Background: Coronavirus disease 2019 (COVID-19) is known to have a high incidence of loss of smell and taste. However, studies in the early stages of the COVID-19 pandemic have evaluated these symptoms using subjective surveys and simple olfactory tests only. Hence, we compared the olfactory and gustatory characteristics of patient groups with COVID-19 olfactory dysfunction (C19OD) and non-COVID-19 postinfectious olfactory dysfunction (PIOD) using an objective olfactory test and evaluated the significance of olfactory training in both patient groups. Methods: We retrospectively analyzed the medical records of 14 patients with a decreased sense of smell after having positive COVID-19 polymerase chain reaction results, and 56 patients with PIOD with no history of confirmed COVID-19. Participants were evaluated using the Korean version of the Sniffin’ stick (KVSS) II, and chemical gustometry and olfactory training was assessed during their first visit. Olfactory training was then re-evaluated after an average of 8 (± 6) weeks. Results: The average age of participants in the C19OD group was lower than in those in the non-COVID-19 PIOD group. The proportion of men in the C19OD group was higher than in the non-COVID-19 PIOD group. At baseline assessment, the C19OD group had better olfactory and gustatory functions. After olfactory training, the non-COVID-19 PIOD patient group showed a significant increase in all KVSS II Total, T, D, and I scores, but there was a non-significant increase in all scores in the C19OD group. Conclusion The C19OD group had better olfactory and gustatory function than the nonCOVID-19 PIOD group at the initial assessment. After olfactory training, there was an increase in olfactory function test scores in both groups. Olfactory training may be helpful in C19OD, as in non-COVID-19 PIOD.

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

Paracrine interactions are imperative for the maintenance of adipose tissue intercellular homeostasis, and intracellular organelle dysfunction results in local and systemic alterations in metabolic homeostasis. It is currently accepted that mitochondrial proteotoxic stress activates the mitochondrial unfolded protein response (UPRmt) in vitro and in vivo. The induction of mitochondrial chaperones and proteases during the UPRmt is a key cell-autonomous mechanism of mitochondrial quality control. The UPRmt also affects systemic metabolism through the secretion of cell non-autonomous peptides and cytokines (hereafter, metabokines). Mitochondrial function in adipose tissue plays a pivotal role in whole-body metabolism and human diseases. Despite continuing interest in the role of the UPRmt and quality control pathways of mitochondria in energy metabolism, studies on the roles of the UPRmt and metabokines in white adipose tissue are relatively sparse. Here, we describe the role of the UPRmt in adipose tissue, including adipocytes and resident macrophages, and the interactive roles of cell non-autonomous metabokines, particularly growth differentiation factor 15, in local adipose cellular homeostasis and systemic energy metabolism.

Objectives: This study examined the responses to standard stimuli to investigate the mechanisms underlying mismatch negativity (MMN) impairments in schizophrenia. Methods: We obtained MMN data from 68 patients diagnosed with schizophrenia or schizoaffective disorder and 38 healthy controls and analyzed the electrophysiological activity of the responses to two standard stimuli before deviants using time-frequency methods. Results: As a result of RM ANOVA at evoked alpha power, there were differences not only between-subjects (F 1,104=4.35, p<0.05) but also within-subjects (F 1,104=8.62, p<0.01) without groupby-stimulus interaction (F 1,104=1.70, p=0.20). But at single-trial alpha power, there was a difference not between-subjects (F 1,104=3.81, p=0.054), but only within-subjects (F 1,104=10.14, p<0.01) with significant group-by-stimulus interaction (F 1,104=5.71, p<0.05). Moreover, between-group differences were significant in evoked alpha power (t 104=2.02, p<0.05, d=0.41) and single-trial alpha power (t 104=2.49, p<0.01, d=0.50) to standard stimuli presented not at the first instance but second. According to the order that the two standards presented, there were increases of evoked alpha power (t 37=-2.54, p<0.05, d=0.58) and single-trial alpha power (t 37=-3.41, p<0.01, d=0.78) in only the healthy controls. The positive correlations were shown in clinical features between years of education completed and event-related potential amplitude at 100 ms to both standard stimuli (Each Pearson Corr.: r=0.22, p<0.05). Conclusion These outputs suggest that the P1 alpha oscillation to standards is associated with deficits in the inhibitory control of selective attention relative to cognitive dysfunction in schizophrenia.We could also hypothesize that these deficits are involved in computing prediction errors based on the predictive coding perspective. However, further studies on this hypothesis are necessary.

Objectives: The optimal duration of maintenance treatment for patients with first-episode schizophrenia (FES) remains unclear. We examined the first antipsychotic treatment duration and its association with re-initiation of treatment using a nationwide claim database. Methods: Data from the Health Insurance Review and Assessment Service database in South Korea for 2007–2016 were used. Linear regression analysis and Cox proportional hazard models were used to evaluate the associations between the duration of the first antipsychotic treatment, time to re-initiation of treatment, and occurrence of treatment re-initiation. Results: Of 30,143 patients with FES, 80.4% (n=24,231) received <2 years of the first antipsychotic treatment. In patients who discontinued treatment (n=23,030), the rate of treatment re-initiation was 74.2% (n=17,086). As the duration of the first antipsychotic treatment increased, the time to re-initiation of treatment decreased (β=-0.146, p<0.001); however, the rate of treatment re-initiation was relatively constant (hazard ratio=1.001, p<0.001). Conclusion Long-term antipsychotic treatment was not significantly associated with the rate of treatment re-initiation but showed a negative association with the time to re-initiation of treatment. Further research is needed to better understand the optimal treatment duration for FES.

Purpose: The safety and efficacy of laparoscopic cholecystectomy (LC) in elderly patients is a matter of concern because morbidity and clinical risk are higher in elderly patients; and some clinicians recommend non-surgical supportive treatments. There is limited data reported in the literature for LC in super-elderly individuals (aged ≥ 80 years). This study compared the clinical outcome for the elderly and super-elderly patients undergoing LC. Methods: Patients who had a cholecystectomy for acute or chronic cholecystitis, and empyema of the gall bladder between January 2011 and June 2018 were analyzed retrospectively. The clinical outcomes of the super-elderly patients (≥ 80 years, Group 2) were compared with elderly patients (65-79 years, Group 1). Complications, conversion rate, postoperative hospital stays were assessed. Results: The conversion rate was 5.5% and 8.4% in Groups 1 and 2, respectively (p = 0.749). The surgical or medical complication rates were similar in both groups. A significant difference in operation time was observed between groups (p < 0.001). Although the super-elderly patients had longer postoperative hospital stays (7.10 ± 6.98) than the elderly patients (4.60 ± 6.06), there was no significant difference with between the 2 groups (p = 1.000). Conclusion The clinical outcomes of the conversion rate, complications, and mortality were similar in patients aged 65 to 79 years and ≥ 80 years. Therefore, LC is deemed to be a safe and simple procedure for the super-elderly.

Purpose: The safety and efficacy of laparoscopic cholecystectomy (LC) in elderly patients is a matter of concern because morbidity and clinical risk are higher in elderly patients; and some clinicians recommend non-surgical supportive treatments. There is limited data reported in the literature for LC in super-elderly individuals (aged ≥ 80 years). This study compared the clinical outcome for the elderly and super-elderly patients undergoing LC. Methods: Patients who had a cholecystectomy for acute or chronic cholecystitis, and empyema of the gall bladder between January 2011 and June 2018 were analyzed retrospectively. The clinical outcomes of the super-elderly patients (≥ 80 years, Group 2) were compared with elderly patients (65-79 years, Group 1). Complications, conversion rate, postoperative hospital stays were assessed. Results: The conversion rate was 5.5% and 8.4% in Groups 1 and 2, respectively (p = 0.749). The surgical or medical complication rates were similar in both groups. A significant difference in operation time was observed between groups (p < 0.001). Although the super-elderly patients had longer postoperative hospital stays (7.10 ± 6.98) than the elderly patients (4.60 ± 6.06), there was no significant difference with between the 2 groups (p = 1.000). Conclusion The clinical outcomes of the conversion rate, complications, and mortality were similar in patients aged 65 to 79 years and ≥ 80 years. Therefore, LC is deemed to be a safe and simple procedure for the super-elderly.

Various trials have been conducted to develop therapies for serious untreatable diseases. Among these, those using stem cells have shown great promise, and adipose-derived mesenchymal stem cells (ADMSCs) are easier to obtain than other types of stem cells. Prior to clinical trials, characterization of ADMSCs with monoclonal antibodies should be performed. However, it is difficult to use species-specific antibodies for veterinarians. This study was conducted to confirm the panel of human antibodies applicable for use in immunophenotypic characterization of canine adipose-derived stem cells and feline ADMSCs extracted from subcutaneous adipose tissue collected during ovariohysterectomy. For flow cytometric immunophenotyping, the third passages of canine ADMSC and feline ADMSC and human CD31, CD34, CD42, CD44, CD62 and CD133 antibodies were used. Of these, CD133 reacted with canine cells (3.74%) and feline cells (1.34%). CD133 is known as a marker related with more primitive stem cell phenotype than other CD series. Because this human CD133 was not a species-specific antibody, accurate percentages of immunoreactivity were not confirmed. Nevertheless, the results of this study confirmed human CD133 as a meaningful marker in canine and feline ADMSCs.
Animals ; Antibodies ; Antibodies, Monoclonal ; Cats ; Dogs ; Humans ; Immunophenotyping ; Mesenchymal Stromal Cells ; Phenotype ; Stem Cells ; Subcutaneous Fat ; Veterinarians

Incorporation of unique barcodes into fission yeast gene deletion collections has enabled the identification of gene functions by growth fitness analysis. For fine tuning, it is important to examine barcode sequences, because mutations arise during strain construction. Out of 8,708 barcodes (4,354 strains) covering 88.5% of all 4,919 open reading frames, 7,734 barcodes (88.8%) were validated as high-fidelity to be inserted at the correct positions by Sanger sequencing. Sequence examination of the 7,734 high-fidelity barcodes revealed that 1,039 barcodes (13.4%) deviated from the original design. In total, 1,284 mutations (mutation rate of 16.6%) exist within the 1,039 mutated barcodes, which is comparable to budding yeast (18%). When the type of mutation was considered, substitutions accounted for 845 mutations (10.9%), deletions accounted for 319 mutations (4.1%), and insertions accounted for 121 mutations (1.6%). Peculiarly, the frequency of substitutions (67.6%) was unexpectedly higher than in budding yeast (~28%) and well above the predicted error of Sanger sequencing (~2%), which might have arisen during the solid-phase oligonucleotide synthesis and PCR amplification of the barcodes during strain construction. When the mutation rate was analyzed by position within 20-mer barcodes using the 1,284 mutations from the 7,734 sequenced barcodes, there was no significant difference between up-tags and down-tags at a given position. The mutation frequency at a given position was similar at most positions, ranging from 0.4% (32/7,734) to 1.1% (82/7,734), except at position 1, which was highest (3.1%), as in budding yeast. Together, well-defined barcode sequences, combined with the next-generation sequencing platform, promise to make the fission yeast gene deletion library a powerful tool for understanding gene function.
DNA* ; Gene Deletion* ; Mutation Rate ; Open Reading Frames ; Polymerase Chain Reaction ; Saccharomycetales ; Schizosaccharomyces*

Various trials have been conducted to develop therapies for serious untreatable diseases. Among these, those using stem cells have shown great promise, and adipose-derived mesenchymal stem cells (ADMSCs) are easier to obtain than other types of stem cells. Prior to clinical trials, characterization of ADMSCs with monoclonal antibodies should be performed. However, it is difficult to use species-specific antibodies for veterinarians. This study was conducted to confirm the panel of human antibodies applicable for use in immunophenotypic characterization of canine adipose-derived stem cells and feline ADMSCs extracted from subcutaneous adipose tissue collected during ovariohysterectomy. For flow cytometric immunophenotyping, the third passages of canine ADMSC and feline ADMSC and human CD31, CD34, CD42, CD44, CD62 and CD133 antibodies were used. Of these, CD133 reacted with canine cells (3.74%) and feline cells (1.34%). CD133 is known as a marker related with more primitive stem cell phenotype than other CD series. Because this human CD133 was not a species-specific antibody, accurate percentages of immunoreactivity were not confirmed. Nevertheless, the results of this study confirmed human CD133 as a meaningful marker in canine and feline ADMSCs.