescent microscopic studies, release of lactate dehydrogenase (LDH) and mitochondrial membrane potential, activation of caspase-9 and -3 and flow cytometric analysis. Results: As revealed by MTT assay, compound 4g was identified as the most potent derivative among the tested series with IC50 values of 5.64 and 29.15μM against HeLa and MCF-7 cells, respectively. The results were compared with cisplatin. Fluorescent microscopic studies using 4′,6-diamidino-2-phenylindole (DAPI) and Propidium Iodide (PI) staining confirmed the occurrence of apoptosis in HeLa cells treated with the most active compound 4g. Moreover, compound 4g also triggered the release of Lactate Dehydrogenase (LDH) in treated HeLa and MCF-7 cells while a fluorescence assay displayed a remarkable increase in the activity of caspase-9 and -3. Moreover, flow cytometric results revealed that compound 4g caused G0/G1 arrest in the treated HeLa cells. Conclusion: Our results demonstrated that the compound 4g possesses chemotherapeutic properties against breast cancer and cervical adenocarcinoma cells, thus warranting further research to test the anticancer potential of this compound at preclinical and clinical level.

Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = −0.111 to −0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.

To assess the reliability and validity of gray level co-occurrence matrices (GLCM) in the quantification of choriocapillaris and describe GLCM features in normal and eyes with resolved acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and serpiginous choroiditis (SC).In this, multicenter, reliability, validity and comparative study; OCTA was performed on eyes with resolved APMPPE and SC and normal individuals. CC texture classification, low flow area measurements and GLCM feature extraction were performed.A total of 13 normal, 8 APMPPE and 15 SC eyes were analyzed. All GLCM parameters demonstrated an excellent reliability. GLCM parameters were differently distributed across the three groups. Decision-tree based on the random forest predictive model provided an overall accuracy of 86% in classifying the three groups using GLCM features.These data demonstrated an excellent reliability and validity of GLCM features in quantifying the choriocapillaris in healthy and diseased eyes.

Background Involuntary admission or treatment for the management of mental illness is a relatively common practice worldwide. Enabling legislation exists in most developed and high-income countries. A few of these countries have attempted to align their legislation with the United Nations Convention on the Rights of Persons with Disabilities. This review examined legislation and associated issues from four diverse South Asian countries (Bangladesh, India, Pakistan and Sri Lanka) that all have a British colonial past and initially adopted the Lunacy Act of 1845. Method A questionnaire based on two previous studies and the World Health Organization checklist for mental health legislation was developed requesting information on the criteria and process for involuntary detention of patients with mental illness for assessment and treatment. The questionnaire was completed by psychiatrists (key informants) from each of the four countries. The questionnaire also sought participants’ comments or concerns regarding the legislation or related issues. Results The results showed that relevant legislation has evolved differently in each of the four countries. Each country has faced challenges when reforming or implementing their mental health laws. Barriers included legal safeguards, human rights protections, funding, resources, absence of a robust wider health system, political support and sub-optimal mental health literacy. Conclusion Clinicians in these countries face dilemmas that are less frequently encountered by their counterparts in relatively more advantaged countries. These dilemmas require attention when implementing and reforming mental health legislation in South Asia.

Eco-friendly green synthesis of nanoparticles using medicinal plants gained immense importance due to its potential therapeutic uses. In the current study, silver nanoparticles (AgNPs) were synthesized using water extract of Jurinea dolomiaea leaf and root at room temperature. MTT assay was used to study anticancer potential of AgNPs against cervical cancer cell line (HeLa), breast cancer cell lines (MCF-7), and mouse embryonic fibroblast (NIH-3 T3) cell line for toxicity evaluation. The antioxidant potential was evaluated using stable DPPH radicals. In addition, the apoptotic nuclear changes prompted by AgNPs in more susceptible HeLa cells were observed using fluorescence microscope through DAPI and PI staining. Physiochemical properties of biosynthesized AgNPs were characterized using various techniques. AgNPs were formed in very short time and UV-vis spectra showed characteristic absorption peak of AgNPs. SEM and TEM showed spherical shape of AgNPs and XRD revealed their crystalline nature. EDX analysis revealed high percentage of silver in green synthesized AgNPs. FTIR analysis indicated involvement of secondary metabolites in fabrication of AgNPs. In vitro cytotoxic and antioxidant study revealed that herb and biosynthesized AgNPs exhibited significant dose-dependent and time-dependent anticancer and antioxidant potential. Furthermore, study on normal cell line and microscopic analysis of apoptosis revealed that AgNPs exhibited good safety profile as compared to cisplatin and induces significant apoptosis effect. Based on the current findings, it is strongly believe that use of J. dolomiaea offers large scale production of biocompatible AgNPs that can be used as alternative anticancer agents against cancer cell lines tested.

BACKGROUND AND OBJECTIVE: To evaluate the flow characteristics and textural properties of choriocapillaris (CC) on optical coherence tomography angiography in eyes with resolved inflammatory choriocapillaropathies and Vogt-Koyanagi-Harada (VKH) disease. PATIENTS AND METHODS: A cohort of eyes with healed acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and VKH disease were included. A 3 mm × 3 mm OCT angiogram of CC was acquired and graded for flow characteristics and textural properties. RESULTS: This study included 16 patients. Texture was heterogeneous in all eyes in the SC and VKH groups, and in four eyes (40%) in the APMPPE group. Most of the eyes with VKH disease had severe low flow, whereas most of the SC and APMPPE eyes demonstrated mild low flow. Heal duration had a strong negative correlation with severity of CC low flow and a weak, statistically nonsignificant correlation with texture heterogeneity. CONCLUSION: Despite the resolution of active inflammation, partial CC hypoperfusion and texture disruptions persist for longer durations and may resolve in a time dependent manner. [ Ophthalmic Surg Lasers Imaging Retina . 2019;50:566–572.]

IntroductionCortical thickness (CT) and surface area (SA) are established biomarkers of brain pathology in posttraumatic stress disorder (PTSD). Structural covariance networks (SCN) constructed from CT and SA may represent developmental associations, or unique interactions between brain regions, possibly influenced by a common causal antecedent. The ENIGMA-PGC PTSD Working Group aggregated PTSD and control subjects’ data from 29 cohorts in five countries (n=3439).MethodsUsing Destrieux Atlas, we built SCNs and compared centrality measures between PTSD subjects and controls. Centrality is a graph theory measure derived using SCN.ResultsNotable nodes with higher CT-based centrality in PTSD compared to controls were left fusiform gyrus, left superior temporal gyrus, and right inferior temporal gyrus. We found sex-based centrality differences in bilateral frontal lobe regions, left anterior cingulate, left superior occipital cortex and right ventromedial prefrontal cortex (vmPFC). Comorbid PTSD and MDD showed higher CT-based centrality in the right anterior cingulate gyrus, right parahippocampal gyrus and lower SA-based centrality in left insular gyrus.ConclusionUnlike previous studies with smaller sample sizes (≤318), our study found differences in centrality measures using a sample size of 3439 subjects. This is the first cross-sectional study to examine SCN interactions with age, sex, and comorbid MDD. Although limited to group level inferences, centrality measures offer insights into a node’s relationship to the entire functional connectome unlike approaches like seed-based connectivity or independent component analysis. Nodes having higher centrality have greater structural or functional connections, lending them invaluable for translational treatments like neuromodulation.

Three new organotin(IV) carboxylate compounds were synthesized and structurally characterized by elemental analysis and FT-IR and multinuclear NMR (1H, 13C, 119Sn) spectroscopy. Single X-ray crystallography reveals that compound C2 has a monoclinic crystal system with space group P21/c having distorted bipyramidal geometry defined by C3SnO2. The synthesized compounds were screened for drug-DNA interactions via UV-Vis spectroscopy and cyclic voltammetry showing good activity with high binding constants. Theoretical investigations also support the reactivity of the compounds as depicted from natural bond orbital (NBO) analysis using Gaussian 09. Synthesized compounds were initially evaluated on two cancer (HeLa and MCF-7) cell lines and cytotoxicity to normal cells was evaluated using a non-cancerous (BHK-21) cell line. All the compounds were found to be active, with IC50 values less than that of the standard drug i.e. cisplatin. The cytotoxic effect of the most potent compound C2 was confirmed by LDH cytotoxicity assay and fluorescence imaging after PI staining. Apoptotic features in compound C2 treated cancer cells were visualized after DAPI staining while regulation of apoptosis was observed by reactive oxygen species generation, binding of C2 with DNA, a change in mitochondrial membrane potential and expression of activated caspase-9 and caspase-3 in cancer cells. Results are indicative of activation of the intrinsic pathway of apoptosis in C2 treated cancer cells.

Traumatic brain injury can cause extensive damage to the white matter (WM) of the brain. These disruptions can be especially damaging in children, whose brains are still maturing. Diffusion magnetic resonance imaging (dMRI) is the most commonly used method to assess WM organization, but it has limited resolution to differentiate causes of WM disruption. Magnetic resonance spectroscopy (MRS) yields spectra showing the levels of neurometabolites that can indicate neuronal/axonal health, inflammation, membrane proliferation/turnover, and other cellular processes that are on-going post-injury. Previous analyses on this dataset revealed a significant division within the msTBI patient group, based on interhemispheric transfer time (IHTT); one subgroup of patients (TBI-normal) showed evidence of recovery over time, while the other showed continuing degeneration (TBI-slow). We combined dMRI with MRS to better understand WM disruptions in children with moderate-severe traumatic brain injury (msTBI). Tracts with poorer WM organization, as shown by lower FA and higher MD and RD, also showed lower N-acetylaspartate (NAA), a marker of neuronal and axonal health and myelination. We did not find lower NAA in tracts with normal WM organization. Choline, a marker of inflammation, membrane turnover, or gliosis, did not show such associations. We further show that multi-modal imaging can improve outcome prediction over a single modality, as well as over earlier cognitive function measures. Our results suggest that demyelination plays an important role in WM disruption post-injury in a subgroup of msTBI children and indicate the utility of multi-modal imaging.

Objective:To examine longitudinal trajectories of white matter organization in pediatric moderate/severe traumatic brain injury (msTBI) over a 12-month period.Methods:We studied 21 children (16 M/5 F) with msTBI, assessed 2–5 months postinjury and again 13–19 months postinjury, as well as 20 well-matched healthy control children. We assessed corpus callosum function through interhemispheric transfer time (IHTT), measured using event-related potentials, and related this to diffusion-weighted MRI measures of white matter (WM) microstructure. At the first time point, half of the patients with TBI had significantly slower IHTT (TBI-slow-IHTT, n = 11) and half were in the normal range (TBI-normal-IHTT, n = 10).Results:The TBI-normal-IHTT group did not differ significantly from healthy controls, either in WM organization in the chronic phase or in the longitudinal trajectory of WM organization between the 2 evaluations. In contrast, the WM organization of the TBI-slow-IHTT group was significantly lower than in healthy controls across a large portion of the WM. Longitudinal analyses showed that the TBI-slow-IHTT group experienced a progressive decline between the 2 evaluations in WM organization throughout the brain.Conclusions:We present preliminary evidence suggesting a potential biomarker that identifies a subset of patients with impaired callosal organization in the first months postinjury who subsequently experience widespread continuing and progressive degeneration in the first year postinjury.

Traumatic brain injury (TBI) is a significant public health concern, and can be especially disruptive in children, derailing on-going neuronal maturation in periods critical for cognitive development. There is considerable heterogeneity in post-injury outcomes, only partially explained by injury severity. Understanding the time course of recovery, and what factors may delay or promote recovery, will aid clinicians in decision-making and provide avenues for future mechanism-based therapeutics. We examined regional changes in brain volume in a pediatric/adolescent moderate-severe TBI (msTBI) cohort, assessed at two time points. Children were first assessed 2–5 months post-injury, and again 12 months later. We used tensor-based morphometry (TBM) to localize longitudinal volume expansion and reduction. We studied 21 msTBI patients (5 F, 8–18 years old) and 26 well-matched healthy control children, also assessed twice over the same interval. In a prior paper, we identified a subgroup of msTBI patients, based on interhemispheric transfer time (IHTT), with significant structural disruption of the white matter (WM) at 2–5 months post injury. We investigated how this subgroup (TBI-slow, N = 11) differed in longitudinal regional volume changes from msTBI patients (TBI-normal, N = 10) with normal WM structure and function. The TBI-slow group had longitudinal decreases in brain volume in several WM clusters, including the corpus callosum and hypothalamus, while the TBI-normal group showed increased volume in WM areas. Our results show prolonged atrophy of the WM over the first 18 months post-injury in the TBI-slow group. The TBI-normal group shows a different pattern that could indicate a return to a healthy trajectory., Highlights • Studied differences in regional volume change longitudinally between TBI and control. • Found decreases in TBI group in white matter, gray matter and subcortical regions • Changes in regional volume were associated with changes in cognitive performance. • Compared subgroups within TBI group based on interhemispheric transfer time (IHTT) • TBI-slow group seems to drive TBI vs. control results, show prolonged degeneration.

BackgroundPTSD and depression commonly co-occur and have been associated with smaller hippocampal volumes compared to healthy and trauma-exposed controls. However, the hippocampus is heterogeneous, with subregions that may be uniquely affected in individuals with PTSD and depression.MethodsWe used random effects regressions and a harmonized neuroimaging protocol based on FreeSurfer (v6.0) to identify sub-structural hippocampal markers of current PTSD (C-PTSD), depression, and the interaction of these conditions across 31 cohorts worldwide (N=3,115;Mage=38.9±13.9 years). Secondary analyses tested these associations by sex and after modeling the simultaneous effects of remitted PTSD, childhood trauma, mild traumatic brain injury, and alcohol use disorder.ResultsA significant negative main effect of depression (n=800, vs. no depression, n=1456) was observed in the hippocampal tail (ß=−0.13) and CA1 (ß=−0.09) after adjusting for covariates and multiple testing (adjusted p’s (q)=0.028). A main effect of C-PTSD (n=1042 vs. control, n=1359) was not significant, but an interaction between C-PTSD and depression was significant in the CA1 (ß=−0.24, q=0.044). Pairwise comparisons revealed significantly smaller CA1 volumes in individuals with C-PTSD+Depression than controls (ß=−0.12, q=0.012), C-PTSD-only (ß=−0.17, q=0.001), and Depression-only (ß=−0.18, q=0.023). Follow-up analyses revealed sex effects in the hippocampal tail of depressed females, and an interaction effect of C-PTSD and depression in the fimbria of males.ConclusionsCollectively our results suggest that depression is a stronger predictor of hippocampal volumetry than PTSD, particularly in the CA1, and provide compelling evidence of more pronounced hippocampal phenotypes in comorbid PTSD and depression compared to either condition alone.

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc.

Following armed conflict in the North Waziristan Agency, a mental health and psychosocial support initiative was launched for internally displaced persons in Bannu, Pakistan. This was convened by volunteer mental health professionals, in collaboration with a variety of agencies (provincial government, military, humanitarian agencies) in a security compromised region. As part of the initiative, monthly camps were held for a period of six months. Mental health needs were assessed. A multidisciplinary team (psychiatrists, psychologists, psychiatric nurses and psychosocial workers) offered mental health care to 680 people who attended the camps, of which 28% were under the age of 18 years old. Twenty-one percent returned for follow-up, while others were followed-up in the community by psychosocial teams. Estimates of common mental disorders were found. Both pharmacological and psychological treatments were offered, according to existing guidelines. Active efforts were made to conduct holistic assessments and avoid a pure biomedical approach. This also provided an opportunity for training non specialist staff and led to formal (World Health Organization) mental health gap action plan training for primary care staff. © 2016 War Trauma Foundation, Diemen, The Netherlands Language: en

Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44-80) who were exposed (n=2,510) or unexposed (n=6,079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volume. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE-) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n=109, unexposed, n=315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

Secondhand smoke exposure is a major public health risk that is especially harmful to the developing brain, but it is unclear if early exposure affects brain structure during middle age and older adulthood. Here we analyzed brain MRI data from the UK Biobank in a population-based sample of individuals (ages 44–80) who were exposed (n = 2510) or unexposed (n = 6079) to smoking around birth. We used robust statistical models, including quantile regressions, to test the effect of perinatal smoke exposure (PSE) on cortical surface area (SA), thickness, and subcortical volumes. We hypothesized that PSE would be associated with cortical disruption in primary sensory areas compared to unexposed (PSE−) adults. After adjusting for multiple comparisons, SA was significantly lower in the pericalcarine (PCAL), inferior parietal (IPL), and regions of the temporal and frontal cortex of PSE+ adults; these abnormalities were associated with increased risk for several diseases, including circulatory and endocrine conditions. Sensitivity analyses conducted in a hold-out group of healthy participants (exposed, n = 109, unexposed, n = 315) replicated the effect of PSE on SA in the PCAL and IPL. Collectively our results show a negative, long term effect of PSE on sensory cortices that may increase risk for disease later in life.

Background: Cancer is a far-reaching and lethal but curable disease. Researchers have investigated numerous anticancer agents with only a few commercially available effective drugs which are very costly. Objective: Herein, we report the synthesis , characterization and anti cancer assays of a series of novel dithiocarbamates derivatives. Methods: All compounds were synthesized from different secondary amines and substituted benzyl chlorides in a single step. The structures of newly synthesized dithiocarbamate derivatives were confirmed by spectroscopic techniques (IR, NMR and HR-MS). Results: The synthesized compounds showed a significant anti-proliferative effect in cancer cells (HeLa) with the maximum inhibitory activity of compound SHD-2 with an IC50 = 0.31 ± 0.09 μM. However, the same compound exhibited 19.2% inhibition towards Baby Hamster Kidney fibroblasts (BHK-21), normal cell lines. Moreover, quantification of cellular DNA by flow cytometry for the evaluation of pro-apoptotic activity in HeLa cells demonstrates that arrest in cell cycle along with apoptosis advance towards drug cytotoxicity. However, molecular docking studies of the potent compound suggested that it binds to the major groove of the DNA. Conclusion: The cytotoxic and pro-apoptotic potential of the potent inhibitor may be further investigated in the animal models to advance their anti-cancer prospective.

Antioxidant properties of grape (GSE) and papaya seed extracts (PSE) were tested in vitro at varied concentrations and growth inhibition were seen against gram positive and gram negative bacteria by disc diffusion method. The results revealed that GSE contain four times higher phenolic and six folds higher flavonoid content than PSE. The antioxidant properties of GSE and PSE showed dose dependent activities and were comparatively much higher in GSE. Linoleic acid model of GSE and PSE displayed 67.67 and 46.43 % of inhibition respectively at 500 mg/L. The effect of dip treatment by GSE and PSE at a concentration of 500 and 1000 mg/L respectively on the quality changes of Indian mackerel (Rastrelliger kanagurta) in iced condition were assessed using chemical, microbiological and sensory parameters along with chilled whole control (CWC). The inhibition of primary and secondary lipid oxidation products by GSE at 500 mg/L was comparable to BHT at 200 mg/L. GSE exhibited higher antimicrobial activity on gram-positive strains compared to PSE and reduced the formation of volatile bases significantly. On the day of sensory rejection for CWC, the formation of trimethylamine and total volatile base nitrogen were reduced by 32.27 and 31.85 % in GSE samples and 19.01 and 24.70 % in PSE samples respectively. The dip treatment of GSE increased the shelflife of mackerel up to 15 days, PSE by 12 and 9 days for CWC during ice storage. Therefore, it can be concluded that, GSE can be used as a promising natural preservative and a substitute to the synthetic counterparts.

Objectives: We sought to determine the role of obesity and insulin resistance (IR) in the pathogenesis of inflammation in metabolic syndrome (MetS). Methods: Our study included 100 patients with MetS and 100 age and gender matched control patients who attended a tertiary care laboratory in Rawalpindi, Pakistan. Anthropometric data was obtained including height and weight to calculate body mass index. A record of patient’s blood pressure (BP), waist circumference (WC) and hip circumference (HC) was made. Biochemical analysis included measurements of fasting glucose, triglycerides (TG), high-density lipoprotein cholesterol (HDL-c), insulin, and high-sensitivity C reactive protein (hsCRP). IR was determined by the homeostasis mode assessment insulin resistance (HOMA-IR) method. Results: The levels of hs-CRP were found to be elevated in all patients with MetS where it correlated significantly with all its components including measures of obesity, fasting insulin and glucose levels, IR, TG and HDL-c. However, on linear regression analysis only WC, fasting insulin, and HOMA-IR remained significantly correlated with hs-CRP. Conclusion: MetS is a condition characterized by chronic low-grade inflammation, which arises because of increased abdominal adiposity and IR. Large multicenter studies are needed to gain insight into its pathogenesis and derive treatment strategies.

Outcome after a traumatic brain injury (TBI) is quite variable, and this variability is not solely accounted for by severity or demographics. Identifying sub-groups of patients who recover faster or more fully will help researchers and clinicians understand sources of this variability, and hopefully lead to new therapies for patients with a more prolonged recovery profile. We have previously identified two subgroups within the pediatric TBI patient population with different recovery profiles based on an ERP-derived (event-related potential) measure of interhemispheric transfer time (IHTT). Here we examine structural network topology across both patient groups and healthy controls, focusing on the ‘rich-club’ - the core of the network, marked by high degree nodes. These analyses were done at two points post-injury - 2-5 months (post-acute), and 13-19 months (chronic). In the post-acute time-point, we found that the TBI-slow group, those showing longitudinal degeneration, showed hyperconnectivity within the rich-club nodes relative to the healthy controls, at the expense of local connectivity. There were minimal differences between the healthy controls and the TBI-normal group (those patients who show signs of recovery). At the chronic phase, these disruptions were no longer significant, but closer analysis showed that this was likely due to the loss of power from a smaller sample size at the chronic time-point, rather than a sign of recovery. We have previously shown disruptions to white matter (WM) integrity that persist and progress over time in the TBI-slow group, and here we again find differences in the TBI-slow group that fail to resolve over the first year post-injury.

Mild traumatic brain injury (mTBI) is characterized clinically by a closed head injury involving differential or rotational movement of the brain inside the skull. Over 3 million mTBIs occur annually in the United States alone. Many of the individuals who sustain an mTBI go on to recover fully, but around 20% experience persistent symptoms. These symptoms often last for many weeks to several months. The thalamus, a structure known to serve as a global networking or relay system for the rest of the brain, may play a critical role in neurorehabiliation and its integrity and connectivity after injury may also affect cognitive outcomes. To examine the thalamus, conventional tractography methods to map corticothalamic pathways with diffusion-weighted MRI (DWI) lead to sparse reconstructions that may contain false positive fibers that are anatomically inaccurate. Using a specialized method to zero in on corticothalamic pathways with greater robustness, we noninvasively examined corticothalamic fiber projections using DWI, in 68 service members. We found significantly lower fractional anisotropy (FA), a measure of white matter microstructural integrity, in pathways projecting to the left pre- and postcentral gyri – consistent with sensorimotor deficits often found post-mTBI. Mapping of neural circuitry in mTBI may help to further our understanding of mechanisms underlying recovery post-TBI.

Neurodegenerative disorders are characterized by a progressive loss of brain function. Improved precision in mapping the altered brain pathways can provide a deep understanding of the trajectory of decline. We propose a tractometry workflow for conducting group statistical analyses of point-wise microstructural measures along white matter fasciculi to identify patterns of abnormalities associated with disease. We combined state-of-the-art tools including fiber registration, tract simplification and fiber matching for accurate point-wise statistical analyses across populations. We test the utility of this method by identifying group differences between Parkinson’s disease (PD) patients and healthy controls. We find statistically significant group differences in diffusion MRI derived measures along the anterior thalamic radiations (ATR), corticospinal tract (CST) and regions of the corpus callosum (CC). These pathways are essential for motor control systems within cortico-cortical and cortico-subcortical brain networks. Moreover, the reported pathological changes were not widespread but rather localized along several tracts. Point-wise tract analyses may therefore offer an advantage in anatomical specificity over traditional methods that assess mean microstructural measures across large regions of interest.

The brain’s white matter fiber tracts are impaired in a range of common and devastating conditions, from Alzheimer’s disease to brain trauma, and in developmental disorders such as autism and neurogenetic syndromes. Many studies now examine the connectivity and microstructure of the brain’s neural pathways, spurring the development of algorithms to extract and measure tracts and fiber bundles. Clustering white matter (WM) fibers, from whole-brain tractography, into anatomically meaningful bundles is still a challenging problem. Existing tract segmentation methods use atlases or regions of interest (ROI) or unsupervised spectral clustering. Even so, atlas-based segmentation does not always partition the brain into a set of recognizable fiber bundles. Deep learning techniques can be applied to automatically segment and cluster white matter fibers. Here we propose a robust approach using convolutional neural networks (CNNs) to learn shape features of the fiber bundles, which we then exploit to cluster WM fibers into bundles. In a range of tests across diverse fiber bundles, we illustrate the accuracy of our method, and its ability to suppress false positive fibers.

Background Cognitive deficit associated with cancer and its treatment is called cancer-related cognitive impairment (CRCI). Increases in cancer survival have made understanding the basis of CRCI more important. CRCI neuroimaging studies have traditionally used dedicated research brain MRIs in breast cancer survivors after chemotherapy with small sample sizes; little is known about other non-central nervous system (CNS) cancers after chemotherapy as well as those not exposed to chemotherapy. However, there may be a wealth of unused data from clinically-indicated MRIs that could be used to study CRCI. Objective Evaluate brain cortical structural differences in those with various non-CNS cancers using clinically-indicated MRIs. Design Cross-sectional. Patients Adult non-CNS cancer and non-cancer control (C) patients who underwent clinically-indicated MRIs. Methods Brain cortical surface area and thickness were measured using 3D T1-weighted images. An age-adjusted linear regression model was used and the Benjamini and Hochberg false discovery rate (FDR) corrected for multiple comparisons. Group comparisons were: cancer cases with chemotherapy (Ch+), cancer cases without chemotherapy (Ch-) and subgroup of lung cancer cases with and without chemotherapy vs C. Results Sixty-four subjects were analyzed: 22 Ch+, 23 Ch- and 19 C patients. Subgroup analysis of 16 lung cancer (LCa) patients was also performed. Statistically significant decreases in either cortical surface area or thickness were found in multiple regions of interest (ROIs) primarily within the frontal and temporal lobes for all comparisons. Effect sizes were variable with the greatest seen in the left middle temporal surface area ROI (Cohen's d -0.690) in the Ch- vs C group comparison. Limitations Several limitations were apparent including a small sample size that precluded adjustment for other covariates. Conclusions Our preliminary results suggest that, in addition to breast cancer, other types of non-CNS cancers treated with chemotherapy may result in brain structural abnormalities. Similar findings also appear to occur in those not exposed to chemotherapy. These results also suggest that there is potentially a wealth of untapped clinical MRIs that could be used for future CRCI studies.

White matter tracts are commonly analyzed in studies of micro-structural integrity and anatomical connectivity in the brain. Over the last decade, it has been an open problem as to how best to cluster white matter fibers, extracted from whole-brain tractography, into anatomically meaningful groups. Some existing techniques use region of interest (ROI) based clustering, atlas-based labeling, or unsupervised spectral clustering. ROI-based clustering is popular for analyzing anatomical connectivity among a set of ROIs, but it does not always partition the brain into recognizable fiber bundles. Here we propose an approach using convolutional neural networks (CNNs) to learn shape features of the fiber bundles, which are then exploited to cluster white matter fibers. To achieve such clustering, we first need to re-parameterize the fibers in an intrinsic space. The clustering is performed in induced parameterized coordinates. To our knowledge, this is one of the first approaches for fiber clustering using deep learning techniques. The results show strong accuracy - on a par with or better than other state-of-the-art methods.

Traumatic brain injury (TBI) is the leading cause of death and disability in children, and can lead to long lasting functional impairment. Many factors influence outcome, but imaging studies examining effects of individual variables are limited by sample size. Roughly 20-40% of hospitalized TBI patients experience seizures, but not all of these patients go on to develop a recurrent seizure disorder. Here we examined differences in structural network connectivity in pediatric patients who had sustained a moderate-severe TBI (msTBI). We compared those who experienced early post-traumatic seizures to those who did not; we found network differences months after seizure activity stopped. We also examined correlations between network measures and a common measure of injury severity, the Glasgow Coma Scale (GCS). The global GCS score did not have a detectable relationship to brain integrity, but sub-scores of the GCS (eyes, motor, verbal) were more closely related to imaging measures.

Brain development is a protracted and dynamic process. Many studies have charted the trajectory of white matter development, but here we sought to map these effects in greater detail, based on a large set of fiber tracts automatically extracted from HARDI (high angular resolution diffusion imaging) at 4 tesla. We used autoMATE (automated multi-atlas tract extraction) to extract diffusivity measures along 18 of the brain’s major fiber bundles in 667 young adults, aged 18–30. We examined linear and non-linear age effects on diffusivity measures, pointwise along tracts. All diffusivity measures showed both linear and non-linear age effects. Tracts with the most pronounced age effects were those that connected the temporal lobe to the rest of the brain. Nonlinear age effects were picked up strongly in the anterior corpus callosum and right temporo-parietal tracts.

The role of the cerebrovascular network and its acute response to TBI is poorly defined and emerging evidence suggests that cerebrovascular reactivity is altered. We explored how cortical vessels are physically altered following TBI using a newly developed technique, vessel painting. We tested our hypothesis that a focal moderate TBI results in global decrements to structural aspects of the vasculature. Rats (naïve, sham-operated, TBI) underwent a moderate controlled cortical impact. Animals underwent vessel painting perfusion to label the entire cortex at 1 day post TBI followed by whole brain axial and coronal images using a wide-field fluorescence microscope. Cortical vessel network characteristics were analyzed for classical angiographic features (junctions, lengths) wherein we observed significant global (both hemispheres) reductions in vessel junctions and vessel lengths of 33% and 22%, respectively. Biological complexity can be quantified using fractal geometric features where we observed that fractal measures were also reduced significantly by 33%, 16% and 13% for kurtosis, peak value frequency and skewness, respectively. Acutely after TBI there is a reduction in vascular network and vascular complexity that are exacerbated at the lesion site and provide structural evidence for the bilateral hemodynamic alterations that have been reported in patients after TBI.

Traumatic brain injury (TBI) causes extensive damage to the white matter (WM) of the brain, which can be evaluated with diffusion-weighted magnetic resonance imaging (dMRI). Diffusion MRI can be used to map the WM tracts and their integrity, but offers limited understanding of the biochemical basis of any differences. Magnetic resonance spectroscopy (MRS) measures neural metabolites that reflect neuronal health, inflammation, demyelination, and other consequences of TBI. We combined whole-brain MRS with dMRI to investigate WM dysfunction following pediatric TBI, using “tract-based spectroscopy”. Deficits in N-acetylaspartate (NAA) correspond to regions of deficits in WM integrity, but choline showed minimal overlap with WM deficits. NAA is a marker of neuronal health, while choline is an inflammatory marker. A partial F-test showed that MRS measures improved our ability to predict long-term cognitive function. This is the first paper to combine MRS with dMRI-derived tracts on a whole-brain scale, offering insights into the biochemical correlates of WM tract dysfunction, following injury and potentially in other WM disorders.

White matter tracts are commonly analyzed in studies of micro-structural integrity and anatomical connectivity in the brain. Over the last decade, it has been an open problem as to how best to cluster white matter fibers, extracted from whole-brain tractography, into anatomically meaningful groups. Some existing techniques use region of interest (ROI) based clustering, atlas-based labeling, or unsupervised spectral clustering. ROI-based clustering is popular for analyzing anatomical connectivity among a set of ROIs, but it does not always partition the brain into recognizable fiber bundles. Here we propose an approach using convolutional neural networks (CNNs) to learn shape features of the fiber bundles, which are then exploited to cluster white matter fibers. To achieve such clustering, we first need to re-parameterize the fibers in an intrinsic space. The clustering is performed in induced parameterized coordinates. To our knowledge, this is one of the first approaches for fiber clustering using deep learning techniques. The results show strong accuracy - on a par with or better than other state-of-the-art methods.

The objective of the study was to evaluate the effect of vacuum packaging in combination with antimelanotic treatment on quality characteristics and melanosis in farmed tiger shrimp (Penaeus monodon) collected from Ratnagiri region of Maharashtra. The processed shrimps were treated with sulfite mixture in water (30 g kg-1) and divided into two lots each with 250 shrimps. One of them was vacuum packed, the other was air packed and stored under ice. The ice stored shrimps were analyzed for quality attributes and melanosis for a period of 27 days. The treated vacuum packed shrimps had a shelf life of 24 days, whereas air packed shrimp had 16 days only. Melanosis was absent in the shrimps from both the lots throughout the storage period. Based on the results, it could be concluded that the combination of antimelanotic treatment (sulphite mixture) and packaging could significantly delay the occurrence of melanosis and increase the storage life of shrimp in ice. DOI: http://dx.doi.org/10.3329/sja.v11i2.18400 SAARC J. Agri., 11(2): 33-47 (2013)

Traumatic brain injury (TBI) can disrupt the white matter (WM) integrity in the brain, leading to functional and cognitive disruptions that may persist for years. There is considerable heterogeneity within the patient group, which complicates group analyses. Here we present improvements to a tract identification workflow, automated multi-atlas tract extraction (autoMATE), evaluating the effects of improved registration. Use of study-specific template improved group classification accuracy over the standard workflow. The addition of a multi-modal registration that includes information from diffusion weighted imaging (DWI), T1-weighted, and Fluid-Attenuated Inversion Recovery (FLAIR) further improved classification accuracy. We also examined whether particular tracts contribute more to group classification than others. Parts of the corpus callosum contributed most, and there were unexpected asymmetries between bilateral tracts.

Purpose To assess the safety and effectiveness of combined radiofrequency (RF) ablation and cementoplasty in the treatment of painful neoplastic lesions of bone. Materials and Methods The authors performed a retrospective analysis of 25 combined treatments comprising RF ablation followed by injection of polymethylmethacrylate cement performed in 19 patients during a 22-month period. Patients ranged in age from 42 to 82 years (mean, 58.9 years) and included five women and 14 men. Eleven vertebrae (eight lumbar and three thoracic), nine acetabulae, three sacra, one pubis, and one humerus were treated with a total of 36 RF ablations (in several instances, overlapping ablations were used). The location of the primary neoplasm, lesion size, pain before and after the procedure (as determined with a 10-point visual analog scale [VAS]), number of RF treatments, type of device used for cementoplasty, RF time, cement volume, and extravasation were documented. Results A total of 25 combined RF ablations and cementoplasties were performed. The technical success rate was 100% (25 of 25 treatments). There were seven minor complications: six limited cement extravasations and a transient thermal nerve injury. The mean RF time was 9.1 minutes (range, 6–12 minutes). The mean cement volume injected was 6.1 mL (range, 0.8–16 mL). The mean preprocedure pain (as measured with a VAS) was 7.9 (range, 7.0–9.0) and the mean posttreatment pain was 4.2 (range, 0–6); the difference was statistically significant (mean score, 4.08; 95% confidence interval: 3.92, 4.87; P t test. Conclusions Combined RF ablation and cementoplasty appears to be safe and effective in the treatment of painful neoplastic lesions of bone.

Percutaneous vertebroplasty is a safe, inexpensive, and effective interventional vertebral augmentation technique that provides pain relief and stabilization in carefully selected patients with severe back pain due to vertebral compression. Complications from percutaneous vertebroplasty can be devastating, but are rare and avoidable with application of a meticulous technique. Percutaneous vertebroplasty has a role in the management pathway of patients presenting with painful vertebral compression fractures. Kyphoplasty uses a balloon tamp with the aim of restoring vertebral body height, improving kyphotic deformity, and creating a cavity into which bone cement is injected. Kyphoplasty is as effective and safe as vertebroplasty in treatment of painful vertebral compression fractures. Skyphoplasty, a modification of kyphoplasty, is a promising new technique.

Objective: The study was carried out to evaluate the frequency and types of gestational. Trophoblastic diseases (GTD) inendometrial curettings received for histopathology examination. Data Source: Pathology Department, Shifa Naval Hospital Karachi. Design ofStudy: It was a Retrospective Descriptive Observational study. Setting: Department of Pathology, Pakistan Naval Ship; Shifa Naval HospitalKarachi. Period: From 2009 till 2010. Material & Methods: A total of 170 cases of endometrial curettage were examined. All specimensreceived with a diagnosis of product of conceptions (POC) or with the clinical suspicion of a gestational trophoblastic disease were included.Results: It was observed that partial mole identified in 57.1 % cases followed by complete mole 21.4%, choriocarcinoma 14.2% and placentalsite Trophoblastic disease 7.1% cases. Nearly half of the cases were diagnosed as having a gestational trophoblastic disease; these were fromthe age groups of 26-30 years followed by 21-25 years. Conclusions: Hydatidiform mole is the commonest gestational trophoblastic disease.Most complete moles are detected clinically but partial moles are misdiagnosed as abortions therefore all cases of abortions should be sent forhistopathological examinations.

Publisher Summary The first section of this chapter focuses on imaging-guided bone biopsy. In many institutions virtually all biopsies are done under imaging guidance—either fluoroscopic, CT (computed tomography) and less frequently MRI (magnetic resonance imaging). The second section focuses on therapeutic embolization. This has become a very important adjunct in facilitating the performance of at times complex and difficult surgery by minimizing the frequently profuse bleeding that would otherwise occur. Embolization is also invaluable in palliating patients with lesions that are unresponsive to other conventional techniques such as chemotherapy, radiation therapy or surgery, either alone or in combination. The last segment is on vertebroplasty and osteoplasty, a very exciting development which particularly in the last 10 years has provided an entirely new avenue for providing high-quality palliation of patients with difficult to treat destructive lesions of the spine and pelvis. Radiofrequency ablation can be used in conjunction with cement injection to provide pain relief as well as structural support of the treated bone.

Radiofrequency Ablation is the use of low-voltage high-frequency electrical energy to heat and destroy abnormal tissues within the human body. It has gained increasing acceptance as both a primary and secondary form of treatment in the musculoskeletal system because of its excellent safety profile, ease of use, and technical success. In the musculoskeletal system, radiofrequency ablation may be used to treat a wide range of lesions that include primary lesions such as osteoid osteomas and a variety of metastases both within the osseous skeleton as well as those lying within the muscles and soft tissues. In this chapter, a background to the principles, physics, and indications of radiofrequency is presented as well as an in-depth description of radiofrequency ablation techniques that may be utilized in the musculoskeletal system.

AJR 2008; 191:W320 0361–803X/08/1916–W320 © American Roentgen Ray Society Radiofrequency Ablation of Solitary Eosinophilic Granuloma of Bone We have read with considerable interest the article by Corby et al. [1], “Radiofrequency Ablation of Solitary Eosinophilic Granuloma of Bone.” The authors correctly point out that radiofrequency ablation potentially may be a useful option in the treatment of this benign but often highly symptomatic disease without entailing the morbidity of more-invasive procedures. This has certainly proven to be the case in the radiofrequency treatment of osteoid osteoma, which as the authors well know is typically an appendicular affliction and has been treated with considerable success over the past 20 years. The two patients reported by Corby et al. [1] had lesions that were considerably larger than the typical osteoid osteoma and would require an umbrella probe of the type Corby et al. used for effective ablation. In the case of their first patient, who had a femoral diaphyseal lesion, virtually the entire crosssectional diameter of the bone was taken up by abnormal tissue. In our experience and that of others, if MRI is performed following radiofrequency ablation, a large area of necrosis is induced. In the case of a long tubular bone with a lesion occupying the entire medullary space, one would expect that the whole of the cross-sectional diameter of the bone would be necrotic. Depending on the amount of heat penetration through the overlying cortex (i.e., the amount of damage), the bone could be appreciably weakened. In this setting, the patient may be prone to a pathologic fracture. In the case of the first patient shown by the authors, considerable buttressing of periosteal new bone was present, which undoubtedly would have been helpful in preventing a pathologic fracture from developing. However, we would caution that it should be borne in mind that this should be carefully considered when offering this therapy, particularly in a long bone that is weight-bearing. Corby et al. [1] correctly point out that in some weight-bearing areas, such as the acetabulum, it may potentially be advantageous to inject methylmethacrolate cement (acetabuloplasty) to provide mechanical support. Certainly, considerable efficacy in the treatment of metastatic disease of the acetabulum has been reported with combined radiofrequency and cement injection therapy by a number of authors as well as by us. Toyota et al. [2] have reported their experience and found it highly effective in palliation. Peter L. Munk David Malfair Faisal Rashid Vancouver General Hospital University of British Columbia Vancouver, BC, Canada William C. Torreggiani Adelaide and Meath Hospitals Tallaght, Dublin, Ireland

A 66-year-old man presented with chronic left knee pain accompanied by instability and locking. A magnetic resonance imaging study was performed, which demonstrated extensive degenerative changes with osteophytosis, cartilage loss, and meniscal damage as well as disruption of the anterior cruciate ligament (Fig. 1). At the posterior aspect of the knee, adjacent to the posterior lateral tibial margin, and medial to the fibular head, a structure was identified surrounded by fibers of the musculotendinous junction of the popliteus muscle. What is your diagnosis? Skeletal Radiol (2009) 38:69 DOI 10.1007/s00256-008-0582-9