An analysis of qualitative and mixed methods abstracts from Japanese,UK and US primary care conferences

Background

As research in family medicine covers varied topics, multiple methodologies such as qualitative research (QR) and mixed methods research (MMR) are crucial. However, we do not know about the difference in the proportion of QR or MMR between Japan, the UK and the US. This knowledge is needed to shape future research within countries with developing primary care such as Japan and other Asian countries. This study aims to describe the use of QR and MMR in Japanese primary care and compare this to the UK and US; then to make informed recommendations for primary care research.

Methods

A repeated cross-sectional study (2012–2016) based on the abstracts submitted to the annual conferences of the Japanese Primary Care Association in Japan, the Royal College of General Practitioners in the UK, and the North American Primary Care Research Group in the US and other North American countries. The proportions of QR/MMR among all the posters and paper presentations for each of these three conferences were assessed. Also examined were trends and types of qualitative techniques for all three countries and participants/settings for Japan.

Results

There were 1080 abstracts for Japan, 575 for UK and 3614 for US conferences. QR/MMR proportions were 7.5%, 15.1% and 28.1%, respectively. Japan’s proportion was lower than that of UK and US (p?<?0.001). The proportion was increasing over time for the UK (p?=?0.02). Steps for coding and analyses was most popular for Japan, thematic analysis for the UK and grounded theory for the US. Primary care doctors and hospitals were the commonest contexts for Japan.

Conclusions

QR and MMR were not as popular in primary care in Japan compared to the UK and the US, whereas their use was increasing in the UK. Approaches, participants and settings may differ among these countries. Education and promotion of QR/MMR and multi-disciplinary collaborations need to be recommended in Japan with developing primary care.

     

Role of Thrombin in Soluble Thrombomodulin-Induced Suppression of Peripheral HMGB1-Mediated Allodynia in Mice

High mobility group box 1 (HMGB1), a nuclear protein, once released into the extracellular space under pathological conditions, plays a pronociceptive role in redox-dependent distinct active forms, all-thiol HMGB1 (at-HMGB1) and disulfide HMGB1 (ds-HMGB1), that accelerate nociception through the receptor for advanced glycation endproducts (RAGE) and Toll-like receptor 4 (TLR4), respectively. Thrombomodulin (TM), an endothelial membrane protein, and soluble TM, known as TMα, promote thrombin-mediated activation of protein C and also sequester HMGB1, which might facilitate thrombin degradation of HMGB1. The present study aimed at clarifying the role of thrombin in TMα-induced suppression of peripheral HMGB1-dependent allodynia in mice. Thrombin-induced degradation of at-HMGB1 and ds-HMGB1 was accelerated by TMα in vitro. Intraplantar (i.pl.) injection of bovine thymus-derived HMGB1 in an unknown redox state, at-HMGB1, ds-HMGB1 or lipopolysaccharide (LPS), known to cause HMGB1 secretion, produced long-lasting mechanical allodynia in mice, as assessed by von Frey test. TMα, when preadministered i.pl., prevented the allodynia caused by bovine thymus-derived HMGB1, at-HMGB1, ds-HMGB1 or LPS, in a dose-dependent manner. The TMα-induced suppression of the allodynia following i.pl. at-HMGB1, ds-HMGB1 or LPS was abolished by systemic preadministration of argatroban, a thrombin-inhibiting agent, and accelerated by i.pl. co-administered thrombin. Our data clearly indicate that TMα is capable of promoting the thrombin-induced degradation of both at-HMGB1 and ds-HMGB1, and suppresses the allodynia caused by either HMGB1 in a thrombin-dependent manner. Considering the emerging role of HMGB1 in distinct pathological pain models, the present study suggests the therapeutic usefulness of TMα for treatment of intractable and/or persistent pain.     

Phosphorylation of the immunosuppressant FK506-binding protein FKBP52 by casein kinase II: Regulation of HSP90-binding activity of FKBP52

FKBP52 (HSP56, p59, HBI) is the 59-kDa immunosuppressant FK506-binding protein and has peptidyl prolyl isomerase as well as a chaperone-like activity in vitro. FKBP52 associates with the heat shock protein HSP90 and is included in the steroid hormone receptor complexes in vivo. FKBP52 possesses a well conserved phosphorylation site for casein kinase II (CK2) that was previously shown to be associated with HSP90. Here we examined whether FKBP52 is phosphorylated by CK2 both in vivo and in vitro. Recombinant rabbit FKBP52 was phosphorylated by purified CK2. We expressed and purified deletion mutants of FKBP52 to determine the site(s) phosphorylated by CK2. Thr-143 in the hinge I region was identified as the major phosphorylation site for CK2. A synthetic peptide corresponding to this region was phosphorylated by CK2, and the peptide competitively inhibited the phosphorylation of other substrates by CK2. The [³²P]phosphate labeling of FKBP52-expressing cells revealed that the same site is also phosphorylated in vivo. FK506 binding to FKBP52 did not affect the phosphorylation by CK2 and, conversely, the FK506-binding activity of FKBP52 was not affected by the phosphorylation. Most importantly, CK2-phosphorylated FKBP52 did not bind to HSP90. These results indicate that CK2 phosphorylates FKBP52 both in vitro and in vivo and thus may regulate the protein composition of chaperone-containing complexes such as those of steroid receptors and certain protein kinases.     

Esophageal Varices in Rat Models of Liver Cirrhosis

Animal models resembling the human situation arevery useful to investigate human disease. However, therehas been no evidence of esophageal varices in rats withliver cirrhosis. In the present study, to determine whether intrahepatic portalhypertension produced by liver cirrhosis inducesesophageal varices in rats, the esophagus was examinedendoscopically in rat models of liver cirrhosis. Allrats given carbon tetrachloride or thioacetamide and sixof seven rats given a choline-deficient diet hadesophageal varices or venous dilatation after 16 weeksof treatment, although the varices in one rat given carbon tetrachloride and in two rats given acholine-deficient diet were reduced from weeks 16 to 18.These findings suggest that timing is important whenstudying esophageal varices in rat models of liver cirrhosis. It is concluded that certain modelsof liver cirrhosis in rats could be used as models ofesophageal varices due to intrahepatic portalhypertension.     

Changes in adiposity and excess body weight correlate with growth responses but not with decreases in low-density lipoprotein cholesterol levels during GH treatment in GH-deficient children

BACKGROUND AND AIMS: GH has profound effects on body composition and lipid metabolism in children as well as in adults. The relationship between such metabolic effects and the growth-promoting effects of GH has not been studied thoroughly in children with GH deficiency. This prospective study was designed to determine the relationship between growth and lipid metabolism during long-term GH treatment. PATIENTS AND METHODS: Twenty-two boys with idiopathic GH deficiency were studied. Height, per cent overweight (%OW), per cent body fat (%BF) and serum low-density lipoprotein (LDL) cholesterol levels were determined every 6 months during 3 years of GH treatment. RESULTS: After 3 years of GH treatment, the mean height SD score had increased significantly from -2.70 SD to -1.59 SD (P < 0.0001), while the mean %OW and LDL cholesterol level had decreased significantly from 7.0% to 1.3% (P < 0.0001) and from 2.69 mmol/l to 2.04 mmol/l (P < 0.0001), respectively. The mean %BF fell significantly from 15.5% to 11.1% during the first 6 months of GH treatment (P < 0.0001). The 6-month reduction in %BF correlated significantly with the 3-year increase in height SD score (r = -0.58, P = 0.008). The decrease in %OW also correlated negatively with the change in height SD score (r = -0.48, P = 0.03). However, there was no correlation between the changes in LDL cholesterol levels and those in %BF, %OW or height SD score. CONCLUSION: We conclude that the growth-promoting effects of GH correlate significantly with the reductions in %BF and %OW but not with the decrease in LDL cholesterol level in children with GH deficiency. The changes in LDL cholesterol did not correlate with any of the changes in body composition parameters, suggesting that the various actions of GH may have different mechanisms of regulation.     

Sleep problems as a risk factor for fall in community-dwelling older persons

Background: Falls cause serious problems for the elderly. Sleep problems impair the control of postural balance and cause falls, and lack of sleep induces sleepiness, which in turn causes inattentiveness. The present study aims to clarify the relation between sleep disorders and falls among the community-dwelling elderly and to determine whether or not sleep disorder is an independent risk factor for falls.

Methods:

Methods: Of 2274 community-dwelling persons aged 65 and older who participated in the first study in July 1998, 1771 (77.9%) who responded to the questions concerning sleep disorders were the subjects in the present study.

Results:

Results: There were 1521 persons (85.9%) who had not experienced any fall during the past year, 194 (11.0%) who had one or two falls, 27 (1.5%) had three to four falls and 29 (1.6%) had more than five falls. The relation between the history of falls and the sleep problems indicates that the odds ratio for the history of falls was significantly higher if the nocturnal sleep disorder was more intense ( P < 0.001) and the sleep hours during the day were longer ( P < 0.01). In order to determine the independent risk factors for falls, the general linear model analysis was conducted using the significantly different background. The nocturnal sleep problems ( F = 4.05; P = 0.018), the daytime sleep ( F = 4.17; P = 0.016) and nocturnal sleep problems and interaction between (*) daytime sleep ( F = 2.54; P = 0.038) were significant independent explanatory variables as the age ( F = 14.4; P < 0.001), difficulty in walking ( F = 4.30; P = 0.038), history of stroke ( F = 64.1; P < 0.001) and arthralgia ( F = 5.31; P = 0.021).

Conclusion:

Conclusion: The data emphasize that the sleep disorder is closely related to falls.     

Integrins play a critical role in mechanical stress-induced p38 MAPK activation

Mechanical stress activates various hypertrophic responses, including activation of mitogen-activated protein kinases (MAPKs) in cardiac myocytes. Stretch activated extracellular signal-regulated kinases partly through secreted humoral growth factors, including angiotensin II, whereas stretch-induced activation of c-Jun NH(2)-terminal kinases and p38 MAPK was independent of angiotensin II. In this study, we examined the role of integrin signaling in stretch-induced activation of p38 MAPK in cardiomyocytes of neonatal rats. Overexpression of the tumor suppressor PTEN, which inhibits outside-in integrin signaling, strongly suppressed stretch-induced activation of p38 MAPK. Overexpression of focal adhesion kinase (FAK) antagonized the effects of PTEN, and both tyrosine residues at 397 and 925 of FAK were necessary for its effects. Stretch induced tyrosine phosphorylation and activation of FAK and Src. Stretch-induced activation of p38 MAPK was abolished by overexpression of FAT and CSK, which are inhibitors of the FAK and Src families, respectively, and was suppressed by overexpression of a dominant-negative mutant of Ras. Mechanical stretch-induced increase in protein synthesis was suppressed by SB202190, a p38 MAPK inhibitor. These results suggest that mechanical stress activates p38 MAPK and induces cardiac hypertrophy through the integrin-FAK-Src-Ras pathway in cardiac myocytes.