A Study on Intelligent Optical Bone Densitometry.

Osteoporosis is a prevalent chronic disease worldwide, particularly affecting the aging population. The gold standard diagnostic tool for osteoporosis is Dual-energy X-ray Absorptiometry (DXA). However, the expensive cost of the DXA machine and the need for skilled professionals to operate it restrict its accessibility to the general public. This paper builds upon previous research and proposes a novel approach for rapidly screening bone density. The method involves utilizing near-infrared light to capture local body information within the human body. Deep learning techniques are employed to analyze the obtained data and extract meaningful insights related to bone density. Our initial prediction, utilizing multi-linear regression, demonstrated a strong correlation (r = 0.98, p-value = 0.003**) with the measured Bone Mineral Density (BMD) obtained from Dual-energy X-ray Absorptiometry (DXA). This indicates a highly significant relationship between the predicted values and the actual BMD measurements. A deep learning-based algorithm is applied to analyze the underlying information further to predict bone density at the wrist, hip, and spine. The prediction of bone densities in the hip and spine holds significant importance due to their status as gold-standard sites for assessing an individual's bone density. Our prediction rate had an error margin below 10% for the wrist and below 20% for the hip and spine bone density.

Effects of self-efficacy on frontal midline theta power and golf putting performance.

Introduction: Self-efficacy (SE), defined as an individual's belief in their ability to complete a task, is linked to top-down attentional control, influencing motor performance in sports. Although the behavioral effects of SE are well-documented, there is a lack of research on the mechanisms through which SE affects sports performance. Our research aims to elucidate the neurophysiological mechanisms that underlie the impact of self-efficacy on sports performance. Specifically, we intend to explore the effects of low and high SE on frontal midline theta (Fmθ) activity, associated with sustained top-down attention, and on motor performance. Methods: We recruited thirty-four professional golfers to perform 60 putts, during which their electroencephalographic activity was monitored. SE levels were assessed using a visual analog scale from 0 to 10 before each putt, with scores categorized into higher or lower SE based on each golfer's individual average score. Results: Paired t-tests indicated that trials with higher SE scores had a higher putting success rate than those with lower SE scores (53.3% vs. 46.7%). Furthermore, trials associated with higher SE scores exhibited lower Fmθ activity compared to those with lower SE scores (4.49 vs. 5.18). Discussion: Our results suggest that higher SE is associated with reduced top-down attentional control, leading to improved putting performance. These findings support Bandura's theory of SE, which suggests that the effects of efficacy beliefs are mediated by cognitive, motivational, emotional, and decision-making processes. This study sheds light on the intermediate processes of SE by examining its impact on the anticipation of outcomes, sports performance, and attentional control prior to putting.

The anti-platelet drug cilostazol enhances heart rate and interrenal steroidogenesis and exerts a scant effect on innate immune responses in zebrafish.

RATIONALE: Cilostazol, an anti-platelet phosphodiesterase-3 inhibitor used for the treatment of intermittent claudication, is known for its pleiotropic effects on platelets, endothelial cells and smooth muscle cells. However, how cilostazol impacts the endocrine system and the injury-induced inflammatory processes remains unclear. METHODS: We used the zebrafish, a simple transparent model that demonstrates rapid development and a strong regenerative ability, to test whether cilostazol influences heart rate, steroidogenesis, and the temporal and dosage effects of cilostazol on innate immune cells during tissue damage and repair. RESULTS: While dosages of cilostazol from 10 to 100 µM did not induce any noticeable morphological abnormality in the embryonic and larval zebrafish, the heart rate was increased as measured by ImageJ TSA method. Moreover, adrenal/interrenal steroidogenesis in larval zebrafish, analyzed by whole-mount 3ß-Hsd enzymatic activity and cortisol ELISA assays, was significantly enhanced. During embryonic fin amputation and regeneration, cilostazol treatments led to a subtle yet significant effect on reducing the aggregation of Mpx-expressing neutrophil at the lesion site, but did not affect the immediate injury-induced recruitment and retention of Mpeg1-expressing macrophages. CONCLUSIONS: Our results indicate that cilostazol has a significant effect on the heart rate and the growth as well as endocrine function of steroidogenic tissue; with a limited effect on the migration of innate immune cells during tissue damage and repair.

Rotablation for Octogenarians in a Modern Cathlab: Short- and Intermediate-Term Results.

Background: There are limited reports on the treatment of complex calcified lesions using rotational atherectomy (RA) in octogenarians, particularly in high-risk patients. Objective: To evaluate procedural and clinical outcomes of RA in octogenarians. Methods: Consecutive RA patients from 2010 to 2018 were selected from our catheterization laboratory database, stratified into two groups (≥ or < 80 years old), and analyzed. Results: A total of 411 patients (269 males and 142 females) with a mean age of 73.8 ± 11.3 years were enrolled, of whom 153 were ≥ 80 years old and 258 were < 80 years old. Most of the patients displayed high-risk features. The baseline Syntax scores were high in both groups, and most lesions were heavily calcified (96.1% vs. 97.3%, p = 0.969, respectively). The use of hemodynamic support intra-aortic balloon pump was more frequent in the octogenarians (21.6% vs. 11.6%, p = 0.007), but the RA completion rate was similarly high (95.9% vs. 99.1%, p = 0.842). There was no difference in acute complications. The total/cardiovascular (CV) death rate within one year was higher in the octogenarians, along with higher major adverse cardiovascular event (MACE)/CV MACE rates in the first month. Cox regression analysis showed that age ≥ 80 years, acute coronary syndrome, ischemic cardiomyopathy/shock, multi-vessel disease and serum creatinine were all predictors of MACE, and that these factors plus peripheral artery disease were predictors of all-cause mortality in these patients. Conclusions: RA is feasible with a very high success rate in high-risk octogenarians with complex anatomies, and with equal safety and no increase in complications. The higher rates of all-cause death and MACE were attributed to an older age and other traditional risk factors.

Referral, Diagnosis, and Pharmacological Management of Peripheral Artery Disease: Perspectives from Taiwan.

Peripheral artery disease (PAD) imposes a heavy burden of major adverse cardiovascular events that are associated with considerable mortality and morbidity, and major adverse limb events (e.g., thrombectomy, revascularization, amputation) that can substantially impact patients' daily functioning and quality of life. Global registry data have indicated that PAD is an underdiagnosed disease in Taiwan, and its associated risk factors remain inadequately controlled. This review discusses the burden of PAD in Taiwan, major guidelines on PAD management, and the latest clinical trial outcomes. Practical experience, opinions, and the latest trial data were integrated to derive a series of clinical algorithms - patient referral, PAD diagnosis, and the antithrombotic management of PAD. These algorithms can be adapted not only by physicians in Taiwan involved in the clinical management of patients with PAD but also by general practitioners in local clinics and regional hospital settings, with the ultimate aim of improving the totality of PAD patient care in Taiwan.

Image-guided brachytherapy following external-beam radiation therapy for patients with inoperable endometrial cancer.

OBJECTIVE: To investigate the outcomes of definitive external-beam radiation therapy (EBRT) plus image-guided brachytherapy (IGBT) in patients with endometrial cancer (EC) unsuitable for surgery. METHODS: A total of 50 patients with inoperable EC were included. The patients received EBRT in a median dose of 45 Gy to the pelvis over 5 weeks. Thereafter, the patients received brachytherapy using tandem and ovoid applicators. High-risk clinical target volume (HR-CTV) and gross tumor volume in brachytherapy (GTVp) were defined by the assistance of patients' pre-IGBT magnetic resonance imaging. RESULTS: The medical records of the 50 patients were analyzed. The main causes of inoperability were anesthesia contraindications, namely medical comorbidities and obesity. The median cumulative D90s (the minimum dose delivered to 90% of the volume) in EQD2 (equivalent dose in 2-Gy fractions) to the HR-CTV and GTVp were 72.9 Gy10 (range, 64.9 to 80.3) and 166.2 Gy10 (range, 123.0 to 189.8), respectively. Over a median follow-up period of 27 months, 8 of the patients died of cancer. The 2-year overall and cancer-specific survival rates were 75% and 83%, respectively. The cumulative incidences of pelvic and distant failure were 4% (n = 2) and 16% (n = 8), respectively. Gastrointestinal complications of grade 2 or above were noted in 2 patients (4%), and a grade 2 genitourinary complication was noted in one. CONCLUSIONS: For patients with inoperable EC, EBRT followed by IGBT is an effective approach for achieving high local control without a high risk of complications.

Linoleate-pazopanib conjugation as active pharmacological ingredient to abolish hepatocellular carcinoma growth.

Small molecule compounds targeting multiple kinases involved in neoangiogenesis have shown survival benefits in patients with unresectable hepatocellular carcinoma (HCC). Nonetheless, despite the beneficial effects of multikinase inhibitors (MKIs), a lack of boosting adjuvant limits their objective response rate. Lipid conjugates have been used to improve delivery efficacy or pharmaceutical benefits for decades. However, the feasibility of utilizing lipid-drug conjugates (LDCs) in HCC regimens remains untested. In this study, oral feeding of linoleate-fluorescein isothiocyanate conjugates showed that the compound was well distributed in a spontaneous HCC mouse model. Therefore, a rationale design was developed for chemically synthesizing a linoleate-pazopanib conjugate (LAPC). The LAPC showed a significantly improved cytotoxicity compared to the parental drug pazopanib. Pazopanib's angiogenic suppressing signals were not observed in LAPC-treated HCC cells, potentially suggesting an altered mechanism of action (MOA). In an efficacy trial comparing placebo, oral pazopanib, and LAPC treatments in the hepatitis B virus transgene-related spontaneous HCC mouse model (HBVtg-HCC), the LAPC treatment demonstrated superior tumor ablating capacity in comparison to both placebo and pazopanib treatments, without any discernible systemic toxicity. The LAPC exposure is associated with an apoptosis marker (Terminal deoxynucleotidyl transferase dUTP nick end labeling [TUNEL]) and an enhanced ferroptosis (glutathione peroxidase 4 [GPX4]) potential in HBVtg-HCC tumors. Therefore, the LAPC showed excellent HCC ablative efficacy with altered MOA. The molecular mechanisms of the LAPC and LDCs for HCC therapeutics are of great academic interest. Further comprehensive preclinical trials (e.g., chemical-manufacture-control, toxicity, distribution, and pharmacokinetics/pharmacodynamics) are expected.

Review of the endocrine organ-like tumor hypothesis of cancer cachexia in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most fatal types of solid tumors, associated with a high prevalence of cachexia (~80%). PDAC-derived cachexia (PDAC-CC) is a systemic disease involving the complex interplay between the tumor and multiple organs. The endocrine organ-like tumor (EOLT) hypothesis may explain the systemic crosstalk underlying the deleterious homeostatic shifts that occur in PDAC-CC. Several studies have reported a markedly heterogeneous collection of cachectic mediators, signaling mechanisms, and metabolic pathways, including exocrine pancreatic insufficiency, hormonal disturbance, pro-inflammatory cytokine storm, digestive and tumor-derived factors, and PDAC progression. The complexities of PDAC-CC necessitate a careful review of recent literature summarizing cachectic mediators, corresponding metabolic functions, and the collateral impacts on wasting organs. The EOLT hypothesis suggests that metabolites, genetic instability, and epigenetic changes (microRNAs) are involved in cachexia development. Both tumors and host tissues can secrete multiple cachectic factors (beyond only inflammatory mediators). Some regulatory molecules, metabolites, and microRNAs are tissue-specific, resulting in insufficient energy production to support tumor/cachexia development. Due to these complexities, changes in a single factor can trigger bi-directional feedback circuits that exacerbate PDAC and result in the development of irreversible cachexia. We provide an integrated review based on 267 papers and 20 clinical trials from PubMed and ClinicalTrials.gov database proposed under the EOLT hypothesis that may provide a fundamental understanding of cachexia development and response to current treatments.

A Novel 3D Culture Scaffold to Shorten Development Time for Multicellular Tumor Spheroids.

Multicellular tumor spheroids and tumoroids are considered ideal in vitro models that reflect the features of the tumor microenvironment. Biomimetic components resembling the extracellular matrix form scaffolds to provide structure to 3-dimensional (3D) culture systems, supporting the growth of both spheroids and tumoroids. Although Matrigel has long been used to support 3D culture systems, batch variations, component complexity, and the use of components derived from tumors are complicating factors. To address these issues, we developed the ACD 3D culture system to provide better control and consistency. We evaluated spheroid and tumoroid formation using the ACD 3D culture system, including the assessment of cell viability and cancer marker expression. Under ACD 3D culture conditions, spheroids derived from cancer cell lines exhibited cancer stem cell characteristics, including a sphere-forming size and the expression of stem cell marker genes. The ACD 3D culture system was also able to support patient-derived primary cells and organoid cell cultures, displaying adequate cell growth, appropriate morphology, and resistance to oxaliplatin treatment. These spheroids could also be used for drug screening purposes. In conclusion, the ACD 3D culture system represents an efficient tool for basic cancer research and therapeutic development.

CYP2C19 loss-of-function alleles predicts clinical outcomes in East Asian patients with acute myocardial infarction undergoing percutaneous coronary intervention and stenting receiving clopidogrel.

Background: CYP2C19 loss-of-function (LOF) alleles reduce the effectiveness of clopidogrel and are associated with high rates of clinical events in patients undergoing percutaneous coronary intervention (PCI) and stenting in Northeast Asians. However, the prevalence and influence of CYP2C19 LOF alleles in Southeast Asians remain unclear. Objectives: This study aims to retrospectively investigate the prevalence of CYP2C19 LOF alleles and clinical outcomes in East Asian patients taking clopidogrel and undergoing PCI. Methods: Between June 2019 and June 2020, volunteer participants in a single medical center were consecutively selected. The genetic data of CYP2C19 were derived from the Taiwan Precision Medicine Initiative (TPMI). Patients receiving clopidogrel while undergoing PCI with stenting were retrospectively analyzed. Results: A total of 999 patients (62.4 ± 11.1 years old, 83.7% men) were enrolled; 39.3% without the CYP2C19 LOF allele (normal metabolizers + rapid metabolizers, NM + RM); 44.9% with one LOF allele (intermediate metabolizers, IM); 15.7% with two LOF alleles (poor metabolizers, PM). The incidence of stroke was higher in the PM subgroup compared to the NM + RM subgroup or IM subgroup in patients presenting with acute myocardial infarction (AMI). The 1-year major adverse cardiac and cerebrovascular events (MACCE)-free survival rates in all participants were similar among the three groups. However, in the AMI group, the 1-year MACCE-free survival rates were significantly lower in the PM subgroup compared to the NM + RM subgroup or IM subgroup. Conclusion: In East Asians presenting with AMI, CYP2C19 PM was associated with deleterious cardiovascular outcomes and stroke. Our results reinforce the crucial role of preemptive CYP2C19 genotyping in East Asian AMI patients receiving clopidogrel treatment.

Multipronged Programmatic Strategy for Preventing Secondary Fracture and Facilitating Functional Recovery in Older Patients after Hip Fractures: Our Experience in Taipei Municipal Wanfang Hospital.

Background and Objectives: The study assessed the effectiveness of a fracture liaison service (FLS) after 1 year of implementation in improving the outcomes of hip fracture surgery in older adult patients at Taipei Municipal Wanfang Hospital. Materials and Methods: The Wanfang hospital's FLS program was implemented using a multipronged programmatic strategy. The aims were to encourage the screening and treatment of osteoporosis and sarcopenia, to take a stratified care approach for patients with a high risk of poor postoperative outcomes, and to offer home visits for the assessment of environmental hazards of falling, and to improve the patient's adherence to osteoporosis treatment. The clinical data of 117 and 110 patients before and after FLS commencement, respectively, were collected from a local hip fracture registry; the data were analyzed to determine the outcomes 1 year after hip fracture surgery in terms of refracture, mortality, and activities of daily living. Results: The implementation of our FLS significantly increased the osteoporosis treatment rate after hip fracture surgery from 22.8% to 72.3%, significantly decreased the 1-year refracture rate from 11.8% to 4.9%, non-significantly decreased 1-year mortality from 17.9% to 11.8%, and improved functional outcomes 1 year after hip fracture surgery. Conclusions: Implementation of our FLS using the multipronged programmatic strategy effectively improved the outcomes and care quality after hip fracture surgery in the older adult population, offering a successful example as a valuable reference for establishing FLS to improve the outcomes in vulnerable older adults.

Ursolic acid silences CYP19A1/aromatase to suppress gastric cancer growth.

INTRODUCTION: Gastric cancer (GCa) is a malignancy with few effective treatments. Ursolic acid (UA), a bioactive triterpenoid enriched in Hedyotis diffusa Willd, known to suppress GCa without identified target. CYP19A1 (cytochrome P450 family 19A1; also known as aromatase, Ar) was correlated to GCa prognosis. Relatedly, Ar silencers, which halt the expression of Ar exhibited anti-GCa effects in experimental models, are currently being investigated. METHOD: The docking simulation score of UA was compared with Ar inhibitors, e.g., letrozole, exemestane, in Ar protein crystallization. Hedyotis diffusa Willd ethanol extract, UA, or 5-fluracil were applied onto AGS, SC-M1, MKN45 GCa cells for cancer inhibition tests. Immunoblot for measuring gene expressions upon drug treatments, or gene knockdown/overexpression. Treatments were also applied in a MKN45 implantation tumor model. A web-based GCa cohort for Ar expression association with prognosis was performed. RESULT: The ethanol extracts of Hedyotis diffusa Willd, enrich with UA, exhibited cytotoxic activity against GCa cells. Molecular docking simulations with the 3D Ar structure revealed an excellent fitting score for UA. UA increase cytotoxic, and suppressed colony, in addition to its Ar silencing capacity. Moreover, UA synergistically facilitated 5-FU, (a standard GCa treatment) regimen in vitro. Consistent with those results, adding estradiol did not reverse the cancer-suppressing effects of UA, which confirmed UA acts as an Ar silencer. Furthermore, UA exhibited tumor-suppressing index (TSI) score of 90% over a 6-week treatment term when used for single dosing in xenograft tumor model. In the clinical setting, Ar expression was found to be higher in GCa tumors than normal parental tissue from the TCGA (The Cancer Genome Atlas) cohort, while high Ar expression associated with poor prognosis. Together, the results indicate UA could be used to treat GCa by silencing Ar expression in GCa. Hedyotis diffusa Willd ethanol extract could be an functional food supplements.

The Procedural and Clinical Outcomes of Rotational Atherectomy in Patients Presenting With Acute Myocardial Infarction.

Background: Rotational atherectomy (RA) is an indispensable tool used for calcified lesion preparation in percutaneous coronary intervention (PCI). However, use of RA in the setting of acute myocardial infarction (AMI) is challenged with limited clinical data. Objectives: This study aims to retrospectively investigate the procedural results, periprocedural complications, and clinical outcomes of RA in patients with AMI. Methods: All possible consecutive patients who received RA in AMI from January 2009 to March 2018 in a single tertiary center were analyzed retrospectively. Patients without AMI during the study period were also enrolled for comparison. Results: A total of 121 patients with AMI (76.0 ± 10.8 years, 63.6% males) and 290 patients without AMI were recruited. Among the AMI group, 81% of patients had non-ST-elevation myocardial infarction (NSTEMI) and 14% presented with cardiogenic shock. RA could be completed in 98.8% of patients in the AMI group and 98.3% in the non-AMI group (p = 1.00). The periprocedural complication rates were comparable between the AMI and non-AMI groups. The risks of in-hospital, 30-day, 90-day, and 1-year cardiovascular major adverse cardiac events (CV MACE) were significantly higher in the AMI group compared with the non-AMI group (in-hospital 13.2 vs. 2.8%, p < 0.001; 30-day 14.2 vs. 4.5%, p < 0.001; 90-day 20.8 vs. 6.9%, p < 0.001; 1-year 30.8 vs. 19.1%, p = 0.01). AMI at initial presentation and cardiogenic shock were predictors for both in-hospital CV MACE and 1-year CV MACE in multivariable binary logistic regression analysis. Other predictors for 1-year CV MACE included serum creatinine level and triple vessel disease. Conclusion: RA in patients with AMI is feasible with a high procedural completion rate and acceptable periprocedural complications. Given unstable hemodynamics and complex coronary anatomy, the in-hospital and 1-year MACE rates remained higher in patients with AMI compared with patients without AMI.

Rotablation in Patients with Advanced Renal Insufficiency through End-Stage Renal Disease: Short- and Intermediate-Term Results.

Objective: Patients with advanced renal insufficiency are at high risk of coronary artery disease (CAD) and complex lesions. Treating complex calcified lesion with rotational atherectomy (RA) in these patients might be associated with higher risks and poorer outcomes. This study was set to evaluate features and outcomes of RA in these patients. Method: Consecutive patients who received coronary RA from April 2010 to April 2018 were queried from the Cath Lab database. The procedural details, angiography, and clinical information were reviewed in detail. Results: A total of 411 patients were enrolled and divided into Group A (baseline serum creatinine <5 mg/dl, n = 338) and Group B (baseline serum creatinine ≥ 5 mg/dl through ESRD, n = 73). Most patients had high-risk features (65.7% of acute coronary syndrome (ACS), 14.1% of ischemic cardiomyopathy, and 5.1% of cardiogenic shock). Group B patients were significantly younger (66.8 ± 11.4 vs. 75.2 ± 10.7 years, p < 0.001) and had more RCA and LCX but less LAD treated with RA. No difference was found in lesion location, vessel tortuosity, bifurcation lesions, chronic total occlusion, total lesion length, or total lesion numbers between the two groups. Less patients in Group B obtained completion of RA (95.9% vs 99.1%, p=0.037). There was no difference in the incidence of procedural complication or acute contrast-induced nephropathy. Group B patients had more deaths and MACE while in the hospital. The MACE and CV MACE were also higher in Group B patients at 180 days and one year, mostly due to TLR and TVR. Multivariate regression analysis showed that ACS, age, peripheral artery disease (PAD), advanced renal insufficiency, ischemic cardiomyopathy/shock, and high residual SYNTAX score were independent risk factors for in-hospital MACE, whereas ACS, advanced renal insufficiency, ischemic cardiomyopathy/shock, triple-vessel disease, and PAD independently predicted MACE at 6 months. Conclusions: Rotablation is feasible, safe, and could be carried out with very high success rate in very-high-risk patients with advanced renal dysfunction through ESRD without an increase in procedural complication.

Rotational atherectomy for chronically and totally occluded coronary lesions: A propensity score-matched outcomes study.

Background: Despite advances being made in techniques and devices, certain chronic total occlusion (CTO) lesions remain uncrossable or undilatable. Rotational atherectomy (RA) is usually necessary for such lesions to achieve successful revascularization. Methods: Information regarding consecutive patients who underwent coronary RA was retrieved from the catheterization laboratory database. Patients who underwent RA for CTO lesion refractory using other conventional devices were recruited, with propensity score-matched cases serving as controls. Results: A total of 411 patients underwent coronary RA in the study period. Most patients had high-risk features (65.7% had acute coronary syndrome (ACS), 14.1% ischemic cardiomyopathy, and 5.1% cardiogenic shock), while only 20.2% of the patients had stable angina. Among them, 44 patients underwent RA for CTO lesions (CTO group), whereas the propensity score matched controls consist of 37 patients (non-CTO group). The baseline characteristics, high-risk features, coronary artery disease (CAD) vessel numbers, left ventricular function and biochemistry profiles of both groups were the same except for more patients with diabetes (67.6% vs. 45.5%, p = 0.046) in the non-CTO group and more 1.25 mm burr uses in the CTO group. There were no significant differences in acute procedural outcomes or incidence of acute contrast-induced nephropathy (CIN), and no patient demanded emergent CABG or died during the procedure. There was no significant difference in major adverse cardiovascular events (MACE), CV MACE or individual components between the two groups in the hospital, at 30, 90, and 180 days or at 1 year. Conclusion: In comparison with the propensity risk factor scores-matched controls, there was no difference in procedural complications, acute CIN or clinical outcomes during various stages of RA for CTO lesions. RA for CTO patients was highly efficient and showed safety and outcome profiles similar to those for non-CTO lesions.

Predictors of In-Hospital Mortality in Older Adults Undergoing Hip Fracture Surgery: A Case-Control Study.

Introduction: Although surgery has been proven to improve the long-term survival of older adults with hip fracture, in-hospital mortality directly resulting from repair of hip fracture is undesirable. This study aimed to identify potential prognostic factors that predict in-hospital mortality risk in elderly patients following hip fracture surgery. Materials and Methods: This case-control study comprehensively collected data from older adults with hip fracture admitted to a single medical centre. Age was selected as the cross-matching factor. Univariate and binary multivariate logistic regression models were used to estimate the odds ratios with 95% confidence intervals. A receiver operating characteristic curve was constructed to quantify the discrimination power of the model. Results: Among a total of 841 older adults who received hip fracture surgery, 17 died during hospitalisation, yielding a 2.0% in-hospital mortality rate. Using a binary multivariate logistic regression model to perform a comparison with 51 age-matched patients in survival groups, the model revealed that estimated glomerular filtration rate (eGFR) and malignant cancer history were the only 2 factors significantly correlated with in-hospital mortality. The prognostic values for the eGFR and malignant cancer history were acceptable, with areas under the curve of .76 and .67, respectively. Conclusion: The prevalence of in-hospital mortality following hip fracture is low. After adjustment for age, eGFR and malignant cancer history were identified as factors significantly correlated with in-hospital mortality. The findings of this study could assist in the early screening and detection of patients with high in-hospital mortality risks.

Add-On Selective Estrogen Receptor Modulators for Methadone Maintenance Treatment.

Methadone maintenance treatment (MMT) remains the cornerstone for the management of opiate abuse. However, MMT can be associated with complex factors, including complications during the tolerance phase, the inability of some patients to maintain treatment effects during the tapering or abstinence phases, and the development of methadone dependence. Previous studies have revealed a sex disparity in MMT efficacy, showing that women undergoing MMT experiencing an increase in psychological symptoms compared with men and suggesting a link between disparate responses and the effects of estrogen signaling on methadone metabolism. More specifically, estradiol levels are positively associated with MMT dosing, and the expression of a single-nucleotide polymorphism (SNP) associated with estrogen receptor (ER) regulation is also associated with MMT dosing. In addition to performing mechanistic dissections of estrogen signaling in the presence of methadone, past studies have also proposed the targeting of estrogen signaling during MMT. The present report provides an overview of the relevant literature regarding sex effects, including differences in sex hormones and their potential impacts on MMT regimens. Moreover, this article provides a pharmacological perspective on the targeting of estrogen signals through the use of selective ER modulators (SERMs) during MMT. Preliminary preclinical experiments were also performed to evaluate the potential effects of targeting estrogen signaling with tamoxifen on methadone metabolism.

Association of Vitamin D Deficiency with Low Serum Albumin in Taiwanese Older Adults with Hip Fracture: A Prospective Cross-Sectional Study.

The world's population is aging, and the prevalence of hip fracture is rising. Vitamin D deficiency is a risk factor for hip fracture and predicts functional recovery and survival following hip fracture surgery. This cross-sectional study identified the prevalence of vitamin D deficiency in Taiwanese older patients with hip fracture and potential risk factors for vitamin D deficiency. Data from older adults with hip fracture admitted to a single medical center in Taipei, Taiwan were prospectively collected. The preoperative serum 25-hydroxyvitamin D [25(OH)D] concentration and comprehensive clinical history of each patient were examined. A multinomial logistic regression model was used to compare the clinical characteristics of deficient, insufficient, and sufficient 25(OH)D concentration groups. The cohort comprised 310 older adults with hip fracture. The mean age was 80±10 y. The deficient, insufficient, and sufficient groups comprised 180, 84, and 46 patients (58.1%, 27.1%, and 14.8%), respectively. Univariate analysis revealed significant intergroup differences in serum albumin level and body fat percentage and marginally significant differences in serum albumin, estimated glomerular filtration rate, body mass index, and comorbidities of affective or psychotic disorders. In the multinomial logistic regression model, albumin level was the only factor significantly correlated with higher 25(OH)D concentrations in the sufficient and insufficient groups compared with the deficient group. No variable, including preinjury functional status, was significantly correlated with vitamin D deficiency except malnutrition. Our findings may aid the establishment of a robust screening and treatment program for vitamin D deficiency.

Androgen/Androgen Receptor Signaling in Ovarian Cancer: Molecular Regulation and Therapeutic Potentials.

Ovarian cancer (OVCA) arises from three cellular origins, namely surface epithelial cells, germ cells, and stromal cells. More than 85% of OVCAs are EOCs (epithelial ovarian carcinomas), which are the most lethal gynecological malignancies. Cancer stem/progenitor cells (CSPCs) are considered to be cancer promoters due to their capacity for unlimited self-renewal and drug resistance. Androgen receptor (AR) belongs to the nuclear receptor superfamily and can be activated through binding to its ligand androgens. Studies have reported an association between AR expression and EOC carcinogenesis, and AR is suggested to be involved in proliferation, migration/invasion, and stemness. In addition, alternative AR activating signals, including both ligand-dependent and ligand-independent, are involved in OVCA progression. Although some clinical trials have previously been conducted to evaluate the effects of anti-androgens in EOC, no significant results have been reported. In contrast, experimental studies evaluating the effects of anti-androgen or anti-AR reagents in AR-expressing EOC models have demonstrated positive results for suppressing disease progression. Since AR is involved in complex signaling pathways and may be expressed at various levels in OVCA, the aim of this article was to provide an overview of current studies and perspectives regarding the relevance of androgen/AR roles in OVCA.

Variants in Maternal Effect Genes and Relaxed Imprinting Control in a Special Placental Mesenchymal Dysplasia Case with Mild Trophoblast Hyperplasia.

Placental mesenchymal dysplasia (PMD) and partial hydatidiform mole (PHM) placentas share similar characteristics, such as placental overgrowth and grape-like placental tissues. Distinguishing PMD from PHM is critical because the former can result in normal birth, while the latter diagnosis will lead to artificial abortion. Aneuploidy and altered dosage of imprinted gene expression are implicated in the pathogenesis of PHM and also some of the PMD cases. Diandric triploidy is the main cause of PHM, whereas mosaic diploid androgenetic cells in the placental tissue have been associated with the formation of PMD. Here, we report a very special PMD case also presenting with trophoblast hyperplasia phenotype, which is a hallmark of PHM. This PMD placenta has a normal biparental diploid karyotype and is functionally sufficient to support normal fetal growth. We took advantage of this unique case to further dissected the potential common etiology between these two diseases. We show that the differentially methylated region (DMR) at NESP55, a secondary DMR residing in the GNAS locus, is significantly hypermethylated in the PMD placenta. Furthermore, we found heterozygous mutations in NLRP2 and homozygous variants in NLRP7 in the mother's genome. NLRP2 and NLRP7 are known maternal effect genes, and their mutation in pregnant females affects fetal development. The variants/mutations in both genes have been associated with imprinting defects in mole formation and potentially contributed to the mild abnormal imprinting observed in this case. Finally, we identified heterozygous mutations in the X-linked ATRX gene, a known maternal-zygotic imprinting regulator in the patient. Overall, our study demonstrates that PMD and PHM may share overlapping etiologies with the defective/relaxed dosage control of imprinted genes, representing two extreme ends of a spectrum.