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1.
Influence of UV-irradiation intensity and exposure duration on the hemobiocompatibility enhancement of a novel synthesized phosphobetaine zwitterions polyethersulfone clinical hemodialysis membranes.
Eduok, U, Camara, H, Abdelrasoul, A, Shoker, A
Journal of biomedical materials research. Part B, Applied biomaterials. 2022;(3):573-586
Abstract
To improve the biocompatibility of polyethersulfone (PES) membranes utilized for biomedical hemodialysis (HD) applications, surface grafting with hydrophilic polymers has become a reliable modification strategy. Like most photochemical catalyzed reactions, UV-assisted grafting is distinctly advantageous for inducing permanent surface chemistry, enhancing hydrophilicity, improving morphology, and surface charge of membranes. PES membranes may be hydrophilic and chemically stable; however, they also have low protein-binding capacity and very susceptible to fouling and target analyte binding. In this study, novel zwitterionic polymers (PVP-ZW) have been synthesized by UV-assisted grafting PVP to a phosphobetaine monomer in a reaction involving dimethylamino and dioxaphospholane-2-oxide terminal groups in an NVP monomer solution at varying UV exposure conditions. The highlight of the present study is the investigation of the hemocompatibility of coated PES HD membranes at varying UV exposure conditions with respect to membrane chemistry and morphology and its influence on human serum protein adsorption. A clinical investigation of inflammatory biomarker release from incubated coated membranes within uremic blood samples of HD patients reveals they are weak complement and coagulation activators compared to bare PES membrane. The trend of fibrinogen adsorption on coated PES membranes was observed to increase with reducing UV intensity and exposure duration. Fibrinogen adhesion only increased with roughened membrane surfaces, and this also led to the formation of biological activation pathways hindering biocompatibility. Resistance against fibrinogen absorption on zwitterionic modified PES membrane could be linked with the creation of electrostatically induced neutral zwitterionic PVP-phosphobetaine hydration layer with hydrophilic character. Experimental results are accompanied by spectroscopic and morphological imaging evidence. Zwitterion coated PES membranes (PES-PVP-ZW) fabricated from higher UV intensities through longer exposure durations showed significant presence of surface deformations in the forms of inherent exfoliations due to harsh UV reaction conditions. The zeta potential and surface roughness of coated membranes also played significant role in the fibrinogen adsorption on PES membranes during ultrafiltration.
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2.
Hypertension and Type 2 Diabetes-The Novel Treatment Possibilities.
Przezak, A, Bielka, W, Pawlik, A
International journal of molecular sciences. 2022;(12)
Abstract
Elevated blood pressure and hyperglycaemia frequently coexist and are both components of metabolic syndrome. Enhanced cardiovascular risk is strongly associated with diabetes and the occurrence of hypertension. Both hypertension and type 2 diabetes, if treated inappropriately, lead to serious complications, increasing the mortality of patients and generating much higher costs of health systems. This is why it is of great importance to find the missing link between hypertension and diabetes development and to simultaneously search for drugs influencing these two disorders or even drugs aimed at their pathological bases. Standard antihypertensive therapy mainly focuses on blood pressure reduction, while novel drugs also possess a wide range of pleiotropic modes of actions, such as cardio- and nephroprotective properties or body weight reduction. These properties are especially desirable in a situation when type 2 diabetes coexists with hypertension. This review describes the connections between diabetes and hypertension development and briefly summarises the current knowledge regarding attempts to define targets for the treatment of high blood pressure in diabetic patients. It also describes the standard hypotensive drugs preferred in patients with type 2 diabetes, as well as novel drugs, such as finerenone, esaxerenone, sodium-glucose co-transporter-2 inhibitors, glucagon-like peptide-1 analogues and sacubitril/valsartan.
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3.
High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer.
Palafox, M, Monserrat, L, Bellet, M, Villacampa, G, Gonzalez-Perez, A, Oliveira, M, Brasó-Maristany, F, Ibrahimi, N, Kannan, S, Mina, L, et al
Nature communications. 2022;(1):5258
Abstract
CDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies.
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4.
Comparison of periprosthetic femoral fracture torque and strain pattern of three types of femoral components in experimental model.
Takegami, Y, Seki, T, Osawa, Y, Imagama, S
Bone & joint research. 2022;(5):270-277
Abstract
AIMS: Periprosthetic hip fractures (PPFs) after total hip arthroplasty are difficult to treat. Therefore, it is important to identify modifiable risk factors such as stem selection to reduce the occurrence of PPFs. This study aimed to clarify differences in fracture torque, surface strain, and fracture type analysis between three different types of cemented stems. METHODS We conducted biomechanical testing of bone analogues using six cemented stems of three different types: collarless polished tapered (CPT) stem, Versys Advocate (Versys) stem, and Charnley-Marcel-Kerboull (CMK) stem. Experienced surgeons implanted each of these types of stems into six bone analogues, and the analogues were compressed and internally rotated until failure. Torque to fracture and fracture type were recorded. We also measured surface strain distribution using triaxial rosettes. RESULTS There was a significant difference in fracture torque between the three stem types (p = 0.036). Particularly, the median fracture torque for the CPT stem was significantly lower than that for the CMK stem (CPT vs CMK: 164.5 Nm vs 200.5 Nm; p = 0.046). The strain values for the CPT stem were higher than those for the other two stems at the most proximal site. The fracture pattern of the CPT and Versys stems was Vancouver type B, whereas that of the CMK stem was type C. CONCLUSION Our study suggested that the cobalt-chromium alloy material, polished surface finish, acute-square proximal form, and the absence of a collar may be associated with lower fracture torque, which may be related to PPF. Cite this article: Bone Joint Res 2022;11(5):270-277.
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5.
What should be the goal of cholesterol-lowering treatment? A quantitative evaluation dispelling guideline myths.
Durrington, PN, Bashir, B, Soran, H
Current opinion in lipidology. 2022;(4):219-226
Abstract
PURPOSE OF REVIEW Guidelines for cholesterol-lowering treatment generally include extensive review of epidemiological and clinical trial evidence. However, the next logical step, the translation of evidence into clinical advice, occurs not entirely by reasoning, but by a form of consensus in which the prejudices and established beliefs of the societies with interests in cardiovascular disease convened to interpret the evidence are prominent. Methods, which are the subject of this review, have, however, been developed by which clinical trial evidence can be translated objectively into best practice. RECENT FINDINGS Guidelines differ in their recommended goals for cholesterol-lowering treatment in the prevention of atherosclerotic cardiovascular disease (ASCVD). Proposed goals are LDL-cholesterol 2.6 mmol/l (100 mg/dl) or less in lower risk, LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less in higher risk, non-HDL-cholesterol decrease of at least 40% or LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. Evidence from clinical trials of statins, ezetimibe and proprotein convertase subtilisin/kexin type 9-inhibitors can be expressed in simple mathematical terms to compare the efficacy on ASCVD incidence of clinical guidance for the use of cholesterol-lowering medication. The target LDL-cholesterol of 2.6 mmol/l (100 mg/dl) is ineffective and lacks credibility. Cholesterol-lowering medication is most effective in high-risk people with raised LDL-cholesterol. The best overall therapeutic target is LDL-cholesterol 1.8 mmol/l (70 mg/dl) or less or decreased by at least 50% whichever is lower. The use of non-HDL-cholesterol as a therapeutic goal is less efficacious. Aiming for LDL-cholesterol 1.4 mmol/l (55 mg/dl) or less as opposed to 1.8 mmol/l produces only a small additional benefit. Evidence for apolipoprotein B targets in hypertriglyceridaemia and in very high ASCVD risk should be more prominent in future guidelines. SUMMARY The LDL-cholesterol goal of 2.6 mmol/l or less should be abandoned. Percentage decreases in LDL-cholesterol or non-HDL-cholesterol concentration are better in people with initial concentrations of less than 3.6 mmol/l. The LDL-cholesterol target of 1.8 mmol/l is most effective when initial LDL-cholesterol is more than 3.6 mmol/l in both primary and secondary prevention.
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6.
Effect of exercise as adjuvant to energy-restricted diets on quality of life and depression outcomes: a meta-analysis of randomized controlled trials.
Rajaie, SH, Soltani, S, Yazdanpanah, Z, Zohrabi, T, Beigrezaei, S, Mohseni-Takalloo, S, Kaviani, M, Forbes, SC, Baker, JS, Salehi-Abargouei, A
Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation. 2022;(11):3123-3137
Abstract
BACKGROUND AND AIM Obesity and related co-morbidities lead to a decrease in health-related quality of life (HRQOL) and mood. Lifestyle strategies may improve these outcomes. However, the efficacy of exercise in conjunction with a weight-loss diet on HRQOL and mood is unclear. The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to examine whether the addition of exercise to energy-restricted dietary programs improves HRQOL and mood status when compared with energy-restricted diets alone in overweight and obese adults. METHODS Eligible RCTs were identified by searching PubMed/MEDLINE, EMBASE, ISI (Web of sciences), Scopus, and Google Scholar up to April 2021. Summary effects were derived using a random-effects model. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS The meta-analysis revealed that an energy-restricted diet plus exercise compared with an energy-restricted diet alone had no significant effects on depression (n = 6, hedges'g = - 0.04, 95% CI: - 0.28,0.20), MOS 36-Item Short-Form Health Survey (SF-36)-physical component summary scores (n = 8, weighted mean difference (WMD) = 1.51, 95% CI: - 0.16, 3.18), SF36-mental component summary scores (n = 7, WMD = 0.64, 95% CI: - 1.00, 2.28), and HRQOL disease-specific questionnaire scores (n = 5, hedges'g = 0.16, 95% CI: - 0.09, 0.40). The GRADE revealed that the quality of evidence was low for disease-specific HRQOL scores, and depression status; and high for physical and mental health assessed by SF-36. CONCLUSION In our sample of overweight and obese adults, no beneficial effect of adding exercise to an energy-restricted diet was found in terms of HRQOL and Depression.
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7.
Current Trends in Organ Preservation Solutions for Pancreas Transplantation: A Single-Center Retrospective Study.
Ferrer-Fàbrega, J, Folch-Puy, E, Lozano, JJ, Ventura-Aguiar, P, Cárdenas, G, Paredes, D, García-Criado, Á, Bombí, JA, García-Pérez, R, López-Boado, MÁ, et al
Transplant international : official journal of the European Society for Organ Transplantation. 2022;:10419
Abstract
Due to the high vulnerability of the pancreas to ischemia-reperfusion injury, choices regarding preservation solution markedly affect pancreas transplant success. A retrospective single-center analysis of 380 pancreas transplants (2000-2019) was performed to correlate current preservation solutions with transplant outcomes. Early graft failure requiring transplantectomy within 30 days post-transplant occurred in 7.5% for University of Wisconsin (UW) group (n = 267), 10.8% of Celsior (CS) group (n = 83), 28.5% of Histidine-Tryptophan-Ketoglutarate (HTK) group (n = 7), and none for Institut Georges Lopez-1 (IGL-1) group (n = 23). The most common causes of technical failures in this cohort included abdominal hemorrhage (8.4%); graft pancreatitis (3.7%); fluid collections (2.6%); intestinal complications (6.6%); and vascular thrombosis (20.5%). Although IGL-1 solution provided lower surgical complication rates, no significant differences were found between studied groups. Nevertheless, HTK solution was associated with elevated pancreatitis rates. The best graft survival was achieved at 1 year using UW and IGL-1, and at 3 and 5 years using IGL-1 (p = 0.017). There were no significant differences in patient survival after a median follow-up of 118.4 months. In this setting therefore, IGL-1 solution appears promising for perfusion and organ preservation in clinical pancreas transplantation, compared to other commonly used solutions.
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8.
Slow and Steady Wins the Race: 25 Years Developing the GLP-1 Receptor as an Effective Target for Weight Loss.
Kumar, N, D'Alessio, DA
The Journal of clinical endocrinology and metabolism. 2022;(8):2148-2153
Abstract
Recent evidence from clinical trials supports the efficacy and tolerability of glucagon-like peptide 1 (GLP-1) receptor agonists as useful agents for weight loss. Although originally developed as glucose lowering agents for people with type 2 diabetes, progress in research over the last 3 decades has demonstrated that GLP-1 receptor agonists act in the central nervous system to reduce food intake. This minireview summarizes key aspects of GLP-1 biology and the clinical studies supporting the utility of the GLP-1 receptor signaling system as a therapeutic target for weight loss.
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9.
Mitigating the Mistletoe Menace: Biotechnological and Smart Management Approaches.
Mudgal, G, Kaur, J, Chand, K, Parashar, M, Dhar, SK, Singh, GB, Gururani, MA
Biology. 2022;(11)
Abstract
Mistletoes have been considered a keystone resource for biodiversity, as well as a remarkable source of medicinal attributes that attract pharmacologists. Due to their hemiparasitic nature, mistletoes leach water and nutrients, including primary and secondary metabolites, through the vascular systems of their plant hosts, primarily trees. As a result of intense mistletoe infection, the hosts suffer various growth and physiological detriments, which often lead to tree mortality. Because of their easy dispersal and widespread tropism, mistletoes have become serious pests for commercial fruit and timber plantations. A variety of physical and chemical treatment methods, along with silvicultural practices, have shaped conventional mistletoe management. Others, however, have either failed to circumvent the growing range and tropism of these parasitic plants or present significant environmental and public health risks. A biocontrol approach that could sidestep these issues has never achieved full proof of concept in real-field applications. Our review discusses the downsides of conventional mistletoe control techniques and explores the possibilities of biotechnological approaches using biocontrol agents and transgenic technologies. It is possible that smart management options will pave the way for technologically advanced solutions to mitigate mistletoes that are yet to be exploited.
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10.
The Influence of Obesity and Weight Loss on the Bioregulation of Innate/Inflammatory Responses: Macrophages and Immunometabolism.
Gálvez, I, Navarro, MC, Martín-Cordero, L, Otero, E, Hinchado, MD, Ortega, E
Nutrients. 2022;(3)
Abstract
Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept "bioregulation of inflammatory/innate responses" was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual's inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.