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The widespread and increasing use of engineered nanomaterials (ENMs) increases the risk of exposure by human beings. This notion has generated concern that ENMs may give rise to adverse health effects. Toxicity of ENMs is determined by both physical aspects and chemical composition. The immune system may respond to ENMs, amongst others by inflammatory reactions. Among the mechanisms underlying inflammation, inflammasome activation (especially the NLRP3 inflammasome) has drawn significant attention because it can be induced by a wide range of stimuli including ENMs and it is associated with various inflammatory diseases, including lung fibrosis, obesity and type 2 diabetes. Inflammasomes are intracellular multiprotein complexes that assemble upon stimulation, resulting in the activation of caspase-1 that in turn induces the production of interleukin (IL)-1β and IL-18. These cytokines are potent mediators of inflammation. This review summarizes the literature on NLRP3 inflammasome activation by ENMs published between 2013 and 2015. Newly identified mechanisms include a role for Endoplasmic Reticulum stress in NLRP3 inflammasome activation by Ag and ZnO ENMs and an initiating role for IL-1. Novel insights in surface functionalization with the aim of reducing NLRP3 inflammasome activation were obtained. In vitro assays for NLRP3 inflammasome activation may predict in vivo fibrogenic potency of ENMs; including such an assay in a test battery for hazard identification is advised.

To test whether glucocorticoids act as the endogenous agonist of cardiac mineralocorticoid receptors, we evaluated the cardiac effects of aldosterone and corticosterone and cardiac steroidogenesis vs. steroid uptake from plasma.

Few studies have investigated the relationships between body composition, functional ability, and age-related disability in postmenopausal women. We investigated the relative role of fat mass, lean mass, and muscle strength in the development of disability in a group of healthy postmenopausal women younger than 75 years.

Age at menopause and age at the start of the preceding period of cycle irregularity (menopausal transition) show considerable individual variation. In this study we explored several markers for their ability to predict the occurrence of the transition to menopause.

We determined whether higher endogenous estradiol levels were associated with lower risk of dementia in older men and women not using hormonal replacement therapy, using a case-cohort design within the Rotterdam Study, a population-based follow-up study on chronic diseases, including dementia, in 7,983 subjects aged 55 years or older, and ongoing since 1990. The analyses were based on a random subcohort of 508 women and 438 men, and on 76 women and 53 men with incident dementia. Cox proportional hazards models with robustly estimated standard errors showed that in women higher levels of total estradiol were associated with higher risk of dementia (age-adjusted hazard ratio per standard deviation increase 1.38; 95% CI 1.04–1.84). Age-adjusted HR's of Alzheimer's disease and vascular dementia associated with higher levels of total estradiol (per SD increase) were 1.24 (95% CI 0.87–1.76) and 2.19 (95% CI 1.22–3.92), respectively. Similar results were observed for bioavailable estradiol. Additional adjustments for potential confounders did not change the results substantially. In men, no clear association was observed between estradiol levels and risk of dementia or its subtypes. The findings do not support the hypothesis that higher levels of endogenous estradiol reduce risk of dementia, neither in women nor in men. Ann Neurol 2003

To investigate the degree and potential cardiovascular determinants of arterial stiffness, assessed by aortic pulse wave velocity (PWV) measurements, and to relate arterial stiffness to absolute 10–12-year risks of stroke, coronary heart disease and death, as estimated by available risk functions, in postmenopausal women.

Body mass index BMI weight per unit surface area is the scientific yardstick by which overweight is gauged relative to the population norm. The contrary association between obesity and diabetes or hypertension is only too well known. Less appreciated is the heightened sensitivity to respiratory depressants such as sedatives and analgesics in the obese BMI ≥ 30 and the increased incidence of sleep apnea in the morbidly obese BMI ≥ 35—either or both of which raise the risk of cosmetic surgery when sedation or anesthesia is contemplated. Guided by the BMI, a genderindependent measure of fatness, the surgeon now can inform the patient of her or his relative operative risk and offer an objective rationale for advising overnight hospitalization rather than officebased day surgery.

Recent qualms about the safety of aesthetic lipoplasty may be attributable more to support system flaws than to technical process deficiencies. The authors here focus on perfunctory patient monitoring when sedative or analgesic drugs are given, cavalier infiltration of megadose lidocaine, cursory intraoperative patient observation by team members with conflicting responsibilities, anesthesia providers unfamiliar with the unique surgical physiology of liposuction, hurrieddischarge policies that virtually ignore the residual depressant effects of sedatives and analgesics, and compressive dressings that impair postoperative chestwall expansion and venous return. Whereas pulmonary embolism remains the leading process cause of morbidity from liposuction, complications from austere resource allocation to dedicated patient monitoring should be largely preventable. Not all lipoplasties require an anesthesia provider but—when heavy sedation, megadose lidocaine, or both, are projected—a trained team member dedicated exclusively to patient safety and comfort should be a minimum patient care standard. The potential role of lidocaine cardiotoxicity in tumescent anesthesia is widely underappreciated and that of hypothermia goes mostly unrecognized. These, plus largely preventable or potentially correctable perioperative events such as pulmonary edema, fluid imbalance, or improperly administered sedative and analgesic drugs, demand upgrading and expansion of monitoring, resuscitative, and recuperative facilities in physician offices. In fact, ASPS guidelines urge that anesthesia services be engaged for dedicated patient care whenever “major” liposuction or conscious sedation is projected, because liposuction is neither as benign nor as simple a procedure as heretofore reputed. To assess objectively the operative and anesthetic risk of obesity, document body mass index for the preoperative record morbid obesity body mass index ≥ 35.0, for instance, is a known risk multiplier for sedatives and analgesics. Other system issues such as the dynamic profile of highdose lidocaine pharmacokinetics, the deportation of fat globules in the bloodstream, and the incidence of intraoperative hypothermia remain as unresolved topics for interdisciplinary, multiinstitutional clinical research. Plast. Reconstr. Surg.107 1039, 2001.

An analysis of medical liability claims for lipoplasty liposuction from January of 1985 through June of 1998 compared the insurance industry experience of plastic surgeons with that of other physicians. The Data Sharing Project database of the Physician Insurers Association of America, a trade association of professional liability companies owned and operated by medical professionals that collectively insure approximately 60 percent of America's private practice physicians, was queried. Of the nearly 45,000 total entries in the database, 292 were claims for adverse events related to lipoplasty or liposuction. These raw data were stratified by physician specialty, severity of complication, practice location, patient gender, indemnity payment, and other insurance industryrelevant variables.

Troubling reports of adverse outcomes after liposuction prompted a census survey of aesthetic plastic surgeons. All 1200 actively practicing North American boardcertified ASAPS members were polled by facsimile, then mail, regarding deaths after liposuction. Patient initials together with case summaries precluded data replication yet assured patient anonymity and preserved surgeon privacy. Incomplete returns or ambiguous findings were authenticated, where feasible, by direct followup. Total number of lipoplasties performed by plastic surgeons was interpolated from the ASPRS procedure database for the survey time frame of 1994 to mid1998. Lacking reliable annual case volume estimates, deaths from lipoplasties performed by nonABPS surgeons were excluded from the actual mortality rate computation but were included in causeofdeath ranking statistics.

Several cancer immune intervention protocols aim at inducing T cell immunity against antigens presented by HLA-A2, the most common human MHC class I molecule. In the context of HLA-A*0201, we previously identified two cytotoxic T lymphocyte epitopes (E711 – 20 and E786 – 93) encoded by the human papillomavirus type 16 E7 (HPV16 E7) oncoprotein, which is a tumor-specific antigen for cervical carcinoma. This study reports that the two HPV16 epitopes and a control hepatitis B virus epitope bind equally well to five HLA-A2 alleles (A*0201, A*0202, A*0203, A*0204, and A*0209). These HLA-A2 variants display comparable binding characteristics in accordance with the A2 supertype (M. F. Del Guercio et al., J. Immunol. 1995. 154: 685 – 693). Cervical carcinoma patients expressing these alleles may benefit from vaccination with the two HPV16 E7 peptides. In contrast, none of the peptides tested bound to A*0207 or A*0208, whereas heterogeneous binding was observed for A*0205 and A*0206. Therefore, the amino acid substitutions that discriminate these HLA-A2 variants from A*0201 affect antigen presentation. Taken together, our findings have implications for application of the A2 supertype concept and for vaccination with A*0201-binding peptides, in particular HPV16 E7 peptides.

We describe the clinical and biochemical characteristics of alcoholinduced pseudo-Cushing's syndrome in two patients with signs and symptoms of Cushing's syndrome and slight disturbances in liver function. An insufficient suppression of plasma cortisol to the overnight administration of 1 mg of dexamethasone was accompanied by an absent diurnal rhythm of plasma cortisol and an increased cortisol secretion rate. The plasma cortisol levels at 8 AM normalized during hospital admission (ie, alcohol withdrawal) at the same rate or parallel with the serum 7-glutamyl transferase concentration. A normal increase of plasma cortisol, adrenocorticotropic hormone, and growth hormone in response to an insulin-induced hypoglycemia was not compatible with the diagnosis Cushing's syndrome. However, the result of a differential diagnostic test with metyrapone was compatible with the presence of Cushing's disease. An erroneous diagnosis of Cushing's disease can be easily made in patients with alcohol-induced pseudo-Cushing's syndrome.(JAMA 242:1640-1643, 1979)

Oestradiol-17β (E2) was measured by radioimmunoassay in the plasma of immature female rats. Maximal E2levels of 55–60 pg/ml were found at 10–15 days of age; from day 25 to day 35 E2levels were low to undetectable. The E2measured appeared to be of ovarian origin: ovariectomy performed on day 13 resulted in a decreased E2level 2 days later (13 pg/ml) as compared with the value from the control litter mates (46 pg/ml); after adrenalectomy the level of circulating E2remained normal (54 pg/ml). The effects of ovariectomy and adrenalectomy on uterine weights followed a similar pattern: ovariectomy resulted in a decrease and adrenalectomy in no change in uterine weight.In the strain of rat used, levels of follicle-stimulating hormone (FSH) in the serum (measured by radioimmunoassay) were high from day 10 to day 20 and showed a steep decrease on day 21. After ovariectomy on day 15 this decrease in serum FSH was not observed.The influence of circulating E2on serum levels of FSH was studied after ovariectomy followed by treatment with varying doses of oestradiol benzoate. Ovariectomy on day 13 resulted in a significantly increased FSH level 2 days later (1770 ng NIAMD-rat-FSH RP-1/ml) as compared with the value obtained from control animals (1033 ng/ml). This increase was not observed after daily injections of 0·1 μg oestradiol benzoate/100 g body weight.The results indicate that E2and FSH concentrations show a similar pattern between 5 and 35 days of age. Furthermore, an inhibitory feedback mechanism between oestrogens and FSH concentrations was found to be operative. The implications of these findings are discussed.

Antimüllerian hormone (AMH), also known as müllerian inhibiting substance (MIS), is viewed as a quantitative marker of ovarian reserve. Serum AMH levels are readily measured and independent of the menstrual cycle, and they correlate closely with antral follicle counts. Unlike follicle counts, however, AMH has not been evaluated as a predictor of reproductive status.

This study investigated planting techniques and natural regeneration of indigenous woody species within degraded wet meadow wetland at Coomonderry Swamp. Planting tubestock directly into existing vegetation was practical and cost-effective. Clearing of plots allowed infiltration of weeds, early growth of tubestock was inhibited, acid sulfate soils were exposed, and open inundated plots were choked by algae. After four years, Melaleuca ericifolia and Melaleuca linariifolia showed good survivorship at upper and lower elevations. Eucalyptus robusta and Casuarina glauca were more successful at upper elevations, and Leptospermum juniperinum did not succeed at either elevation. These results corresponded to patterns of regeneration and to distributions within undisturbed stands. Despite the evidence of natural regeneration, direct seeding was not successful at the experimental site. Given that poor dispersal was indicated at Coomonderry Swamp, it is unlikely that isolated wetlands in the region could rely solely on seed dispersal for woody revegetation. Even where regeneration can occur naturally, some planting or culling might be required if the desired outcome is a species mix comparable to that observed on undisturbed margins.