Investigation of the Approaches to Optimal Exercise Interventions Based on Dementia Type: A Theoretical Review.

The aim of this study is to enhance comprehension of the different types and features of dementia, including their symptoms, diagnosis and medical treatment, and to propose various evidence-based exercise interventions and their clinical applications tailored to each specific type of dementia. The theoretical review includes the analysis of publications in the scientific databases PubMed/Medline, Ebsco, Scielo, and Google. A total of 177 articles were found, of which 84 were studied in depth. With the prevalence of all forms of dementia projected to increase from 57.4 million in 2019 to 152.8 million in 2050, personalized treatment strategies are needed. This review discusses various forms of dementia, including their pathologies, diagnostic criteria, and prevalence rates. The importance of accurate diagnosis and tailored care is emphasized, as well as the effectiveness of physical exercise in improving cognitive function in dementia patients. For Alzheimer's, a combination of drug therapies and exercises is recommended to enhance cerebral blood flow and neurotransmitter activity. To improve cognitive and motor functions in Lewy body dementia, a combination of pharmacological and physical therapies is recommended. For managing frontotemporal dementia, a mix of medication and exercises aimed at emotion regulation, including aerobic exercises, and a unified protocol, is suggested. For mild cognitive impairment, aerobic and functional exercises are important in delaying cognitive decline and enhancing cognitive performance. In conclusion, individualized care and treatment plans tailored to the specific characteristics of each disease type can improve the quality of life for individuals with this condition and effectively manage this growing global health issue.

Transcanal endoscopic ear surgery for glomus tympanicum removal: A case series on the necessity of preoperative embolization.

BACKGROUND: Transcanal endoscopic ear surgery (TEES) has become popular in recent years in the treatment of glomus tympanicum tumors (GTT). The most significant risk for TEES is bleeding. In some cases, preoperative vascular embolization is performed to mitigate bleeding during TEES. However, guidelines regarding the necessity and efficacy of preoperative vascular embolization have not been established yet. CASE PRESENTATION: This report aimed to assess the necessity and usefulness of preoperative vascular embolization in TEES for GTT by comparing the surgical findings of TEES without preoperative vascular embolization (Case 1) and TEES with preoperative vascular embolization (Case 2). Compared to Case 1, Case 2 included less bleeding and a more convenient procedure. However, no significant difference was observed. CONCLUSIONS: For GTT confined to the middle ear cavity (Glasscock-Jackson Grade II or less), when performed by a proficient otolaryngologist, TEES alone is sufficient without preoperative vascular embolization.

Epigenetic MicroRNAs as Prognostic Markers of Postoperative Atrial Fibrillation: A Systematic Review.

Postoperative atrial fibrillation (POAF) is a common complication after cardiac surgery, increasing the risk for adverse outcomes such as perioperative and long-term mortality, stroke, myocardial infarction, and other thromboembolic events. Epigenetic biomarkers show promise as prognostic tools for POAF. Epigenetic changes, such as DNA methylation, histone modification, and microRNAs (miRNA), can result in altered gene expression and the development of various pathological conditions. This systematic review aims to present the current literature on the association between various epigenetic markers and the development of POAF following cardiac surgery. Here, an electronic literature search was performed using MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar to identify studies that reported the role of epigenetic markers in the development of POAF. Five of the 6 studies focused on miRNAs and their association with POAF. In POAF patients, the expression of miR-1 and miR-483-5p were upregulated in the right atrial appendage (RAA), while the levels of miR-133A, miR-208a, miR-23a, miR-26a, miR-29a, miR-29b, and miR-29c were decreased in the RAA and venous blood. One study examined cytosines followed by guanines (CpGs) as DNA methylation markers. Across all studies, 488 human subjects who had undergone cardiac surgery were investigated, and 195 subjects (39.9%) developed new-onset POAF. The current literature suggests that miRNAs may play a role in predicting the development of atrial fibrillation after cardiac surgery. However, more robust clinical data are required to justify their role in routine clinical practice.

Prospective Study of Nonsurgical Auricular Correction According to Timing of Treatment.

BACKGROUND AND PURPOSE: Many studies recommend nonsurgical auricular correction during the early postnatal period, when cartilage plasticity is high; however, many patients are not eligible for the procedure. This study compared different timings of nonsurgical auricular correction to investigate benefit after the optimal period for correction. METHODS: In this prospective study, 53 ears from 35 patients with congenital auricular anomaly were assigned to two groups according to age at correction: the "early-group" with correction within 2 weeks of birth and "late-group" with correction 8 weeks after birth. Aesthetic outcomes, caregiver satisfaction, detachment rates and mean device-wearing periods, were compared. RESULTS: Thirty-one ears from 20 patients comprised the early-group, and 18 ears from 12 patients comprised the late-group. Mean time to treatment after birth was 9.09 days in the early-group and 134.7 days in the late-group. In the early-group, detachment occurred in 4/31 ears (12.9%), and in the late-group, detachment occurred in 12/18 ears (66.7%), which was statistically significant (p<0.01). The average period of applying devices was 4.7 ± 1.2 weeks in the early-group and 8.5 ± 4.1 weeks in the late-group, with a significantly longer treatment time in the late-group (p=0.001). The early-group had 87.1% "good" results vs. 55.6% in the late-group, with a statistically significant difference. CONCLUSIONS: The correction period was shorter, detachment rate was lower, and treatment outcome was better in the early-group. However, successful correction was also present in the late-group, showing that the patients who have passed the optimum correction period should proceed after counselling.

Differences in the metabolomic profile of the human palatine tonsil between pediatrics and adults.

Palatine tonsils (PT) are B cell-predominant lymphoid organs that provide primary immune responses to airborne and dietary pathogens. Numerous histopathological and immunological studies have been conducted on PT, yet no investigations have been conducted on its metabolic profile. We performed high-resolution magic angle spinning nuclear magnetic resonance spectroscopy-based metabolic profiling in 35 pediatric and 28 adult human palatine tonsillar tissue samples. A total of 36 metabolites were identified, and the levels of 10 metabolites were significantly different depending on age. Among them, partial correlation analysis shows that glucose levels increased with age, whereas glycine, phosphocholine, phosphoethanolamine, and ascorbate levels decreased with age. We confirmed the decrease in immunometabolic activity in adults through metabolomic analysis, which had been anticipated from previous histological and immunological studies on the PT. These results improve our understanding of metabolic changes in the PT with aging and serve as a basis for future tonsil-related metabolomic studies.

Multilevel interrogation of H3.3 reveals a primordial role in transcription regulation.

BACKGROUND: Eukaryotic cells can rapidly adjust their transcriptional profile in response to molecular needs. Such dynamic regulation is, in part, achieved through epigenetic modifications and selective incorporation of histone variants into chromatin. H3.3 is the ancestral H3 variant with key roles in regulating chromatin states and transcription. Although H3.3 has been well studied in metazoans, information regarding the assembly of H3.3 onto chromatin and its possible role in transcription regulation remain poorly documented outside of Opisthokonts. RESULTS: We used the nuclear dimorphic ciliate protozoan, Tetrahymena thermophila, to investigate the dynamics of H3 variant function in evolutionarily divergent eukaryotes. Functional proteomics and immunofluorescence analyses of H3.1 and H3.3 revealed a highly conserved role for Nrp1 and Asf1 histone chaperones in nuclear influx of histones. Cac2, a putative subunit of H3.1 deposition complex CAF1, is not required for growth, whereas the expression of the putative ortholog of the H3.3-specific chaperone Hir1 is essential in Tetrahymena. Our results indicate that Cac2 and Hir1 have distinct localization patterns during different stages of the Tetrahymena life cycle and suggest that Cac2 might be dispensable for chromatin assembly. ChIP-seq experiments in growing Tetrahymena show H3.3 enrichment over the promoters, gene bodies, and transcription termination sites of highly transcribed genes. H3.3 knockout followed by RNA-seq reveals large-scale transcriptional alterations in functionally important genes. CONCLUSION: Our results provide an evolutionary perspective on H3.3's conserved role in maintaining the transcriptional landscape of cells and on the emergence of specialized chromatin assembly pathways.

A central chaperone-like role for 14-3-3 proteins in human cells.

14-3-3 proteins are highly conserved regulatory proteins that interact with hundreds of structurally diverse clients and act as central hubs of signaling networks. However, how 14-3-3 paralogs differ in specificity and how they regulate client protein function are not known for most clients. Here, we map the interactomes of all human 14-3-3 paralogs and systematically characterize the effect of disrupting these interactions on client localization. The loss of 14-3-3 binding leads to the coalescence of a large fraction of clients into discrete foci in a client-specific manner, suggesting a central chaperone-like function for 14-3-3 proteins. Congruently, the engraftment of 14-3-3 binding motifs to nonclients can suppress their aggregation or phase separation. Finally, we show that 14-3-3s negatively regulate the localization of the RNA-binding protein SAMD4A to cytoplasmic granules and inhibit its activity as a translational repressor. Our work suggests that 14-3-3s have a more prominent role as chaperone-like molecules than previously thought.

RNA-binding proteins that lack canonical RNA-binding domains are rarely sequence-specific.

Thousands of RNA-binding proteins (RBPs) crosslink to cellular mRNA. Among these are numerous unconventional RBPs (ucRBPs)-proteins that associate with RNA but lack known RNA-binding domains (RBDs). The vast majority of ucRBPs have uncharacterized RNA-binding specificities. We analyzed 492 human ucRBPs for intrinsic RNA-binding in vitro and identified 23 that bind specific RNA sequences. Most (17/23), including 8 ribosomal proteins, were previously associated with RNA-related function. We identified the RBDs responsible for sequence-specific RNA-binding for several of these 23 ucRBPs and surveyed whether corresponding domains from homologous proteins also display RNA sequence specificity. CCHC-zf domains from seven human proteins recognized specific RNA motifs, indicating that this is a major class of RBD. For Nudix, HABP4, TPR, RanBP2-zf, and L7Ae domains, however, only isolated members or closely related homologs yielded motifs, consistent with RNA-binding as a derived function. The lack of sequence specificity for most ucRBPs is striking, and we suggest that many may function analogously to chromatin factors, which often crosslink efficiently to cellular DNA, presumably via indirect recruitment. Finally, we show that ucRBPs tend to be highly abundant proteins and suggest their identification in RNA interactome capture studies could also result from weak nonspecific interactions with RNA.

The Optimized Protocol of Hyperbaric Oxygen Therapy For Sudden Sensorineural Hearing Loss.

OBJECTIVE: This study aimed to determine the optimal protocol of hyperbaric oxygen therapy (HBOT) according to various treatment settings for sudden sensorineural hearing loss (SSNHL). METHODS: A 112 patients with SSNHL were enrolled in this prospective study. All patients were treated with systemic steroid therapy, intratympanic steroid therapy, and HBOT. According to the pressure and duration of HBOT (10 sessions in total), the patients were divided into three groups: group 1, 2.5 atmospheres absolute (ATA) for 1 h; group 2, 2.5 ATA for 2 h; and group 3, 1.5 ATA for 1 h. The pure-tone average (PTA), word discrimination score (WDS), and mean gain were compared. RESULTS: A total of 105 patients completed the 3-month follow-up, and 6 patients were excluded. Differences among groups were found in PTA, WDS, and mean gain. In the post-hoc analysis, group 3 had significantly lower WDS and mean gain than groups 1 and 2; however, group 2 showed no significant differences from group 1. The proportion of patients with hearing recovery after treatment was significantly higher in group 1 (57.6%) and group 2 (58.8%) than in group 3 (31.3%). CONCLUSIONS: When HBOT (10 sessions) was combined with corticosteroids as the initial therapy for SSNHL, a higher pressure (1.5 ATA vs. 2.5 ATA) provided better treatment results; however, increasing the duration (1 h vs. 2 h) under 2.5 ATA did not result in a significant difference. Therefore, HBOT for SSNHL may be performed at 2.5 ATA for 1 h in 10 sessions. Laryngoscope, 133:383-388, 2023.

c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor that regulates early retinal development.

BACKGROUND: The transcription factor orthodenticle homeobox 2 (OTX2) has critical functions in brain and eye development, and its mutations in humans are related to retinal diseases, such as ocular coloboma and microphthalmia. However, the regulatory mechanisms of OTX2 are poorly identified. OBJECTIVE: The identification of JNK1 as an OTX2 regulatory protein through the protein interaction and phosphorylation. METHODS: To identify the binding partner of OTX2, we performed co-immunoprecipitation and detected with a pooled antibody that targeted effective kinases. The protein interaction between JNK1 and OTX2 was identified with the co-immunoprecipitation and immunocytochemistry. In vivo and in vitro kinase assay of JNK1 was performed to detect the phosphorylation of OTX2 by JNK1. RESULTS: JNK1 directly interacted with OTX2 through the transactivation domain at the c-terminal region. The protein-protein interaction and co-localization between JNK1 and OTX2 were further validated in the developing P0 mouse retina. In addition, we confirmed that the inactivation of JNK1 K55N mutant significantly reduced the JNK1-mediated phosphorylation of OTX2 by performing an immune complex protein kinase assay. CONCLUSION: c-Jun N-terminal kinase 1 (JNK1) phosphorylates OTX2 transcription factor through the protein-protein interaction.

CRISPR/Cas9-Mediated Editing of AGAMOUS-like Genes Results in a Late-Bolting Phenotype in Chinese Cabbage (Brassica rapa ssp. pekinensis).

Due to the sudden change in temperature in spring, Chinese cabbage, a leafy vegetable cultivated for consumption, loses its commercial value due to the onset of bolting­the phenomenon of switching from vegetative to reproductive growth. In this study, we applied clustered regularly interspaced short palindromic repeats/(CRISPR)-associated system 9 (CRISPR/Cas9) technology to analyze AGAMOUS-like genes. We performed functional analysis of AGL19 and AGL24 genes related to bolting and flowering using CRISPR/Cas9-mediated Chinese cabbage transformation. Single-guide RNA (sgRNA) sequences were created with a low off-targeting probability to construct gene-editing vectors. Agrobacterium-mediated transformation was conducted, and tentative E0 AGL-edited lines were analyzed using molecular biotechnological methods. Two AGL19-edited lines with nucleotide sequence mutations in the target sequence of the AGL19 genes and four AGL24-edited lines with nucleotide sequence mutations in the target sequence of the AGL24 genes showed particularly late bolting compared to the inbred line 'CT001.' Generational progression using bud pollination obtained T-DNA-free E1 AGL-edited lines, which also showed late bolting. The loss of function of the AGL protein was caused by the occurrence of an indel mutation in the AGL19 and AGL24 genes, which results in an early stop codon. Furthermore, frameshift mutations led to structural changes and the introduction of an early stop codon in the AGL19 and AGL24 proteins. Our results indicate that CRISPR/Cas9-mediated editing of AGAMOUS-like genes results in a late-bolting phenotype and that CRISPR/Cas9 is a useful technology for analyzing gene function in Chinese cabbage (Brassica rapa ssp. pekinensis).

Regulation of alternative polyadenylation by the C2H2-zinc-finger protein Sp1.

Alternative polyadenylation (APA) enhances gene regulatory potential by increasing the diversity of mRNA transcripts. 3' UTR shortening through APA correlates with enhanced cellular proliferation and is a widespread phenomenon in tumor cells. Here, we show that the ubiquitously expressed transcription factor Sp1 binds RNA in vivo and is a common repressor of distal poly(A) site usage. RNA sequencing identified 2,344 genes (36% of the total mapped mRNA transcripts) with lengthened 3' UTRs upon Sp1 depletion. Sp1 preferentially binds the 3' UTRs of such lengthened transcripts and inhibits cleavage at distal sites by interacting with the subunits of the core cleavage and polyadenylation (CPA) machinery. The 3' UTR lengths of Sp1 target genes in breast cancer patient RNA-seq data correlate with Sp1 expression levels, implicating Sp1-mediated APA regulation in modulating tumorigenic properties. Taken together, our findings provide insights into the mechanism for dynamic APA regulation by unraveling a previously unknown function of the DNA-binding transcription factor Sp1.

Using Transcriptome Analysis to Explore Gray Mold Resistance-Related Genes in Onion (Alliumcepa L.).

Gray mold disease caused by Botrytis in onions (Allium cepa L.) during growth and storage negatively affects their yield and quality. Exploring the genes related to gray mold resistance in onion and their application to the breeding of resistant onion lines will support effective and ecological control methods of the disease. Here, the genetic relationship of 54 onion lines based on random amplified polymorphic DNA (RAPD) and in vitro-cultured onion lines infected with gray mold were used for screening resistance and susceptibility traits. Two genetically related onion lines were selected, one with a resistant and one with a susceptible phenotype. In vitro gray mold infection was repeated with these two lines, and leaf samples were collected for gene expression studies in time series. Transcript sequences obtained by RNA sequencing were subjected to DEG analysis, variant analysis, and KEGG mapping. Among the KEGG pathways, 'α-linoleic acid metabolism' was selected because the comparison of the time series expression pattern of Jasmonate resistant 1 (JAR1), Coronatine-insensitive protein 1 (COI 1), and transcription factor MYC2 (MYC2) genes between the resistant and susceptible lines revealed its significant relationship with gray-mold-resistant phenotypes. Expression pattern and SNP of the selected genes were verified by quantitative real-time PCR and high-resolution melting (HRM) analysis, respectively. The results of this study will be useful for the development of molecular marker and finally breeding of gray-mold-resistant onions.

Targeting PGM3 as a Novel Therapeutic Strategy in KRAS/LKB1 Co-Mutant Lung Cancer.

In non-small-cell lung cancer (NSCLC), concurrent mutations in the oncogene KRAS and tumor suppressor STK11 (also known as LKB1) confer an aggressive malignant phenotype, an unfavourability towards immunotherapy, and overall poor prognoses in patients. In a previous study, we showed that murine KRAS/LKB1 co-mutant tumors and human co-mutant cancer cells have an enhanced dependence on glutamine-fructose-6-phosphate transaminase 2 (GFPT2), a rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP), which could be targeted to reduce survival of KRAS/LKB1 co-mutants. Here, we found that KRAS/LKB1 co-mutant cells also exhibit an increased dependence on N-acetylglucosamine-phosphate mutase 3 (PGM3), an enzyme downstream of GFPT2. Genetic or pharmacologic suppression of PGM3 reduced KRAS/LKB1 co-mutant tumor growth in both in vitro and in vivo settings. Our results define an additional metabolic vulnerability in KRAS/LKB1 co-mutant tumors to the HBP and provide a rationale for targeting PGM3 in this aggressive subtype of NSCLC.

Navigating the COVID-19 pandemic in the contingency framework: Antecedents and consequences of public's stance toward the CDC.

This study applied the contingency theory of conflict management to examine how contingency factors influence the public's perceptual and behavioral responses to COVID-19 and stance toward the Centers for Disease Control and Prevention (CDC). In particular, we tested political ideology as an important individual characteristic variable to examine its roles in the contingency theory framework. The findings revealed that two situational variables (i.e., threat appraisal and attitudes toward CDC) positively influenced the public's contingency accommodation stance toward the CDC. Furthermore, greater conservatism was significantly associated with lower levels of threat appraisal and more negative attitudes toward the CDC, however it did not influence the stance toward the CDC. Theoretical and practical implications of the findings and directions for future research are discussed.

SARS-CoV-2 nucleocapsid protein binds host mRNAs and attenuates stress granules to impair host stress response.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) protein is essential for viral replication, making it a promising target for antiviral drug and vaccine development. SARS-CoV-2 infected patients exhibit an uncoordinated immune response; however, the underlying mechanistic details of this imbalance remain obscure. Here, starting from a functional proteomics workflow, we cataloged the protein-protein interactions of SARS-CoV-2 proteins, including an evolutionarily conserved specific interaction of N with the stress granule resident proteins G3BP1 and G3BP2. N localizes to stress granules and sequesters G3BPs away from their typical interaction partners, thus attenuating stress granule formation. We found that N binds directly to host mRNAs in cells, with a preference for 3' UTRs, and modulates target mRNA stability. We show that the N protein rewires the G3BP1 mRNA-binding profile and suppresses the physiological stress response of host cells, which may explain the imbalanced immune response observed in SARS-CoV-2 infected patients.

EEG-Based Evidence of Mirror Neuron Activity from App-Mediated Stroke Patient Observation.

Background and Objectives: The mirror neuron system in the sensorimotor region of the cerebral cortex is equally activated during both action observation and execution. Action observation training mimics the functioning of the mirror neuron system, requiring patients to watch and imitate the actions necessary to perform activities of daily living. StrokeCare is a user-friendly application based on the principles of action observation training, designed to assist people recovering from stroke. Therefore, when observing the daily life behavior provided in the StrokeCare app, whether the MNS is activated and mu inhibition appears. Materials and Methods: We performed electroencephalography (EEG) on 24 patients with chronic stroke (infarction: 11, hemorrhage: 13) during tasks closely related to daily activities, such as dressing, undressing, and walking. The StrokeCare app provided action videos for patients to watch. Landscape imagery observation facilitated comparison among tasks. We analyzed the mu rhythm from the C3, CZ, and C4 regions and calculated the mean log ratios for comparison of mu suppression values. Results: The EEG mu power log ratios were significantly suppressed during action observation in dressing, undressing, walking, and landscape conditions, in decreasing order. However, there were no significant activity differences in the C3, C4 and CZ regions. The dressing task showed maximum suppression after a color spectrum was used to map the relative power values of the mu rhythm for each task. Conclusions: These findings reveal that the human mirror neuron system was more strongly activated during observation of actions closely related to daily life activities than landscape images.

Effect of Immersive Virtual Reality-Based Bilateral Arm Training in Patients with Chronic Stroke.

Virtual reality (VR)-based therapies are widely used in stroke rehabilitation. Although various studies have used VR techniques for bilateral upper limb training, most have been only semi-immersive and have only been performed in an artificial environment. This study developed VR content and protocols based on activities of daily living to provide immersive VR-based bilateral arm training (VRBAT) for upper limb rehabilitation in stroke patients. Twelve patients with chronic stroke were randomized to a VRBAT group or a normal bilateral arm training (NBAT) group and attended 30-min training sessions five times a week for four weeks. At the end of the training, there was a significant difference in upper limb function in both groups (p < 0.05) and in the upper limb function sensory test for proprioception in the NBAT group (p < 0.05). There was no significant between-group difference in upper limb muscle activity after training. The relative alpha and beta power values for electroencephalographic measurements were significantly improved in both groups. These findings indicate that both VRBAT and NBAT are effective interventions for improving upper limb function and electroencephalographic activity in patients with chronic stroke.