Peripheral vascular disease of the lower extremities comprises a clinical spectrum that extends from no symptoms to presentation with critical limb ischemia (CLI). Bone marrow derived Mesenchymal ...Stem Cells (BM- MSCs) may ameliorate the consequences of CLI due to their combinatorial potential for inducing angiogenesis and immunomodulatory environment in situ. The primary objective was to determine the safety of BM- MSCs in patients with CLI.
Prospective, double blind randomized placebo controlled multi-center study was conducted in patients with established CLI as per Rutherford classification in category II-4, III-5, or III-6 with infra-inguinal arterial occlusive disease and were not suitable for or had failed revascularization treatment. The primary end point was incidence of treatment - related adverse events (AE). Exploratory efficacy end points were improvement in rest pain, increase in Ankle Brachial Pressure Index (ABPI), ankle pressure, healing of ulcers, and amputation rates. Twenty patients (BM-MSC: Placebo = 1:1) were administered with allogeneic BM-MSCs at a dose of 2 million cells/kg or placebo (PlasmaLyte A) at the gastrocnemius muscle of the ischemic limb.
Improvement was observed in the rest pain scores in both the arms. Significant increase in ABPI and ankle pressure was seen in BM-MSC arm compared to the placebo group. Incidence of AEs in the BM-MSC arm was 13 vs. 45 in the placebo arm where as serious adverse events (SAE) were similar in both the arms (5 in BM-MSC and 4 in the placebo group). SAEs resulted in death, infected gangrene, amputations in these patients. It was observed that the SAEs were related to disease progression and not related to stem cells.
BM-MSCs are safe when injected IM at a dose of 2 million cells/kg body weight. Few efficacy parameters such as ABPI and ankle pressure showed positive trend warranting further studies.
NIH website (http://www.clinicaltrials.gov/ct2/show/NCT00883870).
Monitoring particulate matter air quality from spaceborne measurements is largely confined to relating columnar satellite retrievals of aerosol optical thickness (AOT) with ground measurements of ...PM2.5 mass concentration. However, vertical distribution of aerosols and meteorological effects such as wind speed, temperature, and humidity also play a major role in this AOT‐PM2.5 relationship. In this study, using 3 years of coincident hourly PM2.5 mass concentration (PM2.5 or PM2.5), Moderate Resolution Imaging Spectroradiometer–derived AOT, and rapid update cycle meteorological fields, we developed multiple regression equations as function of season for 85 P.M2.5 monitors over the southeastern United States. Our goal is to examine whether the use of meteorological fields will improve the relationship between PM2.5 and AOT. Our results indicate that there is up to threefold improvement in the correlation coefficients while using meteorological information through multiple regression methods compared to two variant regression (AOT versus PM2.5) equations. A 20–50% improvement in root‐mean‐square error is observed when adding temperature and boundary layer height to the AOT‐PM2.5 relationship. The best agreement between AOT and PM2.5 was found during summer and in well‐mixed boundary layer regimes. Since boundary layer heights are readily available from model simulations over the United States, they can be used as a good surrogate for estimating aerosol heights in conjunction with space‐ and ground‐based lidars. These results and analysis are useful to research and operational communities that seek to improve the use of satellite information for assessing surface PM2.5.
Osteoarthritis (OA) is a degenerative disease of the connective tissue and progresses with age in the older population or develops in young athletes following sports-related injury. The articular ...cartilage is especially vulnerable to damage and has poor potential for regeneration because of the absence of vasculature within the tissue. Normal load-bearing capacity and biomechanical properties of thinning cartilage are severely compromised during the course of disease progression. Although surgical and pharmaceutical interventions are currently available for treating OA, restoration of normal cartilage function has been difficult to achieve. Since the tissue is composed primarily of chondrocytes distributed in a specialized extracellular matrix bed, bone marrow stromal cells (BMSCs), also known as bone marrow-derived 'mesenchymal stem cells' or 'mesenchymal stromal cells', with inherent chondrogenic differentiation potential appear to be ideally suited for therapeutic use in cartilage regeneration. BMSCs can be easily isolated and massively expanded in culture in an undifferentiated state for therapeutic use. Owing to their potential to modulate local microenvironment via anti-inflammatory and immunosuppressive functions, BMSCs have an additional advantage for allogeneic application. Moreover, by secreting various bioactive soluble factors, BMSCs can protect the cartilage from further tissue destruction and facilitate regeneration of the remaining progenitor cells in situ. This review broadly describes the advances made during the last several years in BMSCs and their therapeutic potential for repairing cartilage damage in OA.
Using a combined Terra and Aqua Moderate Resolution Imaging Spectroradiometer (MODIS) mid-visible aerosol optical depth (AOD) product at 0.1 × 0.1-degree spatial resolution and collocated surface ...PM2.5 (particulate matter with aerodynamic diameter smaller than 2.5 μm) monitors, we provide a global five-year (2015–2019) assessment of the spatial and seasonal AOD–PM2.5 relationships of slope, intercepts, and correlation coefficients. Only data from ground monitors accessible through an open air-quality portal that are available to the worldwide community for air quality research and decision making are used in this study. These statistics that are reported 1 × 1-degree resolution are important since satellite AOD is often used in conjunction with spatially limited surface PM2.5 monitors to estimate global distributions of surface particulate matter concentrations. Results indicate that more than 3000 ground monitors are now available for PM2.5 studies. While there is a large spread in correlation coefficients between AOD and PM2.5, globally, averaged over all seasons, the correlation coefficient is 0.55 with a unit AOD producing 54 μgm−3 of PM2.5 (Slope) with an intercept of 8 μgm−3. While the number of surface PM2.5 measurements has increased by a factor of 10 over the last decade, a concerted effort is still needed to continue to increase these monitors in areas that have no surface monitors, especially in large population centers that will further leverage the strengths of satellite data.
Extra-pulmonary tuberculosis (EPTB) is recognized mainly as a secondary manifestation of a primary tuberculosis (TB) infection in the lungs contributing to a high incidence of morbidity and ...mortality. The TB bacilli upon reactivation maneuver from the primary site disseminating to other organs. Diagnosis and treatment of EPTB remains challenging due to the abstruse positioning of the infected organs and the associated invasiveness of sample acquisition as well as misdiagnosis, associated comorbidities, and the inadequacy of biomarkers. Female genital tuberculosis (FGTB) represents the most perilous form of EPTB leading to poor uterine receptivity (UR), recurrent implantation failure and infertility in females. Although the number of TB cases is reducing, FGTB cases are not getting enough attention because of a lack of clinical awareness, nonspecific symptoms, and inappropriate diagnostic measures. This review provides an overview for EPTB, particularly FGTB diagnostics and treatment challenges. We emphasize the need for new therapeutics and highlight the need for the exaction of biomarkers as a point of care diagnostic. Nuclear receptors have reported role in maintaining UR, immune modulation, and TB modulation; therefore, we postulate their role as a therapeutic drug target and biomarker that should be explored in FGTB.
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•COVID-19 Lockdown in India significantly improved air quality over many cities.•Surface and satellite data shows 42–60 % reduction in PM2.5 and 46–61 % in NO2.•Improved AQI (21–56 %) ...benchmarks the opportunity for Air Quality policy changes.
The strict nationwide lockdown imposed in India starting from 25th March 2020 to prevent the spread of COVID-19 disease reduced the mobility and interrupted several important anthropogenic emission sources thereby creating a temporary air quality improvement. This study conducts a multi-scale (national-regional-city), multi-species, and multi-platform analysis of air pollutants and meteorological data by synergizing surface and satellite observations. Our analysis suggests a significant reduction in surface measurements of nitrogen dioxide (NO2) (46–61 %) and fine particulate matter (PM2.5) (42–60 %) during the lockdown period that are also corroborated by the reduction in satellite observed aerosol optical depth (AOD) (3–56 %) and tropospheric NO2 column density (25–50 %) data over multiple cities. Other species, namely coarse particulate matter (PM10) (24–62 %), ozone (22–56 %) also showed a substantial reduction whereas carbon monoxide (16–46 %), exhibited a moderate decline. In contrast, sulfur dioxide (SO2) levels did not show any defined reduction trend but rather increased in Mumbai, Bengaluru, and Kolkata. The temporary air quality improvement achieved by the painful natural experiment of this pandemic has helped demonstrate the importance of reducing emissions from other sectors along with transportation and industry to achieve the national air quality targets in the future.
The escalation in living standards and adoption of 'Western lifestyle' has an allied effect on the increased allergy and asthma burden in both developed and developing countries. Current scientific ...reports bespeak an association between allergic diseases and metabolic dysfunction; hinting toward the critical requirement of organized lifestyle and dietary habits. The ubiquitous nuclear receptors (NRs) translate metabolic stimuli into gene regulatory signals, integrating diet inflences to overall developmental and physiological processes. As a consequence of such promising attributes, nuclear receptors have historically been at the cutting edge of pharmacy world. This review discusses the recent findings that feature the cardinal importance of nuclear receptors and how they can be instrumental in modulating current asthma pharmacology. Further, it highlights a possible future employment of therapy involving dietary supplements and synthetic ligands that would engage NRs and aid in eliminating both asthma and linked comorbidities. Therefore, uncovering new and evolving roles through analysis of genomic changes would represent a feasible approach in both prevention and alleviation of asthma.
Citrus medica
(Citron) is an underutilized fruit plant having various bioactive components in all parts of the plant. The major bioactive compounds present are iso-limonene, citral, limonene, ...phenolics, flavonones, vitamin C, pectin, linalool, decanal, and nonanal, accounting for several health benefits. Pectin and heteropolysachharides also play a major role as dietary fibers. The potential impact of citron and its bioactive components to prevent or reverse destructive deregulated processes responsible for certain diseases has attracted different researchers' attention. The fruit has numerous nutraceutical benefits, proven by pharmacological studies; for example, anti-catarrhal, capillary protector, anti-hypertensive, diuretic, antibacterial, antifungal, anthelmintic, antimicrobial, analgesic, strong antioxidant, anticancerous, antidiabetic, estrogenic, antiulcer, cardioprotective, and antihyperglycemic. The present review explores new insights into the benefits of citron in various body parts. Throughout the world, citron has been used in making carbonated drinks, alcoholic beverages, syrup, candied peels, jams, marmalade, cordials, and many other value added products, which suggests it is an appropriate raw material to develop healthy processed food. In the present review, the fruit taxonomical classification, beneficial phytochemicals, antioxidant activities, and health benefits are discussed.
Health benefits and products of
Citrus medica
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In addition to the standard resolution product (10km), the MODerate resolution Imaging Spectroradiometer (MODIS) Collection 6 (C006) data release included a higher resolution (3km). Other than ...accommodations for the two different resolutions, the 10 and 3km Dark Target (DT) algorithms are basically the same. In this study, we perform global validation of the higher-resolution aerosol optical depth (AOD) over global land by comparing against AErosol RObotic NETwork (AERONET) measurements. The MODIS-AERONET collocated data sets consist of 161410 high-confidence AOD pairs from 2000 to 2015 for Terra MODIS and 2003 to 2015 for Aqua MODIS. We find that 62.5 and 68.4% of AODs retrieved from Terra MODIS and Aqua MODIS, respectively, fall within previously published expected error bounds of +/-(0.05+0.2 × AOD), with a high correlation (R = 0.87). The scatter is not random, but exhibits a mean positive bias of ∼ 0.06 for Terra and ∼ 0.03 for Aqua. These biases for the 3km product are approximately 0.03 larger than the biases found in similar validations of the 10km product. The validation results for the 3km product did not have a relationship to aerosol loading (i.e., true AOD), but did exhibit dependence on quality flags, region, viewing geometry, and aerosol spatial variability. Time series of global MODIS-AERONET differences show that validation is not static, but has changed over the course of both sensors' lifetimes, with Terra MODIS showing more change over time. The likely cause of the change of validation over time is sensor degradation, but changes in the distribution of AERONET stations and differences in the global aerosol system itself could be contributing to the temporal variability of validation.
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