Lipid bilayer composition modulates the unfolding free energy of a knotted α-helical membrane protein.

α-Helical membrane proteins have eluded investigation of their thermodynamic stability in lipid bilayers. Reversible denaturation curves have enabled some headway in determining unfolding free energies. However, these parameters have been limited to detergent micelles or lipid bicelles, which do not possess the same mechanical properties as lipid bilayers that comprise the basis of natural membranes. We establish reversible unfolding of the membrane transporter LeuT in lipid bilayers, enabling the comparison of apparent unfolding free energies in different lipid compositions. LeuT is a bacterial ortholog of neurotransmitter transporters and contains a knot within its 12-transmembrane helical structure. Urea is used as a denaturant for LeuT in proteoliposomes, resulting in the loss of up to 30% helical structure depending upon the lipid bilayer composition. Urea unfolding of LeuT in liposomes is reversible, with refolding in the bilayer recovering the original helical structure and transport activity. A linear dependence of the unfolding free energy on urea concentration enables the free energy to be extrapolated to zero denaturant. Increasing lipid headgroup charge or chain lateral pressure increases the thermodynamic stability of LeuT. The mechanical and charge properties of the bilayer also affect the ability of urea to denature the protein. Thus, we not only gain insight to the long-sought-after thermodynamic stability of an α-helical protein in a lipid bilayer but also provide a basis for studies of the folding of knotted proteins in a membrane environment.

Seamount egg-laying grounds of the deep-water skate Bathyraja richardsoni.

Highly localized concentrations of elasmobranch egg capsules of the deep-water skate Bathyraja richardsoni were discovered during the first remotely operated vehicle (ROV) survey of the Hebrides Terrace Seamount in the Rockall Trough, north-east Atlantic Ocean. Conductivity-temperature-depth profiling indicated that the eggs were bathed in a specific environmental niche of well-oxygenated waters between 4·20 and 4·55° C, and salinity 34·95-35·06, on a coarse to fine-grained sandy seabed on the seamount's eastern flank, whereas a second type of egg capsule (possibly belonging to the skate Dipturus sp.) was recorded exclusively amongst the reef-building stony coral Solenosmilia variabilis. The depths of both egg-laying habitats (1489-1580 m) provide a de facto refuge from fisheries mortality for younger life stages of these skates.

Hidden impacts of ocean acidification to live and dead coral framework.

Cold-water corals, such as Lophelia pertusa, are key habitat-forming organisms found throughout the world's oceans to 3000 m deep. The complex three-dimensional framework made by these vulnerable marine ecosystems support high biodiversity and commercially important species. Given their importance, a key question is how both the living and the dead framework will fare under projected climate change. Here, we demonstrate that over 12 months L. pertusa can physiologically acclimate to increased CO2, showing sustained net calcification. However, their new skeletal structure changes and exhibits decreased crystallographic and molecular-scale bonding organization. Although physiological acclimatization was evident, we also demonstrate that there is a negative correlation between increasing CO2 levels and breaking strength of exposed framework (approx. 20-30% weaker after 12 months), meaning the exposed bases of reefs will be less effective 'load-bearers', and will become more susceptible to bioerosion and mechanical damage by 2100.

The DeStress for Success Program: effects of a stress education program on cortisol levels and depressive symptomatology in adolescents making the transition to high school.

Various studies have shown that increased activity of the hypothalamic-pituitary-adrenal (HPA) axis can predict the onset of adolescent depressive symptomatology. We have previously shown that adolescents making the transition to high school present a significant increase in cortisol levels, the main product of HPA axis activation. In the present study, we evaluated whether a school-based education program developed according to the current state of knowledge on stress in psychoneuroendocrinology decreases cortisol levels and/or depressive symptoms in adolescents making the transition to high school. Participants were 504 Year 7 high school students from two private schools in the Montreal area. Adolescents of one school were exposed to the DeStress for Success Program while adolescents from the other school served as controls. Salivary cortisol levels and depressive symptomatology were measured before, immediately after as well as 3 months after exposure to the program. Measures of negative mood were obtained at baseline in order to determine whether adolescents starting high school with specific negative moods were differentially responsive to the program. The results show that only adolescents starting high school with high levels of anger responded to the intervention with a significant decrease in cortisol levels. Moreover, we found that adolescents who took part in the intervention and showed decreasing cortisol levels following the intervention (responders) were 2.45 times less at risk to suffer from clinical and subclinical depressive states three months post-intervention in comparison to adolescents who showed increasing cortisol levels following the intervention (nonresponders). This study provides the first evidence that a school-based program on stress is effective at decreasing cortisol levels and depressive symptomatology in adolescents making the transition to high school and it helps explain which adolescents are sensitive to the program and what are some of the characteristics of these individuals.

Weight changes following lower limb arthroplasty: a prospective observational study.

The aim of this study was to assess patterns of weight loss/gain following total hip or knee joint replacement. Four hundred and fifty primary lower limb arthroplasty patients, where the current surgery was the last limiting factor to improved mobility, were selected. Over a one year period 212 gained weight (mean 5.03kg), 92 remained static, and 146 lost weight. The median change was a weight gain of 0.50Kg (p = 0.002). All patients had a significant improvement in Oxford outcome scores. Hip arthroplasty patients were statistically more likely to gain weight than knee arthroplasty patients. A successful arthroplasty, restoring a patient's mobility, does not necessarily lead to subsequent weight loss. The majority of patients put on weight with an overall net weight gain. No adverse effect on functional outcome was noted.

Latex sensitivity in a macaque (Macaca mulatta).

UNLABELLED: BACKGROUND AND HISTORY: An adult Macaca mulatta was examined because of a history of multiple episodes of conjunctivitis and an acute, pruritic, dermatitic eruption that affected the axillary and inguinal regions, forearms, thorax, and neck. METHODS AND RESULTS: Results of corneal staining, examination of skin scrapings and feces, fungal culture, CBC, and a thyroid profile (thyroxine/triiodothyronine concentrations) were negative or normal, with the exception of eosinophilia (1,040/mm3). Examination of a punch biopsy specimen of the skin indicated chronic, nonsuppurative eosinophilic dermatitis. Skin patch testing against 25 contact allergens was negative for a delayed-type hypersensitivity reaction. Allergen-specific IgE testing, using six monkey chow additives, also yielded negative results, but testing against latex revealed a strong positive result (0.74 KU/L) consistent with a latex allergy. A skin prick test performed by use of a latex supernatant revealed significant inflammation at the latex site at 72 h and one week. Vinyl gloves were substituted for latex gloves, and that resulted in a marked decrease in erythema, pruritus, and lichenification with no flares of dermatitis for four years. Repeat skin biopsy fourteen weeks after the original biopsy revealed normal epidermis; however, mild chronic active nonsuppurative, perifolliculitis persisted. CONCLUSION: Latex can induce allergic dermatitis in nonhuman primates and should be included in the differen tial diagnosis for atopic dermatitis.

A Canadian survey of cancer patients' experiences: are their needs being met?

Cancer patients (n = 913) who received treatment within the previous 2 years were interviewed to quantify reports of symptoms associated with cancer, measure the impact of symptoms on lifestyles, document experiences with accessing information and treatment for cancer and its symptoms, and record attitudes about the level of care received. Cancer patients were primarily recruited through newspaper ads placed throughout Canada and asked to complete a self-report questionnaire. Patients called a toll-free number and were interviewed to ensure eligibility. Most respondents were female (66%) with breast cancer (64%). Prostate cancer (40%) was the most common diagnosis among males. Almost all respondents (94%) reported experiencing one or more symptoms. Fatigue and anxiety were the most frequently reported symptoms (78% and 77%, respectively). Fatigue was most likely to be self-rated as moderate to severe and was most likely to interfere in normal daily activities. Respondents who experienced fatigue reported a more frequent use of healthcare services (including complementary therapies) than those who did not experience fatigue. Half of the respondents reported trying to find information on fatigue, but only half of these said they had obtained information. The most helpful sources of information were nurses, specialists, and other cancer patients. Respondents were more likely to be dissatisfied with their treatments for their symptoms than for their cancer. This survey indicates that most cancer patients experience symptoms related to the disease and its treatment. The most prevalent symptoms are fatigue and anxiety; fatigue is the most debilitating.

The impact of postchemotherapy nausea and vomiting on quality of life after moderately emetogenic chemotherapy.

The purpose of the study was to assess the impact of postchemotherapy nausea and vomiting (PCNV) after moderately emetogenic chemotherapy on health-related quality of life (HRQOL) in patients with cancer being treated in a routine clinical practice setting. The European Organization for Research and Treatment in Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was administered on day 2 and day 6 following moderately emetogenic chemotherapy to 119 patients with a variety of cancers. Patients kept daily diaries to record the occurrence and severity of nausea and vomiting. The QLQ-C30 questions were modified, for this study only, to assess the impact of nausea and vomiting on HRQOL in patients who experienced nausea and/or vomiting during the six days following chemotherapy. Those patients who experienced either nausea or vomiting experienced a decrease in HRQOL from prechemotherapy levels on six functioning and five symptom scales at day 2, and on four functioning and four symptom scales on day 6. Comparison of mean scores between the unmodified QLQ-30 and the nausea and vomiting versions demonstrated that the HRQOL rating attributed to nausea and vomiting accounted for much, but not all, of the deterioration in HRQOL scores in patients who experienced these symptoms. It can be concluded that patients who experience PCNV experience a significant negative impact on their HRQOL and that this impact can be attributed in large part to their experience of nausea and vomiting. However, since not all of the deterioration is attributable to these symptoms, other reasons for some of the decrease in HRQOL must also be identified in future studies.

A Canadian survey of issues in cancer pain management.

We report the analysis of a cancer management survey mailed to a representative group of health professionals in 1994. The goals of the study were to gather information on cancer pain treatment practices, and to obtain health professional views on obstacles to ideal pain management. The survey, designed by a working party of pharmacists, nurses and physicians, was distributed to 14,628 physicians. A total of 2,686 physicians responded to the survey, including 39% of medical or radiation oncologists, and 18.19% of physicians who listed their primary interest as Family Medicine. Reflecting the modest emphasis placed on palliative care and cancer pain management in the current Canadian milieu, 67% of physicians rated their past teaching experience as only "fair" or "poor." Lack of exposure to pain education was reflected in the response to a series of hypothetical case scenarios exploring physician choices in managing severe cancer pain. For example, in the initial management of a cancer patient with severe pain, 50% of physicians would not use a strong opioid in the absence of other contraindications to opioid use. A wide variety of analgesics and non-pharmacologic techniques is available to Canadian physicians to assist patients with pain. Few physicians identified the unavailability of analgesics or analgesic techniques as limiting factors in pain management. We conclude that greater emphasis should be placed on pain education in our training programmes. We suggest that further surveys of this type, sponsored by our provincial colleges and medical organizations, can provide feedback which will enhance the adherence by Canadian physicians to published guidelines for pain management.

Focus groups with cancer patients: toward a more comprehensive understanding of the cancer experience.

Six focus groups of 58 individuals (30 women and 28 men) were held in 3 Canadian cities to help develop a survey instrument to be implemented nationally to identify cancer patients' experiences with cancer: treatment, symptoms and symptom management. Patient participants had different cancer diagnoses, but their experience with cancer had been within the year preceding the study. Our intent was to identify as many themes as possible to allow for comparison of different experiences in a national survey. This paper reports on what was learned substantively from these focus groups and discusses the methodological contribution of focus groups in developing survey tools.

Pregnancy status, self-esteem, and ethnicity: some relationships in a sample of adolescents.

PIP: Low self-esteem is presumed to predict self-destructive and deviant behaviors, such as drug use, school dropout, and early sexual involvement. The multidimensional construct of self-esteem was used to investigate the relationships among pregnancy status, self-esteem, and ethnicity among 100 pregnant/parenting and never-pregnant African American and European American female adolescents aged 15-19 years of mean age 16.74 years. The sample was comprised of 41 African Americans and 59 European Americans from two Southern states. Self-esteem and pregnancy status were found to be associated for European American adolescents, but not for African American adolescents. Never-pregnant European American adolescents scored significantly better than their same-race pregnant counterparts on 10 of the 12 self-esteem dimensions examined.^ieng

Impact of migraine and tension-type headache on life-style, consulting behaviour, and medication use: a Canadian population survey.

A large sample of Canadian adults was surveyed by telephone to determine the prevalence and characterization of headache, and the effects of headache on life-style, consulting behaviours and medication use. We reported prevalence and characterization in a previous issue; here, we detail the effects of headaches on sufferers. Sixteen and one-half percent of adult Canadians experience migraine and 29% tension-type headaches. In over 70% of headache sufferers interpersonal relationships are impaired. Regular activities are limited in 78% of migraine attacks and 38% of tension-type headaches. Despite this, only 64% of migraine and 45% of tension-type headache sufferers had ever sought medical attention, and of these only 32% returned for ongoing care. Fourteen percent of migraine and 8% of tension-type headache sufferers had used emergency departments. Most headache sufferers take medication, primarily over-the-counter varieties. Measures to reach the headache population are needed, as are safe effective treatment options that will encourage them to participate in their medical care.

A Canadian population survey on the clinical, epidemiologic and societal impact of migraine and tension-type headache.

Trained telephone interviewers contacted 1,573 adults across Canada about the nature and frequency of headaches suffered by them or by others in their households. Using a table of pain symptoms and other characteristics abstracted from the International Headache Society (IHS) classification, the headaches were assigned to migraine headache, tension-type headache or other diagnostic groups. Of the households sampled, 59% had at least one headache sufferer in residence. The proportion of headache sufferers with migraine was 14%; with tension-type, 36%; and with both, 14%. Migraine headache caused more disability than tension-type headache, with nearly 20% of migraine sufferers taking time off work and disability lasting for a mean of 1 day. It is concluded that the current prevalences of migraine and tension-type headache in Canada fall around the mean of previous studies, that the IHS criteria can form a basis for diagnostic classification and that the functional impact of migraine has been seriously underestimated in the past.

Double-blind cross-over placebo controlled study of flunarizine in patients with therapy resistant epilepsy.

Twenty-five patients with long-standing therapy resistant epilepsy were studied in an eight-month double-blind cross-over add-on trial with a daily dose of 15 mg flunarizine. In five patients the seizure frequency decreased 50% or more. The mean seizure frequency reduction in the patients on flunarizine was 35%. Particularly the control of secondary generalized seizures improved. Flunarizine did not significantly alter the plasma levels of the regular anticonvulsant drugs. Minimal adverse side effects were reported equally in the flunarizine and the placebo group. In three patients depressive symptoms improved and two patients became free of postictal headaches. Flunarizine appears to be a safe adjuvant anticonvulsant.

Pavlovian conditioning of sexual arousal: parametric and background manipulations.

Recent studies have shown that a Pavlovian conditioned stimulus (CS) for unconsummated sexual arousal can increase the rate of copulation in the rat. This report includes five experiments examining the effects of parametric manipulations on the conditioned arousal response. Results show that between six and nine trials are necessary for reliable conditioning, but extinction is somewhat slower than acquisition. The function for the CS-US (unconditioned stimulus) interval is quadratic, with a minimum of several minutes required for effective conditioning. In the first three experiments, it appeared that background cues were conditioned as well as the designated CSs, and this was tested explicitly in the last two studies. In one, the effect of background cues was shown by training and testing in different situations; in the second, background cues were shown to be subject to latent inhibition. These results demonstrate the influence of Pavlovian learning in sexual behavior and help to provide the basis for an animal model of the acquisition of deviant sexual arousal in humans.