USPSTF Perspective on Evidence-Based Preventive Recommendations for Children

The development and use of evidence-based recommendations for preventive care by primary care providers caring for children is an ongoing challenge. This issue is further complicated by the fact that a higher proportion of recommendations by the US Preventive Services Task Force (USPSTF) for pediatric preventive services in comparison with adult services have insufficient evidence to recommend for or against the service. One important root cause for this problem is the relative lack of high quality screening and counseling studies in pediatric primary care settings. The paucity of studies limits the development of additional evidence-based guidelines to enhance best practices for pediatric and adolescent conditions. In this article, we describe the following: (1) evidence-based primary care preventive services as a strategy for addressing important pediatric morbidities, (2) the process of making evidence-based screening recommendations by the USPSTF, (3) the current library of USPSTF recommendations for children and adolescents, and (4) factors influencing the use of USPSTF recommendations and other evidence-based guidelines by clinicians. Strategies to accelerate the implementation of evidence-based services and areas of need for future research to fill key gaps in evidence-based recommendations and guidelines are highlighted.     

F-box protein FBXO16 functions as a tumor suppressor by attenuating nuclear β-catenin function

Aberrant activation of β-catenin has been implicated in a variety of human diseases, including cancer. In spite of significant progress, the regulation of active Wnt/β-catenin-signaling pathways is still poorly understood. In this study, we show that F-box protein 16 (FBXO16) is a putative tumor suppressor. It is a component of the SCF (SKP1-Cullin1-F-box protein) complex, which targets the nuclear β-catenin protein to facilitate proteasomal degradation through the 26S proteasome. FBXO16 interacts physically with the C-terminal domain of β-catenin and promotes its lysine 48-linked polyubiquitination. In addition, it inhibits epithelial-to-mesenchymal transition (EMT) by attenuating the level of β-catenin. Therefore, depletion of FBXO16 leads to increased levels of β-catenin, which then promotes cell invasion, tumor growth, and EMT of cancer cells. Furthermore, FBXO16 and β-catenin share an inverse correlation of cellular expression in clinical breast cancer patient samples. In summary, we propose that FBXO16 functions as a putative tumor suppressor by forming an SCF^FBXO16 complex that targets nuclear β-catenin in a unique manner for ubiquitination and subsequent proteasomal degradation to prevent malignancy. This work suggests a novel therapeutic strategy against human cancers related to aberrant β-catenin activation. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

NITROGEN AND PROTEIN COMPONENTS OF HUMAN MILK

ABSTRACT. The true protein content of human milk is 0.9%, in well-nourished as well as malnourished mothers. Casein constitutes only about 20% of the protein nitrogen in human milk. The remaining 80 % is derived from the whey proteins, the three dominant components being α-lactalbumin, lactoferrin and secretory IgA. α-lactalbumin is a subunit of lactose synthetase. Lactoferrin is an iron-binding glycoprotein which plays a role in the defence against gastro-intestinal infections and is probably also involved in iron transport in the gut. Secretory IgA is comparatively stable at low pH; it is resistant to proteolytic enzymes and plays an essential role in the immunological defence against gastro-intestinal infections. Lysozyme is a minor component of the whey proteins and represents an active enzyme with a bactericidal effect. The nutritional and immunological significance of the marked differences with respect to the nitrogen and protein compositions of human milk and cow's milk should not be underestimated, but need further elucidation.     

Increased levels of hyaluronan and albumin after intestinal challenge in adult patients with cow's milk intolerance

Background The mechanisms for adverse reactions to foods in the gastrointestinal tract are poorly understood. Presently, only hmited possibilities are available for identification of adverse immunological reactions to different foods.
Objective The intestinal inflammatory reactions in adult patients with a history of milk-related gastrointestinal symptoms were studied after intestinal challenges by a jejunal perfusion technique and compared with the reactions in a control group. Methods Five skin-prick test and radioallergosorbent test negative and lactose tolerant patients with a history of milk-related gastrointestinal symptoms, verified by double-blind placebo-controlled challenge, and eight healthy controls were investigated. Perfusions were performed allowing analyses of a well-defined 'closed' jejunal segment. Milk perfusions were performed in patients and controls after an overnight fast. Ten millilitres of milk were administered to the segment at 3 mL/min, The jejunal fluid levels of hyaluronan (hyaluronic acid) and albumin were measured.
Results In the five patients the milk challenges induced as a mean fivefold increased levels of hyaluronan compared with prcstitnulation values, whereas no such increases were seen in the control subjects. Albumin, as a marker of plasma leakage, was also increased in the patients but not in the control subjects.
Conclusion The underlying mechanisms for locally increased levels of hyaluronan and also albutnin in the intestinal lumen may be secretion of lymph rich in hyaluronan and reflect the mucosal oedetna. This capacity of the intestinal mucosa to react with lymph leakage towards a locally infused allergen may be a possible way lo delineate gastrointestinal reactions in food-related disorders.     

Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology

In the United States, colorectal cancer (CRC) is the third most common cancer diagnosed among men and women and the second leading cause of death from cancer. CRC largely can be prevented by the detection and removal of adenomatous polyps, and survival is significantly better when CRC is diagnosed while still localized. In 2006 to 2007, the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology came together to develop consensus guidelines for the detection of adenomatous polyps and CRC in asymptomatic average-risk adults. In this update of each organization's guidelines, screening tests are grouped into those that primarily detect cancer early and those that can detect cancer early and also can detect adenomatous polyps, thus providing a greater potential for prevention through polypectomy. When possible, clinicians should make patients aware of the full range of screening options, but at a minimum they should be prepared to offer patients a choice between a screening test that primarily is effective at early cancer detection and a screening test that is effective at both early cancer detection and cancer prevention through the detection and removal of polyps. It is the strong opinion of these 3 organizations that colon cancer prevention should be the primary goal of screening.