Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children.

Background: Two pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for Plasmodium falciparum malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine.

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant.

Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically.

Human Basigin (CD147) Does Not Directly Interact with SARS-CoV-2 Spike Glycoprotein.

Basigin, or CD147, has been reported as a coreceptor used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to invade host cells. Basigin also has a well-established role in Plasmodium falciparum malaria infection of human erythrocytes, where it is bound by one of the parasite's invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control.

At the birth of pediatric anesthesia in Mexico: An interview with Dr. Estela Melman, a pioneering woman in medicine.

Dr. Estela Melman (1939-present), Professor in the Department of Anesthesiology, the American British Cowdray Medical Center, Mexico, is an influential pioneer who has shaped the scope and practice of pediatric anesthesia in Mexico and throughout the world. Her early work to reintroduce neural blockade into routine pediatric anesthetic care, particularly the caudal approach to the epidural space, helped to transform current anesthesia practice.

Extension of overall survival beyond objective responses in patients with metastatic renal cell carcinoma treated with high-dose interleukin-2.

Purpose: In metastatic renal cell carcinoma (mRCC), survival benefit associated with objective response rates of 16-20 % with high-dose interleukin-2 (HDIL-2) is well established and discussed. Based on recently emerged data on efficacy of cancer immunotherapy, we hypothesized that the survival benefit with HDIL-2 extends beyond those achieving objective responses, i.e.

Assessing the role of alternative response rates and reinforcer rates in resistance to extinction of target responding when combining stimuli.

Studies of behavioral momentum reveal that reinforcing an alternative response in the presence of a target response reduces the rate of target responding but increases its persistence, relative to training the target response on its own. Because of the parallels between these studies and differential-reinforcement techniques to reduce problem behavior in clinical settings, alternative techniques to reduce problem behavior without enhancing its persistence are being explored. One potential solution is to train an alternative response in a separate stimulus context from problem behavior before combining the alternative stimulus with the target stimulus.

Prophage induction is enhanced and required for renal disease and lethality in an EHEC mouse model.

Enterohemorrhagic Escherichia coli (EHEC), particularly serotype O157:H7, causes hemorrhagic colitis, hemolytic uremic syndrome, and even death. In vitro studies showed that Shiga toxin 2 (Stx2), the primary virulence factor expressed by EDL933 (an O157:H7 strain), is encoded by the 933W prophage. And the bacterial subpopulation in which the 933W prophage is induced is the producer of Stx2.

Archaeal intrinsic transcription termination in vivo.

Thermococcus kodakarensis (formerly Thermococcus kodakaraensis) strains have been constructed with synthetic and natural DNA sequences, predicted to function as archaeal transcription terminators, identically positioned between a constitutive promoter and a beta-glycosidase-encoding reporter gene (TK1761). Expression of the reporter gene was almost fully inhibited by the upstream presence of 5'-TTTTTTTT (T(8)) and was reduced >70% by archaeal intergenic sequences that contained oligo(T) sequences. An archaeal intergenic sequence (t(mcrA)) that conforms to the bacterial intrinsic terminator motif reduced TK1761 expression approximately 90%, but this required only the oligo(T) trail sequence and not the inverted-repeat and loop region.

Health status among 28,000 women veterans. The VA Women's Health Program Evaluation Project.

Background: Male veterans receiving Veterans Health Administration (VA) care have worse health than men in the general population. Less is known about health status in women veteran VA patients, a rapidly growing population.

Objective: To characterize health status of women (vs men) veteran VA patients across age cohorts, and assess gender differences in the effect of social support upon health status.

Applications of methodologies of the Veterans Health Study in the VA healthcare system: conclusions and summary.

The Veterans Health Study (VHS) had as its overarching goal the development, testing, and application of patient-centered assessments for monitoring patient outcomes in ambulatory care in large integrated care systems such as the Department of Veterans Affairs (VA). Unlike other previous studies, the VHS has capitalized on rich administrative databases restricted to the VA and linked to patient-centered outcomes. The VHS has developed a comprehensive set of general and disease-specific measures for use by systems of care for ambulatory patients.

Disparities in diabetes care: impact of mental illness.

Background: Emerging evidence indicates that patients with mental health conditions (MHCs) may receive less intensive medical care. Diabetes serves as a useful condition in which to test for MHC-related disparities in care. We examined whether quality measures for diabetes care are worse for patients with or without MHCs.

The illness burden of alcohol-related disorders among VA patients: the veterans health study.

Little is known about the illness burden associated with alcohol-related disorders (ie, problem drinking, alcohol abuse, and alcohol dependence) among patients in outpatient medical care. The objective of this study was to examine several aspects of illness burden-medical comorbidities, patterns of health services use, and functional status-among Veterans Health Administration (VA) ambulatory care patients with alcohol-related disorders. Male participants (N = 2425) were recruited at 1 of 4 Boston-area VA outpatient clinics.

Patient-based measures of illness severity in the Veterans Health Study.

The Veterans Health Study (VHS) was designed to produce patient-based measures of health status suitable for monitoring the health of men served by the Veterans Health Administration. This article summarizes the objectives, conceptual framework, and results of 6 substudies of the VHS that were designed to develop disease-focused measures of illness severity, that is, patient-perceived, clinically significant manifestations of disease processes that are associated with decrements in health-related quality of life. Developmental psychometric studies used cross-sectional survey data from the baseline comprehensive evaluations conducted in the VHS.

Preliminary validation of a patient-based self-assessment measure of severity of illness in type 2 diabetes: results from the pilot phase of the Veterans Health Study.

Measures of case mix are needed to control for patients' clinical status in studies assessing the process and outcomes of care. The Veterans Health Study (VHS) is a longitudinal study of determinants of health outcomes in ambulatory veterans. This study assessed the validity of a case-mix measure developed to quantify severity of illness in ambulatory type 2 diabetic patients.

Utilization of medical services by Veterans Health Study (VHS) respondents.

The first objective of this study was to profile Veterans Health Study (VHS) respondents' use of medical services-the types of services used, use of a regular source of care, and the propensity to use services for selected symptoms. We focused on differential use of VA and non-VA services and highlighted differences in use by age group. The second objective was to use multivariate analysis to identify factors associated with respondents' use of any medical services and with VA services specifically.

The influence of place of administration on health-related quality-of-life assessments: findings from the Veterans Health Study.

Patient-based assessments of functional status and well-being, such as the short form survey (SF-36) developed in the Medical Outcomes Study, are increasingly used to monitor patient health status and the effects of medical care. Although they have been used in many populations under a variety of circumstances, little is known about how environmental factors, such as place of administration, influence patients' responses. We administered the SF-36 as part of comprehensive quality-of-life assessments to 304 participants in the pilot phase of the Veterans Health Study, a large observational study of health outcomes in VA ambulatory care.

Concordance between respondent self-reports and medical records for chronic conditions: experience from the Veterans Health Study.

Researchers have frequently relied on case identification using clinician-based screening as the standard. This study evaluates a self-administered screening questionnaire developed for use in the Veterans Health Study. We compared concordance between elderly patients' reports of selected chronic illnesses and the medical record.

Effect of patient gender on late-life depression management.

Purpose: To determine whether patient gender influences physicians' management of late-life major depression in older and younger elderly patients.

Methods: In 1996-2001, physician subjects viewed a professionally produced videotape vignette portraying an elderly patient meeting diagnostic criteria for major depression, then answered interviewer-administered questions about differential diagnosis and treatment. Patient gender and other characteristics were systematically varied in different versions of the videotape, but clinical content was held constant.

Comorbidity assessments based on patient report: results from the Veterans Health Study.

The objective of the study was to develop a self-reported measure of patients' comorbid illnesses that could be readily administered in ambulatory care settings and that would improve assessment of their health-related quality of life and utilization of health services. Data were analyzed from the Veterans Health Study, an observational study of health outcomes in patients receiving Veterans Administration (VA) ambulatory care. Patients who received ambulatory care services in 4 VA outpatient clinics in the greater Boston area between August 1993 and March 1996 were eligible for inclusion.

Improving the response choices on the veterans SF-36 health survey role functioning scales: results from the Veterans Health Study.

Role functioning and its limitations due to one's health is an important aspect of health-related quality of life (HRQoL). The Medical Outcomes Study (MOS) SF-36 includes 2 role functioning scales: role limitations due to physical health problems (RP) or emotional problems (RE). Although they capture important concepts of HRQoL, these 2 scales have some limitations in their measurement properties.

Comparing the health status of VA and non-VA ambulatory patients: the veterans' health and medical outcomes studies.

The purpose of this study was to compare health status and disease profiles of ambulatory patients in specific Veterans Administration (VA) and civilian healthcare settings. A random sample of 2425 male veterans seeking care at 4 Boston-area VA outpatient clinics, who took part in the Veterans Health Study (VHS) in 1993-1995, were compared to 1318 male patients seeking civilian outpatient care in 3 major metropolitan areas covered in the Medical Outcomes Study (MOS) in 1986. The MOS sampled patients who had 1 of 5 conditions--hypertension, noninsulin-dependent diabetes, recent myocardial infarction, congestive heart failure, or depression.

Burden of medical illness in women with depression and posttraumatic stress disorder.

Background: Depression and posttraumatic stress disorder (PTSD) are important women's health issues. Depression is known to be associated with poor physical health; however, associations between physical health and PTSD, a common comorbidity of depression, have received less attention.

Objectives: To examine number of medical symptoms and physical health status in women with PTSD across age strata and benchmark them against those of women with depression alone or with neither depression nor PTSD.

The relationship between sexual assault, religiosity, and mental health among male veterans.

Objectives: We examine the association between sexual assault, religion and mental health among male veterans.

Methods: We used longitudinal data collected from 2,427 male veterans who received VA outpatient care. Sexual assault was self-reported in the questionnaire.