PRMT7 can prevent neurovascular uncoupling, blood-brain barrier permeability, and mitochondrial dysfunction in repetitive and mild traumatic brain injury.

Mild traumatic brain injury (TBI) comprises the largest percentage of TBI-related injuries, with pathophysiological and functional deficits that persist in a subset of TBI patients. In our three-hit paradigm of repetitive and mild traumatic brain injury (rmTBI), we observed neurovascular uncoupling via decreased red blood cell velocity, microvessel diameter, and leukocyte rolling velocity 3 days post-rmTBI via intra-vital two-photon laser scanning microscopy. Furthermore, our data suggest increased blood-brain barrier (BBB) permeability (leakage), with corresponding decrease in junctional protein expression post-rmTBI. Mitochondrial oxygen consumption rates (measured via Seahorse XFe24) were also altered 3 days post-rmTBI, along with disrupted mitochondrial dynamics of fission and fusion. Overall, these pathophysiological findings correlated with decreased protein arginine methyltransferase 7 (PRMT7) protein levels and activity post-rmTBI. Here, we increased PRMT7 levels in vivo to assess the role of the neurovasculature and mitochondria post-rmTBI. In vivo overexpression of PRMT7 using a neuronal specific AAV vector led to restoration of neurovascular coupling, prevented BBB leakage, and promoted mitochondrial respiration, altogether to suggest a protective and functional role of PRMT7 in rmTBI.

A role for protein arginine methyltransferase 7 in repetitive and mild traumatic brain injury.

Mild traumatic brain injury affects the largest proportion of individuals in the United States and world-wide. Pre-clinical studies of repetitive and mild traumatic brain injury (rmTBI) have been limited in their ability to recapitulate human pathology (i.e. diffuse rotational injury). We used the closed-head impact model of engineered rotation acceleration (CHIMERA) to simulate rotational injury observed in patients and to study the pathological outcomes post-rmTBI using C57BL/6J mice. Enhanced cytokine production was observed in both the cortex and hippocampus to suggest neuroinflammation. Furthermore, microglia were assessed via enhanced iba1 protein levels and morphological changes using immunofluorescence. In addition, LC/MS analyses revealed excess glutamate production, as well as diffuse axonal injury via Bielschowsky's silver stain kit. Moreover, the heterogeneous nature of rmTBI has made it challenging to identify drug therapies that address rmTBI, therefore we sought to identify novel targets in the concurrent rmTBI pathology. The pathophysiological findings correlated with a time-dependent decrease in protein arginine methyltransferase 7 (PRMT7) protein expression and activity post-rmTBI along with dysregulation of PRMT upstream mediators s-adenosylmethionine and methionine adenosyltransferase 2 (MAT2) in vivo. In addition, inhibition of the upstream mediator MAT2A using the HT22 hippocampal neuronal cell line suggest a mechanistic role for PRMT7 via MAT2A in vitro. Collectively, we have identified PRMT7 as a novel target in rmTBI pathology in vivo and a mechanistic link between PRMT7 and upstream mediator MAT2A in vitro.

The First Modified Delphi Consensus-Building Exercise on Surgical Ward Rounds in the United Kingdom National Health Service.

BACKGROUND: The ward round is an integral part of everyday surgical practice. It is a complex clinical activity that requires both sound clinical management and communication skills. This study reports the results of a consensus-building exercise on the common aspects of the general surgical ward rounds. METHODS: The consensus-building committee involving a range of stakeholders from 16 United Kingdom (UK) National Health Service trusts took part in this consensus exercise. The members discussed and suggested a series of statements concerning surgical ward round. An agreement of ≥ 70% among members was regarded as a consensus. RESULTS: Thirty-two members voted on 60 statements. There was a consensus on fifty-nine statements after the first round of voting, and one statement was modified before it reached consensus in the second round. The statements covered nine sections: a preparation phase, team allocation, multidisciplinary approach to the ward round, structure of the round, teaching considerations, confidentiality and privacy, documentation, post-round arrangements, and weekend round. There was a consensus on spending time to prepare for the round, a consultant-led round, involvement of the nursing staff, an MDT round at the beginning and end of the week, a minimum of 5 min allocated to each patient, utilisation of a round checklist, afternoon virtual round, and a clear handover and plan for the weekend. CONCLUSION: The consensus committee achieved agreement on several aspects concerning the surgical ward rounds in the UK NHS. This should help improve the care of surgical patients in the UK.

Influence of Pre-operative HbA1c on Bariatric Surgery Outcomes-the Sunderland (UK) Experience.

PURPOSE: UK guidelines recommend an HbA1c < 8.5% prior to elective surgery. Optimisation of pre-operative glycaemic control can be often difficult. Aim to correlate the effect of pre-operative HbA1c on the peri-operative complication rates and whether elective bariatric surgery should be delayed in poorly controlled diabetics. MATERIAL AND METHODS: Retrospective data of consecutive patients who underwent laparoscopic Roux-en-Y gastric bypass, one-anastomosis gastric bypass and laparoscopic sleeve gastrectomy during January 2014 and April 2018. Patients were categorised into group 1, non-diabetics with an HbA1c < 6.5%; group 2, well-controlled diabetics with HbA1c between 6.5 and 8.4%; and group 3, poorly controlled diabetics with HbA1c ≥ 8.5%. Primary outcome was peri-operative complication rates. RESULTS: Group 1 (n = 978), 81.8% female, median (i.q.r.) age 44.0 (34-52) years, median (i.q.r.) BMI 42.0 (38.7-46.7); group 2 (n = 350), 66.3% female, age 51.0 (45-59) years, BMI 41.8 (37.5-46.5); and group 3 (n = 90), 60% female, age 52.0 (45-56) years and BMI 41.4(36.9-44.8). Early complication rates in each group were low, 1.0% vs 1.7% vs 1.1% (p = 0.592). Mean length of stay was 2 days across the groups (p > 0.05). There was no difference in 30-day re-admission rates between groups 2.8%, 2.9% and 3.3% (p = 0.983). At 6 months and 1 year, there was sustained and equal reduction in HbA1c in all groups (p < 0.05). CONCLUSION: Patients undergoing metabolic surgery for poorly controlled diabetes achieve non-inferior peri-operative outcomes. Hence, delaying metabolic surgery in an attempt to optimise diabetic control is not justifiable.

American Association of Immunologists Recommendations for an Undergraduate Course in Immunology.

Identifying the "essential" components of an undergraduate immunology lecture course can be daunting because of the varying postgraduate pathways students take. The American Association of Immunologists Education Committee commissioned an Ad Hoc Committee, representing undergraduate, graduate, and medical institutions as well as the biotechnology community, to develop core curricular recommendations for teaching immunology to undergraduates. In a reiterative process involving the American Association of Immunologists teaching community, 14 key topics were identified and expanded to include foundational concepts, subtopics and examples, and advanced subtopics, providing a flexible list for curriculum development and avenues for higher-level learning. Recommendations for inclusive and antiracist teaching that outline opportunities to meet the needs of diverse student populations were also developed. The consensus recommendations can be used to accommodate various course settings and will bridge undergraduate and graduate teaching and prepare diverse students for subsequent careers in the biomedical field.

Diagnostic Moderators of the Risk-Recidivism Relationship for Offenders with Mental Illness.

Recent research suggests that early onset of criminality is a potential marker for a subgroup of offenders with mental illness (OMI) for whom general risk/need factors are more relevant. The present study examines whether the presence of certain psychiatric diagnostic categories (i.e., Psychotic Disorders, Mood Disorders, Personality Disorders, Substance use Disorders) moderates the prediction of arrest outcomes using Level of Service Inventory-Revised (LSI-R) total scores in an archival sample of N = 179 OMI probationers. Moderator analyses demonstrated that LSI-R total scores predicted arrest outcomes significantly better for those with a diagnosis of Personality Disorder using path and survival analytic methods. Hierarchical regressions using LSI-R subscales as predictors revealed lower pro-criminal Attitudes for Mood Disordered participants, while more severe Criminal History and Family/Marital problems characterized those diagnosed with Personality Disorders. This study adds to the developing literature on subgroups of OMI for whom general risk/need factors are particularly important and highlights personality disturbance as another potential characterizing feature.

Cytochrome c oxidase oxygen reduction reaction induced by cytochrome c on nickel-coordination surfaces based on graphene oxide in suspension.

BACKGROUND: The electrochemical and spectroscopic investigation of bacterial electron-transfer proteins stabilized on solid state electrodes has provided an effective approach for functional respiratory enzyme studies. METHODS: We assess the biocompatibility of carboxylated graphene oxide (CGO) functionalized with Nickel nitrilotriacetic groups (CGO-NiNTA) ccordinating His-tagged cytochrome c oxidase (CcO) from Rhodobacter sphaeroides. RESULTS: Kinetic studies employing UV-visible absorption spectroscopy confirmed that the immobilized CcO oxidized horse-heart cytochrome c (Cyt c) albeit at a slower rate than isolated CcO. The oxygen reduction reaction as catalyzed by immobilized CcO could be clearly distinguished from that arising from CGO-NiNTA in the presence of Cyt c and dithiothreitol (DTT) as a sacrificial reducing agent. Our findings indicate that while the protein content is about 3.7‰ by mass with respect to the support, the contribution to the oxygen consumption activity averaged at 56.3%. CONCLUSIONS: The CGO-based support stabilizes the free enzyme which, while capable of Cyt c oxidation, is unable to carry out oxygen consumption in solution on its own under our conditions. The turnover rate for the immobilized CcO was as high as 240 O2 molecules per second per CcO unit. GENERAL SIGNIFICANCE: In vitro investigations of electron flow on isolated components of bacterial electron-transfer enzymes immobilized on the surface of CGO in suspension are expected to shed new light on microbial bioenergetic functions, that could ultimately contribute toward the improvement of performance in living organisms.

Patient Perspectives on Adherence with Micronutrient Supplementation After Bariatric Surgery.

BACKGROUND: Adherence to post-bariatric surgery nutritional supplements can be poor and is associated with higher micronutrient deficiency rates. There is currently no available study specifically seeking patients' perspectives on the reasons behind poor adherence and how to address it. METHODS: Bariatric surgery patients living in the UK were invited to take part in an anonymous survey on SurveyMonkey®. RESULTS: A total of 529 patients (92.61% females, mean age 47.7 years) took part. Most of these patients had undergone either a Roux-en-Y gastric bypass (63.0%) or sleeve gastrectomy (24.0%). Most of the patients were in full-time (49.0%, n = 260/529) or part-time (15.7%, n = 83/529) employment. Approximately 54.0% (n = 287/529) of the respondents reported having trouble taking all their supplements. Males were significantly more likely to report complete compliance. The most important reported reason for poor compliance was difficulty in remembering (45.6%), followed by too many tablets (16.4%), side effects (14.3%), cost (11.5%), non-prescribing by GP (10.8%), bad taste (10.1%), and not feeling the need to take (9.4%). Patients suggested reducing the number of tablets (41.8%), patient education (25.7%), GP education (24.0%), reducing the cost (18.5%), and more information from a healthcare provider (12.5%) or a pharmacist (5.2%) to improve the compliance. CONCLUSIONS: This study is the first attempt to understand patient perspectives on poor adherence to post-bariatric surgery nutritional recommendation. Patients offered a number of explanations and also provided with suggestions on how to improve it.

Oral Vitamin B12 Supplementation After Roux-en-Y Gastric Bypass: a Systematic Review.

BACKGROUND: Many respectable guidelines recommend lifelong vitamin B12 injections for Roux-en-Y gastric bypass (RYGB) patients in the absence of lack of consensus on the efficacy of oral route of prophylaxis and the appropriate doses needed for this purpose. The purpose of this review was to examine the published English language scientific literature in accordance with PRISMA principles to find out if orally given vitamin B12 is adequate for prophylactic purposes in RYGB patients and the appropriate dosages needed for this purpose if it is. METHODS: We examined the PubMed database for all English language articles examining various doses of oral vitamin B12 supplementation after proximal RYGB in adult patients. The search revealed 19 such articles. RESULTS: The data suggest that oral vitamin B12 supplementation doses of ≤ 15 µg daily are insufficient to prevent deficiency in RYGB patients. Higher supplementation doses show better results and it appears that a dose of 600.0 µg vitamin B12 daily is superior to 350.0 µg daily suggesting an incremental dose-response curve. It further appears that supplementation doses of 1000.0 µg vitamin B12 daily lead to an increase in B12 levels and are sufficient for the prevention of its deficiency in most RYGB patients. CONCLUSION: The review finds that oral supplementation doses of ≤ 15 µg vitamin B12 daily are inadequate for prophylaxis of vitamin B12 deficiency in adult RYGB patients but doses of 1000 µg vitamin B12 daily might be adequate. Future studies need to examine this and even higher oral doses for vitamin B12 supplementation for patients undergoing RYGB.

Impact of biliopancreatic limb length on severe protein-calorie malnutrition requiring revisional surgery after one anastomosis (mini) gastric bypass.

BACKGROUND: One anastomosis (mini) gastric bypass (OAGB) is believed to be more malabsorptive than Roux-en-Y gastric bypass. A number of patients undergoing this procedure suffer from severe protein-calorie malnutrition requiring revisional surgery. The purpose of this study was to find the magnitude of severe protein-calorie malnutrition requiring revisional surgery after OAGB and any potential relationship with biliopancreatic limb (BPL) length. METHODS: A questionnaire-based survey was carried out on the surgeons performing OAGB. Data were further corroborated with the published scientific literature. RESULTS: A total of 118 surgeons from thirty countries reported experience with 47,364 OAGB procedures. Overall, 0.37% (138/36,952) of patients needed revisional surgery for malnutrition. The highest percentage of 0.51% (120/23,277) was recorded with formulae using >200 cm of BPL for some patients, and lowest rate of 0% was seen with 150 cm BPL. These data were corroborated by published scientific literature, which has a record of 50 (0.56%) patients needing surgical revision for severe malnutrition after OAGB. CONCLUSIONS: A very small number of OAGB patients need surgical correction for severe protein-calorie malnutrition. Highest rates of 0.6% were seen in the hands of surgeons using BPL length of >250 cm for some of their patients, and the lowest rate of 0% was seen with BPL of 150 cm. Future studies are needed to examine the efficacy of a standardised BPL length of 150 cm with OAGB.

Perioperative Practices Concerning One Anastomosis (Mini) Gastric Bypass: A Survey of 210 Surgeons.

BACKGROUND: There is currently little evidence available on the perioperative practices concerning one anastomosis/mini gastric bypass (OAGB/MGB) and no published consensus amongst experts. Even the published papers are not clear on these aspects. The purpose of this study was to understand various perioperative practices concerning OAGB/MGB. METHODS: Bariatric surgeons from around the world were invited to participate in a questionnaire-based survey. Only surgeons performing this procedure were included. RESULTS: Two hundred and ten surgeons from 39 countries with a cumulative experience of 68,442 procedures took the survey. Surgeons described a large number of absolute (n = 55) and relative contraindications (n = 59) to this procedure in their practice. Approximately 71.0% (n = 148/208), 70.0% (n = 147/208) and 65.0% (n = 137/209), respectively, routinely perform a preoperative endoscopy, screening for Helicobacter pylori and ultrasound scan of the abdomen. A minority (35.0%, n = 74/208) of the surgeons used a constant bilio-pancreatic limb (BPL) length for all the patients with remaining preferring to tailor the limb length to the patient and approximately half (49.0%, n = 101/206) routinely approximate diaphragmatic crura in patients with hiatus hernia. Some 48.5% (n = 101/208) and 40.0% (n = 53/205) surgeons, respectively, do not recommend routine iron and calcium supplementation. CONCLUSION: This survey is the first attempt to understand a range of perioperative practices with OAGB/MGB. The findings will help in identifying areas for future research and allow consensus building amongst experts with preparation of guidelines for future practice.

Bariatric Surgery in Septuagenarians: a Comparison with <60 Year Olds.

INTRODUCTION: There is reluctance amongst many healthcare professionals to offer bariatric surgery to septuagenarians. There is only one study in the scientific literature specifically describing any experience with this group of patients and none that compares the outcomes in this group with younger patients. METHODS: We retrospectively examined our prospective database to identify all those who were >70 years old at the time of bariatric surgery. This group was then compared with a matched (for sex, body mass index, surgical procedure, and time of surgery) cohort of younger (<60 year old) patients. Information was obtained from our database, case notes, hospital electronic records, by interviewing team members, and from general practitioners. RESULTS: A total of 10 septuagenarians were compared with 10 younger patients (mean age 41 years). There were one early complication and 1 late complication in the over 70 group as opposed to no early complication and 2 late complications in the younger group. There was no mortality or early reoperation in either group. Excess weight loss of 50.4, 67.4, and 74.0% in the >70 age group at 6, 12, and 24 months, respectively, was no different to 51.3, 70.8, and 73.9% in <60 year olds. The effect on the co-morbidity resolution was similar in the two groups. CONCLUSION: In carefully selected septuagenarians, bariatric surgery can be performed with safety and efficacy comparable to those <60 years old.

Understanding Objections to One Anastomosis (Mini) Gastric Bypass: A Survey of 417 Surgeons Not Performing this Procedure.

BACKGROUND: Despite published experience with thousands of patients, the uptake of One Anastomosis/Mini Gastric Bypass (OAGB/MGB) has been less than enthusiastic and many surgeons still harbour objections to this procedure. The purpose of this study was to understand these objections scientifically. METHODS: Bariatric surgeons from around the world were invited to participate in a questionnaire-based survey on SurveyMonkey®. Surgeons already performing this procedure were excluded. RESULTS: Four hundred seventeen bariatric surgeons (from 42 countries) not currently performing OAGB/MGB took the survey. There were 211/414 (50.97%) and 188/414 (45.41%) respondents who expressed concerns that it will lead to an increased risk of gastric and oesophageal cancers respectively. A total of 62/416 (14.9%) and 201/413 (n = 48.6%) surgeons respectively felt that OAGB/MGB was associated with a higher early (30-day) and late complication rate compared to the RYGB. Moreover, 7.8% (n = 32/411) and 16.26% (n = 67/412) of the respondents were concerned that OAGB/MGB carried a higher early (30-day) and late mortality, respectively, in comparison with the RYGB. There were 79/410 (19.27%) and 88/413 (21.3%) respondents who were concerned that OAGB/MGB was not an effective procedure for weight loss and co-morbidity resolution, respectively. A total of 258/411 (62.77%) respondents reported that OAGB/MGB was not approved by their national society as a mainstream bariatric procedure; 51.0% of these surgeons would start performing this procedure if it was. CONCLUSIONS: Surgeons not performing OAGB/MGB cite a number of concerns for not performing this operation. This survey is the first scientific attempt to understand these objections scientifically.

Management of super-super obese patients: comparison between one anastomosis (mini) gastric bypass and Roux-en-Y gastric bypass.

BACKGROUND: Gastric bypass can be technically challenging in super-super obese patients. Both Roux-en-Y gastric bypass (RYGB) and one anastomosis (mini) gastric bypass (OAGB/MGB) have been described in these patients, but direct comparisons are lacking. The purpose of this study was to compare the early outcomes with these two procedures in patients with body mass index (BMI) of ≥60 kg/m2 in our unit. METHODS: We identified all super-super obese patients who underwent either OAGB/MGB or RYGB from our prospectively maintained database. Information was also obtained from the case notes and from hospital computerized records. We obtained data regarding patient demographics, operative details, complications, and weight loss, in both groups, and compared them using standard statistical methods. RESULTS: This study compares our results with 19 OAGB/MGB and 47 RYGB super-super obese patients performed in our unit between October 2012 and June 2015. OAGB/MGB group patients had a significantly higher weight and body mass index. There was no mortality or major complication in either group. There were two late complications in the OAGB/MGB group compared to six in the RYGB group. One patient in the OAGB/MGB group needed conversion to RYGB for persistent reflux symptoms. OAGB/MGB patients achieved a significantly higher EWL of 70.4% at 2 years compared to 57.1% in the RYGB group. The difference between TWL of 44.4 and 33.4%, respectively, was also significant at 2 years. TWL of 43.0 and 29.3%, respectively, in OAGB/MGB and RYGB groups at 18 months was also significantly different, but the difference in EWL at 18 months did not reach significance. CONCLUSION: One anastomosis (mini) gastric bypass yields superior weight loss at 18 and 24 months in comparison with Roux-en-Y gastric bypass in patients with BMI of ≥60 kg/m2. Findings need confirmation in larger randomized studies.

Monitoring of Liver Function Tests after Roux-en-Y Gastric Bypass: An Examination of Evidence Base.

There is no consensus on the monitoring of liver function tests after Roux-en-Y gastric bypass (RYGB). Since the main objective of such monitoring would be to diagnose early those who will eventually develop liver failure after RYGB, we performed a systematic review on this topic. An extensive search of literature revealed only 10 such cases in 6 published articles. It would hence appear that liver failure is a rare problem after RYGB. Routine lifelong monitoring of liver function tests is therefore unnecessary for otherwise asymptomatic individuals. Such monitoring should hence be reserved for high-risk groups, such as patients with liver cirrhosis, those undergoing extended limb/distal RYGB, patients with new illnesses, those abusing alcohol, those on hepatotoxic drugs and those presenting with a surgical complication.

Current status of mini-gastric bypass.

Mini-gastric bypass (MGP) is a promising bariatric procedure. Tens of thousands of this procedure have been performed throughout the world since Rutledge performed the first procedure in the United States of America in 1997. Several thousands of these have even been documented in the published scientific literature. Despite a proven track record over nearly two decades, this operation continues to polarise the bariatric community. A large number of surgeons across the world have strong objections to this procedure and do not perform it. The risk of symptomatic (bile) reflux, marginal ulceration, severe malnutrition, and long-term risk of gastric and oesophageal cancers are some of the commonly voiced concerns. Despite these expressed fears, several advantages such as technical simplicity, shorter learning curve, ease of revision and reversal, non-inferior weight loss and comorbidity resolution outcomes have prompted some surgeons to advocate a wider adoption of this procedure. This review examines the current status of these controversial aspects in the light of the published academic literature in English.

Management of Super-super Obese Patients: Comparison Between Mini (One Anastomosis) Gastric Bypass and Sleeve Gastrectomy.

Management of super-super obese patients poses a particular challenge for bariatric surgeons. Many staged algorithms exist for these patients. Essentially all of these involve a lower-risk procedure like sleeve gastrectomy first before a definitive second-stage procedure like gastric bypass or duodenal switch. This study compares our results with 19 mini (one anastomosis) gastric bypass and 56 sleeve gastrectomy in super-super obese patients. Sleeve gastrectomy patients were significantly older. There was no mortality or major complication in either group. There was no minor complication in mini (one anastomosis) gastric bypass group compared to two in the sleeve gastrectomy group. Mini (one anastomsosis) gastric bypass patients experienced significantly higher weight loss compared to sleeve gastrectomy patients at 6 months, 1 year, and 2 years after surgery.

Small Bowel Limb Lengths and Roux-en-Y Gastric Bypass: a Systematic Review.

There is currently no consensus on the combined length of small bowel that should be bypassed as biliopancreatic or alimentary limb for optimum results with Roux-en-Y gastric bypass. A number of different limb lengths exist, and there is significant variation in practice amongst surgeons. Inevitably, this means that some patients have too much small bowel bypassed and end up with malnutrition and others end up with a less effective operation. Lack of standardisation poses further problems with interpretation and comparison of scientific literature. This systematic review concludes that a range of 100-200 cm for combined length of biliopancreatic or alimentary limb gives optimum results with Roux-en-Y gastric bypass in most patients.