A single dose of antibody-drug conjugate cures a stage 1 model of African trypanosomiasis.

Infections of humans and livestock with African trypanosomes are treated with drugs introduced decades ago that are not always fully effective and often have severe side effects. Here, the trypanosome haptoglobin-haemoglobin receptor (HpHbR) has been exploited as a route of uptake for an antibody-drug conjugate (ADC) that is completely effective against Trypanosoma brucei in the standard mouse model of infection. Recombinant human anti-HpHbR monoclonal antibodies were isolated and shown to be internalised in a receptor-dependent manner. Antibodies were conjugated to a pyrrolobenzodiazepine (PBD) toxin and killed T. brucei in vitro at picomolar concentrations. A single therapeutic dose (0.25 mg/kg) of a HpHbR antibody-PBD conjugate completely cured a T. brucei mouse infection within 2 days with no re-emergence of infection over a subsequent time course of 77 days. These experiments provide a demonstration of how ADCs can be exploited to treat protozoal diseases that desperately require new therapeutics

MR imaging in sports-related glenohumeral instability

Sports-related shoulder pain and injuries represent a common problem. In this context, glenohumeral instability is currently believed to play a central role either as a recognized or as an unrecognized condition. Shoulder instabilities can roughly be divided into traumatic, atraumatic, and microtraumatic glenohumeral instabilities. In athletes, atraumatic and microtraumatic instabilities can lead to secondary impingement syndromes and chronic damage to intraarticular structures. Magnetic resonance (MR) arthrography is superior to conventional MR imaging in the diagnosis of labro-ligamentous injuries, intrinsic impingement, and SLAP (superior labral anteroposterior) lesions, and thus represents the most informative imaging modality in the overall assessment of glenohumeral instability. This article reviews the imaging criteria for the detection and classification of instability-related injuries in athletes with special emphasis on the influence of MR findings on therapeutic decisions

The ACTIVE cognitive training trial and predicted medical expenditures

<p>Abstract</p> <p>Background</p> <p>Health care expenditures for older adults are disproportionately high and increasing at both the individual and population levels. We evaluated the effects of the three cognitive training interventions (memory, reasoning, or speed of processing) in the ACTIVE study on changes in predicted medical care expenditures.</p> <p>Methods</p> <p>ACTIVE was a multisite randomized controlled trial of older adults (≥ 65). Five-year follow-up data were available for 1,804 of the 2,802 participants. Propensity score weighting was used to adjust for potential attrition bias. Changes in predicted annual<b/>medical expenditures were calculated at the first and fifth annual follow-up assessments using a new method for translating functional status scores. Multiple linear regression methods were used in this cost-offset analysis.</p> <p>Results</p> <p>At one and five years post-training, annual predicted expenditures declined<b/>by $223 (p = .024) and$128 (p = .309), respectively, in the speed of processing treatment group, but there were no statistically significant changes in the memory or reasoning treatment groups compared to the no-contact control group at either period. Statistical adjustment for age, race, education, MMSE scores, ADL and IADL performance scores, EPT scores, chronic condition counts, and the SF-36 PCS and MCS scores at baseline did not alter the one-year ($244; p = .012) or five-year ($143; p = .250) expenditure declines in the speed of processing treatment group.</p> <p>Conclusion</p> <p>The speed of processing intervention significantly reduced subsequent annual predicted medical care expenditures at the one-year post-baseline comparison, but annual savings were no longer statistically significant at the five-year post-baseline comparison.</p

Correlates of loneliness among university students

Background The purpose of this study was to investigate level of loneliness, essential needs during university education, and relationships between loneliness, essential needs, and characteristics of university students. A sample comprising 721 students participated in the study. The mean age was 21.58 (SD = 1.73) with a range from 18 to 25. The majority of the students were female (70.6%) and were living in students' dormitory (67.5%) with low (87.8%) income, away from their parents. Methods The UCLA-R loneliness scale and sociodemographic questionnaire which includes an open-ended question on essential needs during university education were administered. Pearson-Product-Moment correlations were used to explore the relationships between participants' loneliness, needs, and characteristics. Results It was found that 60.2% of the participants experienced loneliness. Economical support (81.6%), social interaction (46.9%) and psychosocial support (35%) were the essential needs during university education reported by the participants. The study findings indicate that there were significant relationships between the needs of economical support, social interaction, and loneliness level of university students. Results also show that there were significant relationships among romantic relationship, parents' status and loneliness. Participants' loneliness levels were relatively higher who had not any romantic relationship and were not from married families. Conclusion The findings of this study provided essential information, about Turkish university students, concerning: level of loneliness and relationships that exist among loneliness, needs and sociodemographic characteristics. The findings also suggest implications for psychosocial practice. Because of the mean of loneliness were found to be high (45.49 ± 10.07), for this study, professionals need to pay attention to Turkish university students' psychosocial state, and need to empower them in establishing social relations

The Gambia National Eye Health Survey 2019: survey protocol.

Two national surveys of vision impairment and blindness were undertaken in The Gambia in 1986 and 1996. These provided data for the inception of The Gambia's National Eye Health Programme (NEHP) within the Ministry of Health and Social Welfare. There have been important developments in the eye health services provided by the NEHP in the last 20 years. At the same time, the population has also undergone major demographic changes that may have led to substantial changes in the burden of eye disease. We conducted a National Eye Health Survey of vision impairment, blindness and its comorbidities in adults in The Gambia in 2019. We examined a nationally representative population-based sample of adults 35 years and above to permit direct comparison with the data available from the previous surveys. Alongside a comprehensive vision and eye examination, the survey provides nationally representative data on important comorbidities in this population: diabetes, hypertension, obesity, hearing impairment, disability and mental health. Secondly, it estimates access to assistive technologies and eye health services. Thirdly, it is powered to allow a five-year follow up cohort study to measure the incidence and progression of eye disease

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion

Why Functional Pre-Erythrocytic and Bloodstage Malaria Vaccines Fail: A Meta-Analysis of Fully Protective Immunizations and Novel Immunological Model

Background: Clinically protective malaria vaccines consistently fail to protect adults and children in endemic settings, and at best only partially protect infants. Methodology/Principal Findings: We identify and evaluate 1916 immunization studies between 1965-February 2010, and exclude partially or nonprotective results to find 177 completely protective immunization experiments. Detailed reexamination reveals an unexpectedly mundane basis for selective vaccine failure: live malaria parasites in the skin inhibit vaccine function. We next show published molecular and cellular data support a testable, novel model where parasite-host interactions in the skin induce malaria-specific regulatory T cells, and subvert early antigen-specific immunity to parasite-specific immunotolerance. This ensures infection and tolerance to reinfection. Exposure to Plasmodium-infected mosquito bites therefore systematically triggers immunosuppression of endemic vaccine-elicited responses. The extensive vaccine trial data solidly substantiate this model experimentally. Conclusions/Significance: We conclude skinstage-initiated immunosuppression, unassociated with bloodstage parasites, systematically blocks vaccine function in the field. Our model exposes novel molecular and procedural strategies to significantly and quickly increase protective efficacy in both pipeline and currently ineffective malaria vaccines, and forces fundamental reassessment of central precepts determining vaccine development. This has major implications fo

Monoaminergic and histaminergic strategies and treatments in brain diseases

The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review.peer-reviewe

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs