The epidemic of T2DM is rising across the globe. Systemic inflammation plays a pivotal role in the pathogenesis and complications of T2DM. Combination of two or more oral hypoglycemic agents (OHA) is ...widely prescribed in patients with T2DM, however many patients have poor glycemic control despite receiving combination therapy. The new antidiabetic drugs are relatively costly or many patients have anxiety over the use of injectable insulin. The objective of this observational study was to investigate the effectiveness and tolerability of hydroxychloroquine (HCQ) in T2DM patients uncontrolled on multiple OHA and despite high sugar level not willing to initiate insulin therapy in a real-world clinical setting.
A prospective, investigator-initiated, observational, single-centred study was conducted where 250 patients (18-65 years) with T2DM for more than 5 years, with uncontrolled glycemia despite on a combination of multiple OHA, HbA1c between ≥7% and <10.5%, FPG >130 mg/dL or PPG >180 mg/dL and BMI between >25 and <39 kg/m2, were prescribed hydroxychloroquine sulphate 400 mg once daily for 48 weeks. Percentage of drugs used at the baseline were as follows: metformin 2000 mg (100%), glimepiride 4 mg (100%), pioglitazone 30 mg (100%), sitagliptin 100 mg (100%), canagliflozin 300 mg (52.4%), empagliflozin 25 mg (22.8%), dapagliflozin 10 mg (17.6%) and voglibose 0.3 mg (62%). Mean change in HbA1c, blood glucose and hs-CRP at baseline, week 12, 24 and 48 were assessed using the paired t-test.
After 48 weeks of add-on treatment with HCQ, almost all SGLT-2 inhibitors were withdrawn; metformin dose was reduced to 1000 mg, glimepiride reduced to 1 mg and sitagliptin reduced to 50 mg OD. Patients continued to have good glycemic control. HbA1c was reduced from 8.83% to 6.44%. Reduction in FPG was 40.78% (baseline 177.30 mg/dL) and PPG was reduced by 58.95% (baseline 329.86 mg/dL). Change in mean body weight was -4.66 Kg. The reduction in glycemic parameters and mean body weight was significant (p < 0.0001). Hs-CRP was significantly reduced from 2.70±1.98 mg/L to 0.71±0.30 mg/L 9 (p < 0.0001). More reduction in glycemic parameters and body weight was observed among the patients with higher hs-CRP (> 3 mg/L) as compared to patients with baseline hs- CRP ≤ 3 mg/L. Most common adverse events reported with the drug therapy were GI irritation (3.6%) and hypoglycemia (2%). None of the patients required medical assistance for hypoglycemia.
Add-on treatment of HCQ effectively improved glycemic control in T2DM patients uncontrolled on multiple antidiabetic drugs. By virtue of its antidiabetic and anti-inflammatory properties, it may emerge as a valuable therapeutic intervention for the patients with T2DM.
In the 21st century, environmental problems are wreaking havoc, and sustainability is now of primary importance. Several external factors like population growth, industrialization, development, and ...overexploitation of natural resources play a crucial role in environmental degradation. Thus, the present study endeavors to explore the impact of price sensitivity, governments green interventions and green product availability on green buying intention through the lenses of the theory of planned behavior and the theory of consumption values. It also intends to examine the moderating effect of demographic factors on green buying intention. A cross‐sectional study was carried out. Responses were gathered through a self‐administered questionnaire‐based survey. The final data set of 708 respondents were subjected to structural equation modeling for hypothesis testing. Price sensitivity, government green interventions, and green product availability show negative and significant interaction effects. Perceived behavioral control shows a relatively more substantial impact on green buying intention. Indian consumers from the age group of 41–50 years relatively have higher intention toward green buying. Overall, gender does not reveal any different approaches to environmentally friendly products. Green marketers must focus on communicating the availability of green products to reduce perceived difficulty.
The world faces continuous environmental degradation because of extreme industrialization, construction, and overexploitation of natural resources. This degradation has started to create ...consciousness and attitude towards pro-environmental buying and consumption. Green consumer behavior has gained significant research attention world-wide attributed to its ability to reduce environmental damage. Thus, this research explores the extended model based on the theory of planned behavior (TPB) and the value-attitude-behavior hierarchy in Indian demography. Environmental and health awareness is used as a human value (internal indirect variable) in the extended TPB model. This study administered a cross-sectional survey on the corporate executive, executive MBA students, and regular MBA students of Indian top business schools and firms. Models are validated, and hypotheses tested using variance-based structured equation modeling on the 350+ clean collected sample. The studies’ outcome reflected the non-linear relationship between the independent variables and dependent variables (green buying behavior) of the modified theory of planned behavior (TPB) model. Perceived behavioral control is found as an important independent factor compelling Indian consumers towards green buying behavior. The modified TPB model also gave considerable outcomes in the Indian demography. Government organizations and corporate shall use the results to inculcate more buying behavior among Indian consumers.
All-electric (AES) ship power system (SPS) generally employs energy storage (ESS) to improve operation efficiency, redundancy, and flexibility while reducing environmental impacts. Depending on the ...operating characteristic, ramp rate, and load variation of the SPS, single or hybrid energy storage systems (HESS) with different operating characteristics are utilized to prevent frequent cycling, high depth of discharge (DOD), and accelerated degradation. Hence, this research work focuses on the coordination of optimal voyage, and multi-objective energy management of AES with HESS to optimize the vessel route, operation cost, emission, and degradation of ESS. The optimal route planning is carried out as a dynamic programming problem based on the sea states, and augmented <inline-formula><tex-math notation="LaTeX">\epsilon</tex-math></inline-formula>-constraint and reactive approach to energy management strategy are adopted to solve the energy dispatch of the AES while addressing the uncertainty present in the load forecasting. The simulation results indicate that the voyage planning with the consideration of the sea states has strong influences on the path taken and velocity of the AES which in term will influence the propulsion power requirement. It also indicates that the operating characteristic of the HESS and uncertainty present in the load forecasting should be carefully addressed to achieve a realistic operation schedule.
The study aims to explore the effect of dimensions of green marketing orientation (GMO) on green innovation and organizational performance utilizing the fundamental concepts of GMO theory, ...institutional theory, and resource‐based theory, or natural resource‐based view. In this research, we mainly explore the unplumbed effect of internal (IGMO), strategic (SGMO), and tactical green marketing orientation (TGMO) of the firm using the GMO theory. Although few scientific attempts tried to measure the effect of IGMO, SGMO, and TGMO, a majority of them disdained the idea of its integrated effect and adopted a futile approach while positioning these constructs in their model. In addition, we investigated stakeholders' role (moderating) in green innovation practices and organizational performance. The proposed model is tested using survey data collected from 201 top and middle‐level working professionals from manufacturing to service industries in India. We used a structured questionnaire and covariance‐based structure equation modeling for the path estimation. All three dimensions showed a direct positive significant effect on green innovation. Only tactical TGMO showed a direct effect on organizational performance, while the other two showed an indirect effect only on organizational performance mediated through green innovation. The study also established the moderating effect of stakeholders' view on the relationships between green innovation and organizational performance. Conclusively, we contribute to GMO theory by extending the scope for further academic/market validation and concurrently advancing managerial inferences for business strategists and market practitioners on sustainable organizational development.
Alloys-based materials have now become advanced from conventional alloys to multi-principal elements and open new areas of applications. High Entropy Alloys are drawn considerable attention because ...of their unique properties, which can be tuned based on the requirements. High entropy materials have extraordinary mechanical properties, corrosion resistance, thermal stability, and other promising functional properties, which makes them to be used as a catalysis for water splitting, electrodes in batteries for charge storage in supercapacitor and as a hydrogen storage material. Thus the high entropy alloy now becomes an emerging advanced material. Moreover, in the last six years, several research articles appeared which described the excellent magnetic properties of high entropy alloys. More than four principal elements help to tune the magnetic properties along with other properties like mechanical, corrosion, etc., which are required for industrial applications of magnetic materials. The magnetic properties of HEAs are highly dependent on the phase structure, microstructure, synthesis route, processing parameter, and alloying elements. This review article summarized the different features of high entropy alloys, core effects, synthesis methods, and state-of-the-art magnetic properties of the High Entropy alloys. A separate section is also devoted to the magnetic properties of high entropy oxide. Also, this review is underlying different principles that have importance on the future development of magnetic HEAsfor industrial applications.
Aluminum electrolytic capacitors are some of the weakest components in a power converter system. Therefore, condition monitoring of capacitors can prevent unexpected system downtime due to capacitor ...failures. This article proposes a condition monitoring system for electrolytic capacitors used as dc-link capacitors in front-end rectifier-fed three-phase inverters. The proposed methodology is based on equivalent series resistance (ESR) and capacitance estimation using the Goertzel algorithm. The ESR is used as the degradation indicator, whereas the capacitance value is used as both degradation indicator and temperature-sensitive electrical parameter to estimate core or hotspot temperature. Even though the use of capacitance to estimate hotspot temperature has already been proposed, this article tackles the practical difficulties associated with capacitor core-temperature estimation using the capacitance and demonstrates a successful implementation strategy for applying this method in power converters to estimate core temperature online. It also introduces a self-calibration procedure to mitigate ageing-related errors in temperature estimation. An experimental setup is used to verify the proposed conditioning monitoring system. The experimental results prove the effectiveness and accuracy of the proposed technique.
The GroEL/ES chaperonin system functions as a protein folding cage. Many obligate substrates of GroEL share the (βα)8 TIM-barrel fold, but how the chaperonin promotes folding of these proteins is not ...known. Here, we analyzed the folding of DapA at peptide resolution using hydrogen/deuterium exchange and mass spectrometry. During spontaneous folding, all elements of the DapA TIM barrel acquire structure simultaneously in a process associated with a long search time. In contrast, GroEL/ES accelerates folding more than 30-fold by catalyzing segmental structure formation in the TIM barrel. Segmental structure formation is also observed during the fast spontaneous folding of a structural homolog of DapA from a bacterium that lacks GroEL/ES. Thus, chaperonin independence correlates with folding properties otherwise enforced by protein confinement in the GroEL/ES cage. We suggest that folding catalysis by GroEL/ES is required by a set of proteins to reach native state at a biologically relevant timescale, avoiding aggregation or degradation.
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•GroEL/ES chaperonin catalyzes folding of proteins with TIM-barrel domains•Protein confinement in the GroEL/ES cage results in segmental folding•Segmental folding reduces the entropic energy barrier to folding•Folding by GroEL/ES resembles that of chaperonin-independent TIM-barrel proteins
A chaperonin catalyzes rapid substrate folding by promoting stepwise transitions in structure formation; in contrast, spontaneous folding is slow and characterized by one major structural transition.
Lipid and protein tyrosine phosphatase, phosphatase and tension homologue (PTEN), is a widely known negative regulator of insulin/phosphoinositide 3-kinase signaling. Down-regulation of PTEN is thus ...widely documented to ameliorate insulin resistance in peripheral tissues such as skeletal muscle and adipose. However, not much is known about its exact role in neuronal insulin signaling and insulin resistance. Moreover, alterations of PTEN in neuronal systems have led to discovery of several unexpected outcomes, including in the neurodegenerative disorder Alzheimer's disease (AD), which is increasingly being recognized as a brain-specific form of diabetes. In addition, contrary to expectations, its neuron-specific deletion in mice resulted in development of diet-sensitive obesity. The present study shows that PTEN, paradoxically, positively regulates neuronal insulin signaling and glucose uptake. Its down-regulation exacerbates neuronal insulin resistance. The positive role of PTEN in neuronal insulin signaling is likely due to its protein phosphatase actions, which prevents the activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK), the kinases critically involved in neuronal energy impairment and neurodegeneration. Results suggest that PTEN acting through FAK, the direct protein substrate of PTEN, prevents ERK activation. Our findings provide an explanation for unexpected outcomes reported earlier with PTEN alterations in neuronal systems and also suggest a novel molecular pathway linking neuronal insulin resistance and AD, the two pathophysiological states demonstrated to be closely linked.
Cancer is an uncontrolled and abnormal growth of cells in the body. Gene that guards the cell cycle and function as tumor suppressor is p53 (also called as the guardian of the genome) which is ...encoded by the TP53 gene. Various events like DNA damage, heat shock, hypoxia and oncogene over expression, results in activation of p53.Thus, it plays a major role as a regulatory protein which regulates various diverse biological responses, responsible for genetic stability by preventing genome mutation. More than 50% mutations in human cancers along with the increase in expression of murine double minute 2 gene (mdm2), has been found as one of the reason for cancer progression. Murine double minute 2 (MDM2) is the negative regulator of p53 gene forming an autoregulatory feedback loop controlling each other cellular levels. Murine double minute 2 is unique E3 ubiquitin ligase protein which is responsible for ubiquitination and degradation of p53 gene. Many drugs/compounds have been developed for reactivation of p53 gene by inhibiting MDM2 interaction with p53, using MDM2 antagonism, inhibiting E3 ubiquitination of p53. Many compounds have entered clinical trials in haematological malignancies. This review will throw some light on reactivation of p53 gene by MDM2 and its homologues.
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