A research agenda to guide progress on childhood obesity prevention in Latin America

Childhood obesity rates in Latin America are among the highest in the world. This paper examines and evaluates the many efforts underway in the region to reduce and prevent further increases in obesity, identifies and discusses unique research challenges and opportunities in Latin America, and proposes a research agenda in Latin America for the prevention of childhood obesity and concomitant non-communicable diseases. Identified research gaps include biological challenges to healthy growth across the life cycle, diet and physical activity dynamics, community interventions promoting healthy child growth, and rigorous evaluation of national food and activity programs and regulatory actions. Addressing these research gaps is critical to advance the evidence-based policy and practice in childhood obesity tailored to the Latin American context that will be effective in addressing obesity

CHOP Contributes to, But Is Not the Only Mediator of, IAPP Induced ß-Cell Apoptosis.

The islet in type 2 diabetes is characterized by ß-cell loss, increased ß-cell apoptosis, and islet amyloid derived from islet amyloid polypeptide (IAPP). When protein misfolding protective mechanisms are overcome, human IAPP (h-IAPP) forms membrane permeant toxic oligomers that induce ß-cell dysfunction and apoptosis. In humans with type 2 diabetes (T2D) and mice transgenic for h-IAPP, endoplasmic reticulum (ER) stress has been inferred from nuclear translocation of CCAAT/enhancer-binding protein homologous protein (CHOP), an established mediator of ER stress. To establish whether h-IAPP toxicity is mediated by ER stress, we evaluated diabetes onset and ß-cell mass in h-IAPP transgenic (h-TG) mice with and without deletion of CHOP in comparison with wild-type controls. Diabetes was delayed in h-TG CHOP(-/-) mice, with relatively preserved ß-cell mass and decreased ß-cell apoptosis. Deletion of CHOP attenuates dysfunction of the autophagy/lysosomal pathway in ß-cells of h-TG mice, uncovering a role for CHOP in mediating h-IAPP-induced dysfunction of autophagy. As deletion of CHOP delayed but did not prevent h-IAPP-induced ß-cell loss and diabetes, we examined CHOP-independent stress pathways. JNK, a target of the IRE-1pTRAF2 complex, and the Bcl-2 family proapoptotic mediator BIM, a target of ATF4, were comparably activated by h-IAPP expression in the presence and absence of CHOP. Therefore, although these studies affirm that CHOP is a mediator of h-IAPP-induced ER stress, it is not the only one. Therefore, suppression of CHOP alone is unlikely to be a durable therapeutic strategy to protect against h-IAPP toxicity because multiple stress pathways are activated.

Human-IAPP disrupts the autophagy/lysosomal pathway in pancreatic ß-cells: protective role of p62-positive cytoplasmic inclusions.

In type II diabetes (T2DM), there is a deficit in ß-cells, increased ß-cell apoptosis and formation of intracellular membrane-permeant oligomers of islet amyloid polypeptide (IAPP). Human-IAPP (h-IAPP) is an amyloidogenic protein co-expressed with insulin by ß-cells. IAPP expression is increased with obesity, the major risk factor for T2DM. In this study we report that increased expression of human-IAPP led to impaired autophagy, due at least in part to the disruption of lysosome-dependent degradation. This action of IAPP to alter lysosomal clearance in vivo depends on its propensity to form toxic oligomers and is independent of the confounding effect of hyperglycemia. We report that the scaffold protein p62 that delivers polyubiquitinated proteins to autophagy may have a protective role against human-IAPP-induced apoptosis, apparently by sequestrating protein targets for degradation. Finally, we found that inhibition of lysosomal degradation increases vulnerability of ß-cells to h-IAPP-induced toxicity and, conversely, stimulation of autophagy protects ß-cells from h-IAPP-induced apoptosis. Collectively, these data imply an important role for the p62/autophagy/lysosomal degradation system in protection against toxic oligomer-induced apoptosis.

Flexible bronchoscopy in children at the University of Puerto Rico Pediatric Hospital. Review of 324 consecutive patients.

Described are the findings resulting from 324 bronchoscopies performed with the flexible bronchoscope during the past 8 years at the University of Puerto Rico Pediatric Hospital. Neonates, infants, children and adolescents were included. The most frequent indications for the procedure were stridor, recurrent or persistent pneumonia, atelectasis, recurrent croup and persistent wheezing. An abnormality was detected in 88 per cent of the patients and the finding often resulted in significant modifications of treatment or allowed for reassurance. Complications were minor and there was no mortality. We conclude that the procedure, as we describe it, is save, effective and useful.

A conservative approach to rhinoplasty.

When a rhinoplasty is performed, one must keep in mind that the nose is a part of a whole structure, the face. In the ideal nose operation all the components of the nose are well balanced among themselves and the nose itself is a harmonic part of the face. The present article briefly reports on how the different excisions of a rhinoplasty should be done to get a well-balanced nose. The objective of the presentation is to emphasize how only a very small amount of osteocartilaginous framework can be removed to obtain a very satisfactory result. The most caudal portion of the septum is almost never removed and the tip elevation is achieved with a logical excision of both lower and upper lateral cartilages. Wedges from the alae are seldom excised, producing a more natural looking nose. In summary, we try to achieve better appearing noses that do not look operated on.