Opposing patterns in self-reported and measured physical activity levels in middle-aged adults

Physical activity brings significant health benefits to middle-aged adults, although the research to date has been focused on late adulthood. This study aims to examine how ageing affects the self-reported and accelerometer-derived measures of physical activity levels in middle-aged adults. We employed the data recorded in the UK Biobank and analysed the physical activity levels of 2,998 participants (1381 men and 1617 women), based on self-completion questionnaire and accelerometry measurement of physical activity. We also assessed the musculoskeletal health of the participants using the dual-energy X-ray absorptiometry (DXA) measurements provided by the UK Biobank. Participants were categorised into three groups according to their age: group I younger middle-aged (40 to 49 years), group II older middle-aged (50 to 59 years), and group III oldest middle-aged (60 to 69 years). Self-reported physical activity level increased with age and was the highest in group III, followed by group II and I (P?<?0.05). On the contrary, physical activity measured by accelerometry decreased significantly with age from group I to III (P?<?0.05), and the same pertained to the measurements of musculoskeletal health (P?<?0.05). It was also shown that middle-aged adults mostly engaged in low and moderate intensity activities. The opposing trends of the self-reported and measured physical activity levels may suggest that middle-aged adults over-report their activity level as they age. They should be aware of the difference between their perceived and actual physical activity levels, and objective measures would be useful to prevent the decline in musculoskeletal health.

     

脑血管介入治疗患者穿刺点压迫方法的研究进展

综述了脑血管介入术穿刺点压迫方法（包括人工压迫、弹力带加压、压迫器加压、血管闭合装置压迫、止血敷料压迫、气囊加压6种）、止血压力以及压迫时间，提出由于穿刺点和压迫方法的不同，其压迫时间、减压时间和压力大小等需要进一步探讨，为脑血管介入术后患者穿刺点的临床护理提供参考。     

Quantification of myocardial fibrosis using noninvasive T2-mapping magnetic resonance imaging: Preclinical models of aging and pressure overload

Noninvasive imaging of cardiac fibrosis is important for early diagnosis and intervention in chronic heart diseases. Here, we investigated whether noninvasive, contrast agent-free MRI T₂-mapping can quantify myocardial fibrosis in preclinical models of aging and pressure overload. Myocardial fibrosis and remodeling were analyzed in two animal models: (i) aging (15-month-old male CF-1 mice vs. young 6- to 8-week-old mice), and (ii) pressure overload (PO; by transverse aortic constriction in 4- to 5-month-old male C57BL/6 mice vs. sham-operated for 14 days). In vivo T₂-mapping was performed by acquiring data during the isovolumic and early diastolic phases, with a modified respiratory and ECG-triggered multiecho TurboRARE sequence on a 7-T MRI. Cine MRI provided cardiac morphology and function. A quantitative segmentation method was developed to analyze the in vivo T₂-maps of hearts at midventricle, apex, and basal regions. The cardiac fibrosis area was analyzed ex vivo by picro sirius red (PSR) staining. Both aged and pressure-overloaded hearts developed significant myocardial contractile dysfunction, cardiac hypertrophy, and interstitial fibrosis. The aged mice had two phenotypes, fibrotic and mild-fibrotic. Notably, the aged fibrotic subgroup and the PO mice showed a marked decrease in T₂ relaxation times (25.3 ± 0.6 in aged vs. 29.9 ± 0.7 ms in young mice, p = 0.002; and 24.3 ± 1.7 in PO vs. 28.7 ± 0.7 ms in shams, p = 0.05). However, no significant difference in T₂ was detected between the aged mild-fibrotic subgroup and the young mice. Accordingly, an inverse correlation between myocardial fibrosis percentage (FP) and T₂ relaxation time was derived (R² = 0.98): T₂ (ms) = 30.45 – 1.05 × FP. Thus, these results demonstrate a statistical agreement between T₂-map–quantified fibrosis and PSR staining in two different clinically relevant animal models. In conclusion, T₂-mapping MRI is a promising noninvasive contrast agent-free quantitative technique to characterize myocardial fibrosis.     

Le traumatisme psychique constitue une blessure du langage par atteinte des réseaux de significations

ObjectivesTrauma appears within the discourse of mentally injured people, materializing what we have recently defined as “post traumatic psycholinguistic syndrome” (SPLIT). Translating unspeakability, revival, and dissociation, this clinical entity associates three significant disturbances : traumatic anomia (missing words, reduction of the elocutionary flow, deictic gestures, etc.); linguistic repetitions (of words and phrases, verbal intrusions, echophrasias, etc.); and phrasal and discursive disorganization (incomplete sentences, tense discordance, dysfluence, lack of logical connectors, etc.). What are the causes of these semiological and psycholinguistic expressions? What are their psychological and/or neuropsychological processes? It is time to come up with a new concept intended to go beyond the previous models in order to better identify people suffering from post-traumatic mental disorders, to better organize and evaluate psychotherapeutic care, and also to help practitioners collaborate more effectively on these first two goals. But how to evoke, affirm, or speak out about the consequences of unspeakability? Nothing is more apparently contradictory than wanting to define the language void. How to account for the fractures of psychic trauma in discourse? Nothing is more uncertain than to try to organize the upheavals, the disorders caused by dissociation in language. Finally, how to specify the reiteration of the trauma using words and sentences without this modeling being dissociative or repetitive? Today, thanks to a psycholinguistic reading, essential dimensions of post-traumatic suffering, hitherto hidden, can be clarified. Why exactly does an event cause trauma in the life of a subject at a given moment in her/his existence? Why is a latency phase structured between the traumatic event and the return of reviviscences under the influence of a re-triggering factor? How to differentiate the notion of dissociation as a normal phenomenon from the so-called traumatic dissociation? How to explain the multiple clinical forms of post-traumatic psychological disorders?MethodsFrom Pierre's clinical history, we chronologically detail the structuring and the consequences of the signified reflection that are constitutive of the psychic trauma: the psycholinguistic tools here help to formulate a new etiopathogenic conception of trauma and its psychological consequences. Then, thanks to Jean's testimony, taking up the retrospective meaning of the clinical analysis from chronic repetition syndrome, we discover the phases of tension regarding signified knowledge, up to the network prior to the traumatic confrontation. Finally, illustrated by Karima's disorder, beyond depersonalization, we explain that the analysis of the disturbances of a singular signified network, and also of an attack on its familial and societal bases, testifies to individual and collective subjectivities.ResultsComing from the real world, and therefore also from the body, the stimuli made up of signals picked up by our senses combine to compose an event that can be objectified by its temporal, spatial, biological, and physico-chemical coordinates. These elements combine into a unit, which is then interpreted by the mind, which attributes meaning to this event, which has become subjective reality. But when the subject is not sufficiently prepared to be confronted with this meaning that appears to be in extreme contradiction with her/his previous cardinal networks of significations, it makes “too much sense:” this irreconcilable hyper-signified (that we call the traumatic signified) results in post-traumatic dissociation. In other words, it is an impossibility of concordance of a signified with certain systems of prior significations that constitutes the pathogenesis of the trauma; and a situation runs a greater risk of being traumatic when it contradicts, or, moreso, endangers some or all of the subject's cardinal meanings. This unbearable signified reflexively blocks the capacities of significations immediately pre- and post-trauma, then dissociates the psychic functions to varying degrees and intensities. The traumatic signified, rejected, becomes unattainable: the stimuli that led to its formation find themselves confined to the state of reviviscences, each replication of which attempts to cross the barrier of inconceivability. Limiting sensory compounds to their raw states without the possibility of representational integration, associative pathways remain blocked. The signifier is referred to a hypo-signifier confined to the infra-linguistic by its confusion with the referent, the “objective and material” components of the traumatic event. Dissociation is therefore only a symptomatic reaction, secondary to the trauma, which it reinforces once again by limiting any possibility of representing the trauma. This dissociation does not involve forgetting the traumatic signified but “protects” the adjacent networks of meanings from it as much as it “keeps” this hypersignified intact, therefore ultimately “protecting” it as well. The traumatic signified persists somewhere, and even ends up being found everywhere: when the networks of meanings turn out to be globally disturbed, the tightest links remain those of the traumatic hypersignified that ultimately governs all the networks of meanings.DiscussionOur insufficient knowledge prevents us from precisely qualifying the architecture of the signified idiosyncratic networks and their evolutionary capacities; we cannot predict, beforehand, the reaction of an individual confronted with a potentially psychotraumatic situation. For most clinical situations, we affirm that the psychological trauma occurs in a psychically healthy subject, that is, not suffering from any psychiatric illness or any obvious psychopathological conflict. Psychotherapy will make it possible to discover the signified, sometimes ancient, origins of a trauma occurring in a singular subject. How was this subjectivity constructed? Beyond individual subjectivity, the intensity of certain confrontations such as serious attacks or macrosocial catastrophes such as genocide, would seem to lead to psychological wounds in any individual, even at the scale of a population. While, throughout existence, each subject produces a system of significations in connection with a unique psychic construction, the latter persists – resulting from, and often remaining overseen by, the community essence of a base of signifying networks, which we call “societal subjectivity.” Here, the psychological trauma can correspond to an individual and “common” injury as a failure of a sharing, or of ancestral beliefs anchored in the collective memory, defining the culture. By the collapse of acquired certainties, the cognitive patterns transmitted by education, language, and everything that establishes one's belonging to a society, trauma shakes the networks of individual and group meanings. Horror has a higher traumatogenic risk, because it defeats the fundamentals of humankind, the foundations of a signified network common to a culture, or even to all cultures, to the human condition. This is the case with murder, rape, torture, wars, genocides. Testifying to an instinct for survival stemming from the biological foundations of every living being, the impossibility of “living death” appears to be anchored in our networks of meanings and is manifested by indescribability, traumatic as such: being deserted by the language collides with the condition of speaking. And yet, it remains possible to say something about it... As a path of progressive desocialization, the occasional loss of the community of language, followed by its lasting traumatic ravages, can be appeased by the reestablishment of a speech link, either within the mind of the subject alone, or promoted by the exchange with others, in a psychotherapeutic setting, for example.ConclusionWhere theoretical discourses have sometimes proved divisive, going beyond the symptoms of indescribability and dissociation, psychodynamic practice today offers to unite. Thanks to psycholinguistic listening, phenomena that have never been explained take on meaning: the singularity of traumatic perception, the chronology of disorders including the latency phase, factors that trigger reviviscences, and the diversity of chronic clinical forms. All these post-traumatic symptoms are consequential to a linguistic wound, a difficulty in accessing meaning, the undermining of two dimensions characterizing and constructing the human being. As much as it integrates extralinguistic determinants, if the traumatic signified is undoubtedly not only speech, language appears the optimal way to identify it as such, while in the same movement appeasing it. The traumatic hypersignified is discovered through clinical analysis and psychotherapy, through deferred action, through the attribution of meaning, through the retrospective reconstruction of an unstable “real,” through a changing narration eternally distancing itself from reviviscences. But what precisely are the mechanisms of effective therapies ? What are the intersubjective links called for in the discussion between patient and practitioner? Could the operations that we call “psychotherapy” be made up of mobilizations of the networks of meanings by speech acts?     

A Phase I Dose Escalation Study of the Safety,Tolerability, and Pharmacokinetics of Ipilimumab in Chinese Patients with Select Advanced Solid Tumors

Lessons Learned

• The overall safety profiles of ipilimumab 3 mg/kg and 10 mg/kg administered every 3 weeks, were consistent between Chinese patients with solid tumors in the current study and patients from previous U.S. ipilimumab monotherapy studies. No new safety signals were identified.
• The mean systemic exposures to ipilimumab (assessed by first dose area under the curve during the dosing interval and maximum serum concentration) were numerically lower in the Chinese patient population than in U.S. patients for both 3 mg/kg and 10 mg/kg doses; however, the range of serum concentrations in the Chinese and U.S. populations overlapped (3 mg/kg and 10 mg/kg), suggesting that ipilimumab pharmacokinetics was ethnically insensitive in this study.

BackgroundThis phase I, open‐label study assessed ipilimumab safety, tolerability, pharmacokinetics (PK), immunogenicity, and antitumor activity in Chinese patients with unresectable, metastatic, recurrent malignant melanoma (MM) or nasopharyngeal carcinoma (NPC).MethodsOf 39 patients enrolled, 25 received ipilimumab (11 patients received 3 mg/kg, and 14 patients received 10 mg/kg). Reasons for not receiving treatment were withdrawal of consent (3 patients), no longer meeting the criteria (10 patients), and one recorded as “other.” During the induction phase, patients received ipilimumab (3 mg/kg, i.v.), on day 1 of a 3‐week cycle, to a maximum of four doses or progressive disease (PD). During the maintenance phase at week 24, patients received ipilimumab (3 mg/kg, i.v.) on day 1 of a 12‐week cycle, to a maximum of 3 years or PD. Considering the co‐primary safety and PK endpoints, the successive dosing required nine patients with two or fewer dose‐limiting toxicities during the 42‐day observation period to proceed with a new cohort of nine patients at 10 mg/kg.ResultsIpilimumab safety and PK profiles were similar in Chinese and predominantly White populations. Ipilimumab was well tolerated. Most adverse events (AEs) were grades 1–2 and experienced by 11 patients treated with 3 mg/kg and 14 patients treated with 10 mg/kg. There were no new safety concerns. Incidence of anti‐ipilimumab antibodies was low (1 of 10 in the 3 mg/kg patients and 2 of 13 in the 10 mg/kg patients) and without safety implications. In the 3 mg/kg group, 8 of 11 patients had PD. In the 10 mg/kg group (all NPC, 0 MM patients), 11 of 14 patients had PD. Three patients had stable disease (one at 3 mg/kg and two at 10 mg/kg).ConclusionIpilimumab was well tolerated in Chinese patients, showing similar safety and PK to previous studies in predominantly White populations.     

《医疗质量管理办法》中医疗质量概念及相关问题探讨

采用文献复习和实证研究经验的方法对《医疗质量管理办法》中涉及的医疗质量概念及相关问题进行探讨。《医疗质量管理办法》中的医疗质量的定义存在重大缺失,没有涉及医疗服务的结果,特别是患者安全。医疗质量的定义应与国际相关权威机构保持一致,应高度重视医疗服务的结果,特别是患者安全。     

Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml^-1 or < 300 ng.ml^-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127–141 [120–172]) g.l^-1, 143 (133–150 [120–179]) g.l^-1, p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77–82 [9–85]) days vs. 81 (79–83 [0–85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.     

Silencing KLF16 inhibits oral squamous cell carcinoma cell proliferation by arresting the cell cycle and inducing apoptosis

Krüppel-like factor 16 (KLF16), a member of the Krüppel-like factor (KLF) family, has been extensively investigated in multiple cancer types. However, the role of KLF16 in oral squamous cell carcinoma (OSCC) remains unknown. Thus, we conducted this study to investigate its related mechanism. KLF16 expression in OSCC cell lines was quantified by western blotting. Then, OECM1 and OC3 cells were divided into Blank, siCtrl, siKLF16#1 and siKLF16#2 groups. Subsequently, cell proliferation was detected using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assays, cell migration and invasion were detected with wound healing and Transwell assays, and cell cycle distribution and cell apoptosis were detected via flow cytometry. KLF16, p21, CDK4, Cyclin D1 and p-Rb expression was detected by western blotting. Finally, xenograft models were established in nude mice to observe the in vivo effects of KLF16 on OSCC. KLF16 protein expression was upregulated in OSCC cells. Compared to the cells in the Blank group, the OECM1 and OC3 cells in the siKLF16#1 group and siKLF16#2 group exhibited a sharp decrease in proliferation but a remarkable increase in apoptosis. Moreover, the proportion of cells in the G0/G1 phase notably increased and that in the S phase decreased, with evident decreases in cell invasion and migration. Moreover, KLF16, cyclin-dependent kinase 4 (CDK4), Cyclin D1 and p-Rb protein expression was upregulated, but p21 expression was downregulated. The mice in the siKLF16#1 and siKLF16#2 xenograft model groups exhibited slower tumour growth and smaller tumours with evident downregulation of Ki67 expression compared to the mice in the Blank group. KLF16 expression was upregulated in OSCC cells, and interfering with KLF16 led to cell cycle arrest, inhibited OSCC cell growth and promoted cell apoptosis.