Photo-damage to Keratinocytes by Quinine Photosensitization under mild Ultraviolet-B Exposure

Simultaneous and sufficient exposure to sunlight and drug cause phototoxic reactions in the skin. In the present study, the photosensitizing activity of quinine (Q) was studied. Evidences obtained by reduction of cell viability, mitochondrial damage, DNA damage, ROS generation, lysosome damage and phosphatidyl serine translocation as a marker of apoptosis indicates that exposure of quinine treated keratinocytes to UV-B radiation results in quinine photosensitization and subsequent reactions which alter normal cellular processes. Quinine absorbs strongly in UV-B region (330 nm). It reduced viability of cells significantly as observed through MTT assay. Reduction of cell viability was confirmed through accumulation of Rhodamine 123 dye which showed that quinine and UV-B treated cells accumulate less than control cells confirmed that mitochondrial membrane potential was disturbed. Increased intracellular ROS production was measured through DCF fluorescence. Early apoptosis was confirmed through phosphatidyl serine translocation in the membrane. Increased lysosome damage was observed through acridine orange accumulation in the lysosmes. Single stranded damage was confirmed through comet assay and apoptosis was confirmed through EB/AO staining.  These results show that UV-B radiation elicits phototoxic effects in keratinocytes through reactive oxygen species generation

Ecological Interactions of Invasive Insects and Native Plant Species in Changing Climate

Invasive insects pose a significant threat to native plant species and ecosystems, particularly in the context of changing climates. Understanding these interactions is crucial for effective conservation and management strategies aimed at mitigating the adverse effects of invasive species on native plant communities. Invasive insects often establish and proliferate in new habitats due to the absence of natural enemies and the availability of suitable resources. As climate change alters the distribution and phenology of plants, it can influence the susceptibility and resilience of native plant species to invasive insects. In some cases, rising temperatures and altered precipitation patterns may favour the spread and population growth of invasive insects, leading to increased herbivory, reduced plant fitness, and ultimately, altered community dynamics. Furthermore, changing climates can disrupt the synchrony between native plants and their pollinators or beneficial insect populations, further exacerbating the impacts of invasive insects. As native plants and pollinators respond differently to shifting climatic conditions, their interactions may become disrupted, potentially reducing the reproductive success and long-term survival of native plant populations. However, it is important to note that climate change can also create novel opportunities for both invasive insects and native plant species. In certain instances, invasive insects may benefit from warmer temperatures and expanded ranges, while some native plants may exhibit adaptive responses and resilience to changing climatic conditions. These complex interactions highlight the need for a comprehensive understanding of the ecological dynamics between invasive insects and native plant species under various climate scenarios. The ecological interactions between invasive insects and native plant species in changing climates have far-reaching consequences for biodiversity conservation and ecosystem functioning. As climates continue to evolve, it is imperative to further investigate these interactions and develop adaptive strategies to mitigate the impacts of invasive insects on native plant communities. By doing so, we can strive to preserve and restore ecological balance in the face of ongoing environmental change

Sustainable green approach to synthesize Fe 3 O 4 /α-Fe 2 O 3 nanocomposite using waste pulp of Syzygium cumini and its application in functional stability of microbial cellulases

Synthesis of nanomaterials following green routes have drawn much attention in recent years due to the low cost, easy and eco-friendly approaches involved therein. Therefore, the current study is focused towards the synthesis of Fe(3)O(4)/α-Fe(2)O(3) nanocomposite using waste pulp of Jamun (Syzygium cumini) and iron nitrate as the precursor of iron in an eco-friendly way. The synthesized Fe(3)O(4)/α-Fe(2)O(3) nanocomposite has been extensively characterized through numerous techniques to explore the physicochemical properties, including X-ray diffraction, Fourier transform infrared spectroscopy, Raman spectroscopy, Ultraviolet-Vis spectroscopy, field emission scanning electron microscope, high resolution transmission electron microscope and vibrating sample magnetometer. Further, efficiency of the Fe(3)O(4)/α-Fe(2)O(3) nanocomposite has been evaluated to improve the incubation temperature, thermal/pH stability of the crude cellulase enzymes obtained from the lab isolate fungal strain Cladosporium cladosporioides NS2 via solid state fermentation. It is found that the presence of 0.5% Fe(3)O(4)/α-Fe(2)O(3) nanocomposite showed optimum incubation temperature and thermal stability in the long temperature range of 50–60 °C for 15 h along with improved pH stability in the range of pH 3.5–6.0. The presented study may have potential application in bioconversion of waste biomass at high temperature and broad pH range

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

OBJECTIVES: To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. PARTICPANTS AND METHODS: Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. RESULTS: A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. CONCLUSION: This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Study on Plastic Coated Overburnt Brick Aggregate as an Alternative Material for Bituminous Road Construction

There are different places in India where natural stone aggregates are not available for constructional work. Plastic coated OBBA can solve the problem of shortage of stone aggregate to some extent. The engineers are always encouraged to use locally available materials. The present investigation is carried out to evaluate the plastic coated OBBA as an alternative material for bituminous road construction. Shredded waste plastics are mixed with OBBA in different percentages as 0.38, 0.42, 0.46, 0.50, 0.54, and 0.60 of the weight of brick aggregates. Marshall Method of mix design is carried out to find the optimum bitumen content of such bituminous concrete mix prepared by plastic coated OBBA. Bulk density, Marshall Stability, flow, Marshall Quotient, ITS, TSR, stripping, fatigue life, and deformations have been determined accordingly. Marshall Stability value of 0.54 percent of plastic mix is comparatively higher than the other mixes except 0.60 percent of plastic mix. Test results are within the prescribed limit for 0.54 percent of plastic mix. There is a significant reduction in rutting characteristics of the same plastic mix. The fatigue life of the mix is also significantly higher. Thus plastic coated OBBA is found suitable in construction of bituminous concrete road

Evaluation of the Properties of Bituminous Concrete Prepared from Brick-Stone Mix Aggregate

The paper describes an investigation into mechanical properties of brick-stone bituminous concrete mix. The effect of brick-stone mix on various mechanical properties of the bituminous concrete such as Marshall stability, flow, Marshall Quotient (stability to flow ratio), Indirect Tensile Strength, stripping, rutting, and fatigue life of bituminous concrete overlay has been evaluated. In this study over-burnt brick aggregate (OBBA) and stone aggregate (SA) have been mixed in different ratios (by weight) such as 20 : 80, 40 : 60, 60 : 40, and 80 : 20, respectively. The laboratory results indicate that bituminous concrete, prepared by 20% brick aggregate and 80% stone aggregate, gives the highest Marshall stability. This bituminous concrete mix shows considerable improvement in various mechanical properties of the mix as compared to the other mixes

<span style="font-size: 19.0pt;mso-bidi-font-size:14.0pt;font-family:"Times New Roman","serif"; color:black">Growth, CO₂<span style="font-size:14.0pt; mso-bidi-font-size:9.0pt;font-family:"Times New Roman","serif";color:black"> <span style="font-size:19.0pt;mso-bidi-font-size:14.0pt;font-family:"Times New Roman","serif"; color:black">exchange rate and dry matter partitioning in mungbean <i>(Vigna radiata </i>L.) grown under elevated CO_{<span style="font-size:14.5pt; mso-bidi-font-size:9.5pt;font-family:"Times New Roman","serif";color:black">2</span>}<span style="font-size:14.5pt;mso-bidi-font-size:9.5pt;font-family:"Times New Roman","serif"; color:black"> </span></span></span></span>

572-577<span style="font-size: 14.0pt;mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif";="" color:black"="">This study was conducted to determine the effects of anticipated future level of CO2 on growth and dry matter partitioning of mungbean <span style="font-size:13.5pt;mso-bidi-font-size:8.5pt; font-family:" times="" new="" roman","serif";color:black"="">(Vigna radiata). Plants were grown from seedlings to maturity inside the open top chamber under <span style="font-size: 14.0pt;mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif";="" color:black"="">amhient CO2<span style="mso-bidi-font-size:6.0pt; font-family:" times="" new="" roman","serif";color:black"=""> (350±25 µ L  L-1 ) <span style="font-size:14.0pt;mso-bidi-font-size:9.0pt; font-family:" times="" new="" roman","serif";color:black"="">and elevated CO2 <span style="font-size:14.0pt;mso-bidi-font-size:9.0pt; font-family:" times="" new="" roman","serif";color:black"="">(600±50 µ L  L-1 <span style="mso-bidi-font-size: 6.0pt;font-family:" times="" new="" roman","serif";color:black"="">) at Indian Agricultural Research Institute, New Delhi (India). Plants were harvested at 20, 35 and 50 days after germination. Mungbean plants grown under elevated CO2 concentration resulted in greater photosynthetic rate on a leaflet area basis and no acclimation in photosynthesis was recorded due to high CO<span style="mso-bidi-font-size: 6.0pt;font-family:" times="" new="" roman","serif";color:black"="">2, <span style="font-size:14.0pt;mso-bidi-font-size:9.0pt; font-family:" times="" new="" roman","serif";color:black"="">Plants grown under CO2<span style="mso-bidi-font-size:6.0pt;font-family: " times="" new="" roman","serif";color:black"=""> <span style="font-size:14.0pt; mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif";color:black"="">enrichment were taller and attained greater leaf area along with more dry matter than ambient CO2<span style="mso-bidi-font-size:6.0pt;font-family: " times="" new="" roman","serif";color:black"=""> <span style="font-size:14.0pt; mso-bidi-font-size:9.0pt;font-family:" times="" new="" roman","serif";color:black"="">grown plants at all growth stages. Response to high <span style="font-size: 13.5pt;mso-bidi-font-size:8.5pt;font-family:" arial","sans-serif";color:black;="" mso-bidi-font-style:italic"="">CO2 depends upon the growth stage of the plant and it was more at early growth stages compared to maturity stages. The high CO2 <span style="font-size:14.0pt;mso-bidi-font-size:9.0pt; font-family:" times="" new="" roman","serif";color:black"="">grown mungbean plants also exhibited increased root growth along with stem and leaves. There was a substantial increase in pod number and seed number/plant under elevated CO2 conditions. The increase in dry matter and growth of root, stem and leaves proved that CO<span style="font-size:11.5pt;mso-bidi-font-size: 6.5pt;font-family:" times="" new="" roman","serif";color:black"="">2 <span style="font-size:14.0pt;mso-bidi-font-size:9.0pt; font-family:" times="" new="" roman","serif";color:black"="">enrichment of the atmosphere can stimulate photosynthetic rate which can ultimately lead to an increase in dry matter and growth. </span

Effect of 5-lipoxygenase inhibitor against lipopolysaccharide-induced hypothermia in mice

1150-1155Bacterial endotoxin produces sepsis associated with alterations in body temperature (fever or hypothermia). The intraperitoneal administration of bacterial endotoxin, lipopolysaccharide (LPS; 50 μg/mouse) led to a decrease in colonic temperature starting 1 hr after the injection. The hypothermic effect was accompanied by a significant increase in hypothalamic leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) levels. 5-lipoxygenase inhibitor, zileuton (200 and 400 Mg/kg. po) administered 30 min before LPS challenge significantly prevented hypothermia. However, non-selective cyclooxygenase inhibitor, indomethacin (10, 20 mg/kg, po) did not reverse the hypothermic response. Further, pretreatment of mice with zileuton prevented LPS-stimulated increase in hypothalamic LTB4 levels and caused a relatively small increase in PGEz levels. Indomethacin had no effect on LTB4 levels but it reduced PGE2 levels. These results suggest a possible involvement of leukotrienes in LPS-induced hypothermia and the potential protective role of 5-lipoxygenase inhibitors in endotoxemia