Glucose responsive hydrogel networks based on protein recognition

Stimuli-responsive materials capable of manifesting physical changes in response to environmental signals are valuable tools for use in a variety of biomedical applications. Herein we describe one such smart glucose-responsive hydrogel material prepared by immobilizing the glucose/galactose binding protein within an acrylamide hydrogel network. This hydrogel demonstrates a quantitative "accordion"-like dynamic response in the presence of glucose. We further show the feasibility of employing this responsive smart material as a gating agent for controlled drug delivery, thus, demonstrating that these hydrogels may eventually lead to the development of implantable drug delivery systems for diabetes management applications

Stimuli-Responsive Hydrogels Based on the Genetically Engineered Proteins: Actuation, Drug Delivery and Mechanical Characterization

Herein, we describe a biomimetic approach aimed at the development of synthetic biohybrid materials inspired by nature's sensing and actuating mechanism of action. The biomaterials are based on the incorporation of the hinge-motion binding protein calmodulin (CaM) and its low affinity ligand phenothiazine (TAPP) within the bulk of an acrylamide hydrogel network, which is accomplished through covalent binding. At the initial state and in the presence of Ca 2+ ions, CaM interacts with TAPP creating chemical (non-covalent) cross-links within the bulk of the hydrogel, forcing the material to assume a constrictive configuration. Upon the removal of Ca 2+ , CaM releases TAPP, breaking the non-covalent cross-links within the bulk of the hydrogel and letting the material relax into a swollen state. The same type of effect is observed when a higher affinity ligand for CaM, like chlorpromazine (CPZ), is employed. In the presence of CPZ, the protein releases TAPP and binds CPZ, allowing the biomaterial to swell into a relaxed state. This swelling response of the biomaterial is reversible, and is directly related to the levels of CPZ used. The sensing and subsequent actuating mechanism of the CaM-based stimuli-sensitive hydrogels makes them suitable for a variety of applications, including sensing, mechanical actuation, high-throughput screening, and drug delivery. Additionally, it is shown that the CaM-based stimuli-sensitive hydrogels developed present unique mechanical properties, suitable for integration within microfluidics and MEMS structures. It is envisioned that these biomaterials will find a number of applications in a variety of fields, including drug delivery

Stimuli-Responsive Hydrogels Based on the Genetically Engineered Proteins: Actuation, Drug Delivery and Mechanical Characterization

Herein, we describe a biomimetic approach aimed at the development of synthetic biohybrid materials inspired by nature's sensing and actuating mechanism of action. The biomaterials are based on the incorporation of the hinge-motion binding protein calmodulin (CaM) and its low affinity ligand phenothiazine (TAPP) within the bulk of an acrylamide hydrogel network, which is accomplished through covalent binding. At the initial state and in the presence of Ca 2+ ions, CaM interacts with TAPP creating chemical (non-covalent) cross-links within the bulk of the hydrogel, forcing the material to assume a constrictive configuration. Upon the removal of Ca 2+ , CaM releases TAPP, breaking the non-covalent cross-links within the bulk of the hydrogel and letting the material relax into a swollen state. The same type of effect is observed when a higher affinity ligand for CaM, like chlorpromazine (CPZ), is employed. In the presence of CPZ, the protein releases TAPP and binds CPZ, allowing the biomaterial to swell into a relaxed state. This swelling response of the biomaterial is reversible, and is directly related to the levels of CPZ used. The sensing and subsequent actuating mechanism of the CaM-based stimuli-sensitive hydrogels makes them suitable for a variety of applications, including sensing, mechanical actuation, high-throughput screening, and drug delivery. Additionally, it is shown that the CaM-based stimuli-sensitive hydrogels developed present unique mechanical properties, suitable for integration within microfluidics and MEMS structures. It is envisioned that these biomaterials will find a number of applications in a variety of fields, including drug delivery

International consensus on a standard set of outcome measures for child and youth anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder

International audienceA major barrier to improving care effectiveness for mental health is a lack of consensus on outcomes measurement. The International Consortium for Health Outcomes Measurement (ICHOM) has already developed a consensus-based standard set of outcomes for anxiety and depression in adults (including the Patient Health Questionnaire-9, the Generalised Anxiety Disorder 7-item Scale, and the WHO Disability Schedule). This Position Paper reports on recommendations specifically for anxiety, depression, obsessive-compulsive disorder, and post-traumatic stress disorder in children and young people aged between 6 and 24 years. An international ICHOM working group of 27 clinical, research, and lived experience experts formed a consensus through teleconferences, an exercise using an adapted Delphi technique (a method for reaching group consensus), and iterative anonymous voting, supported by sequential research inputs. A systematic scoping review identified 70 possible outcomes and 107 relevant measurement instruments. Measures were appraised for their feasibility in routine practice (ie, brevity, free availability, validation in children and young people, and language translation) and psychometric performance (ie, validity, reliability, and sensitivity to change). The final standard set recommends tracking symptoms, suicidal thoughts and behaviour, and functioning as a minimum through seven primarily patient-reported outcome measures: the Revised Children's Anxiety and Depression Scale, the Obsessive Compulsive Inventory for Children, the Children's Revised Impact of Events Scale, the Columbia Suicide Severity Rating Scale, the KIDSCREEN-10, the Children's Global Assessment Scale, and the Child Anxiety Life Interference Scale. The set's recommendations were validated through a feedback survey involving 487 participants across 45 countries. The set should be used alongside the anxiety and depression standard set for adults with clinicians selecting age-appropriate measures

EVALUATION OF LEUKOCYTE ESTERASE REAGENT STRIPS TEST IN THE DIAGNOSIS OF SPONTANEOUS BACTERIAL PERITONITIS IN CHILDREN WITH CIRRHOSIS

BACKGROUND: Spontaneous bacterial peritonitis is defined as an ascetic fluid infection without an evident intra-abdominal surgically treatable source. Spontaneous bacterial peritonitis is one of the severe complications in patients with cirrhosis and ascites. Without early antibiotic treatment, this complication is associated with high mortality rate; therefore, early diagnosis and treatment of spontaneous bacterial peritonitis is necessary for survival. Leukocyte esterase reagent can rapidly diagnose the spontaneous bacterial peritonitis. OBJECTIVE: This study aimed to find out the diagnostic accuracy of leukocyte esterase dipstick test for the diagnosis of spontaneous bacterial peritonitis. METHODS: A single centered hospital-based cross-sectional study was conducted during July 2013 to August 2014 on children with cirrhotic liver disease and ascites who were admitted in the Department of Pediatric Gastroenterology in Nemazee Hospital affiliated to Shiraz University of Medical Sciences (Iran). All patients underwent abdominal paracentesis, and the ascitic fluid was processed for cell count, leukocyte esterase reagent strip test (Combiscreen SL10) and culture. Spontaneous bacterial peritonitis was defined as having a polymorphonuclear count (PMN >/=250/m3) in ascitic fluid. Sensitivity, specificity, positive predictive value and negative predictive value of leukocyte esterase test were calculated according to the formula. RESULTS: Totally, 150 ascitic fluid sample of cirrhotic male patients (53.2) and their mean age (4.33+/-1.88 years) were analyzed. Biliary atresia (n=44, 29.4) and idiopathic neonatal hepatitis (n=29, 19.3) were the most frequent etiology of cirrhosis. Also, abdominal pain (68.6) and distension (64) were the most common presenting complaint. Of all cases, 41 patients (27.35) were diagnosed to have spontaneous bacterial peritonitis (PMN >/=250/mm3). Sensitivity and specificity of leukocyte esterase reagent test according to PMNs >/=250 mm3 were 87.80 and 91.74, also on ascitic fluid culture results were 88.23 and 77.44. Positive predictive value and negative predictive value of this test in PMNs >/=250 mm3 were 80 and 95.23 and in cases with positive culture 33.33 and 98.09 were obtained, respectively. Efficiency of leukocyte esterase reagent test in diagnosing spontaneous bacterial peritonitis, according to PMNs >/=250 mm3 and culture results were 90.66 and 78.66. CONCLUSION: The leukocyte esterase strip test may be used as rapid test for diagnosis of spontaneous bacterial peritonitis due to its high diagnostic validity