Changes in cognitive function after a 12-week POWER rehabilitation in older adults with schizophrenia and frailty.

BACKGROUND: The effectiveness of isolated resistance training (RT) on cognitive function among older adults with schizophrenia is insufficiently investigated. This study investigated the effectiveness of 12-weeks POWER rehabilitation, a novel RT regimen, on cognitive function among older patients with schizophrenia and frailty. METHODS: Thirty-two older adults with schizophrenia and frailty were enrolled and randomized to receive either a 12-week, twice weekly POWER rehabilitation, or without add-on training. Cognitive functioning was assessed using mini-mental state examination (MMSE), digit symbol substitution test, color trail task (CTT), and digit span task (DST). Physical performance was assessed by walking speed and hand grip strength. The generalized estimating equations was used to compare pre- and post-training outcome measure between groups. RESULTS: Between-group analysis revealed significant improvement in CTT1 and hand grip strength in the intervention group compared to the controls. Subgroup analyses showed CTT1 performance significantly improved after 12 weeks of POWER rehabilitation in the intervention group (time, p < .001), independent of age, educational level, global cognition, depressive symptoms, and psychotropic medication use. Increased hand grip strength was significantly associated with improved performance in MMSE, CTT1, and DST forward at study endpoint. CONCLUSION: A 12-week POWER rehabilitation for older patients with schizophrenia and frailty is safe and feasible, and may benefit physical and some domains of cognitive functioning.

Structure-guided identification and characterization of potent inhibitors targeting PhoP and MtrA to combat mycobacteria.

Mycobacteria are causative agents of tuberculosis (TB), which is a global health concern. Drug-resistant TB strains are rapidly emerging, thereby necessitating the urgent development of new drugs. Two-component signal transduction systems (TCSs) are signaling pathways involved in the regulation of various bacterial behaviors and responses to environmental stimuli. Applying specific inhibitors of TCSs can disrupt bacterial signaling, growth, and virulence, and can help combat drug-resistant TB. We conducted a comprehensive pharmacophore-based inhibitor screening and biochemical and biophysical examinations to identify, characterize, and validate potential inhibitors targeting the response regulators PhoP and MtrA of mycobacteria. The constructed pharmacophore model Phar-PR-n4 identified effective inhibitors of formation of the PhoP-DNA complex: ST132 (IC50 = 29 ± 1.6 µM) and ST166 (IC50 = 18 ± 1.3 µM). ST166 (KD = 18.4 ± 4.3 µM) and ST132 (KD = 14.5 ± 0.1 µM) strongly targeted PhoP in a slow-on, slow-off manner. The inhibitory potency and binding affinity of ST166 and ST132 for MtrAC were comparable to those of PhoP. Structural analyses and molecular dynamics simulations revealed that ST166 and ST132 mainly interact with the α8-helix and C-terminal ß-hairpin of PhoP, with functionally essential residue hotspots for structure-based inhibitor optimization. Moreover, ST166 has in vitro antibacterial activity against Macrobacterium marinum. Thus, ST166, with its characteristic 1,2,5,6-tetrathiocane and terminal sulphonic groups, has excellent potential as a candidate for the development of novel antimicrobial agents to combat pathogenic mycobacteria.

Discovery of a potent inhibitor, D-132, targeting AsfvPolX, via protein-DNA complex-guided pharmacophore screening and in vitro molecular characterizations.

The heightened transmissibility and capacity of African swine fever virus (ASFV) induce fatal diseases in domestic pigs and wild boars, posing significant economic repercussions and global threats. Despite extensive research efforts, the development of potent vaccines or treatments for ASFV remains a persistent challenge. Recently, inhibiting the AsfvPolX, a key DNA repair enzyme, emerges as a feasible strategy to disrupt viral replication and control ASFV infections. In this study, a comprehensive approach involving pharmacophore-based inhibitor screening, coupled with biochemical and biophysical analyses, were implemented to identify, characterize, and validate potential inhibitors targeting AsfvPolX. The constructed pharmacophore model, Phar-PolX-S, demonstrated efficacy in identifying a potent inhibitor, D-132 (IC50 = 2.8 ± 0.2 µM), disrupting the formation of the AsfvPolX-DNA complex. Notably, D-132 exhibited strong binding to AsfvPolX (KD = 6.9 ± 2.2 µM) through a slow-on-fast-off binding mechanism. Employing molecular modeling, it was elucidated that D-132 predominantly binds in-between the palm and finger domains of AsfvPolX, with crucial residues (R42, N48, Q98, E100, F102, and F116) identified as hotspots for structure-based inhibitor optimization. Distinctively characterized by a 1,2,5,6-tetrathiocane with modifications at the 3 and 8 positions involving ethanesulfonates, D-132 holds considerable promise as a lead compound for the development of innovative agents to combat ASFV infections.

A facile method to fabricate versatile keratin cryogels for tissue engineering applications.

Human hair keratin (HHK) has been extensively explored as a biomaterial for soft tissue regeneration due to their excellent bioactivity and biocompatibility. The possibility to fabricate HHK into three-dimensional (3D) hydrogels with physical properties resembling soft tissues has been well demonstrated. However, conventional keratin hydrogels often exhibit a dense architecture that could hinder cell filtration. In the present study, HHK-based cryogels were fabricated using a freeze-thaw (FT) method, where oxidized dopamine (ODA) was employed to covalently crosslink thiol/amine rich-keratin molecules at sub-zero temperatures. The obtained HHK-ODA cryogels have micron-sized pores ranging between 100 and 200 µm and mechanical properties that can be tuned by varying the crosslinking density between ODA and HHK. Through optimization of the weight content of ODA and the number of FT cycles, the compressive strengths and stiffnesses of these cryogels achieved 15-fold increments from ∼1.5 kPa to ∼22 kPa and ∼300 Pa to ∼5000 Pa, respectively. The HHK-ODA cryogels competently supported human dermal fibroblast spreading and proliferation. Overall, this study exhibited a facile method to fabricate mechanically superior keratin-based cryogels with cell compatible microarchitecture, circumventing the need for complicated chemical modifications and the use of cytotoxic crosslinkers.

A path analysis investigation into menopausal osteoporosis, sarcopenia risk, and their impact on sleep quality, depressive symptoms and quality of life.

PURPOSE: The objective was to investigate the relationships among disease characteristics, sarcopenia risk, bone function, sleep quality, depressive symptoms, and health-related quality of life in menopausal women. Additionally, we also examined the potential mediating role of coping in the relationship between these factors and health outcomes for individuals with osteoporosis. METHODS: In a cross-sectional approach, 201 participants were referred by a physician from the Family Medicine Department during their outpatient visits at a general hospital in Southern Taiwan. Data collection involved structured one-on-one interviews, and the analysis included descriptive and inferential statistics, along with a structural equation modeling. RESULTS: The participants' bone function was strongly positively related to coping, physical and mental quality of life (QOL), and negatively related to sleep quality and depressive symptoms. The duration of osteoporosis was positively related to pain, sarcopenia risk, sleep quality, but negatively related to bone function, physical and mental QOL. This structural framework explains 36% of the variance in depressive symptoms, 25% in sleep disturbances, 54% in mental QOL, and 72% in physical QOL. The best-fit structural equation modeling showed that physical function, exercise, sarcopenia, pain, and coping were significant predictors of depressive symptoms, with coping acting as a mediator in these relationships. CONCLUSION: Individuals who employed more active coping strategies exhibited fewer depressive symptoms, better sleep quality, and superior physical and mental QOL. Further, individuals with osteoporosis had lower pain levels, less sarcopenia risk, and higher engaged in exercise presentation improved physical and mental QOL. Future longitudinal research holds the promise of providing deeper insights into these complex relationships.

Outcomes of Breast-Conserving Therapy in Patients With Inflammatory Breast Cancer: A Meta-Analysis.

INTRODUCTION: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Currently, patients who respond to neoadjuvant chemotherapy (NAC) are treated with mastectomy and axillary lymph node dissection. This study aimed to synthesize real-world data to evaluate the feasibility of breast-conserving therapy (BCT), sentinel lymph node (SLN), and sentinel lymph node biopsy (SLNB) for patients with IBC who respond to NAC. METHODS: PubMed, Embase, and Cochrane Library databases were searched for relevant articles. Clinical studies that compared mastectomy with BCT for IBC treatment were reviewed. The primary outcomes were local recurrence rate and 5-y survival rate in patients with IBC who responded to NAC. Furthermore, the SLN detection rate and false-negative rate (FNR) for SLNB were also evaluated. RESULTS: In the final analysis, 17 studies were included. The pooled estimates of the local recurrence rate for mastectomy and no surgical intervention were 18.6% and 15.9%, respectively (P = 0.956). Five-y survival was similar for mastectomy, partial mastectomy, and no surgical intervention (45.8%, 57.1%, and 39.4%, respectively). The pooled estimates of the SLN detection rate and FNR for SLNB were 81.9% and 21.8%, respectively. CONCLUSIONS: Among patients with IBC who respond to NAC, the local recurrence and 5-y survival rates in those undergoing BCT are noninferior to the rates in those undergoing mastectomy; therefore, BCT could be a feasible option for surgical management. However, a poor SLN detection rate and a high FNR were found in patients undergoing SLNB. Further large-scale clinical studies are required to confirm our findings.

Aplasia cutis congenita in monozygotic twins.

Aplasia cutis congenita (ACC) is defined as complete or partial loss or absence of skin at birth and it can occur on any part of the body, but most commonly on the scalp. Single offspring with ACC have been reported in most case reports, but cases in twins are rarely reported. Here, we report two cases of ACC, monozygotic twin boys presented with scattered skin absence over the scalp vertex after birth. All the lesions presented as ulcers with no hair and healed with scars, otherwise, the twins were well developed mentally and physically. In addition, the whole exome sequencing of the twins and their parents might provide diagnosis and classification assistance.

Simultaneous determination of tramadol and paracetamol in human plasma using LC-MS/MS and application in bioequivalence study of -fixed-dose combination.

The study aimed to develop a sensitive and high-throughput liquid chromatography coupled with tandem mass spectrometry method to quantify concentrations of tramadol and paracetamol simultaneously in human plasma. Sample preparation involved single-step protein precipitation using methanol and two deuterated internal standards, tramadol D6 and paracetamol D4. Agilent Poroshell 120 EC-C18 (100 × 2.1 mm, 2.1 µm) analytical column was employed to achieve chromatographic separation. Detection was in positive ion multiple reaction monitoring mode. A tailing factor (Tf) of <1.2, separation factor (K prime) of >1.5 from the column dead time and signal-to-noise (S/N) ratio >10, were obtained for analytes and internal standards. The standard curve was linear over the concentration range of 2.5-500.00 ng/mL for tramadol and 0.025-20.00 µg/mL for paracetamol. A small injection volume of 1 µL, low flow rate of 440 µL/min and short analysis time of 3.5 min reduced the solvent consumption, analysis cost and system contamination. The results of method validation parameters fulfilled the acceptance criteria of bioanalytical guidelines. The method was successfully applied to a bioequivalence study of fixed-dose combination products of tramadol and paracetamol in Malaysian healthy subjects.

The effect of sequential combination of mirror therapy and robot-assisted therapy on motor function, daily function, and self-efficacy after stroke.

Robot-assisted therapy and mirror therapy are both effective in promoting upper limb function after stroke and combining these two interventions might yield greater therapeutic effects. We aimed to examine whether using mirror therapy as a priming strategy would augment therapeutic effects of robot-assisted therapy. Thirty-seven chronic stroke survivors (24 male/13 female; age = 49.8 ± 13.7 years) were randomized to receive mirror therapy or sham mirror therapy prior to robot-assisted therapy. All participants received 18 intervention sessions (60 min/session, 3 sessions/week). Outcome measures were evaluated at baseline and after the 18-session intervention. Motor function was assessed using Fugl-Meyer Assessment and Wolf Motor Function Test. Daily function was assessed using Nottingham Extended Activities of Daily Living Scale. Self-efficacy was assessed using Stroke Self-Efficacy Questionnaires and Daily Living Self-Efficacy Scale. Data was analyzed using mixed model analysis of variance. Both groups demonstrated statistically significant improvements in measures of motor function and daily function, but no significant between-group differences were found. Participants who received mirror therapy prior to robot-assisted therapy showed greater improvements in measures of self-efficacy, compared with those who received sham mirror therapy. Our findings suggest that sequentially combined mirror therapy with robot-assisted therapy could be advantageous for enhancing self-efficacy post-stroke.Trial registration: ClinicalTrials.gov Identifier: NCT03917511. Registered on 17/04/2019, https://clinicaltrials.gov/ct2/show/ NCT03917511.

Erianin: A phytoestrogen with therapeutic potential.

Erianin, a phytoestrogen with therapeutic potential, is one of the major active components of Dendrobll caulis. Erianin has a variety of pharmacological effects, such as anti-tumor, anti-inflammatory, anti-diabetic retinopathy, anti-psoriasis, and antibacterial effects. Especially, in regard to the anti-tumor effect of erianin, the underlying molecular mechanism has been partly clarified. In fact, the numerous pharmacological actions of erianin are complex and interrelated, mainly including ERK1/2, PI3K/Akt, JAK2/STAT3, HIF-1α/PD-L1, PPT1/mTOR, JNK/c-Jun, and p38 MAPK signal pathway. However, on account of the poor water solubility and the low bioavailability of erianin, greatly affected and limited its further development and application. And it is worthwhile and meaningful to explore more extensive pharmacological effects and mechanisms, clarify pharmacokinetics, and synthesize the derivatives of erianin. Conclusively, in this paper, the pharmacological effects of erianin and its mechanism, pharmacokinetics, and derivatives studies were reviewed, in order to provide a reference for the development and application of erianin.

Transcatheter Edge-to-Edge Repair for a Patient With Severe Mitral Regurgitation of Carpentier IIIa Classification.

Whether patients diagnosed with mitral regurgitation of Carpentier class IIIa (rheumatic origin) can possibly be treated with balloon mitral commissurotomy followed by transcatheter edge-to-edge repair remains unclear. Here, we report on such a case who was successfully treated with balloon mitral commissurotomy and then transcatheter edge-to-edge repair without aggravating mitral stenosis. (Level of Difficulty: Intermediate.).

Involving a Dedicated Epidural-Caring Nurse in Labor Ward Practice Improves Maternal Satisfaction towards Childbirth: A Retrospective Study.

The quality of healthcare is crucially linked to patient satisfaction, particularly in the provision of neuraxial analgesia for labor pain. Neuraxial analgesia for labor pain control should ideally be readily available when requested. However, in real-world practice, anesthesiologists may not always respond immediately to maternal demands, which can compromise the quality of care. To address this issue, this study aimed to evaluate the effectiveness of involving a dedicated nurse in epidural care to improve maternal satisfaction. This study was conducted in a single tertiary center. Medical records of women with singleton pregnancies above 36 gestational weeks who received neuraxial analgesia for labor pain control were reviewed (N = 354). Among them, 104 women (29%) received care from a dedicated nurse. The results showed that involving a dedicated nurse led to higher maternal satisfaction scores before (4.7 ± 0.5 versus 4.5 ± 0.6, p = 0.001), during (4.7 ± 0.6 versus 4.5 ± 0.6, p = 0.002), and at 24 h postpartum (4.7 ± 0.5 versus 4.5 ± 0.5, p = 0.001), without any adverse impact on maternal, neonatal, or epidural-related complications. These findings suggest that allocating a dedicated nurse to epidural care can effectively enhance maternal satisfaction and potentially improve overall care quality.

Predictors of success in the registered nurse licensure exam for nursing graduates whose education was affected by the COVID-19 pandemic.

The Coronavirus disease 2019 (COVID-19) pandemic has had an unprecedented impact on health-care education. However, the relationship between changes in nursing internships in Taiwan during the COVID-19 pandemic and outcome in the national registered nurse (RN) licensure exam for new nursing graduates is underexplored. The study was to explore the predictors of first-attempt success in the RN licensure exam in 2022. A retrospective review of secondary data was employed in this study. Adjusted binary logistic regression was used to analyze data. A convenience sample of 78 new graduates attempted the exam. Of these graduates, 87.2% passed the RN licensure exam. Age was the main predictor of exam success, followed by grand mean academic score and total alternative (nontraditional in-person) internship hours. Compared with those who failed the exam, the graduates who passed the exam were significantly more likely to be younger, have better academic performance, and have engaged in more alternative internship hours. Nursing faculties should consider implementing supportive strategies early for students who are underperforming or those who are older than their classmates on average to help them pass the RN exam on the first attempt. The optimal duration and long-term consequences of alternative nursing internships must be analyzed in further detail.

Responses to Stress among East Malaysian Students: Psychometric Properties of the Responses to Stress Questionnaire.

Background: Academic stress is part of a student's life. Chronic stress may result in mental health problems, affecting the adolescent's well-being in adulthood. However, not all types of stress result in a negative effect. Therefore, understanding how adolescents adapt to academic stress can lay the groundwork for preventive interventions. The Response to Stress Questionnaire (RSQ) for academic problems centred on a multidimensional model of responses to stress. However, it has not been tested among Malaysians. Thus, this study aimed to validate the questionnaire among Malaysians. Methods: The questionnaire was translated into the Malay language using forward and backward translation. Data were collected via self-administered questionnaires at a secondary school in Kuching. A validity test was conducted using face and content validation by subject matter experts, and construct validation was performed using exploratory factor analysis (EFA). A reliability test was conducted by checking Cronbach's alpha. Results: Results showed that the questionnaire has good validity and reliability. The EFA resulted in only three dimensions of responses to stress among Malaysian adolescents in contrast to the five dimensions in the original RSQ for academic problems. The Cronbach's alpha showed good reliability of the questionnaire. Conclusion: The questionnaire measuring responses to stress was valid and reliable in assessing the responses of adolescents to academic stress.

Obstetric and Neonatal Outcomes Associated With Implementation of a COVID-19 Predelivery Screening Policy in a Taiwan Hospital.

This cohort study examines obstetric and neonatal outcomes associated with predelivery screening policy implementation aimed to prevent COVID-19 in a Taiwan hospital.

An Open Dataset of Annotated Metaphase Cell Images for Chromosome Identification.

Chromosomes are a principal target of clinical cytogenetic studies. While chromosomal analysis is an integral part of prenatal care, the conventional manual identification of chromosomes in images is time-consuming and costly. This study developed a chromosome detector that uses deep learning and that achieved an accuracy of 98.88% in chromosomal identification. Specifically, we compiled and made available a large and publicly accessible database containing chromosome images and annotations for training chromosome detectors. The database contains five thousand 24 chromosome class annotations and 2,000 single chromosome annotations. This database also contains examples of chromosome variations. Our database provides a reference for researchers in this field and may help expedite the development of clinical applications.

Genome-Wide Identification and Analysis of bHLH Transcription Factors Related to Anthocyanin Biosynthesis in Cymbidium ensifolium.

The basic helix-loop-helix (bHLH) transcription factors are widely distributed across eukaryotic kingdoms and participate in various physiological processes. To date, the bHLH family has been identified and functionally analyzed in many plants. However, systematic identification of bHLH transcription factors has yet to be reported in orchids. Here, 94 bHLH transcription factors were identified from the Cymbidium ensifolium genome and divided into 18 subfamilies. Most CebHLHs contain numerous cis-acting elements associated with abiotic stress responses and phytohormone responses. A total of 19 pairs of duplicated genes were found in the CebHLHs, of which 13 pairs were segmentally duplicated genes and six pairs were tandemly duplicated genes. Expression pattern analysis based on transcriptome data revealed that 84 CebHLHs were differentially expressed in four different color sepals, especially CebHLH13 and CebHLH75 of the S7 subfamily. The expression profiles of CebHLH13 and CebHLH75 in sepals, which are considered potential genes regulating anthocyanin biosynthesis, were confirmed through the qRT-PCR technique. Furthermore, subcellular localization results showed that CebHLH13 and CebHLH75 were located in the nucleus. This research lays a foundation for further exploration of the mechanism of CebHLHs in flower color formation.

The mechanism of Croci stigma in the treatment of melasma based on network pharmacology and molecular docking.

PURPOSE: To investigate the molecular mechanism of Croci stigma (CS) in the treatment of melasma by network pharmacology and molecular docking. METHODS: TCMSP, CTD, STITCH, SymMap, GeneCard, GenBank, OMIM and DrugBank databases were used to obtain the components and targets of CS and the targets of chloasma. STRING was used to build a protein-protein interaction (PPI) network of intersecting targets between drugs and diseases. Cytoscape was used to establish drug-compounds-targets-disease network and analyze PPI network. R was used for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and visualization. AutoDock was used for molecular docking and R was used to visualize docking results. RESULTS: Four active compounds were screened out from CS, and 31 target genes intersecting with melasma were found after further analysis. The top 10 hub genes were found after analysis of the PPI network, including TYR, TYRP1, DCT, CREB1, KITLG, MITF, ESR1, EDNRB, CD4, and PTGS2. In the enrichment analysis, melanogenesis was considered as the core pathway through which CS exerts its therapeutic effect on melasma. Molecular docking results showed that the core genes in the regulatory network had high binding activity with related active components, especially crocetin. CONCLUSION: CS may treat melasma by regulating core targets, such as TYR, TYRP1, DCT, CREB1, KITLG, MITF, EDNRB, and PTGS2, and acting on melanogenesis. And crocetin may be the core compound worthy of further study.

Water-soluble extracellular vesicle probes based on conjugated oligoelectrolytes.

We developed a series of transmembrane conjugated oligoelectrolytes (COEs) with tunable optical emissions from the UV to the near IR to address the false-positive problem when detecting nanometer-sized extracellular vesicles (EVs) by flow cytometry. The amphiphilic molecular framework of COEs is defined by a linear conjugated structure and cationic charged groups at each terminal site. Consequently, COEs have excellent water solubility and the absence of nanoaggregates at concentrations up to 50 µM, and unbound COE dyes can be readily removed through ultrafiltration. These properties enable unambiguous and simple detection of COE-labeled small EVs using flow cytometry with negligible background signals. We also demonstrated the time-lapsed tracking of small EV uptake into mammalian cells and the endogenous small EV labeling using COEs. Briefly, COEs provide a class of membrane-targeting dyes that behave as biomimetics of the lipid bilayer and a general and practical labeling strategy for nanosized EVs.