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Experiencing an increasing incidence, chronic heart failure (CHF) demands effective prevention and treatment. Aerobic exercise-based cardiac rehabilitation plays a vital role in managing these patients. However, diverse patient responses underscore the need for precision in intensity prescription. Heart rate variability (HRV), specifically the DFA a1 index, emerges as a cost-effective biomarker for exercise intensity distribution (Rogers et al., 2021a). Previous associations between HRV and ventilatory thresholds in CHF patients suggest its potential utility (Rogers et al., 2021b). This study aims to evaluate the agreement between ventilatory thresholds (VT1 and VT2) and HRV thresholds (HRVT1 and HRVT2) in male and female CHF patients during a cardiopulmonary exercise test. Seventeen males and ten females performed a symptom-limited incremental ramp test on a cycle ergometer. Ventilatory thresholds were determined using a mixed method, and HRV thresholds were calculated using DFA a1 values of 0.75 and 0.5 as the first and second thresholds, respectively. Statistical measures, including the Pearson’s r correlation coefficient, determination coefficient, and Bland-Altman plot with limits of agreement (LoAs), were employed to evaluate the agreement between these methods. Initial findings indicate that HRVT1 shows a non-significant, low positive correlation (r = .36) with VT1, with a determination coefficient of .13, and a mean bias of -5 bpm (LoAs from -35 to 25 bpm). Conversely, HRVT2 demonstrates a significant, strong positive correlation with VT2 (r = .78), presenting a determination coefficient of .62 and a mean bias of 6 bpm (LoAs from -16 to 28 bpm). This suggests promising potential validity for HRVT2 in estimating ventilatory thresholds. In conclusion, while HRVT1 requires further investigation in this population and caution is advised in its application, HRVT2 emerges as a compelling candidate, demonstrating good agreement with VT2 and suggesting its potential validity as a valuable tool for exercise intensity determination in CHF patients.

Brain-derived neurotrophic factor (BDNF), known for its pivotal role in neuroplasticity, has emerged as a promising diagnostic and prognostic biomarker for chronic heart failure (CHF). BDNF, through its interaction with the tropomyosin-related kinase receptor B (TrkB), has been linked with the pathogenesis of various cardiovascular diseases, including coronary artery disease, cardiomyopathy, and hypertension. Patients with CHF exhibit diminished BDNF levels compared to their healthy counterparts. Notably, exercise has been shown to elevate BDNF levels in healthy individuals. However, no study has explored the potential effects of acute exercise on BDNF levels in patients with CHF. Therefore, the aim of the current study was to analyse the acute effect of aerobic exercise on BDNF levels in patients with CHF. Additionally, we investigated the influence of different patient characteristics (e.g., age, weight, and cardiorespiratory fitness) and exercise variables (e.g., duration) on BDNF concentrations. Eleven patients (53.2 ± 5.5 years; seven males) with CHF were finally included. BDNF levels were measured before and immediately after a cardiopulmonary exercise test on a cycle ergometer. Paired t-test, mean change with its 95% confidence interval (CI), and Pearson correlation were used to conduct statistical analyses. Moreover, Mann-Whitney U test was used to carry out between-group comparisons (e.g., sex) in changes in BDNF. Correlations were interpreted as weak (< 0.30), low (0.30 – 0.49), moderate (0.50 – 0.69), strong (0.70 – 0.89), or very strong (> 0.90). The findings showed a statistically significant increase (p = .005) in BDNF levels of 320.7 (CI = 136.4, 505.1) pg·ml-1. No differences were found between male and female patients (p = .269). Moreover, a moderate yet non-significant negative correlation was observed between the acute exercise-induced effect on BDNF levels and patients’ weight (r = –0.593; p = .054) and body mass index (BMI) (r = –0.530; p = .094). Aerobic exercise acutely increases BDNF levels in male and female patients with CHF. Further studies are required to determine the influence of patient characteristics (i.e., weight and BMI).

The ability of microbially produced poly(γ,d-glutamic acid) to form stable polyelectrolyte−opposite charged surfactant complexes was investigated. A sonicated sample of polyacid with a molecular weight about 10⁵ Da and a content of d enantiomer higher than 90% was used in this study. Nearly stoichiometric complexes of poly(γ,d-glutamate) anions and alkyltrimethylammonium cations bearing linear alkyl chains with even numbers of carbon atoms from 12 up to 22 were “synthesized” by precipitation from equimolar mixtures of aqueous solutions of the two components. All complexes were found to adopt stratified supramolecular structures made of alternating layers of poly(γ,d-glutamate) and surfactant with a periodicity increasing from 3.2 up to 4.3 nm according to the length of the alkyl side chain. No definite evidence indicative of the conformation adopted by the main chain in these complexes could be afforded. In all cases, the alkyl chains are in an extended conformation and oriented normal or nearly normal to the layer planes. Polymethylene chains with more than 16 carbon atoms were partially crystallized in the complexes in a separated paraffinic phase, whereas no crystallinity was detected for shorter lengths. The crystallized paraffinic phases were found to melt reversibly at temperatures between 40 and 70 °C. This process was found to happen with a concomitant expansion−contraction that amounts between 2 and 8% of the long period of the structure but without significant alteration of the layered arrangement.

The conformation and crystal structure of the benzyl ester of microbial poly(γ,dl-glutamic acid) with a nearly racemic composition was investigated by X-ray diffraction, polarized infrared spectroscopy and molecular modeling simulations. Three different molecular arrangements were characterized. Form I was found to be a structure made of hydrogen-bonded sheets of chains in a nearly extended conformation with features similar to the well-known γ-form of nylons. Form III consisted of a hexagonal packing of 37/10 helices stabilized by intramolecular hydrogen bonds set between i and i + 3 amide groups. Form II was observed as a poorly oriented phase and identified with the 5/2 helical form previously described for optically pure poly(α-benzyl γ,l-glutamate). Energy calculations indicated that the helical conformations adopted by PAB(DL)G are incompatible with a polymer having a statistical distribution of D and L units and that a polymer made of d- and l-stereoblocks is the most appropriate to describe the crystal structure present in form I.

The synthesis of 2,3-disubstituted poly(β-peptide)s (nylon-3 analogues) bearing the benzyloxy group at position 3 and the diethoxymethyl or the isobutoxycarbonyl group at position 2, is described. Both optically pure and racemic forms were prepared for each case and all them were characterized by standard methods. The structure of these poly(β-peptide)s was preliminary examined by X-ray diffraction and infrared spectroscopy. It was concluded that they do not tend to adopt the α-helixlike conformation characteristic of poly(β-l-aspartate)s but rather a contracted conformation with amide groups in the nonassociated state.

The helix−coil conformational transition taking place in a family of poly(β-peptide)s, namely, poly(α-alkyl-β-aspartate)s (Mw > 100 000), upon addition of acid or by changes in temperature has been investigated. Results obtained for a set of optically pure polymers differing in the size and shape of the alkyl side chain evidenced that the transition is a phenomenon common to all poly(β-l-aspartate)s. Experimental conditions required for transition were found to be independent of the constitution of the poly(β-peptide). Investigation of poly(β-d,l-aspartate)s with different enantiomeric composition and configurational sequence revealed the occurrence of the helix−coil transition in block stereocopolymers for any d/l ratio but not in stereocopolymers with a statistical distribution of the antipode units.

A set of poly(β-l-aspartate)s bearing branched alkyl side groups of varying shapes and sizes has been synthesized, and the crystal structures of these polymers have been investigated by X-ray diffraction and computational methods. The anionic ring-opening polymerization of 4-((S)-alkoxycarbonyl)-β-lactams (the alkyl groups being isopropyl, isopentyl, and neopentyl) afforded the corresponding poly(α-alkyl β-l-aspartate)s with high molecular weights in good yields. The thermal behavior of these poly(β-l-aspartate)s parallels that described for their linear alkyl side chain homologues with a melting−decomposition process taking place above 250 °C. The analysis of fiber X-ray diffraction diagrams complemented with molecular mechanics modeling and LALS refinement revealed that helical conformations of α-helix type were adopted in the three cases. Whereas the isopentyl derivative crystallized in a quasi-hexagonal form with the chains in the right-handed 13/4 helical conformation characteristic of this family of compounds, a hexagonal array of 16/5 helices was found to be the arrangement preferred by the isopropyl and neopentyl derivatives. These two polymers displayed in addition the second crystal form common in poly(β-l-aspartate)s, which consists of a tetragonal structure of right-handed 4/1 helices. Energy calculations showed negligible energy differences between the two crystal forms in both systems. Conformation and crystal packing of linear and branched poly(β-l-aspartate)s were compared and their features discussed with regards to the architecture of the alkyl side group.

The conformation and crystal structure of two nylon 3 derivatives bearing a cycloalkoxycarbonyl group on the β-carbon of the main chain, namely, poly(α-cyclopentyl-β-l-aspartate) and poly(α-cyclohexyl-β-l-aspartate), were examined. X-ray diffraction data revealed that both compounds adopt a 13/4 helical conformation of the type usually found for the hexagonal form of poly(β-l-aspartate)s bearing acyclic alkyl side chains. Whereas poly(α-cyclopentyl-β-l-aspartate) crystallized in a monoclinic structure (pseudohexagonal, space group P21), the cyclohexyl derivative deviated from the general pattern, crystallizing in a slightly distorted hexagonal lattice in the space group P1. AMBER energy optimization algorithms and linked-atom least-squares refinement applied to X-ray data were used to analyze the structure of poly(α-cyclohexyl-β-l-aspartate). Energy calculations made on an isolated chain revealed that the cyclohexyl side group is in the equatorial chair conformation and that the 13/4 helix will be sterically incompatible with the existence of mixed populations of axial and equatorial conformers within the same molecule. The analysis of the mimicked crystal favored the antiparallel arrangement of chains, but it was unable to discriminate between the different crystal models compatible with diffraction data.¹H NMR measurements in solution proved that the helical conformation adopted in the solid state is still retained in the liquid state. ¹³C CP−MAS NMR experiments furnished further evidence on the structural conclusions derived from theoretical methods.

The conformational analysis of (S)-4-(cyclohexoxycarbonyl)-2-azetidinone was carried out using quantum mechanical calculations.¹H NMR spectra at different temperatures were used to estimate the relative populations of axial and equatorial chair forms of the cyclohexyl group. Gas-phase energy calculations of the whole molecule rendered two preferred structures, both of them with the cyclohexyl group in equatorial conformation. The azetidinone ring was found to be in a quasi-planar arrangement with endocyclic dihedrals deviating from the ideal planar conformation by 1−2°. Results showed also that the cyclohexoxycarbonyl group is highly flexible and that the stabilization of the molecule is favored by intramolecular interactions between the amide and the ester group. The occurrence of this type of interaction in nonpolar solution was evidenced by FTIR spectroscopy. Additionally, SCRF calculations revealed that solvent effects on the conformational preferences of this compound are small.

The conformation of three poly(α-alkyl β-l-aspartate)s, abbreviated PAALA-n, with the alkyl group being methyl, ethyl, and propyl (n = 1, 2, and 3), was examined by X-ray diffraction, polarized infrared spectroscopy, and molecular mechanics calculations. The crystal structure was modeled and refined against diffraction data with the linked-atom least-squares methodology (LALS). Two crystal forms reminiscent of the well-known α-helix and pleated β-sheet structures typical of polypeptides were characterized for the methyl derivative. The helical form is a pseudohexagonal lattice of right-handed 17/4 helices stabilized by intramolecular hydrogen bonds. The β form is made of chains in nearly extended conformation and hydrogen bonded to each other to form sheets which stack together in a metrically orthorhombic crystal lattice. In addition to these two forms, a second folded form made of right-handed 4/1 helices arranged in a tetragonal structure was characterized for the ethyl derivative. Poly(α-propyl β-l-aspartate) was found to display a crystal dimorphism entailing the hexagonal and tetragonal helical forms whereas no signs of extended conformation were detected for this polymer. In this case, the hexagonal form was found to be composed of right-handed 13/4 helices, which is the conformation usually observed in poly(β-l-aspartate)s with linear alkyl side chains of medium and larger sizes. The structural behavior exhibited by the three compounds under study is consistent with the general pattern described for PAALA-n with n ranging from 4 to 22 which have been previously studied by us in full detail.