Multiple sclerosis is the most common inflammatory neurological disease in young adults. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic method of ...quantifying various effects of a given condition by demographic variables and geography. In this systematic analysis, we quantified the global burden of multiple sclerosis and its relationship with country development level.
We assessed the epidemiology of multiple sclerosis from 1990 to 2016. Epidemiological outcomes for multiple sclerosis were modelled with DisMod-MR version 2.1, a Bayesian meta-regression framework widely used in GBD epidemiological modelling. Assessment of multiple sclerosis as the cause of death was based on 13 110 site-years of vital registration data analysed in the GBD's cause of death ensemble modelling module, which is designed to choose the optimum combination of mathematical models and predictive covariates based on out-of-sample predictive validity testing. Data on prevalence and deaths are summarised in the indicator, disability-adjusted life-years (DALYs), which was calculated as the sum of years of life lost (YLLs) and years of life lived with a disability. We used the Socio-demographic Index, a composite indicator of income per person, years of education, and fertility, to assess relations with development level.
In 2016, there were 2 221 188 prevalent cases of multiple sclerosis (95% uncertainty interval UI 2 033 866–2 436 858) globally, which corresponded to a 10·4% (9·1 to 11·8) increase in the age-standardised prevalence since 1990. The highest age-standardised multiple sclerosis prevalence estimates per 100 000 population were in high-income North America (164·6, 95% UI, 153·2 to 177·1), western Europe (127·0, 115·4 to 139·6), and Australasia (91·1, 81·5 to 101·7), and the lowest were in eastern sub-Saharan Africa (3·3, 2·9–3·8), central sub-Saharan African (2·8, 2·4 to 3·1), and Oceania (2·0, 1·71 to 2·29). There were 18 932 deaths due to multiple sclerosis (95% UI 16 577 to 21 033) and 1 151 478 DALYs (968 605 to 1 345 776) due to multiple sclerosis in 2016. Globally, age-standardised death rates decreased significantly (change −11·5%, 95% UI −35·4 to −4·7), whereas the change in age-standardised DALYs was not significant (−4·2%, −16·4 to 0·8). YLLs due to premature death were greatest in the sixth decade of life (22·05, 95% UI 19·08 to 25·34). Changes in age-standardised DALYs assessed with the Socio-demographic Index between 1990 and 2016 were variable.
Multiple sclerosis is not common but is a potentially severe cause of neurological disability throughout adult life. Prevalence has increased substantially in many regions since 1990. These findings will be useful for resource allocation and planning in health services. Many regions worldwide have few or no epidemiological data on multiple sclerosis, and more studies are needed to make more accurate estimates.
Bill & Melinda Gates Foundation.
Transition‐metal dichalcogenides (TMDCs) monolayers have been considered a perfect platform for realizing exciton‐polariton at room temperature due to their direct bandgap and large binding energy of ...exciton. It is well established that strong coupling depends on the field enhancement induced by optical nanocavity with a high‐quality factor (Q‐factor). In this work, the enhanced strong coupling between the exciton of TMDC monolayer and the cavity resonance based on a symmetry protected magnetic dipole (MD) bound state in the continuum (BIC) and electric toroidal dipole (TD) BIC is demonstrated. It is found that strong coupling can be realized between the exciton in a TMDC monolayer and quasi‐BIC (QBIC) by varying the incidence angle, period of the grating, the width of the slit, and the position of the slit for symmetry protected BIC. Besides, strong coupling between exciton and TD BIC is also demonstrated by integrating a WSe2 monolayer onto a compound grating. It is found that Rabi‐splitting strongly depends on the location of TMDC monolayer, Q‐factor of the resonator, and the thickness of the structure. By carefully adjusting these three critical parameters, Rabi‐splitting can be up to 38 (1L‐WSe2), 65 (1L‐WS2), 40 (1L‐MoSe2), and 60 meV(1L‐MoS2).
Enhanced strong coupling is realized between the exciton of transition‐metal dichalcogenide (TMDC) monolayers and bound states in the continuum. It is demonstrated that Rabi‐splitting strongly depends on the location of the TMDC monolayer, Q‐factor, and the thickness of the structure. After optimizing the structure, Rabi‐splitting of 38 (1L‐WSe2), 65 (1L‐WS2), 40 (1L‐MoSe2), and 60 meV(1L‐MoS2), have been achieved.
Olaparib (OLA) is a PARP inhibitor drug which has been recently approved by the Food and Drug Administration (FDA) for the treatment of ovarian and breast cancer. A convenient analytical tool for the ...quantitation of OLA in its dosage form and plasma samples was urgently needed. This study describes, for the first time, the development of two different label-free and sensitive fluorescence-based platforms for the pharmaceutical and bioanalysis of OLA. These platforms were microwell-assisted with a fluorescence microplate reader (MW-FLR) and high-performance liquid chromatography with fluorescence detection (HPLC-FD). Both MW-FLR and HPLC-FD employed the native fluorescence of OLA as an analytical signal. The MW-FLR involved measuring the fluorescence signals in 96-well white-opaque plates. The HPLC-FD involved chromatographic separation of OLA and duvelisib (DUV), as an internal standard on a Nucleosil-CN HPLC column (250 mm length × 4.6 mm i.d., 5 µm particle diameter) with a mobile phase composed of acetonitrile: water (25:75, v/v) pumped at a flow rate of 1.7 mL/min. Elution of OLA and DUV was detected using a fluorescence detector. The optimal conditions of both MW-FLR and HPLC-FD were established, and they were validated according to the guidelines of the International Council for Harmonization for the validation of analytical procedures. The linear ranges of MW-FLR and HPLC-FD were 25–1000 and 5–200 ng/mL, respectively, with limits of detection of 15 and 1.7 ng/mL, respectively. The accuracy and precision of both platforms were confirmed as the recovery values were ≥98.2% and the relative standard deviations (RSD) were ≤2.89%. Both methodologies were satisfactorily applied to the quantitation of OLA in its commercial dosage form (Lynparza® tablets) and plasma samples with high accuracy and precision. The greenness of both MW-FLR and HPLC-FD was assessed using two different multiple parameter-based metric tools, and the results proved their greenness and adherence to the requirements of green analytical approaches. Both platforms have simple procedures and acceptable levels of analytical throughput. In conclusion, the proposed MW-FLR and HPLC-FD are valuable tools for routine use in quality control and clinical laboratories for the quantitation of OLA for the purposes of pharmaceutical quality control, pharmacokinetic studies, and bioequivalence testing.
Recently developed halide perovskite semiconductors are viewed as an excellent platform to realize exciton‐polariton at room temperature due to their large oscillation strength. Here, the optimized ...strong coupling between the exciton of perovskite and quasi‐bound state in the continuum (QBIC) with high‐quality factor (Q‐factor), supported by all‐perovskite metagrating, including magnetic dipole (MD)‐QBIC and toroidal dipole (TD)‐QBIC is demonstrated. By taking advantage of extreme electric field confinement enabled by a high‐Q mode, it is found that the maximum Rabi splitting can be enhanced up to a record high value of 400 meV, almost twice the Rabi splitting reported in the same perovskite‐based subwavelength metasurface. The simulation results reveal that both the Q‐factor of QBIC mode and the thickness of the perovskite metasurface play dominant roles in the enhanced strong coupling. It is also demonstrated that adding a protection layer of poly(methyl methacrylate) on the top of the perovskite metagrating has a negligible effect on the maximized Rabi‐splitting. These results suggest a new approach for studying exciton‐polaritons and may pave the way toward flexible, large‐scale, and low‐cost integrated polaritonic devices and the realization of polariton lasing at room temperature.
Strong coupling between the exciton of perovskite and quasi‐bound state in the continuum (QBIC) with high‐quality factor (Q‐factor), supported by all‐perovskite metagrating, including magnetic dipole‐QBIC and toroidal dipole‐QBIC is demonstrated. The simulation results reveal that both the Q‐factor of QBIC mode and the thickness of the perovskite metasurface play dominant roles in the enhanced strong coupling.
suppression of methylation inhibitors (epigenetic genes) in hepatocarcinogenesis induced by diethylnitrosamine using glycyrrhetinic acid.
In the current work, we investigated the effect of sole GA ...combined with different agents such as doxorubicin (DOX) or probiotic bacteria (
) against hepatocarcinogenesis induced by diethylnitrosamine to improve efficiency. The genomic DNA was isolated from rats' liver tissues to evaluate either methylation-sensitive or methylation-dependent resection enzymes. The methylation activity of the targeting genes DLC-1, TET-1, NF-kB, and STAT-3 was examined using specific primers and cleaved DNA products. Furthermore, flow cytometry was used to determine the protein expression profiles of DLC-1 and TET-1 in treated rats' liver tissue.
Our results demonstrated the activity of GA to reduce the methylation activity in TET-1 and DLC-1 by 33.6% and 78%, respectively. As compared with the positive control. Furthermore, the association of GA with DOX avoided the methylation activity by 88% and 91% for TET-1 and DLC-1, respectively, as compared with the positive control. Similarly, the combined use of GA with probiotics suppressed the methylation activity in the TET-1 and DLC-1 genes by 75% and 81% for TET-1 and DLC-1, respectively. Also, GA and its combination with bacteria attenuated the adverse effect in hepatocarcinogenesis rats by altering potential methylomic genes such as NF-kb and STAT3 genes by 76% and 83%, respectively.
GA has an ameliorative effect against methylation inhibitors in hepatocellular carcinoma (HCC) by decreasing the methylation activity genes.
Shigella and enterotoxigenic Escherichia coli (ETEC) are bacterial pathogens that are frequently associated with diarrhoeal disease, and are a significant cause of mortality and morbidity worldwide. ...The Global Burden of Diseases, Injuries, and Risk Factors study 2016 (GBD 2016) is a systematic, scientific effort to quantify the morbidity and mortality due to over 300 causes of death and disability. We aimed to analyse the global burden of shigella and ETEC diarrhoea according to age, sex, geography, and year from 1990 to 2016.
We modelled shigella and ETEC-related mortality using a Bayesian hierarchical modelling platform that evaluates a wide range of covariates and model types on the basis of vital registration and verbal autopsy data. We used a compartmental meta-regression tool to model the incidence of shigella and ETEC, which enforces an association between incidence, prevalence, and remission on the basis of scientific literature, population representative surveys, and health-care data. We calculated 95% uncertainty intervals (UIs) for the point estimates.
Shigella was the second leading cause of diarrhoeal mortality in 2016 among all ages, accounting for 212 438 deaths (95% UI 136 979–326 913) and about 13·2% (9·2–17·4) of all diarrhoea deaths. Shigella was responsible for 63 713 deaths (41 191–93 611) among children younger than 5 years and was frequently associated with diarrhoea across all adult age groups, increasing in elderly people, with broad geographical distribution. ETEC was the eighth leading cause of diarrhoea mortality in 2016 among all age groups, accounting for 51 186 deaths (26 757–83 064) and about 3·2% (1·8–4·7) of diarrhoea deaths. ETEC was responsible for about 4·2% (2·2–6·8) of diarrhoea deaths in children younger than 5 years.
The health burden of bacterial diarrhoeal pathogens is difficult to estimate. Despite existing prevention and treatment options, they remain a major cause of morbidity and mortality globally. Additional emphasis by public health officials is needed on a reduction in disease due to shigella and ETEC to reduce disease burden.
Bill & Melinda Gates Foundation.
Rotavirus infection is the global leading cause of diarrhea-associated morbidity and mortality among children younger than 5 years.
To examine the extent of rotavirus infection among children younger ...than 5 years by country and the number of deaths averted because of the rotavirus vaccine.
This report builds on findings from the Global Burden of Disease Study 2016, a cross-sectional study that measured diarrheal diseases and their etiologic agents. Models were used to estimate burden in data-sparse locations.
Diarrhea due to rotavirus infection.
Rotavirus-associated mortality and morbidity by country and year and averted deaths attributable to the rotavirus vaccine by country.
Rotavirus infection was responsible for an estimated 128 500 deaths (95% uncertainty interval UI, 104 500-155 600) among children younger than 5 years throughout the world in 2016, with 104 733 deaths occurring in sub-Saharan Africa (95% UI, 83 406-128 842). Rotavirus infection was responsible for more than 258 million episodes of diarrhea among children younger than 5 years in 2016 (95% UI, 193 million to 341 million), an incidence of 0.42 cases per child-year (95% UI, 0.30-0.53). Vaccine use is estimated to have averted more than 28 000 deaths (95% UI, 14 600-46 700) among children younger than 5 years, and expanded use of the rotavirus vaccine, particularly in sub-Saharan Africa, could have prevented approximately 20% of all deaths attributable to diarrhea among children younger than 5 years.
Rotavirus-associated mortality has decreased markedly over time in part because of the introduction of the rotavirus vaccine. This study suggests that prioritizing vaccine introduction and interventions to reduce diarrhea-associated morbidity and mortality is necessary in the continued global reduction of rotavirus infection.
Cancer is a severe health condition and considered one of the major healthcare issues and is in need of innovative strategy for a cure. The current study aimed to investigate the chemical profile of
...L. and a potential molecular approach to explain its regulation in cancer progression through an inflammatory mediator (COX-2) in A549 non-small lung cancer cell lines via in silico, mechanistic and molecular aspects.
was extracted and then subjected to a CCK-8 cell viability assay in different cancer cell lines including MDA-MB-231, A549 and HCT-116. Total extract was subjected to several chromatographic techniques to yield orientin (OT); the structure was elucidated by inspection of NMR spectroscopic data. To achieve anticancer effects of OT, a cell viability assay using a CCK-8 kit, immunoprecipitation by Western blot, cell migration using a wound healing assay, cell invasion using a Matrigel-Transwell assay, apoptosis by AO/EB dual staining, flow cytometric analysis and DAPI staining, a silenced COX-2 model to determine PGE-2 production and real-time PCR and Western blot of BCL-2, CYP-1A1, iNOS and COX-2 markers were carried out. The results demonstrated that OT decreased the cell proliferation and controlled cell migration and invasive properties. OT destabilized the COX-2 mRNA and downregulated its expression in A549 cell lines. Virtual binding showed interaction (binding energy -10.43) between OT and COX-2 protein compared to the selective COX-2 inhibitor celecoxib (CLX) (binding energy -9.4). The OT-CLX combination showed a superior anticancer effect. The synergistic effect of OT-CLX combination was noticed in controlling the migration and invasion of A549 cell lines. OT-CLX downregulated the expression of BCL-2, iNOS and COX-2 and activated the proapoptotic gene CYP-1A1. OT mitigated the COX-2 expression via upregulation of miR-26b and miR-146a. Interestingly, COX-2-silenced transfected A549 cells exhibited reduced expression of miR-26b and miR-146a. The findings confirmed the direct interaction of OT with COX-2 protein. PGE-2 expression was quantified in both naïve and COX-2-silenced A549 cells. OT downregulated the release of PGE-2 in both tested conditions. These results confirmed the regulatory effect of OT on A549 cell growth in a COX-2-dependent manner. OT activated apoptosis via activation of CYP-1A1 expression in an independent manner. These results revealed that the OT-CLX combination could serve as a potential synergistic treatment for effective inflammatory-mediated anticancer strategies.
Probiotics can potentially prevent and treat diseases. We examined the inhibitory activity of bacteriocin-like inhibitory substances (BLISs) from potentially probiotic lactobacilli and streptococci ...on
and non-
clinical isolates from women with vulvovaginitis. Using agar well diffusion assays, BLISs inhibited both
and non-
isolates. The BLIS from
isolates had the highest anti-
activity (33/45; 73.3%), followed by BLISs from isolates of
subsp.
(31/45; 68.9%),
(30/45; 66.7%)
subsp.
(30/45; 66.7%), and
(30/45; 66.7%). Upon characterization according to the retained activity under variable physical and chemical conditions, the BLISs showed stability against heat, pH, and surfactants, but were protease-sensitive, which suggests a proteinaceous nature of the active substances. Using crystal violet assays, the BLISs reduced the
biofilm biomass significantly as compared to a control group that lacked BLISs. In vivo testing of the antagonistic activity was performed using the
(
) larvae model. BLISs significantly improved survival in
larvae treated with
isolates on the first, second, and seventh days, as compared to larvae inoculated with
only (
< 0.01). The results show that BLISs can be used as biotherapeutic agents in vulvovaginal candidiasis.
Diarrhoea is a leading cause of death and illness globally among children younger than 5 years. Mortality and short-term morbidity cause substantial burden of disease but probably underestimate the ...true effect of diarrhoea on population health. This underestimation is because diarrhoeal diseases can negatively affect early childhood growth, probably through enteric dysfunction and impaired uptake of macronutrients and micronutrients. We attempt to quantify the long-term sequelae associated with childhood growth impairment due to diarrhoea.
We used the Global Burden of Diseases, Injuries, and Risk Factors Study framework and leveraged existing estimates of diarrhoea incidence, childhood undernutrition, and infectious disease burden to estimate the effect of diarrhoeal diseases on physical growth, including weight and height, and subsequent disease among children younger than 5 years. The burden of diarrhoea was measured in disability-adjusted life-years (DALYs), a composite metric of mortality and morbidity. We hypothesised that diarrhoea is negatively associated with three common markers of growth: weight-for-age, weight-for-height, and height-for-age Z-scores. On the basis of these undernutrition exposures, we applied a counterfactual approach to quantify the relative risk of infectious disease (subsequent diarrhoea, lower respiratory infection, and measles) and protein energy malnutrition morbidity and mortality per day of diarrhoea and quantified the burden of diarrhoeal disease due to these outcomes caused by undernutrition.
Diarrhoea episodes are significantly associated with childhood growth faltering. We found that each day of diarrhoea was associated with height-for-age Z-score (–0·0033 95% CI −0·0024 to −0·0041; p=4·43 × 10−14), weight-for-age Z-score (–0·0077 –0·0058 to −0·0097; p=3·19 × 10−15), and weight-for-height Z-score (–0·0096 –0·0067 to −0·0125; p=7·78 × 10−11). After addition of the DALYs due to the long-term sequelae as a consequence of undernutrition, the burden of diarrhoeal diseases increased by 39·0% (95% uncertainty interval UI 33·0–46·6) and was responsible for 55 778 000 DALYs (95% UI 49 125 400–62 396 200) among children younger than 5 years in 2016. Among the 15 652 300 DALYs (95% UI 12 951 300–18 806 100) associated with undernutrition due to diarrhoeal episodes, more than 84·7% are due to increased risk of infectious disease, whereas the remaining 15·3% of long-term DALYs are due to increased prevalence of protein energy malnutrition. The burden of diarrhoea has decreased substantially since 1990, but progress has been greater in long-term (78·7% reduction 95% UI 69·3–85·5) than in acute (70·4% reduction 95% UI 61·7–76·5) DALYs.
Diarrhoea represents an even larger burden of disease than was estimated in the Global Burden of Disease Study. In order to adequately address the burden of its long-term sequelae, a renewed emphasis on controlling the risk of diarrhoea incidence may be required. This renewed effort can help further prevent the potential lifelong cost on child health, growth, and overall potential.
Bill & Melinda Gates Foundation.
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