Climate change mitigation by coral reefs and seagrass beds at risk: How global change compromises coastal ecosystem services.

Seagrass meadows provide valuable ecosystem services of coastal protection and chemical habitat formation that could help mitigate the impact of sea level rise and ocean acidification. However, the intensification of hydrodynamic forces caused by sea level rise, in addition to habitat degradation threaten the provision of these ecosystem services. With quantitative field measurements of the coastal protection and chemical habitat formation services of seagrass meadows, we statistically model the relationships between hydrodynamic forces, vegetation density and the provision of these ecosystem services. Utilising a high-resolution hydrodynamic model that simulates end of the century hydrodynamic conditions and three scenarios of coral reef degradation (i.e., keep up, remain or loss) we quantify how the environmental conditions within a tropical bay will change given changes to the provision of ecosystem services. Our study shows that increasing hydrodynamic forces lead to a seafloor made up of a larger grain size that is increasingly unstable and more vulnerable to erosion. The loss of a fringing reef leads to larger hydrodynamic forces entering the bay, however, the 0.87 m increase in depth due to sea-level rise reduces the bed shear stress in shallower areas, which limits the change in the ecosystem services provided by the current benthic seagrass meadow. Loss of seagrass constitutes the greatest change in a bay ecosystem, resulting in the sediment surface where seagrass existed becoming unstable and the median sediment grain size increasing by 5-7 %. The loss of seagrass also leads to the disappearance of the unique fluctuating chemical habitat, which leaves the surrounding community vulnerable to ocean acidification. A reduction or complete loss of these ecosystem services would impact the entire community assemblage while also leaving the surrounding coastline vulnerable to erosion, thus exacerbating negative effects brought about by climate change.

Political stringency, infection rates, and higher education students' adherence to government measures in the Nordic countries and the UK during the first wave of the COVID-19 outbreak.

Understanding predictors of adherence to governmental measures to prevent the spread of the COVID-19 is fundamental to guide health communication. This study examined whether political stringency and infection rates during the first wave of the pandemic were associated with higher education students' adherence to COVID-19 government measures in the Nordic countries (Denmark, Finland, Norway, Iceland, and Sweden) and the United Kingdom. Both individual- and country-level data were used in present study. An international cross-sectional subsample (n = 10,345) of higher-education students was conducted in May-June 2020 to collect individual-level information on socio-demographics, study information, living arrangements, health behaviors, stress, and COVID-19-related concerns, including adherence to government measures. Country-level data on political stringency from the Oxford COVID-19 Government Response Tracker and national infection rates were added to individual-level data. Multiple linear regression analyses stratified by country were conducted. Around 66% of students reported adhering to government measures, with the highest adherence in the UK (73%) followed by Iceland (72%), Denmark (69%), Norway (67%), Finland (64%) and Sweden (49%). Main predictors for higher adherence were older age, being female and being worried about getting infected with COVID-19 (individual-level), an increase in number of days since lockdown, political stringency, and information about COVID-19 mortality rates (country-level). However, incidence rate was an inconsistent predictor, which may be explained by imperfect data quality during the onset of the pandemic. We conclude that shorter lockdown periods and political stringency are associated with adherence to government measures among higher education students at the outset of the COVID-19 pandemic.

Depressive symptoms in higher education students during the first wave of the COVID-19 pandemic. An examination of the association with various social risk factors across multiple high- and middle-income countries.

Higher-education students face substantial risks for developing depressive symptoms during the COVID-19 pandemic or experiencing exacerbated pre-existing depressive symptoms. This study uses data from the COVID-19 International Student Well-Being Study, which collected data through a non-representative convenience sample in 125 higher-education institutions (HEI) across 26 high- and middle-income countries (N: 20,103) during the first wave of the COVID-19 pandemic. It describes the prevalence of depressive symptoms in higher-education students. We find substantial cross-national variation in depressive symptoms, with lowest mean levels established in the Nordic countries and France, while highest mean levels of depressive symptoms were found in Turkey, South Africa, Spain and the USA. Elevated risk for depressive symptoms was found in female students, students with fewer social support resources and in a more disadvantaged socioeconomic position, and students with a migrant background. COVID-19 related stressors, such as reduced social contact, increased financial insecurity, and academic stress explained a relatively larger proportion of the variance in depressive symptoms compared to non-COVID-19 related stressors. This finding shows that not the pandemic itself, but rather the secondary effects of the pandemic relate to students' mental health. Our results enable HEIs to be better equipped to target groups that are particularly at risk during a pandemic.

Arthroscopic surgery for degenerative knee arthritis and meniscal tears: a clinical practice guideline

The role of arthroscopic surgery in degenerative knee disease was evaluated in this guideline.

Total hip arthroplasty in patients 16 years of age or younger.

PURPOSE: Total hip arthroplasty (THA) is rarely recommended in skeletally immature patients. The goal of the present study was to report our short- to mid-term results of THA in a series of children aged 16 years or younger, including clinical outcomes and post-operative complications, signs of radiographic loosening of the prostheses, and revision rate. METHODS: The 18 children (two male and 16 female patients, 24 hips) underwent cementless THA at a mean age of 14.6 years (11 to 16). Five patients had a bilateral, one-stage surgical procedure. Clinical assessment of these hips used the Merle d'Aubigné et Postel scale modified by Charnley to facilitate assessment of the function of walking. Clinical and radiographic follow-up was conducted at six weeks, six months and then yearly for the first three years. All post-operative complications were recorded. RESULTS: No intra-operative or early post-operative complications occurred. At a mean follow-up of 3.8 years (1 to 8), all patients had greatly improved pain and function scores. All children in the present study improved from severely impaired gait, including four children who were wheelchair-bound, to completely unrestricted gait. All hips demonstrated good alignment with no evidence of wear or radiographic lucencies. No revision of components has been required. One patient had persistent adductor contracture which was addressed with adductor tendon release. CONCLUSIONS: THA is a successful procedure for unsalvageable hip arthritis in children at a mean follow-up of 3.8 years. Long-term follow-up will be needed to determine implant longevity of the components in these children.

Rectal red blood loss in a healthy toddler is not always a juvenile polyp.

Aim Heterotopic gastric mucosa is a well-known congenital anomaly in Meckel's diverticula and duplication cysts. Solitary heterotopic gastric mucosa in the rectum is a rare and frequently overlooked abnormality. Starting from a patient history, the literature is searched and all cases reported over the past 20 years are reviewed and compared to a summary of the older cases. Differences between adult and childhood presentation are outlined and our patient is compared with prior reported cases. Case A 3-year-old girl presented with recurrent rectal blood loss caused by heterotopic gastric mucosa without duplication cyst. She was endoscopically treated with two-stage endoscopic surgical dissection (ESD). Up to now, rectal heterotopic gastric mucosa has been reported in 34 adults and 24 children, including this patient. There is an overall male dominance (69%). Presenting complaints in children were recurrent fresh blood loss per anum (96%), pain (46%), perineal ulcers (25%), diarrhoea (8%) and one patient had an ano-cutaneous fistula. Endoscopy revealed a mucosal elevation with a slightly different aspect (33%), a polyp (42%) and a solitary ulcer (25%). Endoscopy in adults reveals more frequently polyps compared to children. Treatment in childhood is mainly surgical where adults are more frequently treated with endoscopic techniques. Conclusion In a child with recurrent rectal bleeding in good general health, it is important to withhold heterotopic gastric mucosa in the differential diagnosis and take sufficient biopsies during endoscopy.

Gender differences in psychotropic use across Europe: Results from a large cross-sectional, population-based study.

BACKGROUND: In many epidemiological studies, women have been observed to consume psychotropic medication more often than men. However, the consistency of this relationship across Europe, with differences in mental health care (MHC) resources and reimbursement policies, is unknown. METHODS: Questions on 12-month psychotropic use (antidepressants, benzodiazepines, antipsychotics, mood stabilizers) were asked to 34,204 respondents from 10 European countries of the EU-World Mental Health surveys. Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) criteria were used to determine 12-month prevalence of mood/anxiety disorders using the Composite International Diagnostic Interview (v3.0). RESULTS: For all participating countries, women were significantly more likely than men to use psychotropic medication within the previous 12 months (overall-OR=2.04, 95% CI: 1.81-2.31). This relationship remained significant after adjusting for common sociodemographic factors (age, income level, employment status, education, marital status) and country-level indicators (MHC provision, private household out-of-pocket expenditure, and Gender Gap Index). In multivariable gender-stratified risk-factor analysis, both women and men were more likely to have taken psychotropic medication with increasing age, decreasing income level, and mental health care use within the past 12 months, with no significant differences between genders. When only including participants with a mental disorder, gender differences overall were still significant with any 12-month mood disorder but not with any 12-month anxiety disorder, remaining so after adjusting for sociodemographic characteristics and country-level indicators. CONCLUSIONS: Women use psychotropic medication consistently more often than men, yet reasons for their use are similar between genders. These differences also appear to be contingent on the specific mental disorder.

Amoxicillin plus temocillin as an alternative empiric therapy for the treatment of severe hospital-acquired pneumonia: results from a retrospective audit.

A formulary decision was made at a large provider of acute hospital services in Surrey to replace piperacillin/tazobactam with amoxicillin+temocillin for the empiric treatment of severe hospital-acquired pneumonia. This decision was made because the use of broad-spectrum-ß-lactam antibiotics is a known risk factor for Clostridium difficile infection (CDI) and for the selection of resistance. After the antibiotic formulary was changed, a retrospective audit was conducted to assess the effect of this change. Data from patients hospitalised between January 2011 and July 2012 for severe hospital-acquired pneumonia and treated empirically with piperacillin/tazobactam or amoxicillin+temocillin were reviewed retrospectively. Clinical characteristics of patients, data related to the episode of pneumonia, clinical success and incidence of significant diarrhoea and CDI were analysed. One hundred ninety-two episodes of severe hospital-acquired pneumonia in 188 patients were identified from hospital records. Ninety-eight patients received piperacillin/tazobactam and 94 amoxicillin+temocillin. At baseline, the two treatment groups were comparable, except that more patients with renal insufficiency were treated with piperacillin/tazobactam. Clinical success was comparable (80 versus 82 %; P = 0.86), but differences were observed between piperacillin/tazobactam and amoxicillin+temocillin for the rates of significant diarrhoea (34 versus 4 %, respectively; P < 0.0001) and for CDI (7 versus 0 %, respectively; P < 0.0028). This preliminary study suggests that the combination amoxicillin+temocillin is a viable alternative to piperacillin/tazobactam for the treatment of severe hospital-acquired pneumonia. This combination appears to be associated with fewer gastrointestinal adverse events. Further studies are needed to evaluate the place of amoxicillin+temocillin as empiric treatment of severe hospital-acquired pneumonia.

Feasibility of osteosynthesis of fractured cadaveric hips following preventive elastomer femoroplasty.

BACKGROUND: In vitro cadaveric studies showed that elastomer femoroplasty prevents displacement of fracture parts after proximal hip fracture allowing for conservative treatment. In the event that secondary displacement does occur, the purpose of this present study was to determine the feasibility of performing osteosynthesis of a fractured hip after preventive treatment with elastomer femoroplasty. METHODS: Ten pairs of human cadaveric femurs were fractured in a simulated fall configuration. From each pair, one femur was randomly selected for elastomer femoroplasty prior to fracture generation and the contralateral femur was used as control. Following hip fracture generation, osteosynthesis was performed in all femurs. The operative time per case, technical difficulties during the procedure, and postoperative energy-to-failure load were recorded. RESULTS: The mean (SD) time to perform osteosynthesis was 20 (6) minutes in the control-group and 19 (5) minutes in the elastomer femoroplasty-group (P=0.69). During osteosynthesis of the fractured hip in the elastomer femoroplasty-group, no difficulties including the need for additional instruments to remove elastomer from the proximal femur were recorded. Postoperative energy-to-failure load was similar in the control-group and the elastomer femoroplasty-group. CONCLUSION: Fixation with routine osteosynthesis of displaced cadaveric hip fractures is not hindered by the presence of previously injected elastomer.

Professional care seeking for mental health problems among women and men in Europe: the role of socioeconomic, family-related and mental health status factors in explaining gender differences.

PURPOSE: This comparative study examines cross-national variation in gender differences in primary and specialized mental health care use in Europe. We investigate to what extent socioeconomic, family-related, and mental health factors explain the gender difference, and how the impact of these groups of determinants on gender differences in mental health care use varies between countries. METHODS: Data from the Eurobarometer 248 (2005-2006) for 29 European countries is used and country-specific logistic regression analyses are performed. RESULTS: Gender differences in professional care seeking are largely need based. In almost one-third of the countries examined, the gender difference is mainly attributable to women's poorer mental health status. However, in some countries, family and socioeconomic characteristics also have an independent contribution to the gender difference in mental health care use. Women's higher likelihood of a lower socioeconomic position, might partly explain their higher primary care use, while in some countries, it restricts their specialized care use. In addition, some social conditions, as having children and being widowed, seem to function in a few countries as suppressors of women's care use. CONCLUSIONS: Our study has shown that the gender difference in mental health care use, with women having a higher care use, is not a consistent European phenomenon and is dependent on the type of care provider, with greater gender inequity in the use of primary health care. The social roles adopted by men and women have in some countries on top of the mental health status a relevant influence on the greater tendency among women to contact a care provider. How the socioeconomic and family characteristics moderate the relation between gender and mental health care use is not straightforward and country dependent.

Evaluation of the migration of 15 photo-initiators from cardboard packaging into Tenax(®) using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS).

Photo-initiators are widely used to cure ink on packaging materials used in food applications such as plastic films or cartonboards. In migration studies, food simulants are very often used to simulate food, like Tenax(®), which is the simulant for dry foodstuffs. In this paper a fast and reliable confirmation method for the determination of the following photo-initiators in Tenax(®) is described: benzophenone (BP), 4,4'-bis(diethylamino)benzophenone (DEAB), 2-chloro-9H-thioxanthen-9-one (CTX), 1-chloro-4-propoxy-9H-thioxanthen-9-one (CPTX), 2,4-diethyl-9H-thioxanthen-9-one (DETX), 2,2-dimethoxy-2-phenyl acetophenone (DMPA), 4-(dimethylamino)benzophenone (DMBP), 2-ethylanthraquinone (EA), ethyl-4-dimethylaminobenzoate (EDMAB), 1-hydroxylcyclohexyl phenyl ketone (HCPK), 2-hydroxy-4'-(2-hydroxyethoxy)-2-methylpropiophenone (HMMP), 2-isopropyl-9H-thioxanthen-9-one (ITX), 4-methylbenzophenone (MBP), Michler's ketone (MK), and 4-phenylbenzophenone (PBZ). After the migration study was completed, the simulant Tenax(®) was extracted using acetonitrile, followed by analysis on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Quantification was carried out using benzophenone-d10 (BP-d10) as internal standard. The presented method is validated in terms of matrix effect, specificity, linearity, recovery, precision and sensitivity, showing the method can detect all photo-initiators at very low concentrations (LOD < 0.125 µg g(-1) for all substances). Finally, the procedure was applied to real samples, proving the capabilities of the presented method.

A novel cosmetic approach to treat thinning hair.

BACKGROUND: Many of today's treatments associated with 'thinning hair', such as female pattern hair loss and telogen effluvium, are focused on two of the key aspects of the condition. Over-the-counter or prescription medications are often focused on improving scalp hair density while high-quality cosmetic products work to prevent further hair damage and minimize mid-fibre breakage. Fibre diameter is another key contributor to thinning hair, but it is less often the focus of medical or cosmetic treatments. OBJECTIVES: To examine the ability of a novel leave-on technology combination [caffeine, niacinamide, panthenol, dimethicone and an acrylate polymer (CNPDA)] to affect the diameter and behaviour of individual terminal scalp hair fibres as a new approach to counteract decreasing fibre diameters. METHODS: Testing methodology included fibre diameter measures via laser scan micrometer, assessment of fibre mechanical and behavioural properties via tensile break stress and torsion pendulum testing, and mechanistic studies including cryoscanning electron microscopy and autoradiographic analysis. RESULTS: CNPDA significantly increased the diameter of individual, existing terminal scalp hair fibres by 2-5 µm, which yields an increase in the cross-sectional area of approximately 10%. Beyond the diameter increase, the CNPDA-thickened fibres demonstrated the altered mechanical properties characteristic of thicker fibres: increased suppleness/pliability (decreased shear modulus) and better ability to withstand force without breaking (increased break stress). CONCLUSIONS: Although cosmetic treatments will not reverse the condition, this new approach may help to mitigate the effects of thinning hair.

Rigour of development does not AGREE with recommendations in practice guidelines on the use of ice for acute ankle sprains.

OBJECTIVE This study evaluated whether the Appraisal of Guidelines Research and Evaluation (AGREE) rigour of development score of practice guidelines on ice for acute ankle sprains is related to the convergence between recommendations. DESIGN The authors systematically reviewed guidelines on ice for acute ankle sprains. Four appraisers independently used the AGREE instrument to evaluate the rigour of development of selected guidelines. For each guideline, one reviewer listed the cited evidence on ice and calculated a cited evidence score. The authors plotted the recommended durations and numbers of ice applications over the standardised rigour of development score to explore the relationships. DATA SOURCES Three reviewers searched for guidelines in Medline, Embase, Sportdiscus, PEDro, G-I-N Guideline Library, Trip Database, SumSearch, National Guideline Clearinghouse and the Health Technology Assessment database, and conducted a web-based search for guideline development organisations. ELIGIBILITY CRITERIA Eligible guidelines had a development methodology that included a process to search or use results from scientific studies and the participation of an expert group to formulate recommendations. RESULTS The authors identified 21 guidelines, containing clinically significant variations in recommended durations and numbers of ice applications. The median standardised rigour of development score was 57% (IQR 18 to 77). Variations occurred evenly among guidelines with low moderate or high rigour scores. The median evidence citation score in the guidelines was 7% (IQR 0 to 61). CONCLUSIONS There is no relationship between the rigour of development score and the recommendations in guidelines on ice for acute ankle sprains. The guidelines suffered from methodological problems which were not captured by the AGREE instrument.

[Flanders versus The Netherlands: focus on differences between depressive symptoms in men and women measured on the basis of CES-D8]. / Vlaanderen versus Nederland: verschillen in depressieve klachten bij mannen en vrouwen gemeten met de CES-D8.

BACKGROUND: A consistent finding in international research is the higher prevalence of depression in women than in men, but it is not known to what extent this gender difference is robust in population research. AIM: In this study we focus on gender differences in depressive symptoms of the population of Flanders and the Netherlands. method We made use of the European Social Survey organised in 2006 and 2007 (n = 3014); depression being measured by means of an 8-item version of the Center of Epidemiological Studies Depression Scale, CES-D. First we studied the psychometric properties of the depression inventory, looking closely at both the reliability and factional validity of the scale. Next we compared the gender and regional differences in the prevalence of depressive symptoms as measured by the CES-D8 scale. Finally, using regression analysis, we examined to what extent the gender differences between Flanders and the Netherlands were family-related and linked to socio-economic factors. RESULTS: Our study pointed to the reliability and factional validity of the CES-D8. Our results confirmed a higher prevalence of depressive symptoms among women than among men. On average, Flemish respondents reported fewer depressive symptoms than Dutch respondents, but their scores showed greater dispersion. CONCLUSIONS: These differences can be explained partly by different family and socioeconomic circumstances.

In-vivo time-dependent articular cartilage contact behavior of the tibiofemoral joint.

OBJECTIVE: The purpose of this study was to investigate the in-vivo time-dependent contact behavior of tibiofemoral cartilage of human subjects during the first 300 s after applying a constant full body weight loading and determine whether there are differences in cartilage contact responses between the medial and lateral compartments. DESIGN: Six healthy knees were investigated in this study. Each knee joint was subjected to full body weight loading and the in-vivo positions of the knee were captured by two orthogonal fluoroscopes during the first 300 s after applying the load. Three-dimensional models of the knee were created from MR images and used to reproduce the in-vivo knee positions recorded by the fluoroscopes. The time-dependent contact behavior of the cartilage was represented using the peak cartilage contact deformation and the cartilage contact area as functions of time under the constant full body weight. RESULTS: Both medial and lateral compartments showed a rapid increase in contact deformation and contact area during the first 20s of loading. After 50s of loading, the peak contact deformation values were 10.5+/-0.8% (medial) and 12.6+/-3.4% (lateral), and the contact areas were 223.9+/-14.8 mm(2) (medial) and 123.0+/-22.8 mm(2) (lateral). Thereafter, the peak cartilage contact deformation and contact area remained relatively constant. The respective changing rates of cartilage contact deformation were 1.4+/-0.9%/s (medial) and 3.1+/-2.5%/s (lateral); and of contact areas were 40.6+/-20.8 mm(2)/s (medial) and 24.0+/-11.4 mm(2)/s (lateral), at the first second of loading. Beyond 50 s, both changing rates approached zero. CONCLUSIONS: The peak cartilage contact deformation increased rapidly within the first 20s of loading and remained relatively constant after approximately 50 s of loading. The time-dependent response of cartilage contact behavior under constant full body weight loading was significantly different in the medial and lateral tibiofemoral compartments, with greater peak cartilage contact deformation on the lateral side and greater contact area on the medial side. These data can provide insight into normal in-vivo cartilage function and provide guidelines for the improvement of ex-vivo cartilage experiments and the validation of computational models that simulate human knee joint contact.

In vivo cartilage contact deformation in the healthy human tibiofemoral joint.

OBJECTIVES: In vivo cartilage contact deformation is instrumental for understanding human joint function and degeneration. This study measured the total deformation of contacting articular cartilage in the human tibiofemoral joint during in vivo weight-bearing flexion. METHODS: Eleven healthy knees were magnetic resonance (MR) scanned and imaged with a dual fluoroscopic system while the subject performed a weight-bearing single-leg lunge. The tibia, femur and associated articulating cartilage were constructed from the MR images and combined with the dual fluoroscopic images to determine in vivo cartilage contact deformation from full extension to 120 degrees of flexion. RESULTS: In both compartments, minimum peak compartmental contact deformation occurred at 30 degrees of flexion (24 +/- 6% medial, 17 +/- 7% lateral) and maximum peak compartmental deformation occurred at 120 degrees of flexion (30 +/- 13% medial, 30 +/- 10% lateral) during the weight-bearing flexion from full extension to 120 degrees. Average medial contact areas and peak contact deformations were significantly greater than lateral compartment values (P < 0.05). In addition, cartilage thickness in regions of contact was on average 1.4- and 1.1-times thicker than the average thickness of the tibial and femoral cartilage surfaces, respectively (P < 0.05). CONCLUSIONS: These data may provide base-line knowledge for investigating the effects of various knee injuries on joint contact biomechanics and the aetiology of cartilage degeneration.

Farnesylation of Pex19p is not essential for peroxisome biogenesis in yeast and mammalian cells.

Pex19p exhibits a broad binding specificity for peroxisomal membrane proteins (PMPs), and is essential for the formation of functional peroxisomal membranes. Pex19p orthologues contain a C-terminal CAAX motif common to prenylated proteins. In addition, Saccharomyces cerevisiae and Chinese hamster Pex19p are at least partially farnesylated in vivo. Whether farnesylation of Pex19p plays an essential or merely ancillary role in peroxisome biogenesis is currently not clear. Here, we show that (i) nonfarnesylated and farnesylated human Pex19p display a similar affinity towards a select set of PMPs, (ii) a variant of Pex19p lacking a functional farnesylation motif is able to restore peroxisome biogenesis in Pex19p-deficient cells, and (iii) peroxisome protein import is not affected in yeast and mammalian cells defective in one of the enzymes involved in the farnesylation pathway. Summarized, these observations indicate that the CAAX box-mediated processing steps of Pex19p are dispensable for peroxisome biogenesis in yeast and mammalian cells.

ACE inhibitor captopril reduces ecdysteroids and oviposition in moths.

By using the selective ACE inhibitor captopril, we studied the effect of the angiotensin converting enzyme (ACE) on larval growth, metamorphosis, and reproduction in a lepidopteran species, the cotton leafworm, Spodoptera littoralis. Captopril was detrimental to adult formation and oviposition, and in female moths it elicited decreasing ecdysteroid levels, but increasing trypsin activities. Our results suggest that captopril downregulates oviposition by two independent pathways. Apparently, oviposition is influenced by a complex interaction of ACE, trypsin activity, and ecdysteroid levels.

Nutrient sensing systems for rapid activation of the protein kinase A pathway in yeast.

The cAMP-protein kinase A (PKA) pathway in the yeast Saccharomyces cerevisiae controls a variety of properties that depend on the nutrient composition of the medium. High activity of the pathway occurs in the presence of rapidly fermented sugars like glucose or sucrose, but only as long as growth is maintained. Growth arrest of fermenting cells or growth on a respiratory carbon source, like glycerol or ethanol, is associated with low activity of the PKA pathway. We have studied how different nutrients trigger rapid activation of the pathway. Glucose and sucrose activate cAMP synthesis through a G-protein-coupled receptor system, consisting of the GPCR Gpr1, the Galpha protein Gpa2 and its RGS protein Rgs2. Glucose is also sensed intracellularly through its phosphorylation. Specific mutations in Gpr1 abolish glucose but not sucrose signalling. Activation of the PKA pathway by addition of a nitrogen source or phosphate to nitrogen- or phosphate-starved cells, respectively, is not mediated by an increase in cAMP. Activation by amino acids is triggered by the general amino acid permease Gap1, which functions as a transporter/receptor. Short truncation of the C-terminus results in constitutively activating alleles. Activation by ammonium uses the ammonium permeases Mep1 and Mep2 as receptor. Specific point mutations in Mep2 uncouple signalling from transport. Activation by phosphate is triggered a.o. by the Pho84 phosphate permease. Several mutations in Pho84 separating transport and signalling or triggering constitutive activation have been obtained.

Comparison of closed-loop controlled administration of propofol using Bispectral Index as the controlled variable versus "standard practice" controlled administration.

BACKGROUND: This report describes a new closed-loop control system for propofol that uses the Bispectral Index (BIS) as the controlled variable in a patient-individualized, adaptive, model-based control system, and compares this system with manually controlled administration of propofol using hemodynamic and somatic changes to guide anesthesia. METHODS: Twenty female patients, American Society of Anesthesiologists physical status I or II, who were scheduled for gynecologic laparotomy were included to receive propofolremifentanil anesthesia. In group I, propofol was titrated using a BIS-guided, model-based, closed-loop system. The BIS target was set at 50. In group II, propofol was titrated using classical hemodynamic signs of (in)adequate anesthesia. Performance of control during induction and maintenance of anesthesia were compared between both groups using BIS as the controlled variable in group I and the reference variable in group II, and, conversely, the systolic blood pressure as the controlled variable in group II and the reference variable in group I. At the end of anesthesia, recovery profiles between groups were compared. RESULTS: Although patients undergoing manual induction of anesthesia in group II at 300 ml/h reached a BIS level of 50 faster than patients undergoing open-loop, computer-controlled induction in group I, manual induction caused a more pronounced initial overshoot of the BIS target. This resulted in a more pronounced decrease in blood pressure in group II. During the maintenance phase, better control of BIS and systolic blood pressure was found in group I compared with group II. Recovery was faster in group I. CONCLUSION: A closed-loop system for propofol administration using the BIS as a controlled variable together with a model-based controller is clinically acceptable during general anesthesia.