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1.
Phys Med ; 123: 103394, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38852364

RESUMEN

PURPOSE: To present the results of the first multi-centre real-world validation of autoplanning for whole breast irradiation after breast-sparing surgery, encompassing high complexity cases (e.g. with a boost or regional lymph nodes) and a wide range of clinical practices. METHODS: The 24 participating centers each included 10 IMRT/VMAT/Tomotherapy patients, previously treated with a manually generated plan ('manplan'). There were no restrictions regarding case complexity, planning aims, plan evaluation parameters and criteria, fractionation, treatment planning system or treatment machine/technique. In addition to dosimetric comparisons of autoplans with manplans, blinded plan scoring/ranking was conducted by a clinician from the treating center. Autoplanning was performed using a single configuration for all patients in all centres. Deliverability was verified through measurements at delivery units. RESULTS: Target dosimetry showed comparability, while reductions in OAR dose parameters were 21.4 % for heart Dmean, 16.7 % for ipsilateral lung Dmean, and 101.9 %, 45.5 %, and 35.7 % for contralateral breast D0.03cc, D5% and Dmean, respectively (all p < 0.001). Among the 240 patients included, the clinicians preferred the autoplan for 119 patients, with manplans preferred for 96 cases (p = 0.01). Per centre there were on average 5.0 ± 2.9 (1SD) patients with a preferred autoplan (range [0-10]), compared to 4.0 ± 2.7 with a preferred manplan ([0,9]). No differences were observed regarding deliverability. CONCLUSION: The automation significantly reduced the hands-on planning workload compared to manual planning, while also achieving an overall superiority. However, fine-tuning of the autoplanning configuration prior to clinical implementation may be necessary in some centres to enhance clinicians' satisfaction with the generated autoplans.


Asunto(s)
Automatización , Neoplasias de la Mama , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Planificación de la Radioterapia Asistida por Computador/métodos , Humanos , Neoplasias de la Mama/radioterapia , Radioterapia de Intensidad Modulada/métodos , Órganos en Riesgo/efectos de la radiación , Dosificación Radioterapéutica , Femenino , Radiometría
2.
Artículo en Inglés | MEDLINE | ID: mdl-38466400

RESUMEN

PURPOSE: Soft tissue infections can be severe and life-threatening. Their treatment consists currently in radical surgical wound debridement and combined systemic antimicrobial therapy. Different side effects are possible. Local antibiotic therapy represents a new approach to reduce side effects and improve healing. The aim of this study is to assess the effectiveness of the local sprayed use of antibiotics with fibrin sealing compared with negative pressure wound therapy as an established treatment of soft-tissue infections. METHODS: In this retrospective study, patients with soft tissue infections who underwent surgical treatment were analysed. One group consists of patients, who received local fibrin-antibiotic spray (FAS) (n = 62). Patients treated by vacuum-assisted wound therapy (VAWT) as the established treatment were the control group (n = 57). Main outcomes were differences in the success of healing, the duration until healing and the number of needed operations. RESULTS: Clinical healing could be achieved for 55 patients (98.21%) in the FAS group vs. 47 patients (92.16%) in the VAWT group (p = 0.19). Time to require this was 10.65 ± 10.38 days in the FAS group and 22.85 ± 14.02 days in the VAWT group (p < 0.001). In the FAS group, patients underwent an average of 1.44 ± 0.72 vs.3.46 ± 1.66 operations in the VAWT group (p < 0.001). CONCLUSION: Compared to vacuum-assisted wound therapy in soft tissue infections, local fibrin-antibiotic spray shows faster clinical healing and less needed operations. Leading to shorter hospital stays and more satisfied patients. The combination of sprayed fibrin and antibiotics can be seen as a promising and effective method.

3.
Appl Opt ; 62(18): 4949-4957, 2023 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-37707273

RESUMEN

Endoscopic optical diagnostics for IC engines offer the advantage of retaining the full operating range and thermal properties of the production engine. The custom-designed modular hybrid UV endoscope system is optimized for application in IC engines.; however, its hybrid refractive/diffractive relay element is expensive and has a narrow operating wavelength range. To make the endoscopic imaging more universally applicable, the hybrid relay element of the mentioned endoscope system was replaced by commercial UV camera lenses, and several combinations were characterized in terms of resolution, brightness, and chromatic aberration. With an unintensified CCD camera, endoscope systems using commercial camera lenses had better resolution at investigated magnifications of 0.5 and 1. However, with an intensified camera, the system with the hybrid relay lens had the best overall performance in its design wavelength range. Selected imaging systems were used in a spark-ignition engine to image O H ∗-chemiluminescence, with results consistent with those from bench-top characterization.

4.
Sci Rep ; 13(1): 9953, 2023 06 19.
Artículo en Inglés | MEDLINE | ID: mdl-37337085

RESUMEN

A growing body of research has placed the ventral striatum at the center of a network of cerebral regions involved in anticipating rewards in healthy controls. However, little is known about the functional connectivity of the ventral striatum associated with reward anticipation in healthy controls. In addition, few studies have investigated reward anticipation in healthy humans with different levels of schizotypy. Here, we investigated reward anticipation in eighty-four healthy individuals (44 females) recruited based on their schizotypy scores. Participants performed a variant of the Monetary Incentive Delay Task while undergoing event-related fMRI.Participants showed the expected decrease in response times for highly rewarded trials compared to non-rewarded trials. Whole-brain activation analyses replicated previous results, including activity in the ventral and dorsal striatum. Whole-brain psycho-physiological interaction analyses of the left and right ventral striatum revealed increased connectivity during reward anticipation with widespread regions in frontal, parietal and occipital cortex as well as the cerebellum and midbrain. Finally, we found no association between schizotypal personality severity and neural activity and cortico-striatal functional connectivity. In line with the motivational, attentional, and motor functions of rewards, our data reveal multifaceted cortico-striatal networks taking part in reward anticipation in healthy individuals. The ventral striatum is connected to regions of the salience, attentional, motor and visual networks during reward anticipation and thereby in a position to orchestrate optimal goal-directed behavior.


Asunto(s)
Trastorno de la Personalidad Esquizotípica , Estriado Ventral , Femenino , Humanos , Trastorno de la Personalidad Esquizotípica/diagnóstico por imagen , Encéfalo/fisiología , Motivación , Recompensa , Mapeo Encefálico , Estriado Ventral/diagnóstico por imagen , Imagen por Resonancia Magnética , Anticipación Psicológica/fisiología
6.
Eur Psychiatry ; 64(1): e21, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33726883

RESUMEN

Negative symptoms of schizophrenia remain a major therapeutic challenge. The progress in the conceptualization and assessment is not yet fully reflected by treatment research. Nevertheless, there is a growing evidence base regarding the effects of biological and psychosocial interventions on negative symptoms. The importance of the distinction between primary and secondary negative symptoms for treatment selection might seem evident, but the currently available evidence remains limited. Good clinical practice is recommended for the treatment of secondary negative symptoms. Antipsychotic treatment should be optimized to avoid secondary negative symptoms due to side effects and due to positive symptoms. For most available interventions, further evidence is needed to formulate sound recommendations for primary, persistent, or predominant negative symptoms.However, based on currently available evidence recommendations for the treatment of undifferentiated negative symptoms (including both primary and secondary negative symptoms) are provided. Although it has proven difficult to formulate an evidence-based recommendation for the choice of an antipsychotic, a switch to a second-generation antipsychotic should be considered for patients who are treated with a first-generation antipsychotic. Antidepressant add-on to antipsychotic treatment is an option. Social skills training is recommended as well as cognitive remediation for patients who also show cognitive impairment. Exercise interventions also have shown promise. Finally, access to treatment and to psychosocial rehabilitation should be ensured for patients with negative symptoms. Overall, there is definitive progress in the field, but further research is clearly needed to develop specific treatments for negative symptoms.


Asunto(s)
Guías de Práctica Clínica como Asunto , Esquizofrenia , Antidepresivos/uso terapéutico , Antipsicóticos/uso terapéutico , Humanos , Esquizofrenia/tratamiento farmacológico
7.
Eur. j. psychiatry ; 35(1): 24-32, enero-marzo 2021. tab
Artículo en Inglés | IBECS | ID: ibc-217538

RESUMEN

Background and objectives: Coercion is frequent in psychiatry, with an overall downward trend. Knowledge on the application of seclusion and restraint in open wards remains limited. We aimed to describe the prevalence of coercion in an open inpatient setting and identify risk factors for it.MethodsWe conducted a retrospective analysis of the use of seclusion and restraint in 2017 in the adult psychiatry division of Geneva University Hospital. To identify risk factors for coercion, we estimated incidence rate ratios using multivariable Poisson regressions.ResultsOf 865 patients, 142 (16.4%) experienced at least one coercive measure (mostly seclusion). The incidence of coercion was higher in men, single patients, patients with psychotic or bipolar disorders, patients receiving disability benefits, patients with a higher number of previous psychiatric hospitalizations, and patients with higher global scores and higher scores on item 1 (overactive, aggressive or agitated behaviour) on Health of the Nation Outcome Scales (HoNOS) at admission. Age and referrals from the emergency department were not associated with a higher risk of coercion.ConclusionRisk factors for coercion were being male, being single, having psychotic or bipolar disorders, having previous psychiatric hospitalizations, having high HoNOS scores at admission, and being referred from outpatient centres or private physicians. Ratings on the first HoNOS item at admission might be sufficient for a pertinent aggression risk evaluation and thus for the prevention of coercion due to violence. This study is the first to analyse the risks of seclusion in open wards and calls for further research. (AU)


Asunto(s)
Humanos , Coerción , Psiquiatría , Trastornos Psicóticos , Hospitalización , Factores de Riesgo
8.
Eur Psychiatry ; 64(1): e23, 2021 02 18.
Artículo en Inglés | MEDLINE | ID: mdl-33597064

RESUMEN

BACKGROUND: During the last decades, a renewed interest for negative symptoms (NS) was brought about by the increased awareness that they interfere severely with real-life functioning, particularly when they are primary and persistent. METHODS: In this guidance paper, we provide a systematic review of the evidence and elaborate several recommendations for the conceptualization and assessment of NS in clinical trials and practice. RESULTS: Expert consensus and systematic reviews have provided guidance for the optimal assessment of primary and persistent negative symptoms; second-generation rating scales, which provide a better assessment of the experiential domains, are available; however, NS are still poorly assessed both in research and clinical settings.This European Psychiatric Association (EPA) guidance recommends the use of persistent negative symptoms (PNS) construct in the context of clinical trials and highlights the need for further efforts to make the definition of PNS consistent across studies in order to exclude as much as possible secondary negative symptoms. We also encourage clinicians to use second-generation scales, at least to complement first-generation ones.The EPA guidance further recommends the evidence-based exclusion of several items included in first-generation scales from any NS summary or factor score to improve NS measurement in research and clinical settings. Self-rated instruments are suggested to further complement observer-rated scales in NS assessment.Several recommendations are provided for the identification of secondary negative symptoms in clinical settings. CONCLUSIONS: The dissemination of this guidance paper may promote the development of national guidelines on negative symptom assessment and ultimately improve the care of people with schizophrenia.


Asunto(s)
Esquizofrenia , Humanos , Escalas de Valoración Psiquiátrica , Esquizofrenia/diagnóstico , Psicología del Esquizofrénico , Evaluación de Síntomas
10.
Osteoporos Int ; 32(7): 1313-1320, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33438038

RESUMEN

Prevention of early menopausal bone loss may reduce the future burden of osteoporosis. In this modelling exercise, an osteoporosis prevention strategy involving 5-year infusions of zoledronic acid, beginning early in menopause, reduced long-term fracture risk and the proportion of aging women with femoral neck densitometric osteoporosis. This strategy warrants further evaluation. INTRODUCTION: Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. METHODS: Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. RESULTS: At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. CONCLUSION: Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.


Asunto(s)
Densidad Ósea , Fracturas Osteoporóticas , Anciano , Anciano de 80 o más Años , Canadá , Estudios de Factibilidad , Femenino , Humanos , Menopausia , Persona de Mediana Edad , Fracturas Osteoporóticas/epidemiología , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/prevención & control , Medición de Riesgo
11.
Osteoporos Int ; 31(6): 1145-1153, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32034452

RESUMEN

We examined the underlying relationship between fracture risk factors and their imminent risk. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher imminent fracture risk. Past year falls indirectly predicted imminent risk through physical functioning and general health. INTRODUCTION: This study aimed to examine direct and indirect effects of several factors on imminent (1 year) fracture risk. METHODS: Data from women age 65 and older from population-based Canadian Multicentre Osteoporosis Study were used. Predictors were identified from study years 5 and 10, and imminent fracture data (1-year fracture) came from years 6 and 11 (year 5 predicts year 6, year 10 predicts year 11). A structural equation model (SEM) was used to test the theoretical construct. General health and physical functioning were measured as latent variables using items from the 36-Item Short Form Health Survey (SF-36) and bone mineral density (BMD) T-score was a latent variable based on observed site-specific BMD data (spine L1-L4, femoral neck, total hip). Observed variables were fractures and falls. Model fit was evaluated using root mean square error of approximation (RMSEA), Tucker Lewis index (TLI), and comparative fit index (CFI). RESULTS: The analysis included 3298 women. Model fit tests showed that the SEM fit the data well; χ2(172) = 1122.10 < .001, RMSEA = .03, TLI = .99, CFI = .99. Results suggested that having past year fracture, worse past year general health, worse past year physical functioning, and lower past year BMD T-score directly predicted higher risk of fracture in the subsequent year (p < .001). Past year falls had a statistically significant but indirect effect on imminent fracture risk through physical functioning and general health (p < .001). CONCLUSIONS: We found several direct and indirect pathways that predicted imminent fracture risk in elderly women. Future studies should extend this work by developing risk scoring methods and defining imminent risk thresholds.


Asunto(s)
Densidad Ósea , Fracturas Óseas/epidemiología , Osteoporosis/epidemiología , Anciano , Canadá/epidemiología , Estudios de Cohortes , Femenino , Humanos , Modelos Teóricos , Factores de Riesgo
12.
ACS Omega ; 5(3): 1408-1413, 2020 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-32010812

RESUMEN

Poly(N-isopropylacrylamide) (PNIPAM) is a popular polymer widely used in smart hydrogel synthesis due to its thermo-responsive behavior in aqueous medium. Aqueous PNIPAM hydrogels can reversibly swell and collapse below and above their lower critical solution temperature (LCST), respectively. The present work used molecular dynamics simulations to explore the behavior of water molecules surrounding the side chains of a NIPAM pentamer in response to temperature changes (273-353 K range) near its experimental LCST (305 K). Results suggest a strong inverse correlation of temperature with water density and hydrophobic hydration character of the first coordination shell around the isopropyl groups. Integrity of the first and second coordination shells is further characterized by polygon ring analysis. Predominant occurrence of pentagons suggests clathrate-like behavior of both shells at lower temperatures. This predominance is eventually overtaken by 4-membered rings as temperature is increased beyond 303 and 293 K for the first and second coordination shells, respectively, losing their clathrate-like property. It is surmised that this temperature-dependent stability of the coordination shells is one of the important factors that controls the reversible swell-collapse mechanism of PNIPAM hydrogels.

13.
Nat Commun ; 11(1): 287, 2020 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-31941881

RESUMEN

Recent findings of new Higgs modes in unconventional superconductors require a classification and characterization of the modes allowed by nontrivial gap symmetry. Here we develop a theory for a tailored nonequilibrium quantum quench to excite all possible oscillation symmetries of a superconducting condensate. We show that both a finite momentum transfer and quench symmetry allow for an identification of the resulting Higgs oscillations. These serve as a fingerprint for the ground state gap symmetry. We provide a classification scheme of these oscillations and the quench symmetry based on group theory for the underlying lattice point group. For characterization, analytic calculations as well as full scale numeric simulations of the transient optical response resulting from an excitation by a realistic laser pulse are performed. Our classification of Higgs oscillations allows us to distinguish between different symmetries of the superconducting condensate.

14.
Pathologe ; 41(Suppl 1): 30-38, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31309285

RESUMEN

In 1988, the "father of modern hepatology" Hans Popper died. His medical merits are numerous and outstanding and have already been praised many times. In particular, his research on liver diseases has gained widespread recognition. Much less well known is the fact that Popper was dismissed from the University of Vienna due to his Jewish ancestry after the "Anschluss" ("annexation") of Austria to the Third Reich and subsequently emigrated to the USA.Popper's biographers, who primarily belonged to his close circle of friends and colleagues, were unquestionably aware of this central caesura in Popper's life. However, the scientific analysis and presentation of this very event has been incomplete and, moreover, feeds heavily from the personal memories of the authors, which are inevitably subjective. For precisely this reason, the present contribution focuses on Popper's role as a politically persecuted Jew and the resulting implications.The study comes to the conclusion that Popper shows all the characteristics of a Nazi victim, namely a Jewish background, the dismissal from university, the threat of persecution by the Gestapo, and the subsequent forced emigration. Popper decided against remigration after 1945 and instead earned professional recognition in the USA and later worldwide. In the 1980s, Popper was criticized for his permissive attitude towards his former academic teacher, the doctor and Nazi criminal Hans Eppinger. Even if he did not completely succeed in making his behavior in the "Eppinger Case" understandable and comprehensible, the events gradually fell into oblivion, as evidenced by several recent posthumous statements of honor in German-speaking countries.


Asunto(s)
Gastroenterología/historia , Judíos/historia , Nacionalsocialismo/historia , Austria , Historia del Siglo XX , Humanos
15.
Mol Divers ; 24(4): 1291-1299, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31502188

RESUMEN

Cone snails are slow-moving animals that secure survival by injecting to their prey a concoction of highly potent and stable neurotoxic peptides called conotoxins. These small toxins (~ 10-30 AA) interact with ion channels and their diverse structures account for various variables such as the environment and the prey of preference. This study probed the conformational space of α-conotoxin PnIB from Conus pennaceus by performing all-atom molecular dynamics simulations on the conotoxin in complex solvent systems of water and octanol. Secondary structure analyses showed a uniform conformation for the pure (C100Oc, C100W) and minute (C95Oc, C5Oc) systems. In C50Oc, however, structural changes were observed. The original helices were converted to turns and were shown to happen simultaneously with the elongation of the helix and shortening of end-to-end distance. The transitions complement the orientation of the peptide at the interface. The shift to the broken helix conformation is marked by the rearrangement of solvent molecules to a framework that favors the accumulation of water molecules at residues 6-11 of the H2 region. This promotes specific protein-solvent interactions that facilitate secondary structure transitions. As PnIB has shown favorable binding toward neuronal nicotinic acetylcholine receptors, this study may provide insights on this conotoxin's therapeutic potential. Description: Structural changes in PnIB are accompanied by a simultaneous change in solvent density.


Asunto(s)
Conotoxinas/química , Conotoxinas/metabolismo , Solventes/química , Animales , Simulación por Computador , Neuronas/metabolismo , Péptidos/química , Péptidos/metabolismo , Estructura Secundaria de Proteína , Proteínas/química , Proteínas/metabolismo , Receptores Nicotínicos/química , Receptores Nicotínicos/metabolismo , Caracoles/química , Caracoles/metabolismo
16.
Pathologe ; 40(Suppl 3): 282-287, 2019 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-31732767

RESUMEN

AIMS OF THE STUDY: This explorative study focuses on those pathologists who became victims of the Third Reich by being dismissed, disenfranchised, persecuted, expelled, murdered, or driven to suicide. Accordingly, it examines the question of how many - and which - pathologists were oppressed in the Nazi dictatorship. It also looks at the reasons for this and the effects that repression has had on the lives of those affected - both in the Third Reich and in postwar Germany. MATERIAL AND METHODS: The study is based on archival source material, which was supplemented by a systematic evaluation of the relevant research literature. RESULTS AND DISCUSSION: In total, the biographies of 89 pathologists could be reconstructed and evaluated. Of these, 67 persons were persecuted for "racial" or anti-Semitic reasons. Until their disenfranchisement, the majority were employed at a university. The majority of the examined pathologists fled abroad, with most immigrating to the USA and Great Britain and successfully establishing themselves there professionally. No indications of a return to their homeland could be found in the sample presented here. Reasons included a lack of career options and negative personal experiences in postwar Germany, such as in reparation proceedings. Quite a lot of those who remained in the German Reich died violently, either in concentration camps or by suicide.


Asunto(s)
Nacionalsocialismo , Patólogos , Estudios Transversales , Alemania , Historia del Siglo XX , Humanos , Patólogos/historia
17.
Pathologe ; 40(4): 457-466, 2019 Jul.
Artículo en Alemán | MEDLINE | ID: mdl-31165235

RESUMEN

In 1988, the "father of modern hepatology" Hans Popper died. His medical merits are numerous and outstanding and have already been praised many times. In particular, his research on liver diseases has gained widespread recognition. Much less well known is the fact that Popper was dismissed from the University of Vienna due to his Jewish ancestry after the "Anschluss" ("annexation") of Austria to the Third Reich and subsequently emigrated to the USA.Popper's biographers, who primarily belonged to his close circle of friends and colleagues, were unquestionably aware of this central caesura in Popper's life. However, the scientific analysis and presentation of this very event has been incomplete and, moreover, feeds heavily from the personal memories of the authors, which are inevitably subjective. For precisely this reason, the present contribution focuses on Popper's role as a politically persecuted Jew and the resulting implications.The study comes to the conclusion that Popper shows all the characteristics of a Nazi victim, namely a Jewish background, the dismissal from university, the threat of persecution by the Gestapo, and the subsequent forced emigration. Popper decided against remigration after 1945 and instead earned professional recognition in the USA and later worldwide. In the 1980s, Popper was criticized for his permissive attitude towards his former academic teacher, the doctor and Nazi criminal Hans Eppinger. Even if he did not completely succeed in making his behavior in the "Eppinger Case" understandable and comprehensible, the events gradually fell into oblivion, as evidenced by several recent posthumous statements of honor in German-speaking countries.


Asunto(s)
Nacionalsocialismo , Austria , Alemania , Historia del Siglo XX , Humanos
18.
Osteoporos Int ; 30(4): 817-828, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30607457

RESUMEN

In this prospective cohort of 6120 participants aged 50+, nitrogen-bisphosphonates but not non-nitrogen bisphosphonates were associated with a significant 34% mortality risk reduction compared to non-treated propensity score matched controls. These findings open new avenues for research into mechanistic pathways. INTRODUCTION: Emerging evidence suggests that bisphosphonates (BP), first-line treatment of osteoporosis, are associated with reduced risks for all-cause mortality. This study aimed to determine the association between different BP types and mortality risk in participants with or without a fracture. METHODS: A prospective cohort study of users of different BPs matched to non-users by propensity score (age, gender, co-morbidities, fragility fracture status) and time to starting the BP medication from the population-based Canadian Multicentre Osteoporosis Study from nine Canadian centres followed from 1995 to 2013. Mortality risk for bisphosphonate users vs matched non-users was assessed using pairwise multivariable Cox proportional hazards models. RESULTS: There were 2048 women and 308 men on BP and 1970 women and 1794 men who did not receive medication for osteoporosis. The relationship between BP and mortality risk was explored in three separate 1:1 propensity score-matched cohorts of BP users and no treatment (etidronate, n = 599, alendronate, n = 498, and risedronate n = 213). Nitrogen BP (n-BP) (alendronate and risedronate) was associated with lower mortality risks [pairwise HR, 0.66 (95% CI, 0.48-0.91)] while the less potent non-n-BP, etidronate, was not [pairwise HR: 0.89 (95% CI, 0.66-1.20)]. A direct comparison between n-BP and etidronate (n = 340 pairs) also suggested a better survival for n-BP [paired HR, 0.47 (95%CI, (95% CI, 031-0.70)] for n-BP vs. etidronate]. CONCLUSION: Compared to no treatment, nitrogen but not non-nitrogen bisphosphonates appear to be associated with better survival.


Asunto(s)
Conservadores de la Densidad Ósea/uso terapéutico , Difosfonatos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Fracturas Osteoporóticas/prevención & control , Anciano , Alendronato/uso terapéutico , Canadá/epidemiología , Ácido Etidrónico/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Osteoporosis/mortalidad , Fracturas Osteoporóticas/mortalidad , Estudios Prospectivos , Ácido Risedrónico/uso terapéutico , Factores de Riesgo , Conducta de Reducción del Riesgo
19.
Soft Matter ; 14(13): 2547-2559, 2018 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-29541729

RESUMEN

The present work aims at the preparation of dry adhesives with switchable bonding properties by using the reversible nature of the [4πs+4πs] cycloaddition of anthracenes. Photo-responsive hydrogenated carboxylated nitrile butadiene rubber with photo-responsive pendant anthracene groups is prepared by one-pot synthesis. The formation of 3D networks relies on the photodimerization of the anthracene moieties upon UV exposure (λ > 300 nm). Controlled cleavage of the crosslink sites is achieved by either deep UV exposure (λ = 254 nm) or thermal dissociation at 70 °C. The kinetics of the optical and thermal cleavage routes are compared in thin films using UV-vis spectroscopy and their influence on the reversibility of the network is detailed. Going from thin films to free standing samples the modulation of the network structure and thermo-mechanical properties over repeated crosslinking and cleavage cycles are characterized by low-field NMR spectroscopy and dynamic mechanical analysis. The applicability of the stimuli-responsive networks as adhesives with reversible bonding properties is demonstrated. The results evidence that the reversibility of the crosslinking reaction enables a controlled switching "on" and "off" of adhesion properties. The recovery of the adhesion force amounts to 75 and 80% for photo- and thermal dissociation, respectively. Spatial control of adhesion properties is evidenced by adhesion force mapping experiments of photo-patterned films.

20.
Sci Rep ; 8(1): 3933, 2018 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-29500454

RESUMEN

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients. Abdominal subcutaneous AT biopsies were collected before and after intervention to determine the AT transcriptome and expression of proteins involved in lipolysis, NP signaling and mitochondrial oxidative metabolism. Both sacubitril/valsartan and amlodipine treatment did not significantly induce AT transcriptional changes in pathways related to lipolysis, NP signaling and oxidative metabolism. Furthermore, protein expression of adipose triglyceride lipase (ATGL) (Ptime*group = 0.195), hormone-sensitive lipase (HSL) (Ptime*group = 0.458), HSL-ser660 phosphorylation (Ptime*group = 0.340), NP receptor-A (NPRA) (Ptime*group = 0.829) and OXPHOS complexes (Ptime*group = 0.964) remained unchanged. In conclusion, sacubitril/valsartan treatment for 8 weeks did not alter the abdominal subcutaneous AT transcriptome and expression of proteins involved in lipolysis, NP signaling and oxidative metabolism in obese hypertensive patients.


Asunto(s)
Tejido Adiposo/efectos de los fármacos , Aminobutiratos/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Hipertensión/tratamiento farmacológico , Neprilisina/antagonistas & inhibidores , Obesidad/metabolismo , Proteínas/metabolismo , Tetrazoles/uso terapéutico , Transcriptoma , Tejido Adiposo/metabolismo , Adulto , Aminobutiratos/farmacología , Amlodipino/farmacología , Antagonistas de Receptores de Angiotensina/farmacología , Compuestos de Bifenilo , Método Doble Ciego , Combinación de Medicamentos , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/metabolismo , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Grasa Subcutánea/metabolismo , Tetrazoles/farmacología , Valsartán
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