Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting

Malaria infection induces the production of serum antibodiesto a variety of malaria antigens but the prevalence of antibodiesto any particular antigen ins typically mucb less than 100%.It has been assumed that non-responsiveness to defined antigensin malaria immune subjects is due to HLA mediated restricutionof the Immune response. In this study we have investigated therole of HLA and non-HLA genes in the antibody response to twomerozoite surface antigens (MSP1 and MSP2) and a sexual stageantigen (Pfs260/230) opf P{lasmodium falcpartum, and concludethat host genotype is not a major determinant of responsiveness.Although antibody levels vary in accordance with seasonal variationsin malaria transmission in semi-immune children, antibiody levelsremain stable in clncall immine adults.     

Cloning and analysis of the murine Fanconi anemia group C cDNA

Fanconi anemia (FA) is one of a group of disorders characterizedat the cellular level by a combination of hypersensitivity toDNA-damaging agents, chromosomal instability, and defectiveDNA repair. Clinical features of FA include pancytopenia, oftenaccompanied by specific congenital malformations, and a predispositionto leukemia. Since the hematological manifestations are thecritical defect in terms of prognosis, FA is a candidate diseasefor gene replacement therapy, and the development of a mousemodel system is essential for the initial stages of this work.Previously, we have cloned the gene defective in FA group Cby complementation of the intrinsic sensitivity of FA cellsto DNA cross-linking agents. We have now cloned the murine homologueof the human FACC cDNA. The mouse cDNA (Facc) shares 79% aminoacid sequence similarity with the human gene product. The expressionof the mouse cDNA in human FA(C) cells restores the cellulardrug sensitivity to normal levels. Thus, the function of theprotein has been conserved despite the significant sequencedivergence. PCR analysis of mouse tissue RNA reveals that thegene is expressed in all adult tissues, while in situ RNA hybridizationexperiments show tissue specific expression at late stages offetal development. Cross-hybridizing sequences exist in DNAfrom other mammals, chicken and Drosophila. These results supportthe hypothesis that the FACC gene product has a role in a basicaspect of cellular protection against DNA damaging agents andthat this function has been conserved during evolution.     

Phosphatidylserine externalization in human sperm induced by calcium ionophore A23187: relationship with apoptosis, membrane scrambling and the acrosome reaction

BACKGROUND: Translocation of phosphatidylserine (PS) from the inner to the outer leaflet of the plasma membrane is a modification of the lipid architecture occurring in sperm. This is one of the earliest signs of apoptosis that can be monitored by the calcium-dependent binding of annexin V. METHODS AND RESULTS: Flow cytometric analysis of annexin V binding was performed. Calcium ionophore A23187 led to a significant increase in the proportion of living sperm with PS exposure: 7.3 3.2% of cells in the untreated ejaculate versus 47.5 5.6% of cells after 1 h of incubation with A23187. Conversely, diminution of mitochondrial membrane potential [DiOC6(3)/propidium iodide (PI) assay], caspase activation [fluorescein isothiocyanate (FITC)-Val-Ala-Asp-fluoromethylketone (VAD-FMK)/PI assay], increased plasma membrane permeability (Yo-Pro-1/PI assay) and increased DNA fragmentation [TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay], which are among the main signs of apoptosis, were not observed in sperm, even after 4 h of incubation with A23187. However, A23187 significantly increased the proportion of sperm with plasma membrane scrambling and with a reacted acrosome, as detected with the merocyanine 540 probe (M540) and the monoclonal anti-human CD46-PE antibody respectively. CONCLUSIONS: Our results suggest that PS exposure in human sperm, as induced by A23187, is mainly related to the acrosome reaction rather than to apoptosis.     

Relationship between health beliefs and psychological variables in diabetic patients

The present paper is focused on the relationship between psychological variables and health beliefs in 93 diabetic men. A Diabetes Health Belief Scale was used to assess general health motivation, treatment beneficial, severity, susceptibility, psychological barriers, cues to action, and structural elements. The psychological variables included two measures of locus of control, depression, somatization, interpersonal sensitivity, obsessive—compulsiveness, anxiety, self-esteem, and attitudes toward diabetes, doctor, and medical care. Ten of the 11 psychological variables were correlated with various aspects of health beliefs. This indicates the extent to which the health beliefs are enmeshed with the psychological dynamics of the person. It would seem important to take such a psychological profile into consideration when attempting to understand and even alter the health beliefs.     

An Attempt to Elk it Cardiac Orienting and Defense Responses in the Newborn to Two Types of Facial Stimulation

Cardiac and behavioral reactivity of the human newborn to facial stimulation eliciting approach and escape responses were compared in order to test the distinction between cardiac orienting and defensive reactions. Each infant received 8 trials each of check stimulation (stroking near the mouth) and ear stimulation (pinch on the ear lobe). HR response to both tactile stimuli were accelerations of different amplitude when motor responses were also present. When no overt behavioral response was observed, stroking on the check elicited cardiac deceleration while ear stimulation again elicited acceleration. Thus, cardiac orienting was demonstrated in newborns when a rooting stimulus was presented that did not elicit overt head turning. The HR response to ear stimulation on trials unaccompanied by observed movements was a larger acceleration than to cheek stimulation when movement was present. This finding suggests that movement itself does not produce the observed HR increase, but rather that central processing of the signal value of the stimulus determines both overt and cardiac responding.     

APC from mice harbouring the filarial nematode, Brugia malayi, prevent cellular proliferation but not cytokine production

Specific T cell hyporesponsiveness and depressed antibody productionis a key feature of human infection with the filarial nematodes,Brugia malayi and Wuchereria bancrofti Despite this immune suppression,responses indicative of T_h2 subset activation are present, includingunusually high levels of specific lgG4. We tested the possibilitythat infection with filarial nematodes causes a reduction inthe co-stimulatory or antigen-presenting capacity of macrophagesresulting in a failure to activate specific T cells. Adherentperitoneal exudate cells (PEC) from mice implanted with adultB. malayi were used to present antigen to the conalbumin-specificT cell clone, D10.G4. Proliferation of the D10 cells at evenbackground levels was completely blocked by the presence ofimplant-derived adherent PEC. However, cytokine production bythese cells in response to antigen was intact, and thus PECfrom implanted mice are capable of functionally processing andpresenting antigen. The elicitation of a suppressive cell populationwas specific for live adults as cells from mice implanted withdead adult parasites effectively stimulated D10 proliferation.The block in cellular proliferation is not due to the productionof factors typically associated with macrophage suppressionsuch as nitric oxide, prostaglandins or catalase. These observationsare consistent with the T cell hyporesponsiveness seen in humancases of patent Brugia infection and may provide a murine modelfor the immune suppression seen in lymphatic filariasis.     

Introduction: The Quest for Birth Equity and Justice—Now is the Time

Maternal and Child Health Journal -     

Associations Between LGBTQ-Affirming School Climate and Intimate Partner Violence Victimization Among Adolescents

Prevention Science - Intimate partner violence (IPV) impacts sexual minority adolescents at rates equal to or greater than the rate it impacts heterosexual adolescents. We investigated whether...     

Discrimination Trends and Mental Health Among Native- and Foreign-Born Latinos: Results from National Surveys in 2004 and 2013

Prevention Science - We examined national trends and mental health correlates of discrimination among Latinos in the USA. We used data from two nationally representative surveys based on the...     

Machine Learning Algorithms to Predict Mortality and Allocate Palliative Care for Older Patients With Hip Fracture

ObjectivesTo evaluate a machine learning model designed to predict mortality for Medicare beneficiaries aged >65 years treated for hip fracture in Inpatient Rehabilitation Facilities (IRFs).DesignRetrospective design/cohort analysis of Centers for Medicare & Medicaid Services Inpatient Rehabilitation Facility–Patient Assessment Instrument data.Setting and ParticipantsA total of 17,140 persons admitted to Medicare-certified IRFs in 2015 following hospitalization for hip fracture.MeasuresPatient characteristics include sociodemographic (age, gender, race, and social support) and clinical factors (functional status at admission, chronic conditions) and IRF length of stay. Outcomes were 30-day and 1-year all-cause mortality. We trained and evaluated 2 classification models, logistic regression and a multilayer perceptron (MLP), to predict the probability of 30-day and 1-year mortality and evaluated the calibration, discrimination, and precision of the models.ResultsFor 30-day mortality, MLP performed well [acc = 0.74, area under the receiver operating characteristic curve (AUROC) = 0.76, avg prec = 0.10, slope = 1.14] as did logistic regression (acc = 0.78, AUROC = 0.76, avg prec = 0.09, slope = 1.20). For 1-year mortality, the performances were similar for both MLP (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.96) and logistic regression (acc = 0.68, AUROC = 0.75, avg prec = 0.32, slope = 0.95).Conclusion and ImplicationsA scoring system based on logistic regression may be more feasible to run in current electronic medical records. But MLP models may reduce cognitive burden and increase ability to calibrate to local data, yielding clinical specificity in mortality prediction so that palliative care resources may be allocated more effectively.