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Out of many intracellular bacteria, only the mitochondria and chloroplasts abandoned their independence billions of years ago and became endosymbionts within the host eukaryotic cell. Consequently, one cannot grow eukaryotic cells without their mitochondria, and the mitochondria cannot divide outside of the cell, thus reflecting interdependence. Here, we argue that such interdependence underlies the fundamental role of mitochondrial activities in the emergence of metazoans. Several lines of evidence support our hypothesis (a) Differentiation and embryogenesis rely on mitochondrial function; (b) mitochondrial metabolites are primary precursors for epigenetic modifications (such as methyl and acetyl), which are critical for chromatin remodeling and gene expression, particularly during differentiation and embryogenesis; and (c) mitonuclear coregulation adapted to accommodate both housekeeping and tissue-dependent metabolic needs. We discuss the evolution of the unique mitochondrial genetic system, mitochondrial metabolites, mitonuclear coregulation, and their critical roles in the emergence of metazoans and in human disorders.Prokaryotes have developed numerous defense strategies to combat the constant threat posed by the diverse genetic parasites that endanger them. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas loci guard their hosts with an adaptive immune system against foreign nucleic acids. Protection starts with an immunization phase, in which short pieces of the invader's genome, known as spacers, are captured and integrated into the CRISPR locus after infection. Next, during the targeting phase, spacers are transcribed into CRISPR RNAs (crRNAs) that guide CRISPR-associated (Cas) nucleases to destroy the invader's DNA or RNA. Here we describe the many different molecular mechanisms of CRISPR targeting and how they are interconnected with the immunization phase through a third phase of the CRISPR-Cas immune response primed spacer acquisition. In this phase, Cas proteins direct the crRNA-guided acquisition of additional spacers to achieve a more rapid and robust immunization of the population.

The use of biosimilars for the treatment of patients with chronic inflammatory bowel diseases (IBD) showed to be a valid strategy to reduce the economic burden of biologics on health-care costs and to increase patient access to treatment. However, the nocebo effect constitutes an important limitation to the wide use of biosimilars.

We conducted a literature overview to summarize information on nocebo effect in IBD population and to provide physicians with practical key strategies to prevent the nocebo effect in daily clinical practice and to improve patients' outcomes.

Despite the proven efficacy and safety of biosimilars, further clinical studies are needed to define the effects of reverse and multiple switches in the management of patients with IBD. The development of new subcutaneous formulations, better accepted by patients, could contribute to reduce patients' negative expectations, and limit the nocebo effect.

Despite the proven efficacy and safety of biosimilars, further clinical studies are needed to define the effects of reverse and multiple switches in the management of patients with IBD. The development of new subcutaneous formulations, better accepted by patients, could contribute to reduce patients' negative expectations, and limit the nocebo effect.Objectives Volunteering is associated with positive well-being among older people, providing opportunities to stay active and socially connected. This may be especially relevant for older lesbian and gay people, who are less likely than heterosexual people to have a partner, children or support from their family of origin. Methods Patterns of volunteering and mental, physical and social well-being were examined in a sample of 754 lesbian and gay adults in Australia aged 60 years and older who completed a nationwide survey. Results Volunteers reported greater positive mental health than non-volunteers. Among the gay men, volunteers additionally reported higher self-rated health and social support and lower psychological distress. Both the lesbian women and gay men who volunteered for lesbian, gay, bisexual, transgender or intersex (LGBTI) organisations also reported greater LGBTI community connectedness than volunteers for non-LGBTI organisations. Discussion These findings provide further insight into potential factors associated with the well-being of older lesbian and gay adults.

Increasingly universities are offering international student placements as part of the global internationalisation movement. This review sought to synthesize the findings of studies to further understand the learning outcomes described by allied health students.

To contribute to the understanding of the learning outcomes described by allied health students who have undertaken an international placement.

A qualitative meta-synthesis was conducted. From six databases, twenty-one studies were identified and critically appraised. Data were meta-aggregated, integrated and interpreted to develop new themes, with the experiences of over 259 allied health students synthesized.

Themes include the intertwined personal and professional development experienced by the students; confidence and independence, relationship building, insight into culture, service provision and differences in socio-economic and political contexts.

Universities offering students international placements provide their students with opportunities to achieve unique learning outcomes with significant personal and professional transformational development that cannot be replicated by local placements.

Universities offering students international placements provide their students with opportunities to achieve unique learning outcomes with significant personal and professional transformational development that cannot be replicated by local placements.Purpose The aim of the study was to assess whether sequential cochlear implantation (CI) with a prolonged interimplant interval (M = 15.2 years) between the first and second CIs benefited speech recognition and health-related quality of life. Method This prospective study included 14 prelingually deafened participants who received their second CI after a prolonged interimplant interval (M = 15.2 years). Additionally, speech recognition ability over a 12-month period of bilateral implant use was investigated. The results of the speech recognition test in both quiet and noisy conditions were statistically analyzed for each CI alone and both CIs together. Nijmegen Cochlear Implant Questionnaire scores were also collected at activation and at 12 months after activation. Results Improvements in speech recognition ability were observed following the use of the first implant alone and with the use of both implants together; however, progress was much slower with the use of the second implant alone, following its introduction. Furthermore, a significant difference in the trajectory of speech recognition ability was observed between the first and the second implanted ear. According to Nijmegen Cochlear Implant Questionnaire scores, all participants benefitted from bilateral CI after 12 months. Conclusions Prolonged interimplant intervals resulted in asymmetrical speech recognition abilities. A significant improvement in the speech recognition scores was observed with the first implanted ear, and much slower progress was observed with the second implanted ear. However, the "poorer" second implanted ear could provide a considerable beneficial effect on the improved speech recognition and health-related quality of life with the bilateral CI. read more Supplemental Material https//doi.org/10.23641/asha.12861152.It was classically thought that the function of mammalian red blood cells (RBCs) was limited to serving as a vehicle for oxygen, given the cells' abundance of cytosolic hemoglobin. Over the past decades, however, accumulating evidence indicates that RBCs have the capacity to sense low-oxygen tensions in hypoxic tissues, and, subsequently, release signaling molecules that influence the distribution of blood flow. The precise mechanisms that facilitate RBC modulation of blood flow are still being elucidated, although recent evidence indicates involvement of 1) adenosine triphosphate, capable of binding to purinergic receptors located on the vascular wall before initiating nitric oxide (NO; a powerful vasodilator) production in endothelial cells, and/or 2) nonvascular NO, which is now known to have several modes of production within RBCs, including an enzymatic process via a unique isoform of NO synthase (i.e., RBC-NOS), which has potential effects on the vascular smooth muscle. The physical properties of RBCs, including their tendency to form three-dimensional structures in low shear flow (i.e., aggregation) and their capacity to elongate in high shear flow (i.e., deformability), are only recently being viewed as mechanotransductive processes, with profound effects on vascular reactivity and tissue perfusion. Recent developments in intracellular signaling in RBCs, and the subsequent effects on the mechanical properties of blood, and blood flow, thus present a vivid expansion on the classic perspective of these abundant cells.

The purpose of the study was to examine the effects of sense and functionality changes in the hands on activity and participation in patients with juvenile scleroderma (JS).

Sixteen patients with juvenile localized scleroderma (JLS), 14 patients with Juvenile Systemic Sclerosis (JSS), and 30 healthy controls were included. Light touch-deep pressure sensation was assessed by Semmes-Weinstein monofilament test (SWMT). Localization sensation testing was performed by lightly stroking the patient's skin. The hand joint range of motion was measured with a goniometer, hand grip strength with Dynomometer, the pinch gripping force with pinch meter, and the hand mobility with modified Hand Mobility in Scleroderma (mHAMIS). Children completed their activity and participant performance status with 'Childhood Health Assessment Questionnaire (CHAQ)' and 'Jebson Taylor Hand Function Test (JTHFT)' questionnaire tests. The quality of life was evaluated using the 'Scleroderma Health Assessment Questionnaire (SHAQ)'.

Therffectiveness of rehabilitation.

Sensory and functional disorders caused by hand involvement in JS patients result in limitation of daily living activities and affect negatively the effective usage of the hand. Approximately half of the JS patients had disabilities in performing pinch motor skills of hands. The assessment of sensory symptoms that affect the functionality, activity level and participation of JSS and JLS patients should be considered during the routine clinical examination. We suggest the sensory therapies as an important factor in increasing the effectiveness of rehabilitation.As a result of the coronavirus pandemic, the feasibility of holding secure closed-book examinations in medical education is compromised. In this Personal View, we compare the underlying reasoning for using open-book and closed-book exams. We rethink the role of open-book assessment and offer ways in which we believe they can complement closed-book exams. We highlight the gap in research, highlight future directions, and call on medical educators to seize our current golden opportunity to explore the impact of open-book exams - on their own or combined to closed-book tests, as a blended approach - on learners, educators, and licensing bodies.

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