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Hallux valgus (HV) is a frequent forefoot deformity affecting about 23% of adults and 35.7% of people over 65. The exact etiology is not fully understood. The first ray plays a significant role in walking cause it bears the principal amount of weight and maintains the position of the medial arch. Several factors that deteriorate the integrality of the first ray, such as foot deformities, restrictive footwear, and pes planus, may be ascribed to the HV occurrence. Before any surgical correction, conservative treatment should always be initiated first. Currently, there is no consensus that conservative management by shoe modification and foot orthoses could correct the pathology or terminate the clinical worsening of the condition.From a careful analysis of the literature, proper footwear should be a shoe with an adequate length, wide toe box, cushioned sole, and a lowered heel to not increase the load on the metatarsal heads and cause pain. Personalized 3D printed customized toe spreaders may be applied in patients with HV, improving symptoms and bringing pain relief. Compensating the subtalar joint hyperpronation through foot orthoses plays a fundamental role in the HV development, preventing or at least controlling the condition's progress; this, along with weight reduction and regular physical activity.Data obtained suggest that dynamic foot orthoses prefer a biomechanical type with 3/4-length, which is less likely to negatively affect the dorsal or medial pressures, which instead were noted to increase with the sulcus- and full-length orthoses.Although some studies suggest that foot orthoses would favor the correction of HV deformity, results have been very variable and just in few studies appear to correct HV or reduce its progression, improving symptoms and bringing pain relief. In the case of HV surgical correction, orthoses seem to maintain the correct position acquired over time.
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BACKGROUND: Minimally invasive surgery (MIS) in medial displacement calcaneus osteotomy (MDCO) has been proposed for surgical correction of adult-acquired flat foot deformity (AAFD) to reduce complications of open approaches. The aim of our study is to systematically analyze complications and the clinical and radiological results of MIS- MDCO. METHODS: A systematic review of the English literature was performed on 30th October 2023. Randomized controlled trials and non-randomized trials, cohort studies, case-control studies and case series concerning surgical correction of AAFD with MIS-MDCO and with at least 15 patients were included. Case reports, technical notes, animal or cadaveric studies were excluded. The quality and risk of bias of the studies included were evaluated using GRADE and MINORS systems. Complications rate, clinical and radiological results were inferred from the studies included. RESULTS: Nine articles were included. A total of 501 cases treated with MIS-MDCO were analysed with a mean follow-up of 11.9 ± 5.1 months. The reported wound infection rate was about 3% and sural neuropathy was rated about 1%. Only 4% of the cases required removal of the screw for pain. In the comparative studies (MIS versus Open MDCO), comparable clinical results but with significant differences (P < 0.001) in infection rates (1% versus 14%) and sural neuropathy (2% versus 1%) were observed. CONCLUSION: AAFD correction performed with MIS-MDCO, with the limitation of a poor quality and high risk of bias of the included studies, seems to provide good clinical results and high subjective satisfaction with a lower complication rate compared to open approach. Further high-quality long-term comparative studies could better clarify complications and clinical and radiological outcomes of the MIS technique in the treatment of AAFD. LEVEL OF EVIDENCE: Level IV.
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Calcáneo , Pie Plano , Procedimientos Quirúrgicos Mínimamente Invasivos , Osteotomía , Humanos , Pie Plano/cirugía , Pie Plano/diagnóstico por imagen , Calcáneo/cirugía , Osteotomía/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Deformidades Adquiridas del Pie/cirugía , Complicaciones Posoperatorias/epidemiologíaRESUMEN
The nuclear incompressibility is a key parameter of the nuclear equation of state that can be extracted from the measurements of the so-called "breathing mode" of finite nuclei. The most serious discrepancy so far is between values extracted from Pb and Sn, that has provoked the longstanding question "Why is tin so soft?". To solve this puzzle, a fully self-consistent quasiparticle random-phase approximation plus quasiparticle-vibration coupling approach based on Skyrme-Hartree-Fock-Bogoliubov is developed. We show that the many-body correlations introduced by quasiparticle-vibration coupling, which shift the isoscalar giant monopole resonance energy in Sn isotopes by about 0.4 MeV more than the energy in ^{208}Pb, play a crucial role in providing a unified description of the isoscalar giant monopole resonance in Sn and Pb isotopes. The best description of the experimental strength functions is given by SV-K226 and KDE0, which are characterized by incompressibility values K_{∞}=226 MeV and 229 MeV, respectively, at mean field level.
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Heme, an iron-containing prosthetic group found in many proteins, carries out diverse biological functions such as electron transfer, oxygen storage and enzymatic reactions. Hemin, the oxidised form of heme, is used to treat porphyria and also to activate heme-oxygenase (HO) which catalyses the rate-limiting step in heme degradation. Our group has previously demonstrated that hemin displays antitumor activity in breast cancer (BC). The aim of this work has been to study the effect of hemin on protein expression modifications in a BC cell line to gain insight into the molecular mechanisms of hemin antitumor activity. For this purpose, we carried out proteome analysis by Mass Spectrometry (MS) which showed that 1309 proteins were significantly increased in hemin-treated cells, including HO-1 and the proteases that regulate HO-1 function, and 921 proteins were significantly decreased. Furthermore, the MS-data analysis showed that hemin regulates the expression of heme- and iron-related proteins, adhesion and cytoskeletal proteins, cancer signal transduction proteins and enzymes involved in lipid metabolism. By biochemical and cellular studies, we further corroborated the most relevant in-silico results. Altogether, these results show the multiple physiological effects that hemin treatment displays in BC and demonstrate its potential as anticancer agent.
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Neoplasias de la Mama , Hemina , Humanos , Femenino , Hemina/farmacología , Hemo-Oxigenasa 1/metabolismo , Proteómica , Hemo Oxigenasa (Desciclizante)/metabolismo , Hemo/metabolismo , Hierro/metabolismoRESUMEN
Heme oxygenase-1 (HO-1), which catalyzes heme degradation releasing iron, regulates several processes related to breast cancer. Iron metabolism deregulation is also connected with several tumor processes. However the regulatory relationship between HO-1 and iron proteins in breast cancer remains unclear. Using human breast cancer biopsies, we found that high HO-1 levels significantly correlated with low DMT1 levels. Contrariwise, high HO-1 levels significantly correlated with high ZIP14 and prohepcidin expression, as well as hemosiderin storage. At mRNA level, we found that high HO-1 expression significantly correlated with low DMT1 expression but high ZIP14, L-ferritin and hepcidin expression. In in vivo experiments in mice with genetic overexpression or pharmacological activation of HO-1, we detected the same expression pattern observed in human biopsies. In in vitro experiments, HO-1 activation induced changes in iron proteins expression leading to an increase of hemosiderin, ROS levels, lipid peroxidation and a decrease of the growth rate. Such low growth rate induced by HO-1 activation was reversed when iron levels or ROS levels were reduced. Our findings demonstrate an important role of HO-1 on iron homeostasis in breast cancer. The changes in iron proteins expression when HO-1 is modulated led to the iron accumulation deregulating the iron cell cycle, and consequently, generating oxidative stress and low viability, all contributing to impair breast cancer progression.
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Neoplasias de la Mama , Hierro , Ratones , Animales , Humanos , Femenino , Hierro/metabolismo , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Neoplasias de la Mama/patología , Especies Reactivas de Oxígeno/metabolismo , Hemosiderina , Supervivencia CelularRESUMEN
Brachymetatarsia (BM), or hypoplastic metatarsal, is an abnormal shortening of one or more metatarsal bones with a female-to-male ratio of 10.53:1. Different causes are described in the literature, such as congenital, acquired, or iatrogenic, associated with different conditions and syndromes. Its presence may develop deformity and pain; however, often feet are pain free and the major worries of patients are cosmetics. Non-operative treatments aim to improve the comfort of metatarsal heads and the possible dorsal conflict through comfortable shoes or the use of specific orthotics. The surgical treatment is anything but straightforward, with "one-stage" or "two stage" techniques, the latter better called "by gradual distraction". One-stage procedures are more rapid techniques but have limited ability to restore the desired length due to neurovascular compromise caused by acute lengthening. Insufficient correction is also possible. On the contrary, by gradual distraction procedures allow gradual distraction lengthening of more than 1.5 cm, but require the use of an external fixator, with a higher risk of complications in more than about 50% of surgeries. The adjacent metatarsal shortening should be considered in combination with other techniques, to diminish the excessive lengthening. In each case, surgeries should be always decided on each patient's concerns, deformities, and clinical needs.
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Deformidades Congénitas del Pie , Huesos Metatarsianos , Osteogénesis por Distracción , Fijadores Externos , Femenino , Pie , Deformidades Congénitas del Pie/diagnóstico por imagen , Deformidades Congénitas del Pie/cirugía , Humanos , Masculino , Huesos Metatarsianos/diagnóstico por imagen , Huesos Metatarsianos/cirugía , Osteogénesis por Distracción/métodosRESUMEN
The sacroiliac joint (SIJ) is a possible source of persistent or new onset pain after lumbar or lumbosacral fusion. The aim of this paper is to systematically review and analyze the available literature related to the incidence, diagnosis and management of sacroiliitis after spinal arthrodesis. The authors independently screened the titles and abstracts of all articles identified concerning sacroiliac joint pain after lumbar or lumbosacral fusion, to assess their suitability to the research focus. The average incidence of sacroiliitis after lumbar or lumbosacral arthrodesis was found to be 37 ± 28.48 (range 6-75), increasing directly to the number of fused segments involved, especially when the sacrum is included. The most accurate evaluation is the image-guided injection of anesthetic solutions in the joint. Surgery treatment may be considered when conservative therapy fails, with open surgery or with minimally invasive SIJ fusion. Although the risk of developing SIJ degeneration is unclear, the results indicate that pain and degeneration of SIJ develop more often in patients undergoing lumbosacral fusion regardless of the number of melting segments. The treatment of sacroiliitis appears to be independent of his etiology, with or without previous instrumentation on several levels.
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Complicaciones Posoperatorias/etiología , Sacroileítis/etiología , Fusión Vertebral , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Artrodesis , Niño , Síndrome de Fracaso de la Cirugía Espinal Lumbar/etiología , Síndrome de Fracaso de la Cirugía Espinal Lumbar/cirugía , Síndrome de Fracaso de la Cirugía Espinal Lumbar/terapia , Femenino , Humanos , Incidencia , Inyecciones Intraarticulares , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Articulación Sacroiliaca/fisiopatología , Articulación Sacroiliaca/cirugía , Sacroileítis/diagnóstico , Sacroileítis/epidemiología , Sacroileítis/terapia , Sacro/cirugía , Adulto JovenRESUMEN
One of the few exact results for the description of the time evolution of an inhomogeneous, interacting many-particle system is given by the harmonic potential theorem (HPT). The relevance of this theorem is that it sets a tight constraint on time-dependent many-body approximations. In this contribution, we show that the original formulation of the HPT is valid also for the case of spin-, velocity-, and density-dependent interactions. This result is completely general and relevant, among the rest, for nuclear structure theory both in the case of ab initio and of more phenomenological approaches. As an example, we report on a numerical implementation by testing the small-amplitude limit of the time-dependent Hartree-Fock-also known as the random phase approximation-for the translational frequencies of a neutron system trapped in a harmonic potential.
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We analyze and propose a solution to the apparent inconsistency between our current knowledge of the equation of state of asymmetric nuclear matter, the energy of the isobaric analog state (IAS) in a heavy nucleus such as ^{208}Pb, and the isospin symmetry breaking forces in the nuclear medium. This is achieved by performing state-of-the-art Hartree-Fock plus random phase approximation calculations of the IAS that include all isospin symmetry breaking contributions. To this aim, we propose a new effective interaction that is successful in reproducing the IAS excitation energy without compromising other properties of finite nuclei.
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The first 2^{+} and 3^{-} states of the doubly magic nucleus ^{132}Sn are populated via safe Coulomb excitation employing the recently commissioned HIE-ISOLDE accelerator at CERN in conjunction with the highly efficient MINIBALL array. The ^{132}Sn ions are accelerated to an energy of 5.49 MeV/nucleon and impinged on a ^{206}Pb target. Deexciting γ rays from the low-lying excited states of the target and the projectile are recorded in coincidence with scattered particles. The reduced transition strengths are determined for the transitions 0_{g.s.}^{+}â2_{1}^{+}, 0_{g.s.}^{+}â3_{1}^{-}, and 2_{1}^{+}â3_{1}^{-} in ^{132}Sn. The results on these states provide crucial information on cross-shell configurations which are determined within large-scale shell-model and Monte Carlo shell-model calculations as well as from random-phase approximation and relativistic random-phase approximation. The locally enhanced B(E2;0_{g.s.}^{+}â2_{1}^{+}) strength is consistent with the microscopic description of the structure of the respective states within all theoretical approaches. The presented results of experiment and theory can be considered to be the first direct verification of the sphericity and double magicity of ^{132}Sn.
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Nuclear ß decay in magic nuclei is investigated, taking into account the coupling between particles and collective vibrations, on top of self-consistent random phase approximation calculations based on Skyrme density functionals. The low-lying Gamow-Teller strength is shifted downwards and at times becomes fragmented; as a consequence, the ß-decay half-lives are reduced due to the increase of the phase space available for the decay. In some cases, this leads to a very good agreement between theoretical and experimental lifetimes: this happens, in particular, in the case of the Skyrme force SkM* that can also reproduce the line shape of the high-energy Gamow-Teller resonance as was previously shown.
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The isoscalar monopole response has been measured in the unstable nucleus (68)Ni using inelastic alpha scattering at 50A MeV in inverse kinematics with the active target MAYA at GANIL. The isoscalar giant monopole resonance (ISGMR) centroid was determined to be 21.1 ± 1.9 MeV and indications for a soft monopole mode are provided for the first time at 12.9 ± 1.0 MeV. Analysis of the corresponding angular distributions using distorted-wave-born approximation with random-phase approximation transition densities indicates that the L = 0 multipolarity dominates the cross section for the ISGMR and significantly contributes to the low-energy mode. The L=0 part of this low-energy mode, the soft monopole mode, is dominated by neutron excitations. This demonstrates the relevance of inelastic alpha scattering in inverse kinematics in order to probe both the ISGMR and isoscalar soft modes in neutron-rich nuclei.
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Gamow-Teller (GT) transitions in atomic nuclei are sensitive to both nuclear shell structure and effective residual interactions. The nuclear GT excitations were studied for the mass number A = 42, 46, 50, and 54 "f-shell" nuclei in ((3)He, t) charge-exchange reactions. In the (42)Ca â (42)Sc reaction, most of the GT strength is concentrated in the lowest excited state at 0.6 MeV, suggesting the existence of a low-energy GT phonon excitation. As A increases, a high-energy GT phonon excitation develops in the 6-11 MeV region. In the (54)Fe â (54)Co reaction, the high-energy GT phonon excitation mainly carries the GT strength. The existence of these two GT phonon excitations are attributed to the 2 fermionic degrees of freedom in nuclei.
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Takayasu arteritis (TA) is a rare form of chronic large vessel vasculitis of unknown origin involving the aorta and its major branches. Recently, the involvement of B lymphocytes in TA has been suggested, and active refractory TA patients were successfully treated with B cell depletion therapy (BCDT). We report two cases of patients with TA successfully treated with anti-CD20 monoclonal antibody (rituximab). The favorable outcome of rituximab treatment in our patients also support the view that BCDT can be a useful option for refractory TA, and its potential should be evaluated in controlled trials.
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Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Factores Inmunológicos/uso terapéutico , Arteritis de Takayasu/tratamiento farmacológico , Adulto , Femenino , Humanos , Rituximab , Resultado del TratamientoRESUMEN
The kinetics of in vitro drug release from nanoparticulate systems is extensive, though uncritically, being studied by dialysis. Evaluating the actual relevance of dialysis data to drug release was the purpose of this study. Diclofenac- or ofloxacin-loaded chitosan nanoparticles crosslinked with tripolyphosphate were prepared and characterized. With each drug, dynamic dialysis was applied to nanoparticle dispersion, solution containing dissolved chitosan·HCl, and solution of plain drug. Drug kinetics in receiving phase (KRP), nanoparticle matrix (KNM) and nanoparticle dispersion medium (KDM) were determined. Release of each drug from nanoparticles was also assessed by ultracentrifugation. Although KRP data may be interpreted in terms of sustained release from nanoparticles, KNM and KDM data show that, with both drugs, the process was in fact controlled by permeation across dialysis membrane. Analysis of KRP data reveals a reversible interaction of diclofenac with dispersed nanoparticle surface, similar to the interaction of this drug with dissolved chitosan·HCl. No such interactions are noticed with ofloxacin. The results from the ultracentrifugation method agree with the above interpretation of dialysis data. This case study shows that dialysis data from a nanoparticle dispersion is not necessarily descriptive of sustained-release from nanoparticles, hence, if interpreted uncritically, it may be misleading.
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Diálisis/métodos , Diclofenaco/química , Nanopartículas , Ofloxacino/química , Química Farmacéutica/métodos , Quitosano/química , Reactivos de Enlaces Cruzados/química , Preparaciones de Acción Retardada , Diclofenaco/administración & dosificación , Portadores de Fármacos/química , Cinética , Ofloxacino/administración & dosificación , Polifosfatos/química , Reproducibilidad de los Resultados , Tecnología Farmacéutica/métodos , UltracentrifugaciónRESUMEN
Anti-citrullinated protein/peptide antibodies (ACPA) are a hallmark of rheumatoid arthritis (RA) and can be measured using different citrullinated substrates. In this paper we describe a new viral citrullinated peptide - VCP2 - derived from the Epstein-Barr virus-encoded protein EBNA-2 and analyse its potential as substrate for ACPA detection. Analysing sera from 100 RA patients and 306 controls, anti-VCP2 immunoglobulin (Ig)G were found in 66% of RA sera, IgM in 46% and IgA in 39%, compared with less than 3% of control sera. Anti-VCP2 IgG was associated with erosive arthritis, the presence of rheumatoid factor and anti-VCP1 and anti-cyclic citrullinated peptide (CCP) antibodies. Anti-VCP2 antibodies were detected in 1% and anti-VCP1 antibodies in 4% of CCP-negative RA sera; conversely, 3% of the VCP-negative sera were CCP-positive. Taken together, these data suggest that VCP2 could offer a valuable tool for ACPA detection. Inhibition assays showed that two non-overlapping epitopes - a citrulline-glycine stretch shared between VCP1 and VCP2 and the N-terminal portion of the VCP2 sequence - were targeted by anti-VCP2 antibodies. Moreover, in some RA sera that tested positive in CCP and VCP2 assays, preincubation with VCP2 inhibited binding to CCP, whereas in other sera the binding was unaffected. Thus, the reactivity with more than one ACPA substrate might be due in some RA patients to antibody populations with different specificities, and in others to cross-reactive antibody populations. Finally, affinity-purified anti-VCP2 antibodies immunoprecipitated deiminated Epstein-Barr virus nuclear antigen (EBNA-2) from an EBNA-2-transfected cell line, suggesting that viral sequences may be involved in the generation of the ACPA response.
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Artritis Reumatoide/inmunología , Autoanticuerpos/metabolismo , Antígenos Nucleares del Virus de Epstein-Barr/metabolismo , Herpesvirus Humano 4/inmunología , Fragmentos de Péptidos/metabolismo , Proteínas Virales/metabolismo , Adulto , Anciano , Artritis Reumatoide/diagnóstico , Citrulina/química , Citrulina/metabolismo , Biología Computacional , Mapeo Epitopo , Epítopos , Antígenos Nucleares del Virus de Epstein-Barr/química , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/química , Fragmentos de Péptidos/inmunología , Proteínas Virales/química , Proteínas Virales/inmunologíaRESUMEN
The charge exchange spin-dipole (SD) excitations of 208Pb are studied by using a fully self-consistent Skyrme Hartree-Fock plus random phase approximation formalism which includes the tensor interaction. It is found, for the first time, that the tensor correlations have a unique, multipole-dependent effect on the SD excitations; that is, they produce a softening of 1{-} states, but a hardening of 0{-} and 2{-} states. This paves the way to a clear assessment of the strength of the tensor terms. We compare our results with a recent measurement, showing that our choice of tensor terms improves the agreement with experiment. The robustness of our results is supported by the analytic form of the tensor matrix elements.
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Zero-range effective interactions are commonly used in nuclear physics and in other domains to describe many-body systems within the mean-field model. If they are used within a beyond-mean-field framework, contributions to the total energy that display an ultraviolet divergence are found. We propose a general strategy to regularize this divergence and we illustrate it in the case of the second-order corrections to the equation of state (EOS) of uniform symmetric matter. By setting a momentum cutoff Λ, we show that for every (physically meaningful) value of Λ it is possible to determine a new interaction such that the EOS with the second-order corrections reproduces the empirical EOS, with a fit of the same quality as that obtained at the mean-field level.
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The p160 nuclear receptor co-activators represent a family of molecules, which are recruited by steroid nuclear receptors as well as other transcription factors that are overexpressed in several tumors. We investigated the role of one member of this family on the sensitivity of cells to apoptosis. We observed that overexpression of the RAC3 (receptor-associated co-activator-3) p160 co-activator inhibits hydrogen peroxide-induced cell death in human embryonic kidney 293 (HEK293) cells. The mechanism involves the activation of anti-apoptotic pathways mediated through enhanced nuclear factor kappa B (NF-kappaB) activity, inhibition of caspase-9 activation, diminished apoptotic-inducing factor (AIF) nuclear localization and a change in the activation pattern of several kinases, including an increase in both AKT and p38 kinase activities, and inhibition of ERK2. Moreover, RAC3 has been found associated with a protein complex containing AIF, Hsp90 and dynein, suggesting a role for the co-activator in the cytoplasmatic nuclear transport of these proteins associated with cytoskeleton. These results demonstrate that there are several molecular pathways that could be affected by their overexpression, including those not restricted to steroid regulation or the nuclear action of co-activators, which results in diminished sensitivity to apoptosis. Furthermore, this could represent one mechanism by which co-activators contribute to tumor development.