Factors Impacting Fall Severity in Hospitalized Patients: A Retrospective Cohort Study.

Objectives: This retrospective case-controlled study aimed to evaluate the association between the severity of fall-related injuries and fall-risk-increasing drugs (FRIDs) in hospitalized patients. Methods: Data were collected from Changhua Christian Hospital, Taiwan, of all adult inpatients who experienced falls between January 2017 and December 2021, and were divided into two groups based on whether they sustained severe fall-related injuries. Retrospective data that may affect the severity of fall-related injuries and the use of FRIDs were investigated. Results: Among 1231 documented cases of falls, 26 patients sustained severe fall-related injuries. Older patients and those with osteoporosis were more susceptible to more severe injuries from a fall. The use of mobility aids and osteoporosis medications showed protective effects against fall injuries. No significant association was observed between fall-related injuries and comorbidities or FRIDs. Multivariate analysis confirmed the inverse correlation between the use of mobility aids, osteoporosis medications, and fall severity. Patients with osteoporosis exhibited significantly higher odds of sustaining more severe injuries with a fall (odds ratio = 3.02, 95% confidence interval: 1.21-7.53). Conclusions: This study highlights the importance of addressing risk factors associated with fall severity among hospitalized patients. Providing mobility aids to persons at greater risk.

Associations between doses of fall-risk-increasing drugs (FRIDs) and falls of hospitalized patients.

Falls are a serious public health problem in the aging population because of the associated clinical and socioeconomic impact. Although previous studies have investigated fall-risk-increasing drugs (FRIDs), few studies have focused on dosage among adult inpatients. This study aimed to evaluate associations between fall risk and dosage of different FRIDs classes in hospital inpatients. Inpatients who experienced falls at medical or surgical wards of Changhua Christian Hospital from January 2017 to December 2021 were identified and matched by age, sex, and hospital ward to randomly selected controls (four per case). Anonymous patient data were extracted from the hospital medical data repository, including demographic characteristics, comorbidities, fall-risk scores, and drug prescriptions. Medication dosages were computed using the anatomical therapeutic chemical classification and the defined daily dose system of the World Health Organization. A total of 852 cases and 3408 controls were identified as eligible. Reducing the use of CNS-active medications, administering lower doses of sedative-hypnotics, prescribing sufficient dopaminergic anti-Parkinson agents, and using NSAIDs instead of opioids are imperative in preventing falls among hospitalized patients according to the findings in the study.

Cardiac myofibrillogenesis is spatiotemporally modulated by the molecular chaperone UNC45B.

Sarcomeres are fundamental to cardiac muscle contraction. Their impairment can elicit cardiomyopathies, leading causes of death worldwide. However, the molecular mechanism underlying sarcomere assembly remains obscure. We used human embryonic stem cell (hESC)-derived cardiomyocytes (CMs) to reveal stepwise spatiotemporal regulation of core cardiac myofibrillogenesis-associated proteins. We found that the molecular chaperone UNC45B is highly co-expressed with KINDLIN2 (KIND2), a marker of protocostameres, and later its distribution overlaps with that of muscle myosin MYH6. UNC45B-knockout CMs display essentially no contractility. Our phenotypic analyses further reveal that (1) binding of Z line anchor protein ACTN2 to protocostameres is perturbed because of impaired protocostamere formation, resulting in ACTN2 accumulation; (2) F-ACTIN polymerization is suppressed; and (3) MYH6 becomes degraded, so it cannot replace non-muscle myosin MYH10. Our mechanistic study demonstrates that UNC45B mediates protocostamere formation by regulating KIND2 expression. Thus, we show that UNC45B modulates cardiac myofibrillogenesis by interacting spatiotemporally with various proteins.

Cobalt protoporphyrin promotes human keratinocyte migration under hyperglycemic conditions.

BACKGROUND: Complete healing of diabetic wounds continues to be a clinically unmet need. Although robust therapies such as stem cell therapy and growth factor treatment are clinically applied, these treatments are costly for most diabetic wound patients. Therefore, a cheaper alternative is needed. Cobalt protoporphyrin (CoPP) has recently been demonstrated to promote tissue regeneration. In this study, the therapeutic benefits of CoPP in diabetic wound healing were examined. METHODS: An in vitro wound healing model that mimics re-epithelialization was established to examine the effect of CoPP on the migratory capability of human keratinocytes (HaCaT) in either normal glucose (NG) or high glucose (HG) media, as well as in the presence of either H2O2 or lipopolysaccharide (LPS). At the end of the migration assays, cells were collected and subjected to Western blotting analysis and immunostaining. RESULTS: HaCaT were found to migrate significantly more slowly in the HG media compared to the NG media. CoPP treatment was found to enhance cell migration in HG media, but was found to decrease cell migration and proliferation when HaCaT were cultured in NG media. CoPP treatment induced high levels of expression of Nrf-2/HO-1 and FoxO1 in HaCaT cultured in either glucose concentration, although the FoxO1 expression was found to be significantly higher in HaCaT that underwent the migration assay in NG media compared to those in HG media. The higher level of FoxO1 expression seen in CoPP-treated HaCaT cultured in NG media resulted in upregulation of CCL20 and downregulation of TGFß1. In contrast, HaCaT migrated in HG media were found to have high levels of expression of TGFß1, and low levels of expression of CCL20. Interestingly, in the presence of H2O2, CoPP-pretreated HaCaT cultured in either NG or HG media had similar expression level of Nrf-2/HO-1 and FoxO1 to each other. Moreover, the anti-apoptotic effect of CoPP pretreatment was noticed in HaCaT cultured in either glucose concentration. Additionally, CoPP pretreatment was shown to promote tight junction formation in HaCaT suffering from LPS-induced damage. CONCLUSIONS: CoPP enhances cell migratory capacity under hyperglycemic conditions, and protects cells from oxidative and LPS-induced cellular damage in HG media containing either H2O2 or LPS.

Association between HSPA5 Promoter Polymorphisms and a Reduced Risk of Normal Tension Glaucoma.

INTRODUCTION: In normal tension glaucoma (NTG), factors other than elevated intraocular pressure (IOP) are likely to play a role in the pathogenesis of optic neuropathy. The potential similarities between Alzheimer's disease (AD) and NTG in cellular apoptosis leading to neurodegeneration have been shown in recent studies. Heat Shock Protein family A member 5 (HSPA5) promoter polymorphisms have been reported to be associated with a risk of AD. The purpose of our study was to investigate the role of HSPA5 promoter polymorphisms in NTG patients. METHODS: A total of 222 patients with NTG, along with 236 normal controls were enrolled in this study. Genomic DNA was amplified through a polymerase chain reaction (PCR) and identified for the polymorphic HSPA5 (-415 and -370) by Xmn1 and BstY1 restriction digestion, respectively. PCR fragments with potential polymorphic HSPA5 (-180) were subjected to sequence-analyses by a Hex-labeled primer. Genotypes for both NTG patients and control groups were compared for statistically significant differences. RESULTS: Polymorphisms (-415) G/A and (-180) del/G were completely linked in our population. The genotype and allele frequency distribution at the -415 G/A and -180 del/G sites showed a significant difference between the NTG cases and controls. The genotype frequency of HSPA5 (-415) AA/(-180) GG and the allele frequency of HSPA5 (-415) A/(-180) G were significantly lower (p = 0.04 and p = 0.01, respectively) in the NTG patients when compared with those in the control group. There was no significant difference in genotype or allele frequency distribution of the HSPA5 (-370) C/T between the NTG and control groups. There was a reduced risk of NTG associated with the carriers for the HSPA5 (-415) A/(-180) G allele compared with that in the control population (p = 0.01). CONCLUSION: HSPA5 (-415) A and (-180) G allele polymorphisms may be protective factors in the development of NTG.

Imiquimod Exerts Antitumor Effects by Inducing Immunogenic Cell Death and Is Enhanced by the Glycolytic Inhibitor 2-Deoxyglucose.

The induction of immunogenic cell death (ICD) in cancer cells triggers specific immune responses against the same cancer cells. Imiquimod (IMQ) is a synthetic ligand of toll-like receptor 7 that exerts antitumor activity by stimulating cell-mediated immunity or by directly inducing apoptosis. Whether IMQ causes tumors to undergo ICD and elicits a specific antitumor immune response is unknown. We demonstrated that IMQ-induced ICD-associated features, including the surface exposure of calreticulin and the secretion of adenosine triphosphate and HMGB1, were mediated by ROS and endoplasmic reticulum stress. In a B16F10 melanoma mouse model, vaccinating mice with IMQ-induced ICD cell lysate or directly injecting IMQ in situ reduced tumor growth that was mediated by inducing tumor-specific T-cell proliferation, promoting tumor-specific cytotoxic killing by CD8+ T cells, and increasing the infiltration of various immune cells into tumor lesions. The ICD-associated features were crucial in the induction of specific antitumor immunity in vivo. The glycolytic inhibitor 2-deoxyglucose enhanced IMQ-induced ICD-associated features and strengthened the antitumor immunity mediated by IMQ-induced ICD cell lysate in p53-mutant cancer cells, which were IMQ-resistant in vitro. We conclude that IMQ is an authentic ICD inducer and provide a concept connecting IMQ-induced cancer cell death and antitumor immune responses.

Global stability for epidemic models on multiplex networks.

In this work, we consider an epidemic model in a two-layer network in which the dynamics of susceptible-infected-susceptible process in the physical layer coexists with that of a cyclic process of unaware-aware-unaware in the virtual layer. For such multiplex network, we shall define the basic reproduction number [Formula: see text] in the virtual layer, which is similar to the basic reproduction number [Formula: see text] defined in the physical layer. We show analytically that if [Formula: see text] and [Formula: see text], then the disease and information free equilibrium is globally stable and if [Formula: see text] and [Formula: see text], then the disease free and information saturated equilibrium is globally stable for all initial conditions except at the origin. In the case of [Formula: see text], whether the disease dies out or not depends on the competition between how well the information is transmitted in the virtual layer and how contagious the disease is in the physical layer. In particular, it is numerically demonstrated that if the difference in [Formula: see text] and [Formula: see text] is greater than the product of [Formula: see text], the deviation of [Formula: see text] from 1 and the relative infection rate for an aware susceptible individual, then the disease dies out. Otherwise, the disease breaks out.

Association of depression with sleep quality might be greater than that of pain intensity among outpatients with chronic low back pain.

PURPOSE: No study to date has compared the associations of pain intensity, depression, and anxiety with insomnia among outpatients with chronic low back pain (CLBP). This study aimed to investigate this issue. PATIENTS AND METHODS: A total of 225 outpatients with CLBP were enrolled from a general orthopedics clinic. The Insomnia Severity Index was used to evaluate sleep quality. Major depressive disorder (MDD) and anxiety disorders were diagnosed using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition, text revision, Axis I Disorders. Two psychometric scales were used to evaluate depression and anxiety. The Visual Analog Scale was employed to assess pain intensity. Multiple linear regressions were performed to determine the association of insomnia with pain intensity, depression, and anxiety. RESULTS: Among the 225 subjects, 58 (25.8%) had clinical insomnia; 83 (36.9%) had severe low back pain; 49 (21.8%) had MDD, including 21 (9.3%) with a current major depressive episode (MDE); and 52 (23.1%) had anxiety disorders. More than half (56.9%) of the subjects with CLBP and clinical insomnia had MDD and/or anxiety disorders. Subjects with a current MDE or anxiety disorders had greater severities of pain and insomnia as compared with subjects without these conditions. After controlling for demographic variables, MDE was more strongly associated with insomnia than severe low back pain; moreover, the severity of depression had a greater association with insomnia than pain intensity. CONCLUSION: The association of depression with insomnia was not inferior to that of pain intensity with insomnia. Among patients with CLBP and insomnia, integration of depression and anxiety treatment into treatment of pain might help to improve sleep quality.

Aristolochic acid downregulates monocytic matrix metalloproteinase-9 by inhibiting nuclear factor-κB activation.

Aristolochic acid (AA)-associated nephropathy was described as being characterized by a rapid progressive enhancement of interstitial renal fibrosis. Renal tissue fibrosis occurs because of an imbalance of extracellular matrix (ECM) accumulation and matrix metalloproteinase (MMP) activation. Much evidence indicates that inflammatory renal disease including monocyte and mesangial interactions is linked to the development and progression of renal remodeling. In this study, we found that AA showed concentration-dependent inhibition of tumor necrosis factor (TNF)-α-induced MMP-9 activation with an IC(50) value of 6.4±0.5µM in human monocytic THP-1 cells. A similar effect was also noted with different ratios of AAs (types I and II). However, AA had no inhibitory effect on the intact enzymatic activity of MMP-9 at a concentration of 20µM. On the other hand, the level of tissue inhibitor of metalloproteinase (TIMP)-1 was not induced by AA, but it suppressed TNF-α-induced MMP-9 protein and messenger RNA expressions. AA also significantly inhibited TNF-α-induced IκBα degradation. Furthermore, an electrophoretic mobility shift assay and a reported gene study, respectively, revealed that AA inhibited TNF-α-induced NF-κB translocation and activation. In addition, compared to other NF-κB inhibitors, AA exerted significant inhibition of MMP-9 activation and monocyte chemotactic protein-1-directed invasion. From these results, we concluded that AA, a natural compound, inhibits TNF-α-induced MMP-9 in human monocytic cells possibly through the NF-κB signal pathway. These results also imply that AA may be involved in alteration of matrix homeostasis during renal fibrosis in vivo.

New constituents from stems of Artabotrys uncinatus.

Two new compounds, 4,5-dioxoartacinatine (1) and 24-methylenelanosta-7,9(11)-diene-3-one (2), together with thirty known compounds were isolated and characterized from the stems of Artabotrys uncinatus. Structures of the new compounds were determined by spectral analysis.