Endogenous estrogen modulates phenothiazine stimulated prolactin secretion

The role of endogenous estrogen in the regulation of serum prolactin concentration in man is controversial. To evaluate the possible effect of endogenous fluctuations in serum estrogen on the regulation of prolactin secretion, the authors determined phenothiazine stimulated prolactin secretion in 12 women in the early follicular phase of the menstrual cycle when estrogen levels were low (mean +/- SE E1 + E2 = 82 +/- 7 pg/ml) and compared it to the response during the late follicular phase when estrogen levels were higher (mean E1 + E2 = 320 +/- 63 pg/ml). Mean basal serum prolactin concentrations were similar in the early and late follicular phases of the cylcle (17 +/- 4 and 20 +/- 2 ng/ml, respectively). The integrated prolactin response following phenothiazine administration was significantly higher at mid-cycle (402 +/- 46 ng-hr/ml) than in the early follicular phase (317 +/0 46 ng-hr/ml, P less than .02). Thus, these studies suggest that endogenous estrogen secretion may play a role in the regulation of serum prolactin concentration in man.     

Injection versus surgery in the treatment of trigger finger

A site-specific mutation study was performed on the C-terminal domain, containing a cloned DNA binding region, of the human papillomavirus type11 (HPV11) E2 protein to determine the specific properties of residues directly involved in the DNA binding. The effect of a point mutations on the DNA binding was assessed by means of a gel mobility shift assay. The mutagenesis was concentrated on the residues in the third helix from the N-terminal, that is known as the "recognition helix," in the crystal structure of the bovine papillomavirus (BPV) E2 protein. Most point mutations caused a great decrease in the DNA binding activity. The leucine repeat in the DNA binding region was proved not to be a leucine prerequisite, as the leucines could be substituted by valine without significant loss of the DNA binding ability. Substitution of Leu for Glu caused a significant decrease in the DNA binding, indicating that the hydrophobicity of the residue at this position is important. The results suggest that the individual contribution of each amino acid residue in the DNA binding region is essential for the DNA binding.     

Lung health in relation to hydrogen sulfide exposure in oil and gas workers in Alberta, Canada

A study was undertaken to assess pulmonary health effects of hydrogen sulfide (H2S) exposure in a group of workers (n = 175) extracting and processing oil and natural gas in west-central Alberta. Exposure to H2S was assessed by questioning the workers about "exposures strong enough to cause symptoms," and exposures that resulted in loss of consciousness (a "knockdown"). Exposures strong enough to cause symptoms were reported by 34% of the workers. Fourteen workers (8%) reported having had a knockdown. Exposures severe enough to cause symptoms were not associated with lower spirometric values or excess symptoms. Knockdowns were not associated with lower spirometric values but were associated with statistically significant excesses of (1) shortness of breath while hurrying on the level or walking up a slight hill (OR = 3.55; 95%CI = 1.02-12.4); (2) wheeze with chest tightness (OR = 5.15; 95%CI = 1.29-20.6); and (3) attacks of wheeze (OR = 5.08; 95%CI = 1.28-20.2). The pattern of excess respiratory symptoms is consistent with bronchial hyperresponsiveness, which has been documented in studies of high-level exposure to other irritant gases. Additional study is warranted and should include assessment of bronchial reactivity.     

Recent Advances in Managing Atherosclerosis via Nanomedicine

Atherosclerosis, driven by chronic inflammation of the arteries and lipid accumulation on the blood vessel wall, underpins many cardiovascular diseases with high mortality rates globally, such as stroke and ischemic heart disease. Engineered bio‐nanomaterials are now under active investigation as carriers of therapeutic and/or imaging agents to atherosclerotic plaques. This Review summarizes the latest bio‐nanomaterial‐based strategies for managing atherosclerosis published over the past five years, a period marked by a rapid surge in preclinical applications of bio‐nanomaterials for imaging and/or treating atherosclerosis. To start, the biomarkers exploited by emerging bio‐nanomaterials for targeting various components of atherosclerotic plaques are outlined. In addition, recent efforts to rationally design and screen for bio‐nanomaterials with the optimal physicochemical properties for targeting plaques are presented. Moreover, the latest preclinical applications of bio‐nanomaterials as carriers of imaging, therapeutic, or theranostic agents to atherosclerotic plaques are discussed. Finally, a mechanistic understanding of the interactions between bio‐nanomaterials and the plaque (“athero–nano” interactions) is suggested, the opportunities and challenges in the clinical translation of bio‐nanomaterials for managing atherosclerosis are discussed, and recent clinical trials for atherosclerotic nanomedicines are introduced.     

High‐Strength Nanotwinned Al Alloys with 9R Phase

Light‐weight aluminum (Al) alloys have widespread applications. However, most Al alloys have inherently low mechanical strength. Nanotwins can induce high strength and ductility in metallic materials. Yet, introducing high‐density growth twins into Al remains difficult due to its ultrahigh stacking‐fault energy. In this study, it is shown that incorporating merely several atomic percent of Fe solutes into Al enables the formation of nanotwinned (nt) columnar grains with high‐density 9R phase in Al(Fe) solid solutions. The nt Al–Fe alloy coatings reach a maximum hardness of ≈5.5 GPa, one of the strongest binary Al alloys ever created. In situ uniaxial compressions show that the nt Al–Fe alloys populated with 9R phase have flow stress exceeding 1.5 GPa, comparable to high‐strength steels. Molecular dynamics simulations reveal that high strength and hardening ability of Al–Fe alloys arise mainly from the high‐density 9R phase and nanoscale grain sizes.     

Rules of the game: how public policy affects local health care markets

This paper explores the impact of public policy on local health care systems in a representative sample of twelve U.S. communities. Site visits conducted in those communities suggest that public policy is an important force that shapes health system change, for instance, by establishing the underlying "rules of the game" for private and public actors and by influencing the decisions of national and regional entities to enter and exit local markets. These dynamics are explored through a discussion of several key policy areas, including Medicaid and Medicare managed care programs, state regulation of managed care, regulation of providers' rates, certificate-of-need rules, and oversight of conversions from nonprofit to for-profit status.     

The causes and prevention of cancer: the role of environment

The idea that synthetic chemicals such as DDT are major contributors to human cancer has been inspired, in part, by Rachel Carson's passionate book, Silent Spring. This chapter discusses evidence showing why this is not true. We also review research on the causes of cancer, and show why much cancer is preventable. Epidemiological evidence indicates several factors likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors are avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and possibly red meat. Already, risks of many forms of cancer can be reduced and the potential for further reductions is great. If lung cancer (which is primarily due to smoking) is excluded, cancer death rates are decreasing in the United States for all other cancers combined. Pollution appears to account for less than 1% of human cancer; yet public concern and resource allocation for chemical pollution are very high, in good part because of the use of animal cancer tests in cancer risk assessment. Animal cancer tests, which are done at the maximum tolerated dose (MTD), are being misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half of the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at these high doses. A plausible explanation for the high frequency of positive results is that testing at the MTD frequently can cause chronic cell killing and consequent cell replacement, a risk factor for cancer that can be limited to high doses. Ignoring this greatly exaggerates risks. Scientists must determine mechanisms of carcinogenesis for each substance and revise acceptable dose levels as understanding advances. The vast bulk of chemicals ingested by humans is natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of these natural pesticides tested at the MTD are rodent carcinogens. Reducing exposure to the 0.01% that are synthetic will not reduce cancer rates. On the contrary, although fruits and vegetables contain a wide variety of naturally-occurring chemicals that are rodent carcinogens, inadequate consumption of fruits and vegetables doubles the human cancer risk for most types of cancer. Making them more expensive by reducing synthetic pesticide use will increase cancer. Humans also ingest large numbers of natural chemicals from cooking food. Over a thousand chemicals have been reported in roasted coffee: more than half of those tested (19/28) are rodent carcinogens. There are more rodent carcinogens in a single cup of coffee than potentially carcinogenic pesticide residues in the average American diet in a year, and there are still a thousand chemicals left to test in roasted coffee. This does not mean that coffee is dangerous but rather that animal cancer tests and worst-case risk assessment, build in enormous safety factors and should not be considered true risks. The reason humans can eat the tremendous variety of natural chemical "rodent carcinogens" is that humans, like other animals, are extremely well protected by many general defense enzymes, most of which are inducible (i.e., whenever a defense enzyme is in use, more of it is made). Since the defense enzymes are equally effective against natural and synthetic chemicals one does not expect, nor does one find, a general difference between synthetic and natural chemicals in ability to cause cancer in high-dose rodent tests. The idea that there is an epidemic of human cancer caused by synthetic industrial chemicals is false. In addition, there is a steady rise in life expectancy in the developed countries. Linear extrapolation from the maximum tolerated dose in rodents to low level exposure in humans has led to grossly exaggerated mortality forecasts. Such extrapo     

On the evaluation of the joint distribution of order statistics

Dunnett and Tamhane [Dunnett, C.W., Tamhane, A.C., 1992. A step-up multiple test procedure. J. Amer. Statist. Assoc. 87, 162-170.] proposed a step-up procedure for comparing k treatments with a control and showed that the step-up procedure is more powerful than its counterpart single step and step-down procedures. Since then, several modified step-up procedures have been suggested to deal with different testing environments. In order to establish those step-up procedures, it is necessary to derive approaches for evaluating the joint distribution of the order statistics. In some cases, experimenters may have difficulty in applying those step-up procedures in multiple hypothesis testing because of the computational limitation of existing algorithms in evaluating the critical values for a large number of multiple comparisons. As a result, most procedures are only workable when the design of the experiment is balanced with k≤20 or unbalanced with k≤8. In this paper, new algorithms are proposed in order to effectively compute the joint distribution of order statistics in various situations. An extensive numerical study shows that the proposed algorithms can easily handle the testing situations with a much larger k. Examples of applying the proposed algorithms to evaluate the critical values of two existing step-up procedures are also presented.