Effect of low-dose oral contraceptives on metabolic risk factors in African-American women

CONTEXT: The effect of oral contraceptive pill (OCP) use on cardiovascular risk in African-American women is unknown. OBJECTIVE: Our objective was to examine in African-American women the effect of OCP use on insulin resistance, glucose intolerance, and triglycerides (TGs). DESIGN: This was a cross-sectional study. SETTING: The study was conducted at the National Institutes of Health Clinical Research Center. PARTICIPANTS: A total of 104 healthy nondiabetic African-American women [21 OCP users, 83 controls, age mean +/- sd, 34.7 +/- 7.6 yr, body mass index (BMI) 31 +/- 8.4 kg/m(2)] was included in the study. INTERVENTIONS: Subjects had oral glucose tolerance tests, insulin-modified frequently sampled iv glucose tolerance tests, and fasting lipid profiles. Insulin resistance was determined by the insulin sensitivity index (S(I)). MAIN OUTCOME MEASURES: Insulin resistance, glucose tolerance status, and TG levels were determined. RESULTS: Fasting glucose did not differ between OCP users and controls (P = 0.27). In contrast, compared with controls, 2-h glucose (135 +/- 23 vs.120 +/- 25 mg/dl; P = 0.01) and fasting TGs (73 +/- 31 vs.57 +/- 27 mg/dl; P = 0.02) were higher in OCP users. OCP users tended to be more insulin resistant than controls (S(I): 2.51 +/- 2.01 vs. 3.46 +/- 2.09; P = 0.09). Multiple regression analysis revealed that BMI, age, and OCP use were significant determinants of 2-h glucose (adjusted R(2) = 0.37; P < 0.001) and TG levels (adjusted R(2) = 0.21; P < 0.001). As BMI was a determinant of both 2-h glucose and TGs, participants were divided into nonobese and obese groups, and the analyses repeated. Among the nonobese women, the OCP users were more insulin resistant (S(I): 2.91 +/- 1.58 vs. 4.35 +/- 1.88; P = 0.03) and had a higher prevalence of glucose intolerance than controls (odds ratio 5.7; 95% confidence interval 1.4-24; P = 0.01). CONCLUSION: In African-American women, OCP use is associated with an increase in markers of cardiovascular risk manifested by increased insulin resistance, glucose intolerance, and elevated TGs.     

Inconsistent Access to Food and Cardiometabolic Disease: The Effect of Food Insecurity

Food insecurity is defined as limited or uncertain ability to acquire nutritionally adequate and safe foods in socially acceptable ways. The United States Department of Agriculture (USDA) has divided food insecurity into two categories: low food security and very low food security. Low food security is characterized by irregular access to food, binge eating when food is available, overconsumption of energy-dense foods, obesity, and even type 2 diabetes. This type of food insecurity occurs in impoverished urban areas of high-income countries such as the United States. In contrast, very low food security is distinctly different from low food security and can lead to undernutrition and frank starvation. Very low food security is found in developing countries in both rural areas and urban slums. In these countries, food insecurity is often exacerbated by natural disasters and climate changes that compromise food availability. With a focus on the social, economic, and behavioral factors that promote obesity and cardiometabolic disease in food insecure households in the United States, this review will first define the key terms and concepts associated with food insecurity. Then, the characteristics of food insecure households and the relationship to cardiometabolic disease will be discussed. Finally, the cardiac consequences of food insecurity in developing countries will be briefly described.     

Interferon Alpha May Benefit Cidp Patients Refractory To Standard Therapies: Description Of Long-Term Results On 12 Patients

Although most patients affected by CIDP improve with Corticosteroids, Intravenous Immunoglobulins or Plasma-Exchange, about 20–30% show poor or no response and 7–10% die due to the disease. We describe 12 CIDP patients unresponsive to standard therapies who were treated with Interferon alpha. Follow-up period ranged from 4 months to 8 years. Six patients showed a marked and sustained improvement: three recovered completely; the others, who had a severe quadriparesis (Rankin 5) before treatment disclosed a score 2–3 at last follow up. Beginning of improvement was observed within 2–4 days since starting therapy in most patients. In the remaining 6 patients no improvement was observed and two of them died with quadriplegia and respiratory failure. No significant adverse effects were observed. Over the last decade Interferons have been used in the treatment of CIDP. Some authors reported no significant improvement (Hadden et al., Neurology 1999, 53:57; Kuntzer et al., Neurology 1999, 53:1364) while others documented a clear benefit (Engel and Adornato, Neurology 1992, 42:467; Sabatelli, J Neurol Neurosurg Psych 1995, 58:638; Gorson et al., Neurology 1997, 48:777; Gorson et al., Neurology 1998, 50:84; Harada et al., 2000, MN :295; Ueda et al., Rinsho Shink 2000, 40:155). The ever present problem in clinical studies on CIDP, selection bias, may explain this discrepancy. However, the type of Interferon employed may be crucial because only patients receiving IFN alpha improved. Our data show that 50% of patients treated with IFN alpha disclose a significant improvement thus suggesting that this therapy may represent an effective option in otherwise intractable CIDP patients.     

Amyloid‐β immunotherapy for alzheimer disease: Is it now a long shot?

The amyloid‐β (Aβ) cascade hypothesis of Alzheimer disease (AD) holds that brain accumulation of Aβ initiates the disease process. Accordingly, drug research has targeted Aβ production, clearance, and deposition as therapeutic strategies. Unfortunately, candidate drugs have failed to show clinical benefit in established, early, or prodromal disease, or in those with high AD risk. Currently, monoclonal antibodies specifically directed against the most neurotoxic Aβ forms are undergoing large‐scale trials to confirm initially encouraging results. However, recent findings on the normal physiology of Aβ suggest that accumulation may be compensatory rather than the pathological initiator. If this is true, alternative strategies will be needed to defeat this devastating disease. ANN NEUROL 2019;85:303–315.     

Utility of a next generation framework for assessment of genomic damage: A case study using the industrial chemical benzene

We recently published a next generation framework for assessing the risk of genomic damage via exposure to chemical substances. The framework entails a systematic approach with the aim to quantify risk levels for substances that induce genomic damage contributing to human adverse health outcomes. Here, we evaluated the utility of the framework for assessing the risk for industrial chemicals, using the case of benzene. Benzene is a well-studied substance that is generally considered a genotoxic carcinogen and is known to cause leukemia. The case study limits its focus on occupational and general population health as it relates to benzene exposure. Using the framework as guidance, available data on benzene considered relevant for assessment of genetic damage were collected. Based on these data, we were able to conduct quantitative analyses for relevant data sets to estimate acceptable exposure levels and to characterize the risk of genetic damage. Key observations include the need for robust exposure assessments, the importance of information on toxicokinetic properties, and the benefits of cheminformatics. The framework points to the need for further improvement on understanding of the mechanism(s) of action involved, which would also provide support for the use of targeted tests rather than a prescribed set of assays. Overall, this case study demonstrates the utility of the next generation framework to quantitatively model human risk on the basis of genetic damage, thereby enabling a new, innovative risk assessment concept. Environ. Mol. Mutagen. 61:94–113, 2020. © 2019 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals, Inc. on behalf of Environmental Mutagen Society.     

How current Guidelines for obesity underestimate risk in certain ethnicities and overestimate risk in others

The consequences of the worldwide epidemic of obesity include a global increase in cardiovascular disease and diabetes. Guidelines to achieve early diagnosis of obesity, particularly central obesity, have been created by several organizations. These guidelines have been developed in Caucasian populations, but evidence is emerging that suggests substantial ethnic and sex differences in the relationships between body size, body fat distribution, and the risk of obesity-related long-term diseases. Comparisons by ethnicity and sex have revealed that the universal application of criteria for obesity and central obesity developed in Caucasians leads to an overestimation of risk in African Americans and an underestimation of risk in South Asians. Research is warranted to determine if ethnic-and sex-specific criteria for the diagnosis of obesity improve risk estimation and the development of effective interventions.     

Craniofacial resection for malignant tumours involving the anterior skull base

Ethmoid malignant tumours are rare, but nearly all at least approach or involve the lamina cribrosa. An anterior craniofacial resection is almost always mandatory for a radical resection. While almost everything has been written about technical details, few studies reported meaningful analysis about prognostic factors and long-term results, for a series of reasons: the infrequency of these tumours, the variety of histologies, small patients cohorts presented by each author, a medley of untreated and pre-treated patients, the lack of a universally accepted classification. We perform a review of the literature in the light of our experience of 330 anterior craniofacial resections for ethmoid malignant tumours. We present our classification of ethmoid malignant tumours (called INT, Istituto Nazionale Tumori). It turned out to be more prognostic than AJCC–UICC classification.