In the Era of mRNA Vaccines,Is There Any Hope for HIV Functional Cure?

Over 36 million people worldwide are infected with HIV. Antiretroviral therapy (ART) has proven to be highly effective to prevent HIV-1 transmission, clinical progression and death. Despite this success, the number of HIV-1 infected individuals continues increasing and ART should be taken for life. Therefore, there are two main priorities: the development of preventive vaccines to protect from HIV acquisition and achieve an efficient control of HIV infection in the absence of ART (functional cure). In this sense, in the last few years, there has been a broad interest in new and innovative approaches such as mRNA-based vaccines. RNA-based immunogens represent a promising alternative to conventional vaccines because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. Some mRNA-based vaccines platforms against infectious diseases have demonstrated encouraging results in animal models and humans. However, their application is still limited because the instability and inefficient in vivo delivery of mRNA. Immunogens, design, immunogenicity, chemical modifications on the molecule or the vaccine delivery methods are all crucial interventions for improvement. In this review we, will present the current knowledge and challenges in this research field. mRNA vaccines hold great promises as part of a combined strategy, for achieving HIV functional cure.     

Intimate partner violence as a mechanism of traumatic ocular injury in women

ObjectiveDetermine the prevalence of intimate partner violence (IPV) as a mechanism of traumatic ocular injury in women, typical injury patterns, and the clinical course of affected patients. Encourage IPV screening and safety assessment in patients presenting with characteristic ocular trauma.MethodsMedical records of 211 female patients with traumatic ocular injuries evaluated at the University of Iowa Hospitals and Clinics between January 1995 and January 2015 were reviewed to determine the rate of IPV as a mechanism of ocular trauma. Twenty-one patients were excluded due to no documented trauma.ResultsLeading causes of traumatic ocular injuries in the 190 female patients included were accidental trauma with an inanimate object (n = 70/190, 36.8%), falls (n = 52/190, 27.4%), motor vehicle collisions (n = 21/190, 11.1%), and assault (n = 16/190, 8.4%). In 2.1% of cases (n = 4/190), no mechanism of traumatic injury was documented. Assault was the fourth leading mechanism of injury accounting for 8.4% of cases (n = 16/190), with IPV accounting for more than one third of cases with a documented perpetrator (n = 5/13). No perpetrator was documented in 18.8% (n = 3/16). All 5 patients with IPV-related injuries sustained scleral laceration or rupture; 4 out of 5 patients had no light perception vision and ultimately required enucleation.ConclusionIPV is an important mechanism of traumatic ocular injury. IPV-associated injuries tend to be severe in nature, as demonstrated by the high rate of globe laceration or rupture and subsequent enucleation in the study population. By appropriate screening and referral, ophthalmologists have an opportunity to redirect a potentially devastating course.     

FETAL SCALP BLOOD SAMPLING

Fetal scalp blood sampling (FSBS), in conjunction with fetal heart rate monitoring, is a method of fetal surveillance that may avoid cesarean delivery of the healthy fetus or indicate the need for immediate delivery of a compromised fetus. Some researchers have recently begun to question the efficacy of FSBS. In this article, three nurse-midwives discuss FSBS as a tool in assessing fetal well-being during labor and consider whether FSBS is a nurse-midwifery procedure.     

Total-body protein turnover in parenterally fed neonates: effects of energy source studied by using [15N]glycine and [1-13C]leucine

The effects of nonprotein energy source (ie, glucose only vs glucose and lipid) on nitrogen retention and total-body protein turnover were studied in 20 parenterally fed newborn infants. All infants received approximately 3 g amino acids and 80-90 kcal.kg body wt.d. Total-body protein synthesis was estimated by using three constant-infusion, end-product methods: enrichment of urinary urea and ammonia in response to a [15N]glycine label and exhaled carbon dioxide enrichment in response to a [1-13C]leucine label. No differences were seen in nitrogen retention between the two energy sources. The estimate of total-body protein turnover obtained from the 13C label was similar to that obtained with the [15N]urea label. No differences in turnover rates were observed between the two diet groups. Use of the glucose-plus-lipid fuel system enhanced energy storage and the reutilization of amino acid for protein synthesis.     

Immunologic and pharmacologic concepts of monoclonal antibodies

While monoclonal antibodies have solved many of the difficulties of using immunologic reagents for radioimmunodiagnosis and therapy, in the 13 years since their introduction a number of persistent problems remain, most notably a low yield of antibody-producing cells from the fusion process, difficulty in obtaining high-affinity antibodies, and the potential immunogenicity of murine immunoglobulins (Igs). Several solutions are under development, including fusion techniques that enrich for cells producing desired antibodies, production of human-mouse chimeric antibodies by recombinant DNA technology, and the generation of human monoclonal antibodies by promising new approaches. Until these upcoming methodologies are established, and to better direct their development and application, a sound understanding of the pharmacology of presently available native and modified monoclonal antibodies is crucial. Although much has been already determined in this area, a great deal of further clarification remains necessary.     

The 5-Step family intervention in primary care: II. The views of primary healthcare professionals

Background: This is the second of two papers using qualitative methods from a study of an intervention for family members affected by close relatives' substance misuse problems.

Participants: 168 primary healthcare professionals (PHCPs: GPs, practice nurses and health visitors) working in general practices in two areas of England, and who took part in the study.

Data sources: Recruitment and post-session forms completed by PHCPs; telephone interviews with each PHCP 12 weeks after recruitment of a family member; interviews with PHCPs at the end of the study.

Results: At the end of the project PHCPs were overwhelmingly positive about the family member intervention and about primary care as the appropriate site. Difficulties were encountered, however, in identifying and engaging affected family members, who were often excluded on grounds of the complexity of their problems or the level of their distress. Shortage of PHCP time and other practice-related factors added to the difficulty. Active work by a PHCP was often necessary in order to make the link between presenting symptoms of physical or mental ill-health and the existence of a family substance misuse problem. When family members were identified and recruited, PHCPs were usually positive about what was achieved. Nearly all were in favour of an approach that combined giving a self-help manual with some follow-up contact with a family member as needed.

Conclusions: Taken in conjunction with statistical outcome findings of significant reductions in symptoms and changes in ways of coping, plus qualitative analysis of the views of family members, the present results encourage the view that a flexible form of this intervention should be developed for use in primary healthcare, and that further work should build on existing strengths and attempt to overcome weaknesses identified.     

Doctors as managers: investors and reluctants in a dual role.

Government reform of the NHS in the UK has sought to increase the involvement of doctors (clinicians) in hospital management. Using frameworks from the psychological contract and organisational misbehaviour literatures, this paper examines the processes involved when clinicians assume management roles. This literature seeks to explain breaches to expectations regarding prior agreements with management and subsequent actions of 'getting even' as a result of breaches to the employment relationship. A qualitative methodology using interviews was undertaken, which identified two distinct groups of clinician-manager. Investors actively pursued a management opportunity as an alternative to clinical medicine, whilst reluctants tended to assume a management role to protect particular specialities from outside influence or from those they thought would be inappropriate clinician-managers. Investors and reluctants often had very little prior experience of management and managers and had problems reconciling their dual clinician-management role. Poor relationships with hospital managers who often had no understanding of their dual responsibilities led to tensions and conflict, which questions continued developments in this important area of UK health policy. Suggestions for improving this process are outlined.     

Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures.

Evidence that genetic disposition for adult lactose intolerance significantly affects calcium intake, bone density, and fractures in postmenopausal women is presented. PCR-based genotyping of lactase gene polymorphisms may complement diagnostic procedures to identify persons at risk for both lactose malabsorption and osteoporosis. INTRODUCTION: Lactase deficiency is a common autosomal recessive condition resulting in decreased intestinal lactose degradation. A -13910 T/C dimorphism (LCT) near the lactase phlorizin hydrolase gene, reported to be strongly associated with adult lactase nonpersistence, may have an impact on calcium supply, bone density, and osteoporotic fractures in the elderly. MATERIALS AND METHODS: We determined LCT genotypes TT, TC, and CC in 258 postmenopausal women using a polymerase chain reaction-based assay. Genotypes were related to milk intolerance, nutritional calcium intake, intestinal calcium absorption, bone mineral density (BMD), and nonvertebral fractures. RESULTS: Twenty-four percent of all women were found to have CC genotypes and genetic lactase deficiency. Age-adjusted BMD at the hip in CC genotypes and at the spine in CC and TC genotypes was reduced by -7% to -11% depending on the site measured (p = 0.04). LCT(T/C-13910) polymorphisms alone accounted for 2-4% of BMD in a multiple regression model. Bone fracture incidence was significantly associated with CC genotypes (p = 0.001). Milk calcium intake was significantly lower (-55%, p = 0.004) and aversion to milk consumption was significantly higher (+166%, p = 0.01) in women with the CC genotype, but there were no differences in overall dietary calcium intake or in intestinal calcium absorption test values. CONCLUSION: The LCT(T/C-13910) polymorphism is associated with subjective milk intolerance, reduced milk calcium intake, and reduced BMD at the hip and the lumbar spine and may predispose to bone fractures. Genetic testing for lactase deficiency may complement indirect methods in the detection of individuals at risk for both lactose malabsorption and osteoporosis.