Insights into recent aerosol trends over Asia from observations and CMIP6 simulations.

Aerosols continue to contribute the largest uncertainty in climate change. Over Asia, a global aerosol hotspot, spatial patterns of aerosol emissions are changing mainly because of changes in anthropogenic emissions, producing a dipole in atmospheric aerosol loading between East (decrease in emissions) and South Asia (increase in emissions). The resultant aerosol radiative effects are expected to be different as compared to the last decades of the 20th century because of this emerging Asian aerosol dipole. The projection and assessments of radiative and climate impacts of aerosols rely on simulating accurately the aerosol properties, thus, making it imperative that current climate models involved in climate assessments including the Intergovernmental Panel on Climate Change Assessment Reports, simulate well the magnitude and trends in changing aerosol properties. For the first time, in this study we analyze trends in aerosol properties over Asia from satellite and ground-based observations, and simulations from climate models in Coupled Model Intercomparison Project Phase 6 (CMIP6) experiment with state-of-the-art treatment of aerosol chemistry, physics and meteorology. The results reveal large inter-model differences in model estimates, and discrepancies between model simulations and observations as most models are not able to capture the recent observed magnitudes and trends in aerosol optical depth (AOD) and single scattering albedo (SSA) over Asia. The absolute and the relative (percent) trends (positive and/or negative) in AOD are significantly higher than the trends in SSA. The aerosol-induced effective radiative forcing within the atmosphere simulated with three CMIP6 models show a positive (increasing) trend over Asia. A positive trend in atmospheric heating due to aerosols in model simulations is consistent with model simulated trends in AOD (positive) and SSA (negative). These results on model-observations comparison need to be taken into account while examining the projected/expected future climate impacts due to aerosols, and potential value of various mitigation measures, in particular on regional and decadal climate change in Asia which is largely uncertain. MAIN FINDING: Our analysis of satellite and ground-based observations, and simulations from climate models in CMIP6 experiment with state-of-the-art treatment of aerosol chemistry, physics and meteorology reveal large difference in model calculations, and most models are not able to capture the recent observed trends in aerosol optical depth and single scattering albedo over Asia during 2000-2018.

Organ distribution and biological compatibility of surface-functionalized reduced graphene oxide.

Graphene is an sp2 hybridized allotrope of carbon with a honeycomb lattice structure that has many applications in biomedicine owing to its unique physico-chemical properties. Graphene has attracted much interest from scientists for its biomedical potential, including in drug/gene delivery, fluorescent labeling of target analytes, tissue engineering, regenerative medicine and MRI contrast enhancement. However, there are very limited data available concerning the toxicity of graphene, and efforts have been made to study the bio-nano interactions of Pluronic functionalized reduced graphene oxide (rGO-P) in animal models. The present study aimed to evaluate the systemic toxicity of rGO-P and its ability to cross the blood-brain barrier in Swiss Albino mice subject to acute exposure to 10 mg kg-1 body weight of rGO-P. Prolonged exposure was evaluated in female Wistar rats by analyzing feto-placental transmission and any associated developmental neurotoxicity after intravenous administration of 5 mg kg-1 and 10 mg kg-1 body weight of rGO-P. Biodistribution analysis using confocal Raman mapping indicated that tiny amounts of rGO-P accumulated in major organs of both dams and pups, with no evident toxic response. The accumulation of rGO-P in various tissues of rat pups born to treated dams is ample evidence of feto-placental transmission. The present study clearly suggests that rGO-P is not toxic under any of the experimental conditions. These findings can therefore be carried forward for application of rGO-P in drug/gene delivery, early diagnosis and treatment of various diseases in neonates and adults. The results of the study show that rGO-P is an auspicious and promising material for future healthcare applications.

Green synthesis of Pluronic stabilized reduced graphene oxide: Chemical and biological characterization.

The wonder material graphene has numerous potential applications in nanoelectronics, biomedicine, storage devices, etc. Synthesis of graphene is highly challenging due to the toxic chemicals used and its low yield. In the present study, a facile green route for synthesis of reduced graphene oxide (rGO) was carried out using ascorbic acid as reducing agent. rGO was stabilized using Pluronic P123 polymer to give Pluronic stabilized reduced graphene oxide (rGO-P) and gave superior yield (15 mg graphene oxide yielded ˜13 mg rGO-P). Despite the potential neuroscience applications of graphene, the impending toxicological outcome upon interaction with neurons is not well understood. Here, differentiated PC-12 neuron-like cells exposed to rGO-P showed a dose-dependent cytotoxicity. Membrane disruption and cytoskeletal integrity remained uncompromised after 24 h exposure. Oxidative stress in PC-12 was evident due to an increase in ROS generation in dose and time-dependent manner. In vivo acute toxicity was assessed in mice administered with 10 mg/kg body weight of rGO-P. There were no evident changes in behaviour, motor function or other morphological changes. In conclusion, rGO-P was successfully synthesized and provided superior yield. Even though in vitro toxicity testing showed dose-dependent toxicity, in vivo toxic effect was not apparent.

Decreased hippocampal translocator protein (18 kDa) expression in alcohol dependence: a [11C]PBR28 PET study.

Repeated withdrawal from alcohol is clinically associated with progressive cognitive impairment. Microglial activation occurring during pre-clinical models of alcohol withdrawal is associated with learning deficits. We investigated whether there was microglial activation in recently detoxified alcohol-dependent patients (ADP), using [11C]PBR28 positron emission tomography (PET), selective for the 18kDa translocator protein (TSPO) highly expressed in activated microglia and astrocytes. We investigated the relationship between microglial activation and cognitive performance. Twenty healthy control (HC) subjects (45±13; M:F 14:6) and nine ADP (45±6, M:F 9:0) were evaluated. Dynamic PET data were acquired for 90 min following an injection of 331±15 MBq [11C]PBR28. Regional volumes of distribution (VT) for regions of interest (ROIs) identified a priori were estimated using a two-tissue compartmental model with metabolite-corrected arterial plasma input function. ADP had an ~20% lower [11C]PBR28 VT, in the hippocampus (F(1,24) 5.694; P=0.025), but no difference in VT in other ROIs. Hippocampal [11C]PBR28 VT was positively correlated with verbal memory performance in a combined group of HC and ADP (r=0.720, P<0.001), an effect seen in HC alone (r=0.738; P=0.001) but not in ADP. We did not find evidence for increased microglial activation in ADP, as seen pre-clinically. Instead, our findings suggest lower glial density or an altered activation state with lower TSPO expression. The correlation between verbal memory and [11C]PBR28 VT, raises the possibility that abnormalities of glial function may contribute to cognitive impairment in ADP.

Presence or absence of intestinal metaplasia but not its burden is associated with prevalent high-grade dysplasia and cancer in Barrett's esophagus.

Universal agreement on the inclusion of intestinal metaplasia to diagnose Barrett's esophagus (BE) is lacking. Our aim was to determine the association of intestinal metaplasia and its density with the prevalence of dysplasia/cancer in columnar lined esophagus (CLE). Patients with CLE but no intestinal metaplasia (CLE-no IM) were identified by querying the clinical pathology database using SNOMED codes for distal esophageal biopsies. CLE-IM patients were identified from a prospectively maintained database of BE patients. Subsequently, relative risks for prevalent dysplasia and cancer were calculated. Since patients with CLE-no IM are not usually enrolled in surveillance, only prevalent dysplasia/cancer on index endoscopy was analyzed. Goblet cell density and percent intestinal metaplasia were estimated. All biopsy slides were reviewed for dysplasia by two experienced gastrointestinal pathologists. Two hundred sixty-two CLE-IM and 260 CLE-no IM patients were included (age 64±12 vs. 60±11 years, P=0.001; whites 92% vs. 82%, P=0.001; males 99.7% vs. 99.3%, P=NS; CLE length 3.4±3.2 vears 1.4±0.4 cm, P=0.001 and hiatus hernia 64% vs. 56%, P=0.013). The odds of finding low-grade dysplasia and of high-grade dysplasia (HGD)/cancer were 12.5-fold (2.9-53.8, P=0.007) and 4.2-fold (95% CI 1.4-13, P=0.01) higher, respectively, in the CLE-IM group. Reanalysis after controlling for important variables of age, race, and length did not significantly alter the overall results. In CLE-IM group, when patients with high (>50/LPF) versus low goblet cell density (<50/LPF) and <10% versus >10% intestinal metaplasia were compared, the odds of HGD/cancer, OR 1.5 (0.5-4.9, P=0.5) and 1.97 (0.54-7.22), respectively, were not significantly higher. Demonstration of intestinal metaplasia continues to be an essential element in the definition of BE, but its quantification may not be useful for risk stratification of HGD/cancer in BE.

Evaluation of the updated confocal laser endomicroscopy criteria for Barrett's esophagus among gastrointestinal pathologists.

Previously developed novel probe-based confocal laser endomicroscopy (pCLE) criteria have been found to have high accuracy and substantial interobserver agreement (IOA) for diagnosing dysplasia in Barrett's esophagus (BE) when used by endoscopists. These updated criteria are: (i) epithelial surface: saw toothed, (ii) cells: enlarged, (iii) cells: pleomorphic, (iv) glands: not equidistant, (v) glands: unequal in size and shape, and (vi) goblet cells: not easily identified. The accuracy and IOA among pathologists in the diagnosis of dysplasia using the novel pCLE criteria is not known. The primary objective of the study was to evaluate the accuracy, overall IOA and learning curve among three gastrointestinal (GI) pathologists in diagnosing dysplasia in BE using the updated pCLE criteria. The secondary aim was to compare the accuracy and IOA between GI pathologists and gastroenterology endoscopists. Ninety pCLE videos and respective histology were retrieved from a previously conducted multicenter, prospective, randomized, controlled trial evaluating the utility of pCLE in BE patients. Videos were obtained from 101 BE patients previously enrolled for surveillance or endoscopic treatment of high-grade dysplasia or early esophageal adenocarcinoma. Three GI pathologists reviewed 90 pCLE video clips for dysplasia versus no dysplasia, confidence in their diagnosis, and image quality. The overall accuracy for the diagnosis of dysplasia (low-grade dysplasia/high-grade dysplasia/esophageal adenocarcinoma) was 77.8% (95% confidence interval [CI]: 72.4-82.3). The accuracy was higher when pathologists had 'high confidence' in their assessment of the videos (93.8% vs. 69.3%, P < 0.001). There was no significant difference in accuracy between the first set of 30 and second set of 60 videos (84% vs. 74%, P = 0.065). IOA among GI pathologists was substantial, k = 0.65 (95% CI: 0.53-0.73). The sensitivity for detecting dysplasia was 85% (95% CI: 78.1-90.7) and the specificity was 70% (95% CI: 61.91-77.92). These results were comparable with the evaluation of the same set of videos by endoscopists. GI pathologists have high accuracy and substantial IOA for diagnosing BE dysplasia with pCLE. Pathologists appear to have similar accuracy and IOA as endoscopists. These results provide further support of endoscopists accurately interpreting the in vivo optical histology provided by pCLE.

Leukaemic transformation of Philadelphia chromosome-negative myeloproliferative neoplasms: are Asian patients different?

BACKGROUND: Leukaemic transformation (LT) is rare in the natural history of Philadelphia(Ph) chromosome-negative myeloproliferative disorders (MPD), and has a dismal prognosis. Little literature is available on Asian patients. AIMS: The aim of this study is to report a single institution experience of Asian patients who developed acute leukaemia after being diagnosed and treated for Ph chromosome-negative MPDs, and to compare the findings of this series with similar studies from the literature. METHODS: Patients were recruited from the MPD registry of Singapore General Hospital, Department of Hematology. Clinical data including treatment modalities and duration of use in myeloproliferative phase, latency to LT, characteristics of leukaemia, chemotherapy administered and survival after LT were examined. RESULTS: Over a 29-year period from 1980 to 2009, there were 22 Asian patients with LT of Ph chromosome-negative MPD of which four had polycythaemia vera (PV), nine had essential thrombocythaemia (ET), seven had myelofibrosis (MF) and two had unspecified MPD at diagnosis. Primary treatment modality was Hydroxyurea (HU) during MPD phase. Median latency to LT was 14 years for PV, 10 years for ET and 1 year for MF. Median age at LT diagnosis was 67.5 years. Nine patients had complex cytogenetics, with abnormalities of chromosomes 5 and 7 being common. Overall, median survival was 2 months after LT. Eight patients who received induction chemotherapy had a median survival of 2.5 months. Survival was independent of MPD type and treatment administered. None received stem cell transplantation. CONCLUSIONS: LT of Ph chromosome-negative MPD is rare and uniformly fatal. Despite chemotherapy, survival was poor, and patients succumbed to refractory disease and infections. Asian patients did not have a more favourable outcome. It remains to be investigated whether upfront stem cell transplant may be a treatment option.

Imaging cortical lesions in multiple sclerosis with ultra-high-field magnetic resonance imaging.

OBJECTIVE: To determine the sensitivity of T2*-weighted gradient-echo (T2*GRE) and inversion recovery turbo-field-echo (TFE) sequences for cortical multiple sclerosis lesions at 7 T. DESIGN, SETTING, AND PARTICIPANTS: Autopsied brain tissue from individuals with multiple sclerosis was scanned with 3-dimensional T2*GRE and 3-dimensional inversion recovery white matter-attenuated TFE sequences at 7 T. Cortical lesions visible with either sequence were scored for each anatomical lesion type. Imaged brain tissue was then processed for immunohistochemical analysis, and cortical lesions were identified by labeling with antibody against myelin basic protein and CD68 for microglia. Magnetic resonance images were matched with corresponding histological sections and scored retrospectively to determine the sensitivity for each cortical lesion type. Main Outcome Measure Cortical lesion detection by 3-dimensional T2*GRE and white matter-attenuated TFE sequences. RESULTS: The 3-dimensional T2*GRE and white matter-attenuated TFE sequences retrospectively detected 93% and 82% of all cortical lesions, respectively (with varying sensitivities for different lesion types). Lesion visibility was primarily determined by size as all undetected lesions were smaller than 1.1 mm at their smallest diameter. The T2*GRE images showed hypointense rings in some cortical lesions that corresponded with increased density of activated microglia. CONCLUSIONS: Three-dimensional T2*GRE and white matter-attenuated TFE sequences at a 7-T field strength detect most cortical lesions in postmortem multiple sclerosis tissue. This study indicates the potential of T2*GRE and white matter-attenuated TFE sequences in ultra-high-field magnetic resonance imaging for cortical lesion detection in patients with multiple sclerosis.

Dual arterial supply to normal lung: within the sequestration spectrum.

We report a rare case of dual arterial supply to an otherwise normal left lower lobe. In addition to normal pulmonary arterial supply, the lower lobe of the left lung also received systemic arterial supply from the coeliac axis. The relevant anatomy and literature are reviewed. To the best of our knowledge, there are no other reported cases of anomalous systemic arterial supply from the coeliac axis to the basal segments of the left lower lobe with normal bronchial branching and pulmonary arterial supply.

Polymorphism in factor VII gene modifies phenotype of severe haemophilia.

The basis for 10-15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as 'mild' (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n = 14) or 'severe' (all others, n = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores (P < or = 0.001) and life-time clotting factor use (P < or = 0.007) were different. Patients with severe molecular defects had a 4.1-fold increased risk for a severe phenotype (95% CI: 1.18-14.42, P = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04-12.05, P = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.

The "dot-in-circle" sign -- a characteristic MRI finding in mycetoma foot: a report of three cases.

Three patients referred for MRI of the foot were found to have imaging features characteristic of mycetoma. Two patients presented with recurrent soft tissue masses, which were operated on several times and not suspected to be of infective aetiology. The third patient had typical clinical features with a history of blackish granule discharge. In all three patients, MRI showed conglomerate areas of small round discrete T(2) weighted hyperintense lesions, representing granulation tissue surrounded by a low-signal-intensity rim representing intervening fibrous septa. Within many of these hyperintense lesions, there was a central low-signal-intensity dot, which gives rise to the "dot-in-circle" sign that has been very rarely described in the literature. This sign is an easily recognisable and unique appearance that is highly suggestive of mycetoma.

Is pneumorrhachis a poor prognostic sign in acute gangrenous abdominal emergencies?

Pneumorrhachis (air in the spinal canal) is an uncommon radiological finding. Its detection in gangrenous abdominal emergencies is rarer with uncertain prognostic significance. We illustrate the computed tomography features and assess the patient outcomes in two cases of pneumorrhachis identified in gangrenous pathologies of the abdomen (emphysematous pyelonephritis and bowel gangrene). Patient outcome was poor in the current and previously reported cases. Pneumorrhachis could be an additional imaging sign of poor prognosis in acute gangrenous abdominal emergencies.

MRI of brachial plexopathies.

Magnetic resonance imaging (MRI) has become the primary imaging technique in the evaluation of brachial plexus pathology, and plays an important role in the identification, localization, and characterization of the cause. Improvements in MRI technique have helped in detecting changes in the signal intensity of nerves, subtle enhancement, and in detecting perineural pathology, thereby refining the differential diagnosis. The present review of the visualization of brachial plexus abnormalities using MRI is based on a review of 26 cases. The causes include trauma and a spectrum of non-traumatic causes, such as acute idiopathic/viral plexitis, metastases, immune-mediated plexitis, and mass lesions compressing the brachial plexus.

Telangiectatic osteosarcoma of the spine: a case report.

Telangiectatic osteosarcoma (TOS) of the spine is rare accounting for only 0.08% of all primary osteosarcomas. Though a well described radio-pathological entity it is not often thought of as a cause of paraplegia. We describe the clinical, radiological and pathological features and discuss the treatment options of telangiectatic osteosarcoma of the dorsal spine presenting in a young man. The diagnostic pitfalls are discussed emphasising the fact that the diagnosis of TOS of the spine requires not only a multi modal approach of appropriate radiological and pathological tests but also an awareness of this condition.

Psychometric analysis of the Functional Independence Score in Haemophilia (FISH).

Joint morbidity in haemophilia has traditionally been measured using clinical and radiological scores. There have been no reliable, validated tools for the assessment of functional independence in persons with haemophilia till recently. The Functional Independence Score in Haemophilia (FISH) has been developed as a performance based assessment tool to address this need. The FISH is designed to measure the patient's independence in performing activities of daily living (grooming and eating, bathing and dressing), transfers (chair and floor), and mobility (walking, step climbing and running). On assessment of its psychometric properties in 63 patients with haemophilia (mean age 14 years), FISH was found to have good internal consistency (Cronbach's alpha of 0.85). It had moderate correlation with the World Federation of Hemophilia clinical score (r = -0.61), and a correlation with the Pettersson score of -0.38. It had good correlation with other self-rated functional scores, such as the Stanford Health Assessment Questionnaire (r = -0.75); the Western Ontario and McMaster Universities Osteoarthritis Index (r = -0.66) and the Haemophilia Activities List (HAL) (r = -0.66). It had good reliability with a pooled intra class correlation of 0.98. On assessing responsiveness following treatment of flexion deformities of the knee in 12 patients, the FISH showed significant changes in the score with a standardized responsiveness mean of -1.93. In conclusion, the FISH was found to be a reliable and valid tool with good internal consistency and responsiveness to therapy, for the assessment of functional independence in persons with haemophilia.

Multiple cavitating masses in an immunocompromised host with rheumatoid arthritis-related interstitial lung disease: an unusual expression of cytomegalovirus pneumonitis.

Cytomegalovirus is a known opportunistic infection in immunocompromised individuals. We document multiple cavitating lung masses caused by cytomegalovirus in a patient with rheumatoid arthritis-induced interstitial lung disease on immunosuppressant medication, an unusual expression of CMV pneumonitis. With increasing use of immunosuppressive therapy and increase in AIDS, pulmonary cytomegalovirus infection is expected to be a more frequently encountered disease and familiarity with its uncommon radiological manifestations will be advantageous.

Magnification chromoendoscopy for the detection of intestinal metaplasia and dysplasia in Barrett's oesophagus.

BACKGROUND: The presence of intestinal metaplasia (IM) in the columnar lined distal oesophagus defines Barrett's oesophagus with the risk of future malignant transformation. The distribution of both IM and dysplasia (low grade (LGD) and high grade (HGD)) within the columnar lined oesophagus is patchy and mosaic requiring random biopsies. Techniques that could help target areas of high yield within Barrett's mucosa would be helpful. AIM: To study the utility of high magnification chromoendoscopy (MCE) in the detection of IM, LGD, and HGD in patients with Barrett's oesophagus. METHODS: Consecutive patients detected with columnar mucosa in the distal oesophagus were studied using an Olympus magnification endoscope (GIF-Q16OZ, 115x). The distal oesophagus was sprayed with indigo carmine solution and the oesophageal columnar mucosa patterns were noted under high magnification and targeted for biopsy. All biopsies were read by pathologists blinded to the endoscopic findings. RESULTS: Eighty patients with suspected Barrett's oesophagus (that is, columnar lined distal oesophagus) were studied: mean age 62.7 years (range 35-81). Mean length of columnar mucosa was 3.7 cm (range 0.5-17). Three types of mucosal patterns were noted within the columnar mucosa after spraying indigo carmine and using MCE: ridged/villous pattern, circular pattern, and irregular/distorted pattern. The yield of IM on target biopsies according to the patterns was: ridged/villous 57/62 (97%) and circular 2/12 (17%). Six patients had an irregular/distorted pattern and all had HGD on biopsy (6/6 (100%)). Eighteen patients had LGD on target biopsies; all had the ridged/villous pattern. All patients with long segment Barrett's were identified using MCE whereas 23/28 patients (82%) with short segment Barrett's had the ridged/villous pattern. CONCLUSIONS: MCE helps visually identify areas with IM and HGD having specific patterns but not patients with LGD (appear similar to IM). MCE may be a useful clinical tool for the increased detection of patients with IM as well as for surveillance of patients for the detection of HGD. If these preliminary results are validated, MCE would help identify high yield areas, potentially eliminating the need for random biopsies.