Distribution of Illness and Medical Expenditure: A Survey in Two Villages in Rural Beijing

Background

The main goal of this study is to examine the distributions of illness conditions and resulting medical expenditures and their associated factors. To achieve this goal, an in-house survey was conducted in August of 2012 in rural Beijing, the capital city of China.

Results

The survey was conducted in Nanjianchang and Beijianchang, which are two villages 20 KM away from Miyun, a satellite city of Beijing. Data was collected on 346 households, which included 834 members. Variables measured included household characteristics, household head characteristics, illness conditions, and medical expenditures. Illness conditions and corresponding expenditure were measured for inpatient treatment, outpatient treatment, and self-treatment separately. Multivariate analysis suggested that the presence of inpatient treatment was associated with household head characteristics including age, gender, and education. The presence of a high level of outpatient treatment was associated with household head characteristics including gender and education. The presence of a high level of self-treatment was significantly associated with household size. In the analysis of overall out-of-pocket (OOP) medical expenditure, only age of household head was borderline significant. In the analysis of OOP inpatient expenditure, age and gender of household head were borderline significant. The OOP outpatient expenditure was associated with household size, presence of members older than 60, household head''s gender, marital status, and occupation. The OOP self-treatment expenditure was not associated with any household characteristic.

Conclusions

For the surveyed households, medical expenditure made up a considerable proportion of the total consumption. This study suggested that the presence of illness conditions and resulting OOP medical expenditure were associated with certain household and household head characteristics. Such results may help identify the subgroup that is the most affected by illness conditions. As this study collected recent data on inpatient, outpatient, and self-treatment separately, it may provide a useful complement to the existing studies.     

Identification of a Small Peptide That Inhibits PCSK9 Protein Binding to the Low Density Lipoprotein Receptor

PCSK9 (proprotein convertase subtilisin/kexin type 9) is a negative regulator of the hepatic LDL receptor, and clinical studies with PCSK9-inhibiting antibodies have demonstrated strong LDL-c-lowering effects. Here we screened phage-displayed peptide libraries and identified the 13-amino acid linear peptide Pep2-8 as the smallest PCSK9 inhibitor with a clearly defined mechanism of inhibition that has been described. Pep2-8 bound to PCSK9 with a K_D of 0.7 μm but did not bind to other proprotein convertases. It fully restored LDL receptor surface levels and LDL particle uptake in PCSK9-treated HepG2 cells. The crystal structure of Pep2-8 bound to C-terminally truncated PCSK9 at 1.85 Å resolution showed that the peptide adopted a strand-turn-helix conformation, which is remarkably similar to its solution structure determined by NMR. Consistent with the functional binding site identified by an Ala scan of PCSK9, the structural Pep2-8 contact region of about 400 Ų largely overlapped with that contacted by the EGF(A) domain of the LDL receptor, suggesting a competitive inhibition mechanism. Consistent with this, Pep2-8 inhibited LDL receptor and EGF(A) domain binding to PCSK9 with IC₅₀ values of 0.8 and 0.4 μm, respectively. Remarkably, Pep2-8 mimicked secondary structural elements of the EGF(A) domain that interact with PCSK9, notably the β-strand and a discontinuous short α-helix, and it engaged in the same β-sheet hydrogen bonds as EGF(A) does. Although Pep2-8 itself may not be amenable to therapeutic applications, this study demonstrates the feasibility of developing peptidic inhibitors to functionally relevant sites on PCSK9.     

Psychosocial perception of adults with onychomycosis: a blinded,controlled comparison of 1,017 adult Hong Kong residents with or without onychomycosis

Background

A survey was conducted amongst 1,017 Hong Kong residents ages 18 and over to determine their knowledge of fungal nail infections (onychomycosis) and the psychosocial impact of the disease on the relationships, social lives and careers of sufferers.

Methods

The Fungal Nail Perception Survey was conducted by email and online between May 29th and June 10th, 2013. Participants were shown three photographs of people with and without onychomycosis of the toenails. Respondents were asked ten questions (repeated for each picture) to ascertain their perceptions of the people in the pictures. Questions were related to perceptions around the ability of sufferers and non-sufferers to form relationships with others, social activities of sufferers and non-sufferers, perceptions of the effect of the disease on the potential for career success, and awareness of fungal nail disease and health. The sub-population who themselves suffered from onychomycosis were asked about self-perception as well as their perception of others with onychomycosis.

Results

Compared with non-sufferers, survey respondents perceived those with onychomycosis as less likely to be able to form good relationships. They also indicated that they would be more likely to exclude sufferers than non-sufferers from social activities and that they would be more likely to feel uncomfortable when sitting or standing beside an infected person than beside an uninfected person. Respondents perceived people with onychomycosis to be less able to perform well in their chosen career than with someone without onychomycosis. Interestingly, those respondents who themselves were infected felt socially excluded, upset and embarrassed by their infection.

Conclusions

Onychomycosis may lead to stigmatization and social exclusion. Misconceptions of onychomycosis are high and education about the disease needs to be improved. Early recognition and treatment of the disease is essential to avoid complications and improve treatment outcomes, which would lead to reduced psychosocial impact on those with fungal nail infections.

     

In vitro modification of human centromere protein CENP-C fragments by small ubiquitin-like modifier (SUMO) protein: definitive identification of the modification sites by tandem mass spectrometry analysis of the isopeptides

Protein sumoylation by small ubiquitin-like modifier (SUMO) proteins is an important post-translational regulatory modification. A role in the control of chromosome dynamics was first suggested when SUMO was identified as high-copy suppressor of the centromere protein CENP-C mutants. CENP-C itself contains a consensus sumoylation sequence motif that partially overlaps with its DNA binding and centromere localization domain. To ascertain whether CENP-C can be sumoylated, tandem mass spectrometry (MS) based strategy was developed for high sensitivity identification and sequencing of sumoylated isopeptides present among in-gel-digested tryptic peptides of SDS-PAGE fractionated target proteins. Without a predisposition to searching for the expected isopeptides based on calculated molecular mass and relying instead on the characteristic MS/MS fragmentation pattern to identify sumolylation, we demonstrate that several other lysine residues located not within the perfect consensus sumoylation motif psiKXE/D, where psi represents a large hydrophobic amino acid, and X represents any amino acid, can be sumolylated with a reconstituted in vitro system containing only the SUMO proteins, E1-activating enzyme and E2-conjugating enzyme (Ubc9). In all cases, target sites that can be sumoylated by SUMO-2 were shown to be equally susceptible to SUMO-1 attachments which include specific sites on SUMO-2 itself, Ubc9, and the recombinant CENP-C fragments. Two non-consensus sites on one of the CENP-C fragments were found to be sumoylated in addition to the predicted site on the other fragment. The developed methodologies should facilitate future studies in delineating the dynamics and substrate specificities of SUMO-1/2/3 modifications and the respective roles of E3 ligases in the process.