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OBJECTIVE: Selective androgen receptor modulators (SARMs) are potential treatments for ameliorating age-related physical dysfunctions caused by sarcopenia, cachexia and chronic illnesses such as cancer. The purpose of this systematic review is to analyse the effect of SARMs on physical performance and body and evaluate their safety profile. METHODS: A systematic review search criteria following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was performed in three databases for studies reporting physical parameter outcomes after SARM intervention. Study variables included title, author, publication date, study year, number of patients, dosage, mean age, mean follow-up time, pre and post-intervention outcomes and rates of complications. RESULTS: Nine studies, including 970 patients with a mean age of 57.1 years (35.3-75.9) and a mean follow-up of 80 days (14-180), were included. Six SARMs were analysed: LGD-4033, PF-06260414, GSK2881078, GTx-024, MK-0773 and OPK-88004. Mean pre-intervention stair climbing power (five studies), one repetition maximum leg press (four studies) and short physical performance battery (SPPB) score (two studies), lean body mass (seven studies) and fat mass (five studies) were 352.24 W (69.79-678.7), 1822.77 N (1176.8-2407.3), 9.15 (7.95-9.9), 49.46 kg (30.94-63.9) and 21.99 kg (13.3-33), respectively. Mean post-intervention values were 315.16 W (89.46-525.73 W), 2191.27 N (1375.87-2462.9 N), 9.79 (8.88-10.4), 50.86 kg (31.02-67.29) and 21.85 kg (12.54-32.16), respectively. CONCLUSION: SARMs have a positive effect on physical performance and body composition and are associated with moderate rates of mild to moderate adverse effects (AEs) and a low rate of severe AEs.

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Nicotinamide adenine dinucleotide (NAD+) is essential in the proper function of many essential cellular processes in the human body. The purpose of this review is to investigate the effect of nicotinamide mononucleotide (NMN), a NAD+ precursor, on physical performance and evaluate the safety profile of supplementation. A systematic review search criteria following the guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was performed in four databases for randomized controlled trials on NMN supplementation. Study variables included title, author, publication date, study year, number of patients, dosage, mean age, mean follow-up time, pre- and post-intervention reported outcomes, and rates of complications. Ten studies, including 437 patients, with a mean age of 58.0 years (35.1 to 81.1 years) and a mean follow-up time of 9.6 weeks (4 to 12 weeks) were included in this study. NMN dosages ranged from 150 to 1200 mg/day. Mean pre-intervention grip strength (two studies) and skeletal mass index (two studies) were 29.9 kilograms (kg) (range: 21.4-40.1 kg) and 7.4 kg/m2 (range: 6.9-7.65 kg/m2), respectively. Mean post-intervention grip strength and skeletal mass index were 30.5 kg (range: 21.7-41.9 kg) and 7.4 kg/m2 (6.8-7.64 kg/m2), respectively. There were no serious adverse effects observed. Moreover, of the reported side effects, they were determined to be independent of NMN supplementation. Therefore, patients taking NMN supplementation demonstrated non-significantly improved physical performance parameters. NMN is well tolerated with no serious adverse effects observed.

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Background  Orthopedic surgery is one of the most competitive specialties to match into a residency. With a plethora of qualified applicants and the subjective nature of matching into any residency program, it can be difficult to accurately assess the chances of successfully matching into orthopedic surgery and the types of programs an applicant will match into. The purpose of this study is to compare the types of programs that students from medical schools with and without home programs match. Methods This was a five-year retrospective study (2019 to 2023) analyzing 155 United States Doctor of Medicine (M.D.) programs and their orthopedic residency-matched students. Of the 155 programs, 40 were excluded from the study due to the lack of obtainable data. For each medical school, we analyzed several variables: the presence of a home program, the total number of orthopedic residency matches, residency program matches, and residency program affiliation (academic, community, university-affiliated community-based, military). Results Of the 2066 total matched applicants from institutions with home programs, 1508 (73%) matched into academic centers, 315 (15.3%) into university-affiliated community programs, 172 (8.3%) into community programs, and 71 (3.4%) into military programs. In contrast, of the 219 total matched applicants from institutions without home programs (orphan applicants), 144 (67.8%) matched into academic programs, 36 (16.4%) into university-affiliated community programs, 28 (12.8%) into community programs, and 11 (5%) into military programs. Conclusion A greater proportion of students from institutions with home programs matched into academic centers compared to orphan applicants (73% vs. 65.8%). A greater proportion of orphan applicants matched into community programs (12.8% vs. 8.3%).

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INTRODUCTION: Between 1994 and 2014, despite an increase in applicants, successful matches into general surgery (GS) decreased by 13%. We aim to (1) understand the trends in competitiveness for a GS residency, and ascertain the associations between (2) geographical distribution and (3) research experiences on matching. METHODS: National Resident Matching Program data (2013-2022) were analyzed for (1) annual positions and matches, (2) United States Medical Licensing Examination scores, and (3) research experiences. Geographical locations of general surgery residency programs (GSRPs) for matched US seniors were obtained from medical school websites and through contacting institutions. Distances between medical schools and respective matches were assessed for the proportion of students matching within 100 miles, in the same state or same region, or in a different geographical region than their medical school. RESULTS: Of 28,690 applicants, 15,242 (53.12%) matched into a GS residency. Matched GS applicants had higher United States Medical Licensing Examination scores compared to applicants who matched in Emergency Medicine and Family Medicine (P < 0.001). US Medical Doctor (MD) match rates into GS were lower compared to Neurosurgery (P < 0.01), possibly due to competition from non-US MD applicants within GS. More applicants matched into GSRPs in the same region as their medical school, with 14% matching into home programs or within the same state as their medical school. CONCLUSIONS: Higher board examination scores and research participation are associated with successful matches. GS competition from non-US MDs may be driving the match rates for US MDs lower. More than half of students matched into GSRPs in the same region as their medical school.

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ABSTRACT: Physical Medicine and Rehabilitation (PM&R) has rapidly been garnering interest as healthcare increases the emphasis on rehabilitation and management for acute and chronic diseases. This study analyzes recent geographical trends of PM&R residents via PM&R residents from 2019 to 2023 which were identified from publicly available data. The relative distribution from medical school to residency, medical school to preliminary program, and preliminary program to residency were analyzed. These locations were categorized as within 100 miles, same state, same region, or different region. Odds ratio (OR) were calculated for the aforementioned relative locations with respect to the presence of a home residency program. A total of 1836 residents were included. The majority of residents (51%) stayed within the same region as their medical school. Residents from medical schools with a home program were more likely to stay within 100 miles (OR: 3.64), the same state (OR: 3.19), and same region (OR: 2.56). Overall, PM&R residents are likely to stay within the same region as their medical school and preliminary year. Additionally, the presence of a home program significantly increases the odds of matching within 100 miles, same state, and same region.

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BACKGROUND: As of 2022, patient adherence to postoperative guidelines can reduce the risk of complications by up to 52.4% following laparoscopic abdominal surgery. With the availability of various preoperative education interventions (POEIs), understanding which POEI results in improvement in patient outcomes across the procedures is imperative. OBJECTIVE: This study aims to determine which POEI could be the most effective on patient outcomes by systematically reviewing all the POEIs reported in the literature. METHODS: In total, 4753 articles investigating various POEIs (eg, videos, presentations, mobile apps, and one-on-one education or coaching) were collected from the PubMed, Embase, and Scopus databases. Inclusion criteria were adult patients undergoing abdominal laparoscopic surgery, randomized controlled trials, and studies that provided postoperative outcomes. Exclusion criteria included studies not published in English and with no outcomes reported. Title and abstract and full-text articles with POEI randomized controlled studies were screened based on the above criteria through a blinded, dual review using Covidence (Veritas Health Innovation). Study quality was assessed through the Cochrane Risk of Bias tool. The included articles were analyzed for educational content, intervention timing, intervention type, and postoperative outcomes appropriate for a particular surgery. RESULTS: Only 17 studies matched our criteria, with 1831 patients undergoing laparoscopic cholecystectomy, bariatric surgery (gastric bypass and gastric sleeve), and colectomy. In total, 15 studies reported a statistically significant improvement in at least 1 patient postoperative outcome. None of these studies were found to have an overall high risk of bias according to Cochrane standards. In total, 41% (7/17) of the included studies using direct individual education improved outcomes in almost all surgery types, while educational videos had the greatest statistically significant impact for anxiety, nausea, and pain postoperatively (P<.01). Direct group education demonstrated significant improvement in weight, BMI, exercise, and depressive symptoms in 33% (2/6) of the laparoscopic gastric bypass studies. CONCLUSIONS: Direct education (individual or group based) positively impacts postoperative laparoscopic surgery outcomes. TRIAL REGISTRATION: PROSPERO CRD42023438698; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=438698.

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There exists a considerable amount of evidence regarding short-term outcomes of shoulder arthroscopy in athletes; however, mid- to long-term data are limited. Therefore, the purpose of this review is to evaluate studies assessing mid- to long-term outcomes and rates of return to sport in athletes undergoing primary shoulder arthroscopy. A search for the systematic review was performed in PubMed, Scopus, and Embase on 14 March 2023. Study parameters, as well as their respective outcomes, were described in detail and compiled into diagrams. Five studies were included, which contained data on a total of 307 shoulders in patients with mean ages ranging from 20.3 to 26.9 years and mean follow-up times ranging from 6.3 to 14 years. The arthroscopic Bankart repair was the primary surgical intervention performed in all five studies. The overall rate of return to sport was 84% (range, 70-100%) across the studies. The rate of return to sport at pre-injury level was 65.2% (range, 40-82.6%) across four studies. The overall rate of recurrent instability was 17.3%, with redislocation specifically occurring in 13.7% of patients across all studies. The overall rate of revision surgery was 11.1%. Athletes who underwent primary shoulder arthroscopy demonstrated favorable outcomes and a high rate of RTS at a minimum follow-up of 5 years. However, rates of recurrent instability, redislocation, and revision surgery occurred at less than favorable numbers, which emphasizes the importance of proper patient selection when considering candidates for arthroscopic versus open repairs.

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Functional nucleic acids lose activity when their sequence is prepared in the backbone architecture of a different genetic polymer. The only known exception to this rule is a subset of aptamers whose binding mechanism involves G-quadruplex formation. We refer to such examples as transliteration-a synthetic biology concept describing cases in which the phenotype of a nucleic acid molecule is retained when the genotype is written in a different genetic language. Here, we extend the concept of transliteration to include nucleic acid enzymes (XNAzymes) that mediate site-specific cleavage of an RNA substrate. We show that an in vitro selected 2'-fluoroarabino nucleic acid (FANA) enzyme retains catalytic activity when its sequence is prepared as α-l-threofuranosyl nucleic acid (TNA), and vice versa, a TNA enzyme that remains functional when its sequence is prepared as FANA. Structure probing with DMS supports the hypothesis that FANA and TNA enzymes having the same primary sequence can adopt similarly folded tertiary structures. These findings provide new insight into the sequence-structure-function paradigm governing biopolymer folding.

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The discovery of synthetic genetic polymers (XNAs) with catalytic activity demonstrates that natural genetic polymers are not unique in their ability to function as enzymes. However, all known examples of in vitro selected XNA enzymes function with lower activity than their natural counterparts, suggesting that XNAs might be limited in their ability to fold into structures with high catalytic activity. To explore this problem, we evaluated the catalytic potential of FANAzyme 12-7, an RNA-cleaving catalyst composed entirely of 2'-fluoroarabino nucleic acid (FANA) that was evolved to cleave RNA at a specific phosphodiester bond located between an unpaired guanine and a paired uracil in the substrate recognition arm. Here, we show that this activity extends to chimeric DNA substrates that contain a central riboguanosine (riboG) residue at the cleavage site. Surprisingly, FANAzyme 12-7 rivals known DNAzymes that were previously evolved to cleave chimeric DNA substrates under physiological conditions. These data provide convincing evidence that FANAzyme 12-7 maintains the catalytic potential of equivalent DNAzymes, which has important implications for the evolution of XNA catalysts and their contributions to future applications in synthetic biology.

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