Stimulation and Early Child Development in China: Caregiving at Arm's Length.

OBJECTIVE: To provide an empirical overview of the parenting landscape in rural China, focusing on 18- to 30-month-old children and their caregivers in rural Shaanxi province. METHODS: We collected unique data on 1442 caregiver-toddler dyads in rural areas of Shaanxi province and examined caregiver attitudes toward parenting, sources of information about parenting, and interactive parenting practices, and how each of these differed across generations. We measured how parenting attitudes and sources of information informed parenting practices. Finally, we measured levels of child development in our sample and the association between parenting practices and children's developmental outcomes. RESULTS: Most of the caregivers did not engage with children in a way that encouraged early development. Caregivers rarely told stories, sang, or used toys to play with their children. Grandmothers were more stressed by the children in their care and engaged significantly less than mothers did in the 3 stimulating interactions. Professional sources of information about parenting were underutilized by all caregivers. We found high rates of developmental delay in our sample and showed that these delays were associated with the lack of caregiver engagement. CONCLUSION: Our findings suggest that the major economic and social shifts occurring in rural China have not led to a widespread prevalence of stimulative parenting practices. Although caregivers report positive attitudes toward child-rearing, reliable sources of scientific information are lacking. Our results show a troubling generational disconnect between the information-seeking behaviors and parenting practices of rural caregivers.

Diagnostic ability and inappropriate antibiotic prescriptions: a quasi-experimental study of primary care providers in rural China.

Background: China has one of the highest rates of antibiotic resistance. Existing studies document high rates of antibiotic prescription by primary care providers but there is little direct evidence on clinically inappropriate use of antibiotics or the drivers of antibiotic prescription. Methods: To assess clinically inappropriate antibiotic prescriptions among rural primary care providers, we employed unannounced standardized patients (SPs) who presented three fixed disease cases, none of which indicated antibiotics. We compared antibiotic prescriptions of the same providers in interactions with SPs and matching vignettes assessing knowledge of diagnosis and treatment to assess overprescription attributable to deficits in diagnostic knowledge, therapeutic knowledge and factors that lead providers to deviate from their knowledge of best practice. Results: Overall, antibiotics were inappropriately prescribed in 221/526 (42%) SP cases. Compared with SP interactions, prescription rates were 29% lower in matching clinical vignettes (42% versus 30%, P < 0.0001). Compared with vignettes assessing diagnostic and therapeutic knowledge jointly, rates were 67% lower in vignettes with the diagnosis revealed (30% versus 10%, P < 0.0001). Antibiotic prescription in vignettes was inversely related to measures of diagnostic process quality (completion of checklists). Conclusions: Clinically inappropriate antibiotic prescription is common among primary care providers in rural China. While a large proportion of overprescription may be due to factors such as financial incentives tied to drug sales and perceived patient demand, our findings suggest that deficits in diagnostic knowledge are a major driver of unnecessary antibiotic prescriptions. Interventions to improve diagnostic capacity among providers in rural China are needed.

Factor XIIIA transglutaminase expression and secretion by osteoblasts is regulated by extracellular matrix collagen and the MAP kinase signaling pathway.

Osteoblast differentiation is regulated by the presence of collagen type I (COL I) extracellular matrix (ECM). We have recently demonstrated that Factor XIIIA (FXIIIA) transglutaminase (TG) is required by osteoblasts for COL I secretion and extracellular deposition, and thus also for osteoblast differentiation. In this study we have further investigated the link between COL I and FXIIIA, and demonstrate that COL I matrix increases FXIIIA levels in osteoblast cultures and that FXIIIA is found as cellular (cFXIIIA) and extacellular matrix (ecmFXIIIA) forms. FXIIIA mRNA, protein expression, cellular localization and secretion were enhanced by ascorbic acid (AA) treatment and blocked by dihydroxyproline (DHP) which inhibits COL I externalization. FXIIIA mRNA was regulated by the MAP kinase pathway. Secretion of ecmFXIIIA, and its enzymatic activity in conditioned medium, were also decreased in osteoblasts treated with the lysyl oxidase inhibitor ß-aminopropionitrile, which resulted in a loosely packed COL I matrix. Osteoblasts secrete a latent, inactive dimeric ecmFXIIIA form which is activated upon binding to the matrix. Monodansyl cadaverine labeling of TG substrates in the cultures revealed that incorporation of the label occurred at sites where fibronectin co-localized with COL I, indicating that ecmFXIIIA secretion could function to stabilize newly deposited matrix. Our results suggest that FXIIIA is an integral part of the COL I deposition machinery, and also that it is part of the ECM-feedback loop, both of which regulate matrix deposition and osteoblast differentiation.

Plasma membrane factor XIIIA transglutaminase activity regulates osteoblast matrix secretion and deposition by affecting microtubule dynamics.

Transglutaminase activity, arising potentially from transglutaminase 2 (TG2) and Factor XIIIA (FXIIIA), has been linked to osteoblast differentiation where it is required for type I collagen and fibronectin matrix deposition. In this study we have used an irreversible TG-inhibitor to 'block -and-track' enzyme(s) targeted during osteoblast differentiation. We show that the irreversible TG-inhibitor is highly potent in inhibiting osteoblast differentiation and mineralization and reduces secretion of both fibronectin and type I collagen and their release from the cell surface. Tracking of the dansyl probe by Western blotting and immunofluorescence microscopy demonstrated that the inhibitor targets plasma membrane-associated FXIIIA. TG2 appears not to contribute to crosslinking activity on the osteoblast surface. Inhibition of FXIIIA with NC9 resulted in defective secretory vesicle delivery to the plasma membrane which was attributable to a disorganized microtubule network and decreased microtubule association with the plasma membrane. NC9 inhibition of FXIIIA resulted in destabilization of microtubules as assessed by cellular Glu-tubulin levels. Furthermore, NC9 blocked modification of Glu-tubulin into 150 kDa high-molecular weight Glu-tubulin form which was specifically localized to the plasma membrane. FXIIIA enzyme and its crosslinking activity were colocalized with plasma membrane-associated tubulin, and thus, it appears that FXIIIA crosslinking activity is directed towards stabilizing the interaction of microtubules with the plasma membrane. Our work provides the first mechanistic cues as to how transglutaminase activity could affect protein secretion and matrix deposition in osteoblasts and suggests a novel function for plasma membrane FXIIIA in microtubule dynamics.