Regional sources of NH3, SO2 and CO in the Third Pole.

The Third Pole (TP) is a high mountain region in the world, and is well-known for its pristine environment, but recent development activities in the region have degraded its air quality. Here, we investigate the spatial and temporal changes of the air pollutants ammonia (NH3), sulphur dioxide (SO2) and carbon monoxide (CO) in TP, and reveal their sources using satellite measurements and emission inventory. We observe a clear seasonal cycle of NH3 in TP, with high values in summer and low values in winter. The intense agriculture activities in the southern TP are the cause of high NH3 (6-8 × 1016 molec./cm2) there. Similarly, CO shows a distinct seasonal cycle with high values in spring in the southeast TP due to biomass burning. In addition, the eastern boundary of TP in the Sichuan and Qinghai provinces also show high values of CO (about 1.5 × 1018 mol/cm2), primarily owing to the industrial activities. There is no seasonal cycle found for SO2 distribution in TP, but relatively high values (8-10 mg/m2) are observed in its eastern boundary. The high-altitude pristine regions of inner TP are also getting polluted because of increased human activities in and around TP, as we estimate positive trends in CO (0.5-1.5 × 1016 mol/cm2/yr) there. In addition, positive trends are also found in NH3 (0.025 × 1016 molec./cm2/yr) during 2008-2020 in most regions of TP and SO2 (about 0.25-0.75 mg/m2/yr) in the Sichuan and Qinghai region during 2000-2020. As revealed by the emission inventory, there are high anthropogenic emissions of NH3, SO2 and CO within TP. There are emissions of pollutants from energy sectors, oil and refinery, agriculture waste burning and manure management within TP. These anthropogenic activities accelerate the ongoing development in TP, but severely erode its environment.

Clonal KEAP1 mutations with loss of heterozygosity share reduced immunotherapy efficacy and low immune cell infiltration in lung adenocarcinoma.

BACKGROUND: KEAP1 mutations have been associated with reduced survival in lung adenocarcinoma (LUAD) patients treated with immune checkpoint inhibitors (ICIs), particularly in the presence of STK11/KRAS alterations. We hypothesized that, beyond co-occurring genomic events, clonality prediction may help identify deleterious KEAP1 mutations and their counterparts with retained sensitivity to ICIs. PATIENTS AND METHODS: Beta-binomial modelling of sequencing read counts was used to infer KEAP1 clonal inactivation by combined somatic mutation and loss of heterozygosity (KEAP1 C-LOH) versus partial inactivation [KEAP1 clonal diploid-subclonal (KEAP1 CD-SC)] in the Memorial Sloan Kettering Cancer Center (MSK) MetTropism cohort (N = 2550). Clonality/LOH prediction was compared to a streamlined clinical classifier that relies on variant allele frequencies (VAFs) and tumor purity (TP) (VAF/TP ratio). The impact of this classification on survival outcomes was tested in two independent cohorts of LUAD patients treated with immunotherapy (MSK/Rome N = 237; DFCI N = 461). Immune-related features were studied by exploiting RNA-sequencing data (TCGA) and multiplexed immunofluorescence (DFCI mIF cohort). RESULTS: Clonality/LOH inference in the MSK MetTropism cohort overlapped with a clinical classification model defined by the VAF/TP ratio. In the ICI-treated MSK/Rome discovery cohort, predicted KEAP1 C-LOH mutations were associated with shorter progression-free survival (PFS) and overall survival (OS) compared to KEAP1 wild-type cases (PFS log-rank P = 0.001; OS log-rank P < 0.001). Similar results were obtained in the DFCI validation cohort (PFS log-rank P = 0.006; OS log-rank P = 0.014). In both cohorts, we did not observe any significant difference in survival outcomes when comparing KEAP1 CD-SC and wild-type tumors. Immune deconvolution and multiplexed immunofluorescence revealed that KEAP1 C-LOH and KEAP1 CD-SC differed for immune-related features. CONCLUSIONS: KEAP1 C-LOH mutations are associated with an immune-excluded phenotype and worse clinical outcomes among advanced LUAD patients treated with ICIs. By contrast, survival outcomes of patients whose tumors harbored KEAP1 CD-SC mutations were similar to those with KEAP1 wild-type LUADs.

A gradual increase of aerosol pollution in the Third Pole during the past four decades: Implication for regional climate change.

We analyse the long-term (1980-2020) changes in aerosols over the Third Pole (TP) and assess the changes in radiative forcing (RF) using satellite, ground-based and reanalysis data. The annual mean aerosol optical depth (AOD) varies from 0.06 to 0.24, with the highest values of around 0.2 in the north and southwest TP, which are dominated by dust from Taklimakan and Thar deserts, respectively. However, Organic Carbon (OC), Black Carbon (BC) and sulphate aerosols have significant contributions to the total AOD in the south and east TP. High amounts of dust are observed in spring and summer, but BC in winter. Trajectory analysis reveals that the air mass originated from East and South Asia carries BC and OC, whereas the air from South Asia, Central Asia and Middle East brings dust to TP. Significant positive trends in AOD is found in TP, with high values of about 0.002/yr in the eastern and southern TP. There is a gradual increase in BC and OC concentrations during 1980-2020, but the change from 2000 is phenomenal. The RF at the top of the atmosphere varies from -10 to 2 W/m2 in TP, and high positive RF of about 2 W/m2 is estimated in Pamir, Karakoram and Nyainquentanglha mountains, where the massive glacier mass exists. The RF has increased in much of TP during recent decades (2001-2020) with respect to previous decades (1981-2000), which can be due to the rise in BC and dust during the latter period. Therefore, the positive trend in BC and its associated change in RF can amplify the regional warming, and thus, the melting of glaciers or ice in TP. This is a great concern as it is directly connected to the water security of many South Asian countries.

Mid-term outcome of arthroscopic TightRope fixation of displaced lateral end clavicular fractures: Average follow-up of 6.1 years.

PURPOSE: Various surgical modalities are available to treat Neer types 2 and 5 unstable fractures of lateral end clavicle but none of them are standardized. Arthroscopic fixation of the displaced lateral end clavicle fractures provides good short-term results but mid- to long-term outcomes are not available. The purpose of this study was to show the mid- to long-term radiological and functional outcomes of these fractures treated arthroscopically by a TightRope device, and to show the complications associated with this procedure. METHODS: A retrospective study was conducted over 2 years from January 2014 to December 2015 with a minimum 5-year follow-up. Active patients aged 18-50 years with acute (less than 3 weeks) displaced fracture of lateral end of the clavicle, with a minimum 5-year follow-up were included in the study. Patients with associated fractures of the proximal humerus, glenoid, scapula and acromioclavicular joint injuries were excluded from the study along with open fractures and neurovascular injuries. The outcomes were assessed by objective (complications and radiographic examination) and subjective criteria (quick disabilities of the arm, shoulder and hand score, the Constant-Murley score and the visual pain analogue scale). The data were analyzed by SPSS version 21.0. RESULTS: Totally, 42 patients were operated during the study period and 37 were available with a minimum 5-year follow-up. Thirty were male and 7 were female with a mean age of 29.5 years and a mean follow-up of 6.1 years. The mean quick disabilities of the arm, shoulder and hand score was 68.2 ± 4.6 preoperatively and 1.27 ± 2.32 at final follow-up (p < 0.001); the mean visual pain analogue scale score was 6.85 ± 2.2 preoperatively and 0.86 ± 1.60 at final follow-up (p < 0.001). The average Constant-Murley score was 93.38 ± 3.25 at the end of the follow-up. There were 2 fixation failures, with established non-union and 3 patients developed radiographic acromioclavicular joint arthritis. CONCLUSIONS: Arthroscopic TightRope fixation of displaced lateral end clavicular fractures provides good radiological and functional outcomes at mid- to long-term follow-up. With the low complication rates and high patient satisfaction, this technique can be considered as a primary option in the surgical treatment of these fractures.

Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRASG12D-mutated non-small-cell lung cancer.

BACKGROUND: Allele-specific KRAS inhibitors are an emerging class of cancer therapies. KRAS-mutant (KRASMUT) non-small-cell lung cancers (NSCLCs) exhibit heterogeneous outcomes, driven by differences in underlying biology shaped by co-mutations. In contrast to KRASG12C NSCLC, KRASG12D NSCLC is associated with low/never-smoking status and is largely uncharacterized. PATIENTS AND METHODS: Clinicopathologic and genomic information were collected from patients with NSCLCs harboring a KRAS mutation at the Dana-Farber Cancer Institute (DFCI), Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, and Imperial College of London. Multiplexed immunofluorescence for CK7, programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), Foxp3, and CD8 was carried out on a subset of samples with available tissue at the DFCI. Clinical outcomes to PD-(L)1 inhibition ± chemotherapy were analyzed according to KRAS mutation subtype. RESULTS: Of 2327 patients with KRAS-mutated (KRASMUT) NSCLC, 15% (n = 354) harbored KRASG12D. Compared to KRASnon-G12D NSCLC, KRASG12D NSCLC had a lower pack-year (py) smoking history (median 22.5 py versus 30.0 py, P < 0.0001) and was enriched in never smokers (22% versus 5%, P < 0.0001). KRASG12D had lower PD-L1 tumor proportion score (TPS) (median 1% versus 5%, P < 0.01) and lower tumor mutation burden (TMB) compared to KRASnon-G12D (median 8.4 versus 9.9 mt/Mb, P < 0.0001). Of the samples which underwent multiplexed immunofluorescence, KRASG12D had lower intratumoral and total CD8+PD1+ T cells (P < 0.05). Among 850 patients with advanced KRASMUT NSCLC who received PD-(L)1-based therapies, KRASG12D was associated with a worse objective response rate (ORR) (15.8% versus 28.4%, P = 0.03), progression-free survival (PFS) [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.45-2.00, P = 0.003], and overall survival (OS; HR 1.45, 1.05-1.99, P = 0.02) to PD-(L)1 inhibition alone but not to chemo-immunotherapy combinations [ORR 30.6% versus 35.7%, P = 0.51; PFS HR 1.28 (95%CI 0.92-1.77), P = 0.13; OS HR 1.36 (95%CI 0.95-1.96), P = 0.09] compared to KRASnon-G12D. CONCLUSIONS: KRASG12D lung cancers harbor distinct clinical, genomic, and immunologic features compared to other KRAS-mutated lung cancers and worse outcomes to PD-(L)1 blockade. Drug development for KRASG12D lung cancers will have to take these differences into account.

Radiology of Castleman disease: the pivotal role of imaging in diagnosis, staging, and response assessment of this rare entity.

Castleman Disease (CD) is a rare entity that typically presents as an enhancing nodal mass in the mediastinum or head and neck region on computed tomography (CT). It may manifest as unicentric or multicentric regions of lymph node enlargement. A key clinical issue in the context of CD is delayed diagnosis, which contributes adversely to patient outcome, given that accurate diagnosis facilitates earlier treatment of this curable disease. This article will address relevant imaging aspects, with reference to typical and atypical imaging features of CD, illustrated using examples from our specialist centre; the imaging journey for patients with CD; and will provide practical pointers to radiologists in differentiating CD from other benign and malignant causes of enhancing lymphadenopathy, including lymphoma and neoplastic adenopathy. We will also review current classification tools and staging challenges with reference to World Health Organization guidelines, International Working Group guidelines as well as the Lugano classification. Finally, we will discuss the potential role of additional imaging techniques in CD, highlighting novel imaging methods and expanded utilities from our specialist centre.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): a good practice guide, pictorial review, and new perspectives.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare but emerging T-cell non-Hodgkin lymphoma. It has two distinct subtypes, "effusion-only" or "mass-forming" disease, arising around implants in patients with in situ or previous history of textured-surface breast implants. The clinical, histopathological and imaging features are unique and nuanced as compared to primary breast malignancy and other lymphoma categories. Prompt recognition and diagnosis triggers referral to appropriate BIA-ALCL centres and initiation of treatment, with potential for excellent prognosis. Definitive management of both subtypes involves implant and capsule removal; systemic therapy is reserved for mass-forming disease and advanced-stage disease. There have been recent crucial advances in the diagnostic pathway, with publication of national and international guidelines: from the UK Medicines Healthcare products Regulatory Agency (MHRA) Plastic, Reconstructive and Aesthetic Surgery Expert Advisory Group (PRASEAG), and the United States National Comprehensive Cancer Network (NCCN). This review provides a practical guide to the clinical work-up of BIA-ALCL, enabling optimisation of the diagnostic imaging pathway, with representative cases.

Body adiposity measures and risk of adolescent hypertension among the postpubescents Northeast India.

OBJECTIVES: The present study attempts to associate and predict adolescent hypertension in Northeast India through body adiposity measures. METHOD: A total of 728 adolescents aged 15 years and above were included in the present study after consent. Blood pressure and related anthropometric data were collected. The prevalence rate was calculated. Significant tests and correlation analyses were conducted between the blood pressure parameters and anthropometric body adiposity measures. The odds ratio (OR) was also calculated to assess the likelihood of risks. The receiver operating characteristic (ROC) curve analysis was performed to find the measured parameters' predictive cut-off values. RESULTS: The prevalence of adolescent hypertension is 29.12%, and elevated blood pressure is 20.47%. Boys are more hypertensive than girls. Obese adolescents are more prone to hypertension. Overweight, obese, and abdominal volume index (AVI) has 2.31, 5.15, and 3.41 OR to develop hypertension significantly, irrespective of gender. Among the boys, waist circumference (WC), AVI, and waist to height ratio (WHtR) significantly correlate with hypertension at adjusted for age; they are better predictors with area under curve (AUC) value reach 0.7. Among the females, the BMI reaches AUC 0.7, making it a better assessment for hypertension. CONCLUSION: The study highlights the concerns of adolescent hypertension among Northeast Indian adolescents, which needs attention. More studies in different regions must be conducted to understand the problem's crux to enable health policymakers to promote adolescent health.

Bioremediation: an alternative approach for detoxification of polymers from the contaminated environment.

The industries and metropolitan wastes produced by anthropogenic activities are of great concern for nature as it causes soil contamination and deteriorate the environment. Plastic utilization is rapidly enhancing globally with passing days that last for a more extended period in the environment due to slow decomposition and natural degradation. Excessive use of polymer has risked the life of both marine, freshwater and terrestrial organisms. Lack of proper waste management and inappropriate disposal leads to environmental threats. Bioremediation processes involve microbes such as fungi, bacteria, etc. which contribute a crucial role in the breakdown of plastics. Extremophiles secrete extremozymes that are functionally active in extreme conditions and are highly crucial for polymer disaggregation in those conditions.

Impact of COVID-19 on cancer care in India: a cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted health-care systems, leading to concerns about its subsequent impact on non-COVID disease conditions. The diagnosis and management of cancer is time sensitive and is likely to be substantially affected by these disruptions. We aimed to assess the impact of the COVID-19 pandemic on cancer care in India. METHODS: We did an ambidirectional cohort study at 41 cancer centres across India that were members of the National Cancer Grid of India to compare provision of oncology services between March 1 and May 31, 2020, with the same time period in 2019. We collected data on new patient registrations, number of patients visiting outpatient clinics, hospital admissions, day care admissions for chemotherapy, minor and major surgeries, patients accessing radiotherapy, diagnostic tests done (pathology reports, CT scans, MRI scans), and palliative care referrals. We also obtained estimates from participating centres on cancer screening, research, and educational activities (teaching of postgraduate students and trainees). We calculated proportional reductions in the provision of oncology services in 2020, compared with 2019. FINDINGS: Between March 1 and May 31, 2020, the number of new patients registered decreased from 112 270 to 51 760 (54% reduction), patients who had follow-up visits decreased from 634 745 to 340 984 (46% reduction), hospital admissions decreased from 88 801 to 56 885 (36% reduction), outpatient chemotherapy decreased from 173634 to 109 107 (37% reduction), the number of major surgeries decreased from 17 120 to 8677 (49% reduction), minor surgeries from 18 004 to 8630 (52% reduction), patients accessing radiotherapy from 51 142 to 39 365 (23% reduction), pathological diagnostic tests from 398 373 to 246 616 (38% reduction), number of radiological diagnostic tests from 93 449 to 53 560 (43% reduction), and palliative care referrals from 19 474 to 13 890 (29% reduction). These reductions were even more marked between April and May, 2020. Cancer screening was stopped completely or was functioning at less than 25% of usual capacity at more than 70% of centres during these months. Reductions in the provision of oncology services were higher for centres in tier 1 cities (larger cities) than tier 2 and 3 cities (smaller cities). INTERPRETATION: The COVID-19 pandemic has had considerable impact on the delivery of oncology services in India. The long-term impact of cessation of cancer screening and delayed hospital visits on cancer stage migration and outcomes are likely to be substantial. FUNDING: None. TRANSLATION: For the Hindi translation of the abstract see Supplementary Materials section.

Chronic lymphocytic leukaemia and Richter's transformation: multimodal review and new imaging paradigms.

Chronic lymphocytic leukaemia (CLL) is the most common leukaemia in adults. It is a malignancy of CD5 B-cells characterised by small, mature-appearing lymphocytes accumulating in the blood, bone marrow, and lymphoid tissues. Richer transformation (RT) is an important adverse complication. Detection of RT is critical to allow initiation of appropriate therapy. CLL staging and response evaluation is complicated and nuanced. From our extensive tertiary centre experience of several hundred CLL cases over the last decade, we detail key computed tomography (CT) and positron-emission tomography (PET) imaging features of the natural history of CLL. The authors present an original imaging-based patient-management paradigm for the investigation of potential RT, which will inform global practice. Potential applications of whole-body diffusion weighted imaging, novel PET radiotracers, minimal residual disease, and ct-DNA are addressed.

Current and future best practice in imaging, staging, and response assessment for Non-Hodgkin's lymphomas: the Specialist Integrated Haematological Malignancy Imaging Reporting (SIHMIR) paradigm shift.

Non-Hodgkin's lymphoma (NHL) encompasses over 40 different haematological malignancies, including low and high-grade neoplasms, such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) respectively. A key clinical issue in the context of NHL is delayed and inaccurate diagnosis, which contributes adversely to patient morbidity and mortality. This article will address relevant imaging aspects, with particular reference to advancements in NHL imaging, including computed tomography (CT), integrated positron-emission tomography (PET)-CT, and magnetic resonance imaging (MRI). We provide multiparametric (anato-functional) imaging display items, including histological correlation. We will also introduce our original concept of "Specialist Integrated Haematological Malignancy Imaging Reporting" (SIHMIR), a paradigm shift in lymphoma radiology.

Multi-drug Resistant and Extended Spectrum ß-lactamase Producing Salmonella Species Isolated from Fresh Chicken Liver Samples.

Background Emergence of antibiotic resistance among microbes contaminating the fresh meat products is a global public health concern as they can be easily transmitted to humans through their consumption and contact. Objective The current study was conducted to determine the distribution of antimicrobial resistance among Salmonella species isolated from fresh chicken liver samples with special emphasis on extended spectrum beta-lactamase (ESBL) production. Method A total of 200 fresh chicken liver samples were cultivated for the isolation of Salmonella and further subcultivated to detect extended spectrum beta-lactamase production among them. Antimicrobial susceptibility testing (AST) was done by disk diffusion method using a panel of 7 antimicrobials. Result Out of 200 samples analyzed, 61 (30.5%) samples harbored Salmonella species out of which 15 (7.5%) samples showed the presence of Salmonella Typhi. A significant association was noted in the incidence of Salmonella with various factors pertaining to the butchers, such as age, sex, literacy rate, practices of washing knives and chopping board, wearing aprons and gloves and type of water used (p < 0.05). Salmonella isolates were highly sensitive to amikacin (82.0%) and least sensitive to tetracycline (3.3%). All the isolates were resistant to colistin. Sixty (98.4%) isolates were identified as multi-drug resistant (MDR). The total number of extended spectrum betalactamase producers reported among Salmonella isolates was 29 (47.5%). Conclusion The results indicate that the fresh chicken liver samples sold in Bharatpur Metropolis are reservoirs of multi-drug resistant Salmonella, including extended spectrum betalactamase producers, that could potentially be transmitted to the humans by direct contact or through inadequate cooking.

Aetiology and trends of rates of stillbirth in a tertiary care hospital in the north of India over 10 years: a retrospective study.

OBJECTIVE: To analyse the aetiology of stillbirth and its changing trends in a single tertiary care referral institute of northern India over a 10-year period (2007-2016). DESIGN: Retrospective study. SETTING: Tertiary care hospital in the north of India. SAMPLE: Medical records of all mothers who delivered a stillborn at the institute. METHODS: Data was collected from monthly and annual perinatal audits and causes of stillbirths were classified using Simplified CODAC classification. Annual reduction rate was calculated by linear regression analysis and Cusick test for the changing trends over 9 years. MAIN OUTCOME MEASURES: Of 54 160 births, 3678 babies were stillborn. Over 9 years, the annual stillbirth rate has reduced significantly from 73.6 to 62.0 per 1000 total births with an average annual reduction rate of 1%. The most common causes of stillbirths were hypertensive disorders of pregnancy (27.6%), antepartum haemorrhage (19.5%), and congenital anomalies (9.3%). CONCLUSION: The annual reduction rate (1%) of stillbirth remains low. The aetiology of stillbirths remains unchanged over a 10-year period and hypertensive disorder of pregnancy remains the single most preventable cause of stillbirth. TWEETABLE ABSTRACT: Analysis of stillbirths over a 10-year period in an Indian institute showed a high but declining trend with annual reduction rate of 1%.

Allergic Bronchopulmonary Mycosis due to fungi other than Aspergillus.

Summary: Allergic bronchopulmonary mycosis (ABPM) is a clinical syndrome associated with immune sensitivity to various fungi that colonize the airways. Early diagnosis and treatment with systemic corticosteroids is the key in preventing the progression of the disease to irreversible lung fibrosis. Although Aspergillus has progressively gained recognition as a causative agent in past few decades, other fungi, that have been reported to cause ABPM, are not yet widely evaluated. We studied hundred and two patients with asthma for occurrence of ABPM. Patients were tested for cutaneous hypersensitivity and serum precipitin to 12 common fungal antigens. The positive cases were further evaluated for ABPM using standard criteria. Out of 102 asthma patients screened, 18 patients had either skin prick test (SPT) and/or serum precipitin positive. While 14 patients were SPT positive for one or more fungal antigen, two patients were serum precipitin positive for one or more fungi. Two patients had both serum precipitin positive as well as SPT positive. Six (5.8%) patients were diagnosed as ABPM as they fulfilled the criteria. Three of these were because of Aspergillus sp. Two were because of fungi other than Aspergillus namely Schizophyllum and Curvularia. One patient had ABPM because of both Aspergillus and Curvularia. In our study absolute eosinophil count (AEC), total IgE, serum precipitin and SPT had sensitivity of 100%, 100% 50% and 83.3% respectively for diagnosing ABPM. The specificity of these tests was 44.79%, 64.58% 98.96% and 88.54% respectively. Specfic IgE was positive in 50% of patients with either serum precipitin or SPT positivity. SPT or serum precipitin followed by specific IgE had sensitivity of 100% and specificity of 96.88% for diagnosing ABPM. SPT alone followed by Specific IgE had a sensitivity of 83.33% and specificity of 96.88% for diagnosing ABPM. We found that fungi other than Aspergillus such as schizophyllum, and curvularia, can be implicated in ABPM. Multiple fungal agents may be responsible for ABPM in an individual. There is a subset of patients of BA who have fungal sensitization but do not fulfil the criteria for ABPM. SPT was the single most sensitive and specific test, AEC >350 and total IgE more than 417IU were most sensitive tests and SPT followed by specific IgE was most effective strategy for diagnosing ABPM.

Lentiviral-based reporter constructs for profiling chondrogenic activity in primary equine cell populations.

Successful clinical translation of mesenchymal stem cell (MSC)-based therapies for cartilage repair will likely require the implementation of standardised protocols and broadly applicable tools to facilitate the comparisons among cell types and chondroinduction methods. The present study investigated the utility of recombinant lentiviral reporter vectors as reliable tools for comparing chondrogenic potential among primary cell populations and distinguishing cellular-level variations of chondrogenic activity in widely used three-dimensional (3D) culture systems. Primary equine MSCs and chondrocytes were transduced with vectors containing combinations of fluorescent and luciferase reporter genes under constitutive cytomeglavirus (CMV) or chondrocyte-lineage (Col2) promoters. Reporter activity was measured by fluorescence imaging and luciferase assay. In 3D cultures of MSC aggregates and polyethylene glycol-hyaluronic acid (PEG-HA) hydrogels, transforming growth factor beta 3 (TGF-ß3)-mediated chondroinduction increased Col2 reporter activity, demonstrating close correlation with histology and mRNA expression levels of COL2A1 and SOX9. Comparison of chondrogenic activities among MSC populations using a secretable luciferase reporter revealed enhanced chondrogenesis in bone-marrow-derived MSCs relative to MSC populations from synovium and adipose tissues. A dual fluorescence reporter - enabling discrimination of highly chondrogenic (Col2-GFP) cells within an MSC population (CMV-tdTomato) - revealed marked heterogeneity in differentiating aggregate cultures and identified chondrogenic cells in chondrocyte-seeded PEG-HA hydrogels after 6 weeks in a subcutaneous implant model - indicating stable, long-term reporter expression in vivo. These results suggested that lentiviral reporter vectors may be used to address fundamental questions regarding chondrogenic activity in chondroprogenitor cell populations and accelerate clinical translation of cell-based cartilage repair strategies.

Effects of alpha lipoic acid on acrylamide-induced hepatotoxicity in rats.

Acrylamide (ACR) is a neurotoxicant, reproductive toxicant, and carcinogen in animal species.  It is used in many industries and has been found to form naturally in foods cooked at high temperatures. Alpha-lipoic acid (ALA) is a naturally occurring antioxidant whose therapeutic effect has been related to its antioxidant activity.  This study was carried out to study the protective effect of alpha lipoic acid on acrylamide induced perturbations in rat liver.  Four groups of rats were studied viz., control rats, acrylamide treated rats, alpha lipoic acid treated rats, and alpha lipoic acid plus acrylamide treated rats. ACR and ALA treatment alone and together caused a signifi-cant increase in hepatic reduced glutathione content while a decrease in hepatic ascorbic content was observed when compared to control group.  ALA pretreatment of acrylamide exposed rats caused no a signifi-cant alteration in superoxide dismutase activity but resulted in a tendency towards restoration of glutathione peroxidase and catalase activity to near normal levels.  Gel electrophoresis showed fragmentation of DNA in the treated groups.  The dose of ALA used in the present study afforded partial restoration of oxidative indices altered by ACR in rat liver.

Curcumin mediated attenuation of carbofuran induced toxicity in the heart of Wistar rats.

Carbofuran is used to improve the agricultural productivity as well as to protect the house hold and industrial products, but due to accumulation in the biological system, it causes serious side effects in many non-targets mammalian systems. The aim of present study is to evaluate the carbofuran induced oxidative stress in rat heart and its attenuation by using herbal product curcumin. Rats were divided into four groups; one group received 20 % LD50 of carbofuran another group of rats received same doses of carbofuran was  pretreated with curcumin (100 mg kg-1 body weight) and remaining two other groups served as control and curcumin treated animals. The activity of lactate dehydrogenase (LDH) in the heart tissues and serum was evaluated and the activity of enzymatic antioxidants superoxide dismutase (SOD) and catalase (CAT) was estimated in the heart tissues. The level of malondialdehyde (MDA) in heart tissues was also measured. The Total cholesterol (TC) and high density lipoprotein (HDL) was measured in the serum of the entire animals group. The results of present study showed that the activity of LDH in heart tissues were decreased and in serum was elevated. The MDA level was significantly elevated due to exposure of carbofuran. The enzymatic antioxidants, SOD and CAT activities were also inhibited. The ratio of pro-oxidant (P)/antioxidant (A) was also found to be sharply increased in the rat heart tissues of carbofuran exposed animals. The alterations in all the parameter were recovered by the pretreatment of curcumin (100 mg kg-1 body weight).

A qualitative exploration of work-related head injury: vulnerability at the intersection of workers' decision making and organizational values.

BACKGROUND: Work-related head injury is a critical public health issue due to its rising prevalence; the association with profound disruption of workers' lives; and significant economic burdens in terms of medical costs and lost wages. Efforts to understand and prevent these types of injuries have largely been dominated by epidemiological research and safety science, which has focused on identifying risk at the level of the individual worker, population group, or organizational sector. Limited research has focused on the perspectives of the workers, a key stakeholder group for informing understanding of vulnerability to work-related head injury. This study explored workers' perspectives to better understand their decision-making and how and why their injuries occurred. METHODS: We conducted a qualitative study using in-depth semi-structured interviews with thirty-two adult workers who had sustained a work-related head injury. Workers were recruited from an urban clinic in central Ontario, Canada. Labour Process Theory informed the thematic analysis. RESULTS: Three hazardous work conditions were identified: insufficient training; inadequate staffing; and inattention to the physical environment. In addition, professional and organizational norms were implicated in vulnerability to head injury including putting the client before the worker and the pressure to work unsafely. The findings also highlight a complex interrelationship between workers' decision-making and professional and organizational norms that produces vulnerability to head injury, a vulnerability which oftentimes is reproduced by workers' decisions to work despite hazardous conditions. CONCLUSIONS: Our findings suggest that, beyond the need to redress the inattention to hazards in the physical environment, there is a need to address norms that influence worker decision-making to improve the safety of workers. Using Labour Process Theory highlights an important social dynamic within workplace sectors that could inform future development and implementation of multi-level and integrated public health strategies to reduce work-related head injury.