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1.
J Abdom Wall Surg ; 1: 10909, 2022.
Article in English | MEDLINE | ID: mdl-38314149

ABSTRACT

Background and Aim: The definition and management of Diastasis Recti Abdominis (DRA) is under debate. This study aimed to understand the correlation between the post-partum inter-recti distance (IRD) and functional impairments associated with core instability, with the hypothesis that IRD could serve as a proxy for core instability symptoms and constitute a tool in decision-making for DRA treatment. Material and Methods: A cohort of post-partum women with abdominal core instability symptoms combined with DRA were studied. The size of IRD was measured with ultrasonography and cross-sectionally analysed against functional impairments registered with the self-report Disability Rating Index (DRI), which grades the ability to perform 12 different daily activities. Results: A total of 224 women were included in the study. In univariable analysis, IRD was associated with impairment of the activities running (p = 0.007), heavy work (p = 0.036) and exercise/sports (p = 0.047), but not with dressing, walking, sitting for long periods, standing bent over a sink, carrying a suitcase, making a bed, light manual labour or heavy lifting. No significant correlations were seen in the multivariable analysis when adjustments were made for BMI and parity. Conclusion: IRD and post-partum functional impairments had no significant correlation in multivariable analysis. The post-partum core instability condition is complex and probably associated with more factors than solely the IRD. The IRD alone does not seem to be a sufficient proxy for decision-making regarding optimal treatment. A more complete instrument to assess the post-partum abdominal core is warranted.

2.
Br J Surg ; 108(12): 1506-1512, 2021 12 01.
Article in English | MEDLINE | ID: mdl-34642735

ABSTRACT

BACKGROUND: Each year 13 000 patients undergo cholecystectomy in Sweden, and routine intraoperative cholangiography (IOC) is recommended to minimize bile duct injuries. The risk of requiring endoscopic retrograde cholangiopancreatography (ERCP) following cholecystectomy for common bile duct (CBD) stones where IOC is omitted and in patients with CBD stones left in situ is not well known. METHODS: Data were retrieved from the population-based Swedish Registry of Gallstone Surgery and ERCP between 1 January 2009 and 10 December 2019. Primary outcome was risk for postoperative ERCP for retained CBD stones. RESULTS: A total of 134 419 patients that underwent cholecystectomy were included and 2691 (2.0 per cent) subsequently underwent ERCP for retained CBD stones. When adjusting for emergency or planned cholecystectomy, preoperative symptoms suggestive of CBD stones, sex and age, there was an increased risk for ERCP when IOC was not performed (hazard ratio (HR) 1.4, 95 per cent c.i. 1.3 to 1.6). The adjusted risk for ERCP was also increased if CBD stones identified by IOC were managed with surveillance (HR 5.5, 95 per cent c.i. 4.8 to 6.4). Even for asymptomatic small stones (less than 4 mm), the adjusted risk for ERCP was increased in the surveillance group compared with the intervention group (HR 3.5, 95 per cent c.i. 2.4 to 5.1). CONCLUSION: IOC plus an intervention to remove CBD stones identified during cholecystectomy was associated with reduced risk for retained stones and unplanned ERCP, even for the smallest asymptomatic CBD stones.


This population-based registry study shows that when common bile duct (CBD) stones are identified by intraoperative cholangiography (IOC) and not removed, there is a risk for retained stones requiring endoscopic retrograde cholangiopancreatography. For asymptomatic stones less than 4 mm diameter, 10.7 per cent in the surveillance group had a retained stone following surgery. These findings imply that even the smallest CBD stones identified by IOC should be removed.


Subject(s)
Cholangiography , Choledocholithiasis/diagnostic imaging , Choledocholithiasis/surgery , Intraoperative Care , Watchful Waiting , Adult , Aged , Aged, 80 and over , Asymptomatic Diseases , Cholangiopancreatography, Endoscopic Retrograde/statistics & numerical data , Cholecystectomy , Female , Humans , Male , Middle Aged , Registries , Retrospective Studies , Sweden/epidemiology , Young Adult
3.
BJS Open ; 5(2)2021 03 05.
Article in English | MEDLINE | ID: mdl-33688957

ABSTRACT

BACKGROUND: Bile duct injury (BDI) is a severe complication following cholecystectomy. Early recognition and treatment of BDI has been shown to reduce costs and improve patients' quality of life. The aim of this study was to assess the effect and cost-effectiveness of routine versus selective intraoperative cholangiography (IOC) in cholecystectomy. METHODS: A systematic review and meta-analysis, combined with a health economic model analysis in the Swedish setting, was performed. Costs per quality-adjusted life-year (QALY) for routine versus selective IOC during cholecystectomy for different scenarios were calculated. RESULTS: In this meta-analysis, eight studies with more than 2 million patients subjected to cholecystectomy and 9000 BDIs were included. The rate of BDI was estimated to 0.36 per cent when IOC was performed routinely, compared with to 0.53 per cent when used selectively, indicating an increased risk for BDI of 43 per cent when IOC was used selectively (odds ratio 1.43, 95 per cent c.i. 1.22 to 1.67). The model analysis estimated that seven injuries were avoided annually by routine IOC in Sweden, a population of 10 million. Over a 10-year period, 33 QALYs would be gained at an approximate net cost of €808 000 , at a cost per QALY of about €24 900. CONCLUSION: Routine IOC during cholecystectomy reduces the risk of BDI compared with the selective strategy and is a potentially cost-effective intervention.


Subject(s)
Bile Duct Diseases/economics , Bile Ducts/diagnostic imaging , Cholangiography/economics , Cholecystectomy/economics , Iatrogenic Disease/economics , Bile Duct Diseases/diagnosis , Bile Duct Diseases/etiology , Bile Duct Diseases/therapy , Bile Ducts/injuries , Cholecystectomy/adverse effects , Cost Savings , Cost-Benefit Analysis , Humans , Iatrogenic Disease/prevention & control , Intraoperative Care/economics , Intraoperative Complications/etiology , Models, Economic , Quality-Adjusted Life Years , Sweden
4.
J Biol Chem ; 296: 100159, 2021.
Article in English | MEDLINE | ID: mdl-33277360

ABSTRACT

Synaptotagmin-like protein 4 (Slp-4), also known as granuphilin, is a Rab effector responsible for docking secretory vesicles to the plasma membrane before exocytosis. Slp-4 binds vesicular Rab proteins via an N-terminal Slp homology domain, interacts with plasma membrane SNARE complex proteins via a central linker region, and contains tandem C-terminal C2 domains (C2A and C2B) with affinity for phosphatidylinositol-(4,5)-bisphosphate (PIP2). The Slp-4 C2A domain binds with low nanomolar apparent affinity to PIP2 in lipid vesicles that also contain background anionic lipids such as phosphatidylserine but much weaker when either the background anionic lipids or PIP2 is removed. Through computational and experimental approaches, we show that this high-affinity membrane binding arises from concerted interaction at multiple sites on the C2A domain. In addition to a conserved PIP2-selective lysine cluster, a larger cationic surface surrounding the cluster contributes substantially to the affinity for physiologically relevant lipid compositions. Although the K398A mutation in the lysine cluster blocks PIP2 binding, this mutated protein domain retains the ability to bind physiological membranes in both a liposome-binding assay and MIN6 cells. Molecular dynamics simulations indicate several conformationally flexible loops that contribute to the nonspecific cationic surface. We also identify and characterize a covalently modified variant that arises through reactivity of the PIP2-binding lysine cluster with endogenous bacterial compounds and binds weakly to membranes. Overall, multivalent lipid binding by the Slp-4 C2A domain provides selective recognition and high-affinity docking of large dense core secretory vesicles to the plasma membrane.


Subject(s)
Cholesterol/chemistry , Liposomes/chemistry , Phosphatidylcholines/chemistry , Phosphatidylinositol 4,5-Diphosphate/chemistry , Vesicular Transport Proteins/chemistry , Animals , Binding Sites , Cell Line, Tumor , Cholesterol/metabolism , Cloning, Molecular , Crystallography, X-Ray , Escherichia coli/genetics , Escherichia coli/metabolism , Gene Expression , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Humans , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/metabolism , Lipid Bilayers/chemistry , Lipid Bilayers/metabolism , Liposomes/metabolism , Mice , Molecular Docking Simulation , Molecular Dynamics Simulation , Phosphatidylcholines/metabolism , Phosphatidylethanolamines/chemistry , Phosphatidylethanolamines/metabolism , Phosphatidylinositol 4,5-Diphosphate/metabolism , Phosphatidylinositols/chemistry , Phosphatidylinositols/metabolism , Phosphatidylserines/chemistry , Phosphatidylserines/metabolism , Protein Binding , Protein Conformation, beta-Strand , Protein Interaction Domains and Motifs , Recombinant Proteins/chemistry , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , Sphingomyelins/chemistry , Sphingomyelins/metabolism , Vesicular Transport Proteins/genetics , Vesicular Transport Proteins/metabolism
5.
Hernia ; 23(6): 1081-1091, 2019 12.
Article in English | MEDLINE | ID: mdl-31754953

ABSTRACT

INTRODUCTION: The Accreditation and Certification of Hernia Centers and Surgeons (ACCESS) Group of the European Hernia Society (EHS) recognizes that there is a growing need to train specialist abdominal wall surgeons. The most important and relevant argument for this proposal and statement is the growing acceptance of the increasing complexity of abdominal wall surgery due to newer techniques, more challenging cases and the required 'tailored' approach to such surgery. There is now also an increasing public awareness with social media, whereby optimal treatment results are demanded by patients. However, to date the complexity of abdominal wall surgery has not been properly or adequately defined in the current literature. METHODS: A systematic search of the available literature was performed in May 2019 using Medline, PubMed, Scopus, Embase, Springer Link, and the Cochrane Library, with 75 publications identified as relevant. In addition, an analysis of data from the Herniamed Hernia Registry was performed. The percentage of patients with hernia- or patient-related characteristics which unfavorably impacted the outcome of inguinal and incisional hernia repair was also calculated. RESULTS: All present guidelines for abdominal wall surgery recommend the utilization of a 'tailored' approach. This relies on the prerequisite that any surgical technique used has already been mastered, as well as the recognized learning curves for each of the several techniques that can be used for both inguinal hernia (Lichtenstein, TEP, TAPP, Shouldice) and incisional hernia repairs (laparoscopic IPOM, open sublay, open IPOM, open onlay, open or endoscopic component separation technique). Other hernia- and patient-related characteristics that have recognized complexity include emergency surgery, obesity, recurrent hernias, bilateral inguinal hernias, groin hernia in women, scrotal hernias, large defects, high ASA scores, > 80 years of age, increased medical risk factors and previous lower abdominal surgery. The proportion of patients with at least one of these characteristics in the Herniamed Hernia Registry in the case of both inguinal and incisional hernia is noted to be relatively high at around 70%. In general surgery training approximately 50-100 hernia repairs on average are performed by each trainee, with around only 25 laparo-endoscopic procedures. CONCLUSION: A tailored approach is now employed and seen more so in hernia surgery and this fact is referred to and highlighted in the contemporaneous hernia guidelines published to date. In addition, with the increasing complexity of abdominal wall surgery, the number of procedures actually performed by trainees is no longer considered adequate to overcome any recognized learning curve. Therefore, to supplement general surgery training young surgeons should be offered a clinical fellowship to obtain an additional qualification as an abdominal wall surgeon and thus improve their clinical and operative experience under supervision in this field. Practicing general surgeons with a special interest in hernia surgery can undertake intensive further training in this area by participating in clinical work shadowing in hernia centers, workshops and congresses.


Subject(s)
Abdominal Wall/surgery , General Surgery/education , Hernia, Abdominal/surgery , Herniorrhaphy/education , General Surgery/standards , Hernia, Abdominal/complications , Herniorrhaphy/standards , Humans , Laparoscopy , Learning Curve , Recurrence , Registries , Treatment Outcome
6.
Hernia ; 23(2): 185-203, 2019 04.
Article in English | MEDLINE | ID: mdl-30671899

ABSTRACT

INTRODUCTION: There is a need for hernia centers and specialist hernia surgeons because of the increasing complexity of hernia surgery procedures due to new techniques, more difficult cases and a tailored approach with an increasing public awareness demanding optimal treatment results. Therefore, the requirements for accredited/certified hernia centers and specialist hernia surgeons should be formulated by the international and national hernia societies, while taking account of the respective health care systems. METHODS: The European Hernia Society (EHS) has appointed a working group composed of 18 hernia experts from all regions of Europe (ACCESS Group-Hernia Accreditation and Certification of Centers and Surgeons-Working Group) to formulate scientifically based requirements for hernia centers and specialist hernia surgeons while taking into consideration different health care systems. A consensus was reached on the key questions by means of a meeting, a telephone conference and the exchange of contributions. The requirements formulated below were deemed implementable by all participating hernia experts in their respective countries. RESULTS: The ACCESS Group suggests for an adequately equipped hernia center the following requirements: (a) to be accredited/certified by a national or international hernia society, (b) to perform a higher case volume in all types of hernia surgery compared to an average general surgery department in their country, (c) to be staffed by experienced hernia surgeons who are beyond the learning curve for all types of hernia surgery recommended in the guidelines and are responsible for education and training of hernia surgery in their department, (d) to treat hernia patients according to the current guidelines and scientific recommendations, (e) to document each case prospectively in a registry or quality assurance database (f) to perform follow-up for comparison of their own results with benchmark data for continuous improvement of their treatment results and ensuring contribution to research in hernia treatment. To become a specialist hernia surgeon, the ACCESS Group suggests a general surgeon to master the learning curve of all open and laparo-endoscopic hernia procedures recommended in the guidelines, perform a high caseload and additionally to implement and fulfill the other requirements for a hernia center. CONCLUSION: Based on the above requirements formulated by the European Hernia Society for accredited/certified hernia centers and hernia specialist surgeons, the national and international hernia societies can now develop their own programs, while taking account of their specific health care systems.


Subject(s)
Accreditation/standards , Certification/standards , Herniorrhaphy/standards , Hospitals, Special/standards , Consensus , Europe , Herniorrhaphy/methods , Humans , Learning Curve , Surgeons/standards
7.
Aquat Toxicol ; 200: 73-82, 2018 Jul.
Article in English | MEDLINE | ID: mdl-29727773

ABSTRACT

In many human-altered ecosystems, organisms are increasingly faced with more diverse and complex environmental stressors and pollutant mixtures, to which the adaptations necessary to survive exposure are likely to be numerous and varied. Improving our understanding of the molecular mechanisms that underlie complex polygenic adaptations in natural settings requires significant toxicological, biochemical, physiological, and genomic data rarely available for non-model organisms. Here, we build upon two decades of study of adaptation to anthropogenic pollutants in a population of Atlantic killifish (Fundulus heteroclitus) that inhabits the creosote-contaminated Atlantic Wood Industries Superfund (AW) site on the Elizabeth River, Virginia in the United States. To better understand the genotypes that underlie previously characterized resistance to PCBs and PAHs, we performed Restriction site-Associated DNA sequencing (RADseq) on killifish from AW and two relatively clean reference sites (King's Creek-KC, and Mains Creek-MC). Across the genome, we analyzed over 83,000 loci and 12,000 single nucleotide polymorphisms (SNPs). Shared across both comparisons of killifish from polluted (AW) and relatively unpolluted (KC and MC) sites, we found eight genomic regions with smoothed FST values significantly (p < 0.001) elevated above background. Using the recently published F. heteroclitus reference genome, we identified candidate genes in these significant regions involved in the AHR pathway (e.g. AIP, ARNT1c), as well as genes relating to cardiac structure and function. These genes represent both previously characterized and potentially novel molecular adaptations involved with various aspects of resistance to these environmental toxins.


Subject(s)
Adaptation, Physiological/drug effects , Fundulidae/genetics , Genome , Water Pollutants, Chemical/toxicity , Adaptation, Physiological/genetics , Animals , Creosote/metabolism , Creosote/toxicity , DNA/chemistry , DNA/isolation & purification , DNA/metabolism , Ecosystem , Heart/drug effects , Myocardium/metabolism , Polychlorinated Biphenyls/chemistry , Polychlorinated Biphenyls/metabolism , Polychlorinated Biphenyls/toxicity , Polycyclic Aromatic Hydrocarbons/chemistry , Polycyclic Aromatic Hydrocarbons/metabolism , Polycyclic Aromatic Hydrocarbons/toxicity , Polymorphism, Single Nucleotide , Rivers/chemistry , Sequence Analysis, DNA , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/metabolism
8.
Br J Surg ; 105(1): 121-127, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29044465

ABSTRACT

BACKGROUND: There is a strong association between obesity and gallstones. However, there is no clear evidence regarding the optimal order of Roux-en-Y gastric bypass (RYGB) and cholecystectomy when both procedures are clinically indicated. METHODS: Based on cross-matched data from the Swedish Register for Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography (GallRiks; 79 386 patients) and the Scandinavian Obesity Surgery Registry (SOReg; 36 098 patients) from 2007 to 2013, complication rates, reoperation rates and operation times related to the timing of RYGB and cholecystectomy were explored. RESULTS: There was a higher aggregate complication risk when cholecystectomy was performed after RYGB rather than before (odds ratio (OR) 1·35, 95 per cent c.i. 1·09 to 1·68; P = 0·006). A complication after the first procedure independently increased the complication risk of the following procedure (OR 2·02, 1·44 to 2·85; P < 0·001). Furthermore, there was an increased complication risk when cholecystectomy was performed at the same time as RYGB (OR 1·72, 1·14 to 2·60; P = 0·010). Simultaneous cholecystectomy added 61·7 (95 per cent c.i. 56·1 to 67·4) min (P < 0·001) to the duration of surgery. CONCLUSION: Cholecystectomy should be performed before, not during or after, RYGB.


Subject(s)
Cholecystectomy/methods , Gastric Bypass/methods , Operative Time , Postoperative Complications/etiology , Reoperation/statistics & numerical data , Adult , Databases, Factual , Female , Humans , Linear Models , Logistic Models , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/prevention & control , Risk Factors , Sweden
10.
Hernia ; 20(3): 387-91, 2016 06.
Article in English | MEDLINE | ID: mdl-27094763

ABSTRACT

PURPOSE: To investigate which type of hernia that has the highest risk of a recurrence after a primary Lichtenstein repair. METHODS: Male patients operated on with a Lichtenstein repair for a primary direct or indirect inguinal hernia and with a TEP for a later recurrence, with both operations recorded in the Swedish Hernia Register (SHR), were included in the study. The study period was 1994-2014. RESULTS: Under the study period, 130,037 male patients with a primary indirect or direct inguinal hernia were operated on with a Lichtenstein repair. A second operation in the SHR was registered in 2236 of these patients (reoperation rate 1.7 %). TEP was the chosen operation in 737 in this latter cohort. The most likely location for a recurrence was the same as the primary location. If the recurrences change location from the primary place, we recognized that direct hernias had a RR of 1.51 to having a recurrent indirect hernia compared to having a direct recurrence after an indirect primary hernia repair. CONCLUSIONS: Recurrent hernias after Lichtenstein are more common on the same location as the primary one, compared to changing the location.


Subject(s)
Groin/surgery , Hernia, Inguinal/surgery , Herniorrhaphy/adverse effects , Adolescent , Adult , Aged , Aged, 80 and over , Hernia, Inguinal/epidemiology , Herniorrhaphy/methods , Herniorrhaphy/statistics & numerical data , Humans , Male , Middle Aged , Recurrence , Registries , Reoperation/statistics & numerical data , Sweden/epidemiology , Young Adult
11.
Arch Environ Contam Toxicol ; 70(2): 311-20, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26498942

ABSTRACT

Selenium (Se) is an essential micronutrient that can be found at toxic concentrations in surface waters contaminated by runoff from agriculture and coal mining. Zebrafish (Danio rerio) embryos were exposed to aqueous Se in the form of selenate, selenite, and l-selenomethionine (SeMet) in an attempt to determine if oxidative stress plays a role in selenium embryo toxicity. Selenate and selenite exposure did not induce embryo deformities (lordosis and craniofacial malformation). l-selenomethionine, however, induced significantly higher deformity rates at 100 µg/L compared with controls. SeMet exposure induced a dose-dependent increase in the catalytic subunit of glutamate-cysteine ligase (gclc) and reached an 11.7-fold increase at 100 µg/L. SeMet exposure also reduced concentrations of TGSH, RGSH, and the TGSH:GSSG ratio. Pretreatment with 100 µM N-acetylcysteine significantly reduced deformities in the zebrafish embryos secondarily treated with 400 µg/L SeMet from approximately 50­10 % as well as rescued all three of the significant glutathione level differences seen with SeMet alone. Selenite exposure induced a 6.6-fold increase in expression of the glutathione-S-transferase pi class 2 (gstp2) gene, which is involved in xenobiotic transformation and possibly oxidative stress. These results suggest that aqueous exposure to SeMet can induce significant embryonic teratogenesis in zebrafish that are at least partially attributed to oxidative stress.


Subject(s)
Embryo, Nonmammalian/drug effects , Selenomethionine/toxicity , Water Pollutants, Chemical/toxicity , Zebrafish/embryology , Acetylcysteine/metabolism , Animals , Glutamate-Cysteine Ligase/metabolism , Glutathione/metabolism , Teratogenesis
12.
Biochemistry ; 54(37): 5684-95, 2015 Sep 22.
Article in English | MEDLINE | ID: mdl-26322740

ABSTRACT

The synaptotagmin (Syt) family of proteins plays an important role in vesicle docking and fusion during Ca(2+)-induced exocytosis in a wide variety of cell types. Its role as a Ca(2+) sensor derives primarily from its two C2 domains, C2A and C2B, which insert into anionic lipid membranes upon binding Ca(2+). Syt isoforms 1 and 7 differ significantly in their Ca(2+) sensitivity; the C2A domain from Syt7 binds Ca(2+) and membranes much more tightly than the C2A domain from Syt1, at least in part because of greater contributions from the hydrophobic effect. While the structure and membrane activity of Syt1 have been extensively studied, the structural origins of differences between Syt1 and Syt7 are unknown. This study used site-directed spin labeling and electron paramagnetic resonance spectroscopy to determine depth parameters for the Syt7 C2A domain, for comparison to analogous previous measurements with the Syt1 C2A domain. In a novel approach, the membrane docking geometry of both Syt1 and Syt7 C2A was modeled by mapping depth parameters onto multiple molecular dynamics-simulated structures of the Ca(2+)-bound protein. The models reveal membrane penetration of Ca(2+) binding loops 1 (CBL1) and 3 (CBL3), and membrane binding is more sensitive to mutations in CBL3. On average, Syt7 C2A inserts more deeply into the membrane than Syt1 C2A, although depths vary among the different structural models. This observation provides a partial structural explanation for the hydrophobically driven membrane docking of Syt7 C2A.


Subject(s)
Molecular Docking Simulation , Synaptotagmins/chemistry , Unilamellar Liposomes/chemistry , Binding Sites , Electron Spin Resonance Spectroscopy , Kinetics , Mutagenesis, Site-Directed , Protein Structure, Tertiary , Synaptotagmins/genetics
13.
Biochemistry ; 54(37): 5696-711, 2015 Sep 22.
Article in English | MEDLINE | ID: mdl-26333120

ABSTRACT

The C2A domain of synaptotagmin 7 (Syt7) is a Ca(2+) and membrane binding module that docks and inserts into cellular membranes in response to elevated intracellular Ca(2+) concentrations. Like other C2 domains, Syt7 C2A binds Ca(2+) and membranes primarily through three loop regions; however, it docks at Ca(2+) concentrations much lower than those required for other Syt C2A domains. To probe structural components of its unusually strong membrane docking, we conducted atomistic molecular dynamics simulations of Syt7 C2A under three conditions: in aqueous solution, in the proximity of a lipid bilayer membrane, and embedded in the membrane. The simulations of membrane-free protein indicate that Syt7 C2A likely binds three Ca(2+) ions in aqueous solution, consistent with prior experimental reports. Upon membrane docking, the outermost Ca(2+) ion interacts directly with lipid headgroups, while the other two Ca(2+) ions remain chelated by the protein. The membrane-bound domain was observed to exhibit large-amplitude swinging motions relative to the membrane surface, varying by up to 70° between a more parallel and a more perpendicular orientation, both during and after insertion of the Ca(2+) binding loops into the membrane. The computed orientation of the membrane-bound protein correlates well with experimental electron paramagnetic resonance measurements presented in the preceding paper ( DOI: 10.1021/acs.biochem.5b00421 ). In particular, the strictly conserved residue Phe229 inserted stably ∼4 Å below the average depth of lipid phosphate groups, providing critical hydrophobic interactions anchoring the domain in the membrane. Overall, the position and orientation of Syt7 C2A with respect to the membrane are consistent with experiments.


Subject(s)
Lipid Bilayers/chemistry , Molecular Dynamics Simulation , Synaptotagmins/chemistry , Calcium/chemistry , Hydrophobic and Hydrophilic Interactions , Protein Binding , Protein Structure, Tertiary , Static Electricity
14.
Vet Rec ; 165(14): 404-8, 2009 Oct 03.
Article in English | MEDLINE | ID: mdl-19801593

ABSTRACT

Groups of six, 10-week-old pigs were inoculated with 0.65 x 10(3), 0.65 x 10(6) or 0.65 x 10(9) colony-forming units (cfu) of Salmonella Cubana or Salmonella Derby and then monitored for eight weeks for the faecal excretion of Salmonella species and the presence of serum antibodies. Eight tissue samples were collected postmortem from each pig and analysed for Salmonella species. In general, the dose had a greater impact on the responses of the pigs than the serovar. However, in the groups inoculated with 0.65 x 10(6) cfu, S Cubana were excreted only by one pig during the first two days after infection, whereas the pigs inoculated with S Derby all shed the bacteria constantly for two weeks and then intermittently for several weeks. In the low dose groups none of the pigs excreted any detectable salmonella whereas all the pigs in both high dose groups shed salmonella constantly or intermittently throughout the eight weeks. All the 12 pigs inoculated with 0.65 x 10(6) or 0.65 x 10(9) cfu of S Derby seroconverted during the study period, whereas all the pigs inoculated with 0.65 x 10(3) remained seronegative. No serological response could be detected in the three groups of pigs inoculated with S Cubana. In the postmortem samples both serovars were re-isolated from the caecal contents and the colonic tissue, but the other organs and tissues were all negative except for one ileocaecal lymph node from a pig inoculated with 0.65 x 10(6) cfu of S Derby.


Subject(s)
Antibodies, Bacterial/blood , Salmonella Infections, Animal/microbiology , Salmonella/classification , Swine Diseases/microbiology , Animals , Feces/microbiology , Salmonella Infections, Animal/immunology , Swine , Swine Diseases/immunology
15.
Vet Rec ; 162(18): 580-6, 2008 May 03.
Article in English | MEDLINE | ID: mdl-18453377

ABSTRACT

The epidemiology of a feed-associated Salmonella serotype (Salmonella Yoruba) was compared with that of a 'classical' serotype (Salmonella Typhimurium) by inoculating pigs aged 10 weeks with 0.65 x 10(3), 0.65 x 10(6) or 0.65 x 10(9) colony-forming units (cfu) of either serotype. The pigs were then monitored for eight weeks with respect to the faecal excretion of Salmonella species and the presence of serum antibodies. Only minor differences were observed between the two serotypes but the dose inoculated had significant effects. The pigs inoculated with 0.65 x 10(9) cfu shed Salmonella species in faeces constantly for four weeks, and intermittently during the subsequent four weeks; the pigs inoculated with 0.65 x 10(6) cfu shed Salmonella species intermittently for four weeks, but not for longer, and the pigs inoculated with 0.65 x 10(3) cfu generally did not excrete Salmonella species. The pigs inoculated with 0.65 x 10(9) cfu S Typhimurium seroconverted at a high titre within two weeks, the pigs inoculated with 0.65 x 10(6) cfu seroconverted later and with lower titres of antibodies, and the pigs inoculated with 0.65 x 10(3) cfu did not seroconvert. A similar pattern was observed with S Yoruba, but the responses were slower and at lower titres.


Subject(s)
Antibodies, Bacterial/biosynthesis , Salmonella/immunology , Swine/immunology , Animals , Antibodies, Bacterial/blood , Dose-Response Relationship, Immunologic , Enzyme-Linked Immunosorbent Assay , Feces/microbiology , Salmonella/isolation & purification , Salmonella typhimurium/immunology , Salmonella typhimurium/isolation & purification , Sweden , Swine/microbiology
16.
Br J Surg ; 93(9): 1060-8, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16862612

ABSTRACT

BACKGROUND: Laparoscopic herniorrhaphy has emerged as a recognized operative method for inguinal hernia repair. This study compared the short-term results of two tension-free methods of repair: totally extraperitoneal (TEP) laparoscopic patch repair and the open Lichtenstein mesh technique. METHODS: A total of 1513 men from 11 hospitals who presented with a primary unilateral inguinal hernia were randomized to one of the two methods. Operating time, short-term complications, reoperations, postoperative pain, consumption of analgesics, sick leave and time to resumption of normal physical activities were recorded. RESULTS: Some 1371 of the 1513 men underwent surgery, 665 in the TEP group and 706 in the Lichtenstein group. The median duration of operation was 55 min for both procedures and 91.0 percent of the patients in both groups were discharged on the day of operation. Patients in the TEP group experienced less postoperative pain (P<0.001), consumed fewer analgesics (P<0.001), had a shorter period of sick leave (7 versus 12 days; P<0.001) and a shorter time to resumption of normal physical activity (20 versus 31 days; P<0.001). CONCLUSION: The TEP technique took no longer to perform, and was associated with less postoperative pain, a shorter period of sick leave and a faster recovery, compared with open Lichtenstein hernia repair.


Subject(s)
Digestive System Surgical Procedures/methods , Hernia, Inguinal/surgery , Laparoscopy/methods , Surgical Mesh , Adult , Aged , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/etiology , Treatment Outcome
17.
Br J Surg ; 93(9): 1056-9, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16862613

ABSTRACT

BACKGROUND: This randomized trial examined whether lightweight (LW) polypropylene mesh (large pore size, partially absorbable) could have long-term benefits in reducing chronic pain and inflammation after inguinal hernia repair. METHODS: Six hundred men with a primary unilateral inguinal hernia were randomized to Lichtenstein repair using a standard polypropylene mesh or a LW mesh in one of six centres. The patients were blinded to which mesh they received. Clinical examination was performed and a pain questionnaire completed 3 years after surgery. RESULTS: Of the 590 men who had surgery, 243 (82.7 percent) of 294 in the standard mesh group and 251 (84.8 percent) of 296 in the LW mesh group were examined in the clinic, a median of 37 (range 30-48) months after hernia repair. There were nine recurrent hernias in each group (3.7 percent with standard mesh and 3.6 per cent with LW mesh). Patients who had LW mesh had less pain on examination, less pain on rising from lying to sitting, fewer miscellaneous groin problems and felt the mesh less often than patients with standard mesh. CONCLUSION: Use of LW mesh for Lichtenstein hernia repair did not affect recurrence rates, but improved some aspects of pain and discomfort 3 years after surgery.


Subject(s)
Hernia, Inguinal/surgery , Pain, Postoperative/prevention & control , Polypropylenes/therapeutic use , Surgical Mesh , Adult , Follow-Up Studies , Humans , Male , Pain Measurement , Quality of Life , Recurrence , Surveys and Questionnaires , Treatment Outcome
18.
Acta Vet Scand ; 47: 13-21, 2006.
Article in English | MEDLINE | ID: mdl-16722302

ABSTRACT

In 2003, a feed-borne outbreak of Salmonella Cubana occurred in Sweden as a result of contamination in a feed plant. Salmonella Cubana was detected in 49 out of 77 pig farms having received possibly contaminated feed. In this study, potential risk factors for farms being salmonella positive were examined, and a survival analysis was performed to investigate risk factors affecting the restriction period for salmonella positive farms. The median restriction time for all 49 farms was 17 weeks. An increased risk for farms being salmonella infected (positive in feed and/or faeces) was seen for fattening farms and farms feeding soy. The survival analysis showed that herds with a low level of infection and farms with a high hygiene level had shorter restriction times. This study is unique as it investigates a real outbreak of feed-borne salmonella, where the source of infection was reliably identified, the period of exposure could be defined and data were collected from all exposed farms.


Subject(s)
Animal Feed/microbiology , Food Contamination/analysis , Food Microbiology , Salmonella Food Poisoning/veterinary , Swine Diseases/epidemiology , Animals , Disease Outbreaks/veterinary , Female , Male , Risk Factors , Salmonella Food Poisoning/epidemiology , Survival Analysis , Sweden/epidemiology , Swine
19.
Hernia ; 10(1): 34-40, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16088358

ABSTRACT

The purpose of this study was to compare a lightweight mesh to a standard polypropylene hernia mesh in endoscopic extraperitoneal hernioplasty in recurrent hernias. A total of 140 men with recurrent unilateral inguinal hernias were randomised to a totally extraperitoneal endoscopic hernioplasty (TEP) with Prolene or VyproII in a single-blinded multi-center trial. The randomisation and all data handling were performed through the Internet. 137 patients were operated as allocated. Follow-up was completed in 88% of the patients. The median operation times were 55 (24-125) min and 53.5 (21-123) min for the Prolene and VyproII groups, respectively. The meshes had comparable results in the surgeon's assessment of the handling of the mesh, return to work, return to daily activities, complications, postoperative pain and quality of life during the first 8 weeks of rehabilitation, except in General Health (GH) SF-36, where the VyproII-group had a significantly better score (P=0.045). The use of Prolene and VyproII-meshes in endoscopic repair of recurrent inguinal hernia seems to result in similar short-term outcomes and quality of life.


Subject(s)
Hernia, Inguinal/surgery , Polyglactin 910/therapeutic use , Polypropylenes/therapeutic use , Surgical Mesh , Adult , Aged , Equipment Design , Humans , Male , Middle Aged , Quality of Life , Recurrence , Reoperation
20.
Surg Endosc ; 19(4): 536-40, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15759178

ABSTRACT

BACKGROUND: The use of mesh in inguinal hernia surgery has become increasingly popular despite the potentially harmful effects that foreign material may exert on human tissue. The purpose of this study was to compare the use of a lightweight mesh vs a standard hernia mesh in bilateral endoscopic hernioplasty. METHODS: This single-blinded multicenter trial, 140 men with bilateral inguinal hernias were randomized to undergo totally extraperitoneal endoscopic hernioplasty (TEP) with either Prolene or VyproII. The randomization and all data management were done via the Internet. RESULTS: A total of 139 patients were operated on as allocated. The follow-up was complete in 94% of the patients. The median (range) operating times were 85 min (45-140) and 73 min (35-165) for the Prolene and VyproII groups, respectively. (p = 0.01). The difference was due to uneven distribution of the allocated patients to study groups among individual surgeons. The time to return to work was similar (11 vs 9 days, p = 0.08). The time to return to normal daily activities was 19 days (1-133) in the Prolene group and 12.5 days (0-237) in the VyproII group (p = 0.06). There were no significant differences between the groups in their scores on the Visual Analogue Scale or SF-36 Health Scores during the 8-week follow-up. CONCLUSIONS: The use of Prolene and VyproII meshes in bilateral endoscopic repair of inguinal hernia seems to result in similar short-term outcome and quality of life. However, there was a tendency toward faster return to normal activity among VyproII patients.


Subject(s)
Endoscopy/methods , Hernia, Inguinal/surgery , Polyglactin 910 , Polypropylenes , Surgical Mesh , Adult , Aged , Elasticity , Elective Surgical Procedures , Equipment Design , Follow-Up Studies , Humans , Intraoperative Complications/epidemiology , Male , Middle Aged , Pain, Postoperative , Peritoneum/injuries , Postoperative Complications/epidemiology , Recurrence , Single-Blind Method , Treatment Outcome
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