NF-Y recruitment of TFIID, multiple interactions with histone fold TAF(II)s

The nuclear factor y (NF-Y) trimer and TFIID contain histone fold subunits, and their binding to the CCAAT and Initiator elements of the major histocompatibility complex class II Ea promoter is required for transcriptional activation. Using agarose-electrophoretic mobility shift assay we found that NF-Y increases the affinity of holo-TFIID for Ea in a CCAAT- and Inr-dependent manner. We began to dissect the interplay between NF-Y- and TBP-associated factors PO1II (TAF(II)s)-containing histone fold domains in protein-protein interactions and transfections. hTAF(II)20, hTAF(II)28, and hTAF(II)18-hTAF(II)28 bind to the NF-Y B-NF-YC histone fold dimer; hTAF(II)80 and hTAF(II)31-hTAF(II)80 interact with the trimer but not with the NF-YB-NF-YC dimer. The histone fold alpha2 helix of hTAF(II)80 is not required for NF-Y association, as determined by interactions with the naturally occurring splice variant hTAF(II)80delta. Expression of hTAF(II)28 and hTAF(II)18 in mouse cells significantly and specifically reduced NF-Y activation in GAL4-based experiments, whereas hTAF,120 and hTAF(II)135 increased it. These results indicate that NF-Y (i) recruits purified holo-TFIID in vitro and (ii) can associate multiple TAF(II)s, potentially accommodating different core promoter architectures

The Rising Tide of Revisional Surgery: Tracking Changes in Index Cases Among Bariatric-Accredited Fellowships

BACKGROUND: The field of bariatric surgery has seen peaks and troughs in the types of metabolic procedures performed. Our primary aim was to evaluate bariatric case volumes among fellows enrolled in bariatric Fellowship Council (FC)-accredited programs. Our secondary aim was to assess trends in revisional case volumes. METHODS: We reviewed de-identified FC case logs for all bariatric surgery-accredited programs from 2010 through 2019. The number of primary sleeve gastrectomy, gastric band, gastric bypass, biliopancreatic diversion, and major revisional bariatric surgical procedures (defined as a revision with creation of a new anastomosis) were graphed for each academic year. Fellows were stratified into quartiles based on the number of revisional operations per year and graphed over ten years. Volumes of primary gastric bypass, major revisions, and total anastomotic cases were compared over time using ANOVA with p \u3c 0.05 considered significant. RESULTS: Case volumes for 822 fellows were evaluated. Sleeve gastrectomy had a significant surge in 2010 and plateaued in 2016. The fellows\u27 number of primary gastric bypasses had a non-significant decrease from 84 to 75 cases/fellow from 2010 to 2019. This decrease was offset by a significant increase in major revisional surgery from 8 to 19 cases/fellow. As a result, the number of anastomotic cases did not change significantly over the study time period. Interestingly, as revisional volume has grown, the gap between quartiles of fellowship programs has widened with the 95th percentile growing at a much faster rate than lower quartiles. CONCLUSION: The volume of bariatric procedures performed in the last decade among FC fellows follows similar trends to national data. Major revisional cases have doubled with the most robust growth isolated to a small number of programs. As revisional surgery continues to increase, applicants interested in a comprehensive bariatric practice should seek out training programs that offer strong revisional experience

Palliative Endoscopic Salvage of a Functionally Obstructed Gastrojejunostomy - Report of Technique

BACKGROUND: Gastric outlet obstruction secondary to foregut gastrointestinal malignancies can be managed with a variety of medical, endoscopic, and surgical options. Laparoscopic gastrojejunostomy is an option for those patients who are able to tolerate an operation as a long-term palliative option. This operation may be associated with some significant postoperative technical and nontechnical complications, including delayed gastric emptying. This paper describes an incision-less, endoscopic option that we propose can be used to salvage a functionally obstructed gastrojejunostomy. CASE DESCRIPTION: A 57-year old male patient had a history of pancreatic adenocarcinoma causing gastric outlet obstruction and underwent a previously created surgical gastrojejunostomy at an outside hospital. His procedure was complicated by anastomotic leak and essentially persistent obstructive symptoms secondary to delayed gastric emptying. Though his anastomosis was demonstrably patent, these symptoms were thought to be secondary to a functional obstruction at the gastrojejunostomy. After repeated workups and many failed attempts to treat these symptoms, he ultimately underwent endoscopic placement of an uncovered colonic stent into the efferent limb of his gastrojejunostomy. This allowed for preferential drainage of gastric contents down the efferent limb, and improvement of his delayed gastric emptying. CONCLUSIONS: In a select group of patients with advanced foregut malignancy, and with high re-operative risks, salvage endoscopic stenting may be useful in the palliation of symptoms from a functionally obstructed gastrojejunostomy

Absence of diabetic retinopathy in a patient who has had diabetes mellitus for 69 years, and inadequate glycemic control: case presentation

The main risk factors for the development and progression of diabetic retinopathy (DR) are chronic hyperglycemia, disease duration and systemic blood pressure. So far chronic hyperglycemia is the strongest evidence concerning the risk of developing DR. However there are some patients with poor metabolic control who never develop this diabetic complication. We present a case of a 73-year-old woman with type 1 diabetes mellitus, diagnosed 69 years ago. The patient is 73 years old, with no evidence of DR, despite poor glycemic control and several risk factors for DR. This case suggests the presence of a possible protection factor, which could be genetic

The effect of a preoperative subconjuntival injection of dexamethasone on blood–retinal barrier breakdown following scleral buckling retinal detachment surgery: a prospective randomized placebo-controlled double blind clinical trial

textabstractBackground: Blood-retinal barrier breakdown secondary to retinal detachment and retinal detachment repair is a factor in the pathogenesis of proliferative vitreoretinopathy (PVR). We wished to investigate whether an estimated 700 to 1000 ng/ml subretinal dexamethasone concentration at the time of surgery would decrease the blood-retinal barrier breakdown postoperatively. Methods: Prospective, placebo-controlled, double blind clinical trial. In 34 patients with rhegmatogenous retinal detachment scheduled for conventional scleral buckling retinal detachment surgery, a subconjunctival injection of 0.5 ml dexamethasone diphosphate (10 mg) or 0.5 ml placebo was given 5-6 hours before surgery. Differences in laser flare photometry (KOWA) measurements taken 1, 3 and 6 weeks after randomisation between dexamethasone and placebo were analysed using mixed model ANOVA, while correcting for the preoperative flare measurement. Results: Six patients did not complete the study, one because of recurrent detachment within 1 week, and five because they missed their postoperative laser flare visits. The use of dexamethasone resulted in a statistically significant decrease in laser flare measurements at the 1-week postoperative visit. Conclusion: The use of a preoperative subconjunctival injection of dexamethasone decreased 1-week postoperative blood-retina barrier breakdown in patients undergoing conventional scleral buckling retinal detachment surgery. This steroid priming could be useful as a part of a peri-operative regime that would aim at decreasing the incidence of PVR

Left Ventricular Assist Device Support and Longitudinal Sleeve Gastrectomy Combined With Diet in Bridge to Heart Transplant

Combining left ventricular assist device (LVAD) implantation and longitudinal sleeve gastrectomy may enable patients with morbid obesity to lose enough weight for heart transplant eligibility. In a retrospective study, we evaluated long-term outcomes of patients with body mass indexes ≥35 who underwent LVAD implantation and longitudinal sleeve gastrectomy during the same hospitalization (from January 2013 through July 2018) and then adhered to a dietary protocol. We included 22 patients (mean age, 49.9 ± 12.5 yr; mean preoperative body mass index, 43.3 ± 6.2). Eighteen months after gastrectomy, all 22 patients were alive, and 16 (73%) achieved a body mass index of less than 35. Myocardial recovery in 2 patients enabled LVAD removal. As of October 2020, 10 patients (45.5%) had undergone heart transplantation, 5 (22.3%) were waitlisted, 5 (22.3%) still had a body mass index ≥35, and 2 (9%) had died. With LVAD support, longitudinal sleeve gastrectomy, and dietary protocols, most of our patients with morbid obesity and advanced heart failure lost enough weight for transplant eligibility. Support from physicians and dietitians can maximize positive results in these patients

Tight junctions and the modulation of barrier function in disease

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease

Multilocus ISSR Markers Reveal Two Major Genetic Groups in Spanish and South African Populations of the Grapevine Fungal Pathogen Cadophora luteo-olivacea

Cadophora luteo-olivacea is a lesser-known fungal trunk pathogen of grapevine which has been recently isolated from vines showing decline symptoms in grape growing regions worldwide. In this study, 80 C. luteo-olivacea isolates (65 from Spain and 15 from South Africa) were studied. Inter-simple-sequence repeat-polymerase chain reaction (ISSR-PCR) generated 55 polymorphic loci from four ISSR primers selected from an initial screen of 13 ISSR primers. The ISSR markers revealed 40 multilocus genotypes (MLGs) in the global population. Minimum spanning network analysis showed that the MLGs from South Africa clustered around the most frequent genotype, while the genotypes from Spain were distributed all across the network. Principal component analysis and dendrograms based on genetic distance and bootstrapping identified two highly differentiated genetic clusters in the Spanish and South African C. luteo-olivacea populations, with no intermediate genotypes between these clusters. Movement within the Spanish provinces may have occurred repeatedly given the frequent retrieval of the same genotype in distant locations. The results obtained in this study provide new insights into the population genetic structure of C. luteo-olivacea in Spain and highlights the need to produce healthy and quality planting material in grapevine nurseries to avoid the spread of this fungus throughout different grape growing regions