Apathy and depression are frequently observed as behavioral and psychological symptoms of dementia, respectively, and are important for ensuring adequate care. This study aims to explore effective non-pharmacological interventions for apathy and depression with mild cognitive impairment and dementia. Five search engines including PubMed, Scopus, CINAHL, PsycInfo, and Web of Science were used to extract relevant studies. Inclusion criteria were studies that involved participants who were diagnosed with MCI or dementia, included quantitative assessments of each symptom, and employed randomized controlled (...) trials. Twenty studies were extracted, with interventions have been conducted in care facilities, the community, and hospitals. Participants in many studies had MCI or mild-to-moderate dementia but were not diagnosed with the subtypes of dementia. Few studies had set apathy and depression as the primary outcomes of non-pharmacological interventions. The findings suggested that emotional and stimulation-oriented approaches to apathy and depression would be useful for people with MCI or mild-to-moderate dementia. It would be helpful for therapists to assess the clinical features of the target symptoms for selecting suitable interventions. Additionally, increasing the number of randomized controlled trials focusing on apathy or depression as primary outcomes would offer a more definite conclusion for future systematic reviews. (shrink)

Antigen presentation to CD8+ T cells by MHC class I molecules is essential for host defense against viral infections. Various mechanisms have evolved in multiple viruses to escape immune surveillance and defense to support viral proliferation in host cells. Through in vitro SARS‐CoV‐2 infection studies and analysis of COVID‐19 patient samples, we found that SARS‐CoV‐2 suppresses the induction of the MHC class I pathway by inhibiting the expression and function of NLRC5, a major transcriptional regulator of MHC class I genes. (...) In this review, we discuss the molecular mechanisms for suppression of the MHC class I pathway and clinical implications for COVID‐19. (shrink)

The activity of the left and right central pattern generators is efficiently coordinated during locomotion. To achieve this coordination, the interplay between the CPG controlling one leg and that controlling another must be present. Previous findings in aquatic vertebrates and mammalians suggest that the alternate activation of the left and right CPGs is mediated by the commissural interneurons crossing the midline of the spinal cord. Especially, V0 commissural interneurons mediate crossed inhibition during the alternative activity of the left and right (...) CPGs. Even in humans, phase-dependent modulation of the crossed afferent inhibition during gait has been reported. Based on those previous findings, crossed inhibition of the CPG in one leg side caused by the activation of the contralateral CPG is a possible mechanism underlying the coordination of the anti-phase rhythmic movement of the legs. It has been hypothesized that the activity of the flexor half center in the CPG inhibits the contralateral flexor half center, but crossed inhibition of the extensor half center is not present because of the existence of the double limb support during gait. Nevertheless, previous findings on the phase-dependent crossed inhibition during anti-phase bilateral movement of the legs are not in line with this hypothesis. For example, extensor activity caused crossed inhibition of the flexor half center during bilateral cycling of the legs. In another study, the ankle extensor was inhibited at the period switching from extension to flexion during anti-phase rhythmic movement of the ankles. In this review article, I provide a critical discussion about crossed inhibition mediating the coordination of the anti-phase bilateral rhythmic movement of the legs. (shrink)

Social or relational egalitarians try to defend democracy non-instrumentally as a constitutive element of a society where no one stands as inferior or superior to anyone else. However, they face an instrumentalist challenge from within: Why not uphold a non-democratic regime if it outperforms democracy in protecting or promoting egalitarian social relations, for example, by stably producing substantive political decisions that guard against social hierarchies? This article explores the best response to this challenge from the social egalitarian non-instrumentalist standpoint. It (...) argues that the instrumentalist challenge can be accommodated without abandoning the essential non-instrumentalist commitment to democracy; while a nondemocratic regime may be justified under less-than-ideal circumstances as a contingently effective means to realize more social equality, democracy can nevertheless be viewed as a necessary condition for the realization of full social equality. (shrink)

How is it possible to say that truth can be of one kind at the conventional level and totally different in the ultimate plane? As Matilal ( 1971 , p. 154) points out, Kumārila (ca. 600–650), a Mīmāṃsaka philosopher, claims that the Buddhist doctrine of two truths is “a kind of philosophical ‘double-talk’.” It is Prajñākaragupta (ca. 750–810), a Buddhist logician, who tries to give a direct answer to this question posed by Kumārila from the Buddhist side. He argues that (...) even a Mīmāṃsaka cannot demonstrate the validity ( prāmāṇya ) of the Veda without accepting two truth levels. His point is this. Consider the proposition to be proved: the Veda is valid. If the Veda is already known as valid, then it is useless to prove this proposition. But if it is already known as invalid, then it is impossible to prove this proposition. Therefore in the argument to prove the proposition, the Veda is not to be regarded either as valid or as invalid. This means that at the first stage of the argument one has the concept of the Veda as neutral in validity. However, as soon as one acquires the knowledge of the Veda as valid through the argument, one has to repudiate such a conception of the Veda. The acceptance of the Veda as neutral in validity is to the acceptance of the Veda as valid as the conventional truth is to the ultimate truth. (shrink)

Parable is a literary genre. The knowledge of a literary parable makes us cognizant of the use of a technique used by the great philosophers to make known or transfer new ideas by making analogies or putting on one side a known fact to communicate a new or something incomprehensible. Jesus used the parable constantly, in his preaching and in the proclamation of the Kingdom of Heaven.

The prevailing model for encouraging innovation based on patents and market-oriented raises at least two economic and ethical issues: it imposes barriers on individuals and developing countries governments' access to medicines by defining prices that do not match their income, and the unavailability of new or appropriate products to address the health problems of these populations. In the last decade, this scenario has undergone some changes due to the emergence of new actors, the contribution of aid resources, the introduction to (...) the market of new products against neglected diseases, the development of new governmental healthcare policies and research programs, etc. One example of such initiatives is the Fixed-Dose Artesunate Combination Therapy (FACT) project consortium, which brought together institutions with different natures from both the North and the South, for the development of two antimalarial fixed-dose combinations recommended by the WHO – artesunate-amodiaquine (ASAQ) and artesunate-mefloquine (ASMQ). This paper proposes to describe and analyze the ASMQ consortium, which is the result of a new pharmaceutical development approach, based on a different paradigm – needs-driven instead of market-driven –, collaborative, with strategic participation of institutions from the South, funded by alternative resources (public and philanthropic). Thus, it represents an interesting object of study for bioethical debates on intellectual property and innovation, and its analysis is justified in light of the current debate on ways of stimulating needs-driven pharmaceutical innovation. (shrink)

In particular, as we shall see, Collingwood is often dismissed as having held an indefensible, outmoded ‘ideal’ theory, according to which the work of art is primarily ‘mental’, while his potential role in current debates is simply ignored. I will argue that this view is largely mistaken.

We consider the problem of fair allocation in economies with indivisible goods. Our primary concept is that of an envy-free allocation, that is, an allocation such that no agent would prefer anyone else's bundle to his own. Since there typically is a large set (a continuum) of such allocations, the need arises to identify well-behaved selections from the no-envy solution. First we establish the non-existence of ‘population monotonic’ selections. Then we propose a variety of selections motivated by intuitive considerations of (...) fairness. (shrink)

Ethical aspects in engineering design have become increasingly important in recent years. A typical example is the recent rise of artificial intelligence (AI) ethics. This paper applies user studies of a design support tool to empirically verify that our ethical framework improves the creativity of an engineer’s design activity. The design support tool provides an environment for the promotion of ethical design perspectives and description. The experiments focus on two functionalities: semi-automatic generation and scenario path recommendation. These functions are designed (...) around the application of ethical design theory, which extends the hierarchical representation of artifacts. Doing this enables users to reconsider their themes at the highest level of the hierarchy and to apply a wider conceptual space of design solutions. For example, by reconsidering the positions of their research themes in the space of the representation field, users can semi-automatically edit them and identify focal areas. Using the scenario path recommendation, designers can update their research themes after considering the ethical impacts of those themes on stakeholders. Both functions are realized by exploiting a knowledge base of ethical and technological discourses. Finally, the ethical design theory is updated based on some unexpected results of our user studies with regards to the cyclic relationship among theory, tools (i.e., experimental equipment), and observed data. For example, temporal dimensional aspects were confirmed as important. (shrink)

We investigate stationarity of types over models in simple theories. In particular, we show that in simple theories with finite SU-rank, any complete type over a model having Cantor-Bendixson rank is stationary.

The nucleolus is a region of the nucleus with high protein density and it acts as a ribosome factory. The nucleolus contains a distinct region of the genome, the ribosomal RNA gene repeats (rDNA) that supply ribosomal RNA (rRNA) molecules. The rDNA is the most‐abundant gene and occupies a large part of the genome, for example, there are thousands of rDNA copies in the genomes of plant cells. Therefore, it is natural to suppose that the condition of the rDNA, such (...) as its stability, might affect cellular functions. Here I would like to propose a new model regarding the roles of the rDNA and nucleolus. The key point of this model is that they act to preserve genome stability and trigger aging. BioEssays 30:267–272, 2008. © 2008 Wiley Periodicals, Inc. (shrink)

In his book Bad Beliefs, Neil Levy defends the engineering of our epistemic environment by removing epistemic pollutions and by nudging people through second-order evidence. Although we agree with his core ideas, in this commentary, we aim at supplementing his approach in light of the participation of the general public in science. In the first part, we argue that the issue of participatory epistemic injustice in the scientific community remains unaddressed in Levy’s discussion and that addressing the issue is equal (...) to removing an epistemic pollution. In the second part, we address the issue of transparency in nudging. Here, we discuss the significance of public engagement in controlling the system of nudges to respect our rational and autonomous choices. (shrink)