Kinetic analysis of interactions between bispecific monoclonal antibodies and immobilized antigens using a resonant mirror biosensor

A resonant mirror biosensor (IAsys) protocol is described for the comparative kinetic analysis of the ability of monoclonal antibodies (Mabs) and bispecific antibodies (Babs) to bind immobilized antigens. The protocol has been optimized and validated using the panel of affinity-purified antibodies, including two parental Mabs, one specific to human immunoglobulin G (hIgG) and another specific to horseradish peroxidase (HRP), and a Bab derived thereof by cell fusion (anti-hIgG/HRP Bab). The real-time kinetic analysis of antigen–antibody interactions using this protocol allows to demonstrate the differences in the avidity of bivalently binding Mabs and monovalent Babs. As shown in our previous study [J. Immunol. Methods 261 (2002) 103], the observed equilibrium association constants (K_ass) determined by IAsys using this protocol yield figures almost overlapping with those obtained by solid-phase radioimmunoassay (RIA). The described protocol is suited for the investigation of the effects of valency on the binding properties of antibodies. It also may be applied for the selection of Mabs and Babs with desired features, for different fields of application.     

Electroconvulsive therapy in adolescent and adult psychiatric inpatients--a retrospective chart design

BACKGROUND: The knowledge available on electroconvulsive therapy (ECT) in adolescents is largely anecdotal, or based on findings from adults. The aim of the present study is to compare the use of ECT in adolescent and adult inpatients. METHODS: We retrospectively analyzed the files of all 36 adolescent (between the ages of 13 and 19) and 57 randomly selected adult inpatients (above the age of 20) treated with ECT in a university-affiliated mental heath center in Israel between 1991 and 1997. RESULTS: Sixty one percent of the adolescents improved by the end of treatment, and 53% were not hospitalized in the subsequent year. The respective percentages among adults were 83% and 49%. Whereas most adults were treated with ECT because of schizophrenic disorders, almost half of the adolescents received ECT for affective disorders. Significantly more adolescents were treated with ECT because of acute life-endangering conditions (catatonia or severe suicidal risk). No significant adverse effects were found in both groups. LIMITATIONS: Our study is based on a retrospective chart review. The adolescent and adult groups are different in psychiatric morbidity, diagnosis and outcome, have not been assessed in a blind manner, and we have not used standardized psychometric batteries for the evaluation of ECT-related memory disturbances. CONCLUSIONS: ECT may be an effective, well-tolerated and safe procedure in both adult and adolescent inpatients.     

DNA immunization efficiently targets conserved functional domains of protease and ATPase/helicase of nonstructural 3 protein (NS3) of human hepatitis C virus

Nonstructural protein 3 (NS3) of human hepatitis C virus (HCV) is a conserved multi-functional protein essential for replication and translation of viral RNA and polyprotein processing. Early T-cell response against NS3 is capable of restricting viremia. We aimed at characterizing the immunogenicity in gene immunization of the conserved regions of NS3 critical for protein folding and activity. C57BL/6 mice were injected with NS3 gene of Russian HCV 1b isolate 274933RU. Immunization did not exert any overt histological changes and had no long-term effects on the immune status of NS3 gene-recipients. The immune response in NS3 gene-recipients was screened by antibody ELISA, T-cell proliferation test and immune assays for specific cytokine production. T-lymphocytes of NS3 gene-recipients proliferated in response to peptides representing conserved regions of protease and ATPase/helicase. Stimulated T-lymphocytes produced IL-2, and in response to protease-derived peptides, also IFN-gamma. Potent and long-lasting antibody response was raised against conserved NS3 regions including "Greek-key" motif of protease, motifs II, V and polynucleotide-binding domains of ATPase/helicase. Thus, gene immunization effectively targeted conserved regions critical for NS3 protease and helicase function. In type and specificity, immune response of NS3 gene-immunized mice mimicked immunity achieved in the acute self-limiting HCV infection of human and primates and in virus-exposed healthy individuals, indicating promiscuity of NS3 as immunogen.     

Adherence to COVID-19 Nutrition Guidelines Is Associated with Better Nutritional Management Behaviors of Hospitalized COVID-19 Patients

Good nutritional support is crucial for the immune system to fight against coronavirus disease 2019 (COVID-19). However, in the context of a pandemic with a highly transmissible coronavirus, implementation of nutrition practice may be difficult. A multicenter electronic survey involving 62 dieticians was conducted, in order to understand barriers associated with dieticians’ adherence to nutrition guidelines for hospitalized COVID-19 patients in Indonesia. 69% of dieticians felt under stress when performing nutrition care, and 90% took supplements to boost their own immunity against the coronavirus. The concerns related to clinical practice included a lack of clear guidelines (74%), a lack of access to medical records (55%), inadequate experience or knowledge (48%), and a lack of self-efficacy/confidence (29%) in performing nutritional care. Half (52%) of the dieticians had performed nutrition education/counseling, 47% had monitored a patient’s body weight, and 76% had monitored a patient’s dietary intake. An adjusted linear regression showed that guideline adherence independently predicted the dieticians’ nutrition care behaviors of nutrition counselling (ß: 0.24 (0.002, 0.08); p = 0.04), and monitoring of body weight (ß: 0.43 (0.04, 0.11); p = 0.001) and dietary intake (ß: 0.47(0.03, 0.10); p = 0.001) of COVID-19 patients. Overall, adherence to COVID-19 nutrition guidelines is associated with better nutritional management behaviors in hospitalized COVID-19 patients.     

Predictors and consequences of HIV status disclosure to adolescents living with HIV in Eastern Cape,South Africa: a prospective cohort study

IntroductionThe World Health Organization recommends full disclosure of HIV‐positive status to adolescents who acquired HIV perinatally (APHIV) by age 12. However, even among adolescents (aged 10–19) already on antiretroviral therapy (ART), disclosure rates are low. Caregivers often report the child being too young and fear of disclosure worsening adolescents’ mental health as reasons for non‐disclosure. We aimed to identify the predictors of disclosure and the association of disclosure with adherence, viral suppression and mental health outcomes among adolescents in sub‐Saharan Africa.MethodsAnalyses included three rounds (2014–2018) of data collected among a closed cohort of adolescents living with HIV in Eastern Cape, South Africa. We used logistic regression with respondent random‐effects to identify factors associated with disclosure, and assess differences in ART adherence, viral suppression and mental health symptoms between adolescents by disclosure status. We also explored differences in the change in mental health symptoms and adherence between study rounds and disclosure groups with logistic regression.ResultsEight hundred and thirteen APHIV were interviewed at baseline, of whom 769 (94.6%) and 729 (89.7%) were interviewed at the second and third rounds, respectively. The proportion aware of their HIV‐positive status increased from 63.1% at the first round to 85.5% by the third round. Older age (adjusted odds ratio [aOR]: 1.27; 1.08–1.48) and living in an urban location (aOR: 2.85; 1.72–4.73) were associated with disclosure between interviews. There was no association between awareness of HIV‐positive status and ART adherence, viral suppression or mental health symptoms among all APHIV interviewed. However, among APHIV not aware of their status at baseline, adherence decreased at the second round among those who were disclosed to (N = 131) and increased among those not disclosed to (N = 151) (interaction aOR: 0.39; 0.19–0.80). There was no significant difference in the change in mental health symptoms between study rounds and disclosure groups.ConclusionsAwareness of HIV‐positive status was not associated with higher rates of mental health symptoms, or lower rates of viral suppression among adolescents. Disclosure was not associated with worse mental health. These findings support the recommendation for timely disclosure to APHIV; however, adherence support post‐disclosure is important.     

Bioceramics Based on β-Calcium Pyrophosphate

Ceramic samples based on β-calcium pyrophosphate β-Ca₂P₂O₇ were prepared from powders of γ-calcium pyrophosphate γ-Ca₂P₂O₇ with preset molar ratios Ca/P = 1, 0.975 and 0.95 using firing at 900, 1000, and 1100 °C. Calcium lactate pentahydrate Ca(C₃H₅O₃)₂⋅5H₂O and monocalcium phosphate monohydrate Ca(H₂PO₄)₂⋅H₂O were treated in an aqua medium in mechanical activation conditions to prepare powder mixtures with preset molar ratios Ca/P containing calcium hydrophosphates with Ca/P = 1 (precursors of calcium pyrophosphate Ca₂P₂O₇). These powder mixtures containing calcium hydrophosphates with Ca/P = 1 and non-reacted starting salts were heat-treated at 600 °C after drying and disaggregation in acetone. Phase composition of all powder mixtures after heat treatment at 600 °C was presented by γ-calcium pyrophosphate γ-Ca₂P₂O₇ according to the XRD data. The addition of more excess of monocalcium phosphate monohydrate Ca(H₂PO₄)₂·H₂O (with appropriate molar ratio of Ca/P = 1) to the mixture of starting components resulted in lower dimensions of γ-calcium pyrophosphate (γ-Ca₂P₂O₇) individual particles. The grain size of ceramics increased both with the growth in firing temperature and with decreasing molar ratio Ca/P of powder mixtures. Calcium polyphosphate (t _melt = 984 °C), formed from monocalcium phosphate monohydrate Ca(H₂PO₄)₂⋅H₂O, acted similar to a liquid phase sintering additive. It was confirmed by tests in vitro that prepared ceramic materials with preset molar ratios Ca/P = 1, 0.975, and 0.95 and phase composition presented by β-calcium pyrophosphate β-Ca₂P₂O₇ were biocompatible and could maintain bone cells proliferation.     

Validation of semi-automatic device UA-704 for self-measurement of blood pressure

OBJECTIVE: To perform a clinical validation for a semi-automatic arm-type device UA-704 (A&D Company, Ltd., Tokyo, Japan) according to the British Hypertension Society protocol. METHODS: Eighty-five study participants (37 men) were included. The mean age was 50.1+/-17.0 years, systolic blood pressure range was 79-212 mmHg and diastolic blood pressure range was 43-118 mmHg. For each participant, three readings of the UA-704 were compared with simultaneous auscultatory measurements by two trained independent observers. The observers used a mercury calibrated sphygmomanometer and a dual stethoscope. The results were graded according to the 1993 British Hypertension Society protocol. RESULTS: The average difference between mercury sphygmomanometer and UA-704 readings was -1.85+/-4.26 mmHg (mean+/-SD) for systolic blood pressure and -1.44+/-3.97 mmHg for diastolic blood pressure. The proportions of values agreeing to within 5, 10 and 15 mmHg were 79.2%, 96.5% and 99.6% for systolic blood pressure and 86.7%, 96.9% and 99.6% for diastolic blood pressure for the observers and device (A/A grade for British Hypertension Society). CONCLUSIONS: For an adult population, the UA-704 device for self-measurement of blood pressure achieved a British Hypertension Society grade A/A and therefore can be recommended for home blood pressure monitoring.