Supraspan verbal list-learning tests, such as the Rey Auditory Verbal Learning Test (RAVLT), are classic neuropsychological tests for assessing verbal memory. In this study, we investigated the impact of the meaning of the words to be learned on 3 memory stages (short-term recall, learning, and delayed recall) in a cohort of 447 healthy adults. First, we compared scores obtained from the RAVLT (word condition) to those of an alternative version of this test using phonologically similar but meaningless items (pseudoword (...) condition) and observed how each score varied as a function of age and sex. Then, we collected the participants’ self-reported strategies to retain the word and pseudoword lists and examined if these strategies mediated the age and sex effects on memory scores. The word condition resulted in higher memory scores than pseudoword condition at each memory stage and even canceled out, for the learning stage, the detrimental effect of age that was observed for the short-term and delayed recall. When taking sex into account, the word advantage was observed only in women for short-term recall. The self-reported strategies, which were similar for words and pseudowords, were based on the position of the item on the list (word: 53 %, pseudoword: 37%) or the meaning of the item (word: 64%, pseudoword: 58%) and were used alone or in combination. The best memory performance was associated with the meaning strategy in the word condition and with the combination of the meaning and position strategies in the pseudoword condition. Finally, we found that the word advantage observed in women for short-term recall was mediated by the use of the meaning strategy. The RAVLT scores were thus highly dependent on word meaning, notably because it allowed efficient semantic knowledge-based strategies. Within the framework of Tulving’s declarative memory model, these results are at odds with the depiction of the RAVLT as a verbal episodic memory test as it is increasingly referred to in the literature. (shrink)

Tremendous development in recent medical science and the consequent discoveries resulting in successful prevention and also cure of different diseases are shared by clinical research involving the human volunteers. Preceding the trials in the human subjects, and to ensure safety, the proposed drug and other interventions are either tested in animals (vivo) or in laboratory (vitro) to evaluate initial safe starting dose for the human beings and to key out the benchmarks for the clinical monitoring for (...) the potential unfavorable effects. These pre human trials might not necessarily protect against the untoward effects in the human beings as happened in the case of thalidomide tragedy, which caused disability and killed thousands of babies born to the mothers, those who took this medicine. Use of healthy human volunteers in the preliminary experiments or phase I clinical trials either reduces or excludes risks of subsequent undesirable effects in the future trails (1). Phase-1 trials are conducted in order to test the safety, reactions and immunogenicity of vaccines in volunteers. Novel treatments for the cancer are first tested in phase 1 trials enrolling the patients with advanced disease, who have exhausted the standard treatment options. Phase-1 oncology trials are the pivot point in the translation of new cancer therapies from bench to bedside. Nevertheless, these trials remain ethically controversial. The controversy stems from the fact that, classically, phase-1 oncology clinical trials involve first-in-human testing of experimental treatment candidates in patients with a terminal diagnosis, who typically have exhausted standard treatment options. Commentators on the ethics of phase-1 clinical trials make diametrically opposed claims about the prospect of direct medical benefit from participation in these trials-benefits that can be attributed to receiving the experimental treatment intervention. One camp of benefit skeptics, inhabited mainly by bioethicists, characterizes this form of research as lacking any reasonable prospect of direct medical benefit. They see an ethical cloud hovering over phase-1 trials, because the vast majority of patients volunteer for phase-1 trials out of a motivation to receive medical benefit. In the view of these skeptics, such patients therefore harbor a ‘therapeutic misconception’ about research participation. This misconception calls into question the validity of informed consent and thereby undercuts the ethical basis of these trials (2). In this paper, I will discuss the ethical justification of the participation of human volunteers in phase-1 trials. (shrink)

The Gait Deviation Index is a multivariate measure of overall gait pathology based on 15 gait features derived from three-dimensional kinematic data. GDI aims at providing a comprehensive, easy to interpret, and clinically meaningful metric of overall gait function. It has been used as an outcome measure to study gait in several conditions: cerebral palsy, post-stroke hemiparetic gait, Duchenne muscular dystrophy, and Parkinson’s disease, among others. Nevertheless, its use in population with Spinal Cord Injury has not been studied yet. The (...) aim of the present study was to investigate the applicability of the GDI to SCI through the assessment of the relationship of the GDI with the Walking Index for Spinal Cord Injury II. 3D gait kinematics of 34 patients with incomplete SCI was obtained. Besides, 3D gait kinematics of a sample of 50 healthy volunteers was also gathered with Codamotion motion capture system. A total of 302 and 446 strides were collected. GDI was calculated for each stride and grouped for each WISCI II level. HV data were analyzed as an additional set. Normal distribution for each group was assessed with Kolmogorov-Smirnov tests. Afterward, ANOVA tests were performed between each pair of WISCI II levels to identify differences among groups. The results showed that the GDI was normally distributed across all WISCI II levels in both iSCI and HV groups. Furthermore, our results showed an increasing relationship between the GDI values and WISCI II levels in subjects with iSCI, but only discriminative in WISCI II levels 13, 19, and 20. The index successfully distinguished HV group from all the individuals with iSCI. Findings of this study indicated that the GDI is not an appropriate multivariate walking metric to represent the deviation of gait pattern in adult population with iSCI from a normal gait profile when it is compared with the levels of walking impairment described by the WISCI II. Future work should aim at defining and validating an overall gait index derived from 3D kinematic gait variables appropriate for SCI, additionally taking into account other walking ability outcome measures. (shrink)

Here we identify approximately 40,000 healthy human volunteers who were intentionally exposed to infectious pathogens in clinical research studies dating from late World War II to the early 2000s. Microbial challenge experiments continue today under contemporary human subject research requirements. In fact, we estimated 4,000 additional volunteers who were experimentally infected between 2010 and the present day. We examine the risks and benefits of these experiments and present areas for improvement in protections of participants with (...) respect to safety. These are the absence of maximum limits to risk and the potential for institutional review boards to include questionable benefits to subjects and society when weighing the risks and benefits of research protocols. The lack of a duty of medical care by physician–investigators to research subjects is likewise of concern. The transparency of microbial challenge experiments and the safety concerns raised in this work may stimulate further dialogue on the risks to participants of human experimentation. (shrink)

There is a long history of medical research that involves intentionally infecting healthy people in order to study diseases and their treatments. Such research—what might be called “human challenge studies”—are an important strand of much current research—for example, in the development of vaccinations. The many international and national guidelines about the proper conduct of medical research do not specifically address human challenge studies. In this paper we review the guidelines on the risk of harm that healthy (...) volunteers may be exposed to in the course of medical research. We examine the ethical arguments that are implicit or explicit in these guidelines. We then ask whether there is reason for limiting such studies on grounds independent of risk of harm. We conclude that the major ethical concern with challenge studies is that of risk of harm and that the fact that a study is a challenge study is not a wrong in itself. (shrink)

Healthy Volunteers (HVs) who participate in clinical trials are a vulnerable group that deserves specific protection. We assessed the number and types of studies that involve HVs around the world and outline the methodological barriers to their analysis. We found that tens of thousands of HVs are involved every year in clinical trials in a large variety of countries and that the overwhelming majority of studies are not “first-in-human” but pharmacokinetic studies. The two cornerstones for both ethical (...) and safe participation of HVs in clinical trials are properly obtained informed consent, and a minimization of exposure to risk, in particular by avoiding concealed participation in multiple trials. To minimize the risk of exploitation of HVs and their exposure to risk, we propose ways to ensure genuine informed consent, and advocate setting up national Healthy Volunteer volunteer registries as established in France and the U.K. (shrink)

Healthy volunteers in biomedical research often face significant risks in studies that offer them no medical benefits. The U.S. federal research regulations and laws adopted by other countries place no limits on the risks that these participants face. In this essay, I argue that there should be some limits on the risks for biomedical research involving healthy volunteers. Limits on risk are necessary to protect human participants, institutions, and the scientific community from harm. With the (...) exception of self-experimentation, limits on research risks faced by healthy volunteers constitute a type of soft, impure paternalism because participants usually do not fully understand the risks they are taking. I consider some approaches to limiting research risks and propose that healthy volunteers in biomedical research should not be exposed to greater than a 1% chance of serious harm, such as death, permanent disability, or severe illness or injury. While this guideline would restrict research risks, the limits would not be so low that they would prevent investigators from conducting valuable research. They would, however, set a clear upper boundary for investigators and signal to the scientific community and the public that there are limits on the risks that healthy participants may face in research. This standard provides guidance for decisions made by oversight bodies, but it is not an absolute rule. Investigators can enroll healthy volunteers in studies involving a greater than 1% chance of serious harm if they show that the research addresses a compelling public health or social problem and that the risk of serious harm is only slightly more than 1%. The committee reviewing the research should use outside experts to assess these risks. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 47-54 [Access article in PDF] Ethical Guidelines for Human Embryonic Stem Cell Research*(A Recommended Manuscript) Adopted on 16 October 2001Revised on 20 August 2002 Ethics Committee of the Chinese National Human Genome Center at Shanghai, Shanghai 201203 Human embryonic stem cell (ES) research is a great project in the frontier of biomedical science for the twenty-first century. Be- cause (...) the research involves the use of human embryos, it triggers serious debate on ethical issues. Opponents consider the embryo to be an early form of human life that should be respected and not destroyed. However, the majority of scientists support embryonic stem cell research, believing that it offers good prospects for the treatment of diseases that have remained incurable until now and so will benefit humankind. The Ethics Committee of the Department of Ethical, Legal, and Social Implications of the Chinese National Human Genome Center at Shanghai seriously discussed the ethical debate initiated by embryonic stem cell research. We concluded that we should support the scientists of our country in actively carrying out human embryonic stem cell research for the noble cause of "medicine being a beneficent art." For the healthy and orderly development of human embryonic stem cell research in our country, we put forward the following recommended Ethical Guidelines for Human Embryonic Stem Cell Research as a reference for leaders, administrative departments, and related scientists. Preface Article 1. Human embryonic stem cells are the primitive cells that play the main role in the growth and development of a human body. These [End Page 47] primitive cells have the potential for infinite proliferation, self-renewal, and multi-directional differentiation. If scientists can discover the mechanism of differentiation of human embryonic stem cells, it will be possible to induce differentiation of human embryonic stem cells to form various types of human cells for clinical cell therapy. If human embryonic stem cell research can be integrated with modern biomedical engineering techniques, it also will be possible to make repair and replacement of human tissues and organs a reality. Article 2. There are two ways to classify human embryonic stem cells. One way is to classify them according to their potential for differentiation. There could be three kinds of stem cells: totipotent stem cells, pluripotent stem cells, and unipotent stem cells.A totipotent stem cell has the potential to develop into a whole individual. It can differentiate into the more than 200 cell types in the whole body, construct any tissue or organ of the body, and finally develop into a whole individual. The fertilized egg and the cleavage cells at the very early stage of embryonic development are totipotent stem cells.A pluripotent stem cell has the potential to differentiate into many cell types derived from the three embryonic layers. However, it has lost the capacity to develop into a complete organism.A unipotent stem cell is derived from the further differentiation of the pluripotent stem cell. It can differentiate only into one cell type such as a hematopoietic stem cell, neural stem cell, and others.The other way is to classify human stem cells according to their source. There could be two kinds of human stem cells: embryonic stem cells and tissue stem cells (also called adult stem cells). The former involves experimentation with embryos, which has serious ethical implications. Ethical issues associated with the latter are mainly expressed in the various opinions regarding the allocation of health resources. Article 3. Human embryonic stem cells are the group of cells called the blastocyst inner cell mass during the early stage of embryonic development. They are the main source of totipotent stem cells, and hence the focal and hot point in stem cell research. Studies on the clinical application of embryonic stem cells probably will involve use of the somatic cell nucleus transfer (SCNT) technique, which destroys the early human embryo. At present, the ethical and moral debate is very serious in human embryonic stem cell research regarding whether the research will develop... (shrink)

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in‐depth interviews and non‐participant observation. Sixty‐nine participants were involved, (...) including CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive‐deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context. (shrink)

Clinical investigators must engage in just subject recruitment and selection and avoid unduly influencing research participation. There may be tension between the practice of keeping payments to participants low to avoid undue influence and the requirements of justice when recruiting normal healthy volunteers for phase 1 drug studies. By intentionally keeping payments low to avoid unduly influenced participation, investigators, on the recommendation or insistence of institutional review boards, may be targeting or systematically recruiting healthy adult members (...) of lower socio-economic groups for participation in phase 1 studies. Investigators are at risk of routinely failing to fulfill the obligation of justice, which prohibits the systematic targeting and recruiting of subjects for reasons unrelated to the nature of the study. Insofar as we take seriously the obligation to engage in just subject recruitment and selection, I argue that we must acknowledge the implications low payments might have for subject recruitment and selection and examine the effect of low payments. If low payments de facto target the less well-off for phase 1 studies, we must defend the priority ranking of the obligation to avoid undue influence over the obligation of justice or adopt an alternative recruitment approach. This paper identifies a number of alternatives to the current system of low-value payments to research participants. (shrink)

Phase I clinical trials are the first stage of testing new pharmaceuticals in humans. The majority of these studies are conducted under controlled, inpatient conditions using healthy volunteers who are paid for their participation. This article draws on an ethnographic study of six phase I clinics in the United States, including 268 semistructured interviews with research staff and healthy volunteers. In it, I argue that an institutional banalization of risk structures the perceptions of research staff and (...) healthy volunteers participating in the studies. For research staff, there are three mechanisms by which risk becomes banal: a perceived homogeneity of studies, Fordist work regimes, and data-centric discourse. For healthy volunteers, repeat study participation contributes to the institutional banalization of risk both through the process of desensitization to risk and the formation of trust in the clinics. I argue that the institutional banalization of risk also renders invisible ethical concerns about exploitation of underprivileged groups in pharmaceutical research. (shrink)

Human Infection Studies have emerged as an important research approach with the potential to fast track the global development of vaccines and treatments for infectious diseases, including in low resource settings. Given the high level of burdens involved in many HIS, particularly prolonged residency and biological sampling requirements, it can be challenging to identify levels of study payments that provide adequate compensation but avoid ‘undue’ levels of inducement to participate. Through this embedded ethics study, involving 97 healthy (...) class='Hi'>volunteers and other research stakeholders in a malaria HIS programme in Kenya, and using in-depth interviews, focus group discussions and observations during and after a malaria HIS, we give a grounded account of ethical issues emerging in relation to study payments in this setting. While careful community, national, international scientific and ethics review processes meant that risks of serious harm were highly unlikely, the levels of motivation to join HIS seen could raise concerns about study payments being too high. Particular value was placed on the reliability, rather than level, of study payment in this setting, where subsistence livelihoods are common. Study volunteers were generally clear about the study aims at the point of recruitment, and this knowledge was retained over a year later, although most reported experiencing more burdens than anticipated at enrolment. Strict study screening procedures, regular clinical and laboratory monitoring of volunteers, with prompt treatment with antimalarial at predetermined endpoints suggested that the risks of serious harm were highly unlikely. Ethical concerns emerged in relation to volunteers’ attempts to conceal symptoms, hoping to prolong residency periods and increase study payments; and volunteers making decisions that compromised important family relationships and personal values. Our findings support an interpretation that, although study volunteers were keen to join the study to access cash payments, they also paid attention to other features of the study and the general clinical research landscape, including levels of risk associated with study participation. Overall, our analysis shows that the ethical concerns emerging from the study payments can be addressed through practical measures, hinged on reducing burdens and strengthening communication, raising important issues for research policy and planning. (shrink)

Background Healthy aging is one of the essential aspects of a health promotion program in the elderly. Aim Exploring ethical challenges in healthy elderly care from the perspective of nurses, older adults, and families in the Iranian context. Research Design This qualitative study was conducted using a content analysis approach in 4 health centers in northeastern Iran from 2017 to 2019. Semi-structured interviews, observation, review of elderly files, and focus groups were used to collect data. Ethical considerations The (...) ethics committee of the university approved this study in Iran. This study adhered to the principles of the Helsinki Declaration. Ethical principles autonomy, confidentiality, and anonymity were considered for the participants. Participants were informed about the purpose of the study and submitted written informed consent regarding their participation. Findings The central theme was: An unfair approach to caring for healthy older adults. The three categories were as follows: Forgotten human care, disrespect, and lack of a meaningful and trustworthy relationship. The 14 subcategories highlighted the ethical challenges of healthy aging care in health centers. Discussion The findings showed that due to nurses’ unfamiliarity with the concept of healthy aging, older adults are discriminated against in care centers. Creating a standard care program for healthy older adults ensures that ethical principles are followed for these clients. Conclusion Various individual and organizational factors lead to an unfair approach to caring for healthy elderly in health centers. The following factors can help improve the care of healthy aging and reduce ethical challenges in this area: Introducing nurses to the concept of healthy old age and its dimensions, creating a community-based approach in health centers, prioritizing health issues over health issues, Involvement of families and older adults in needs assessment-goal setting-implementation and evaluation of health services, and design of home visit programs to provide services to healthy elderly. (shrink)

While risk of harm is an important focus for whether clinical research on humans can and should proceed, there is uncertainty about what constitutes harm to a trial participant. In Phase I trials on healthy volunteers, the purpose of the research is to document and measure safety concerns associated with investigational drugs, and participants are financially compensated for their enrollment in these studies. In this article, we investigate how characterizations of harm are narrated by healthy volunteers (...) in the context of the adverse events they experience during clinical trials. Drawing upon qualitative research, we find that participants largely minimize, deny, or re-attribute the cause of these AEs. We illustrate how participants' interpretations of AEs may be shaped both by the clinical trial environment and their economic motivation to participate. While these narratives are emblematic of the larger ambiguity surrounding harm in the context of clinical trial participation, we argue that these interpretations also problematically maintain the narrative of the safety of clinical trials, the ethics of testing investigational drugs on healthy people, and the rigor of data collected in the specter of such ambiguity. (shrink)

Previous studies using the dot-perspective task postulated that people automatically take into account others' perspective even when it prevents them from achieving their own goals. This human ability may be of key importance for the ascription of mental states and social interactions. The cognitive and emotional determinants of automatic perspective taking is still matter of debate. To address this issue, we examined the performance in the Samson et al. APT task in 91 healthy adults who underwent a detailed (...) neuropsychological testing including assessment of their general intelligence, attention and impulsivity, alexithymia, and measures of affective empathy and explicit theory of mind. Univariate and multiple linear regression models were used to explore the association between mean reaction times in the APT task, and the CPT-II parameters, WAIS global score, TAS, and GeSoCS and mini-SEA scores. Only the CPT-II parameters were significantly associated with the mean reaction times. Increased omissions, commissions, and detectability as well as hit reaction time standard error in CPT-II were all related to worse performances both in Self and Other conditions. The mean number of errors was negatively associated with the GeSoCS score. Among the variables studied, only CPT-II parameters had a significant impact on egocentric and altercentric interference. Neither global intelligence nor alexithymia have an effect on dot-perspective task performance. The present findings suggest that people with lower attentional resources and increased impulsivity display worse performances in the APT task and are less responsive to both egocentric and altercentric interference. (shrink)

Working memory (WM) is a fundamental cognitive ability to support complex thought, but it is limited in capacity. WM training has shown the potential to make benefit for those in need. Many studies have shown the potential of transcranial direct current stimulation (tDCS) to transiently enhance WM performance by delivering low current to the brain cortex of interest via electrodes on the scalp. TDCS has also been revealed as a promising intervention to augment WM training in a few studies. However, (...) those few tDCS-paired WM training studies focused more on the effect of tDCS on WM enhancement and its transferability after training but paid less attention to the variation of cognitive performance during the training procedure. The current study attempted to explore the effect of tDCS on the variation of performance during WM training in healthy young adults. All the participant received WM training with the load-adaptive verbal N-back task for five days. During the training procedure, active/sham anodal high-definition tDCS (HD-tDCS) was used to stimulate the left dorsolateral prefrontal cortex (DLPFC). To examine the training effect, pre- and post-test were performed respectively one-day before and after the training sessions respectively. At the beginning of each training session, stable-load WM tasks were performed to examine the performance variation during training. Compared to the sham stimulation, higher learning rates of performance metrics during the training procedure were found when WM training was combined with active anodal HD-tDCS. The performance improvements (post-pre) of the active group were also found to be higher than those of sham group and were transferred to a similar untrained WM task. Further analysis revealed that the negative relation between the training improvements and baseline performance. These findings show the potential that tDCS may be leveraged as an intervention to facilitate WM training for those in need of higher WM ability. (shrink)

Long-term potentiation is one of the most extensively studied forms of neuroplasticity and is considered the strongest candidate mechanism for memory and learning. The use of event-related potentials and sensory stimulation paradigms has allowed for the translation from animal studies to non-invasive studies of LTP-like synaptic plasticity in humans. Accumulating evidence suggests that synaptic plasticity as measured by stimulus-specific response modulation is reduced in neuropsychiatric disorders such as major depressive disorder, bipolar disorders and schizophrenia, suggesting that impaired synaptic plasticity plays (...) a part in the underlying pathophysiology of these disorders. This is in line with the neuroplasticity hypothesis of depression, which postulate that deficits in neuroplasticity might be a common pathway underlying depressive disorders. The current study aims to replicate and confirm earlier reports that visual stimulus-specific response modulation is a viable probe into LTP-like synaptic plasticity in a large sample of healthy adults. Further, this study explores whether impairments in LTP-like synaptic plasticity is associated with self-reported subclinical depressive symptoms and stress in a healthy population. Consistent with prior research, the current study replicated and confirmed reports demonstrating significant modulation of visual evoked potentials following visual high-frequency stimulation. Current results further indicate that reduced LTP-like synaptic plasticity is associated with higher levels of self-reported symptoms of depression and perceived stress. This indicate that LTP-like plasticity is sensitive to sub-clinical levels of psychological distress, and might represent a vulnerability marker for the development of depressive symptoms. (shrink)

Mismatch brain responses to unpredicted rare stimuli are suggested to be a neural indicator of prediction error, but this has rarely been studied in the somatosensory modality. Here, we investigated how the brain responds to unpredictable and predictable rare events. Magnetoencephalography responses were measured in adults frequently presented with somatosensory stimuli that were occasionally replaced by two consecutively presented rare stimuli [unpredictable rare stimulus and predictable rare stimulus ; p = 0.1 for each]. The FRE and PR were electrical stimulations (...) administered to either the little finger or the forefinger in a counterbalanced manner between the two conditions. The UR was a simultaneous electrical stimulation to both the forefinger and the little finger. The grand-averaged responses were characterized by two main components: one at 30–100 ms and the other at 130–230 ms latency. Source-level analysis was conducted for the primary somatosensory cortex and the secondary somatosensory cortex. The M55 responses were larger for the UR and PR than for the FRE in both the SI and the SII areas and were larger for the UR than for the PR. For M150, both investigated areas showed increased activity for the UR and the PR compared to the FRE. Interestingly, although the UR was larger in stimulus energy and had a larger prediction error potential than the PR, the M150 responses to these two rare stimuli did not differ in source strength in either the SI or the SII area. The results suggest that M55, but not M150, can possibly be associated with prediction error signals. These findings highlight the need for disentangling prediction error and rareness-related effects in future studies investigating prediction error signals. (shrink)

Pinch force sense plays an important role in the performance of daily finger movements, including tip, key, palmar pinch. The present study investigated the roles of pinch type in the sensation of pinch force among healthy participants in the ipsilateral force reproduction trial. This study instructed forty healthy adult subjects (20 women and 20 men) in producing reference forces at different levels [10, 30, 50% maximal voluntary isometric contraction (MVIC)] by adopting 3 pinch types (tip, key, and (...) palmar pinches) and in reproducing the above force levels with the identical hand. Our study revealed that subjects are significantly more sensitive detecting alterations of pinching forces with tip pinch but not key or palmar pinch under high forces (30 and 50% MVIC) but not at lower force levels (10% MVIC). (shrink)

The cosmetics, detergents and food industries trial development products using healthy human volunteer studies. They also use human tissue for in vitro investigations. Hitherto, the ethics of such work has not been regulated. The UK Human Tissue Act will have legal implications on current arrangements for such studies within the industry, especially with regards to informed consent and seeking ethical review of research proposals. At present, however, it is unclear who will fund ethical review for use (...) of ‘relevant material’ in non-medical research, and on the required status of ethics committees to review such work. The principles behind the sampling, storage and processing of ‘relevant material’ are largely identical whether it be for medical or non-medical investigations. It is argued, therefore, that this is further justification for industry and professional bodies to adopt best practice of ethical review for all studies in ‘grey areas’ outside the scope of regulations. This would follow closely those standards applied to biomedical research. (shrink)

The output from motor neuron pools is influenced by the integration of synaptic inputs originating from descending corticomotor and spinal reflex pathways. In this study, using paired non-invasive brain and peripheral nerve stimulation, we investigated how descending corticomotor pathways influence the physiologic recruitment order of the soleus Hoffmann reflex. Eleven neurologically unimpaired adults completed an assessment of transcranial magnetic stimulation -conditioning of the soleus H-reflex over a range of peripheral nerve stimulation intensities. Unconditioned H-reflex recruitment curves were obtained by delivering (...) PNS pulses to the posterior tibial nerve. Subsequently, TMS-conditioned H-reflex recruitment curves were obtained by pairing PNS with subthreshold TMS at short and long intervals. We evaluated unconditioned and TMS-conditioned H-reflex amplitudes along the ascending limb, peak, and descending limb of the H-reflex recruitment curve. Our results revealed that, for long-interval facilitation, TMS-conditioned H-reflex amplitudes were significantly larger than unconditioned H-reflex amplitudes along the ascending limb and peak of the H-reflex recruitment curve. Additionally, significantly lower PNS intensities were needed to elicit peak H-reflex amplitude for long-interval facilitation compared to unconditioned. These findings suggest that the influence of descending corticomotor pathways, particularly those mediating long-interval facilitation, contribute to changing the recruitment gain of the motor neuron pool, and can inform future methodological protocols for TMS-conditioning of H-reflexes. By characterizing and inducing short-term plasticity in circuitry mediating short- and long-interval TMS-conditioning of H-reflex amplitudes, future studies can investigate supraspinal and spinal circuit contributions to abnormal motor control, as well as develop novel therapeutic targets for neuromodulation. (shrink)

To reduce the global burden of the COVID-19 pandemic, there is an urgent need to develop a safe vaccine. Vaccine development usually takes many years as it goes through several different phases. To hasten COVID-19 vaccine development, it has been suggested that the final stage could be replaced with a human challenge trial. Volunteers would be intentionally infected with SARS-CoV-2 to see how the vaccine candidate works. To intentionally infect a healthy human being with a potentially (...) deadly virus is contrary to the highest ethical standards in medical research. This article highlights the benefits and risks of COVID-19 HCTs and summarises what research ethics committees need to consider during the ethical assessment of such trials including risk reduction, strict containment measures, specific informed consent measures and avoiding high monetary inducements. (shrink)

BackgroundIn recent years, there have been many studies using the Affective Neuroscience Personality Scales (ANPS) to investigate individual differences in primary emotion traits. However, in contrast to other primary emotion traits proposed by Jaak Panksepp and colleagues, there is a considerable lack of research on the LUST (L) dimension – defined as an individual’s capacity to attain sexual desire and satisfaction – a circumstance mainly caused by its exclusion from the ANPS. Therefore, this study aims to take a first step (...) toward the development of a standardized self-rate measurement for the L-disposition. For this purpose, two versions of the L-scales (L-12 and L-5) were developed and evaluated regarding reliability and aspects of validity.Materials and MethodsAfter a pilot study (N= 204; female: 81%) with an initial 20-item pool item reductions were conducted. This led to the construction of a 12-item (L-12) version and a 5-item version (L-5), which were assessed in a second sample consisting of 371 German-speaking healthy adults (58.50% female) aged 18–69 years (M= 28;SD= 9.75). Aspects of external validity were assessed by investigation of correlations with the ANPS, psychiatric symptoms (Brief Symptom Inventory-18), attachment security (Adult Attachment Scales) and personality functioning (Operationalized Psychodynamic Diagnostics Structure Questionnaire). To evaluate structural validity, both L-scales were investigated via confirmatory factor analysis (CFA).ResultsCronbach’s α indicated excellent internal consistency regarding L-12 (α = 0.90), while L-5 showed acceptable reliability (α = 0.82). CFA of a bifactor model of the L-12 indicated excellent model fit. Moreover, an excellent model fit was observed regarding a single factor model of L-5. For both scales small to moderate positive correlations were observed with SEEKING, PLAY, and secure attachment, while they exhibited small to moderate negative correlations with SADNESS, insecure attachment, lower personality functioning, and increased psychiatric symptom load.ConclusionBoth newly developed scales exhibit satisfying psychometric properties, indicating high reliability, good structural validity and plausible correlations with external criteria. Hence, this study poses an important step toward the operationalization of the LUST concept. However, more research is needed in particular with respect to the scale’s external validity and its applicability in clinical populations. (shrink)

Public attention on embryo research has never been greater. Modern reproductive medicine technology and the use of embryos to generate stem cells ensure that this will continue to be a topic of debate and research across many disciplines. This multidisciplinary book explores the concept of a 'healthy' embryo, its implications on the health of children and adults, and how perceptions of what constitutes child and adult health influence the concept of embryo 'health'. The concept of human embryo (...) health is considered from preconception to pre-implantation genetic diagnosis to recent foetal surgical approaches. Burgeoning capacities in both genetic and reproductive science and their clinical implications have catalysed the necessity to explore the concept of a 'healthy' embryo. The authors are from five countries and 13 disciplines in the social sciences, humanities, biological sciences and medicine, ensuring that the book has a broad coverage and approach. (shrink)

Physical fatigue negatively affects postural control, resulting in impaired balance performance in young and older adults. Similar effects on postural control can be observed for mental fatigue mainly in older adults. Controversial results exist for young adults. There is a void in the literature on the effects of fatigue on balance and cortical activity. Therefore, this study aimed to examine the acute effects of PF and MF on postural sway and cortical activity. Fifteen healthy young adults aged 28 ± (...) 3 years participated in this study. MF and PF protocols comprising of an all-out repeated sit-to-stand task and a computer-based attention network test, respectively, were applied in random order. Pre and post fatigue, cortical activity and postural sway were tested during a challenging bipedal balance board task. Absolute spectral power was calculated for theta, alpha-2, beta-1, and beta-2 in frontal, central, and parietal regions of interest and baseline-normalized. Inference statistics revealed a significant time-by-fatigue interaction for CoPd and CoPv, and a significant main effect of time for CoP variability. Post hoc analyses showed a significant increase in CoPd and CoPv following PF but not MF. For cortical activity, a significant time-by-fatigue interaction was found for relative alpha-2 power in parietal areas. Post hoc tests indicated larger alpha-2 power increases after PF compared to MF. In addition, changes in parietal alpha-2 power and measures of postural sway did not correlate significantly, irrespective of the applied fatigue protocol. No significant changes were found for the other frequency bands, irrespective of the fatigue protocol and ROI under investigation. Thus, the applied PF protocol resulted in increased postural sway and CoP variability accompanied by enhanced alpha-2 power in the parietal ROI while MF led to increased CoP variability and alpha-2 power in our sample of young adults. Potential underlying cortical mechanisms responsible for the greater increase in parietal alpha-2 power after PF were discussed but could not be clearly identified as cause. Therefore, further future research is needed to decipher alternative interpretations. (shrink)

ObjectiveThis systematic review aims to analyze existing literature of the effects of transcranial direct current stimulation (tDCS) on motor skills learning of healthy adults and discuss the underlying neurophysiological mechanism that influences motor skills learning.MethodsThis systematic review has followed the recommendations of the Preferred Reporting Items for Systematic reviews and Meta-Analyses. The PubMed, EBSCO, and Web of Science databases were systematically searched for relevant studies that were published from database inception to May 2022. Studies were included based on the (...) Participants, Intervention, Comparison, Outcomes, and Setting inclusion strategy. The risk of bias was evaluated by using the Review manager 5.4 tool. The quality of each study was assessed with the Physiotherapy Evidence Database (PEDro) scale.ResultsThe electronic search produced 142 studies. Only 11 studies were included after filtering. These studies performed well in terms of distribution, blinding availability and selective reporting. They reported that tDCS significantly improved motor skills learning. The main outcomes measure were the improvement of the motor sequence tasks and specific motor skills. Nine studies showed that tDCS interventions reduced reaction time to complete motor sequence tasks in healthy adults and two studies showed that tDCS interventions improved golf putting task performance.ConclusionThe included studies showed that tDCS can help healthy adults to improve the motor skills learning by activating different brain regions, such as the primary motor cortex, left dorsolateral prefrontal cortex and right cerebellum. However, the number of included studies was limited, and the sample sizes were small. Therefore, more studies are urgently needed to validate the results of current studies and further explore the underlying neurophysiological mechanisms of tDCS in the future. (shrink)

Background: Cognitive Training may contribute to the maintenance and even enhancement of cognitive functions in healthy older adults. However, the question who benefits most from multi-domain CTs is still highly under-investigated.Objective: The goal is to investigate prognostic factors and models for changes in cognitive test performance in healthy older adults after a multi-domain CT.Methods: The data bases MEDLINE, Web of Science Core Collection, CENTRAL, and PsycInfo were searched up to July 2019. Studies investigating prognostic factors and/or models on (...) cognitive outcomes after conducting a multi-domain CT in healthy older adults were included. Risk of Bias was assessed using the QUIPS and the PROBAST tool.Results: 23 prognostic factor and model studies were included. Results indicate a high heterogeneity regarding the conducted multi-domain CTs, the investigated prognostic factors, the investigated outcomes, and the used statistical approaches. Age and neuropsychological performance at study entry were the most investigated predictors, yet they show inconsistent results.Conclusion: Data on prognostic factors and models of changes after multi-domain CT are still too rare and inconsistent to draw clear conclusions due to statistical shortcomings and low reporting quality. Approaches for future research are outlined.Registration:https://www.crd.york.ac.uk/prospero/, ID: CRD42020147531. (shrink)

ObjectiveThe studies showed the benefits of virtual reality training for functional mobility and balance in older adults. However, a large variance in the study design and results is presented. We, thus, completed a systematic review and meta-analysis to quantitatively examine the effects of VRT on functional mobility and balance in healthy older adults.MethodsWe systematically reviewed the publications in five databases. Studies that examine the effects of VRT on the measures of functional mobility and balance in healthy older adults (...) were screened and included if eligible. Subgroup analyses were completed to explore the effects of different metrics of the intervention design on those outcomes related to functional mobility and balance.ResultsFifteen studies of 704 participants were included. The quality of these studies was good. Compared to traditional physical therapy, VRT induced greater improvement in TUG and one-leg stance with open eyes. Subgroup analyses revealed that immersive VRT with more than 800 min of total intervention time over 8 weeks and at least 120 min per week and/or designed by the two motor-learning principles was optimal for functional mobility and balance.ConclusionVirtual reality training can significantly improve functional mobility and balance in healthy older adults compared to TPT, and the findings provided critical knowledge of the optimized design of VRT that can inform future studies with more rigorous designs.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42021297085]. (shrink)

Research has shown that both physical exercise and cognitive training help to maintain cognition in older adults. The question is whether combined training might produce additive effects when the group comparisons are equated in terms of exercise intensity and modality. We conducted a systematic electronic search in MEDLINE, PsycInfo, and Cochrane Central Register of Controlled Trials databases to identify relevant studies published up to February 2021. Seven hundred and eighty-three effect sizes were obtained from 50 published intervention studies, involving 6,164 (...) healthy older adults, and submitted to a three-level meta-analysis. Results showed that combined training produced a small advantage in comparison to single cognitive training on executive functions, whereas both types of training achieved similar effects on attention, memory, language, processing speed, and global cognition. Combined training achieved higher training gains in balance than single physical training, indicating a transfer from cognitive training to balance. Performing cognitive and physical exercise simultaneously, and interactive training produced the largest gains in executive functions, speed, and global cognition, as well as the largest improvements in physical functions. Aerobic training was associated with higher effects in attention and fitness, whereas non-aerobic training produced larger effects in global cognition and balance. For all cognitive and physical outcomes, training resulted more advantageous when performed in a social context, even though individual training obtained similar results in balance as group training.Systematic Review Registration:www.crd.york.ac.uk/prospero/, identifier: CRD42020175632. (shrink)

Previous research on Physical Activity has been highly valuable in elucidating how PA affects the structure and function of the hippocampus in elderly populations that take part in structured interventions. However, how PA affects the hippocampus in younger populations that perform PA during daily-life activities remains poorly understood. In addition, this research has not examined the impact of PA on the internal structure of the hippocampus. Here, we performed a cross-sectional exploration of the way structural and functional aspects of the (...) hippocampus are associated with habitual PA performed during work, leisure time, and sports in the daily lives of healthy young adults. We assessed PA in these three different contexts through a validated questionnaire. The results show that PA performed during work time correlated with higher subicular volumes. In addition, we found that PA changed functional connectivity between a location in the middle/posterior hippocampus and regions of the default mode network, and between a location in the anterior hippocampus and regions of the somatomotor network. No statistical effects of PA performed during leisure time and sports were found. The results generalize the impact of PA on younger populations and show how PA performed in daily-life situations correlates with the precise internal structure and functional connectivity of the hippocampus. (shrink)

BackgroundSeveral investigations have addressed the process of balance adaptation to external perturbations. The adaptation during unperturbed stance has received little attention. Further, whether the current sensory conditions affect the adaptation rate has not been established. We have addressed the role of vision and haptic feedback on adaptation while standing on foam.MethodsIn 22 young subjects, the analysis of geometric and spectral variables of the oscillation of the centre of feet pressure identified the effects of vision, light-touch or both in the anteroposterior (...) and mediolateral direction over 8 consecutive 90 s standing trials.ResultsAdaptation was obvious without vision and tenuous with vision. With trial repetition, path length and median frequency diminished with EC while sway area and mean level of the spectrum increased. The low- and high-frequency range of the spectrum increased and decreased in AP and ML directions, respectively. Touch compared to no-touch enhanced the rate of increase of the low-frequency power. Spectral differences in distinct sensory conditions persisted after adaptation.ConclusionBalance adaptation occurs during standing on foam. Adaptation leads to a progressive increase in the amplitude of the lowest frequencies of the spectrum and a concurrent decrease in the high-frequency range. Within this common behaviour, touch adds to its stabilising action a modest effect on the adaptation rate. Stabilisation is improved by favouring slow oscillations at the expense of sway minimisation. These findings are preliminary to investigations of balance problems in persons with sensory deficits, ageing, and peripheral or central nervous lesion. (shrink)