Orofacial clefting is the most common congenital craniofacial malformation, appearing in approximately 1 in 700 live births. Orofacial clefting includes several distinct anatomic malformations affecting the upper lip and hard and soft palate. The etiology of orofacial clefting is multifactorial, including genetic or environmental factors or their combination. A large body of work has focused on the molecular etiology of cleft lip and clefts of the hard palate, but study of the underlying etiology of soft palate clefts is an emerging field. Recent advances in the understanding of soft palate development suggest that it may be regulated by distinct pathways from those implicated in hard palate development. Soft palate clefting leads to muscle misorientation and oropharyngeal deficiency and adversely affects speech, swallowing, breathing, and hearing. Hence, there is an important need to investigate the regulatory mechanisms of soft palate development. Significantly, the anatomy, function, and development of soft palatal muscles are similar in humans and mice, rendering the mouse an excellent model for investigating molecular and cellular mechanisms of soft palate clefts. Cranial neural crest–derived cells provide important regulatory cues to guide myogenic progenitors to differentiate into muscles in the soft palate. Signals from the palatal epithelium also play key roles via tissue-tissue interactions mediated by Tgf-β, Wnt, Fgf, and Hh signaling molecules. Additionally, mutations in transcription factors, such as Dlx5, Tbx1, and Tbx22, have been associated with soft palate clefting in humans and mice, suggesting that they play important regulatory roles during soft palate development. Finally, we highlight the importance of distinguishing specific types of soft palate defects in patients and developing relevant animal models for each of these types to improve our understanding of the regulatory mechanism of soft palate development. This knowledge will provide a foundation for improving treatment for patients in the future.

The soft palate is a key component of the oropharyngeal complex that is critical for swallowing, breathing, hearing and speech. However, complete functional restoration in patients with cleft soft palate remains a challenging task. New insights into the molecular signaling network governing the development of soft palate will help to overcome these clinical challenges. In this study, we investigated whether key signaling pathways required for hard palate development are also involved in soft palate development in mice. We described the dynamic expression patterns of signaling molecules from well-known pathways, such as Wnt, Hh, and Fgf, during the development of the soft palate. We found that Wnt signaling is active throughout the development of soft palate myogenic sites, predominantly in cells of cranial neural crest (CNC) origin neighboring the myogenic cells, suggesting that Wnt signaling may play a significant role in CNC-myogenic cell-cell communication during myogenic differentiation in the soft palate. Hh signaling is abundantly active in early palatal epithelium, some myogenic cells, and the CNC-derived cells adjacent to the myogenic cells. Hh signaling gradually diminishes during the later stages of soft palate development, indicating its involvement mainly in early embryonic soft palate development. Fgf signaling is expressed most prominently in CNC-derived cells in the myogenic sites and persists until later stages of embryonic soft palate development. Collectively, our results highlight a network of Wnt, Hh, and Fgf signaling that may be involved in the development of the soft palate, particularly soft palate myogenesis. These findings provide a foundation for future studies on the functional significance of these signaling pathways individually and collectively in regulating soft palate development.

Look AHEAD was a randomized clinical trial designed to examine the long-term health effects of weight loss in overweight and obese individuals with type 2 diabetes. The primary result was that the incidence of cardiovascular events over a median follow up of 9.6 years was not reduced in the intensive lifestyle group relative to the control group. This finding is discussed, with emphasis on its implications for design of clinical trials and clinical treatment of obese people with type 2 diabetes.

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The association between 100% FJ consumption with nutrient intake, diet quality, and weight was examined in children (n=6,090) using NHANES (2007‐2010) data. Consumers (n=2,337; 34%) were defined by four categories of 100% FJ consumption using a 24‐hour diet recall. Trend analysis (covariate adjusted) was conducted using appropriate sample weights. Logistic regression was used to determine odds ratios. Diet quality was calculated using the Healthy Eating Index‐2010 (HEI). Mean 100% FJ consumption was 3.6 oz/d, which contributed a mean of 47 kcal (2.6% of total energy intake). Compared with non‐consumers, children consuming 100% FJ had significantly increased (p<0.01) intakes of energy, carbohydrates, potassium, magnesium, and vitamins C and B6 and significantly (p<0.01) lower intakes of total fat, SFA, solid fat, added sugar, and sodium. Children consuming 100% FJ consumed significantly (p<0.01) more servings of whole fruit than non‐consumers; no differences were found in milk consumption. The total HEI score significantly increased (p<0.0001) with increased 100% FJ consumption (43.8 for 0 oz. to 52.3 for (>12 oz). There was no difference in the likelihood of being overweight/obese between 100% FJ consumers and non‐consumers. 100% FJ consumption was not excessive and was associated with better nutrient intakes and was not associated with the likelihood of being overweight/obese in children. Grant Funding Source: Supported by: Juice Products Association & USDA