Strategy For Treatment Of Type Research Articles

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.

PHYSICAL ACTIVITY DURING THE TREATMENT OF WOMEN WITH BREAST CANCER

ABSTRACT
 Breast cancer incidence increases with age, and its treatment usually has side effects such as joint pain, depression and fatigue. Insufficient physical activity can decrease muscle strength, increase fatigue and reduce quality of life. Given the above, the purpose of this systematic review was to identify the main intervention strategies based on physical activities for women during breast cancer treatment. This study considered four databases: PubMed, SportDiscus, Lilacs, and Scielo, taking into consideration studies of the last five years. The descriptors for physical activity variable were “exercise", “physical activity”, and “motor activity”. For breast cancer variable, the descriptors were “breast neoplasm”, and for participants: “women” and “adults”. Seven studies related to the benefits of physical activity were found, one of those was carried out in Brazil. The variables studied were fatigue, anthropometry, physical activity level (PAL), pain threshold, sleep quality, life quality (LQ), physical fitness (PF), and cortisol level. The types of intervention strategies were in most part through aerobic exercises, resistance/strength training, hydrotherapy, relaxation, yoga and belly dancing. Although there is no consensus on which physical activity, intensity, and frequency are best for the patients, in general, all patients increased their level of physical activity and quality of life, reduced fatigue, and were not impeded by the treatment or found necessary to interrupt it while performing such physical activities.

Prevention and treatment strategies for type 2 diabetes based on regulating intestinal flora.

Diabetes along with related comorbidities associated with high disability rates severely threatens human health. The etiology of diabetes is complex. Genetics, environmental factors, eating habits, drug usage, aging, and lack of movement play important roles in the development of diabetes. Intestinal flora is reportedly closely related to the occurrence and development of type 2 diabetes. Herein, we review changes in abundance and proportion of intestinal flora in patients with type 2 diabetes and regulation of intestinal flora through diet, drugs, and surgery to prevent and treat type 2 diabetes. A more appropriate clinical diagnosis and treatment plan could be made considering changes in intestinal flora in the future.

Dual Targeting of PTP1B and Aldose Reductase with Marine Drug Phosphoeleganin: A Promising Strategy for Treatment of Type 2 Diabetes.

An in-depth study on the inhibitory mechanism on protein tyrosine phosphatase 1B (PTP1B) and aldose reductase (AR) enzymes, including analysis of the insulin signalling pathway, of phosphoeleganin, a marine-derived phosphorylated polyketide, was achieved. Phosphoeleganin was demonstrated to inhibit both enzymes, acting respectively as a pure non-competitive inhibitor of PTP1B and a mixed-type inhibitor of AR. In addition, in silico docking analyses to evaluate the interaction mode of phosphoeleganin with both enzymes were performed. Interestingly, this study showed that phosphoeleganin is the first example of a dual inhibitor polyketide extracted from a marine invertebrate, and it could be used as a versatile scaffold structure for the synthesis of new designed multiple ligands.

A Scenario-Based Management of Water Resources and Supply Systems Using a Combined System Dynamics and Compromise Programming Approach

Long-term sustainability in water supply systems is a major challenge due to water resources depletion, climate change and population growth. This paper presents a scenario-based approach for performance assessment of intervention strategies in water resources and supply systems (WRSS). A system dynamics approach is used for modelling the key WRSS components and their complex interactions with natural and human systems and is combined with a multi-criteria decision analysis for sustainability performance assessment of strategies in each scenario. The scenarios combine population growth rates with groundwater extraction limits against two types of intervention strategies. The methodology was demonstrated on a real-world case study in Iran. Results show scenario-based analysis can provide suitable strategies leading to long-term sustainability of water resources for each scenario externally imposed on the water systems. For scenarios with either no threshold or one threshold of groundwater extraction limit, the only effective strategies for sustainable groundwater preservation are those involving agricultural water demand decrease with an average recovery rate of 130% for groundwater resources while other strategies of agricultural groundwater abstraction (constant/increase rates) fail to sustainably recover groundwater resources. However, all analysed strategies can provide sustainability of water resources with an average recovery rate of 33% for groundwater resources only when scenarios with two threshold limits are in place. The impact of scenarios with population growth rates on groundwater conservation is quite minor with an average recovery rate of 11% compared to scenarios of groundwater extraction limits with an average recovery rate of 79% between no threshold and two threshold limits.

A Zwitterionic Polyurethane Nanoporous Device with Low Foreign‐Body Response for Islet Encapsulation

Encapsulation of insulin-producing cells is a promising strategy for treatment of type 1 diabetes. However, engineering an encapsulation device that is both safe (i.e., no cell escape and no breakage) and functional (i.e., low foreign-body response (FBR) and high mass transfer) remains a challenge. Here, a family of zwitterionic polyurethanes (ZPU) with sulfobetaine groups in the polymer backbone is developed, which are fabricated into encapsulation devices with tunable nanoporous structures via electrospinning. The ZPU encapsulation device is hydrophilic and fouling-resistant, exhibits robust mechanical properties, and prevents cell escape while still allowing efficient mass transfer. The ZPU device also induces a much lower FBR or cellular overgrowth upon intraperitoneal implantation in C57BL/6 mice for up to 6 months compared to devices made of similar polyurethane without the zwitterionic modification. The therapeutic potential of the ZPU device is shown for islet encapsulation and diabetes correction in mice for ≈3 months is demonstrated. As a proof of concept, the scalability and retrievability of the ZPU device in pigs and dogs are further demonstrated. Collectively, these attributes make ZPU devices attractive candidates for cell encapsulation therapies.

P–707 Does the dose or type of gonadotropin affect the reproductive outcomes of poor responders undergoing modified natural cycle IVF (MNC-IVF)?

Abstract Study question Does the dose or type of gonadotropin affect the reproductive outcomes of poor responders undergoing MNC-IVF? Summary answer Neither the type nor the dose of gonadotropins affects the reproductive outcomes of poor responders undergoing MNC-IVF. What is known already Poor ovarian response (POR) to ovarian stimulation remains a major therapeutic challenge in routine IVF practice, because of the association with low live birth rates and high cancellation rates. Although high doses of gonadotropins are traditionally used to stimulate the ovaries in women with predicted POR, MNC-IVF has been proposed as a mild-approach alternative in this population. Typically, the MNC protocol includes GnRH-antagonists to avoid premature ovulation and gonadotropin add-back stimulation at the late follicular phase. However, evidence is sparse, and there is no consensus regarding a specific dose or type of gonadotropins in this mild stimulation protocol. Study design, size, duration This is a retrospective cohort study including patients attending a tertiary referral University Hospital from 1st January 2017 until 1st March 2020. Participants/materials, setting, methods All women who underwent MNC-IVF in our center were included. Gonadotropins [recombinant FSH (rFSH), urinary FSH (uFSH) or highly purified human menopausal gonadotrophin (hp-hMG)] were started when a follicle with a mean diameter of 12–14 mm was observed on ultrasound scan, followed by GnRH antagonists (0.25mg/day) from the next day onwards. Mature oocytes were inseminated using ICSI. Main results and the role of chance In total, 484 patients undergoing 1398 cycles were included. Mean (SD) age and serum AMH were 38.2 (3.7) years and 0.46 (0.78) 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 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%)]. Biochemical and clinical pregnancy rates were 142/1398 (10.1%) and 119/1398 (8.5%). Live birth was achieved in 80/1398 (5.7%) of cycles. Live birth rates (LBR) were similar between the different type and doses of gonadotropins (p-value 0.3 and 0.51, respectively). The GEE multivariate regression analysis adjusting for relevant confounders (age, BMI, number of MII oocytes) showed that the type of treatment strategy (rFSH/uFSH/hp-hMG) and the dose of gonadotropins were not significantly associated with LBR (coefficient 0.01 and –0.02, p value 0.09 and 0.3, respectively). Limitations, reasons for caution The main limitation is the retrospective design of our study, with an inherent risk of bias. Wider implications of the findings: This is the first and largest study evaluating MNC-IVF protocol modalities. Our data demonstrate that any type of gonadotropin can be used and there is no benefit from daily doses beyond 75IU. Trial registration number N/A

Pathomechanisms Underlying Hypoxemia in Two COVID-19-Associated Acute Respiratory Distress Syndrome Phenotypes: Insights From Thrombosis and Hemostasis.

ABSTRACTBackground:The pathomechanisms of hypoxemia and treatment strategies for type H and type L acute respiratory distress syndrome (ARDS) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced coronavirus disease 2019 (COVID-19) have not been elucidated.Main text:SARS-CoV-2 mainly targets the lungs and blood, leading to ARDS, and systemic thrombosis or bleeding. Angiotensin II-induced coagulopathy, SARS-CoV-2-induced hyperfibrin(ogen)olysis, and pulmonary and/or disseminated intravascular coagulation due to immunothrombosis contribute to COVID-19-associated coagulopathy. Type H ARDS is associated with hypoxemia due to diffuse alveolar damage-induced high right-to-left shunts. Immunothrombosis occurs at the site of infection due to innate immune inflammatory and coagulofibrinolytic responses to SARS-CoV-2, resulting in microvascular occlusion with hypoperfusion of the lungs. Lung immunothrombosis in type L ARDS results from neutrophil extracellular traps containing platelets and fibrin in the lung microvasculature, leading to hypoxemia due to impaired blood flow and a high ventilation/perfusion (VA/Q) ratio. COVID-19-associated ARDS is more vascular centric than the other types of ARDS. D-dimer levels have been monitored for the progression of microvascular thrombosis in COVID-19 patients. Early anticoagulation therapy in critical patients with high D-dimer levels may improve prognosis, including the prevention and/or alleviation of ARDS.Conclusions:Right-to-left shunts and high VA/Q ratios caused by lung microvascular thrombosis contribute to hypoxemia in type H and L ARDS, respectively. D-dimer monitoring-based anticoagulation therapy may prevent the progression to and/or worsening of ARDS in COVID-19 patients.

Fucoidan Hydrogels Significantly Alleviate Oxidative Stress and Enhance the Endocrine Function of Encapsulated Beta Cells

AbstractMicroencapsulating pancreatic islets in immunoprotective alginate hydrogels is a promising strategy for treatment of type 1 diabetes. However, this strategy is limited by inflammation and hypoxia mediated oxidative stress, due to encapsulation and the hydrogel itself, leading to impaired insulin secretion and limited short and long term cell survival. Herein, the antioxidant effect of fucoidan, an algae derived polysaccharide, on beta cells, and its positive effects on encapsulated beta cell viability and function is presented. Fucoidan from Fucus vesiculosus (FF) exhibits a high total antioxidant capacity, and free radical scavenging activity, and is able to significantly alleviate intracellular oxidative stress in rat insolinoma beta cells (INS1E). In addition, FF significantly increases insulin secretion in a dose‐ and time‐dependent manner. When FF is incorporated in ultrapure alginate used for microencapsulation of primary rat islets, both viability and glucose responsiveness of rat islets in these socalled Fucogel microcapsules (Fucocaps) are found to be significantly higher compared to islets encapsulated in alginate alone. Similar results are obtained with INS1E pseudoislets and neonatal pig islets. Fucocaps can provide a redox‐modulatory niche and an immune barrier for islets and beta cells in the same time leading to significantly improved survival and endocrine function by mitigating oxidative stress.

Measuring parent strategy use in early intervention: Reliability and validity of the Naturalistic Developmental Behavioral Intervention Fidelity Rating Scale across strategy types.

Children with autism spectrum disorder benefit from early intervention to improve social communication, and parent-implemented interventions are a feasible and family-centered way to increase the amount of treatment they receive. For these treatments to be effective, it is important for the parent to implement the strategies as intended. However, measurement of parent strategy use is inconsistent across studies of parent-implemented interventions. This study evaluates the quality of the NDBI-Fi, an efficient measure, compared to a more time-consuming measure that is known to be precise. Videos of parents playing with their children were used to compare these two measurement methods. Results demonstrated that the NDBI-Fi was of good quality: scorers had high levels of agreement, the NDBI-Fi was similar to the more precise measure in rating parents after intervention, it detected changes from before to after intervention, and it detected differences when parents learned different types of intervention strategies. The NDBI-Fi was not as precise as the other measure across all strategies before parents learned intervention. Taken together, the findings of this study support the use of the NDBI-Fi as a high-quality outcome measure.

POS-011 THE EFFECT IN RENAL FUNCTION AND VASCULAR DECONGESTION IN TYPE 1 CARDIORENAL SYNDROME TREATED WITH TWO STRATEGIES OF DIURETICS, A RANDOMIZED CLINICAL TRIAL

The 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).

Analysis of yellow fever prevention strategy from the perspective of mathematical model and cost-effectiveness analysis

<abstract><p>We developed a new mathematical model for yellow fever under three types of intervention strategies: vaccination, hospitalization, and fumigation. Additionally, the side effects of the yellow fever vaccine were also considered in our model. To analyze the best intervention strategies, we constructed our model as an optimal control model. The stability of the equilibrium points and basic reproduction number of the model are presented. Our model indicates that when yellow fever becomes endemic or disappears from the population, it depends on the value of the basic reproduction number, whether it larger or smaller than one. Using the Pontryagin maximum principle, we characterized our optimal control problem. From numerical experiments, we show that the optimal levels of each control must be justified, depending on the strategies chosen to optimally control the spread of yellow fever.</p></abstract>

IN VIVO ANTI-CD45RB ANTIBODY-INDUCED REGULATORY T CELLS DEMONSTRATE SPECIES-SPECIFIC TOLERANCE TO DISCORDANT HUMAN XENOGENIC ISLETS

Organ transplantation-Sichuan Youth Science and Technology Innovation Research Team. Background: Although islet xenotransplantation has been proven to be a promising strategy for treatment of type 1 diabetes, it’s application in clinical setting would have to overcome acute cellular rejection and challenging species barrier. The aim of this study was to determine the role of Foxp3+ regulatory T cells (Treg) in anti-CD45RB induced dominant and specific tolerance to human islet cells in mice. Methods: One thousand and five hundred IEQ human islets were isolated from deceased donors and transplanted under the kidney capsule of B6 diabetic mice, B6µMT-/- mice and thymectomized µMT-/- mice. The recipients were then temporarily treated with low dose anti-CD45RB. CD4+Foxp3+Tregs were identified in the blood, spleen, draining lymph nodes and within the graft of tolerant and rejecting mice by FCM and immunohistochemistry. Additional anti-CD25 mAb was applied in the tolerant B6µMT-/-mice, which received another human islets simultaneously. The CD4+CD25+ Tregs sorted from the tolerant mice were adoptively transferred to diabetic Scid mice which were grafted with another human islets to assess the suppressive function. Results: In vitro, CD4+CD25-Foxp3-T cells which were activated with anti-CD3/anti-CD28 beads and cultured with anti-CD45RB demonstrated significant increase in Foxp3+ expression. In vivo, an increase of Foxp3+ T cells was observed in treated mice and more significant increase in tolerant mice, compared with a negligible increase in rejected mice. Anti-CD45RB alone allowed indefinite graft survival in 26.6% of B6 mice and 88.9% in µMT-/- mice, whereas none of xenografts were accepted in these mice treated simultaneously with anti-CD25. µMT-/-mice which were thymectomized and treated by anti-CD45 yielded 100% of grafts with long-term survival, which indicated that the transplant tolerance was thymus-derived Tregs independent. Moreover, the µMT-/-mice which tolerated to the first human islets accepted the re-transplanted second party of islets from another human, whereas the tolerance was hampered by anti-CD25 treatment. Adoptive cell transfer model showed the CD4+CD25+ Tregs from the mice tolerant to the first human islets prolonged survival of the second human islets, compared to natural Tregs (p < 0.05). Conclusions: These data suggest that anti-CD45RB-induced tolerance in islet xenotransplantation is mediated by Tregs expansion. These tolerant Tregs had the potent capacity to transfer dominant and species-specific tolerance. The National Natural Science Foundation of China (No. 81172832, 81771723). Sichuan Youth Science and Technology Foundation (2013JQ0020). Special Program for Sichuan Youth Science and Technology Innovation Research Team (2014TD0010).

Hybrid drug combination: A new treatment strategy for type 2 diabetes- A review

Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia arising from deregulation in insulin secretion, insulin action, or both. The current synthetic drugs have dose-dependent side effects which confined their uses. The phytochemicals are the natural compounds that have better therapeutic efficacy and interacts synergistically with oral hypoglycemic drugs. The addition of phytochemicals with OHDs may reduce the dose of synthetic drugs as well as their side effects and toxicity. A detailed outline about such combinations like Ferulic acid &amp; THZ/Metformin, Ellagic acid &amp; Pioglitazone (THZ), Chlorogenic acid &amp; THZ/Metformin, Caffeic acid &amp; THZ/Metformin, eugenol acid &amp; THZ/Metformin, cinnamic acid &amp; THZ/Metformin, p- coumaric acid &amp; THZ/Metformin, Arecoline &amp;Vanillic acid with the THZ/ Metformin have been illustrated. This review has also discussed the synergy and mechanism of phytochemical with the OHDs to combat hyperglycemia and other risk associated with it. A comprehensive review was conducted to pile up the information about polyphenols &amp; synthetic drug combinations used for the treatment of diabetes mellitus, which has been carried out in-vitro or in-vivo and may contribute to identifying novel strategies in the treatment of T2D condition. This review shows the importance of the responsible bioactive agents present in medicinal plants in the drive to demonstrate their antidiabetic effects.

Foreign influence and domestic policy

In an interconnected world, economic and political interests inevitably reach beyond national borders. Since policy choices generate external economic and political costs, foreign state and non-state actors have an interest in influencing policy actions in other sovereign countries to their advantage. Foreign influence is a strategic choice aimed at internalizing these externalities and takes many forms. We distinguish three broad types of intervention strategies, (i) voluntary agreement interventions between the intervening foreign power and the target country, (ii) policy interventions based on rewarding or sanctioning the target country to obtain a specific change in policy and (iii) instiutional interventions aimed at influencing the policy choice by changing the political institutions in the target country, (with or without a cival war). We propose a unifying theoretical framework to understand when and which form of foreign influence is chosen and use it to organize and evaluate the new political economics literature on foreign influence along with work in cognate disciplines. Foreign intervention plays a more important role for a proper understanding of domestic policy choices, for institutional dynamics and for internal conflict than is commonly acknowledged in both empirical and theoretical research.

Pharmacist-led therapeutic carbohydrate restriction as a treatment strategy for type 2 diabetes: the Pharm-TCR randomized controlled trial protocol

BackgroundThe current treatment paradigm for type 2 diabetes mellitus (T2D) typically involves use of multiple medications to lower glucose levels in hope of reducing long-term complications. However, such treatment does not necessarily address the underlying pathophysiology of the disease and very few patients achieve partial, complete, or prolonged remission of T2D after diagnosis. The therapeutic potential of nutrition has been highlighted recently based on results of clinical trials reporting remission of T2D with targeted dietary approaches. During the initial phase of such interventions that restrict carbohydrates and/or induce rapid weight loss, hypoglycemia presents a notable risk to patients. We therefore hypothesized that delivering very low-carbohydrate, low-calorie therapeutic nutrition through community pharmacies would be an innovative strategy to facilitate lowering of glycated hemoglobin (A1C) while safely reducing the use of glucose-lowering medications in T2D.MethodsA community-based randomized controlled trial that is pragmatic in nature, following a parallel-group design will be conducted (N = 200). Participants will have an equal chance of being randomized to either a pharmacist-led, therapeutic carbohydrate restricted (Pharm-TCR) diet or guideline-based treatment as usual (TAU). Pharm-TCR involves a 12-week very low carbohydrate, calorie-restricted commercial diet plan led by pharmacists and lifestyle coaches with pharmacists responsible for managing medications in collaboration with the participants’ family physicians. Main inclusion criteria are diagnosis of T2D, currently treated with glucose-lowering medications, age 30–75 years, and body mass index ≥ 30. The primary outcome is a binary measure of use of glucose-lowering medication. Secondary outcomes include A1C, anthropometrics and clinical blood markers.DiscussionThere are inherent risks involved if patients with T2D who take glucose-lowering medications follow very low carbohydrate diets. This randomized controlled trial aims to determine whether engaging community pharmacists is a safe and effective way to deliver therapeutic carbohydrate restriction and reduce/eliminate the need for glucose-lowering medications in people with T2D.Trial registrationClinicalTrials.gov, NCT03181165. Registered on 8 June 2017.

Development of a shear-thinning biomaterial as an endovascular embolic agent for the treatment of type B aortic dissection

False lumen embolisation is a promising treatment strategy in type B aortic dissection (TBAD) but it is limited by the lack of a disease-specific embolic agent. Our aim was to develop a biomaterial that could be delivered minimally-invasively into the TBAD false lumen and embolise the region. We created 24 shear-thinning biomaterials from blends of gelatin, silicate nanoparticles and silk fibroin, and evaluated their suitability as a false lumen embolic agent in TBAD. We determined the stability of mechanical properties by measuring the compressive modulus of samples stored in physiological conditions over a 21 day period. We quantified injectability by measuring the force required to inject each biomaterial through catheters of varying diameter. We also assessed in vitro degradation rates by measuring weight change over 30 days. Finally, we developed an in vitro experimental pulsatile flow setup with two different anatomically-correct TBAD geometries and performed 78 false lumen occlusion experiments under different operating conditions. We found that the compressive moduli changed rapidly on exposure to 37 °C before stabilising by Day 7. A high silicate nanoparticle to gelatin ratio resulted in greater compressive moduli, with a maximum of 117.6 ± 15.2 kPa. By reducing the total solid concentration, we could improve injectability and biomaterials with 8% (w/v) solids required <80 N force to be injected through a 4.0 mm catheter. Our in vitro degradation rates showed that the biomaterial only degraded by 1.5-8.4% over a 30 day period. We found that the biomaterial could occlude flow to the false lumen in 99% of experiments. In conclusion, blends with high silicate nanoparticle and low silk fibroin content warrant further investigation for their potential as false lumen embolic agents and could be a promising alternative to current TBAD repair methods.

Modified natural cycle IVF versus conventional stimulation in advanced-age Bologna poor responders.

Do ongoing pregnancy rates (OPR) differ between modified natural cycle IVF (MNC-IVF) and conventional high-dose ovarian stimulation (HDOS) in advanced-age Bologna poor responders? This was a retrospective cohort study including patients with poor ovarian response (POR) attending a tertiary referral university hospital from 1 January 2011 to 1 March 2017. All women who fulfilled the Bologna criteria for POR and aged ≥40 years who underwent their first intracytoplasmic sperm injection (ICSI) cycle in the study centre were included. In total, 476 advanced-age Bologna poor responder patients were included in the study: 189 in the MNC-IVF group and 287 in the HDOS group. OPR per patient were significantly lower in the MNC-IVF group (5/189, 2.6%) compared with the HDOS group (29/287, 10.1%) (P=0.002). However, after adjustment for relevant confounders (number of oocytes and presence of at least one top-quality embryo), the multivariate logistic regression analysis showed that the type of treatment strategy (HDOS versus MNC-IVF) was not significantly associated with OPR (odds ratio 2.56, 95% confidence interval 0.9-7.6). In advanced-age Bologna poor responders, MNC-IVF, which is a more patient-friendly approach, could be a reasonable alternative in this difficult-to-treat group of women.