Strategy For Treatment Of Type Research Articles

Effectiveness of workplace choice architecture modification for healthy eating and daily physical activity

BackgroundModifying the choice architecture of behavioural contexts can facilitate health behaviour change, but existing evidence builds mostly on small-scale interventions limited in duration, targets, strategies, and settings. We evaluated the effectiveness of a one-year hybrid type 2 implementation-effectiveness trial aimed at promoting healthy eating and daily physical activity with subtle modifications to the choice architecture of heterogeneous worksites. The intervention was contextualised to and integrated into the routine operations of each worksite. Effectiveness was evaluated in a quasi-experimental pre-post design.MethodsIntervention sites (n = 21) implemented a median of two (range 1–9) intervention strategies for healthy eating and one (range 1–5) for physical activity. Questionnaires pre (n = 1126) and post (n = 943) intervention surveyed employees’ behavioural patterns at work (food consumption: vegetables/roots, fruit/berries, nuts/almonds/seeds, sweet treats, fast food, water; physical activity: restorative movement, exercise equipment use, stair use). The post-intervention questionnaire also measured employees’ perception of and response to three intervention strategies: a packed lunch recipe campaign, a fruit crew-strategy, and movement prompts. Multi- and single-level regression models evaluated effectiveness, treating intervention as a continuous predictor formed of the site-specific dose (n intervention strategies employed) and mean quality (three-point rating per strategy halfway and at the end of the intervention) of implementation relevant to each outcome.ResultsMultinomial logistic regression models found the intervention significantly associated with a favourable change in employees’ fruit and berry consumption (interaction effect of time and implementation p = 0.006) and with an unfavourable change in sweet treat consumption (p = 0.048). The evidence was strongest for the finding concerning fruit/berry consumption—an outcome that sites with greater dose and quality of implementation targeted by using strategies that reduced the physical effort required to have fruit/berries at work and by covering multiple eating-related contexts at the worksite. The quality of implementation was positively associated with the perception of (p = 0.044) and response to (p = 0.017) the packed lunch recipes, and with response to the fruit crew-strategy (p < 0.001).ConclusionsThe results suggest that a contextualised, multicomponent choice architecture intervention can positively influence eating behaviour in diverse real-world settings over a one-year period, and that higher implementation quality can enhance intervention perception and response. However, outcomes may depend on the type of intervention strategies used and the extent of their delivery.

Strategies to increase the coverage of influenza and pneumonia vaccination in older adults: a systematic review and network meta-analysis.

It is urgent to implement interventions to increase vaccination rates of influenza/pneumonia vaccines in older adults, yet the effectiveness of different intervention strategies has not been thoroughly evaluated. We aimed to assess the effectiveness of intervention strategies for increasing the coverage of influenza/pneumonia vaccination in older adults. PubMed, Web of Science, Cochrane Library, Embase, China Biology Medicine disc, China National Knowledge Infrastructure and Wanfang were searched from 1 January 2000 to 1 October 2022. RCTs that assessed any intervention strategies for increasing influenza/pneumonia vaccination coverage or willingness in older adults were included. A series of random-effects network meta-analysis was conducted by using frequentist frameworks. Twenty-two RCTs involving 385,182 older participants were eligible for further analysis. Eight types of intervention strategies were evaluated. Compared with routine notification, health education (odds ratio [OR], 1.85 [95%CI, 1.19 to 2.88]), centralised reminder (OR, 1.63 [95%CI, 1.07 to 2.47]), health education + onsite vaccination (OR, 2.89 [95%CI, 1.30 to 6.39]), and health education + centralised reminder + onsite vaccination (OR, 20.76 [95%CI, 7.33 to 58.74]) could effectively improve the vaccination rate. The evidence grade was low or very low due to the substantial heterogeneity among studies. Our findings suggest that health education + centralised reminder + onsite vaccination may potentially be an effective strategy regardless of cost, but the evidence level was low. More rigorous trials are needed to identify the association between strategies and vaccination rates among older adults and to integrate such evidence into clinical care to improve vaccination rates.

Re-exploration of prognosis in type B thymomas: establishment of a predictive nomogram model

ObjectiveTo explore the risk factors for disease progression after initial treatment of type B thymomas using a predictive nomogram model.MethodsA single-center retrospective study of patients with type B thymoma was performed. The Cox proportional hazard model was used for univariate and multivariate analyses. Variables with statistical and clinical significance in the multivariate Cox regression were integrated into a nomogram to establish a predictive model for disease progression.ResultsA total of 353 cases with type B thymoma were retrieved between January 2012 and December 2021. The median follow-up was 58 months (range: 1–128 months). The 10-year progression-free survival (PFS) was 91.8%. The final nomogram model included R0 resection status and Masaoka stage, with a concordance index of 0.880. Non-R0 resection and advanced Masaoka stage were negative prognostic factors for disease progression (p < 0.001). No benefits of postoperative radiotherapy (PORT) were observed in patients with advanced stage and non-R0 resection (p = 0.114 and 0.284, respectively).ConclusionThe best treatment strategy for type B thymoma is the detection and achievement of R0 resection as early as possible. Long-term follow-up is necessary, especially for patients with advanced Masaoka stage and who have not achieved R0 resection. No prognostic benefits were observed for PORT.

Modern strategies for the treatment of type 2 diabetes in patients with stable coronary artery disease. Old goals, new opportunities (literature review)

The review summarizes and analyzes the available literature to provide information to clinicians about the best treatment strategies for type 2 diabetes in stable coronary artery disease. This data should help health care professionals make decisions in routine practice. 2023 European and Russian guidelines on type 2 diabetes suggest giving preference to glucose-lowering agents with proven benefits for the cardiovascular system, followed by drugs with proven safety for the cardiovascular system.

Supporting academic achievement of children in out-of-home care through effective interventions: results of a systematic review and meta-analyses

As students in out-of-home care are at high risk of school failure, it is imperative to promote academic skills through effective interventions. A systematic review of interventions aimed at improving academic achievement of out-of-home care was conducted to identify the most effective strategies for supporting literacy and mathematical skills. Data from 21 interventions, involving 2,049 children in out-of-home care, were synthesized through meta-analysis. Overall, the interventions had a significant impact on literacy (g = .242, 95 % CI [.180, .305], k = 21) and mathematical skills (g = .229, 95 % CI [.115, .343], p <.001, k = 14). Three main direct academic support strategies were compared to determine if one was superior to the others: tutoring, individualized support, and distribution of academic material. The results of subgroup analysis failed to detect any differences between effect sizes, most likely due to low statistical power. Thus, the main trends were discussed. Tutoring, as the most rigorously evaluated intervention, appeared to outperform other types of intervention strategies, especially in respect to mathematical skills, where the results remained robust despite potential methodological bias. However, it is essential to consider significant limitations when interpreting these results. Implications for practice and research are discussed.

LncRNA Malat1 regulates iPSC-derived β-cell differentiation by targeting the miR-15b-5p/Ihh axis

BackgroundDifferentiation of induced pluripotent stem cells (iPSCs)-derived β-like cells is a novel strategy for treatment of type 1 diabetes. Elucidation of the regulatory mechanisms of long noncoding RNAs (lncRNAs) in β-like cells derived from iPSCs is important for understanding the development of the pancreas and pancreatic β-cells and may improve the quality of β-like cells for stem cell therapy. Methodsβ-like cells were derived from iPSCs in a three-step protocol. RNA sequencing and bioinformatics analysis were carried out to screen the differentially expressed lncRNAs and identify the putative target genes separately. LncRNA Malat1 was chosen for further research. Series of loss and gain of functions experiments were performed to study the biological function of LncRNA Malat1. Quantitative real-time PCR (qRT-PCR), Western blot (WB) analysis and immunofluorescence (IF) staining were carried out to separately detect the functions of pancreatic β-cells at the mRNA and protein levels. Cytoplasmic and nuclear RNA fractionation and fluorescence in situ hybridization (FISH) were used to determine the subcellar location of lncRNA Malat1 in β-like cells. Enzyme-linked immunosorbent assays (ELISAs) were performed to examine the differentiation and insulin secretion of β-like cells after stimulation with different glucose concentrations. Structural interactions between lncRNA Malat1 and miR-15b-5p and between miR-15b-5p/Ihh were detected by dual luciferase reporter assays (LRAs). ResultsWe found that the expression of lncRNA Malat1 declined during differentiation, and overexpression (OE) of lncRNA Malat1 notably impaired the differentiation and maturation of β-like cells derived from iPSCs in vitro and in vivo. Most importantly, lncRNA Malat1 could function as a competing endogenous RNA (ceRNA) of miR-15b-5p to regulate the expression of Ihh according to bioinformatics prediction, mechanistic analysis and downstream experiments. ConclusionThis study established an unreported regulatory network of lncRNA Malat1 and the miR-15b-5p/Ihh axis during the differentiation of iPSCs into β-like cells. In addition to acting as an oncogene promoting tumorigenesis, lncRNA Malat1 may be an effective and novel target for treatment of diabetes in the future.

How to Regain Green Consumer Trust after Greenwashing: Experimental Evidence from China

Greenwashing leads to consumer skepticism of all green products as well as doubts about company claims regarding sustainability. However, the understanding of how to regain green consumer trust after greenwashing is rather limited. The authors fill this gap by exploring the psychological process of green consumers following intervention strategies designed to reduce greenwashing. We collect and interpret quantitative data from two psychological experiments, the first experiment identified two types of intervention strategies that serve to counter the negative impact of greenwashing and based on our findings from the first studies, we proposed and tested the moderating effect of two factors—implicit beliefs of consumers and companies who implement intervention strategies after greenwashing. The results indicate that distrust regulation (quantifying a product’s green attributes) and trustworthiness demonstration (visualizing environmental behaviors) are effective intervention strategies that can enable consumers to re-evaluate the cost-benefit of green products, and which may serve as critical psychological factors for green consumers and contribute to the degree of trust. Validation and comparative study of the derived results show that distrust regulation, followed by trustworthiness demonstration, has the best effect on increasing green trust after intervention. If the sequence is reversed, the effect of the intervention strategy is worse than if only one strategy had been applied. The implicit beliefs of green consumers play a moderating role between intervention strategies and reconsideration of the cost-benefit of green products. The behavior of genuinely green companies and the incremental beliefs of consumers can promote the intervention effect after greenwashing. Alternatively, the behavior of greenwashing companies can easily counter these effects. These findings contribute to knowledge about which psychological factors can promote or hinder the effectiveness of an intervention.

Application of External Torque Enhances the Detection of Subtle Syndesmotic Ankle Instability in a Weightbearing CT

Category: Sports; Trauma Introduction/Purpose: Syndesmotic ankle injuries are present in one-fourth of all ankle trauma and may lead to syndesmotic instability or posttraumatic ankle osteoarthirtis on the long term. At present, they continue to impose a diagnostic dilemma our clinical practice. While magnetic resonance imaging lacks application of load to the ankle joint, plain weightbearing radiographs are skewed by superposition of the osseous structures. The recent advent of weightbearing cone-beam CT (WBCT) overcomes these drawbacks by imaging both ankles during bipedal stance. However, it remains debated whether syndesmotic ankle injuries should be imaged under weightbearing conditions and/or during application of external rotation. Therefore, we aimed to implement both weightbearing and external rotation in the assessment of syndesmotic ankle injuries using WBCT imaging combined with 3D measurement techniques. Methods: In this retrospective study, patients with an acute syndesmotic ankle injury were analyzed using a WBCT (N= 21; Age= 31.64±14.07 years old). Inclusion criteria were an MRI confirmed syndesmotic ligament injury imaged by a WBCT of the ankle during weightbearing and combined weightbearing-external rotation. Exclusion criteria consisted of fracture associated syndesmotic injuries. For the external rotation protocol, the patient was asked to internally rotate the shin while ensuring that the foot remained firmly plantigrade until pain (Visual Analogue Scale &gt; 8/10) or a maximal range of motion was reached. 3D models were generated from the CT slices. Tibiofibular displacement and Talar Rotation were quantified by automated 3D measurements using a custom-made Matlab® script; Anterior Tibiofibular distance (ATFD), Alpha angle, posterior Tibiofibular distance (PTFD) and Talar rotation (TR) angle in comparison to the contralateral non-injured ankle. Results: The difference in neutral-stressed Alpha angle and ATFD showed a significant difference between patients with a syndesmotic ankle lesion and contralateral control (P = 0.046 and P = 0.039, respectively). The difference in neutral-stressed PTFD and TR angle did not show a significant difference between patients with a syndesmotic ankle lesion and healthy ankles (P = 0.492; P = 0.152, respectively). Conclusion: Application of combined weightbearing-external rotation reveals an increased ATFD in patients with syndesmotic ligament injuries (Figure 1). This study provides the first insights based on 3D measurements to support the potential relevance of applying external rotation during WBCT imaging. In clinical practice, this could enhance the current diagnostic accuracy of subtle syndesmotic instability in a non-invasive manner. However, future studies are required to determine cut-off values that may indicate the amount of displacement that might lead to chronic instability and require a certain type of treatment strategy.

Increasing Household Diet Diversity and Food Security in Rural Rwanda Using Small-Scale Nutrition-Sensitive Agriculture: A Community-Engaged Proof-of-Concept Study.

Malnutrition and food insecurity remain high in rural Rwanda, where residents consume a low-diversity diet provided through subsistence farming. Agricultural interventions using kitchen gardens may improve diet diversity in some populations. However, little is known about their efficacy when developed using community-based participatory research in combination with nutrition education focused on the empowerment of women. The objective of this study was to develop and implement a kitchen garden and nutrition education intervention using a community-engaged model and examine its impact on household diet diversity and food security. Using a mixed methods community-level design, we assessed a 16-week intervention implemented in Cyanika, Rwanda. Stratified purposeful sampling was used to select women participants representing 42 households. Household diet diversity scores (HHDS) and hunger scores were calculated at the baseline, post-intervention and one-year follow-up. HDDS increased after intervention from a pre-intervention intake of 2.59 [1.3] food groups/day, to 4.85 [1.6] at four months post-intervention and at one year post-intervention, reaching 5.55 [1.3]. There were no significant changes in household hunger scores. Our results indicate that collaborative community-engaged nutrition-sensitive agricultural interventions can increase household diet diversity; however, future work should explore whether this type of intervention strategy can lead to sustained changes and impact nutritional adequacy in this population.

Strategies to increase HIV testing among men who have sex with men and transgender women: an integrative review

BackgroundMen who have sex with men (MSM) and transgender women (TGW) are disproportionately affected by HIV, with much higher incidence and prevalence rates than in the general population in different countries. There are several barriers to testing among MSM and TGW, such as low risk perception, anticipation of HIV-related stigma, discrimination of sexual orientation, in addition to difficulties related to care and access to health services. Therefore, analyzing the available evidence of the effectiveness of strategies for scaling up HIV testing among key populations is essential to point out potential knowledge gaps which may need to be addressed and develop public health policies to promote testing and early diagnosis of HIV infection.MethodsAn integrative review was carried out to evaluate strategies for scaling up HIV testing in these populations. Search strategy was performed on eight electronic databases, without language restriction. We included clinical trials, quasi-experimental studies, and non-randomized studies. Study selection and data extraction were both performed independently by pairs and disagreements were solved by a third revisor. The screening of the studies was carried out through the selection of titles/abstracts and the reading of the full texts of the pre-selected studies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Data extraction was performed using a structured form.ResultsThirty-seven publications referring to 35 studies were included, mostly being carried out in the United States of America and Australia. No studies were found evaluating disaggregated data on TGW. The studies were grouped into four types of intervention strategies: self-test distribution system (n = 10), organization of health services (n = 9), peer education (n = 6), and social marketing campaign (n = 10). Strategies that focused on the first three groups, combined or not, were more effective in increasing HIV testing among MSM.ConclusionsConsidering the diversity of interventions and the methodological heterogeneity of the included studies, strategies especially involving self-test distribution systems, associated with new information and communication technologies, should be evaluated in different communities and social contexts. Research evaluating specific studies on TGW population is still needed.

Clinical and school-based intervention strategies for youth obesity prevention: A systematic review.

In the last couple of decades, numerous intervention strategies (ISs) have been formulated in school/community or clinical sectors using physical activity (PA) in order to prevent youth obesity because they have been highly effective in addressing this issue. These two sectors have revealed some interesting information in terms of efficient results and best practice mechanisms, but comparisons between them to learn about their functioning have been rare. Therefore, the aim of this systematic review was to analyze and synthesize PA ISs from school/community or clinical domains for the period 2013-2017, in French or English, targeting youths aged 5-19 years old through primary, secondary, and tertiary prevention. In total, 68 full articles were reserved for data extraction and synthesis and 617 were excluded because they did not meet eligibility criteria (61 of 68 were kept for the final analysis). The results identified a number of differences between the studies of the various IS sectors and also a third type of IS, mixed sector. Mixed ISs (clinical and school-community) have a special advantage because they can benefit from the strengths of both school/community-based and clinical-based ISs. Mixed ISs showed the most promising results. This review also highlighted the differences between sectors and their ISs in terms of intervention teams, prevention objectives, duration, materials, and efficiency. Future studies should focus on establishing a prevention program in a given geographical area involving all stakeholders with their respective skills/knowledge, in the area of decision-making and in the development of ISs, to ensure that the program is the most efficient and best adapted to its environment.

A Common Identity Intervention to Improve Service Quality for Consumers Experiencing Vulnerabilities

Prior research shows that consumers act in ways to avoid associating with conflicting social identities. However, it is unclear how such conflicting social identities influence the behaviors of service providers when interacting with consumers experiencing vulnerabilities, leading to potential marketplace discrimination. Additionally, research has yet to adequately identify what type of intervention strategy may be introduced in order to improve service quality when discrimination occurs. Across six studies, within the context of highly religious service providers or highly conservative service employees interacting with LGBTQIA + consumers, we demonstrate that the motivation to avoid being associated with undesirable social identities negatively influences their service quality toward these consumers experiencing vulnerabilities, leading to discrimination against such consumers. This occurs because of an increase in social identity threat perceptions associated with providing service to these consumers. We also identify an important boundary condition, such that this effect manifests when providing service that is high (vs. low) in identity relevance. Importantly, we provide evidence for a common identity intervention (i.e., focusing on the commonalities between actors) as a strategy that increases service quality and show its effectiveness across multiple contexts and using real businesses.

Annals for Educators - January 2023.

Annals for Educators - January 2023.

The adipocyte-enriched secretory protein tetranectin exacerbates type 2 diabetes by inhibiting insulin secretion from β cells.

Pancreatic β cell failure is a hallmark of diabetes. However, the causes of β cell failure remain incomplete. Here, we report the identification of tetranectin (TN), an adipose tissue–enriched secretory molecule, as a negative regulator of insulin secretion in β cells in diabetes. TN expression is stimulated by high glucose in adipocytes via the p38 MAPK/TXNIP/thioredoxin/OCT4 signaling pathway, and elevated serum TN levels are associated with diabetes. TN treatment greatly exacerbates hyperglycemia in mice and suppresses glucose-stimulated insulin secretion in islets. Conversely, knockout of TN or neutralization of TN function notably improves insulin secretion and glucose tolerance in high-fat diet–fed mice. Mechanistically, TN binds with high selectivity to β cells and inhibits insulin secretion by blocking L-type Ca2+ channels. Our study uncovers an adipocyte–β cell cross-talk that contributes to β cell dysfunction in diabetes and suggests that neutralization of TN levels may provide a new treatment strategy for type 2 diabetes.

Does the dose or type of gonadotropins affect the reproductive outcomes of poor responders undergoing modified natural cycle IVF (MNC-IVF)?

ObjectiveDoes the dose or type of gonadotropin affect the reproductive outcomes of poor responders undergoing IVF in a modified natural cycle (MNC-IVF)? Study DesignThis is a retrospective cohort study including patients attending a tertiary referral University Hospital from 1st January 2017 until 1st March 2020. All predicted poor responders (Poseidon groups 3 and 4) who underwent MNC-IVF in our center were included. Mild ovarian stimulation (rFSH/uFSH/hp-hMG) was started when a follicle with a mean diameter of 12–14 mm was observed on ultrasound scan; GnRH antagonist was added from the next day onwards. Mature oocytes were inseminated using ICSI. ResultsIn total 484 patients undergoing 1398 cycles were included. Mean (SD) age and serum AMH were 38.2 (3.7) years and 0.28 (0.26) ng/ml, respectively. The daily dose of gonadotropins was either < 75 IU/d [11/1398 (0.8 %)] or 75 to < 100 IU/d [1303/1398 (93.2 %)] or ≥ 100 to 150 IU/d [84/1398 (6 %)]. Patients were stimulated with rFSH [251/1398 (18 %)], uFSH [45/1398 (3.2 %)] or hp-hMG [1102/1398 (78.8 %)]. Clinical pregnancy rate was 119/1398 (8.5 %). Live birth was achieved in 80/1398 (5.7 %) of cycles. There was no significant difference in rates of pregnancy and live birth across different types and doses of gonadotropins. The GEE multivariate regression analysis, adjusting for relevant confounders, showed that the type of treatment strategy (rFSH/uFSH/hp-hMG) and the daily dose of gonadotropins were not associated with live birth rates (LBR) (p value 0.08 and 0.8, respectively). ConclusionsThe type and daily dose of gonadotropins do not affect the reproductive outcome of poor responders undergoing MNC-IVF.

Natural 8-C-ascorbyl-(−)-epigallocatechin as antidiabetic agent: α-glucosidase and PTP-1B signaling pathway dual regulators

α-Glucosidase and protein tyrosine phosphatase 1B (PTP1B) signaling pathway dual regulators decrease postprandial blood glucose levels and improve insulin sensitivity, making it a new treatment strategy for type 2 diabetes. This study examined in vitro antidiabetic activities of 8-C-ascorbyl-(−)-epigallocatechin (AE), found in oolong tea. AE inhibited α-glucosidase (IC50 = 142.8 μM) with activity higher than that of acarbose (IC50 = 250.2 μM). AE significantly promoted glucose-consumption and activated the insulin signaling pathway through enhancing the protein levels of p-GSK3β and p-Akt and inhibiting the expression of PTP1B, along with slightly inhibitory activity against PTP1B. Docking analysis showed AE inhibited α-glucosidase activity via binding to the catalytic site through hydrogen bonds and Pi-Pi interactions, as well as a good shape match to the active pocket. In addition, AE could relieve oxidative damage and possessed good antioxidant capacity. Taken together, the results of this study indicate that AE exhibits antidiabetic activity in vitro, making it a potential functional food ingredient and drug candidate for management of type 2 diabetes.

The impact of the spatial heterogeneity of resistant cells and fibroblasts on treatment response.

A long-standing practice in the treatment of cancer is that of hitting hard with the maximum tolerated dose to eradicate tumors. This continuous therapy, however, selects for resistant cells, leading to the failure of the treatment. A different type of treatment strategy, adaptive therapy, has recently been shown to have a degree of success in both preclinical xenograft experiments and clinical trials. Adaptive therapy is used to maintain a tumor’s volume by exploiting the competition between drug-sensitive and drug-resistant cells with minimum effective drug doses or timed drug holidays. To further understand the role of competition in the outcomes of adaptive therapy, we developed a 2D on-lattice agent-based model. Our simulations show that the superiority of the adaptive strategy over continuous therapy depends on the local competition shaped by the spatial distribution of resistant cells. Intratumor competition can also be affected by fibroblasts, which produce microenvironmental factors that promote cancer cell growth. To this end, we simulated the impact of different fibroblast distributions on treatment outcomes. As a proof of principle, we focused on five types of distribution of fibroblasts characterized by different locations, shapes, and orientations of the fibroblast region with respect to the resistant cells. Our simulation shows that the spatial architecture of fibroblasts modulates tumor progression in both continuous and adaptive therapy. Finally, as a proof of concept, we simulated the outcomes of adaptive therapy of a virtual patient with four metastatic sites composed of different spatial distributions of fibroblasts and drug-resistant cell populations. Our simulation highlights the importance of undetected metastatic lesions on adaptive therapy outcomes.

The Effect in Renal Function and Vascular Decongestion in Type 1 Cardiorenal Syndrome Treated with Two Strategies of Diuretics, a Pilot Randomized Trial

AimThe main treatment strategy in type 1 cardiorenal syndrome (CRS1) is vascular decongestion. It is probable that sequential blockage of the renal tubule with combined diuretics (CD) will obtain similar benefits compared with stepped-dose furosemide (SF).MethodsIn a pilot double-blind randomized controlled trial of CRS1 patients were allocated in a 1:1 fashion to SF or CD. The SF group received a continuous infusion of furosemide 100 mg during the first day, with daily incremental doses to 200 mg, 300 mg and 400 mg. The CD group received a combination of diuretics, including 4 consecutive days of oral chlorthalidone 50 mg, spironolactone 50 mg and infusion of furosemide 100 mg. The objectives were to assess renal function recovery and variables associated with vascular decongestion.ResultsFrom July 2017 to February 2020, 80 patients were randomized, 40 to the SF and 40 to the CD group. Groups were similar at baseline and had several very high-risk features. Their mean age was 59 ± 14.5 years, there were 37 men (46.2%). The primary endpoint occurred in 20% of the SF group and 15.2% of the DC group (p = 0.49). All secondary and exploratory endpoints were similar between groups. Adverse events occurred frequently (85%) with no differences between groups (p = 0.53).ConclusionIn patients with CRS1 and a high risk of resistance to diuretics, the use of CD compared to SF offers the same results in renal recovery, diuresis, vascular decongestion and adverse events, and it can be considered an alternative treatment. ClinicalTrials.gov with number NCT04393493 on 19/05/2020 retrospectively registered.

A review on α-glucosidase inhibitory activity of first row transition metal complexes: a futuristic strategy for treatment of type 2 diabetes.

Type 2 diabetes mellitus (T2DM) is characterized by high blood glucose levels and has emerged as a controversial public health issue worldwide. The increasing number of patients with T2DM on one hand, and serious long-term complications of the disease such as obesity, neuropathy, and vascular disorders on the other hand, have induced a huge economic impact on society globally. In this regard, inhibition of α-glucosidase, the enzyme responsible for the hydrolysis of carbohydrates in the body has been the main therapeutic approach to the treatment of T2DM. As α-glucosidase inhibitors (α-GIs) have occupied a special position in the current research and prescription drugs are generally α-GIs, researchers have been encouraged to design and synthesize novel and efficient inhibitors. Previously, the presence of a sugar moiety seemed to be crucial for designing α-GIs since they can attach to the carbohydrate binding site of the enzyme mimicking the structure of disaccharides or oligosaccharides. However, inhibitors lacking glycosyl structures have also shown potent inhibitory activity and development of non-sugar based inhibitors is accelerating. In this respect, in vitro anti-α-glucosidase activity of metal complexes has attracted lots of attention and this paper has reviewed the inhibitory activity of first-row transition metal complexes toward α-glucosidase and discussed their probable mechanisms of action.

Glucokinase as a therapeutic target based on findings from the analysis of mouse models.

I investigated mouse models to elucidate the pathophysiology and to establish a new treatment strategy for type 2 diabetes, with a particular focus on glucokinase. The decrease in pancreatic beta-cell function and mass are important factors in the pathophysiology of type 2 diabetes. My group have shown that glucokinase plays an important role in high-fat diet-induced and high-starch diet-induced beta-cell expansion. The findings indicated that the mechanism of short-term high-fat diet-induced beta-cell proliferation involved a glucokinase-independent pathway, suggesting that there are different pathways and mechanisms in the proliferation of pancreatic beta-cells during short-term versus long-term high-fat diets. Because enhancement of glucose signals via glucokinase is important for beta-cell proliferation, it was thought that beta-cell mass would be increased and insulin secretion would be maintained by glucokinase activators. However, sub-chronic administration of a glucokinase activator in db/db mice produced an unsustained hypoglycemic effect and promoted hepatic fat accumulation without changes in beta-cell function and mass. In contrast, my group have shown that inactivating glucokinase in beta-cells prevented beta-cell failure and led to an improvement in glucose tolerance in db/db mice. Regulation of glucokinase activity has an influence on the pathophysiology of type 2 diabetes and can be one of the therapeutic targets.