Attachment to Caregivers and Type 1 Diabetes in Children

Attachment is a behavioral and physiological system, which enables individual’s dynamic adaptation to its environment. Attachment develops in close interaction between an infant and his/her mother, plays an important role in the development of the infant’s brain, and influences the quality of interpersonal relationships throughout life.Security of attachment is believed to influence individual response to stress, exposing insecurely organized individuals to deregulated autonomic nervous system and exaggerated hypothalamic-pituitary-adrenal activity, which, in turn, produces increased and prolonged exposure to stress-hormones. Such stress responses may have considerable implications for the development of diverse health-risk conditions, such as insulin resistance and hyperlipidemia, shown by numerous studies.Although the mechanisms are not yet fully understood, there is compelling evidence highlighting the role of psychological stress in the development of type 1 diabetes (T1D). One of the possible contributing factors for the development of T1D may be the influence of attachment security on individual stress reactivity. Thus, the suggestion is that insecurely attached individuals are more prone to experience increased and prolonged influence of stress hormones and other mechanisms causing pancreatic beta-cell destruction.The present paper opens with a short overview of the field of attachment in children, the principal attachment classifications and their historic development, describes the influence of attachment security on individual stress-reactivity and the role of the latter in the development of T1D. Following is a review of recent literature on the attachment in patients with T1D with a conclusion of a proposed role of attachment organization in the etiology of T1D.     

Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital

Background. Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.Methods. We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.Results. Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.Conclusion. HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.     

Impact of overweight and obesity on US renal cell carcinoma incidence trends (1995-2018)

In the United States, renal cell carcinoma (RCC) incidence and the prevalence of obesity, an established risk factor for RCC, have been increasing for several decades. RCC is more common among older individuals. We sought to quantify the contribution of excess adiposity to the rising incidence of RCC among individuals 60 years or older. National Institutes of Health-American Association of Retired Persons Diet and Health Study data (n = 453 859 participants, enrolled in 1995-1996, age at enrollment 50-71 years) were used to estimate multivariable-adjusted hazard ratios (HRs) for RCC across body mass index categories and HRs associated with smoking. Population attributable fractions (PAFs) were calculated using estimated HRs and annual overweight/obesity prevalence from the National Health Interview Survey (1985-2008). PAF estimates were combined with RCC incidence from Surveillance, Epidemiology and End Results-13 to calculate annual percent changes in RCC incidence attributable (and unrelated) to overweight/obesity. We found that between 1995 and 2018, among individuals aged 60 years and older, PAF for overweight/obesity increased from 18% to 29% for all RCCs. In comparison, the PAF for smoking declined from 12% to 9%. RCC incidence increased 1.8% per year (95% confidence interval [CI] 1.5%-2.1%) overall, while RCC incidence attributable to overweight/obesity increased 3.8% per year (95%CI 3.5%-4.2%) and RCC incidence unrelated to overweight/obesity increased 1.2% per year (95% CI 0.9%-1.4%). In conclusion, overweight/obesity appears to have contributed importantly to the rising incidence of RCC in the United States since the mid-1990s. Public health interventions focused on reducing overweight and obesity could help substantially in curbing this trend.     

African-American Adolescents’ Weight Loss Skills Utilization: Effects on Weight Change in a Sequential Multiple Assignment Randomized Trial

Objective

Successful weight loss interventions for African-Americans adolescents are lacking. Cognitive-behavioral interventions seek to develop weight loss skills (e.g., counting calories, goal setting, managing one's environment). Little is known about how well adolescents implement such skills in their daily lives. Study aims were to (1) examine weight loss skills utilization at midpoint and end of a 6-month cognitive-behavioral/motivational interviewing weight loss sequential multiple assignment randomized trial (SMART), and (2) determine if greater skill utilization predicted weight loss at treatment end and 3 months post-treatment.

Germline gain-of-function MMP11 variant results in an aggressive form of colorectal cancer

Matrix metalloproteinase-11 (MMP11) is an enzyme with proteolytic activity against matrix and nonmatrix proteins. Although most MMPs are secreted as inactive proenzymes and are later activated extracellularly, MMP11 is activated intracellularly by furin within the constitutive secretory pathway. It is a key factor in physiological tissue remodeling and its alteration may play an important role in the progression of epithelial malignancies and other diseases. TCGA colon and colorectal adenocarcinoma data showed that upregulation of MMP11 expression correlates with tumorigenesis and malignancy. Here, we provide evidence that a germline variant in the MMP11 gene (NM_005940: c.232C>T; p.(Pro78Ser)), identified by whole exome sequencing, can increase the tumorigenic properties of colorectal cancer (CRC) cells. P78S is located in the prodomain region, which is responsible for blocking MMP11's protease activity. This variant was detected in the proband and all the cancer-affected family members analyzed, while it was not detected in healthy relatives. In silico analyses predict that P78S could have an impact on the activation of the enzyme. Furthermore, our in vitro analyses show that the expression of P78S in HCT116 cells increases tumor cell invasion and proliferation. In summary, our results show that this variant could modify the structure of the MMP11 prodomain, producing a premature or uncontrolled activation of the enzyme that may contribute to an early CRC onset in these patients. The study of this gene in other CRC cases will provide further information about its role in CRC development, which might improve patient treatment in the future.