Objective: To evaluate the in vitro anti-diabetic effects of Bryonia dioica roots extracts, including water-acetone extracts and their ethyl acetate and butanol fractions, and chloroform-methanol extracts. Methods: The total phenolic, flavonoid, flavonol, and saponin contents in the Bryonia dioica root extracts (chloroform-methanol extracts, water-acetone extracts and their ethyl acetate and butanol fractions) were determined using colorimetric methods with Folin-Ciocalteu, aluminum trichloride, and vanillin reagents, respectively. The in vitro anti-diabetic activity was evaluated by measuring the half-maximal inhibitory concentration (IC50) values of these root extracts against α-amylase and α-glucosidase activities, evaluating their effects on α-amylase kinetics, quantifying the inhibition of bovine serum albumin (BSA) glycation using fluorometry to assess advanced glycation end products (AGE) production, and determining glucose uptake by isolated rat hemidiaphragm. Additionally, molecular docking analysis was conducted to investigate the binding affinity and interaction types between Bryonia dioica ligands (cucurbitacin B, bryogénin, vitexin, and isovitexin) and target enzymes, and a phytochemical-targets interaction network was constructed. Results: For α-amylase inhibition, ethyl acetate fraction demonstrated the most potent activity (IC50 = 145.95 µg/mL), followed by chloroform-methanol extract (IC50 = 300.86 µg/mL). Water-acetone root extracts and their ethyl acetate and butanol fractions inhibited the α-glucosidase activity with IC50 values ranging from 562.88 to 583.90 µg/mL. Both ethyl acetate and butanol fractions strongly inhibited non-enzymatic BSA glycation (IC50 = 318.26 and 323.12 µg/mL, respectively). The incubation of isolated rat hemidiaphragms with the ethyl acetate fraction (5 mg/mL) significantly increased glucose uptake (35.16%; P < 0.0001), exceeding the effects of insulin (29.27%), chloroform-methanol extract (24.07%), and catechin (15.27%). Molecular docking revealed that cucurbitacin B exhibited the strongest docking scores against α-amylase (– 16.4 kcal/mol), and α-glucosidase (– 14.2 kcal/mol). Compared with other ligands, isovitexin formed the maximum number of hydrogen bonds with the α-amylase active site residues (Asp300, Asp197, and Glu233), α-glucosidase residues (Ser13, Arg44, Met86, Gly10, Asp39, and Tyr131) and other residues (Arg195, Trp59, His299, and Tyr62). Network analysis identified 36 overlapping targets between Bryonia dioica phytochemicals and type 2 diabetes mellitus-associated genes, with cucurbitacins and polyphenols interacting with α-amylase, α-glucosidase, and Glut4 translocation pathway targets. Conclusion Bryonia dioica root extracts demonstrated promising in vitro anti-diabetic activity through multiple mechanisms, including the inhibitory effect on digestive enzymes, protein antiglycation potential, and enhancement of glucose uptake, suggesting their potential as a source for anti-diabetic drugs development.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Background/Aims: Multiple myeloma (MM) predominantly affects elderly individuals, but studies on older patients with MM are limited. The clinical characteristics and survival outcomes of patients with MM aged 80 years or over were retrospectively analyzed. Methods: This retrospective multicenter study was conducted to investigate the clinical characteristics, treatment patterns, and survival outcomes of patients aged 80 years or over who were newly diagnosed with MM at five academic hospitals in Daegu, Korea, between 2010 and 2019. Results: A total of 127 patients with a median age of 83 years (range, 80–93 yr) were enrolled: 52 (40.9%) with Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, 84 (66.1%) with International Staging System (ISS) stage III disease, and 93 (73.2%) with a Charlson comorbidity index (CCI) > 4. Chemotherapy was administered to 86 patients (67.7%). The median overall survival was 9.3 months. Overall survival was significantly associated with ECOG PS > 2 (HR 2.26, 95% CI 1.43–3.59), ISS stage III (HR 1.99, 95% CI 1.18–3.34), and chemotherapy (HR 0.34, 95% CI 0.21–0.55). There was no statistically significant difference in event-free survival according to the type of anti-myeloma chemotherapy administered. The early mortality (EM) rate was 28.3%. Conclusions Even in patients with MM aged 80 years or over, chemotherapy can result in better survival outcomes than supportive care. Patients aged ≥ 80 years should not be excluded from chemotherapy based on age alone. However, reducing EM in elderly patients with newly diagnosed MM remains challenging.

Objective: Epothilone D (EpoD), microtubule (MT) stabilizing agent, demonstrated promising results in the animal models of Alzheimer’s disease, Parkinson’s disease and schizophrenia. The present study sought to investigate preventive effects of EpoD on altered changes of MT related proteins and endoplasmic reticulum (ER) stress proteins induced by social defeat stress (SDS). Methods: We measured protein expression levels of -tubulin and its post-translational modifications, MT-associated protein 2, stathmin1 and 2 with their phosphorylated forms, and ER stress markers, 78-kDa glucose-regulated protein (GRP-78) and CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP) in the prefrontal cortex (PFC) and hippocampus (HIP) of C57BL/6J strain mice treated with EpoD (2 mg/kg) or its vehicle, dimethylsulfoxide (DMSO), and exposed to SDS. Results: We observed lower levels of acetylated -tubulin, MAP2, p-STMN (Ser16), and GRP-78 in the PFC of the EpoD-Con group when compared to the DMSO-Con group. On the other hand, in the HIP, there were significantly higher levels of tyrosinated -tubulin and GRP-78 in the EpoD-Defeat group compared to the DMSO-Defeat group.Furthermore, the level of MAP2 in the HIP was found to be lower in the EpoD-Con group compared to the DMSO-Con group. Conclusion Our results suggest that EpoD exhibits a dual impact, manifesting both beneficial and detrimental effects on the aberrant changes of MT-related proteins and ER stress proteins induced by SDS, depending on the brain regions.These findings underscore the complexity of EpoD’s effects, necessitating further exploration to understand its intricate mechanisms in cellular pathways linked to SDS.

Background: Cognitive decline is commonly seen in brain tumor (BT) patients and is associatedwith a worsened prognosis. Cognitive rehabilitation (CR) for cancer-related cognitive dysfunction has been widely studied for non-central nervous system cancers; however, recent emerging research has commenced documenting CR strategies for BT patients and survivors. Our objective was to review the current literature on various CR modalities in patients and BT survivors. Methods: The review was conducted in accordance with the PRISMA guidelines. The studieson CR were searched across 3 databases using a predefined search strategy. After removing duplicates, performing initial and full-text screenings, and applying inclusion criteria, relevant articles were selected. The demographic details, CR technique, cognitive tasks/tests administered, cognitive functions assessed, follow-up time, and outcomes of the intervention were assessed. Results: A total of 15 studies were included in the review. Neuropsychologist-guided trainingsessions to improve memory, attention, and executive functioning are effective in improving the mentioned domains. Younger and more educated patients benefited the most. Holistic mnemonic training and neurofeedback were not shown to affect overall cognitive functioning. Computer-based training programs showed improvements in executive functions of pediatric BT survivors, however, feasibility studies showed conflicting results. Aerobic exercises improved executive functions and decreased symptoms of the tumor. Both yoga and combined aerobic and strength training improved overall cognitive functioning. Active video gaming may improve motor and process skills; however, no effect was seen on cognitive functioning. Conclusion Neuropsychologic training, computer-based programs, and physical exercise havebeen found effective in improving or preventing decline in cognitive functions of BT patients. Given the limited trials and methodological variations, a standardized CR program cannot be established at present. Ongoing trials are expected to provide valuable data in the near future.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Background/Aims: Multiple myeloma (MM) predominantly affects elderly individuals, but studies on older patients with MM are limited. The clinical characteristics and survival outcomes of patients with MM aged 80 years or over were retrospectively analyzed. Methods: This retrospective multicenter study was conducted to investigate the clinical characteristics, treatment patterns, and survival outcomes of patients aged 80 years or over who were newly diagnosed with MM at five academic hospitals in Daegu, Korea, between 2010 and 2019. Results: A total of 127 patients with a median age of 83 years (range, 80–93 yr) were enrolled: 52 (40.9%) with Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, 84 (66.1%) with International Staging System (ISS) stage III disease, and 93 (73.2%) with a Charlson comorbidity index (CCI) > 4. Chemotherapy was administered to 86 patients (67.7%). The median overall survival was 9.3 months. Overall survival was significantly associated with ECOG PS > 2 (HR 2.26, 95% CI 1.43–3.59), ISS stage III (HR 1.99, 95% CI 1.18–3.34), and chemotherapy (HR 0.34, 95% CI 0.21–0.55). There was no statistically significant difference in event-free survival according to the type of anti-myeloma chemotherapy administered. The early mortality (EM) rate was 28.3%. Conclusions Even in patients with MM aged 80 years or over, chemotherapy can result in better survival outcomes than supportive care. Patients aged ≥ 80 years should not be excluded from chemotherapy based on age alone. However, reducing EM in elderly patients with newly diagnosed MM remains challenging.

Objective: Impact of Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) changes on the criteria for schizophrenia (SZ) has been reported to be minimal in previous studies. However, this could be different in first-episode schizophrenia spectrum disorders (FE-SSDs). We investigated what proportion of patients with FE-SSDs was diagnosed based on the sole presence of bizarre delusions (BDs) or first rank auditory hallucinations (FRAHs). Their alternative diagnosis by the DSM-5 was established and diagnostic stability over 1-year was identified. Methods: This was a retrospective review study on the medical records, case report forms for the subjects with FE-SSDs (n=404) participated in the Korea Early Psychosis Study. The two Japanese sites reviewed retrospectively only medical records of the subjects with FE-SSDs (n=103). We used three different definitions of BDs (strict, narrow, and broad) and specified subtypes of Other Specified Schizophrenia spectrum and Other psychotic disorders (OSSOs). To ensure inter-rater reliability between the hospitals, regular zoom meetings were held. Results: Forty (7.89%) subjects out of 507 were found to be diagnosed as SSDs based on the sole presence of BDs or FRAHs. All these patients met the criteria of OSSOs and were classified as having pure delusion (n=22), delusion with attenuated auditory hallucinations (AHs) (n=5), pure AHs (n=3) and AHs with attenuated delusion (n=10). The patients with first and second subtypes (n=27) were found to have BDs. The BDs fulfilled mostly strict definitions or satisfied the next broadest definition. The diagnostic stability of FE-OSSOs and its subgroups (first and second subtypes) over 1-year was substantially high (70.27% and 84% respectively). Conclusion These findings suggest that more rigorous diagnostic assessment should be performed especially to differentiate OSSOs from SZ in patients with FE-SSDs and more refined classification of the subtypes for OSSOs considered in the next DSM revision.

Background/Aims: Multiple myeloma (MM) predominantly affects elderly individuals, but studies on older patients with MM are limited. The clinical characteristics and survival outcomes of patients with MM aged 80 years or over were retrospectively analyzed. Methods: This retrospective multicenter study was conducted to investigate the clinical characteristics, treatment patterns, and survival outcomes of patients aged 80 years or over who were newly diagnosed with MM at five academic hospitals in Daegu, Korea, between 2010 and 2019. Results: A total of 127 patients with a median age of 83 years (range, 80–93 yr) were enrolled: 52 (40.9%) with Eastern Cooperative Oncology Group Performance Status (ECOG PS) > 2, 84 (66.1%) with International Staging System (ISS) stage III disease, and 93 (73.2%) with a Charlson comorbidity index (CCI) > 4. Chemotherapy was administered to 86 patients (67.7%). The median overall survival was 9.3 months. Overall survival was significantly associated with ECOG PS > 2 (HR 2.26, 95% CI 1.43–3.59), ISS stage III (HR 1.99, 95% CI 1.18–3.34), and chemotherapy (HR 0.34, 95% CI 0.21–0.55). There was no statistically significant difference in event-free survival according to the type of anti-myeloma chemotherapy administered. The early mortality (EM) rate was 28.3%. Conclusions Even in patients with MM aged 80 years or over, chemotherapy can result in better survival outcomes than supportive care. Patients aged ≥ 80 years should not be excluded from chemotherapy based on age alone. However, reducing EM in elderly patients with newly diagnosed MM remains challenging.