Relational Capacity: Broadening the Notion of Decision-Making Capacity in Paediatric Healthcare

Problems arise when applying the current procedural conceptualization of decision-making capacity to paediatric healthcare: Its emphasis on content-neutrality and rational cognition as well as its implicit assumption that capacity is an ability that resides within a person jeopardizes children’s position in decision-making. The purpose of the paper is to challenge this dominant account of capacity and provide an alternative for how capacity should be understood in paediatric care. First, the influence of developmental psychologist Jean Piaget upon the notion of capacity is discussed, followed by an examination of Vygostky’s contextualist view on children’s development, which emphasizes social interactions and learning for decision-making capacity. In drawing parallels between autonomy and capacity, substantive approaches to relational autonomy are presented that underline the importance of the content of a decision. The authors then provide a relational reconceptualization of capacity that leads the focus away from the individual to include important social others such as parents and physicians. Within this new approach, the outcome of adults’ decision-making processes is accepted as a guiding factor for a good decision for the child. If the child makes a choice that is not approved by adults, the new conceptualization emphasizes mutual exchange and engagement by both parties.     

Free-Roaming Dog Population Estimation and Status of the Dog Population Management and Rabies Control Program in Dhaka City,Bangladesh

Beginning January 2012, a humane method of dog population management using a Catch-Neuter-Vaccinate-Release (CNVR) program was implemented in Dhaka City, Bangladesh as part of the national rabies control program. To enable this program, the size and distribution of the free-roaming dog population needed to be estimated. We present the results of a dog population survey and a pilot assessment of the CNVR program coverage in Dhaka City. Free-roaming dog population surveys were undertaken in 18 wards of Dhaka City on consecutive days using mark-resight methods. Data was analyzed using Lincoln-Petersen index-Chapman correction methods. The CNVR program was assessed over the two years (2012–2013) whilst the coverage of the CNVR program was assessed by estimating the proportion of dogs that were ear-notched (processed dogs) via dog population surveys. The free-roaming dog population was estimated to be 1,242 (95 % CI: 1205–1278) in the 18 sampled wards and 18,585 dogs in Dhaka City (52 dogs/km²) with an estimated human-to-free-roaming dog ratio of 828:1. During the two year CNVR program, a total of 6,665 dogs (3,357 male and 3,308 female) were neutered and vaccinated against rabies in 29 of the 92 city wards. A pilot population survey indicated a mean CNVR coverage of 60.6% (range 19.2–79.3%) with only eight wards achieving > 70% coverage. Given that the coverage in many neighborhoods was below the WHO-recommended threshold level of 70% for rabies eradications and since the CNVR program takes considerable time to implement throughout the entire Dhaka City area, a mass dog vaccination program in the non-CNVR coverage area is recommended to create herd immunity. The findings from this study are expected to guide dog population management and the rabies control program in Dhaka City and elsewhere in Bangladesh.     

The plasma peptidome

Background

It may be possible to discover new diagnostic or therapeutic peptides or proteins from blood plasma using LC–ESI–MS/MS to identify, with a linear quadrupole ion trap to identify, quantify and compare the statistical distributions of peptides cleaved ex vivo from plasma samples from different clinical populations.

Methods

A systematic method for the organic fractionation of plasma peptides was applied to identify and quantify the endogenous tryptic peptides from human plasma from multiple institutions by C18 HPLC followed nano electrospray ionization and tandem mass spectrometry (LC–ESI–MS/MS) with a linear quadrupole ion trap. The endogenous tryptic peptides, or tryptic phospho peptides (i.e. without exogenous digestion), were extracted in a mixture of organic solvent and water, dried and collected by preparative C18. The tryptic peptides from 6 institutions with 12 different disease and normal EDTA plasma populations, alongside ice cold controls for pre-analytical variation, were characterized by mass spectrometry. Each patient plasma was precipitated in 90% acetonitrile and the endogenous tryptic peptides extracted by a stepwise gradient of increasing water and then formic acid resulting in 10 sub-fractions. The fractionated peptides were manually collected over preparative C18 and injected for 1508 LC–ESI–MS/MS experiments analyzed in SQL Server R.

Results

Peptides that were cleaved in human plasma by a tryptic activity ex vivo provided convenient and sensitive access to most human proteins in plasma that show differences in the frequency or intensity of proteins observed across populations that may have clinical significance. Combination of step wise organic extraction of 200 μL of plasma with nano electrospray resulted in the confident identification and quantification ~?14,000 gene symbols by X!TANDEM that is the largest number of blood proteins identified to date and shows that you can monitor the ex vivo proteolysis of most human proteins, including interleukins, from blood. A total of 15,968,550 MS/MS spectra ≥?E4 intensity counts were correlated by the SEQUEST and X!TANDEM algorithms to a federated library of 157,478 protein sequences that were filtered for best charge state (2+ or 3+) and peptide sequence in SQL Server resulting in 1,916,672 distinct best-fit peptide correlations for analysis with the R statistical system. SEQUEST identified some 140,054 protein accessions, or some ~?26,000 gene symbols, proteins or loci, with at least 5 independent correlations. The X!TANDEM algorithm made at least 5 best fit correlations to more than 14,000 protein gene symbols with p-values and FDR corrected q-values of ~?0.001 or less. Log₁₀ peptide intensity values showed a Gaussian distribution from E8 to E4 arbitrary counts by quantile plot, and significant variation in average precursor intensity across the disease and controls treatments by ANOVA with means compared by the Tukey–Kramer test. STRING analysis of the top 2000 gene symbols showed a tight association of cellular proteins that were apparently present in the plasma as protein complexes with related cellular components, molecular functions and biological processes.

Conclusions

The random and independent sampling of pre-fractionated blood peptides by LC-ESI-MS/MS with SQL Server-R analysis revealed the largest plasma proteome to date and was a practical method to quantify and compare the frequency or log₁₀ intensity of individual proteins cleaved ex vivo across populations of plasma samples from multiple clinical locations to discover treatment-specific variation using classical statistics suitable for clinical science. It was possible to identify and quantify nearly all human proteins from EDTA plasma and compare the results of thousands of LC–ESI–MS/MS experiments from multiple clinical populations using standard database methods in SQL Server and classical statistical strategies in the R data analysis system.

     

Current approaches to micro-RNA analysis and target gene prediction

It is becoming increasingly evident that micro-RNAs (miRNA) play a significant role in regulating the cellular machinery. These ∼22-nt non-coding RNAs function as negative regulators of gene expression. Since their discovery, considerable information has been obtained on miRNA biology and the mechanism of their action. Guidelines have been established for miRNA nomenclature and databases have been built to house all miRNA from many species. A number of methodologies are available for miRNA analysis. There is a lot of interest in developing bioinformatics approaches to predict miRNA target genes. This article will bring together the information on our current knowledge of miRNA biology, the approaches for miRNA analysis, and computational strategies to gain insight in miRNA functional roles.     

Murine diet/tissue and human brain tumorigenesis alter <Emphasis Type="Italic">Mthfr/MTHFR</Emphasis> 5′-end methylation

Polymorphisms and decreased activity of methylenetetrahydrofolate reductase (MTHFR) are linked to disease, including cancer. However, epigenetic regulation has not been thoroughly studied. Our goal was to generate DNA methylation profiles of murine/human MTHFR gene regions and examine methylation in brain and liver tumors. Pyrosequencing in four murine tissues revealed minimal DNA methylation in the CpG island. Higher methylation was seen in liver or intestine in the CpG island shore 5′ to the upstream translational start site or in another region 3′ to the downstream start site. In the latter region, there was negative correlation between expression and methylation. Three orthologous regions were investigated in human MTHFR, as well as a fourth region between the two translation start sites. We found significantly increased methylation in three regions (not the CpG island) in pediatric astrocytomas compared with control brain, with decreased expression in tumors. Methylation in hepatic carcinomas was also increased in the three regions compared with normal liver, but the difference was significant for only one CpG. This work, the first overview of the Mthfr/MTHFR epigenetic landscape, suggests regulation through methylation in some regions, demonstrates increased methylation/decreased expression in pediatric astrocytomas, and should serve as a resource for future epigenetic studies.     

Disclosure of Past Crimes: An Analysis of Mental Health Professionals’ Attitudes Towards Breaching Confidentiality

Ensuring confidentiality is the cornerstone of trust within the doctor–patient relationship. However, health care providers have an obligation to serve not only their patient’s interests but also those of potential victims and society, resulting in circumstances where confidentiality must be breached. This article describes the attitudes of mental health professionals (MHPs) when patients disclose past crimes unknown to the justice system. Twenty-four MHPs working in Swiss prisons were interviewed. They shared their experiences concerning confidentiality practices and attitudes towards breaching confidentiality in prison. Qualitative analysis revealed that MHPs study different factors before deciding whether a past crime should be disclosed, including: (1) the type of therapy the prisoner-patient was seeking (i.e., whether it was court-ordered or voluntary), (2) the type of crime that is revealed (e.g., a serious crime, a crime of a similar nature to the original crime, or a minor crime), and (3) the danger posed by the prisoner-patient. Based on this study’s findings, risk assessment of dangerousness was one of the most important factors determining disclosures of past crimes, taking into consideration both the type of therapy and the crime involved. Attitudes of MHPs varied with regard to confidentiality rules and when to breach confidentiality, and there was thus a lack of consensus as to when and whether past crimes should be reported. Hence, legal and ethical requirements concerning confidentiality breaches must be made clear and known to physicians in order to guide them with difficult cases.     

A critical review on antiviral peptides derived from viral glycoproteins and host receptors to decoy herpes simplex virus

The health of the human population has been continuously challenged by viral infections. Herpes simplex virus (HSV) is one of the common causes of illness and can lead to death in immunocompromised patients. Existing anti-HSV therapies are not completely successful in eliminating the infection due to anti-viral drug resistance, ineffectiveness against the latent virus and high toxicity over prolonged use. There is a need to update our knowledge of the current challenges faced in anti-HSV therapeutics and realize the necessity of developing alternative treatment approaches. Protein therapeutics are now being explored as a novel approach due to their high specificity and low toxicity. This review highlights the significance of HSV viral glycoproteins and host receptors in the pathogenesis of HSV infection. Proteins or peptides derived from HSV glycoproteins gC, gB, gD, gH and host cell receptors (HSPG, nectin and HVEM) that act as decoys to inhibit HSV attachment, entry, or fusion have been discussed. Few researchers have tried to improve the efficacy and stability of the identified peptides by modifying them using a peptidomimetic approach. With these efforts, we think developing an alternative treatment option for immunocompromised patients and drug-resistant organisms is not far off.