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Nutrition and resilience are linked, though it is not yet clear how diet confers stress resistance or the breadth of stressors that it can protect against. We have previously shown that transiently restricting an essential amino acid can protect Drosophila melanogaster against nicotine poisoning. Here, we sought to characterize the nature of this dietary-mediated protection and determine whether it was sex, amino acid and/or nicotine specific. When we compared between sexes, we found that isoleucine deprivation increases female, but not male, nicotine resistance. Surprisingly, we found that this protection afforded to females was not replicated by dietary protein restriction and was instead specific to individual amino acid restriction. To understand whether these beneficial effects of diet were specific to nicotine or were generalizable across stressors, we pre-treated flies with amino acid restriction diets and exposed them to other types of stress. We found that some of the diets that protected against nicotine also protected against oxidative and starvation stress, and improved survival following cold shock. Interestingly, we found that a diet lacking isoleucine was the only diet to protect against all these stressors. These data point to isoleucine as a critical determinant of robustness in the face of environmental challenges.

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This systematic review and meta-analysis compare the incidences of complications, reoperations and hardware removal between anterior and dorsal plating after corrective osteotomy for dorsally angulated distal radial malunions. A total of 403 patients were included; 253 patients underwent anterior corrective osteotomy and 150 underwent dorsal corrective osteotomy. Mean follow-up was 30 months. Anterior plating was associated with fewer reoperations (9% vs. 28%), less hardware removal (3% vs. 18%) and comparable major complications (5% vs. 6%) compared to dorsal plating. The adjusted model showed a significant reduction (approximately 85%) in the odds of reoperation and hardware removal in the anterior group. There was no difference in major or minor complications between the groups. Surgeons should be fully aware of the increased risks when using dorsal plate fixation after corrective osteotomy for dorsally angulated distal radial malunions.

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BACKGROUND: Delayed union and nonunion of the scaphoid is a common complication often requiring surgical reconstruction and bone grafting. Our goal was to systematically assess the healing time and clinical outcomes following arthroscopic-assisted versus open non-vascularized bone grafting of the scaphoid. METHODS: A comprehensive search of the MEDLINE, Embase, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central databases was completed from inception to September 2023. We included randomized trials and observational studies that reported outcomes following scaphoid delayed union/nonunion comparing arthroscopic-assisted vs. open non-vascularized bone grafting. Two reviewers independently extracted data and assessed the risk of bias. One investigator assessed certainty of evidence and a senior investigator confirmed the assessment. We pooled effects using random-effects models, when possible, for all outcomes reported by more than 1 study. RESULTS: Overall, 26 studies and 822 patients were included in the study. Very low certainty evidence demonstrated that arthroscopic-assisted surgery may decrease healing time compared to open surgery (weighted mean difference [WMD] -7.8 weeks; 95%CI -12.8 to -2.8). Arthroscopic bone grafting did not result in an improvement in union rate (relative risk 1.01; 95%CI 0.9 to 1.09). The pooled data in arthroscopic graft group showed mean time to union of 11.4 weeks (95%CI: 10.4 to 12.5) with union rate of 95% (95%CI 91-98%). A single comparative study reported very low certainty evidence that arthroscopy-assisted vs. open surgery may not have an effect on pain relief (MD 0 cm, 95%CI -0.4 to 0.5 on VAS 10 cm for pain) or improving function (MD -1.2, 95% CI -4.8 to 2.3 on 100 points DASH). CONCLUSION AND FUTURE DIRECTIONS: Our results suggest that arthroscopic-assisted non-vascularized bone grafting may be associated with improved average weeks to heal in comparison with open surgery for scaphoid delayed union/nonunion reconstruction with overall comparable union rates. There is insufficient evidence to assess the effects of arthroscopic-assisted reconstruction on union rate, time to union, and patient-reported outcomes in patients with other important nonunion characteristics such as established humpback deformity.

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Purpose This systematic review summarizes the existing evidence on treatment options and outcomes for partial scapholunate interosseous ligament (pSLIL) injuries. Methods A systematic electronic search of Medline, Embase, and CINAHL was performed from inception through to February 13, 2022. All primary research articles addressing the treatment of pSLIL tears were eligible for inclusion regardless of timing of surgery, surgical technique, or rehabilitation. The PRISMA Checklist guided the reporting and data abstraction. Descriptive statistics and forest plots are presented. Results A total of 14 studies with 342 patients were included for analysis. Treatments were categorized into four groups: electrothermal shrinkage (ES), arthroscopic capsuloplasty (AC), open capsulodesis (OC), and no treatment (NT). There were five studies in the ES group ( N = 69, mean age = 34.3 ± 3.3 years), three studies in the AC group ( N = 138, mean age = 32.2 ± 3.8 years), five studies in the OC group ( N = 123, mean age of 30.7 ± 7.8 years), and one study in the NT group ( N = 12, mean age = 43 years, range = 28-67 years). The average postintervention visual analog scale pain score for the ES group was 1.4 ± 0.5 (from 5.7 ± 1.8), for the AC group was 3.2 ± 1.3 (from 6.6 ± 0), for the OC group was 2.3 ± 2.1 (from 5.6 ± 1.6), and for the NT group was 3.2 (from 7.6). The wrist extension range of motion improved postoperatively for all intervention groups (ES = 66.3°-70.7°; AC = 67°-74.5°; and OC = 48.9°-63.5°), whereas it remained unchanged for the NT group (46°-45°). Grip strength also improved in all intervention groups (ES = 17.9-29.9 kg; AC = 24.0-32.2 kg; and OC = 15.8-26.6 kg), while the NT group remained unchanged (25-24 kg). The radiographic scapholunate gap improved postoperatively in all groups that reported pre- and postintervention (ES = 2.2-1.9 mm; OC = 2.5-1.8 mm) and slightly worsened in the NT group (2.5-2.7 mm). In the ES group, there were three complications (11.5%, no major complications), in the AC group there was one major complication (0.9%, complex regional pain syndrome [CRPS]), and in the OC group there were six complications (15.4%, four major complications-CRPS). Conclusion All interventional treatment options (ES, AC, and OC) provided significant improvements in patient-reported pain, range of motion, grip strength, and radiographic parameters, with low complication rates. In comparison, no improvement in range of motion or grip strength was noted in the NT group. Therefore, surgical management of pSLIL injuries is an effective and relatively safe treatment option. Further studies comparing the outcomes of specific surgical treatments are warranted to further elucidate the optimal management option for pSLIL tears. Level of Evidence Level III, systematic review of Level III-IV studies.

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INTRODUCTION: This study aimed to report the screening performance of cell-free DNA (cfDNA) testing for chromosomal abnormalities in twins, triplets, and vanishing twin pregnancies. MATERIAL AND METHODS: Data were obtained from pregnant women with a multiple pregnancy or a vanishing twin pregnancy at ≥10 weeks' gestation who requested self-financed cfDNA testing between May 2015 and December 2021. Those that had positive screening results had diagnostic confirmatory procedures after counseling and consent. The performance of screening of the cfDNA test was determined by calculating confirmation rate and combined false-positive rate (cFPR). RESULTS: Data from 292 women were included after exclusion of those lost to follow-up, with no-result on cfDNA testing, or had reductions. Of the 292 pregnancies, 10 (3.4%) were triplets, including no cases of trisomy 21 and trisomy 18; 249 (85.3%) were twins, including 3 cases of trisomy 21 and no cases of trisomy 18 and 13; and 33 (11.3%) were vanishing twins, including 3 cases of trisomy 21 and 1 case of trisomy 18. The median (IQR) maternal age was 34 years (31-37). For triplet pregnancies, the initial no-result rate was 10.3% (95% confidence interval [CI] 3.6-26.4), all with results after redraw. For twin pregnancies, the initial no-result rate was 12.9% (95% CI 9.6-17.0), and the no-result rate after redraw was 1.6% (95% CI 0.7-3.6). For vanishing twins, there were no cases with no-result. All triplets had low-risk cfDNA results. The confirmation rate for trisomy 21 was 100% with a FPR at 0% due to the small number of positive cases for twins. For vanishing twins, one high-risk case for trisomy 21 and the only high-risk case for trisomy 18 were confirmed with a cFPR of 8.3% (n = 2/24; 95% CI 2.3-25.9). CONCLUSIONS: cfDNA testing in twin pregnancies has sufficient screening performance for trisomy 21 but the number of affected cases for other conditions is limited to draw any meaningful conclusion. The use of cfDNA testing in triplet pregnancies and vanishing twins remains an area for further research.

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Crohn's disease (CD) is a chronic, relapsing and remitting inflammatory bowel disease (IBD) that is increasing in incidence and prevalence globally. Management aims to achieve endoscopic healing, symptom resolution and improvement in quality of life. Therapeutic approaches in CD vary depending on disease phenotype. Thiopurines are important in steroid-sparing maintenance therapy, while anti-tumour necrosis factor agents play a fundamental role, especially in fistulising CD. Suboptimal response to these medications may require escalation to other immunosuppressive and biologic therapies, and surgical intervention is still required in a proportion of patients. Tailoring treatment to target specific patient phenotypes, disease severity and patient wishes is becoming more feasible with the growing array of therapeutic options in CD.

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The transient receptor potential melastatin 4 (TRPM4) channel contributes extensively to cardiac electrical activity, especially cardiomyocyte action potential formation. Mechanical stretch can induce changes in heart rate and rhythm, and the mechanosensitive channel Piezo1 is expressed in many cell types within the myocardium. Our previous study showed that TRPM4 and Piezo1 are closely co-localized in the t-tubules of ventricular cardiomyocytes and contribute to the Ca2+ -dependent signalling cascade that underlies hypertrophy in response to mechanical pressure overload. However, there was no direct evidence showing that Piezo1 activation was related to TRPM4 activation in situ. In the present study, we employed the HL-1 mouse atrial myocyte-like cell line as an in vitro model to investigate whether Piezo1-TRPM4 coupling can affect action potential properties. We used the small molecule Piezo1 agonist, Yoda1, as a surrogate for mechanical stretch to activate Piezo1 and detected the action potential changes in HL-1 cells using FluoVolt, a fluorescent voltage sensitive dye. Our results demonstrate that Yoda1-induced activation of Piezo1 changes the action potential frequency in HL-1 cells. This change in action potential frequency is reduced by Piezo1 knockdown using small intefering RNA. Importantly knockdown or pharmacological inhibition of TRPM4 significantly affected the degree to which Yoda1-evoked Piezo1 activation influenced action potential frequency. Thus, the present study provides in vitro evidence of a functional coupling between Piezo1 and TRPM4 in a cardiomyocyte-like cell line. The coupling of a mechanosensitive Ca2+ permeable channel and a Ca2+ -activated TRP channel probably represents a ubiquitous model for the role of TRP channels in mechanosensory transduction. KEY POINTS: The transient receptor potential melastatin 4 (TRPM4) and Piezo1 channels have been confirmed to contribute to the Ca2+ -dependent signalling cascade that underlies cardiac hypertrophy in response to mechanical pressure overload. However, there was no direct evidence showing that Piezo1 activation was related to TRPM4 activation in situ. We employed the HL-1 mouse atrial myocyte-like cell line as an in vitro model to investigate the effect of Piezo1-TRPM4 coupling on cardiac electrical properties. The results show that both pharmacological and genetic inhibition of TRPM4 significantly affected the degree to which Piezo1 activation influenced action potential frequency in HL-1 cells. Our findings provide in vitro evidence of a functional coupling between Piezo1 and TRPM4 in a cardiomyocyte-like cell line. The coupling of a mechanosensitive Ca2+ permeable channel and a Ca2+ -activated TRP channel probably represents a ubiquitous model for the role of TRP channels in mechanosensory transduction in various (patho)physiological processes.

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Background: Orthopaedic surgery suffers from gender disparity, and annual conferences are visible opportunities to quantify gender representation within a field. Therefore, the purpose of this manuscript was to investigate the prevalence of female speakers and moderators, and male-only panel sessions, at 10 major Orthopaedic Surgery meetings. Methods: Conference programs and details of faculty moderating or presenting in 10 Orthopaedic Surgery annual meetings in 2021 were retrieved. Conferences were selected with the aim of size and diversity in subspecialty topics and included American Association of Hip and Knee Surgeons, American Association for Hand Surgery, American Academy of Orthopaedic Surgeons, American Orthopaedic Society for Sports Medicine, Canadian Orthopaedic Association (COA), European Federation of National Associations of Orthopaedics and Traumatology, North American Spine Society, Orthopaedic Research Society (ORS), Orthopaedic Trauma Association, and Pediatric Orthopaedic Society of North America (POSNA). Primary outcomes included percentage of female chairs and speakers and percentage of male-only panels, while secondary outcomes included number of publications, number of citations, and H-indexes of faculty. Further subgroup comparisons were performed between male-only panels and non-male-only panels and female members and male members. Results: Of 207 included sessions, 121 (58.5%) were male-only panels and 150 (12.6%) of 1,188 faculty members were women. Conferences organized by the COA, ORS, and POSNA had higher percentages of female representation, while spine surgery and adult hip/knee reconstruction sessions had more than 70% male-only panels and fewer than 10% female members. There were no significant differences between male members and female members regarding years of practice; however, male members were more likely to hold the title of professor (p < 0.001). Male members and female members stratified by quartiles of publications, citations, and H-indexes, moderated or participated in similar numbers of sessions, indicating an absence of selection bias. Conclusions: There is a high prevalence of male-only panels (58.5%) and an overall lack of female representation (12.6%) in 10 major Orthopaedic Surgery meetings. Male members and female members from these conferences were found to have similar qualifications academically. Specific strategies such as the elimination of male-only panels, selecting diverse conference organizers, and forming conference equity, diversity, and inclusion committees can help achieve cultural change. Level of Evidence: Level V.

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Introduction: Hardware prominence is one of the major established complications following volar plating of distal radius fractures. In particular, dorsal prominence of screws is the leading risk factor associated with post-surgical extensor pollicis longus (EPL) tendon rupture. Although there are many descriptions of attritional EPL ruptures in the literature, concomitant presentation of attritional EPL and extensor digitorum communis (EDC) ruptures following volar plating of distal radius fractures are minimal. Case Report: We present a case of concomitant rupture of the EPL and occult rupture of the EDC to the index finger following volar plating of the distal radius. This was discovered intraoperatively and complicated the proposed tendon transfer reconstruction. Conclusion: Locked volar plate fixation has become the preferred technique for surgical management of distal radius fractures. The complication of multiple extensor tendon ruptures is rare but nevertheless may be encountered. We discuss strategies for diagnosis, treatment, and prevention. Surgeons should be aware of and prepared to proceed with alternative reconstructive procedures if this complication is discovered.

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PURPOSE: It remains unclear whether time-to-surgery for distal radius fractures affects clinical, functional, or radiographic outcomes or health care costs/use. This systematic review investigated the outcomes of early versus delayed surgery for closed, isolated distal radius fractures in adult patients. METHODS: A comprehensive search of MEDLINE, Embase, and CINAHL databases was completed for all original case series, observational studies, and randomized controlled trials reporting clinical outcomes of both early and delayed surgically-treated distal radius fractures from database inception to July 01, 2022. A consistent threshold of two weeks was used to define early versus delayed treatment arms. RESULTS: Nine studies, including 16 intervention arms and 1,189 patients (858 early, 331 delayed), were included. Mean age was 58 years (range, 33-76). At more than one year, the frequency-weighted mean Disabilities of the Arm, Shoulder, and Hand score was 4 in the early group (n = 208; range, 1-17) and 21 in the delayed group (n = 181; range, 4-27). Range of motion, grip strength, and radiographic outcomes were comparable. The pooled mean complication rate (7% vs 5%) and revision rate (3.6% vs 1%) were very low in both groups. CONCLUSIONS: A delay in time-to-surgery greater than two weeks for distal radius fractures may be associated with inferior patient-reported outcomes. Early surgery was associated with improved long-term Disabilities of the Arm, Shoulder, and Hand scores. On the basis of the available evidence, range of motion, grip strength, and radiographic outcomes are similar. The complication and revision rates were very low in both groups and comparable. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

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Since 1892, it has been widely assumed that somatic mutations are evolutionarily irrelevant in animals because they cannot be inherited by offspring. However, some nonbilaterians segregate the soma and germline late in development or never, leaving the evolutionary fate of their somatic mutations unknown. By investigating uni- and biparental reproduction in the coral Acropora palmata (Cnidaria, Anthozoa), we found that uniparental, meiotic offspring harbored 50% of the 268 somatic mutations present in their parent. Thus, somatic mutations accumulated in adult coral animals, entered the germline, and were passed on to swimming larvae that grew into healthy juvenile corals. In this way, somatic mutations can increase allelic diversity and facilitate adaptation across habitats and generations in animals.

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Primary cardiomyocytes are invaluable for understanding postnatal heart development. However, a universal method to obtain freshly purified cardiomyocytes without using different age-dependent isolation procedures and cell culture, is lacking. Here, we report the development of a standardised method that allows rapid isolation and purification of high-quality cardiomyocytes from individual neonatal through to adult C57BL/6J murine hearts. Langendorff retrograde perfusion, which is currently limited to adult hearts, was adapted for use in neonatal and infant hearts by developing an easier in situ aortic cannulation technique. Tissue digestion conditions were optimised to achieve efficient digestion of hearts of all ages in a comparable timeframe (<14 min). This resulted in a high yield (1.56-2.2 × 106 cells/heart) and viability (~70-100%) of cardiomyocytes post-isolation. An immunomagnetic cell separation step was then applied to yield highly purified cardiomyocytes (~95%) as confirmed by immunocytochemistry, flow cytometry, and qRT-PCR. For cell type-specific studies, cardiomyocyte DNA, RNA, and protein could be extracted in sufficient yields to conduct molecular experiments. We generated transcriptomic datasets for neonatal cardiomyocytes from individual hearts, for the first time, which revealed nine sex-specific genes (FDR < 0.05) encoded on the sex chromosomes. Finally, we also developed an in situ fixation protocol that preserved the native cytoarchitecture of cardiomyocytes (~94% rod-shaped post-isolation), and used it to evaluate cell morphology during cardiomyocyte maturation, as well as capture spindle-shaped neonatal cells undergoing cytokinesis. Together, these procedures allow molecular and morphological profiling of high-quality cardiomyocytes from individual hearts of any postnatal age.

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BACKGROUND: Many patients with constriction band syndrome will seek treatment to improve limb function and cosmesis. Although several techniques for excision are reported, cosmetic and functional deficits can persist, including hourglass deformity, lymphedema, and inadequate band excision with resultant neurovascular compromise, which may lead to revision surgery, including amputation. The authors present a novel technique that uses multiple continuous opposing Y-to-V-plasties in a single or staged manner to correct extremity constriction bands. METHODS: Seven patients with 10 involved extremities were included in this retrospective case series. Patient demographics, associated abnormalities, and operative indications were collected from medical records. The primary outcome measures were primary wound healing and release of the constriction band. Secondary outcomes measures were perioperative complications and the need for revision surgery. RESULTS: All patients achieved primary closure with excellent healing in one or two stages. No infections or scar complications occurred, and no revision surgery of the band was required. One patient had mild indentation of scar tissue after their second stage, which improved with scar massage. One patient who had preoperative sciatic compression neuropathy and an insensate foot secondary to band constriction developed chronic calcaneal osteomyelitis requiring a subsequent Syme amputation. Postoperative lymphedema occurred in two patients, which resolved with the use of compression bandages over several weeks. CONCLUSION: Use of multiple continuous opposing Y-to-V-plasties is a safe and effective technique for adequate constriction band excision without residual hourglass deformity and good functional outcomes for patients with partial or circumferential constriction bands. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

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Background Spinal deformity correction is associated with the risk of intra-operative neurological injury. Surgeon-directed monitoring (SDM) of transcranial motor-evoked potentials (TcMEP) is an option to monitor intra-operative spinal cord function. We report a retrospective analysis of a prospective database to assess the safety of this technique in spinal deformity correction in adolescent patients. Methods Surgeon-directed neuro-monitoring was utilised in 142 consecutive deformity correction surgeries (2012-2017). Surgeons were responsible for electrode placement, intra-operative stimulation, and interpretation of TcMEP data. If waveform disappearance occurred in the lower limb (LL), the surgeon would re-stimulate after excluding technical or anaesthetic factors. Failure to return normal waveforms led to maneuver reversal and reducing distractive force and ensuring subsequent return to baseline. Wake up test and ankle clonus followed by staging surgery was considered if the LL waveforms failed to return indicating potential motor injury. Results Of 142 patients, three cases (2.11%) had a complete visual loss of LL signals that did not resolve with anaesthetic stabilisation, leading to reversed surgical manoeuvre and staged surgery. No cases with permanent neurological dysfunction were recorded. This outcome supports surgeon-directed monitoring as a safe monitoring option, as an alternative to neurophysiologist-led monitoring. It also provides evidence in support of the waveform disappearance criteria as a safe TcMEP warning criterion with a 100% negative predictive value. Conclusions Where there is a lack of availability of trained neurophysiologists, surgeon-directed neuro-monitoring is a safe and reliable method of preventing intra-operative neurological injury amongst adolescent patients undergoing deformity correction.

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Pathological left ventricular hypertrophy (LVH) occurs in response to pressure overload and remains the single most important clinical predictor of cardiac mortality. The molecular pathways in the induction of pressure overload LVH are potential targets for therapeutic intervention. Current treatments aim to remove the pressure overload stimulus for LVH, but do not completely reverse adverse cardiac remodelling. Although numerous molecular signalling steps in the induction of LVH have been identified, the initial step by which mechanical stretch associated with cardiac pressure overload is converted into a chemical signal that initiates hypertrophic signalling remains unresolved. In this study, we show that selective deletion of transient receptor potential melastatin 4 (TRPM4) channels in mouse cardiomyocytes results in an approximately 50% reduction in the LVH induced by transverse aortic constriction. Our results suggest that TRPM4 channel is an important component of the mechanosensory signalling pathway that induces LVH in response to pressure overload and represents a potential novel therapeutic target for the prevention of pathological LVH.

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CASE: A 29-year-old right-hand dominant woman with thrombocytopenia-absent radii syndrome was surgically treated for a right olecranon fracture. Given her forearm deformity and short lever arm, a custom-modified corrective elbow flexion splint was used during rehabilitation. Radiographic union was achieved. Although functional outcome scores were similar to the ones previously reported in the general population, the patient had persistent extension contracture. CONCLUSION: Despite good functional outcomes, the patient had reduced range of motion. With severe limb deformity, the greatest challenge is to provide optimal rehabilitation protocols and individualized tools.

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Prior studies have reported that dietary protein dilution (DPD) or amino acid dilution promotes heightened water intake (i.e., hyperdipsia) however, the exact dietary requirements and the mechanism responsible for this effect are still unknown. Here, we show that dietary amino acid (AA) restriction is sufficient and required to drive hyperdipsia during DPD. Our studies demonstrate that particularly dietary essential AA (EAA) restriction, but not non-EAA, is responsible for the hyperdipsic effect of total dietary AA restriction (DAR). Additionally, by using diets with varying amounts of individual EAA under constant total AA supply, we demonstrate that restriction of threonine (Thr) or tryptophan (Trp) is mandatory and sufficient for the effects of DAR on hyperdipsia and that liver-derived fibroblast growth factor 21 (FGF21) is required for this hyperdipsic effect. Strikingly, artificially introducing Thr de novo biosynthesis in hepatocytes reversed hyperdipsia during DAR. In summary, our results show that the DPD effects on hyperdipsia are induced by the deprivation of Thr and Trp, and in turn, via liver/hepatocyte-derived FGF21.

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Both obesity and sarcopenia are frequently associated in ageing, and together may promote the progression of related conditions such as diabetes and frailty. However, little is known about the pathophysiological mechanisms underpinning this association. Here we show that systemic alanine metabolism is linked to glycaemic control. We find that expression of alanine aminotransferases is increased in the liver in mice with obesity and diabetes, as well as in humans with type 2 diabetes. Hepatocyte-selective silencing of both alanine aminotransferase enzymes in mice with obesity and diabetes retards hyperglycaemia and reverses skeletal muscle atrophy through restoration of skeletal muscle protein synthesis. Mechanistically, liver alanine catabolism driven by chronic glucocorticoid and glucagon signalling promotes hyperglycaemia and skeletal muscle wasting. We further provide evidence for amino acid-induced metabolic cross-talk between the liver and skeletal muscle in ex vivo experiments. Taken together, we reveal a metabolic inter-tissue cross-talk that links skeletal muscle atrophy and hyperglycaemia in type 2 diabetes.

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The 'fight or flight' response to physiological stress involves sympathetic nervous system activation, catecholamine release and adrenergic receptor stimulation. In the heart, this induces positive inotropy, previously attributed to the ß1-adrenergic receptor subtype. However, the role of the α1A-adrenergic receptor, which has been suggested to be protective in cardiac pathology, has not been investigated in the setting of physiological stress. To explore this, we developed a tamoxifen-inducible, cardiomyocyte-specific α1A-adrenergic receptor knock-down mouse model, challenged mice to four weeks of endurance swim training and assessed cardiac outcomes. With 4-OH tamoxifen treatment, expression of the α1A-adrenergic receptor was knocked down by 80-89%, without any compensatory changes in the expression of other adrenergic receptors, or changes to baseline cardiac structure and function. Swim training caused eccentric hypertrophy, regardless of genotype, demonstrated by an increase in heart weight/tibia length ratio (30% and 22% in vehicle- and tamoxifen-treated animals, respectively) and an increase in left ventricular end diastolic volume (30% and 24% in vehicle- and tamoxifen-treated animals, respectively) without any change in the wall thickness/chamber radius ratio. Consistent with physiological hypertrophy, there was no increase in fetal gene program (Myh7, Nppa, Nppb or Acta1) expression. In response to exercise-induced volume overload, stroke volume (39% and 30% in vehicle- and tamoxifen-treated animals, respectively), cardiac output/tibia length ratio (41% in vehicle-treated animals) and stroke work (61% and 33% in vehicle- and tamoxifen-treated animals, respectively) increased, regardless of genotype. These findings demonstrate that cardiomyocyte α1A-adrenergic receptors are not necessary for cardiac adaptation to endurance exercise stress and their acute ablation is not deleterious.

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PURPOSE: Several surgical approaches to the medial elbow are described; however, it remains unclear which exposure provides the optimal view of relevant medial elbow structures. The purpose of this anatomic study was to determine the visible surface area of the coronoid process, distal humerus, and radial head through 5 approaches to the medial elbow. METHODS: Eight fresh-frozen cadaveric upper extremity specimens were dissected. Five surgical approaches were performed on each specimen. The Smith muscle-splitting approach to the ulnar collateral ligament was performed first (Smith), followed by the Hotchkiss medial "Over the top" approach (Hotchkiss), the extended medial elbow approach (EMEA), the flexor carpi ulnaris splitting approach (FCU-Split), and the Taylor and Scham approach (T&S). Bony visualization was determined using laser surface scanning (Artec Space Spider; Artec 3D). The scans were segmented using commercially available digital software (Geomagic Wrap; 3D Systems Corporation), and the surface area visualized was determined. A descriptive analysis of the joint areas visible using the medial collateral ligament (MCL) as a clinical landmark was performed. RESULTS: The EMEA visualized the highest proportion of the total elbow joint from the medial side showing 13.9 ± 6.0 cm2, or 15% ± 4% of the joint. It also provided the best visualization of the coronoid (3.2 ± 1.7 cm2 of surface area, or 26% ± 9%) and distal humerus (9.9 ± 4.3 cm2, or 15% ± 4%). The Hotchkiss approach was best at visualizing the radial head (0.8 ± 0.3 cm2, or 7% ± 3%). The EMEA, Hotchkiss, and Smith approaches showed primarily the anterior bundle of the MCL, its insertion, and the regions anterior to it, whereas the FCU-Split showed the anterior bundle of the MCL and regions both anterior and posterior to it. The T&S showed primarily the areas posterior to the anterior bundle of the MCL; the anterior regions were not visible. The FCU-Split and the T&S allowed visualization of the posterior bundle of the MCL. The intraclass correlation coefficients (ICCs) for intraobserver reliability were 0.997, 0.992, and 0.974 for the test distal humerus, test coronoid, and test radial head, respectively. The ICCs for interobserver reliability were 0.915 for the test distal humerus, 0.66 for the coronoid, and 0.583 for the radial head. CONCLUSION: The EMEA provides the most visualization of the coronoid and distal humerus, whereas the Hotchkiss showed the most radial head. However, these approaches mainly visualize structures anterior to the MCL. If exposure of structures posterior to the MCL is required, the FCU-Split and T&S approaches are more appropriate.

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