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We have studied the effect of transient vibrational inversion of population in trans-β-apo-8'-carotenal on the time-resolved femtosecond stimulated Raman scattering (TR-FSRS) signal. The experimental data are interpreted by applying a quantum mechanical approach, using the formalism of projection operators for constructing the theoretical model of TR-FSRS. Within this theoretical frame we explain the presence of transient Raman losses on the Stokes side of the TR-FSRS spectrum as the effect of vibrational inversion of population. In view of the obtained experimental and theoretical results, we conclude that the excited S2 electronic level of trans-β-apo-8'-carotenal relaxes towards the S0 ground state through a set of four vibrational sublevels of S1 state. [ABSTRACT FROM AUTHOR]

The inter- and intramolecular interactions of the carbonyl moieties at the polar interface of a phospholipid membrane are probed by using nonlinear femtosecond infrared spectroscopy. Two-dimensional IR correlation spectra separate homogeneous and inhomogeneous broadenings and show a distinct cross-peak pattern controlled by electrostatic interactions. The inter- and intramolecular electrostatic interactions determine the inhomogeneous character of the optical response. Using molecular dynamics simulation and the nonlinear exciton equations approach, we extract from the spectra short-range structural correlations between carbonyls at the interface. [ABSTRACT FROM AUTHOR]

Knee arthroplasty, commonly performed to treat osteoarthritis, necessitates precise surgical techniques for optimal outcomes. The introduction of systems such as the Persona Knee System (Zimmer Biomet, Warsaw, IN, USA) has revolutionized knee arthroplasty, promising enhanced precision and better patient outcomes. This study investigates the application of robotic planning specifically in knee prosthetic surgeries, with a focus on Persona Knee System prostheses. We conducted a retrospective analysis of 300 patients who underwent knee arthroplasty using the Persona Knee System between January 2020 and November 2023, including demographic data, surgical parameters, and preoperative imaging. Robotic planning was employed to simulate surgical procedures. The planning process integrated preoperative imaging data from a specific program adopted for conducting digital preoperative planning, and statistical analyses were conducted to assess correlations between patient characteristics and surgical outcomes. Out of 300 patients, 85% presented with minor deformities, validating the feasibility of robotic planning. Robotic planning demonstrated precise prediction of optimal arthroplasty sizes and alignment, closely aligning with preoperative imaging data. This study highlights the potential benefits of robotic planning in knee arthroplasty surgeries, particularly in cases with minor deformities. By leveraging preoperative imaging data and integrating advanced robotic technologies, surgeons can improve precision and efficacy in knee arthroplasty. Moreover, robotic technology allows for a reduced level of constraint in the intraoperative choice between Posterior-Stabilized and Constrained Posterior-Stabilized liners compared with an imageless navigated procedure., Competing Interests: F.B. and SMP.R. declare a teaching contract with the manufacturer (Zimmer Biomet). The other authors declare no conflicts of interest related to the present study.

Background : Pelvic insufficiency fractures (PIF) are typical in geriatric populations with reduced bone quality, most commonly in elderly postmenopausal women. These fractures are usually caused by low-energy forces over the bones during ordinary life and cause disabling pain. Treatment options range from conservative to operative. The aim of this study is to assess the outcomes of treatments for pelvic insufficiency fractures, determining optimal approaches between surgical intervention and conservative management. Methods : This literature review systematically examines articles focusing on patients with PIF, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and using PubMed, Medline, and the Cochrane Library database. We took into account only full-text articles in indexed journals with available English abstracts, considering data about patient demographics, surgery, and outcomes. Results: After screening 128 articles, this study reviewed 20 manuscripts involving 1499 patients, mostly elderly females and focusing on sacrum fractures. Common treatments included conservative methods and sacroplasty, with a few complications reported. Osteoporosis was the prevalent comorbidity, and the survival rate post-treatment was high at 92.3%. Mobility outcomes varied, with some patients experiencing significant autonomy loss. The average follow-up period was over 17 months. Conclusions : This study found a cautious approach to surgery (timing of three weeks), which is reserved only for specific patterns, and it leads to increased autonomy and a lower risk of mortality. Due to the lack of pre- and postoperative scores as well as conflicting results, it is imperative to undertake further studies and research to be able to compare the alternative treatments efficiently.

By means of one- and two-dimensional transient infrared spectroscopy and femtosecond stimulated Raman spectroscopy, we investigated the excited state dynamics of peridinin, a carbonyl carotenoid occurring in natural light harvesting complexes. The presence of singly and doubly excited states, as well as of an intramolecular charge transfer (ICT) state, makes the behavior of carbonyl carotenoids in the excited state very complex. In this work, we investigated by time resolved spectroscopy the relaxation of photo-excited peridinin in solvents of different polarities and as a function of the excitation wavelength. Our experimental results show that a characteristic pattern of one- and two-dimensional infrared bands in the C=C stretching region allows monitoring the relaxation pathway. In polar solvents, moderate distortions of the molecular geometry cause a variation of the single/double carbon bond character, so that the partially ionic ICT state is largely stabilized by the solvent reorganization. After vertical photoexcitation at 400 nm of the S2 state, the off-equilibrium population moves to the S1 state with ca. 175 fs time constant; from there, in less than 5 ps, the non-Franck Condon ICT state is reached, and finally, the ground state is recovered in 70 ps. That the relevant excited state dynamics takes place far from the Franck Condon region is demonstrated by its noticeable dependence on the excitation wavelength.

In this work we analyzed the infrared and visible transient absorption spectra of all-trans-β-apo-8'-carotenal in several solvents, differing in both polarity and polarizability at different excitation wavelengths. We correlate the solvent dependence of the kinetics and the band shape changes in the infrared with that of the excited state absorption bands in the visible, and we show that the information obtained in the two spectral regions is complementary. All the collected time-resolved data can be interpreted in the frame of a recently proposed relaxation scheme, according to which the major contributor to the intramolecular charge transfer (ICT) state is the bright 1Bu(+) state, which, in polar solvents, is dynamically stabilized through molecular distortions and solvent relaxation. A careful investigation of the solvent effects on the visible and infrared excited state bands demonstrates that both solvent polarity and polarizability have to be considered in order to rationalize the excited state relaxation of trans-8'-apo-β-carotenal and clarify the role and the nature of the ICT state in this molecule. The experimental observations reported in this work can be interpreted by considering that at the Franck-Condon geometry the wave functions of the S1 and S2 excited states have a mixed ionic/covalent character. The degree of mixing depends on solvent polarity, but it can be dynamically modified by the effect of polarizability. Finally, the effect of different excitation wavelengths on the kinetics and spectral dynamics can be interpreted in terms of photoselection of a subpopulation of partially distorted molecules.

Lung cancer is the leading cause of cancer-related death around the world; the addition of chemotherapy to treatment of this disease has been shown to significantly increase progression-free survival and overall survival. Despite newer chemotherapies, it is important to personalize the care (treatment and dose) upon each single patient's susceptibility for controlling and reducing adverse side-effects, at best. The present review describes the current status of pharmacogenomics studies regarding germline DNA variants that may alter response and tolerability to chemotherapeutic agents used to treat lung cancer, including perspective studies., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

The excited state dynamics of carbonyl carotenoids is very complex because of the coupling of single- and doubly excited states and the possible involvement of intramolecular charge-transfer (ICT) states. In this contribution we employ ultrafast infrared spectroscopy and theoretical computations to investigate the relaxation dynamics of trans-8'-apo-β-carotenal occurring on the picosecond time scale, after excitation in the S2 state. In a (slightly) polar solvent like chloroform, one-dimensional (T1D-IR) and two-dimensional (T2D-IR) transient infrared spectroscopy reveal spectral components with characteristic frequencies and lifetimes that are not observed in nonpolar solvents (cyclohexane). Combining experimental evidence with an analysis of CASPT2//CASSCF ground and excited state minima and energy profiles, complemented with TDDFT calculations in gas phase and in solvent, we propose a photochemical decay mechanism for this system where only the bright single-excited 1Bu(+) and the dark double-excited 2Ag(-) states are involved. Specifically, the initially populated 1Bu(+) relaxes toward 2Ag(-) in 200 fs. In a nonpolar solvent 2Ag(-) decays to the ground state (GS) in 25 ps. In polar solvents, distortions along twisting modes of the chain promote a repopulation of the 1Bu(+) state which then quickly relaxes to the GS (18 ps in chloroform). The 1Bu(+) state has a high electric dipole and is the main contributor to the charge-transfer state involved in the dynamics in polar solvents. The 2Ag(-) → 1Bu(+) population transfer is evidenced by a cross peak on the T2D-IR map revealing that the motions along the same stretching of the conjugated chain on the 2Ag(-) and 1Bu(+) states are coupled.

Carbon monoxide recombination dynamics in a mutant of the truncated hemoglobin from Thermobida fusca (3F-Tf-trHb) has been analyzed by means of ultrafast Visible-pump/MidIR-probe spectroscopy and compared with that of the wild-type protein. In 3F-Tf-trHb, three topologically relevant amino acids, responsible for the ligand stabilization through the formation of a H-bond network (TyrB10 TyrCD1 and TrpG8), have been replaced by Phe residues. X-ray diffraction data show that Phe residues in positions B10 and G8 maintain the same rotameric arrangements as Tyr and Trp in the wild-type protein, while Phe in position CD1 displays significant rotameric heterogeneity. Photodissociation of the ligand has been induced by exciting the sample with 550 nm pump pulses and the CO rebinding has been monitored in two mid-IR regions respectively corresponding to the ν(CO) stretching vibration of the iron-bound CO (1880-1980 cm(-1)) and of the dissociated free CO (2050-2200 cm(-1)). In both the mutant and wild-type protein, a significant amount of geminate CO rebinding is observed on a subnanosecond time scale. Despite the absence of the distal pocket hydrogen-bonding network, the kinetics of geminate rebinding in 3F-Tf-trHb is very similar to the wild-type, showing how the reactivity of dissociated CO toward the heme is primarily regulated by the effective volume and flexibility of the distal pocket and by caging effects exerted on the free CO on the analyzed time scale.

Lung cancer is the leading cause of cancer-related death worldwide, with approximately 1.2 million deaths annually. The standard-of-care in patients with advanced disease is platinum-based doublet chemotherapy. Recent advances in the understanding of biological mechanisms of tumor growth have allowed for identification of some molecular targets for cancer treatment, such as vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR). VEGF is a pro-angiogenetic factor, which binds membrane receptors, and whose intra-cytoplasmatic domain presents tyrosine kinase activity. Pathological angiogenesis promotes tumor growth and metastasis. Targeted action against angiogenesis can lead to regression or normalization of neovascular structures and to inhibition of new blood vessel growth. The most commonly used mechanism is mediated by bevacizumab, a monoclonal antibody that selectively binds to VEGF and prevents interaction with its receptor. Currently bevacizumab is the only anti-angiogenic agent approved for the first-line treatment of non-small cell lung cancer (NSCLC) in selected patients. In the present review, we discuss the most important trials that demonstrate the efficacy and safety of bevacizumab. We also present an overview of the types of patients eligible for this treatment and a cost-effectiveness analysis. In conclusion, the possibility of administering a treatment with bevacizumab must be carefully analyzed case by case. It is important to identify those patients who can really benefit from the use of this drug, through the identification of specific response markers.

We present a case report of a 75-years-old woman affected by renal clear cell carcinoma with a synchronous pancreatic metastasis and a metachronous lung metastasis. This case has two peculiarities. First the pancreatic metastasis was treated just with medical therapy, that is, Sunitinib, instead of the surgical therapy that is mostly considered. Secondly, the pancreatic lesion showed different characteristics on the computed tomography scan compared to the usual pancreatic metastases from renal clear cell carcinoma. The pancreatic metastasis totally regressed after medical treatment and nowadays, four years after the diagnosis, the patient is disease-free.

In this work, we studied the valence tautomerism process on two different Co-dioxolene complexes by means of transient infrared spectroscopy (TRIR). The molecules investigated are ls-Co(III)(Cat-N-BQ)(Cat-N-SQ) (DQ2) and [ls-Co(III)(tpy)(Cat-N-SQ)]PF6 (tpy), where Cat-NBQ = 2-(2-hydroxy-3,5-ditert-butylphenyl-imino)-4,6-ditert-butylcyclohexa-3,5-dienone, Cat-N-SQ is the dianionic radical analogue, and tpy = 2,2'-6-2″-terpyridine. DFT calculations of the harmonic frequencies for the two complexes allow us to pinpoint the normal modes to be used as markers of the semiquinonate and benzoquinonate isomers. The photoinduced one-electron charge transfer process from the radical semiquinonate ligand to the metal center leads to a ls-Co(II)(x)(Cat-N-BQ) electronic state (where x is the other ligand). Following this first step, an ultrafast ISC process (τ < 200 fs) takes places, yielding the benzoquinonate isomer (hs-Co(II)(x)(Cat-N-BQ)). In the experiments, we employed different excitation wavelengths on resonance with different absorption bands of the two samples. Excitation in the ligand-to-metal charge transfer (LMCT) band at ∼520 nm and in the semiquinonate band at ∼1000 nm induces the valence tautomerism (VT) in both samples. From the time evolution of the TRIR spectra, we determine the time constants of the vibrational cooling in the tautomeric state (7-14 ps) and the ground state recovery times (∼350 ps for tpy and ∼450 ps for DQ2). In contrast, when the pump frequency is set at 712 nm, on resonance with the benzoquinonate absorption band of the second active ligand of the DQ2, no electron transfer takes place: the TRIR spectra basically show only ground state bleaching bands and no marker band of the tautomeric conversion shows up.

Carbon monoxide recombination dynamics upon photodissociation with visible light has been characterized by means of ultrafast visible-pump/MidIR probe spectroscopy for the truncated hemoglobins from Thermobifida fusca and Bacillus subtilis. Photodissociation has been induced by exciting the sample at two different wavelengths: 400 nm, corresponding to the heme absorption in the B-band, and 550 nm, in the Q-bands. The bleached iron-CO coordination band located at 1850-1950 cm(-1) and the free CO absorption band in the region 2050-2200 cm(-1) have been observed by probe pulses tuned in the appropriate infrared region. The kinetic traces measured at 1850-1950 cm(-1) reveal multiexponential subnanosecond dynamics that have been interpreted as arising from fast geminate recombination of the photolyzed CO. A compared analysis of the crystal structure of the two proteins reveals a similar structure of their distal heme pocket, which contains conserved polar and aromatic amino acid residues closely interacting with the iron ligand. Although fast geminate recombination is observed in both proteins, several kinetic differences can be evidenced, which can be interpreted in terms of a different structural flexibility of the corresponding heme distal pockets. The analysis of the free CO band-shape and of its dynamic evolution brings out novel features about the nature of the docking site inside the protein cavity.

The hydrogen-bond dynamics of lithium nitrate trihydrate has been studied by a combined approach based on ab initio molecular dynamics simulations and wavelet analysis. The simultaneous bifurcated interaction between one hydrogen atom of water molecules and two oxygen atoms of nitrate ions is the pivotal feature of the crystal structure: this bifurcated interaction has deep effects on the O-H stretching region of the vibrational spectrum. The structural, dynamic, spectroscopic, and electronic properties of the bifurcated hydrogen bond have been investigated computationally, elucidating at the molecular level the differences with weak and strong hydrogen bonds present in the crystal. These studies corroborate the very recent IR experiments performed on the lithium nitrate trihydrate crystal, offering new perspectives to interpreting the vibrational spectra. In fact, this approach allows obtaining two-dimensional plots, which summarize the essential features of both the hydrogen-bond network and IR spectra, resulting in a peculiar "signature" of the bifurcated interaction.