This review discusses the spectrin superfamily of proteins that function to connect cytoskeletal elements to each other, the cell membrane, and the nucleus. The signature domain is the spectrin ...repeat, a 106-122-amino-acid segment comprising three α-helices. α-actinin is considered to be the ancestral protein and functions to cross-link actin filaments. It then evolved to generate spectrin and dystrophin that function to link the actin cytoskeleton to the cell membrane, as well as the spectraplakins and plakins that link cytoskeletal elements to each other and to junctional complexes. A final class comprises the nesprins, which are able to bind to the nuclear membrane. This review discusses the domain organization of the various spectrin family members, their roles in protein-protein interactions, and their roles in disease, as determined from mutations, and it also describes the functional roles of the family members as determined from null phenotypes.
It remains unknown whether the administration of a deep neuromuscular block (NMB) during bariatric surgery improves surgical conditions and patient outcome. The authors studied the effect of deep ...versus moderate NMB in laparoscopic bariatric surgery on surgical conditions and postoperative pain.
One hundred patients scheduled to undergo elective bariatric surgery were randomized to a deep NMB (post-tetanic-count 2-3) or a moderate NMB (train-of-four 1-2). The quality of the surgical field was scored using the Leiden-Surgical Rating Scale (L-SRS), a 5-point scale ranging from 1 (extremely poor conditions) to 5 (optimal conditions). Three surgeons scored the L-SRS at 10-min intervals during surgery; postoperative pain scores were obtained in the postanesthesia-care-unit (PACU) and on the ward. Mean (95% confidence interval) L-SRS scores in moderate NMB 4.2 (4.0-4.4) versus 4.8 (4.7-4.9) in deep NMB (p < 0.001). Moderate NMB resulted in 17% of scores at L-SRS scores of 1-3, while deep NMB resulted in 100% scores at the high end of the L-SRS (4-5). Deep NMB led to improved pain scores in the PACU (4.6 (4.2-4.9) versus 3.9 (3.6-4.4), p = 0.03) and reduced shoulder pain on the ward (1.8 (1.5-2.1) versus 1.3 (1.1-1.5), p = 0.03). A composite score of pain and opioid use in the PACU favoured deep NMB (p = 0.001).
In bariatric surgery, deep relaxation has advantages for surgeon and patient. Compared to moderate NMB, deep NMB produced stable and improved surgical conditions with less postoperative pain.
Plakins in development and disease Sonnenberg, Arnoud; Liem, Ronald K.H.
Experimental cell research,
06/2007, Letnik:
313, Številka:
10
Journal Article
Recenzirano
Plakins are large multi-domain molecules that have various functions to link cytoskeletal elements together and to connect them to junctional complexes. Plakins were first identified in epithelial ...cells where they were found to connect the intermediate filaments to desmosomes and hemidesmosomes Ruhrberg, C., and Watt, F.M. (1997). The plakin family: versatile organizers of cytoskeletal architecture. Curr Opin Genet Dev 7, 392–397.. They were subsequently found to be important for the integrity of muscle cells. Most recently, they have been found in the nervous system, where their functions appear to be more complex, including cross-linking of microtubules (MTs) and actin filaments Leung, C.L., Zheng, M., Prater, S.M., and Liem, R.K. (2001). The BPAG1 locus: Alternative splicing produces multiple isoforms with distinct cytoskeletal linker domains, including predominant isoforms in neurons and muscles. J Cell Biol 154, 691–697., Leung, C.L., Sun, D., Zheng, M., Knowles, D.R., and Liem, R.K. (1999). Microtubule actin cross-linking factor (MACF): a hybrid of dystonin and dystrophin that can interact with the actin and microtubule cytoskeletons. J Cell Biol 147, 1275–1286.. These plakins have also indicated their relationship to the spectrin superfamily of proteins and the plakins appear to be evolutionarily related to the spectrins, but have diverged to perform different specialized functions. In invertebrates, a single plakin is present in both
Drosophila melanogaster and
Caenorhabditis elegans, which resemble the more complex plakins found in mammals Roper, K., Gregory, S.L., and Brown, N.H. (2002). The ‘spectraplakins’: cytoskeletal giants with characteristics of both spectrin and plakin families. J Cell Sci 115, 4215–4225.. In contrast, there are seven plakins found in mammals and most of them have alternatively spliced forms leading to a very complex group of proteins with potential tissue specific functions Jefferson, J.J., Leung, C.L., and Liem, R.K. (2004). Plakins: goliaths that link cell junctions and the cytoskeleton. Nat Rev Mol Cell Biol 5, 542–553.. In this review, we will first describe the plakins, desmoplakin, plectin, envoplakin and periplakin and then describe two other mammalian plakins, Bullous pemphigoid antigen 1 (BPAG1) and microtubule actin cross-linking factor 1 (MACF1), that are expressed in multiple isoforms in different tissues. We will also describe the relationship of these two proteins to the invertebrate plakins, shortstop (shot) in
Drosophila and VAB-10 in
C. elegans. Finally, we will describe an unusual mammalian plakin, called epiplakin.
The compartmental organization of eukaryotic cells is maintained dynamically by vesicular trafficking. SNARE proteins play a crucial role in intracellular membrane fusion and need to be targeted to ...their proper donor or acceptor membrane. The molecular mechanisms that allow for the secretory vesicles carrying the v-SNARE TI-VAMP/VAMP7 to leave the cell center, load onto microtubules, and reach the periphery to mediate exocytosis are largely unknown. Here, we show that the TI-VAMP/VAMP7 partner Varp, a Rab21 guanine nucleotide exchange factor, interacts with GolginA4 and the kinesin 1 Kif5A. Activated Rab21-GTP in turn binds to MACF1, an actin and microtubule regulator, which is itself a partner of GolginA4. These components are required for directed movement of TI-VAMP/VAMP7 vesicles from the cell center to the cell periphery. The molecular mechanisms uncovered here suggest an integrated view of the transport of vesicles carrying a specific v-SNARE toward the cell surface.
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► Rab21 coordinates a molecular network moving secretory vesicles to the cell periphery ► The Rab21 GEF Varp links a Golgin and a kinesin motor to the v-SNARE TI-VAMP/VAMP7 ► Rab21 further organizes these interactions at the Golgi, via the spectraplakin MACF1 ► This network regulates anterograde transport of secretory vesicles on microtubules
Mechanisms delivering SNAREs to their cognate cellular subcompartments remain unclear. Burgo et al. uncover a protein network involving Rab21, its GEF (Varp), GolginA4, a Kif5 kinesin, and the spectraplakin MACF1. This network regulates vesicular transport of a v-SNARE from the Golgi apparatus to the cell periphery, where it mediates exocytosis.
Introduction
In the Netherlands, the number of bariatric procedures increased exponentially in the 90s. To ensure and improve the quality of bariatric surgery, the nationwide Dutch Audit for ...Treatment of Obesity (DATO) was established in 2014. The audit was coordinated by the Dutch Institute for Clinical Auditing (DICA). This article provides a review of the aforementioned process in establishing a nationwide registry in the Netherlands.
Materials and Methods
In collaboration with the DATO’s scientific committee and other stakeholders, an annual list of several external quality indicators was formulated. This list consists of volume, process, and outcome indicators.
In addition to the annual external indicators, the database permits individual hospitals to analyze their own data. The dashboard provides several standardized reports and detailed quality indicators, which are updated on a weekly base.
Results
Since the start, all 18 Dutch bariatric centers participated in the nationwide audit. A total of 21,941 cases were registered between 2015 and 2016. By 2016, the required variables were registered in 94.3% of all cases. A severe complicated course was seen in 2.87%, and mortality in 0.05% in 2016. The first-year follow-up shows a > 20% TWL in 86.1% of the registered cases.
Discussion
The DATO has become rapidly a mature registry. The well-organized structure of the national audit institution DICA and governmental funding were essential. However, most important were the bariatric teams themselves. The authors believe reporting the results from the registry has already contributed to more knowledge and acceptance by other health care providers.
Intermediate filaments (IFs) are abundant structures found in most eukaryotic cells, including those in the nervous system. In the CNS, the primary components of neuronal IFs are alpha-internexin and ...the neurofilament triplet proteins. In the peripheral nervous system, a fifth neuronal IF protein known as peripherin is also present. IFs in astrocytes are primarily composed of glial fibrillary acidic protein (GFAP), although vimentin is also expressed in immature astrocytes and some mature astrocytes. In this Review, we focus on the IFs of glial cells (primarily GFAP) and neurons as well as their relationship to different neurodegenerative diseases.
Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy is the most prevalent inherited peripheral neuropathy and is associated with over 90 causative genes. Mutations in ...neurofilament light polypeptide gene, NEFL cause CMT2E, an axonal form of CMT that results in abnormal structures and/or functions of peripheral axons in spinal cord motor neurons and dorsal root ganglion neurons. We have previously generated and characterized a knock-in mouse model of CMT2E with the N98S mutation in Nefl that presented with multiple inclusions in spinal cord neurons. In this report, we conduct immunofluorescence studies of cultured dorsal root ganglia (DRG) from NeflN98S/+ mice, and show that inclusions found in DRG neurites can occur in embryonic stages. Ultrastructural analyses reveal that the inclusions are disordered neurofilaments packed in high density, segregated from other organelles. Immunochemical studies show decreased NFL protein levels in DRG, cerebellum and spinal cord in NeflN98S/+ mice, and total NFL protein pool is shifted toward the triton-insoluble fraction. Our findings reveal the nature of the inclusions in NeflN98S/+ mice, provide useful information to understand mechanisms of CMT2E disease, and identify DRG from NeflN98S/+ mice as a useful cell line model for therapeutic discoveries.
Introduction
A large variation in outcome has been reported after sleeve gastrectomy (SG) across countries and institutions. We aimed to evaluate the effect of surgical technique on total weight loss ...(TWL) and gastro-esophageal reflux disease (GERD).
Methods
Observational cohort study based on data from the national registries for bariatric surgery in the Netherlands, Norway, and Sweden. A retrospective analysis of prospectively obtained data from surgeries during 2015–2017 was performed based on 2-year follow-up. GERD was defined as continuous use of acid-reducing medication. The relationship between TWL,
de novo
GERD and operation technical variables were analyzed with regression methods.
Results
A total of 5927 patients were included. The average TWL was 25.6% in Sweden, 28.6% in the Netherlands, and 30.6% in Norway (
p
< 0.001 pairwise). Bougie size, distance from the resection line to the pylorus and the angle of His differed between hospitals. A minimized sleeve increased the expected total weight loss by 5–10 percentage points. Reducing the distance to the angle of His from 3 to just above 0 cm increased the risk of
de novo
GERD five-fold (from 3.5 to 17.8%).
Conclusion
Smaller bougie size, a shorter distance to pylorus and to the angle of His were all associated with greater weight loss, whereas a shorter distance to angle of His was associated with more
de novo
reflux.
Graphical Abstract
Background
Since 2014, the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) has produced an annual report of all bariatric surgery submitted to the Global Registry. ...We describe baseline demographics of international practice from the 4th report.
Methods
The IFSO Global Registry amalgamated data from 51 different countries, 14 of which provided data from their national registries. Data were available from 394,431 individual records, of which 190,177 were primary operations performed since 2014.
Results
Data were submitted on 72,645 Roux en Y gastric bypass operations (38.2%), 87,467 sleeve gastrectomy operations (46.0%), 14,516 one anastomosis gastric bypass procedures (7.6%) and 9534 gastric banding operations (5.0%) as the primary operation since 2014. The median patient body mass index (BMI) pre-surgery was 41.7 kg m
2
(inter-quartile range: 38.3–46.1 kg m
2
). Following gastric bypass, 84.1% of patients were discharged within 2 days of surgery; and 84.5% of sleeve gastrectomy patients were discharged within 3 days. Assessing operations performed between 2012 and 2016, at one year after surgery, the mean recorded percentage weight loss was 28.9% and 66.1% of those taking medication for type 2 diabetes were recorded as not using them. The proportion of patients no longer receiving treatment for diabetes was highly dependent on weight loss achieved. There was marked variation in access and practice.
Conclusions
A global description of patients undergoing bariatric surgery is emerging. Future iterations of the registry have the potential to describe the operated patients comprehensively.
OBJECTIVE:The aim of this study was to compare the use and short-term outcome of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) in Sweden, Norway, and the Netherlands.
...BACKGROUND:Although bariatric surgery is performed in high volumes worldwide, no consensus exists regarding the choice of bariatric procedure for specific groups of patients.
METHODS:Data from 3 national registries for bariatric surgery were used. Patient selection, perioperative data (severe complications, mortality, and rate of readmissions within 30 days), and 1-year results (follow-up rate and weight loss) were studied.
RESULTS:A total of 47,101 primary operations were registered, 33,029 (70.1%) RYGB and 14,072 (29.9%) SG. Patients receiving RYGB met international guidelines for having bariatric surgery more often than those receiving SG (91.9% vs 83,0%, P < 0.001). The 2 procedures did not differ in the rate of severe complications (2.6% vs 2.4%, P = 0.382), nor 30-day mortality (0.04% vs 0.03%, P = 0.821). Readmission rates were higher after RYGB (4.3% vs 3.4%, P < 0.001).One-year post surgery, less RYGB-patients were lost-to follow-up (12.1% vs 16.5%, P < 0.001) and RYGB resulted in a higher rate of patients with total weight loss of more than 20% (95.8% vs 84.6%, P < 0.001). While the weight-loss after RYGB was similar between hospitals, there was a great variation in weight loss after SG.
CONCLUSION:This study reflects the pragmatic use and short-term outcome of RYGB and SG in 3 countries in North-Western Europe. Both procedures were safe, with RYGB having higher weight loss and follow-up rates at the cost of a slightly higher 30-day readmission rate.
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