Evaluation of unexpected protecting group removal in solid-phase peptide synthesis: Quantified using continuous flow methods.

As peptides gained interest as new drugs in the past years, their synthetic routes had been the subject of review and improvement. Fmoc/tBu-based solid-phase peptide synthesis (SPPS) is the most convenient technique, and the implementation in continuous flow has allowed for single-pass coupling and deprotection reactions. The focus of this research is to evaluate the relationship between undesired solvent-promoted reactions and final crude purity, by studying volume changes of a variable bed flow reactor through the synthesis. Based on the temperature, typical solvents for SPPS such as dimethylformamide (DMF) or N-methyl-2-pyrrolidone (NMP) can cause unwanted Fmoc removal during wash steps. It was found that for every millilitre of DMF used at 80°C, up to 1 µmol of Fmoc-protected peptide is deprotected, leading to additional impurities. This effect can, however, be minimised by adding additives such as HOBt, which reduces such unwanted deprotection to just 0.1 µmol/ml.

Decatungstate-Mediated C(sp3 )-H Heteroarylation via Radical-Polar Crossover in Batch and Flow.

Photocatalytic hydrogen atom transfer is a very powerful strategy for the regioselective C(sp3 )-H functionalization of organic molecules. Herein, we report on the unprecedented combination of decatungstate hydrogen atom transfer photocatalysis with the oxidative radical-polar crossover concept to access the direct net-oxidative C(sp3 )-H heteroarylation. The present methodology demonstrates a high functional group tolerance (40 examples) and is scalable when using continuous-flow reactor technology. The developed protocol is also amenable to the late-stage functionalization of biologically relevant molecules such as stanozolol, (-)-ambroxide, podophyllotoxin, and dideoxyribose.

pH-Dependent absorption spectrum of oxyluciferin analogues in the active site of firefly luciferase.

In the quest for the identification of the light emitter(s) responsible for the firefly bioluminescence, the study of oxyluciferin analogues with controlled chemical and electronic structures is of particular importance. In this article, we report the results of our experimental and computational investigation of the pH-dependent absorption spectra characterizing three analogues bound into the luciferase cavity, together with adenosine-monophosphate (AMP). While the analogue microscopic pKa values do not differ much from their reference values, it turns out that the AMP protonation state is analogue-dependent and never doubly-deprotonated. A careful analysis of the interactions evidences the main role of E344 glutamic acid, as well as the flexibility of the cavity which can accommodate any oxyluciferin analogue. The consideration of the absorption spectra suggests that the oxyluciferin enolate form has to be excluded from the list of the bioluminescence reaction products.

Classification of pro-inflammatory status for interleukin-6 affects relative muscle strength in obese elderly women.

BACKGROUND: Obesity, defined by an excess amount of body fat or a percent body fat higher than 30 % for women is a complex chronic disorder with multifactorial etiology and is accompanied by chronic low-grade inflammation, which results in elevated pro-inflammatory cytokines. AIMS: The aim of this study was to compare muscle strength between high and low pro-inflammatory status in obese elderly women and to verify the relationship of IL-6 with muscle strength and fat-free mass. METHODS: Eighty-nine elderly women (age 69.47 ± 6.07 years; body mass 64.70 ± 12.04 kg; height 1.52 ± 0.06 m; body mass index 27.78 ± 4.75 kg/m(2)) were divided into two groups: high and low inflammatory status for IL-6. Lower limb muscle strength was tested using bilateral leg extension with the ten repetitions maximum test, IL-6 was measured by ELISA and body composition by dual-energy X-ray absorptiometry. RESULTS: Women classified from the high pro-inflammatory status presented lower relative muscle strength (P = 0.056) when compared with the low inflammatory status group, with no differences for absolute muscle strength (P = 0.18). There was a significant negative correlation of IL-6 with relative muscle strength (P = 0.03, R = -0.22) and a considerable trend toward significance (P = 0.06, R = -0.19) and negative association with fat-free mass (P = 0.84, R = -0.02). CONCLUSIONS: This study provides insights that a high pro-inflammatory status in sedentary obese elderly women might impair muscle strength and negatively affect fat-free mass. Thus, elderly women classified with high pro-inflammatory status for IL-6 should receive further health care attention to prevent this deleterious condition.

Multiphase photochemistry in flow mode via an integrated continuous stirred tank reactor (CSTR) approach.

A new photochemical CSTR system capable of handling solids in scaled continuous processes is presented. High-power UV-LEDs are integrated in these CSTRs containing an insoluble base that aids in generating pyrazolines via cycloaddition between alkenes and in situ generated diazo species. Contrary to reported batch methods product degradation via ring contraction is suppressed whilst generating gram quantities of spirocyclic pyrazolines.

Association of cardiovascular response to an acute resistance training session with the ACE gene polymorphism in sedentary women: a randomized trial.

BACKGROUND: The aim of the present study was to verify the effects of an acute resistance training (RT) session and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) on systolic (SBP), diastolic (DBP) and mean blood pressure (MBP), and heart rate (HR). METHODS: The sample consisted of 27 sedentary women (33.3 ± 8.2 yrs; 69.1 ± 13.8 kg; 1.57 ± 0.05 m; 27.6 ± 5.1 kg/m2) divided into two groups according to their polymorphism I/D (DD = 9; II + ID = 18). Volunteers underwent two experimental sessions: RT - an acute session performed with three sets at 60% of one-repetition maximum (1RM) interspersed with 1 minute rest interval between exercises and sets, and a control session (CON) in which they remained seated for 30 minutes in the laboratory. SBP, DBP, MBP and HR were measured before exercise and during one hour every 10 minutes after sessions, in the seated position. A two-way ANOVA for repeated measures with Tukey's post hoc test was used for the intra and inter-group comparisons. RESULTS: There were no statistically significant differences on SBP, DBP and MBP after the experimental protocols, and no effect of ACE polymorphism (P > 0.05). However, comparing CON versus exercise effect size values (ES), homozygotic carriers of the allele D presented a drop in SBP which was considered moderate, while in allele I carriers it was small, 30 minutes after exercise. In MBP, homozygotic D carriers exhibited a large ES 20 minutes post-exercise. HR was higher at 10, 20 and 30 minutes after exercise as compared to pre-exercise only for carriers of the I allele ( < 0.05). CONCLUSIONS: Therefore, an acute RT session reduces clinical BP. In addition to this; it seems that ACE polymorphism had some influence on cardiovascular response to exercise. TRIAL REGISTRATION: RBR-6GDYVZ.

Resistance exercise leading to failure versus not to failure: effects on cardiovascular control.

BACKGROUND: The aim of the present study was to evaluate the acute effects of resistance exercise (RE) leading to failure and RE that was not to failure on 24 h blood pressure (BP) and heart rate variability (HRV) in sedentary normotensive adult women. METHODS: Ten women (33.2 ± 5.8 years; 159.3 ± 9.4 cm; 58.0 ±6.4 kg; body fat 28.4 ± 2.8%) randomly underwent three experimental sessions: control (40 minutes of seated rest), RE leading to failure with 3 sets of 10 repetitions maximum (10-RM), and RE not to failure at 60% of 10-RM with 3 sets of 10 repetitions. Immediately post session BP and HRV were measured for 24 h. RESULTS: Ratings of perceived exertion and heart rate were higher during the 10-RM session when compared with 60% of 10-RM (6.4 ± 0.5 vs 3.5 ± 0.8 and 123.7 ± 13.9 vs 104.5 ± 7.3 bpm, respectively). The systolic, diastolic and mean BP decreased at 07:00 a.m. after the 10-RM session when compared with the control session (-9.0 ± 7.8 mmHg, -16.0 ± 12.9 mmHg and -14.3 ± 11.2 mmHg, respectively). The root mean square of the squared differences between R-R intervals decreased after both the 60% of 10-RM and 10-RM sessions compared with the control session. CONCLUSIONS: An acute RE session leading to failure induced a higher drop of BP upon awakening, while both RE sessions reduced cardiac parasympathetic modulation. RE may be an interesting training strategy to acutely decrease BP in adult women.

Physical literacy assessment in adults: A systematic review.

Physical literacy is a multidimensional construct that has been defined and interpreted in various ways, one of the most common being "the motivation, confidence, physical competence, knowledge and understanding to maintain physical activity throughout the life course". Although its improvement can positively affect many behavioral, psychological, social, and physical variables, debate remains over an appropriate method of collecting empirical physical literacy data. This systematic review sought to identify and critically evaluate all primary studies (published and unpublished, regardless of design or language) that assessed physical literacy in adults or have proposed measurement criteria. Relevant studies were identified by searching four databases (Pubmed, SportDiscus, APA PsycINFO, Web of Science), scanning reference lists of included articles, and manual cross-referencing of bibliographies cited in prior reviews. The final search was concluded on July 15, 2022. Thirty-one studies, published from 2016 to 2022, were analyzed. We found seven instruments measuring physical literacy in adults, of which six were questionnaires. The Perceived Physical Literacy Instrument was the first developed for adults and the most adopted. The included studies approached physical literacy definition in two ways: by pre-defining domains and assessing them discretely (through pre-validated or self-constructed instruments) and by defining domains as sub-scales after factorial analyses. We found a fair use of objective and subjective measures to assess different domains. The wide use of instruments developed for other purposes in combined assessments suggests the need for further instrument development and the potential oversimplification of the holistic concept, which may not result in a better understanding of physical literacy. Quality and usability characteristics of measurements were generally insufficiently reported. This lack of data makes it impossible to compare and make robust conclusions. We could not identify if any of the existing physical literacy assessments for adults is appropriate for large-scale/epidemiological studies.

Acute Effect of the "Zero Point" Method on Muscle Thickness and Muscle Damage in Trained Men.

The "zero point" method allows for lower intensities for an exercise session without impairing the total training volume. This study aimed to compare the effects of the "zero point" versus the traditional method on muscle responses and muscle damage in trained men. Fifteen experienced men (age: 27.7 ± 6.4 years; body mass: 78.4 ± 11.4 kg; height: 174.8 ± 4.9 cm; experience: 5.86 ± 4.7 years; relative bench press strength: 1.38 ± 0.17 kg·kg-1) were subjected to two exercise protocols in a randomized order and separated by a week. The traditional and "zero point" methods were applied in the bench press, with loads of 70% and 50% of one repetition maximum (1RM), respectively, for 10 sets until concentric failure, with 3-min intervals between sets. The zero point method displayed a higher number of repetitions and time under tension than the traditional method, with no difference in the total training volume, echo intensity, algometry, lactate, and myoglobin. For the muscle thickness, no differences between the groups were presented, except for the deltoid muscle thickness, in which a higher post-training volume was observed compared to traditional training. The "zero point" method increases the demand on the deltoid muscles in the bench press exercise, but not on the pectoralis and triceps brachii.

Different cardiovascular responses to a resistance training session in hypertensive women receiving propanolol compared with normotensive controls.

The aim of the present study was to compare the responses of blood pressure, heart rate, and rate-pressure product of hypertensive women using beta-blockers with healthy controls during resistance exercise (by the end of the concentric phase of the contractions) and in the postexercise period (5 and 30 minutes after). Ten untrained normotensive women (N) and 10 mildly hypertensive females receiving 40 mg/day of propanolol (H) were selected. Three sets of 10 repetitions at 80% of 10 repetitions maximum with 30 s rest interval were performed on the leg press exercise. The H group exhibited lower systolic blood pressure after the second set compared with N. Heart rate and rate-pressure product were lower in H in all analyzed periods compared with N. Propanolol attenuates the cardiovascular response to a leg press resistance exercise in mildly hypertensive women.

Arthroscopic treatment of tenosynovitis of the flexor hallucis longus tendon.

BACKGROUND: Tenosynovitis of the flexor hallucis longus (FHL) tendon is a condition typically found in ballet dancers and sometimes in soccer players and is related to chronic overuse. A traumatic cause for this situation, such as an ankle sprain, is considered rare. In case of failure of conservative treatment, the tendon can be surgically released, which is usually done through an open procedure. This article presents the results of an arthroscopic release of the FHL. METHODS: Twenty-seven patients underwent surgery for FHL tenosynovitis over a period of 18 months. The mean age of the patients was 34 years. All patients related the onset of the condition with an ankle sprain. Eighteen patients were on worker's compensation and five had sport-related accidents. None of the patients was a professional athlete or a ballet dancer. The mean follow-up was 32 months. The outcome was measured with a satisfaction questionnaire and with the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot scoring system. RESULTS: The mean postoperative AOFAS score was 89 with 70% excellent or good results. Mean satisfaction rate was 4 (range, 0 to 5); 89% of the patients would undergo the procedure again. Twenty-two patients (81%) returned to the same level of activity in work and sports. A complication rate of 18% (five patients) and reoperation rate of 4% (one patient) were found. CONCLUSION: Arthroscopic release of the FHL tendon was a valid procedure. It was a minimally invasive surgery that allowed good visualization of the involved structures and yielded good results. This condition can be related to trauma and is not an exclusive disease of ballet dancers or overuse.

Membrane-based TBADT recovery as a strategy to increase the sustainability of continuous-flow photocatalytic HAT transformations.

Photocatalytic hydrogen atom transfer (HAT) processes have been the object of numerous studies showcasing the potential of the homogeneous photocatalyst tetrabutylammonium decatungstate (TBADT) for the functionalization of C(sp3)-H bonds. However, to translate these studies into large-scale industrial processes, careful considerations of catalyst loading, cost, and removal are required. This work presents organic solvent nanofiltration (OSN) as an answer to reduce TBADT consumption, increase its turnover number and lower its concentration in the product solution, thus enabling large-scale photocatalytic HAT-based transformations. The operating parameters for a suitable membrane for TBADT recovery in acetonitrile were optimized. Continuous photocatalytic C(sp3)-H alkylation and amination reactions were carried out with in-line TBADT recovery via two OSN steps. Promisingly, the observed product yields for the reactions with in-line catalyst recycling are comparable to those of reactions performed with pristine TBADT, therefore highlighting that not only catalyst recovery (>99%, TON > 8400) is a possibility, but also that it does not happen at the expense of reaction performance.

Modular allylation of C(sp3)-H bonds by combining decatungstate photocatalysis and HWE olefination in flow.

The late-stage introduction of allyl groups provides an opportunity to synthetic organic chemists for subsequent diversification, furnishing a rapid access to new chemical space. Here, we report the development of a modular synthetic sequence for the allylation of strong aliphatic C(sp3)-H bonds. Our sequence features the merger of two distinct steps to accomplish this goal, including a photocatalytic Hydrogen Atom Transfer and an ensuing Horner-Wadsworth-Emmons (HWE) reaction. This practical protocol enables the modular and scalable allylation of valuable building blocks and has been applied to structurally complex molecules.

The Merger of Benzophenone HAT Photocatalysis and Silyl Radical-Induced XAT Enables Both Nickel-Catalyzed Cross-Electrophile Coupling and 1,2-Dicarbofunctionalization of Olefins.

A strategy for both cross-electrophile coupling and 1,2-dicarbofunctionalization of olefins has been developed. Carbon-centered radicals are generated from alkyl bromides by merging benzophenone hydrogen atom transfer (HAT) photocatalysis and silyl radical-induced halogen atom transfer (XAT) and are subsequently intercepted by a nickel catalyst to forge the targeted C(sp3)-C(sp2) and C(sp3)-C(sp3) bonds. The mild protocol is fast and scalable using flow technology, displays broad functional group tolerance, and is amenable to a wide variety of medicinally relevant moieties. Mechanistic investigations reveal that the ketone catalyst, upon photoexcitation, is responsible for the direct activation of the silicon-based XAT reagent (HAT-mediated XAT) that furnishes the targeted alkyl radical and is ultimately involved in the turnover of the nickel catalytic cycle.

Time Course of Recovery Following CrossFit® Karen Benchmark Workout in Trained Men.

The establishment of fatigue following the acute exercise stimulus is a complex and multi-factorial process, that might arise due to a range of distinct physiological mechanisms. However, a practical method of assessing CrossFit® athletes' recovery status has been neglected entirely in real-world sporting practice. The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4 ± 6.4 years; 1RM back squat 139.1 ± 26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls (9 kg), aiming to hit a target 3 m high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24, 48 and 72 h after the session. The creatine kinase concentration 24 h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; p = 0.040). At 48h and 72 h following exercise, CK concentration had returned to baseline levels (p > 0.05). The general, lower and upper limbs PRS scores were lower in the 24-h post-exercise compared to pre-exercise (general PRS: 4.7 ± 1.5 and 7.7 ± 1.7; p = 0.013; upper limbs PRS: 6.6 ± 1.3 and 7.5 ± 1.3; p = 0.037; lower limbs PRS: 3.9 ± 2.5 and 7.3 ± 0.1; p = 0.046). Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches and practitioners when planning training programs. Moreover, recovery status can be useful to optimize training monitoring and to minimize the potential detrimental effects associated with the performance of repeated high-intensity sessions of CrossFit®.

Time-course effects of functional fitness sessions performed at different intensities on the metabolic, hormonal, and BDNF responses in trained men.

BACKGROUND: To investigate the time-course effects of a self-regulated training session (performed at an rating perceived exertion of 6/10), all-out session, and a control session on the metabolic, hormonal, and brain derived neurotrophic factor (BDNF) responses in Functional-Fitness (FFT) participants. METHODS: In a randomized, crossover fashion, eight healthy males (age 28.1 ± 5.4 years old; body mass 77.2 ± 4.4 kg; VO2max: 52.6 ± 4.6 mL.(kg.min)-1; 2000 m rowing test 7.35 ± 0.18 min; 1RM back squat 135.6 ± 21.9 kg) performed a FFT session under two different conditions: all-out, or with the intensity controlled to elicit an rating perceived exertion (RPE) of 6 in the Borg 10-point scale (RPE6). A control session (no exercise) was also completed. Metabolic (lactate and creatine kinase), hormonal (testosterone and cortisol), and BDNF responses were assessed pre, post-0 h, 1 h, 2 h and 24 h after the sessions. RESULTS: Creatine kinase concentrations were significantly higher (p ≤ 0.05) after 24 h for both training sessions. Total and free testosterone concentrations were lower post-2 h for all-out when compared to the RPE6 session (p ≤ 0.05). Serum cortisol concentration increased post-0 h (p = 0.011) for RPE6 and post-0 h (p = 0.003) and post-1 h (p = 0.030) for all-out session when comparing to baseline concentrations. BDNF was significantly higher (p = 0.002) post-0 h only for the all-out session when compared to baseline. A positive correlation between blood lactate concentrations and BDNF (r = 0.51; p = 0.01) was found for both effort interventions. CONCLUSIONS: A single FFT session when performed in all-out format acutely increases the concentrations of serum BDNF. However, physiological stress markers show that the all-out session requires a longer recovery period when compared to the RPE6 protocol. These findings can be helpful to coaches and practitioners design FFT session.

Case study in treatment of diabetic foot ulcer with alimentary gelatin.

The patient with diabetic foot ulceration is undoubtedly one of the major challenges faced by nurses and physicians working in the field of wound treatment. About 15% of diabetic patients experience foot ulceration in the course of their disease. This article reports the adoption of an unconventional treatment, based on gelatin, in a case of a stagnant diabetic foot ulcer, resulting in the successful healing of the wound and the limb being saved. Gelatin is fundamentally denatured collagen; its presence is paramount in the natural healing process, and this may be one of the reasons that the treatment obtained a good result. The fact that the gelatin used is of animal origin does not appear to compromise the outcome of treatment.

Incremental and decremental cardiopulmonary exercise testing protocols produce similar maximum oxygen uptake in athletes.

The aim of the study was to evaluate and compare the maximal oxygen uptake ([Formula: see text]O2max) achieved during incremental and decremental protocols in highly trained athletes. Nineteen moderate trained runners and rowers completed, on separate days, (i) an initial incremental [Formula: see text]O2max test (INC) on a treadmill, followed by a verification phase (VER); (ii) a familiarization of a decremental test (DEC); (iii) a tailored DEC; (iv) a test with decremental and incremental phases (DEC-INC); (v) and a repeated incremental test (INCF). During each test [Formula: see text]O2, carbon dioxide production, ventilation, heart and breath rates and ratings of perceived exertion were measured. No differences were observed in [Formula: see text]O2max between INC (61.3 ± 5.2 ml kg-1 min-1) and DEC (61.1 ± 5.1 ml kg-1 min-1; average difference of ~ 11.58 ml min-1; p = 0.831), between INC and DEC-INC (60.9 ± 5.3 ml kg-1 min-1; average difference of ~ 4.8 ml min-1; p = 0.942) or between INC and INCF (60.7 ± 4.4 ml kg-1 min-1; p = 0.394). [Formula: see text]O2max during VER (59.8 ± 5.1 ml kg-1 min-1) was 1.50 ± 2.20 ml kg-1 min-1 lower (~ 2.45%; p = 0.008) compared with values measured during INC. The typical error in the test-to-test changes for evaluating [Formula: see text]O2max over the five tests was 2.4 ml kg-1 min-1 (95% CI 1.4-3.4 ml kg-1 min-1). Decremental tests do not elicit higher [Formula: see text]O2max than incremental tests in trained runners and rowers, suggesting that a plateau in [Formula: see text]O2 during the classic incremental and verification tests represents the maximum ceiling of aerobic power.

Local Muscle Endurance and Strength Had Strong Relationship with CrossFit® Open 2020 in Amateur Athletes.

This study analyzed the relationship between anthropometric measures, cardiorespiratory capacity, strength, power, and local muscle endurance with performance in the CrossFit® Open 2020. For this, 17 volunteers (6 women) (29.0 ± 7.2 years) completed, on separate weeks, tests for body composition (dual-energy X-ray absorptiometry), maximal oxygen consumption (2 km row test), muscle strength (one repetition maximum (1 RM) back and front squat, isometric peak torque), muscle power (1 RM snatch and clean and jerk) and muscle endurance (Tibana test), which were compared with performance during the CrossFit® Open 2020. Specific tests of localized muscular endurance and muscle strength had the strongest relationship with performance in the CrossFit® Open 2020. On the other hand, the percentage of fat and cardiorespiratory capacity were not significantly correlated with CrossFit® Open 2020 workout performance. Coaches and practitioners should therefore utilize these findings to assess physical fitness and organize the distribution of the training session based on less developed physical needs, in order to ensure an appropriate physiological adaptation for a given competition.