Butyrate and tributyrin reduce LPS-induced inflammatory cytokine production from human visceral fat.

INTRODUCTION: The current obesity crisis has resulted in many people with excess adipose tissue suffering from chronic inflammation. This inflammation is largely due to the release of cytokines and chemokines from visceral fat. The aim of this study was to identify potential anti-inflammatory agents that might alleviate obesity-induced chronic inflammation. METHODS: To identify agents that might alleviate this obesity-induced chronic inflammation we have developed a simple protocol for incubating intact pieces of human visceral adipose tissue in 35 mm tissue culture plates, in the presence of low-dose lipopolysaccharide (LPS) and co-incubating these samples with potential anti-inflammatory agents. RNA-Seq analysis was performed to identify enriched gene expression signatures among the most significantly differentially expressed genes. RESULTS: From this screen, we have identified the short-chain fatty acid (SCFA) sodium butyrate and its triacylglyceride form, tributyrin, as effective agents, significantly reducing the production of LPS-induced inflammatory cytokines and chemokines from all adipose tissue samples tested. As well, these agents appear to be non-toxic at the concentrations tested. RNA-Seq analysis has revealed that IL36γ is one of the most upregulated genes in response to LPS and one of the most downregulated when sodium butyrate is added to human fat samples stimulated with LPS. IL-36γ ELISAs confirmed this holds true at the protein level as well. CONCLUSIONS: These studies suggest that the short-chain fatty acid, sodium butyrate, and its triacylglyceride form, tributyrin, might alleviate the chronic inflammation that is associated with many individuals with obesity.

Biguanides and glucagon like peptide 1 receptor agonists in the amelioration of post liver transplant weight gain; a scoping review of the mechanism of action, safety and efficacy.

Weight gain post-liver transplant can lead to adverse patient outcomes in the post-transplant period. Pharmacotherapy and other measures can be utilised to reduce the burden and occurrence of weight gain in this population. We explored the mechanism of action, safety, and efficacy of these medications, specifically GLP-1 receptor agonists and metformin, focusing on liver transplant patients. This scoping review was conducted in line with the scoping review structure as outlined by the PRISMA guidelines. Metformin and GLP-1 receptor agonists have been observed to be safe and effective in liver transplant patients. Experimental models have found liver-centric weight loss mechanisms in this drug cohort. There is a paucity of evidence about the use of antihyperglycemics in a post-transplant population for weight loss purposes. However, some small studies have shown strong safety and efficacy data. The evidence in relation to using these medications in patients with metabolic syndrome for weight loss warrants further study in a transplant population.

Silver(I)-Catalyzed Synthesis of Cuneanes from Cubanes and their Investigation as Isosteres.

Bridged or caged polycyclic hydrocarbons have rigid structures that project substituents into precise regions of 3D space, making them attractive as linking groups in materials science and as building blocks for medicinal chemistry. The efficient synthesis of new or underexplored classes of such compounds is, therefore, an important objective. Herein, we describe the silver(I)-catalyzed rearrangement of 1,4-disubstituted cubanes to cuneanes, which are strained hydrocarbons that have not received much attention since they were first described in 1970. The synthesis of 2,6-disubstituted or 1,3-disubstituted cuneanes can be achieved with high regioselectivities, with the regioselectivity being dependent on the electronic character of the cubane substituents. A preliminary assessment of cuneanes as scaffolds for medicinal chemistry suggests cuneanes could serve as isosteric replacements of trans-1,4-disubstituted cyclohexanes and 1,3-disubstituted benzenes. An analogue of the anticancer drug sonidegib was synthesized, in which the 1,2,3-trisubstituted benzene was replaced with a 1,3-disubstituted cuneane.

Compressed and Expanded Lattices - Barriers to Spin-State Switching in Mn3+ Complexes.

We report the structural and magnetic properties of two new Mn3+ complex cations in the spin crossover (SCO) [Mn(R-sal2323)]+ series, in lattices with seven different counterions in each case. We investigate the effect on the Mn3+ spin state of appending electron-withdrawing and electron-donating groups on the phenolate donors of the ligand. This was achieved by substitution of the ortho and para positions on the phenolate donors with nitro and methoxy substituents in both possible geometric isomeric forms. Using this design paradigm, the [MnL1]+ (a) and [MnL2]+ (b) complex cations were prepared by complexation of Mn3+ to the hexadentate Schiff base ligands with 3-nitro-5-methoxy-phenolate or 3-methoxy-5-nitro-phenolate substituents, respectively. A clear trend emerges with adoption of the spin triplet form in complexes 1a-7a, with the 3-nitro-5-methoxy-phenolate donors, and spin triplet, spin quintet and thermal SCO in complexes 1b-7b with the 3-methoxy-5-nitro-phenolate ligand isomer. The outcomes are discussed in terms of geometric and steric factors in the 14 new compounds and by a wider analysis of electronic choices of Mn3+ with related ligands by comparison of bond length and angular distortion data of previously reported analogues in the [Mn(R-sal2323)]+ family. The structural and magnetic data published to date suggest a barrier to switching may exist for high spin forms of Mn3+ in those complexes with the longest bond lengths and highest distortion parameters. A barrier to switching from low spin to high spin is less clear but may operate in the seven [Mn(3-NO2-5-OMe-sal2323)]+ complexes 1a-7a reported here which were all low spin in the solid state at room temperature.

A single centre experience of prosthetic joint infection outcomes with outpatient parenteral antimicrobial therapy.

Objectives: Prosthetic joint infection (PJI) is a serious complication following arthroplasties. This study assessed the clinical outcomes, readmission rates and financial impact of PJIs treated with outpatient parenteral antimicrobial therapy (OPAT). Methods: The study used prospectively collected data from the OPAT patient database at a tertiary care Irish hospital for PJI cases managed between 2015 and 2020. Data was analyzed using IBM-SPSS. Results: Forty-one patients with PJIs were managed via OPAT over five years, with median age of 71.6 years. Median duration of OPAT was 32 days. Hospital readmission occurred in 34% of cases. Reasons for readmission included progression of infection in 64.3%, unplanned reoperation in 21.4% and planned admission for joint revision in 14.3%. Type 2 Diabetes Mellitus (T2DM) was found to have a statistically significant association with unplanned readmission (OR 8.5, CI 95% 1.1-67.6; p < 0.01). OPAT saved a mean of 27.49 hospital-bed days per patient. 1,127 bed days were saved in total, estimating a total savings of 963,585 euros and median savings of 26,505 euros. Conclusions: The readmission rate observed was comparable to international data. Most readmissions were related to primary infections rather than due to OPAT-specific complications. Our main findings were that patients with PJIs can be safely managed via OPAT, and the finding of association between T2DM and increased risk of readmission.

Conservative surgery versus colorectal resection for endometriosis with rectal involvement: a systematic review and meta-analysis of surgical and long-term outcomes.

PURPOSE: The optimal surgical approach for removal of colorectal endometrial deposits is unclear. Shaving and discoid excision of colorectal deposits allow organ preservation but risk recurrence with associated functional issues and re-operation. Formal resection risks potential higher complications but may be associated with lower recurrence rates. This meta-analysis compares peri-operative and long-term outcomes between conservative surgery (shaving and disc excision) versus formal colorectal resection. METHODS: The study was registered with PROSPERO. A systematic search was performed on PubMed and EMBASE databases. All comparative studies examining surgical outcomes in patients that underwent conservative surgery versus colorectal resection for rectal endometrial deposits were included. The two main groups (conservative versus resection) were compared in three main blocks of variables including group comparability, operative outcomes and long-term outcomes. RESULTS: Seventeen studies including 2861 patients were analysed with patients subdivided by procedure: colorectal resection (n = 1389), shaving (n = 703) and discoid excision (n = 742). When formal colorectal resection was compared to conservative surgery there was lower risk of recurrence (p = 0.002), comparable functional outcomes (minor LARS, p = 0.30, major LARS, p = 0.54), similar rates of postoperative leaks (p = 0.22), pelvic abscesses (p = 0.18) and rectovaginal fistula (p = 0.92). On subgroup analysis, shaving had the highest recurrence rate (p = 0.0007), however a lower rate of stoma formation (p < 0.00001) and rectal stenosis (p = 0.01). Discoid excision and formal resection were comparable. CONCLUSION: Colorectal resection has a significantly lower recurrence rate compared to shaving. There is no difference in complications or functional outcomes between discoid excision and formal resection and both have similar recurrence rates.

Postoperative considerations based on graft type after anterior cruciate ligament reconstruction a narrative review.

Background and Objective: Graft selection for anterior cruciate ligament reconstruction (ACLR) affects rehabilitation throughout the course of postoperative care. Methods: A search of PubMed and EBSCO was performed and abstracts independently reviewed by two authors. This search was also supplemented with additional evidence relevant to each phase of ACLR rehabilitation. Key Content and Findings: Direct implications of graft type on clinical decisions vary throughout treatment phases, transitioning from potential differences in acute postoperative pain management immediately after surgery to facilitating sufficient and appropriate lower extremity loading in subsequent weeks. Regardless of graft type, surgical limb weakness persists throughout the course of rehabilitation; however, harvest site selection for autografts contributes to disproportionate weakness of the harvested muscle group and the potential for surgical-induced tendinopathy. In later phases of rehabilitation, as athletes are transitioning into return to sport (RTS), treatment decisions and protocols are less affected by graft type but expectations for meeting clinical milestones and the time required to do so does differ between graft types. Conclusions: Targeted strengthening interventions to address muscle weakness following graft harvest in autografts should be continued throughout the rehabilitation process. Lingering deficits in quadriceps strength symmetry may also influence time to meet progression and RTS criteria following graft harvest from the extensor mechanism.

Gold(I)-Catalyzed Nucleophilic Allylation of Azinium Ions with Allylboronates.

Gold(I)-catalyzed nucleophilic allylations of pyridinium and quinolinium ions with various allyl pinacolboronates are reported. The reactions are completely selective with respect to the site of the azinium ion that is attacked, to give various functionalized 1,4-dihydropyridines and 1,4-dihydroquinolines. Evidence suggests that the reactions proceed through nucleophilic allylgold(I) intermediates formed by transmetalation from allylboronates. Density functional theory (DFT) calculations provided mechanistic insight.

A systematic review and meta-analysis comparing surgical and oncological outcomes of upper rectal, rectosigmoid and sigmoid tumours.

AIM: Management paradigms for tumours from the sigmoid colon to the lower rectum vary significantly. The upper rectum (UR) represents the transition point both anatomically and in treatment protocols. Above the UR is clearly defined and managed as colon cancer and below is managed as rectal cancer. This study compares outcomes between sigmoid, rectosigmoid and UR tumours to establish if differences exist in operative and oncological outcomes. METHODS: Electronic databases were searched for published studies with comparative data on peri-operative and oncological outcome for upper rectal and sigmoid/rectosigmoid (SRS) tumours treated without neoadjuvant radiation. The search adhered to PRISMA guidelines (Preferred Reporting Items in Systematic Reviews and Meta-analyses) guidelines. Data was combined using random-effects models. RESULTS: Seven comparative series examined outcomes in 4355 patients. There was no difference in ASA grade (OR, 1.28; 95% CI, 0.99-1.67; P = 0.06), T3/T4 tumours (OR, 1.24; 95% CI, 0.95-1.63; P = 0.12), or lymph node positivity (OR, 0.97; 95% CI, 0.70-1.36; P = 0.87). UR cancers had higher rates of operative morbidity (OR, 0.72; 95% CI, 0.55-0.93; P = 0.01) and anastomotic leak (OR, 0.47; 95% CI, 0.31-0.71; P = 0.0004). There was no difference in local recurrence (OR, 0.63; 95% CI, 0.37-1.08; P = 0.10). SRS tumours had lower rates of distant recurrence (OR, 0.83; 95% CI, 0.68-1.0; P = 0.05). Rectosigmoid operative and cancer outcomes were closer to UR than sigmoid. CONCLUSIONS: Based on existing data, UR and rectosigmoid tumours have higher morbidity, leak rates and distant recurrence than more proximal tumours.

Exploring Sports Nutrition Knowledge in Elite Gaelic Footballers.

Nutrition intake plays a crucial role in improving athletic performance, enhancing adaptations to training, and augmenting recovery from exercise. However, research has reported that Gaelic footballers consistently fail to meet energy and carbohydrate recommendations. Sports nutrition knowledge (SNK) can influence the dietary intake of athletes, and therefore has the potential to have a significant impact on athletic performance. The aim of this study was to investigate the current level of SNK in elite Gaelic footballers (n = 100). An online version of the Nutrition for Sport Knowledge Questionnaire (NSKQ) was used to assess sports SNK. The overall mean SNK scores for Gaelic footballers and practitioners were 47.6 ± 12.3% and 78.1 ± 8.3%, respectively. There were no differences in knowledge between age groups, education level or divisional status. The top three sources of nutrition information identified by participants were team dietitian/nutritionists (84.0%), athletic trainers/strength and conditioning coaches (73%), and social media (37%). The results show that there is a major gap in the SNK of Gaelic footballers, while practitioners demonstrated a promising SNK, that could support Gaelic footballers. There is a need for development of interventions and knowledge transfer partnerships, including more effective methods of educating Gaelic footballers and translating sports nutrition principles to players. Developing appropriate nutritional education strategies using online resources and mobile applications could help to improve nutritional knowledge and practice of Gaelic footballers.

The Effects of Pre-Game Carbohydrate Intake on Running Performance and Substrate Utilisation during Simulated Gaelic Football Match Play.

BACKGROUND: Previous research has reported that elite Gaelic football players' carbohydrate (CHO) intakes are sub-optimal, especially, in the lead up to competitive matches. Despite clear decrements in running performance across elite Gaelic football matches, there are no studies that have investigated nutrition interventions on match-related Gaelic football performance. The aim of this study was to determine whether a higher-CHO diet in line with sports nutrition guidelines can improve Gaelic football-related performance compared to lower CHO intakes previously observed in Gaelic footballers. METHODS: Twelve Gaelic football players completed a Gaelic football simulation protocol (GFSP) on two occasions after consuming a high-CHO diet (7 g·kg-1) (HCHO) or an energy-matched lower-CHO diet (3.5 g·kg-1) (L-CHO) for 48 h. Movement demands and heart rate were measured using portable global positioning systems devices. Countermovement jump height (CMJ) and repeated-sprint ability (RSA) were measured throughout each trial. Expired respiratory gases were collected throughout the trial using a portable gas analyser. Blood samples were taken at rest, half-time, and post-simulation. RESULTS: There was no significant difference in total distance (p = 0.811; η2 = 0.005) or high-speed running distance (HSRD) covered between both trials. However, in the second half of the HCHO trial, HSRD was significantly greater compared to the second half of the LCHO trial (p = 0.015). Sprint distance covered during GFSP was significantly greater in HCHO (8.1 ± 3.5 m·min-1) compared with LCHO (6.4 ± 3.2 m·min-1) (p = 0.011; η2 = 0.445). RSA performance (p < 0.0001; η2 = 0.735) and lower body power (CMJ) (p < 0.0001; η2 = 0.683) were significantly greater during the HCHO trial compared to LCHO. Overall CHO oxidation rates were significantly greater under HCHO conditions compared to LCHO (3.3 ± 0.5 vs. 2.7 ± 0.6 g·min-1) (p < 0.001; η2 = 0.798). Blood lactate concentrations were significantly higher during HCHO trial versus LCHO (p = 0.026; η2 = 0.375). There were no significant differences in plasma glucose, non-esterified fatty acids (NEFAs), and glycerol concentration between trials. In both trials, all blood metabolites were significantly elevated at half-time and post-trial compared to pre-trial. CONCLUSION: These findings indicate that a higher-CHO diet can reduce declines in physical performance during simulated Gaelic football match play.

Rhodium-catalyzed arylative cyclization of alkynyl malonates by 1,4-rhodium(i) migration.

The synthesis of functionalized 1-tetralones by the rhodium(i)-catalyzed reaction of alkynyl malonates with arylboronic acids is described. These arylative cyclizations proceed via an alkenyl-to-aryl 1,4-Rh(i) migration as a key step. Preliminary results of an enantioselective variant of these reactions are also presented.

Single-Stage Multiple-Ligament Knee Reconstructions for Sports-Related Injuries: Outcomes in 194 Patients.

BACKGROUND: Outcomes after sports-related multiple-ligament knee reconstructions are limited. PURPOSE: To evaluate outcomes after single-stage surgical treatment of sports-related multiple-ligament knee injuries and to compare outcomes after anterior cruciate ligament (ACL)-based and posterior cruciate ligament (PCL)-based multiple-ligament knee reconstructions. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Skeletally mature patients with at least 2 major knee ligaments torn during a sporting activity that required surgery with a minimum of 2 years' follow-up were included. The Lysholm score, Tegner activity scale, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and 12-Item Short Form Health Survey Physical Component Summary were collected preoperatively and at a minimum of 2 years' follow-up. Clinical data, including range of motion and knee stability, were also recorded at final follow-up. RESULTS: A total of 276 patients with multiple-ligament knee injuries incurred during sport participation from 2010 to 2016 were identified. Of the 276 patients, 194 (70.5%) had complete follow-up at a mean 3.5 years (range, 2-8 years). There was a significant improvement in all outcome scores as compared with the preoperative scores (P < .001 for all scores). The median (first and third quartiles) Tegner activity score improved from 1 (0, 2) preoperatively to 6 (4, 7) postoperatively. Significant improvements were from 41 (22, 57) to 90 (78, 95) and 44 (24, 60) to 3 (1, 8) for median Lysholm and WOMAC scores, respectively. There was no significant difference in postoperative outcome scores between patients treated in the acute and chronic phases. Furthermore, there was no significant difference between PCL- and ACL-based multiple-ligament knee injuries. Eighteen (9.3%) patients developed arthrofibrosis requiring reintervention surgery. CONCLUSION: These results demonstrated that single-stage anatomic-based knee ligament reconstructions with immediate postoperative rehabilitation in the setting of sports-related multiligament injuries yielded significantly improved outcomes irrespective of the ligament injury pattern. In addition, there was no difference in outcomes between ACL- and PCL-based injuries in the setting of sports-related multiligament injuries.

The Warrior Athlete Part 2-Return to Duty in the US Military: Advancing ACL Rehabilitation in the Tactical Athlete.

Rehabilitation following an anterior cruciate ligament reconstruction is a crucial component of the healing and recovery process and full return to duty/play in the tactical modern-day warfighter. The burden of anterior cruciate ligament injuries and subsequent loss of readiness in these military warfighters highlights one of the most significant gaps in musculoskeletal injury care today. Emphasis must be placed on early weight-bearing and range of motion (ROM), namely in this athlete population, to best facilitate a timely care and recovery process. Preoperative rehabilitation should commence immediately following the diagnosis of an anterior cruciate ligament tear, because one of the best predictors of postoperative ROM is preoperative ROM. Recent advances in rehabilitation technology such as Alter-G treadmills, inertial measurement units, and blood flow restriction therapy systems, have demonstrated success in the early rehabilitation of tactical athletes. Alter-G treadmills allow for early weight-bearing with reduced impact and progression in ROM following operative management, while inertial measurement units have been applied to tailoring rehabilitation protocols specifically to an athlete's unique functional deficits. When used in conjunction with a fined tune rehabilitation protocol, implemented by a well versed clinical team, these treatment techniques can greatly expedite the return to duty process and limit long-term complications.

Dietary Intake and Energy Expenditure Assessed during a Pre-Season Period in Elite Gaelic Football Players.

There is currently a lack of research into the energy demands and associated nutritional intakes of elite Gaelic football players during the pre-season period, which is a crucial time of year for physical development. The aim of the current study was to investigate the dietary intake and energy expenditure (EE) of elite Gaelic football players during a typical pre-season week. Over a seven-day period, which included four training days and three rest days, dietary intake (validated self-reported estimated food diary) and EE (Sensewear Pro armband) were recorded in 18 male players from a single elite inter-county Gaelic football team. Average energy intake (EI) (3283 ± 483 kcal) was significantly (p = 0.002) less than average EE (3743 ± 335 kcal), with a mean daily energy deficit of -460 ± 503 kcal. Training days elicited the greatest deficits between intake and expenditure. The mean carbohydrate (CHO) intake was 3.6 ± 0.7 g/kg/day, protein intake was 2.1 ± 0.5 g/kg/day, and fat intake was 1.6 ± 0.2 g/kg/day. These findings indicate that the dietary practices of the sampled players were inadequate to meet EE and CHO recommendations. Training days are of particular concern, with the players not altering energy and CHO intake to encounter increased energy demands. Education on nutritional strategies for elite Gaelic footballers should be considered in relation to training demands to avoid detriments to performance and health.

The use of columns of the zeolite clinoptilolite in the remediation of aqueous nuclear waste streams.

Mud Hills clinoptilolite has been used in an effluent treatment plant (SIXEP) at the Sellafield nuclear reprocessing site. This material has been used to remove 134/137Cs and 90Sr successfully from effluents for 3 decades. Samples of the zeolite have been tested in column experiments to determine their ability to remove radioactive Cs+ and Sr2+ ions under increasing concentrations of competing ions, Ca2+, Mg2+, Na+ and K+. These ions caused increased elution of Cs+ and Sr2+. Ca2+, Mg2+ and K+ were more effective competitors than Na+. For Na+, it was found that if concentration was reduced, then column performance recovered rapidly.

Blood Flow Restriction Therapy After Knee Surgery: Indications, Safety Considerations, and Postoperative Protocol.

Blood flow restriction (BFR) training involves occluding venous outflow while maintaining arterial inflow by the application of an extremity tourniquet after surgery. BFR ultimately reduces oxygen delivery to muscle cells, similar to an anaerobic environment, and allows patients to exercise with low resistance and stimulates muscle hypertrophy and strength using heavy resistance. Thus orthopaedic surgeons and physical therapists are incorporating this type of training into their postoperative rehabilitation protocols, particularly after injuries or surgical procedures about the knee joint. The purpose of this Technical Note is to describe a BFR clinical application technique and to report on the indications, safety considerations, and postoperative knee surgery rehabilitation protocols for BFR.

The Role of Blood Flow Restriction Therapy Following Knee Surgery: Expert Opinion.

Blood flow restriction (BFR) therapy is becoming increasingly popular in musculoskeletal injury rehabilitation. In particular, this form of therapy is being utilized more often in the postoperative setting following knee surgery, including anterior cruciate ligament reconstruction. BFR therapy provides patients and clinicians an alternative treatment option to standard muscle strengthening and hypertrophy guidelines in the setting of postoperative pain, weakness, and postoperative activity restrictions that contribute to muscle atrophy. The ability to complete exercise in a low load environment and achieve similar physiological adaptations as high-intensity strength training makes this modality appealing. With poor patient-related outcomes associated with continued muscle atrophy, pain, and muscle weakness, some researchers have investigated BFR training postoperatively following arthroscopic knee surgery with promising results. However, owing to the current paucity of research studies, inconsistency among reported protocols, and mixed results, it may be some time before a mass adoption of BFR therapy is made into the world of orthopaedic rehabilitation. Although the current data is inconclusive, we choose to utilize BFR in postoperative knee patients, regardless of weight-bearing status, for whom maintenance of existing muscle mass or improvement of decreased postoperative strength levels is important. Therefore, the purpose of this expert opinion is to review the background of BFR, describe the clinical evidence of BFR following knee surgery, and report the authors' current recommendations for application of BFR postoperatively.

POST-OPERATIVE CRITERION BASED REHABILITATION OF ACL REPAIRS: A CLINICAL COMMENTARY.

The anterior cruciate ligament (ACL) is the most commonly reconstructed ligament of the knee. Most often, the goal of surgical reconstruction is to recreate stability within the knee and prevent joint degeneration. To date, clinical studies have not demonstrated the ability of various reconstruction techniques in establishing complete knee stability when comparing rates of osteoarthritis. Rates of osteoarthritis commonly resemble those of knees which have not be reconstructed and in this light, may not demonstrate a successful outcome. As modern medicine continues to develop and in the understanding of underlying biological processes grows, some surgeons have turned their attention back to an ACL repair technique. The purpose of this clinical commentary is to discuss the parameters associated with a phase progression for an isolated ACL repair. Physiological healing time frames, along with objective clinical assessment, following a criterion-based progression is described in accordance with post-operative healing parameters to serve as a reference for a rehabilitation specialist. LEVEL OF EVIDENCE: 5.