Sharing Detailed Research Data Is Associated with Increased Citation Rate

BACKGROUND: Sharing research data provides benefit to the general scientific community, but the benefit is less obvious for the investigator who makes his or her data available. PRINCIPAL FINDINGS: We examined the citation history of 85 cancer microarray clinical trial publications with respect to the availability of their data. The 48% of trials with publicly available microarray data received 85% of the aggregate citations. Publicly available data was significantly (p = 0.006) associated with a 69% increase in citations, independently of journal impact factor, date of publication, and author country of origin using linear regression. SIGNIFICANCE: This correlation between publicly available data and increased literature impact may further motivate investigators to share their detailed research data

CD4-Specific Designed Ankyrin Repeat Proteins Are Novel Potent HIV Entry Inhibitors with Unique Characteristics

Here, we describe the generation of a novel type of HIV entry inhibitor using the recently developed Designed Ankyrin Repeat Protein (DARPin) technology. DARPin proteins specific for human CD4 were selected from a DARPin DNA library using ribosome display. Selected pool members interacted specifically with CD4 and competed with gp120 for binding to CD4. DARPin proteins derived in the initial selection series inhibited HIV in a dose-dependent manner, but showed a relatively high variability in their capacity to block replication of patient isolates on primary CD4 T cells. In consequence, a second series of CD4-specific DARPins with improved affinity for CD4 was generated. These 2nd series DARPins potently inhibit infection of genetically divergent (subtype B and C) HIV isolates in the low nanomolar range, independent of coreceptor usage. Importantly, the actions of the CD4 binding DARPins were highly specific: no effect on cell viability or activation, CD4 memory cell function, or interference with CD4-independent virus entry was observed. These novel CD4 targeting molecules described here combine the unique characteristics of DARPins—high physical stability, specificity and low production costs—with the capacity to potently block HIV entry, rendering them promising candidates for microbicide development

Selective gene silencing by viral delivery of short hairpin RNA

RNA interference (RNAi) technology has not only become a powerful tool for functional genomics, but also allows rapid drug target discovery and in vitro validation of these targets in cell culture. Furthermore, RNAi represents a promising novel therapeutic option for treating human diseases, in particular cancer. Selective gene silencing by RNAi can be achieved essentially by two nucleic acid based methods: i) cytoplasmic delivery of short double-stranded (ds) interfering RNA oligonucleotides (siRNA), where the gene silencing effect is only transient in nature, and possibly not suitable for all applications; or ii) nuclear delivery of gene expression cassettes that express short hairpin RNA (shRNA), which are processed like endogenous interfering RNA and lead to stable gene down-regulation. Both processes involve the use of nucleic acid based drugs, which are highly charged and do not cross cell membranes by free diffusion. Therefore, in vivo delivery of RNAi therapeutics must use technology that enables the RNAi therapeutic to traverse biological membrane barriers in vivo. Viruses and the vectors derived from them carry out precisely this task and have become a major delivery system for shRNA. Here, we summarize and compare different currently used viral delivery systems, give examples of in vivo applications, and indicate trends for new developments, such as replicating viruses for shRNA delivery to cancer cells

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population

Protocol for Pilot Cluster RCT of Project Respect: A school-based intervention to prevent dating and relationship violence and address health inequalities among young people

Background Dating and relationship violence (DRV) – intimate partner violence during adolescence – encompasses physical, sexual and emotional abuse. DRV is associated with a range of adverse health outcomes including injuries, sexually transmitted infections, adolescent pregnancy and mental health issues. Experiencing DRV also predicts both victimisation and perpetration of partner violence in adulthood. Prevention targeting early adolescence is important because this is when dating behaviours begin, behavioural norms become established and DRV starts to manifest. Despite high rates of DRV victimisation in England, from 22-48% among girls and 12-27% among boys ages 14-17 who report intimate relationships, no RCTs of DRV prevention programmes have taken place in the UK. Informed by two school-based interventions that have shown promising results in RCTs in the United States – Safe Dates and Shifting Boundaries – Project Respect aims to optimise and pilot a DRV prevention programme for secondary schools in England. Methods Design: Optimisation and pilot cluster RCT. Trial will include a process evaluation and assess the feasibility of conducting a phase III RCT with embedded economic evaluation. Cognitive interviewing will inform survey development. Participants: Optimisation involves four schools and pilot RCT involves six (four intervention, two control). All are secondary schools in England. Baseline surveys conducted with students in Years 8 and 9 (ages 12-14). Follow-up surveys conducted with the same cohort, 16 months post-baseline. Optimisation sessions to inform intervention and research methods will involve consultations with stakeholders, including young people. Intervention: School staff training, including guidance on reviewing school policies and addressing ‘hotspots’ for DRV and gender-based harassment; information for parents; informing students of a help-seeking app; and a classroom curriculum for students in years 9 and 10, including a student-led campaign. Primary Outcome: The primary outcome of the pilot RCT will be whether progression to a phase III RCT is justified. Testing within the pilot will also determine which of two existing scales is optimal for assessing DRV victimisation and perpetration in a phase III RCT. Discussion This will be the first RCT of an intervention to prevent DRV in the UK. If findings indicate feasibility and acceptability, we will undertake planning for a phase III RCT of effectiveness. Trial registration ISRCTN, ISRCTN 65324176. Registered 8 June 2017, https://doi.org/10.1186/ISRCTN6532417

Riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas

Introduction: cardiovascular diseases are the first cause of death in Cuba; as a result, the identification of cardiovascular risks from early ages allows the implementation of health promotion and prevention strategies to reduce their impact in the futureObjective: to identify the cardiovascular risk in medical students in Puerto Padre Municipality, Las Tunas province.Methods: an observational, descriptive and cross-sectional study was conducted. The target group included 545 medical students, 237 of whom were selected by means of a simple random sample. The body mass index and waist-hip ratio were studied. Descriptive statistics was applied.Results: the predominant age group was 18-21 years old (50,2 %). The 51,47 % of the students presented a high waist-hip ratio, 54,02 % a high abdominal circumference, 52,74 % a high body mass index, and in all groups 35,44 % presented blood pressure figures lower than 120/80 mmHg; 39 % had a cardiovascular risk.Conclusions: low percentages of cardiovascular risk were identified in medical students from Puerto Padre Municipality, Las Tunas province, determined by high values of waist-hip index, body mass index and abdominal circumference.Introducción: las enfermedades cardiovasculares constituyen la primera causa de mortalidad en Cuba; por lo cual la identificación de riesgos cardiovasculares desde edades tempranas permite implementar estrategias de promoción y prevención de salud para disminuir su impacto en el futuroObjetivo: identificar el riesgo cardiovascular en estudiantes de medicina del municipio Puerto Padre de Las Tunas.Método: se realizó un estudio observacional, descriptivo y transversal. El universo estuvo constituido por 545 estudiantes de medicina, seleccionándose 237 mediante un muestreo aleatorio simple. Se estudió el índice de masa corporal, la circunferencia abdominal y la índice cintura cadera. Se empleó estadística descriptiva.Resultados: se encontró predominio del grupo etario de 18 a 21 años (50,2 %). El 51,47 % de los estudiantes presentó un índice cintura-cadera alto, el 54,02 % una circunferencia abdominal alta, el 52,74 % un índice de masa corporal alta, así como en todos los grupos el 35,44 % presentó cifras de tensión arterial inferiores a 120/80 mmHg. El 39 % presentó riesgo cardiovascular.Conclusiones: se identificaron bajos porcientos de riesgo cardiovascular en los estudiantes de medicina del municipio Puerto Padre de Las Tunas, determinado por altos valores los índice cintura-cadera, índice de masa corporal y circunferencia abdominal