Postoperative Complications and Readmission Rates in Robotic-Assisted Versus Manual Total Knee Arthroplasty: Large, Propensity Score-Matched Patient Cohorts.

INTRODUCTION: There is a paucity of research comparing postoperative complication rates between manual total knee arthroplasty (M-TKA) and robotic-assisted total knee arthroplasty (RA-TKA). This study aims to compare 90-day postoperative complication, readmission, and emergency department rates between RA-TKA and M-TKA. METHODS: A retrospective review of a multihospital database identified patients who underwent TKA between January 2016 and May 2023. Surgeons who used the robotic-assisted surgery technique in <10% or >90% of their cases annually were excluded. This resulted in 15,999 cases (8,853 RA-TKAs; 7,146 M-TKAs) from 282 surgeons. RA-TKA and M-TKA cohorts were one-to-one matched based on patient sex, age, body mass index, hospital setting, surgeon experience, primary payer, and anesthesia type. Each cohort consisted of 7,146 patients (N = 14,292). 90-day revisits, specifically readmissions, readmissions with >23 hours of observation, and ED visit rates were compared between cohorts. Complications were classified according to the Clinical Classification Software schema and compared between cohorts. Mann-Whitney U, chi-squared, and Fisher exact tests, along with Bonferroni correction, were used to statistically compare cohorts. RESULTS: All-cause 90-day readmission rates were 2.4% for RA-TKA and 2.6% for M-TKA (P = 0.36). RA-TKA had fewer revisits (RA-TKA: 7.8%; M-TKA: 8.8%, P = 0.027) and rates of readmission with >23 hours of observation (RA-TKA: 1.4%; M-TKA: 2.0%, P = 0.003). RA-TKA had fewer hospital revisits due to joint stiffness (RA-TKA: 17 revisits; M-TKA: 42 revisits, P = 0.002) and chronic pain (RA-TKA: 1 revisit; M-TKA: 8 revisits, P = 0.039). Fewer readmissions were observed for acute injuries (lower extremity muscle/tendon strains) in the RA-TKA cohort (RA-TKA: 1; M-TKA: 9, P = 0.021). RA-TKA had fewer ED visits due to hematomas (RA-TKA: 0 visits; M-TKA: 7 visits, P = 0.016). CONCLUSION: In this retrospective matched cohort analysis, RA-TKA was associated with markedly fewer revisits and readmissions with >23 hours of observation compared with M-TKA. No differences in all-cause 90-day readmission were observed between cohorts. LEVEL OF EVIDENCE: Level III. STUDY DESIGN: Retrospective review.

Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment.

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by ~300× compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, vastly expanding its applicability within solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in TF in response to neoadjuvant immunotherapy in lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables plasma-only (non-tumor-informed) disease monitoring in advanced melanoma and lung cancer, yielding clinically informative TF monitoring for patients on immune-checkpoint inhibition.

Modulation of the allosteric and vasoregulatory arms of erythrocytic oxygen transport.

Efficient distribution of oxygen (O2) to the tissues in mammals depends on the evolved ability of red blood cell (RBC) hemoglobin (Hb) to sense not only O2 levels, but metabolic cues such as pH, PCO2, and organic phosphates, and then dispense or take up oxygen accordingly. O2 delivery is the product of not only oxygen release from RBCs, but also blood flow, which itself is also governed by vasoactive molecular mediators exported by RBCs. These vascular signals, including ATP and S-nitrosothiols (SNOs) are produced and exported as a function of the oxygen and metabolic milieu, and then fine-tune peripheral metabolism through context-sensitive vasoregulation. Emerging and repurposed RBC-oriented therapeutics can modulate either or both of these allosteric and vasoregulatory activities, with a single molecule or other intervention influencing both arms of O2 transport in some cases. For example, organic phosphate repletion of stored RBCs boosts the negative allosteric effector 2,3 biphosphoglycerate (BPG) as well as the anti-adhesive molecule ATP. In sickle cell disease, aromatic aldehydes such as voxelotor can disfavor sickling by increasing O2 affinity, and in newer generations, these molecules have been coupled to vasoactive nitric oxide (NO)-releasing adducts. Activation of RBC pyruvate kinase also promotes a left shift in oxygen binding by consuming and lowering BPG, while increasing the ATP available for cell health and export on demand. Further translational and clinical investigation of these novel allosteric and/or vasoregulatory approaches to modulating O2 transport are expected to yield new insights and improve the ability to correct or compensate for anemia and other O2 delivery deficits.

Stereoselective Polymerization of 3,6-Disubstituted N-Vinylcarbazoles.

Poly(N-vinylcarbazole) (PNVC-H) is a valuable nonconjugated photoconductive polymer, but the free radical polymerization conditions typically used for its synthesis do not control polymer stereochemistry and are not tolerant to many substituted N-vinylcarbazoles. Here, we report the stereoselective cationic polymerization of a series of 3,6-disubtituted N-vinylcarbazole derivatives using a chiral scandium-bis(oxazoline) Lewis acid catalyst. The combination of asymmetric ion-pairing catalysis and inherent monomer stereoelectronics facilitated stereoselective polymerization at room temperature, which enabled the polymerization of less soluble 3,6-disubstituted-N-vinylcarbazole derivatives. Isotactic halogen-substituted PNVCs demonstrated self-assembly in solution through halogen-halogen bonding, which was not observed in their atactic counterparts. Initial spectral characterization displayed a wide range of excitation-emission profiles for substituted PNVCs, which demonstrate the promise of these materials as a new class of nonconjugated photoconductive polymers for optoelectronic applications. Overall, these results showcase a diverse class of isotactic poly(N-vinylcarbazoles), highlight the benefits of identifying alternative stereocontrol mechanisms for polymerization, and expand the suite of accessible nonconjugated hole-transport materials.

Redescription of adults and first description of the larva of Haemaphysalis (Rhipistoma) adleri Feldman-Muhsam, 1951 (Acari: Ixodidae), parasite of carnivorans in Western Asia.

The adults of Haemaphysalis (Rhipistoma) adleri Feldman-Muhsam, 1951 (Acari: Ixodidae) are redescribed and the larva of this species is described for the first time here. The adults of H. adleri that we studied were collected from various canid, felid and hyaenid carnivorans (Carnivora: Canidae, Felidae, Hyaenidae) as well as a hedgehog (Erinaceomorpha: Erinaceidae) in Iraq, Israel and West Bank. The males, females and larvae of H. adleri can be differentiated from Haemaphysalis (Rhipistoma) species occurring in the Palearctic portion of West Asia and Egypt as well those in the H. asiatica subgroup by the length of idiosomal setae, development and size of spurs on palpi, dental formula on the hypostome and size of spur on coxae. A lectotype of H. adleri has been designated and the geographic distribution and hosts of this tick species are discussed.

Leveraging the Stereochemical Complexity of Octahedral Diastereomeric-at-Metal Catalysts to Unlock Regio-, Diastereo-, and Enantioselectivity in Alcohol-Mediated C-C Couplings via Hydrogen Transfer.

Experimental and computational studies illuminating the factors that guide metal-centered stereogenicity and, therefrom, selectivity in transfer hydrogenative carbonyl additions of alcohol proelectrophiles catalyzed by chiral-at-metal-and-ligand octahedral d6 metal ions, iridium(III) and ruthenium(II), are described. To augment or invert regio-, diastereo-, and enantioselectivity, predominantly one from among as many as 15 diastereomeric-at-metal complexes is required. For iridium(III) catalysts, cyclometalation assists in defining the metal stereocenter, and for ruthenium(II) catalysts, iodide counterions play a key role. Whereas classical strategies to promote selectivity in metal catalysis aim for high-symmetry transition states, well-defined low-symmetry transition states can unlock selectivities that are otherwise difficult to achieve or inaccessible.

Firearm exposure and safety training of rural Iowa youth.

PURPOSE: Our objective was to investigate rural adolescents' use of firearms and whether they had received firearm training. METHODS: 2019 Iowa FFA Leadership Conference attendees were surveyed. Descriptive and comparative analyses were performed. RESULTS: One thousand three hundred and eighty-two FFA members aged 13-18 years participated. The vast majority (85%) had fired a rifle/shotgun; 58% reported firing them >20 times. Of those who had fired rifles/shotguns, 32% had done so before 9 years old; 79% before 13 years. Most had also fired a handgun (62%), with 30% having fired handguns >20 times. Of those who had fired handguns, 34% had done so before 11 years old. The average age for first firing rifles/shotguns was 10.1 (SD 2.9) years, and 11.9 (SD 2.8) years for handguns. Males, older teenagers, and those living on farms or in the country had significantly greater percentages that had fired a rifle/shotgun or a handgun. Greater proportions of males had used firearms >20 times and started firing them at younger ages. Over half (55%) reported having gone hunting. Of those, 24% first hunted before 9 years old; 48% before 11 years. Of those who had used a firearm, 61% had completed a firearm safety training course. For hunters, 80% had taken a course. CONCLUSIONS: Most participants had used firearms, and many did so at very young ages. Substantial numbers had not received formal training. The authors believe that families should be counseled when it is developmentally appropriate to introduce youth to firearms, and all should take firearm safety training before using them.

Living with trimethylaminuria and body and breath malodour: personal perspectives.

BACKGROUND: Many people suffer from body and breath malodour syndromes. One of these is trimethylaminuria, a condition characterized by excretion in breath and bodily fluids of trimethylamine, a volatile and odorous chemical that has the smell of rotting fish. Trimethylaminuria can be primary, due to mutations in the gene encoding flavin-containing monooxygenase 3, or secondary, due to various causes. To gain a better understanding of problems faced by United Kingdom residents affected by body and breath malodour conditions, we conducted a survey. METHODS: Two anonymous online surveys, one for adults and one for parents/guardians of affected children, were conducted using the Opinio platform. Participants were invited via a trimethylaminuria advisory website. Questions were a mix of dropdown, checkbox and open-ended responses. Forty-four adults and three parents/guardians participated. The dropdown and checkbox responses were analysed using the Opinio platform. RESULTS: All participants reported symptoms of body/breath odour. However, not all answered every question. Twenty-three respondents experienced difficulties in being offered a diagnostic test for trimethylaminuria. Problems encountered included lack of awareness of the disorder by medical professionals and reluctance to recognise symptoms. Of those tested, 52% were diagnosed with trimethylaminuria. The main problems associated with living with body/breath malodours were bullying, harassment and ostracism in either the workplace (90%) or in social settings (88%). All respondents thought their condition had disadvantaged them in their daily lives. Open-ended responses included loss of confidence, stress, exclusion, isolation, loneliness, depression and suicidal thoughts. Respondents thought their lives could be improved by greater awareness and understanding of malodour conditions by medical professionals, employers and the general public, and appreciation that the malodour was due to a medical condition and not their fault. CONCLUSIONS: Breath and body malodour conditions can cause immense hardship and distress, both mentally and socially, having devastating effects on quality of life. It would be advantageous to establish a standardised pathway from primary care to a specialist unit with access to a robust and reliable test and diagnostic criteria. There is a need to recognise malodour disorders as a disability, giving affected individuals the same rights as those with currently recognised disabilities.

FluoMALDI Microscopy: Matrix Co-Crystallization Simultaneously Enhances Fluorescence and MALDI Imaging.

Here, the authors report that co-crystallization of fluorophores with matrix-assisted laser desorption/ionization (MALDI) imaging matrices significantly enhances fluorophore brightness up to 79-fold, enabling the amplification of innate tissue autofluorescence. This discovery facilitates FluoMALDI, the imaging of the same biological sample by both fluorescence microscopy and MALDI imaging. The approach combines the high spatial resolution and specific labeling capabilities of fluorescence microscopy with the inherently multiplexed, versatile imaging capabilities of MALDI imaging. This new paradigm simplifies registration by avoiding physical changes between fluorescence and MALDI imaging, allowing to image the exact same cells in tissues with both modalities. Matrix-fluorophore co-crystallization also facilitates applications with insufficient fluorescence brightness. The authors demonstrate  feasibility of FluoMALDI imaging with endogenous and exogenous fluorophores and autofluorescence-based FluoMALDI of brain and kidney tissue sections. FluoMALDI will advance structural-functional microscopic imaging in cell biology, biomedicine, and pathology.

Myocardial plasma cell tumor with intratumoral amyloidosis in a dog.

A 12-year-old mixed breed dog was evaluated for marked hypercalcemia that was identified during assessment for acute polydipsia and polyuria. Physical examination identified a new grade II/VI left apical systolic murmur. A mass involving the left ventricular posterior wall and left atrium was identified by echocardiography, suggesting neoplastic invasion into the myocardium. The patient was euthanized, and post-mortem cardiac evaluation identified an intramyocardial amyloid-producing plasma cell tumor. Multiple myeloma was suspected but could not be confirmed due to the limited post-mortem evaluation. This case is the first report of myocardial amyloidosis in a dog with a myeloma-related disorder (MRD). Dogs with MRD and myocardial involvement may not exhibit clinical signs that localize to the cardiovascular system; therefore, echocardiography should be considered during the staging process.

Skeletal Muscle Adaptations to High-Load Resistance Training With Pre-Exercise Blood Flow Restriction.

ABSTRACT: Hammert, WB, Moreno, EN, Martin, CC, Jessee, MB, and Buckner, SL. Skeletal muscle adaptations to high-load resistance training with pre-exercise blood flow restriction. J Strength Cond Res 37(12): 2381-2388, 2023-This study aimed to determine if blood flow restriction (BFR) could augment adaptations to a high-load training protocol that was inadequate for muscle growth. Forty nontrained individuals had each arm assigned to 1 of 3 elbow flexion protocols: (a) high-load resistance training [TRAD; 4 sets to muscular failure at 70% 1 repetition maximum (1RM)], (b) low repetition high-load resistance training with pre-exercise BFR (PreBFR; 4 sets of 3 repetitions at 70% 1RM + 3 min of pre-exercise BFR), and (c) low repetition high-load resistance training (LRTRAD); 4 sets of 3 repetitions at 70% 1RM). Muscle thickness (MT), 1RM strength, and local muscular endurance (LME) of the elbow flexors were measured before and after 8 weeks. An alpha level of 0.05 was used for all comparisons. For the 50% site, MT increased for TRAD (0.211 cm, 95% confidence interval [95% CI]: 0.143-0.280), PreBFR (0.105 cm, 95% CI: 0.034-0.175), and LRTRAD (0.073 cm, 95% CI: 0.000-0.146). The change for TRAD was greater than PreBFR and LRTRAD. For the 60% site, MT increased for TRAD (0.235 cm, 95% CI: 0.153-0.317), PreBFR (0.097 cm, 95% CI: 0.014-0.180), and LRTRAD (0.082 cm, 95% CI: 0.000-0.164). The change for TRAD was greater than PreBFR and LRTRAD. For the 70% site MT increased for TRAD (0.308 cm, 95% CI: 0.247-0.369), PreBFR (0.103 cm, 95% CI: 0.041-0.166), and LRTRAD (0.070 cm, 95% CI: 0.004-0.137). The change for TRAD was greater than PreBFR and LRTRAD. One repetition maximum and LME significantly increased for each condition, with no differences between conditions. Collapsed across conditions 1RM strength increased 2.094 kg (95% CI: 1.771-2.416) and LME increased 7.0 repetitions (95% CI: 5.7-8.3). In conclusion, the application of BFR to low-repetition, high-load training did not enhance the adaptative response.

RaMALDI: Enabling simultaneous Raman and MALDI imaging of the same tissue section.

Multimodal tissue imaging techniques that integrate two complementary modalities are powerful discovery tools for unraveling biological processes and identifying biomarkers of disease. Combining Raman spectroscopic imaging (RSI) and matrix-assisted laser-desorption/ionization (MALDI) mass spectrometry imaging (MSI) to obtain fused images with the advantages of both modalities has the potential of providing spatially resolved, sensitive, specific biomolecular information, but has so far involved two separate sample preparations, or even consecutive tissue sections for RSI and MALDI MSI, resulting in images with inherent disparities. We have developed RaMALDI, a streamlined, integrated, multimodal imaging workflow of RSI and MALDI MSI, performed on a single tissue section with one sample preparation protocol. We show that RaMALDI imaging of various tissues effectively integrates molecular information acquired from both RSI and MALDI MSI of the same sample, which will drive discoveries in cell biology, biomedicine, and pathology, and advance tissue diagnostics.

Value of Routine Troponin Measurement in Open Abdominal Aortic Aneurysm Repair.

BACKGROUND: Cardiovascular complications are a major cause of morbidity and mortality in the postoperative period after major vascular surgery. Depending on the study population, up to 25% of patients have troponin elevation after noncardiac surgery, yet many do not meet the diagnosis of myocardial infarction (MI). Although outcomes of routine troponin elevation in patients undergoing mixed major vascular surgery have been evaluated, this has not been studied exclusively in elective, open abdominal aortic aneurysm repair (oAAA), especially regarding perioperative and overall mortality. METHODS: We conducted a single-center, retrospective review of routine troponin surveillance for consecutive, oAAA from 2014 to 2019. A total of 319 patients were identified and analyzed for management patterns and interventions. The cohort was stratified into groups for comparison based on those in whom troponin was routinely checked (RC) as part of a care strategy during the study period, not routinely checked (NRC), elevated troponin (ET) >0.001 ng/mL, and not elevated. The median follow-up was 21.5 ± 23.8 months. Groups were compared on demographic data, cardiac comorbidities, 30-day and 3-year outcomes for MI and death using two-sample t-tests, Wilcoxon rank sum tests, Pearson chi-square tests, and Fisher exact tests when appropriate. RESULTS: Troponin was measured in 83.7% (267/319) of patients who underwent elective oAAA repair. Routine troponin checks were obtained in 79.9% (255/319) of patients. ET was identified in 16.5% of those with RC (42/255) and 4.7% of those with NRC (3/64). Of patients with ET, 37.8% (17/45) had a cardiology consultation, 4.4% (2/45) had a percutaneous coronary intervention (PCI), and 4.4% (2/45) had another cardiac intervention. All 4 patients undergoing PCI or other cardiac intervention had received routine troponin checks. Patients with ET were older (71.2 vs. 68.6; P = 0.04), more likely to receive intraoperative blood products (P = 0.003), had longer operative times (P = 0.011), higher length of stay (9 vs. 7 days; P < 0.01), and higher 30-day MI rate (3 vs. 0; P = 0.04). They had neither longer aortic clamp times nor worse preoperative cardiac function, and the proximal clamp position during oAAA repair did not impact troponin detection. Additionally, 3-year overall mortality was increased in patients who had ET but there was not a significant difference in 3-year mortality between groups receiving routine troponin checks versus not. CONCLUSIONS: ET, identified after elective oAAA repair, was associated with a higher risk of 30-day MI and lower overall survival. However, it was not demonstrated that routine assessment of troponin levels postoperatively leads to decreased 3-year mortality in this setting.

Effects of abdominal aortic aneurysm appropriateness dashboard on clinical practice.

OBJECTIVE: The Society for Vascular Surgery published abdominal aortic aneurysm (AAA) practice guidelines in 2003, 2009, and 2018 to improve the management and treatment of AAAs. In 2014, our vascular surgery department implemented a quarterly AAA dashboard (AAAdb) to record the perioperative outcomes and guideline compliance with a focus on intervention appropriateness and procedural follow-up, which supplemented our Vascular Quality Initiative data. From the available reported evidence and expert consensus opinions, nine additional criteria for the appropriate treatment of AAAs <5 cm in women and <5.5 cm in men were noted, when applicable. The purpose of our study was to assess the effects of AAAdb implementation on adherence to society and institutional guidelines, documentation of treatment rationale, and the quality of follow-up. METHODS: We performed a retrospective review of elective open and endovascular AAA repair at a single institution from 2010 to 2018. The AAAdb was implemented in the middle of this period in 2014. The patient demographics, aortic size, repair indication, repair type, 30-day mortality, and postoperative and 1-year follow-up imaging findings were analyzed. The primary outcome was adherence to intervention appropriateness and the follow-up guidelines. The categorical factors were summarized using frequencies and percentages and compared using the Pearson χ2 test or Fisher exact test. Continuous measures were summarized using the mean ± standard deviation and compared between study periods using two-sample t tests. RESULTS: From 2010 to 2018, 1549 patients had undergone elective AAA repair: 657 before and 892 after AAAdb implementation. No differences were found in AAA size after AAAdb (5.6 ± 1.2 cm vs 5.6 ± 1.1 cm; P = .88). However, the proportion of size-appropriate repairs increased (64.1% vs 71.3%; P = .003). The proportion of small AAA repairs with a documented rationale had increased (64.4% vs 80.5%; P < .001), with rapid disease progression cited most often. No difference was found in 30-day mortality (1.2% vs 1.5%; P = .69). Follow-up imaging after endovascular abdominal aortic aneurysm repair increased at <60 days postoperatively (76% vs 84%; P = .004) and at 1 year of follow-up (78% vs 86%; P = .0005). The proportion of patients with endoleak at <60 days postoperatively had increased in the post-AAAdb cohort (21% vs 29%; P = .012). CONCLUSIONS: The AAAdb served as a centerpiece for improving the appropriateness of care and compliance with national and institutional guidelines, including treatment of small AAAs in special circumstances. Its implementation was associated with higher quality follow-up and surveillance in a high-volume, regional aortic center. Consideration should be given to adding additional criteria to the Society for Vascular Surgery guidelines and Vascular Quality Initiative reporting.

O-Acetyl 1,3-Propanediol as an Acrolein Proelectrophile in Enantioselective Iridium-Catalyzed Carbonyl Allylation.

O-Acetyl 1,3-propanediol serves as an acrolein proelectrophile in π-allyliridium-C,O-benzoate-catalyzed carbonyl allylations mediated by racemic α-substituted allylic acetates. Using the iridium catalyst modified by (R)-SEGPHOS, a variety of 3-hydroxy-1,5-hexadienes are formed with uniformly high levels of regio-, anti-diastereo-, and enantioselectivity.

Allyl Alcohol as an Acrolein Equivalent in Enantioselective C-C Coupling: Total Synthesis of Amphidinolides R, J, and S.

The first systematic study of catalytic enantioselective 1,2-additions to acrolein is described. Specifically, using allyl alcohol as a tractable, inexpensive acrolein proelectrophile, iridium-catalyzed acrolein allylation is achieved with high levels of regio-, anti-diastereo-, and enantioselectivity. This process delivers 3-hydroxy-1,5-hexadienes, a useful compound class that is otherwise challenging to access via enantioselective catalysis. Two-fold use of this method unlocks concise total syntheses of amphidinolide R (9 vs 23 steps, LLS) and amphidinolide J (9 vs 23 or 26 steps, LLS), which are prepared in fewer than half the steps previously possible, and the first total synthesis of amphidinolide S (10 steps, LLS).

Acute muscular and cardiovascular responses to high load training with pre-exercise blood flow restriction.

PURPOSE: The purpose of this study is to examine the acute muscular and cardiovascular responses to applying blood flow restriction (BFR) before high-load training. METHODS: Forty trained individuals visited the lab on three occasions. On Visit 1, participants completed paperwork and performed strength assessments. During Visits 2 and 3, participants completed four exercise conditions (one in each arm during each visit) as follows: (1) traditional resistance training (TRAD), (2) low load training with BFR (LLBFR), (3) low repetition high load training with pre-exercise BFR (PreBFR), and (4) low repetition traditional training (LRTRAD). Blood pressure, muscle thickness (MT), and isometric strength (ISO) were measured before and after exercise. RESULTS: Data are displayed as means (SD). Immediately following exercise, MT in TRAD was greater compared with PreBFR (mean difference = 0.18[0.30] cm, p < 0.001) and LRTRAD (mean difference = 0.28[0.30] cm, p < 0.001). In addition, LLBFR demonstrated greater MT compared with PreBFR (mean difference = 0.24[0.30] cm, p < 0.001]. Immediately following exercise, ISO was lower in TRAD compared with PreBFR (mean difference = 33.8[46.9]N, p < 0.001) and the LRTRAD condition (mean difference = 32.8[50.4]N, p < 0.001). In addition, ISO was lower in LLBFR compared with PreBFR (mean difference = 43.9 [47.4]N, p < 0.001) and LRTRAD (mean difference = 42.9 [43.8]N, p < 0.001). Immediately following exercise, systolic blood pressure was greater in TRAD compared with PreBFR and LRTRAD. CONCLUSION: The application of BFR before engaging in high-load training does not seem to augment the muscular responses to exercise when compared with traditional high loads alone; however, it may pose less demand on the cardiovascular system.

Iridium-, Ruthenium-, and Nickel-Catalyzed C-C Couplings of Methanol, Formaldehyde, and Ethanol with π-Unsaturated Pronucleophiles via Hydrogen Transfer.

In this Perspective, the use of methanol and ethanol as C1 and C2 feedstocks in metal-catalyzed C-C couplings to π-unsaturated pronucleophiles via hydrogen auto-transfer is surveyed. In these processes, alcohol oxidation to form an aldehyde electrophile is balanced by reduction of an π-unsaturated hydrocarbon to form a transient organometallic nucleophile. Mechanistically related reductive couplings of paraformaldehyde mediated by alcohol reductants or formic acid also are described. These processes encompass the first catalytic enantioselective C-C couplings of methanol and ethanol and, more broadly, illustrate how the native reducing ability of alcohols enable the departure from premetalated reagents in carbonyl addition.

Mechanistic Insights into the Stereoselective Cationic Polymerization of N-Vinylcarbazole.

The synthesis of stereoregular polymers through ionic mechanisms using asymmetric ion-pairing (AIP) catalysis is emerging as an effective strategy to achieve differentiated material properties from readily available building blocks. Stereoselective cationic polymerization in particular is primed for advancement using AIP by leveraging the breadth of Brønsted and Lewis acid small-molecule catalysis literature; however, mechanistic studies that address polymer-specific phenomena are scarce and, as a result, the lack of mechanistic understanding has limited catalyst design. In a recent study, we demonstrated the only example of a stereoselective and helix-sense-selective cationic vinyl polymerization of N-vinylcarbazole using chiral scandium-bis(oxazoline) Lewis acids. To better understand the mechanism of this highly stereoselective polymerization and elicit design principles for future advances, we present a combined experimental and computational study into the relevant factors that determine tacticity and helicity control. Key mechanistic experiments suggest two competing elementary steps-chain-end conformation equilibration and propagation-whose relative rates can be influenced by monomer concentration, isotope effects, and catalyst design to tune tacticity. In contrast, helicity is influenced by complex relationships between the stereoselectivity of the first monomer propagation and a time-dependent initiator-catalyst mixing time. The more complete understanding of stereoselective cationic polymerization through AIP developed herein provides insights into polymer-specific mechanisms for stereocontrol, which we believe will motivate continued catalyst discovery and development for stereoselective vinyl polymerization.

Stereoselective Helix-Sense-Selective Cationic Polymerization of N-Vinylcarbazole Using Chiral Lewis Acid Catalysis.

Helical polymers with a defined main-chain atropoisomeric conformation are important materials in high value applications such as nonlinear optics and chiral separations. Currently, no methods exist for the cationic helix-sense-selective polymerization of prochiral vinyl monomers, which limits access to a number of potentially valuable optically active helical polymers. Here, we demonstrate the first stereoselective cationic helix-sense-selective polymerization of a prochiral vinyl monomer, which provides access to optically active helices of poly(N-vinylcarbazole). Chiral bis(oxazoline)-scandium Lewis acids serve as chiral counterions to polymerize N-vinylcarbazole into highly isotactic (up to 94% meso triads) polymers. Mechanistic investigations uncovered the distinct phenomenon that are responsible for independent control of conformational (i.e., helicity) and configurational (i.e., tacticity) stereochemistry. Polymer helicity was strongly influenced by the stereoselectivity of the first monomer propagation, whereas polymer tacticity was dictated by the thermodynamically controlled conformation of the growing polymer chain end. Overall, this method expands the suite of accessible helical polymers through helix-sense-selective polymerization and provides mechanistic insight into how polymer tacticity and helicity can be controlled independently.