[Palliative care of patients receiving opioid substitution therapy]. / Palliativversorgung von Patienten in Opioidsubstitutionsbehandlung.

Patients with opioid use disorder survive longer and reach higher ages due to harm reduction and maintenance programs. Therefor and because of concomitant comorbidities there is an increased incidence of life-limiting diseases. Thus, increasing numbers of patients with opioid use disorder or in maintenance programs will require palliative care. However, both inpatient and outpatient service providers are uncertain about providing palliative care for these patients. Home-care teams and inpatient hospices have been known to refuse admission for patients with opioid use disorder. Providing medical care to patients receiving substitution therapy can be challenging because maintenance programs require strict compliance with their rules and regulations; however, an individualized approach with knowledge of basic legal requirements enables good palliative care. In this manner, it is possible to ensure healthcare for these aging patients.

Ultra-broadband EPR spectroscopy in field and frequency domains.

Electron paramagnetic resonance (EPR) is a powerful technique to investigate the electronic and magnetic properties of a wide range of materials. We present the first combined terahertz (THz) field and frequency domain electron paramagnetic resonance (HFEPR/FDMR) spectrometer designed to investigate the electronic structure and magnetic properties of molecular systems, thin films and solid state materials in a very broad frequency range of 85-1100 GHz. In this paper, we show high resolution frequency-field (Zeeman) maps (170-380 GHz by 0-15 T) recorded on two single-molecule magnets, [Mn2(saltmen)2(ReO4)2] and [Mn2(salpn)2(H2O)2](ClO4)2, which give direct access to the field-dependence of the energy level diagram. Furthermore, supression of standing waves in the described system and the sensitivity in field and frequency domain operations is evaluated and discussed.

Repin1 deficiency in adipose tissue improves whole-body insulin sensitivity, and lipid metabolism.

BACKGROUND/OBJECTIVES: Replication initiator 1 (Repin1) gene encodes for a zinc-finger protein and has been implicated in the regulation of adipocyte cell size and glucose transport in vitro. Here, we investigate the consequences of reduced adipose tissue (AT) Repin1 expression in vivo. SUBJECTS/METHODS: We have inactivated the Repin1 gene in adipose tissue (iARep-/-) at an age of 4 weeks using tamoxifen-inducible gene targeting strategies on the background of C57BL/6NTac mice. Furthermore, we differentiated human primary adipocytes derived from subcutaneous AT in vitro and knocked down REPIN1 using siRNA technique to measure glycerol release. RESULTS: Conditional Repin1 inactivation results in decreased AT mass, smaller adipocytes in both, subcutaneous and epigonadal AT compared to controls. Compared to controls, iARep-/- mice were more insulin sensitive, had better glucose tolerance and lower LDL-, HDL- and total cholesterol. Significantly lower AT expression of the Repin1 target genes Cd36 and Lcn2 may contribute to the phenotype of iARep-/- mice. Knockdown of REPIN1 in human in vitro differentiated adipocytes revealed an increased glycerol release. CONCLUSIONS: In conclusion, deficiency of Repin1 in AT causes alterations in AT morphology and function, which may underlay lower body weight and improved parameters of insulin sensitivity, glucose and lipid metabolism.

Pain and discomfort following immediate and delayed loading by overdentures in the single mandibular implant study (SMIS).

OBJECTIVES: This randomized clinical trial compares immediate and delayed loading of single implants to support mandibular overdentures. The aim of this preliminary analysis is to test the hypothesis whether patients with immediate loading will experience less pain and discomfort through the intervention than patients with delayed loading. MATERIALS AND METHODS: Edentulous patients in nine German dental schools received a midline implant with a length of 11 mm. Implants with a minimum insertion torque of 30 Ncm and an implant stability quotient of ≥60 were randomly allocated to group A for immediate loading using ball attachments or to group B for delayed loading after 3 months. Patients completed questionnaires with 100-mm visual analogue scales about the items pain, pain during chewing, swelling, bleeding, and perception of the intervention at the day of surgery and 1, 2, 3, and 7 days, thereafter. Groups were compared by Wilcoxon-Mann-Whitney tests (P ≤ 0.05). RESULTS: The questionnaires of 81 patients in group A and 74 patients in group B were completed. The medians for pain and discomfort were moderate (<30). Participants of group A felt significantly more pain from the first day and more swelling from the third day after implantation than participants of group B. The individual perception of interventions showed no significant differences between groups. CONCLUSIONS: Immediate loading evoked more postoperative pain and swelling than the two stages of delayed loading. CLINICAL RELEVANCE: Immediate loading of a single mandibular midline implant supporting overdentures should be carefully considered.

Single mandibular implant study - denture satisfaction in the elderly.

To investigate whether there are differences in patients' denture satisfaction when an implant placed in the midline of the edentulous mandible is loaded either immediately or three months later, after second-stage surgery. One hundred and fifty-eight edentulous patients received a single implant in the midline of the mandible. After randomisation, it was loaded either immediately after implant placement (N = 81, group A) or three months later, after a submerged healing phase and a second-stage surgery (N = 77, group B). Patients' denture satisfaction aspects were assessed, using visual analogue scales (VAS), before treatment, one month after implant placement during the submerged healing phase (only group B) and one and four months after implant loading. The statistical analysis was performed using the Wilcoxon signed-rank and rank-sum tests. One month after loading, a significant improvement in comfort, function and stability of the mandibular denture could be observed in both groups (P ≤ 0·05). A slight but not significant improvement was found between one and four months after loading. Patients with second-stage surgery and delayed loading rated the stability and fit of the mandibular denture as significantly better than patients who had immediate loading. A single implant in the edentulous mandible significantly increased patients' denture satisfaction. After four months, stability and fit of the mandibular denture were considered better when a delayed loading protocol had been followed. A single mandibular implant in the edentulous mandible significantly increases patients' denture satisfaction, regardless of the loading protocol.

Novel genes on rat chromosome 10 are linked to body fat mass, preadipocyte number and adipocyte size.

BACKGROUND: The genetic architecture of obesity is multifactorial. We have previously identified a quantitative trait locus (QTL) on rat chromosome 10 in a F2 cross of Wistar Ottawa Karlsburg (WOKW) and Dark Agouti (DA) rats responsible for obesity-related traits. The QTL was confirmed in congenic DA.WOKW10 rats. To pinpoint the region carrying causal genes, we established two new subcongenic lines, L1 and L2, with smaller refined segments of chromosome 10 to identify novel candidate genes. METHODS: All lines were extensively characterized under different diet conditions. We employed transcriptome analysis in visceral adipose tissue (VAT) by RNA-Seq technology to identify potential underlying genes in the segregating regions. Three candidate genes were measured in human paired samples of VAT and subcutaneous (SC) AT (SAT) (N=304) individuals with a wide range of body weight and glucose homeostasis parameters. RESULTS: DA.WOKW and L1 subcongenic lines were protected against body fat gain under high-fat diet (HFD), whereas L2 and DA had significantly more body fat after high-fat feeding. Interestingly, adipocyte size distribution in SAT and epigonadal AT of L1 subcongenic rats did not undergo typical ballooning under HFD and the number of preadipocytes in AT was significantly elevated in L2 compared with L1 and parental rats. Transcriptome analysis identified three candidate genes in VAT on rat chromosome 10. In humans, these candidate genes were differentially expressed between SAT and VAT. Moreover, HID1 mRNA significantly correlates with parameters of obesity and glucose metabolism. CONCLUSIONS: Our data suggest novel candidate genes for obesity that map on rat chromosome 10 in an interval 102.2-104.7 Mb and are strongly associated with body fat mass regulation, preadipocyte number and adipocyte size in rats. Among those genes, AT head involution defective (HID1) mRNA expression may be relevant for human fat distribution and glucose homeostasis.

The effect of two doses of dried plum on bone density and bone biomarkers in osteopenic postmenopausal women: a randomized, controlled trial.

UNLABELLED: Daily consumption of 50 g of dried plum (equivalent to 5-6 dried plums) for 6 months may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. To some extent, these results may be attributed to the inhibition of bone resorption with the concurrent maintenance of bone formation. INTRODUCTION: The objective of our current study was to examine the possible dose-dependent effects of dried plum in preventing bone loss in older osteopenic postmenopausal women. METHODS: Forty-eight osteopenic women (65-79 years old) were randomly assigned into one of three treatment groups for 6 months: (1) 50 g of dried plum; (2) 100 g of dried plum; and (3) control. Total body, hip, and lumbar bone mineral density (BMD) were evaluated at baseline and 6 months using dual-energy X-ray absorptiometry. Blood biomarkers including bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRAP-5b), high-sensitivity C-reactive protein (hs-CRP), insulin-like growth factor-1 (IGF-1), and sclerostin were measured at baseline, 3 months, and 6 months. Osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), calcium, phosphorous, and vitamin D were measured at baseline and 6 months. RESULTS: Both doses of dried plum were able to prevent the loss of total body BMD compared with that of the control group (P < 0.05). TRAP-5b, a marker of bone resorption, decreased at 3 months and this was sustained at 6 months in both 50 and 100 g dried plum groups (P < 0.01 and P < 0.04, respectively). Although there were no significant changes in BAP for either of the dried plum groups, the BAP/TRAP-5b ratio was significantly (P < 0.05) greater at 6 months in both dried plum groups whereas there were no changes in the control group. CONCLUSIONS: These results confirm the ability of dried plum to prevent the loss of total body BMD in older osteopenic postmenopausal women and suggest that a lower dose of dried plum (i.e., 50 g) may be as effective as 100 g of dried plum in preventing bone loss in older, osteopenic postmenopausal women. This may be due, in part, to the ability of dried plums to inhibit bone resorption. This clinical trial was registered at ClinicalTrials.gov: NCT02325895 .

Clinically used adhesive ceramic bonding methods: a survey in 2007, 2011, and in 2015.

OBJECTIVES: The objective of the study is to evaluate practices of dentists regarding adhesive cementation of all-ceramic restorations over a period of 8 years. MATERIALS AND METHODS: The authors developed a questionnaire regarding adhesive cementation procedures for all-ceramic restorations. Restorations were distinguished between made out of silicate ceramic or oxide ceramic. The questionnaire was handed out to all dentists participating in a local annual dental meeting in Northern Germany. The returned questionnaires were analyzed to identify incorrect cementation procedures based upon current evidence-based technique from the scientific dental literature. The survey was conducted three times in 2007, 2011, and 2015 and their results were compared. RESULTS: For silicate ceramic restorations, 38-69 % of the participants used evidence-based bonding procedures; most of the incorrect bonding methods did not use a silane containing primer. In case of oxide ceramic restorations, most participants did not use air-abrasion prior to bonding. Only a relatively low rate (7-14 %) of dentists used evidence-based dental techniques for bonding oxide ceramics. CONCLUSION: In adhesive cementation of all-ceramic restorations, the practices of surveyed dentists in Northern Germany revealed high rates of incorrect bonding. During the observation period, the values of evidence-based bonding procedures for oxide ceramics improved while the values for silicate ceramics declined. Based on these results, some survey participants need additional education for adhesive techniques. CLINICAL RELEVANCE: Neglecting scientifically accepted methods for adhesive cementation of all-ceramic restorations may result in reduced longevity of all-ceramic restorations.

Implant placement under existing removable dental prostheses and its effect on masticatory performance.

OBJECTIVE: The aim of this within-subject study was to evaluate the outcome with implant-tooth-supported removable partial dental prostheses (RPDP group) and implant-supported removable complete dental prostheses (edentulous group) in terms of masticatory performance and self-assessment. MATERIALS AND METHODS: Thirty patients participated in this prospective clinical study (RPDP group: n = 12; edentulous group: n = 18). The prostheses were supported in strategically advantageous regions by placing implants with ball attachments and corresponding matrices in the existing dentures. The masticatory performance was evaluated with the Swallowing Threshold Test Index (STTI), the number of chewing strokes, and the time needed until swallowing at pre-treatment and 6 weeks after integration of ball attachments. Additionally, patients scored chewing satisfaction before and after implantation on a visual analogue scale. RESULTS: The STTI increased significantly (p ≤ 0.05) after implant therapy in the edentulous group but not in the RPDP group. Furthermore, the STTI was significantly higher (p ≤ 0.05) in the RPDP group than in the edentulous group at pre-treatment, however, not after therapy (P > 0.05). All patients were very satisfied after therapy concerning ability of speaking, chewing, and stability of their prosthesis. CONCLUSIONS: Patients of the edentulous group benefit more from strategically placed implants under the existing dentures than patients from the RPDP group. However, according to the subjective assessment, the chewing satisfaction generally increased for both groups after implant therapy. CLINICAL RELEVANCE: Patients with a strongly reduced dentition and edentulous patients benefit from strategically placed implants under the existing removable dentures.

The effects of oxygen level and glucose concentration on the metabolism of porcine TMJ disc cells.

OBJECTIVE: To determine the combined effect of oxygen level and glucose concentration on cell viability, ATP production, and matrix synthesis of temporomandibular joint (TMJ) disc cells. DESIGN: TMJ disc cells were isolated from pigs aged 6-8 months and cultured in a monolayer. Cell cultures were preconditioned for 48 h with 0, 1.5, 5, or 25 mM glucose DMEM under 1%, 5%, 10%, or 21% O2 level, respectively. The cell viability was measured using the WST-1 assay. ATP production was determined using the Luciferin-Luciferase assay. Collagen and proteoglycan synthesis were determined by measuring the incorporation of [2, 3-(3)H] proline and [(35)S] sulfate into the cells, respectively. RESULTS: TMJ disc cell viability significantly decreased (P < 0.0001) without glucose. With glucose present, decreased oxygen levels significantly increased viability (P < 0.0001), while a decrease in glucose concentration significantly decreased viability (P < 0.0001). With glucose present, decreasing oxygen levels significantly reduced ATP production (P < 0.0001) and matrix synthesis (P < 0.0001). A decreased glucose concentration significantly decreased collagen synthesis (P < 0.0001). The interaction between glucose and oxygen was significant in regards to cell viability (P < 0.0001), ATP production (P = 0.00015), and collagen (P = 0.0002) and proteoglycan synthesis (P < 0.0001). CONCLUSIONS: Although both glucose and oxygen are important, glucose is the limiting nutrient for TMJ disc cell survival. At low oxygen levels, the production of ATP, collagen, and proteoglycan are severely inhibited. These results suggest that steeper nutrient gradients may exist in the TMJ disc and it may be vulnerable to pathological events that impede nutrient supply.

Viscoelastic shear properties of porcine temporomandibular joint disc.

OBJECTIVES: To investigate the intrinsic viscoelastic shear properties in porcine TMJ discs. MATERIALS AND METHODS: Twelve fresh porcine TMJ discs from young adult pigs (6-8 months) were used. Cylindrical samples (5 mm diameter) with uniform thickness (~1.2 mm) were prepared from five regions of the TMJ disc. Torsional shear tests were performed under 10% compressive strain. Dynamic shear was applied in two methods: 1) a frequency sweep test over the frequency range of 0.1-10 rad/s with a constant shear strain amplitude of 0.05 rad and 2) a strain sweep test over the range of 0.005-0.15 rad at a constant frequency of 10 rad/s. Transient stress relaxation tests were also performed to determine the equilibrium shear properties. RESULTS: As the frequency increased in the frequency sweep test, the dynamic shear complex modulus increased, with values ranging from 7 to 17 kPa. The phase angle, ranging from 11 to 15 degrees, displayed no pattern of regional variation as the frequency increased. The dynamic shear modulus decreased as the shear strain increased. The equilibrium shear modulus had values ranging from 2.6 to 4 kPa. The posterior region had significantly higher values for dynamic shear modulus than those in the anterior region, while no significant regional difference was found for equilibrium shear modulus. CONCLUSION: Our results suggest that the intrinsic region-dependent viscoelastic shear characteristics of TMJ disc may play a crucial role in determining the local strain of the TMJ disc under mechanical loading.

The randomized shortened dental arch study: oral health-related quality of life.

OBJECTIVES: Although the shortened dental arch (SDA) concept is a widely accepted strategy to avoid overtreatment, little is known on its impact on oral health-related quality of life (OHRQoL). This multicenter randomized controlled trial aimed to investigate the OHRQoL for removable partial dental prostheses (RPDP) with molar replacement versus the SDA concept. MATERIAL AND METHODS: In both groups, missing anterior teeth were replaced with fixed dental prosthesis. Two hundred fifteen patients with bilateral molar loss in at least one jaw were included. The Oral Health Impact Profile (OHIP-49) was completed before; 6 weeks (baseline), 6 months, and 12 months after treatment; and thereafter annually until 5 years. RESULTS: Of the initial cohort, 81 patients were assigned to the RPDP group and 71 to the SDA group (age, 34 to 86 years). Before treatment, the median OHIP score was similar in both groups (RPDP, 38.0; SDA, 40.0; n.s.). Results indicate marked improvements in OHRQoL in both groups between pretreatment and baseline (RPDP, 27.0; SDA, 19.0; p ≤ 0.0001) which continued in the RPDP group until the 1-year follow-up (p = 0.0002). These significant reductions in OHIP scores are reflected in its subscales. No further differences were seen within and between groups during the remainder observation period. CONCLUSION: Both treatments show a significant improvement in OHRQoL which continued in the RPDP group until the 1-year follow-up. No significant differences were seen between groups. CLINICAL RELEVANCE: For improving OHRQoL, it is not necessary to replace missing molars with a RPDP.

Management of shortened dental arches and periodontal health: 5-year results of a randomised trial.

In a multicentre randomised trial (German Research Association, grants DFG WA 831/2-1 to 2-6, WO 677/2-1.1 to 2-2.1.; controlled-trials.com ISRCTN97265367), patients with complete molar loss in one jaw received either a partial removable dental prosthesis (PRDP) with precision attachments or treatment according to the SDA concept aiming at pre-molar occlusion. The objective of this current analysis was to evaluate the influence of different treatments on periodontal health. Linear mixed regression models were fitted to quantify the differences between the treatment groups. The assessment at 5 years encompassed 59 patients (PRDP group) and 46 patients (SDA group). For the distal measuring sites of the posterior-most teeth of the study jaw, significant differences were found for the plaque index according to Silness and Löe, vertical clinical attachment loss (CAL-V), probing pocket depth (PPD) and bleeding on probing. These differences were small and showed a slightly more unfavourable course in the PRDP group. With CAL-V and PPD, significant differences were also found for the study jaw as a whole. For CAL-V, the estimated group differences over 5 years amounted to 0.27 mm (95% CI 0.05; 0.48; P = 0.016) for the study jaw and 0.25 mm (95% CI 0.05; 0.45; P = 0.014) for the distal sites of the posterior-most teeth. The respective values for PPD were 0.22 mm (95% CI 0.03; 0.41; P = 0.023) and 0.32 mm (95% CI 0.13; 0.5; P = 0.001). It can be concluded that even in a well-maintained.patient group statistically significant although minor detrimental effects of PRDPs on periodontal health are measurable.

Impact of loading protocol of a mandibular single implant-supported complete denture on oral health-related quality of life over a period of 5 years: A randomized controlled trial.

OBJECTIVES: The aim of the present study was to assess the long-term course of OHRQoL and the impact of the loading protocol in patients receiving a single mandibular implant supporting a complete denture over a period of five years. METHODS: In this multicenter RCT, a total of 158 edentulous patients were initially included and were randomly allocated immediately after placement of a mandibular midline implant to either immediate loading (IL) or to conventional loading (CL) with submerged healing. The assessment of OHRQoL was performed with the 49-item Oral Health Impact Profile (OHIP) at baseline and 1, 4, 12, 24, and 60 months after loading. At 5-year follow-up, 100 patients (mean age: 69.2 years; 45.0% female) with completed OHIP were available for analyses. A mixed-effects model with patients as random effect and an unstructured covariance matrix was developed to address repeated outcome measurement. RESULTS: The OHRQoL improved substantially after loading, indicated by a decrease of mean OHIP summary scores from 51.0 points at baseline, by 14.2 (95%-CI: 9.4 - 19.1; p<0.001) points to 37.2 points at 1-month follow-up, and by continuous improvement to 20.4 OHIP points at final follow-up. Considering constant treatment effects, the loading protocol had no significant effect on OHIP scores (-3.7, 95%-CI: -9.4 - 2.2; p = 0.204). Time effect was statistically significant with -0.21 (95%-CI: -0.28 - -0.15; p<0.001) points per month. CONCLUSION: Both the immediate and conventional loading of a single mandibular midline implant supporting a complete denture offer long-lasting high levels of OHRQoL, with no significant or clinically relevant long-term differences. CLINICAL SIGNIFICANCE: The study firstly presents long-term data for OHRQoL by investigating the loading protocol of single mandibular implant-supported complete dentures. Since immediate loading has been associated with a reduced implant survival rate for this concept, information on patient benefits is essential for evidence-based decision making.

Taking off the brakes: T cell immunity in the liver.

In lymphatic tissue, professional antigen-presenting cells (APCs) such as dendritic cells (DCs), mature after sensing microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs), and subsequently activate T cell immunity. Non-pathogenic MAMPs, derived for example from commensal bacteria, are delivered to the liver from the gastrointestinal tract via the portal vein. However, in contrast to splenic DCs, PRRs-expressing liver APCs induce T cell tolerance rather than immunity. This is explained partly by the distinct effects of PRRs on the maturation of liver APCs: these cells activate T cell immunity only when PRRs stimulation is accompanied by microbial infection through mechanisms that are not employed by DCs in lymphatic tissue. Understanding the molecular basis of T cell tolerance and immunity in the liver may help develop novel immune therapy for persistent viral infection or liver cancer.

The randomized shortened dental arch study: tooth loss over five years.

OBJECTIVES: The study was designed to provide clinical outcome data for two treatments of the shortened dental arch (SDA). MATERIAL AND METHODS: In a multicenter randomized controlled clinical trial, patients with complete molar loss in one jaw were provided with either a partial removable dental prosthesis (PRDP) retained with precision attachments or treated according to the SDA concept preserving or restoring a premolar occlusion. No implants were placed. The primary outcome was tooth loss. RESULTS: Of 152 treated patients, 132 patients reached the 5-year examination. Over 5 years, 38 patients experienced tooth loss. For the primary outcome tooth loss, the Kaplan-Meier survival rates at 5 years were 0.74 (95% CI 0.64, 0.84) in the PRDP group and 0.74 (95% CI 0.63, 0.85) in the SDA group. For tooth loss in the study jaw, the survival rates at 5 years were 0.88 (95% CI 0.80, 0.95) in the PRDP group and 0.84 (95% CI 0.74, 0.93) in the SDA group. The differences were not significant. No Cox regression models of appropriate fit explaining tooth loss on the patient level could be found. CONCLUSIONS: The overall treatment goals of a sustainable oral rehabilitation and the avoidance of further tooth loss over longer periods were not reliably achievable. The influence of the type of prosthetic treatment on tooth loss might have been overestimated. CLINICAL RELEVANCE: Regarding our results, the patient's view will gain even more importance in the clinical decision between removable and fixed restorations in SDAs.

CAD/CAM single retainer zirconia-ceramic resin-bonded fixed dental prostheses: clinical outcome after 5 years.

PURPOSE: This study evaluated the clinical outcome of CAD/CAM zirconia-ceramic resin-bonded fixed dental prostheses (RBFDPs) with a cantilevered single-retainer design. MATERIALS AND METHODS: Thirty anterior zirconia-ceramic RBFDPs fabricated with the Cerec CAD/CAM system were inserted using either a phosphate monomer containing resin (Panavia 21 TC; N = 16) or an adhesive bonding system with a phosphoric acid acrylate primer (Multilink-Automix with Metal/Zirconia primer; N = 14). RESULTS: During a mean observation time of 64.2 months, one debonding occurred in each group. Both RBFDPs could be rebonded successfully resulting in a five-year survival rate of 100%. CONCLUSION: Independent of the bonding system, cantilevered zirconia-ceramic RBFDPs showed promising results during the first five years. (ClinicalTrials.gov Identifier: NCT01411592). CLINICAL SIGNIFICANCE: Single-retainer zirconia ceramic RBFDPs present an alternative treatment option offering good esthetics, a minimally invasive preparation, a high biocompatibility and can even be used to treat juvenile patients who do not yet come into consideration for implant placement. No significant influence of the bonding system used has been detected so far.

Transcription profiling associated with life cycle of Anopheles gambiae.

Complex biological events occur during the developmental process of the mosquito Anopheles gambiae (Giles). Using cDNA expression microarrays, the expression patterns of 13,440 clones representing 8,664 unique transcripts were revealed from six different developmental stages: early larvae (late third instar/early fourth instar), late larvae (late fourth instar), early pupae (< 30 min after pupation), late pupae (after tanning), and adult female and male mosquitoes (24 h postemergence). After microarray analysis, 560 unique transcripts were identified to show at least a fourfold up- or down-regulation in at least one developmental stage. Based on the expression patterns, these gene products were clustered into 13 groups. In total, eight genes were analyzed by quantitative real-time polymerase chain reaction to validate microarray results. Among 560 unique transcripts, 446 contigs were assigned to respective genes from the An. gambiae genome. The expression patterns and annotations of the genes in the 13 groups are discussed in the context of development including metabolism, transport, protein synthesis and degradation, cellular processes, cellular communication, intra- or extra-cellular architecture maintenance, response to stress or immune-related defense, and spermatogenesis.

Retrospective determination of fallout radionuclides and 236U/238U, 233U/236U and 240Pu/239Pu atom ratios on air filters from Vienna and Salzburg, Austria.

137Cs and 241Pu (via 241Am) concentrations were measured γ-spectrometrically on air filters from the early 1960s (mainly from 1964-66) from Vienna, Austria, and an alpine station in Salzburg, Austria. Accelerator mass spectrometry (AMS) was used to determine 240Pu/239Pu, 236U/238U and 233U/236U atom ratios as well as 236U, 239Pu and 240Pu atom concentrations. The maximum 236U/238U atom ratio of these unique undisturbed global fallout samples was (1.19 ± 0.31) × 10-5 in spring 1964. The 233U/236U atom ratios were found within (0.15-0.49) × 10-2 and indicate that the weapons tests of the early 1960s can be excluded as 233U source. The 236U/239Pu atom ratios were calculated in the range of 0.22-0.48.

Central vaspin administration acutely reduces food intake and has sustained blood glucose-lowering effects.

AIMS/HYPOTHESIS: Vaspin (visceral adipose tissue-derived serpin) was first identified as an adipokine in a rat model of type 2 diabetes, in which it is predominantly secreted from visceral adipose tissue. Serum concentrations of vaspin show a food intake-related diurnal variation. We therefore tested the hypothesis that vaspin plays a role in the regulation of food intake. METHODS: Vaspin levels in the hypothalamus and human stomach were determined by western blotting. The cerebrospinal fluid concentration of vaspin was measured in five healthy volunteers using an ELISA. Fed 11-week-old female db/db mice were given intraperitoneal injections of 1 mg/kg body weight of vaspin (n = 6) or saline (n = 6) on experimental days 1, 3 and 4. Changes in food intake and fed plasma glucose concentrations were determined after one intracerebroventricular administration of either 1 µg vaspin or artificial cerebrospinal fluid into 11-week-old female db/db (n = 8) and C57BL/6 mice (n = 8) up to 6 days after injection. RESULTS: We detected vaspin in the hypothalamus of db/db and C57BL/6 mice and in the cerebrospinal fluid of healthy individuals. Both peripheral and central vaspin administration decrease food intake in obese db/db and lean C57BL/6 mice. In db/db mice, vaspin treatment is associated with sustained glucose-lowering effects for at least 6 days after injection. In addition, we demonstrated expression of the gene encoding vaspin in the gastric mucosa in humans, and found that this was subject to regional variations. CONCLUSIONS/INTERPRETATION: Our data suggest a previously unrecognised role of vaspin in the regulation of food intake. We postulate that vaspin inhibits a protease that degrades an anti-orexigenic factor.