Implementation of different relationship estimate methodologies in breeding value prediction in kiwiberry (Actinidia arguta).

In dioecious crops such as Actinidia arguta (kiwiberries), some of the main challenges when breeding for fruit characteristics are the selection of potential male parents and the long juvenile period. Currently, breeding values of male parents are estimated through progeny tests, which makes the breeding of new kiwiberry cultivars time-consuming and costly. The application of best linear unbiased prediction (BLUP) would allow direct estimation of sex-related traits and speed up kiwiberry breeding. In this study, we used a linear mixed model approach to estimate narrow sense heritability for one vine-related trait and five fruit-related traits for two incomplete factorial crossing designs. We obtained BLUPs for all genotypes, taking into consideration whether the relationship was pedigree-based or marker-based. Owing to the high cost of genome sequencing, it is important to understand the effects of different sources of relationship matrices on estimating breeding values across a breeding population. Because of the increasing implementation of genomic selection in crop breeding, we compared the effects of incorporating different sources of information in building relationship matrices and ploidy levels on the accuracy of BLUPs' heritability and predictive ability. As kiwiberries are autotetraploids, multivalent chromosome formation and occasionally double reduction can occur during meiosis, and this can affect the accuracy of prediction. This study innovates the breeding programme of autotetraploid kiwiberries. We demonstrate that the accuracy of BLUPs of male siblings, without phenotypic observations, strongly improved when a tetraploid marker-based relationship matrix was used rather than parental BLUPs and female siblings with phenotypic observations. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01419-8.

Variation in the Anatomy of the Normal Human Optic Chiasm: An MRI Study.

BACKGROUND: Compression of the optic chiasm typically leads to bitemporal hemianopia. This implies that decussating nasal fibers are selectively affected, but the precise mechanism is unclear. Stress on nasal fibers has been investigated using finite element modeling but requires accurate anatomical data to generate a meaningful output. The precise shape of the chiasm is unclear: A recent photomicrographic study suggested that nasal fibers decussate paracentrally and run parallel to each other in the central arm of an "H." This study aimed to determine the population variation in chiasmal shape to inform future models. METHODS: Sequential MRI scans of 68 healthy individuals were selected. 2D images of each chiasm were created and analyzed to determine the angle of elevation of the chiasm, the width of the chiasm, and the offset between the points of intersection of lines drawn down the centers of the optic nerves and contralateral optic tracts. RESULTS: The mean width of the chiasm was 12.0 ± 1.5 mm (SD), and the mean offset was 4.7 ± 1.4 mm generating a mean offset:width ratio of 0.38 ± 0.09. No chiasm had an offset of zero. The mean incident angle of optic nerves was 56 ± 7°, and for optic tracts, it was 51 ± 7°. CONCLUSIONS: The human optic chiasm is "H" shaped, not "X" shaped. The findings are consistent with nasal fibers decussating an average of 2.4 mm lateral to the midline before travelling in parallel across the midline. This information will inform future models of chiasmal compression.

Correlation of MRI Findings With Patterns of Visual Field Loss in Patients With Pituitary Tumors.

BACKGROUND: Compression of the optic chiasm by pituitary tumors typically results in bitemporal hemianopia, implying that nasal retinal fibers are preferentially damaged. The reason for this is not clear. One theory suggests that nasal fibers are selectively vulnerable simply because they cross each other. This study investigated the "crossing theory" by correlating visual field (VF) loss with chiasmal elevation and with the degree of eccentric compression on MRI scans. METHODS: Our hospital database was searched to identify patients with a) chiasmal compression by a pituitary tumor; b) documented preoperative evidence of VF loss; and c) preoperative MRI scan performed within 1 month of VF testing. Temporality and bitemporality indices were derived from pattern deviation VF plots. Elevations of the central and peripheral parts of the chiasm were obtained from MRI scans, from which the eccentricity of compression was calculated. Temporality indices and hemifield loss were compared with central chiasmal elevation, and nasal hemifield loss in each eye was plotted against eccentricity. RESULTS: Eleven patients were suitable for analysis. The degree of bitemporal VF involvement was significantly correlated with elevation of the central chiasm (P = 0.004). However, there was minimal involvement of nasal VFs, and no demonstrable increase in nasal field loss with increasing eccentricity of compression. CONCLUSIONS: This study provides support for the crossing theory. These findings will inform further finite element models of chiasmal compression. A larger, prospective study is planned.

Fifteen years of quantitative trait loci studies in fish: challenges and future directions.

Understanding the genetic basis of phenotypic variation is a major challenge in biology. Here, we systematically evaluate 146 quantitative trait loci (QTL) studies on teleost fish over the last 15 years to investigate (i) temporal trends and (ii) factors affecting QTL detection and fine-mapping. The number of fish QTL studies per year increased over the review period and identified a cumulative number of 3632 putative QTLs. Most studies used linkage-based mapping approaches and were conducted on nonmodel species with limited genomic resources. A gradual and moderate increase in the size of the mapping population and a sharp increase in marker density from 2011 onwards were observed; however, the number of QTLs and variance explained by QTLs changed only minimally over the review period. Based on these findings, we discuss the causative factors and outline how larger sample sizes, phenomics, comparative genomics, epigenetics and software development could improve both the quantity and quality of QTLs in future genotype-phenotype studies. Given that the technical limitations on DNA sequencing have mostly been overcome in recent years, a renewed focus on these and other study design factors will likely lead to significant improvements in QTL studies in the future.

Magnetic sphincter augmentation and fundoplication for GERD in clinical practice: one-year results of a multicenter, prospective observational study.

BACKGROUND: The techniques available for antireflux surgery have expanded with the introduction of the magnetic sphincter augmentation device (MSAD) for gastroesophageal reflux disease (GERD). METHODS: A prospective, multicenter registry evaluated MSAD and laparoscopic fundoplication (LF) in clinical practice (ClinicalTrials.gov identifier: NCT01624506). Data collection included baseline characteristics, reflux symptoms, proton-pump inhibitor (PPI) use, side effects, and complications. Post-surgical evaluations were collected at one year. RESULTS: At report, 249 patients (202 MSAD patients and 47 LF patients) had completed one-year follow-up. The LF group was older and had a greater frequency of large hiatal hernias and Barrett's esophagus than the MSAD group (P < 0.001). The median GERD-health related quality of life score improved from 20.0 to 3.0 after MSAD and 23.0 to 3.5 after LF. Moderate or severe regurgitation improved from 58.2 to 3.1% after MSAD and 60.0 to 13.0% after LF (P = 0.014). Discontinuation of PPIs was achieved by 81.8% of patients after MSAD and 63.0% after LF (P = 0.009). Excessive gas and abdominal bloating were reported by 10.0% of patients after MSAD and 31.9% following LF (P ≤ 0.001). Following MSAD, 91.3% of patients were able to vomit if needed, compared with 44.4% of those undergoing LF (P < 0.001). Reoperation rate was 4.0% following MSAD and 6.4% following LF. CONCLUSION: Antireflux surgery should be individualized to the characteristics of each patient, taking into consideration anatomy and propensity and tolerance of side effects. Both MSAD and LF showed significant improvements in reflux control, with similar safety and reoperation rates. In the treatment continuum of antireflux surgery, MSAD should be considered as a first-line surgical option in appropriately selected patients without Barrett's esophagus or a large hiatal hernia in order to avoid unnecessary dissection and preserve the patient's native gastric anatomy. MSAD is an important treatment option and will expand the surgeon's role in treating GERD.

Body fat distribution in relation to smoking and exogenous hormones in British women.

OBJECTIVE: Both cigarette smoking and use of exogenous hormones are associated with changes in regional distribution of body fat, but their combined effects are less investigated. We examined the interrelation between smoking, exogenous hormones and fat distribution in premenopausal and postmenopausal women. METHOD: We used data from 20, 962 women without known cardiovascular disease (CVD) who were employees of a major department store in Britain. They completed a health questionnaire and attended a clinical examination that included waist and hip circumference measurements. The cross-sectional analyses were conducted using linear regression models. RESULTS: Cigarette smoking, particularly smoking ≥20 cigarettes/day, was associated with larger waist circumference and higher waist/hip ratio (WHR) in pre- and postmenopausal women after adjusting for potential confounding factors (all P < 0·001). Premenopausal women using combined oral contraceptive (COC) and postmenopausal women using oestrogen-only hormone replacement therapy (HRT) had lower WHR than non-hormone users in both smokers and nonsmokers. However, smokers had higher WHR than nonsmokers in both groups of hormone users and nonusers. There was no significant interaction between smoking and hormone use in premenopausal and postmenopausal women (P > 0·05). CONCLUSION: Although exogenous hormones use was related to a more favourable fat distribution in women, smoking was associated with greater abdominal fat accumulation.

Evaluating new species for aquaculture: A genomic dissection of growth in the New Zealand silver trevally (Pseudocaranx georgianus).

Aquaculture is the fastest-growing food production sector worldwide, yet industry has been slow to implement genomic techniques as routine tools. Applying genomics to new breeding programmes can provide important information about pedigree structure and genetic diversity; key parameters for a successful long-term breeding programme. It can also provide insights on potential gains for commercially important, yet complex, quantitative traits such as growth rate. Here we investigated a population of 1100 captive-bred F1 silver trevally (Pseudocaranx georgianus), a promising new species for New Zealand aquaculture. We used whole-genome information, coupled with image-based phenotypic data collected over two years, to build the pedigree of the population, assess its genetic diversity, describe growth patterns of ten growth traits and estimate their genetic parameters. Successful parentage assignment of 664 F1 individuals showed that the pedigree consisted of a complex mixture of full- and half-sib individuals, with skewed reproductive success among parents, especially in females. Growth patterns showed seasonal fluctuations (average increase across all traits of 27.3% in summer and only 7% in winter) and strong inter-family differences. Heritability values for growth traits ranged from 0.27 to 0.76. Genetic and phenotypic correlations between traits were high and positive, ranging from 0.57 to 0.94 and 0.50 to 1.00 respectively. The implications of these findings are threefold: first, the best on-growing conditions are in warmer months, where highest growth peaks can be achieved; second, size- and family-based selection can be used as early selection criterion if pedigree structure and inbreeding risks are closely monitored; third, selection for body length results in concomitant increases in height and weight, traits of paramount importance for aquaculture. It is concluded that there is substantial potential for genetic improvement of economically important traits, suggesting that silver trevally is a promising species for selective breeding for enhanced growth.

The gastric band: first-choice procedure for obesity surgery.

The advent of laparoscopic adjustable gastric banding (LAGB) during the latter part of the 20th century represents a watershed in the management of chronic obesity. In this paper we provide an overview of LAGB with respect to its development, clinical outcomes, and future role. We also address current controversies, including a comparison of LAGB with Roux-en-Y gastric bypass (RYGBP). At present LAGB seems to be increasing in popularity in the United States, whereas in Europe there seems to be a trend away from gastric banding toward RYGBP. Optimal outcomes after LAGB are a function of correct laparoscopic technique, an experienced surgical team, a well-engineered device, and intensive long-term follow-up. The majority of studies show that LAGB is an extremely safe and effective procedure, with an operative mortality of 0-0.1% and excess weight loss (%EWL) of 50-60%. Commensurate with this degree of weight loss, almost all studies show substantial improvements in obesity-related co-morbidities, such as hypertension, type II diabetes, and dyslipidemia. In addition, LAGB has been shown to be both safe and effective in the super-obese, in adolescents, and in older patients and can be delivered as an ambulatory procedure. Operative mortality and early complication rates are significantly higher for RYGBP and, whilst gastric bypass results in greater weight loss than LAGB in the first 2 years, at 3 years and beyond the difference appears to be less marked. Overall, LAGB provides a safe, effective intervention for obese patients and remains our first-choice procedure for bariatric surgery.

High-Density Linkage Map and QTLs for Growth in Snapper (Chrysophrys auratus).

Characterizing the genetic variation underlying phenotypic traits is a central objective in biological research. This research has been hampered in the past by the limited genomic resources available for most non-model species. However, recent advances in sequencing technologies and related genotyping methods are rapidly changing this. Here we report the use of genome-wide SNP data from the ecologically and commercially important marine fish species Chrysophrys auratus (snapper) to 1) construct the first linkage map for this species, 2) scan for growth QTL, and 3) search for putative candidate genes in the surrounding QTL regions. The newly constructed linkage map contained ∼11K SNP markers and is one of the densest maps to date in the fish family Sparidae. Comparisons with genome scaffolds of the recently assembled snapper genome indicated that marker placement was mostly consistent between the scaffolds and linkage map (R = 0.7), but that at fine scales (< 5 cM) some precision limitations occurred. Of the 24 linkage groups, which likely reflect the 24 chromosomes of this species, three were found to contain QTL with genome-wide significance for growth-related traits. A scan of 13 candidate growth genes located the growth hormone, myogenin, and parvalbumin genes within 5.3, 9.6, and 25.0 cM of these QTL, respectively. The linkage map and QTL found in this study will advance the investigation of genome structure and aquaculture breeding efforts in this and related species.

Preoperative psychological testing--another form of prejudice.

Preoperative psychological screening of bariatric surgery candidates has become routine, and a significant proportion of patients have their surgery deferred as a consequence. If psychological testing is being used as a form of preoperative triage, both patients and surgeons are entitled to know whether there is sufficient evidence to justify its use in this way. We define the argument for psychological screening as consisting of four premises (p1-p4) and a conclusion (C) as follows: (p1) A significant minority of obese patients will not be successful in losing weight following bariatric surgery-the "failure" group; (p2) A significant minority of patients will exhibit abnormal psychological profiles during preoperative testing; (p3) The majority of individuals referred to in (p2) will be found in group (p1) i.e., abnormal psychological profiles identified preoperatively predict less favorable weight loss outcomes postoperatively; (p4) Identifying patients with adverse psychological profiles preoperatively would allow either exclusion of those at high risk of failure or provide a more secure rationale for targeted pre- and postoperative support; (C) Psychological screening should be part of the routine preoperative assessment for patients undergoing obesity surgery. We reviewed the literature to find evidence to support the premises and show that (p1) can be justified but that (p2) is problematic and can only be accepted in a heavily qualified version. We find no evidence for (p3) and since (p4) and (C) are predicated on (p3), the argument clearly fails. There is no evidence to suggest that preoperative psychological screening can predict postoperative outcomes and no justification for using such testing as a means of discriminating between candidates presenting themselves for bariatric surgery.

Medium and long-term results of gastric banding: outcomes from a large private clinic in UK.

BACKGROUND: Laparoscopic adjustable gastric band (LAGB) has been an established bariatric procedure for the last three decades and was, for many years, the first-choice procedure for the treatment of chronic obesity. However, more recently, the popularity of the LAGB has been in sharp decline and has been replaced by other procedures such as the Roux-En-Y gastric bypass and sleeve gastrectomy. A key driver in this decline has been the high revision and early explanation rates reported in some studies. METHODS: This was a retrospective study of 2246 patients who underwent LAGB at a large private clinic in the UK between June 2004 and October 2014. RESULTS: 2246 patients were included in the study; 1945 (84.6%) were women. All patients were followed up for 2 years following their procedure and subsequent follow up was at the discretion of patients. Mean follow up duration was 43.7 +/- 29.3 months. Operative mortality was zero and there were no in-hospital returns to theatre. Mean preoperative weight and body mass index (BMI) were 111.2 ± 22.1 kg and 39.9 ± 6.7 kg/m2 respectively. Mean excess % BMI loss at 1-, 2-, 5- and 8-years of follow-up was 43.1 ± 25.4, 47.9 ± 31.9, 52.4 ± 41.7 and 57.1% ± 28.6 respectively. There was no significant difference in mean excess % BMI loss between those < 50 or ≥ 50 years old (p value = 0.23) or between patients with an initial BMI of < or ≥ 50 kg/m2 (p value = 0.65). Complications over nine years occurred in 130 (5.8%) patients and included: 39 (1.7%) slippage or pouch dilatation, 2 (0.04%) erosions and 76 (3.4%) problems related to the access port or LAGB tubing. The overall re-operation rate for LAGB complications was 4.2% over 9 years with a LAGB explantation rate of 1.5%. 39 LAGBs were converted to a sleeve or gastric bypass procedure, 11 of these due to complications. CONCLUSION: This is the first study to report on LAGB outcomes from a private clinic in the UK. LAGB is a safe procedure, which delivers significant and durable weight loss with acceptable complications rates and low re-operation rate.

Transversus abdominis plane block with liposomal bupivacaine for pain control after cesarean delivery: a retrospective chart review.

BACKGROUND: Adverse effects of opioid analgesics and potential for chronic use are limitations in the cesarean setting. Regional anesthesia using transversus abdominis plane (TAP) block post-cesarean delivery may improve analgesia and reduce opioid consumption. Effectiveness of TAP block using liposomal bupivacaine (LB) to reduce post-cesarean pain is unknown. METHODS: We performed a single-center retrospective chart review of patients aged ≥18 years who underwent cesarean delivery with a multimodal pain management protocol with or without TAP block with LB 266 mg. Assessments included postsurgical opioid consumption; area under the curve (AUC) of numeric rating scale pain scores from 0 to 3 days; proportion of opioid-free patients; discharge- and post-anesthesia care unit (PACU)-ready time; times to ambulation, solid food, and bowel movement; hospital length of stay (LOS); and adverse events (AEs). Data were analyzed in the total population and in first- and repeat-cesarean subgroups using Wilcoxon, chi-squared, and Student's t-tests. RESULTS: Of 201 patients, 101 were treated with LB TAP block (LB-TAPB) and 100 without LB-TAPB. Treatment with LB-TAPB vs without LB-TAPB significantly reduced mean post-surgical opioid consumption (total, 47%; first-cesarean, 54%; repeat-cesarean, 42%; P<0.001 each) and mean AUC of pain scores (total, 46%; first-cesarean, 57%; repeat-cesarean, 40%; P<0.001 each). Patients treated with LB-TAPB had significantly shorter mean discharge-ready times (2.9 vs 3.6 days; P=0.006), PACU-ready times (138 vs 163 minutes; P=0.028), and LOS (2.9 vs 3.9 days; P<0.001). LB-TAPB significantly decreased mean times to ambulation and solid food by 39% and 31% (P<0.01 each), respectively, and numerically reduced mean time to bowel movement (26%; P=0.05). Fewer patients treated with LB-TAPB vs without LB-TAPB reported an AE (34% vs 50%; P=0.026). CONCLUSION: These results suggest multimodal pain management incorporating TAP block with LB 266 mg is an effective approach to reducing opioid requirements and improving analgesia post-cesarean delivery.

Laparoscopic adjustable gastric banding in 1,791 consecutive obese patients: 12-year results.

BACKGROUND: This study examines 1,791 consecutive laparoscopic adjustable gastric banding (LAGB) procedures with up to 12 years follow-up. Long-term results of LAGB with a high follow-up rate are not common. METHODS: Between September 1993 and December 2005, 1,791 consecutive patients (75.1% women, mean age 38.7 years, mean weight 127.7 +/- 24 kg, mean BMI 46.2 +/- 7.7) underwent LAGB by the same surgical team. Perigastric dissection was used in 77.8% of the patients, while subsequently pars flaccida was used in 21.5% and a mixed approach in 0.8%. Data were analyzed according to co-morbidities, conversion, short- and long-term complications and weight loss. Fluoroscopy-guided band adjustments were performed and patients received intensive follow-up. The effects of LAGB on life expectancy were measured in a case/control study involving 821 surgically-treated patients versus 821 treated by medical therapy. RESULTS: Most common baseline co-morbidities (%) were hypertension (35.6), osteoarthritis (57.8), diabetes (22), dyslipidemia (27.1), sleep apnea syndrome (31.4), depression (21.2), sweet eating (22.5) and binge eating (18.5). Conversion to open was 1.7%: due to technical difficulties (1.2) and due to intraoperative complications (0.5). Together with the re-positioning of the band, additional surgery was performed in 11.9% of the patients: hiatal hernia repair (2.4), cholecystectomy (7.8) and other procedures (1.7). There was no mortality. Reoperation was required in 106 patients (5.9%): band removal 55 (3.7%), band repositioning 50 (2.7 %), and other 1 (0.05 %). Port-related complications occurred in 200 patients (11.2%). 41 patients (2.3%) underwent further surgery due to unsatisfactory results: removal of the band in 12 (0.7%), biliopancreatic diversion in 5 (0.27%) and a biliopancreatic diversion with gastric preservation ("bandinaro") in 24 (1.3%). Weight in kg was 103.7 +/- 21.6, 102.5 +/- 22.5, 105.0 +/- 23.6, 106.8 +/- 24.3, 103.3 +/- 26.2 and 101.4 +/- 27.1 at 1, 3, 5, 7, 9, 11 years after LAGB. BMI at the same intervals was 37.7 +/- 7.1, 37.2 +/- 7.2, 38.1 +/- 7.6, 38.5 +/- 7.9, 37.5 +/- 8.5 and 37.7 +/- 9.1. The case/control study found a statistically significant difference in survival in favor of the surgically-treated group. CONCLUSIONS: LAGB can achieve effective, safe and stable long-term weight loss. In experienced hands, the complication rate is low. Follow-up is paramount.

Harnessing the Power of Genomics to Secure the Future of Seafood.

Best use of scientific knowledge is required to maintain the fundamental role of seafood in human nutrition. While it is acknowledged that genomic-based methods allow the collection of powerful data, their value to inform fisheries management, aquaculture, and biosecurity applications remains underestimated. We review genomic applications of relevance to the sustainable management of seafood resources, illustrate the benefits of, and identify barriers to their integration. We conclude that the value of genomic information towards securing the future of seafood does not need to be further demonstrated. Instead, we need immediate efforts to remove structural roadblocks and focus on ways that support integration of genomic-informed methods into management and production practices. We propose solutions to pave the way forward.

Quantitative analysis of the major constituents of St John's wort with HPLC-ESI-MS.

A method was developed to profile the major constituents of St John's wort extracts using high-performance liquid chromatography-electrospray mass spectrometry (HPLC-ESI-MS). The objective was to simultaneously separate, identify and quantify hyperforin, hypericin, pseudohypericin, rutin, hyperoside, isoquercetrin, quercitrin and chlorogenic acid using HPLC-MS. Quantification was performed using an external standardisation method with reference standards. The method consisted of two protocols: one for the analysis of flavonoids and glycosides and the other for the analysis of the more lipophilic hypericins and hyperforin. Both protocols used a reverse phase Luna phenyl hexyl column. The separation of the flavonoids and glycosides was achieved within 35 min and that of the hypericins and hyperforin within 9 min. The linear response range in ESI-MS was established for each compound and all had linear regression coefficient values greater than 0.97. Both protocols proved to be very specific for the constituents analysed. MS analysis showed no other signals within the analyte peaks. The method was robust and applicable to alcoholic tinctures, tablet/capsule extracts in various solvents and herb extracts. The method was applied to evaluate the phytopharmaceutical quality of St John's wort preparations available in the UK in order to test the method and investigate if they contain at least the main constituents and at what concentrations.

Isolated hypoglycorrachia: leptomeningeal carcinomatosis causing subacute confusion.

We report a 76-year-old caucasian man who presented with a 3-week history of progressive confusion. His past medical history included a left nephro-uretectomy for poorly differentiated transitional cell carcinoma 9 years previously. Besides his confusion, his clinical and neurological examination was unremarkable. Extensive investigation revealed only isolated hypoglycorrachia and mildly elevated CSF protein. Cerebral CT and MRI scans without contrast did not reveal any abnormalities. As his condition continued to decline, an MRI scan of the brain with gadolinium was performed which revealed extensive nodular enhancement of the surface of the cerebellum and brainstem and both temporal lobe convexities. Repeat lumbar puncture showed malignant cells in the CSF and confirmed the diagnosis of leptomeningeal carcinomatosis. This case illustrates that leptomeningeal carcinomatosis should be considered in the differential diagnosis of cognitive decline in the elderly, after other common aetiologies have been excluded. The index of suspicion should be increased in patients with a prior history of cancer.

The Gastric Band That Is Not to Be : Efficacy, Safety and Performance of the Easyband™: a Multicenter Experience.

BACKGROUND: Access port problems after laparoscopic adjustable gastric banding can be significant complications. The Easyband™ is an innovative type of gastric band, whose internal diameter can be adjusted by a telemetrically activated motor. The aim of this study was to evaluate safety, efficacy and performance of the Easyband™. METHODS: A total of 110 morbidly obese patients were prospectively enrolled. The Easyband™ was implanted laparoscopically by experienced bariatric surgeons in six different hospital locations. Patient characteristics, surgery details, postoperative weight loss, and complications were recorded. Follow-up lasted 2 years. RESULTS: Follow-up was completed by 78.2 % of the patients. Surgeons rated 71 % of each aspect of Easyband™ implantation as "easy" or "very easy". Adjustments were successful in 91 % of the attempts. One or more adverse events occurred in 79.1 % of the patients. Thirty-six serious adverse events were reported, of which 50 % was device-related. One or more functional tests failed in 20.9 % of the devices, 8.2 % passed after a repeated test. A reintervention was necessary in 15.5 % of the patients. Mean weight loss after 2 years was 24.2 ± 14.0 kg, mean excess weight loss was 46.1 ± 24 %. CONCLUSION: Excess weight loss with the Easyband™ was comparable with other gastric banding devices. Adjustment of the device was simple, non-invasive and more acceptable to patients than with a standard access port. However, a high incidence of device-related problems requiring surgical explantation occurred. The Easyband™ represents a major advance in gastric band design, but significant technical problems need to be resolved before further implants can be recommended.

Anxiolytic- and antidepressant-like profile of a new CRF1 receptor antagonist, R278995/CRA0450.

1-[8-(2,4-dichlorophenyl)-2-methylquinolin-4-yl]-1,2,3,6-tetrahydropyridine-4-carboxamide benzenesulfonate (R278995/CRA0450) is a newly synthesized corticotropin-releasing factor subtype 1 (CRF(1)) receptor antagonist. In the present study, in vitro and in vivo pharmacological profiles of R278995/CRA0450 were investigated. R278995/CRA0450 showed high affinity for recombinant and native CRF(1) receptors without having affinity for the CRF(2) receptor. R278995/CRA0450 attenuated CRF-induced cyclic AMP formation in AtT-20 cells and CRF-induced forepaw treading in gerbils, indicating that R278995/CRA0450 is an antagonist of the CRF(1) receptor. In addition to CRF(1) receptor antagonism, R278995/CRA0450 showed high affinity for the sigma(1) receptor, and attenuated (+)-SKF10,047-induced head-weaving behavior, suggesting sigma(1) receptor antagonism. R278995/CRA0450 showed dose-dependent in vivo occupancy when assessed by ex vivo receptor binding, indicating good brain penetration. R278995/CRA0450 did not alter spontaneous anxiety when tested in the rat elevated plus maze (up to 3 mg/kg, p.o.) or lick suppression test (up to 10 mg/kg, i.p.). However, potent anxiolytic-like properties were observed in rats subjected to swim stress prior to testing on the elevated plus-maze, indicating activity primarily in tests taxing stress-induced anxiety. R278995/CRA0450 was inactive in mouse tail suspension, rat forced swim and rat differential-reinforcement-of-low-rate 72-s (DRL72), while it showed dose-dependent antidepressant-like effects in the rat learned helplessness paradigm and the olfactory bulbectomy model, demonstrating activity in a subset of animal models of depression associated with subchronic stress exposure. No or only mild effects were seen in tests of locomotor activity, motor coordination and sedation. These results indicate that R278995/CRA0450 is an orally active CRF(1) and sigma(1) receptor antagonist with potent anxiolytic-like and antidepressant-like activities.