OBJECTIVE: The selection of valve prostheses for patients undergoing surgical aortic valve replacement (SAVR) remains controversial. In this study, we compared the long-term outcomes of patients undergoing aortic valve replacement with biological or mechanical aortic valve prostheses.
METHODS: We evaluated late results among 5,762 patients aged 45-74 years who underwent biological or mechanical aortic valve replacement with or without concomitant coronary artery bypass from 1989 to 2019 at four medical centers. The Cox proportional hazards model was used to compare late survival; the age-dependent effect of prosthesis type on long-term survival was evaluated by an interaction term between age and prosthesis type. Incidences of stroke, major bleeding, and reoperation on the aortic valve following the index procedure were compared between prosthesis groups.
RESULTS: Overall, 61% (n=3,508) of patients received a bioprosthesis. The 30-day mortality rate was 1.7% (n=58) in the bioprosthesis group and 1.5% (n=34) in the mechanical group (P=0.75). During a mean follow-up of 9.0 years, the adjusted risk of mortality was higher in the bioprosthesis group (HR=1.30, P<0.001). The long-term survival benefit associated with mechanical prosthesis persisted until 70 years of age. Bioprosthesis (vs mechanical prosthesis) was associated with a similar risk of stroke (P=0.20), lower risk of major bleeding (P<0.001), and higher risk of reoperation (P<0.001).
CONCLUSIONS: Compared to bioprostheses, mechanical aortic valves are associated with a lower adjusted risk of long-term mortality in patients aged 70 years or younger. Patients <70 years old undergoing SAVR should be informed of the potential survival benefit of mechanical valve substitutes.

When one walks toward a crowd of pedestrians, dealing with their biological motion while controlling one\'s own self-motion is a difficult perceptual task. Limb articulation of a walker is naturally coupled to the walker\'s translation through the scene and allows the separation of optic flow generated by self-motion from the biological motion of other pedestrians. Recent research has shown that if limb articulation and translation mismatch, such as for walking in place, self-motion perception becomes biased. This bias may reflect an illusory motion attributed to the pedestrian crowd from the articulation of their limbs. To investigate this hypothesis, we presented observers with a simulation of forward self-motion toward a laterally moving crowd of point-light walkers and asked them to report the perceived lateral speed of the crowd. To investigate the dependence of the crowd speed percept on biological motion, we also included conditions in which the points of the walker were spatially scrambled to destroy body form and limb articulation. We observed illusory crowd speed percepts that were related to the articulation rate of the biological motion. Scrambled walkers also produced illusory motion but it was not related to articulation rate. We conclude that limb articulation induces percepts of crowd motion that can be used for interpreting self-motion toward crowds.

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OBJECTIVE: Eating disorders (EDs) represent a major public health burden. Increasingly, studies suggest mental health (MH) fields are failing to improve the effectiveness of treatments and that alternative models of care must be considered. Precision mental health (PMH) seeks to tailor treatment to individual needs and relies on a comprehensive understanding of the neurobiological and physiological underpinnings of mental illness.
METHODS: In this narrative review, published literature with focus on biological application of PMH strategies for EDs is reviewed and summarised.
RESULTS: A total of 39 articles were retained for the review covering a variety of themes with relevance to PMH. Many studies of biological markers with PMH applicability focused on anorexia nervosa. Although a variety of potential PMH research applications were identified, the review failed to identify any evidence of implementation into routine ED practice.
CONCLUSIONS: Despite the theoretical merit of biological application of PMH in ED treatment, clinical applications for standard practice are lacking. There is a need to invest further in studies that seek to identify biological markers and investigate neurobiological underpinnings of disease in hopes of targeting and developing treatments that can be better tailored to the individualised needs of patients.

UNASSIGNED: After 17 years on the market, biosimilar medicines have contributed significantly to the sustainability of healthcare in Spain, providing cost-effective treatment options and savings of more than €1 billion by 2022 alone. To fully exploit this potential and meet the European pharmaceutical strategy\'s objectives of increased access and a resilient supply chain, Member States need to optimize their biosimilars policies.
UNASSIGNED: We conducted an exhaustive review of biosimilar medicines in Spain, first describing their regulatory framework. Biosimilar policies at both national and regional level have been collected and updated figures on the biosimilars market are provided based on official data. Knowledge and acceptance of biosimilar medicines among patients and medical societies based on biosimilar positioning documents is reviewed. National evidence on the contribution of biosimilars to savings and sustainability is also included in this study.
UNASSIGNED: In Spain, there is a need to further build confidence in biosimilars, develop a strong national biosimilars policy and address regional variability, improve public procurement and adapt clinical practice guidelines following the commercialization of biosimilars. By implementing a holistic and evidence-based policy, Spain can fully exploit the benefits of biosimilar medicines and ensure better and equitable access across the healthcare system.

Clay soils are rock-decomposed materials comprised of both clay- and non-clay-like minerals. Clays\' physiochemical and mineralogical composition determines their applicability use in cosmetics. Because of their high bioburden, they must be effectively characterized before being incorporated into cosmetics. The scope of the current study was to characterize two different samples of red and white clays for their physical, chemical and biological properties; mined from Durban, South Africa. Characterization was performed using techniques like X-ray fluorescence, X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscope, hydrogen potential, soil colour, oil absorption, swelling capacity, texture, bulk density, plastic and apparent viscosity, sun protection factor and microbiological analysis.

UNASSIGNED: Designed to help treat pain and loss of function after rotator cuff repair, allograft spacer procedures utilize a graft to act as a spacer in the subacromial space, decreasing pain from impingement of the greater tuberosity on the acromion at the extremes of overhead motion.
UNASSIGNED: To evaluate the biomechanical characteristics of secured versus unsecured tensor fascia lata allografts used in an allograft spacer procedure.
UNASSIGNED: Controlled laboratory study.
UNASSIGNED: A total of 8 fresh-frozen cadaveric shoulder specimens were used. There were 4 conditions tested: (1) intact rotator cuff, (2) stage III rotator cuff tear (complete supraspinatus tendon and superior one-half of the infraspinatus tendon), (3) unsecured tensor fascia lata graft, and (4) secured tensor fascia lata graft. Both superior and posterior translation of the humeral head were calculated in each condition. A 4-cm × 5-cm × 6-mm tensor fascia lata graft was used in the subacromial space to act as a spacer. Grafts were secured at the lateral edge of the native rotator cuff footprint with 2 knotless anchors.
UNASSIGNED: With unbalanced loading, both secured and unsecured grafts varied in their ability to limit superior and posterior translation at various rotation angles back to levels seen with intact rotator cuffs at 0° and 20° of abduction. During balanced loading, both unsecured and secured grafts limited superior and posterior translation more than those seen in the rotator cuff-deficient condition (P < .01) and similar to those seen in the intact condition (P > .05). The secured and unsecured grafts allowed similar amounts of translation at every position with both unbalanced and balanced loading (P > .05). Finally, total graft motion was <7 mm in all positions.
UNASSIGNED: Unsecured tensor fascia lata grafts were biomechanically equivalent to secured grafts when used during allograft spacer procedures.
UNASSIGNED: While both grafts were successful at limiting superior and posterior translation of the humeral head during early range of motion, the unsecured graft represents a cheaper, easier option to utilize during allograft spacer procedures.

UNASSIGNED: To analyze the referral patterns and the clinical and therapeutic features of patients diagnosed with uveitis in an Italian tertiary referral center to provide a comparison with previously published series from the same center.
UNASSIGNED: Retrospective retrieval of data on all new referrals to the Ocular Immunology Unit in Reggio Emilia (Italy) between November 2015 and April 2022 and comparison with previously published series from the same center.
UNASSIGNED: Among the 1557 patients, the male-to-female ratio was 1:1.27. Anterior uveitis was the most common diagnosis (53.7%), followed by posterior (21.6%), pan- (18.5%), and intermediate (6.2%) uveitis. The most identifiable specific diagnoses were anterior herpetic uveitis (18.4%), Fuchs uveitis (12.8%), and tuberculosis (6.1%). Infectious etiologies were the most frequent (34.1%) and were more diffuse among non-Caucasian patients (p < 0.001), followed by systemic disease-associated uveitis (26.5%), and ocular-specific conditions (20%). Idiopathic uveitis accounted for 19.4% of cases. Fuchs uveitis presented the longest median diagnostic delay (21 months). Immunosuppressants were administered to 25.2% of patients. Antimetabolites, calcineurin inhibitors, and biologicals were prescribed to 18.4%, 3%, and 11.4% of cases, respectively. Compared to our previous reports, we observed a significant increase in foreign-born patients and in infectious uveitis, a decrease in idiopathic conditions, and an increasing use of non-biological and biological steroid-sparing drugs.
UNASSIGNED: The patterns of uveitis in Italy have been changing over the last 20 years, very likely due to migration flows. Diagnostic improvements and a more widespread interdisciplinary approach could reduce the incidence of idiopathic uveitis as well as diagnostic delay.

Objective.Hybrid proton-photon radiotherapy (RT) is a cancer treatment option to broaden access to proton RT. Additionally, with a refined treatment planning method, hybrid RT has the potential to offer superior plan quality compared to proton-only or photon-only RT, particularly in terms of target coverage and sparing organs-at-risk (OARs), when considering robustness to setup and range uncertainties. However, there is a concern regarding the underestimation of the biological effect of protons on OARs, especially those in close proximity to targets. This study seeks to develop a hybrid treatment planning method with biological dose optimization, suitable for clinical implementation on existing proton and photon machines, with each photon or proton treatment fraction delivering a uniform target dose.Approach.The proposed hybrid biological dose optimization method optimized proton and photon plan variables, along with the number of fractions for each modality, minimizing biological dose to the OARs and surrounding normal tissues. To mitigate underestimation of hot biological dose spots, proton biological dose was minimized within a ring structure surrounding the target. Hybrid plans were designed to be deliverable separately and robustly on existing proton and photon machines, with enforced uniform target dose constraints for the proton and photon fraction doses. A probabilistic formulation was utilized for robust optimization of setup and range uncertainties for protons and photons. The nonconvex optimization problem, arising from minimum monitor unit constraint and dose-volume histogram constraints, was solved using an iterative convex relaxation method.Main results.Hybrid planning with biological dose optimization effectively eliminated hot spots of biological dose, particularly in normal tissues surrounding the target, outperforming proton-only planning. It also provided superior overall plan quality and OAR sparing compared to proton-only or photon-only planning strategies.Significance.This study presents a novel hybrid biological treatment planning method capable of generating plans with reduced biological hot spots, superior plan quality to proton-only or photon-only plans, and clinical deliverability on existing proton and photon machines, separately and robustly.

OBJECTIVE: Seventeen percent of patients with ulcerative colitis that undergo proctocolectomy with pouch surgery will develop chronic pouchitis. We evaluated the efficacy of ustekinumab for these patients.
METHODS: We performed a prospective study of patients with chronic pouchitis receiving ustekinumab intravenously at baseline (∼6 mg/kg) and 90 mg ustekinumab subcutaneously every 8 weeks thereafter. The Modified Pouchitis Disease Activity Index (mPDAI) was assessed at baseline and weeks 16 and 48. The primary endpoint was the proportion of patients achieving steroid-free remission (mPDAI <5 and reduction by ≥2 points) at week 16. Secondary endpoints included the proportion of patients achieving remission at week 48, the proportion of patients achieving response (reduction of mPDAI by ≥2 points) at weeks 16 and 48, and change in mPDAI.
RESULTS: We enrolled 22 patients (59% male; median age, 42.2 years). Remission was achieved in 27.3% at week 16 and 36.4% at week 48. Response was achieved in 54.5% both at weeks 16 and 48. The median mPDAI decreased from 8 (interquartile range [IQR], 7-10) to 7 (IQR, 4-9) at week 16 (P = .007) and 4 (IQR, 1.75-7.25) at week 48 (P < .001). The clinical mPDAI subscore decreased from 3.5 (IQR, 2-4) to 2 (IQR, 1-3) at week 16 (P = .009) and 1 (IQR, 0-2.25) at week 48 (P = .001). The endoscopic mPDAI subscore decreased from 5.5 (IQR, 4-6) to 4 (IQR, 3-6) at week 16 (P = .032) and 3 (IQR, 1.75-4.25) at week 48 (P = .001).
CONCLUSIONS: Ustekinumab was efficacious in one-half of the patients suffering from chronic pouchitis. Ustekinumab should therefore be positioned in the treatment algorithm of chronic pouchitis. (ClinicalTrials.gov Number NCT04089345).