Comparative effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies and onabotulinumtoxinA in chronic migraine: A multicenter, real-world study in Taiwan.

OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.

A simple scoring algorithm based on intrinsic capacity for functional ability in community-dwelling older adults in Taiwan.

BACKGROUND: Intrinsic capacity (IC) is a comprehensive indicator of the overall well-being of older adults, and assessing of IC can help identify early stage of disability and tailor intervention to individual needs. However, there is a lack of effective and simple IC assessment tools. This study aimed to establish predictive scoring algorithms of IC to identify older adults at high risk of impaired functional ability. METHODS: We conducted a cross-sectional study in Southern Taiwan, measuring IC using 7 subitems: cognition, locomotion, vitality, vision, hearing, psychological well-being, and medication usage were measured. Functional ability outcomes included frailty, basic activities of daily living, and instrumental activities of daily living (IADL). The capability of 7 domains of IC in predicting functional ability was assessed by multivariable logistic regression. The prediction of capability of scoring algorithms was indicated by receiver operating characteristic (AUC) curves and measures of sensitivity and specificity. RESULTS: A total of 1,152 older adults were recruited and analyzed. Locomotion emerged as a significant predictor of IADL disability and worsening frailty. The IC-based weighted scoring algorism for predicting IADL demonstrated satisfactory capability (AUC: 0.80), as did the algorithm for predicting worsening frailty (AUC: 0.90). The optimal cutoff points for predicting IADL disability and frailty worse were estimated respectively at 13 and 16, with sensitivity/specificity values of 0.74/0.75 for the IADL prediction algorithm and 0.92/0.77 for the frailty prediction algorithm. CONCLUSION: Our 7-domain IC screening tool proves to be sensitive and practical for early identification of functional disability and frailty among community-dwelling older adults in Taiwan.

Assessing intrinsic capacity in Taiwan: Initial psychometric properties of the Integrated Care for Older People Screening Tool for Taiwanese (ICOPES-TW).

BACKGROUND: The World Health Organization (WHO) proposed the concept of intrinsic capacity (comprising composite physical and mental capacity) which aligns with their concepts of healthy aging and functional ability. Consequently, the WHO promotes the Integrated Care for Older People (ICOPE) framework as guidance for geriatric care. Consequently, each government should have a screening tool corresponding to ICOPE framework to promote geriatric care. The present study examined the initial psychometric properties of the Taiwan version of ICOPE (i.e., ICOPES-TW). METHODS: Older people (n = 1235; mean age = 72.63 years; 634 females [51.3%]) were approached by well-trained interviewers for participation. A number of measures were administered including the ICOPES-TW, WHOQOL-AGE (assessing quality of life [QoL]), Clinical Frailty Scale (assessing frailty), Barthel Index (assessing basic activity of daily living [BADL]), and Lawton Instrumental Activities of Daily Living Scale (assessing instrumental activity of daily living [IADL]). RESULTS: The ICOPES-TW had a two-factor structure (body functionality [eigenvalue = 1.932] and life adaptation [eigenvalue = 1.170]) as indicated by the results of exploratory factor analysis. Internal consistency of the ICOPES-TW was low (Cronbach's α = 0.55 [entire ICOPES-TW], 0.45 (body functionality factor), and 0.52 (life adaptation factor). ICOPES-TW scores were significantly (i) positively correlated with age (r = 0.321), IADL (r = 0.313), and frailty (r = 0.601), and (ii) negatively correlated with QoL (r=-0.447), and BADL (r=-0.447), with all p-values < 0.001. CONCLUSION: The ICOPES-TW could be a useful screening tool for healthcare providers to quickly evaluate intrinsic capacity for Taiwanese older people given that it has moderate to strong associations with age, BADL, IADL, QoL, and frailty.

6-shogaol is a potential treatment for Head and Neck Squamous Cell Carcinoma.

Objective: Natural products in diet have shown a potential role in the prevention and treatment of cancer. Ginger (Zingiber officinale Roscoe) is a great candidate because of its properties of anti-inflammatory, antioxidant, and anti-cancer, but little is known about its effect on head and neck cancer. 6-Shogaol is an active compound derived from Ginger. Thus, this study aimed to investigate the possible anticancer effects of 6-shogaol, a major ginger derivate, on head and neck squamous cell carcinomas (HNSCCs) and the underlying mechanisms. Material and Methods: Two HNSCC cell lines, SCC4 and SCC25, were used in this study. Both SCC4 and SCC25 cells were kept as control or treated with 6-shogaol for 8 and 24 hours and then the cell apoptosis and cell cycle progression of treated cells were examined by PI and Annexin V-FITC double stain and flow cytometry analysis. The Cleaved caspase 3, phosphorylations of ERK1/2 and p38 kinases were examined by Western blot analysis. Results: The results showed that 6-shogaol significantly initiated the G2/M phase arrest of the cell cycle and apoptosis to inhibit the survival of both cell lines. Moreover, these responses could be regulated by ERK1/2 and p38 signaling. And, finally, we also demonstrated that 6-shogaol could enhance the cytotoxicity of cisplatin in HNSCC cells. Conclusion: Our data provided new insights to understand the potential pharmaceutical efficacy of a ginger derivate, 6-shogaol, in antagonizing HNSCC survival. The present study suggests that 6-shogaol is a potential novel candidate for anti-HNSCCs therapy.

Dihydroisotanshinone I and BMAL-SIRT1 Pathway in an In Vitro 6-OHDA-Induced Model of Parkinson's Disease.

Danshen has been widely used for the treatment of central nervous system diseases. We investigated the effect of dihydroisotanshinone I (DT), a compound extracted from Danshen, as well as the corresponding mechanisms in an in vitro-based 6-OHDA-induced Parkinson's disease (PD) model. SH-SY5Y human neuroblastoma cell lines were pretreated with 6-hydroxydopamine (6-OHDA) and challenged with DT. Subsequently, the cell viability and levels of reactive oxygen species (ROS) and caspase-3 were analyzed. The effect of DT on the 6-OHDA-treated SH-SY5Y cells and the expression of the core circadian clock genes were measured using a real-time quantitative polymerase chain reaction. Our results indicated that DT attenuated the 6-OHDA-induced cell death in the SH-SY5Y cells and suppressed ROS and caspase-3. Moreover, DT reversed both the RNA and protein levels of BMAL1 and SIRT1 in the 6-OHDA-treated SH-SY5Y cells. Additionally, the SIRT1 inhibitor attenuated the effect of DT on BMAL1 and reduced the cell viability. The DT and SIRT1 activators activated SIRT1 and BMAL1, and then reduced the death of the SH-SY5Y cells damaged by 6-OHDA. SIRT1 silencing was enhanced by DT and resulted in a BMAL1 downregulation and a reduction in cell viability. In conclusion, our investigation suggested that DT reduces cell apoptosis, including an antioxidative effect due to a reduction in ROS, and regulates the circadian genes by enhancing SIRT1 and suppressing BMAL1. DT may possess novel therapeutic potential for PD in the future, but further in vivo studies are still needed.

Clinical and Cellular Evidence of Glycyrrhiza glabra and Platycodon grandiflorus for Vocal Fold Nodules Complementary Treatment.

Vocal fold nodules (VFNs) are the most frequent cause of hoarseness. The management comprised medical, surgical and physical therapy but the effectiveness is not always satisfactory. In this study, we try to figure out an alternative treatment from our clinical experience summary. We retrospectively reviewed VFNs patients who received traditional Chinese medicine (TCM) treatments from July 2018 to August 2020 and traced their Chinese Voice Handicap Index-10 (VHI-C10) and multidimensional voice program (MDVP) analysis results. For further evaluation, we conducted an inflammatory response of porcine vocal fold epithelial (PVFE) cells with 50 ng/mL TNF-alpha. The inflamed PVFE cells were separately cultured in the aqueous extract of Glycyrrhiza glabra (G. glabra) and Platycodon grandifloras (P. grandifloras). In these VFNs patients (n = 22), the average VHI-C10 score decreased from 17.6 to 6.6 (p < 0.001). MDVP analysis revealed improvements in jitter, shimmer, noise-harmonic ratio, and GRBAS scoring system. Of the TCM prescription patterns, G. glabra and P. grandiflorus were used most frequently. In the MTT assay of PVFE cells, no adverse effects of our extracts were observed at doses of 1-200 µg/mL. Western blot analysis revealed downregulation of p65 and mitogen activated protein kinase pathway proteins. The results from both the clinical and in vitro aspects of this study revealed that the herbs G. glabra and P. grandiflorus may offer beneficial outcomes as alternative treatments for VFNs after precise diagnosis.

Comparative effectiveness of neuraminidase inhibitors in patients with influenza: A systematic review and network meta-analysis.

The aim of this study was to use a network meta-analysis (NWA) to evaluate the relative efficacy and safety of various neuraminidase inhibitors (NAIs) in reducing the duration of influenza symptoms, and thereby, informing the selection of suitable therapeutic regimens for patients with influenza. We conducted a systematic review of randomized controlled trials comparing the clinical effects of four NAIs administered to patients with influenza and placebo. Relevant studies were found in the PubMed and Cochrane databases. Unpublished studies were collected from the ClinicalTrials.gov registry and through hand searching. We carried out NWA to compare the different regimens with each other and across subgroups of age and medical status (high-risk patients). A total of 58 two-arm studies were identified. Five regimens were efficacious in reducing the time to alleviation of influenza symptoms in all populations; this efficacy was comparable. No significant improvements were seen in combination therapy groups. The mean difference in the time to alleviation of symptoms ranged from 12.78 to 19.51 h. According to the summarized mean difference and surface under the cumulative ranking curve (SUCRA), peramivir (SUCRA = 82.6%), zanamivir (SUCRA = 64%), and oseltamivir (SUCRA = 55.1%) were the three top-ranking drugs for treating influenza. Zanamivir and peramivir were the preferred pharmacologic intervention among all investigated interventions based on the calculated "value preference of SUCRA." This study is a network meta-analysis to explore the therapeutic effects of NAIs in patients with influenza. Peramivir might be the best choice for reducing the time to alleviation of symptoms.

Fear of falling as a potential complication of Ramsay Hunt syndrome in older adults: a case report.

BACKGROUND: Fear of falling (FOF) is a common and major health concern in older adults. The consequences of FOF include reduced physical performance, social activity, and health-related quality of life. Ramsay Hunt syndrome (RHS) is a herpes zoster-related facial nerve dysfunction accompanied by an erythematous vesicular rash on the ear or mouth that may complicate ipsilateral facial paralysis and otalgia, vertigo, tinnitus, hearing loss, and meningoencephalitis. However, repeated falls and subsequent FOF due to RHS have not been reported in older adults. CASE PRESENTATION: A 65-year-old woman diagnosed with RHS experienced repeated falls during hospital admission and after discharge. Despite recovery of balance and no subsequent falls, the patient presented with persistent FOF at the geriatric outpatient follow-up visit 1 year after the RHS episode. The fear sensation impaired the patient's instrumental daily activities and was confirmed by documentation of serial comprehensive geriatric assessments, especially the Timed Up and Go test scores. CONCLUSIONS: RHS may cause repeated falls and FOF, leading to impairment in daily activities and psychosocial function in older adults. Therefore, clinicians should be mindful of falls and FOF when caring for older patients with RHS and should develop multidimensional strategies for fall prevention and FOF.

Detailed risks and characteristics of postepilepsy stroke in non-traumatic adult-onset epilepsy.

BACKGROUND: Patients with epilepsy have an increased risk of stroke. However, the detailed risk and characteristics of postepilepsy stroke have not been investigated. METHODS: This study utilized the National Health Insurance Research Database in Taiwan. We classified adult patients with newly diagnosed epilepsy from 2003 to 2016 as the epilepsy cohort. Patients in the nonepilepsy cohort were selected with propensity score matching at a case-control ratio of 1:5. The incidence, hazard ratio (HR), period-specific HR, recurrent HR in the Wei-Lin-Weissfeld model, stroke severity index, complications, and mortality of all stroke, ischemic stroke (IS) and hemorrhagic stroke events in the two cohorts were analyzed. RESULTS: We enrolled 23,810 patients in the epilepsy cohort and 119,050 persons in the nonepilepsy cohort. The period-specific HRs of all stroke, IS and hemorrhagic stroke peaked immediately after epilepsy diagnosis and trended downward [Adjusted HRs of all stroke: 4.88 (3.88-6.14), 4.47 (3.50-5.70), 3.17 (2.62-3.84), 2.81 (2.27-3.48), 2.81 (2.36-3.34) and 2.33 (2.07-2.62) in 0-0.5, 0.5-1, 1-2, 2-3, 3-5 and ≥5 years after epilepsy diagnosis, respectively]. The recurrent stroke HRs in the epilepsy cohort were >1 from the first [3.06 (2.71-3.34)] to the fourth events [6.33 (1.08-37.03)]. IS events in the epilepsy cohort were associated with a younger onset age, a higher IS severity index, a higher rate of urinary tract infection, a lower in-hospital mortality, while 90-day stroke mortality was similar between the 2 cohorts. CONCLUSION: Since the increased risk of stroke in epilepsy cohort peaked immediately after epilepsy diagnosis, early implementation of prevention strategies is considered.

Ceftriaxone therapy attenuates brain trauma in rats by affecting glutamate transporters and neuroinflammation and not by its antibacterial effects.

BACKGROUND: Ceftriaxone is a ß-lactam antibiotic used to treat central nervous system infections. Whether the neuroprotective effects of ceftriaxone after TBI are mediated by attenuating neuroinflammation but not its antibacterial actions is not well established. METHODS: Anesthetized male Sprague-Dawley rats were divided into sham-operated, TBI + vehicle, and TBI + ceftriaxone groups. Ceftriaxone was intraperitoneally injected at 0, 24, and 48 h with 50 or 250 mg/kg/day after TBI. During the first 120 min after TBI, we continuously measured heart rate, arterial pressure, intracranial pressure (ICP), and cerebral perfusion pressure. The infarct volume was measured by TTC staining. Motor function was measured using the inclined plane. Glutamate transporter 1 (GLT-1), neuronal apoptosis and TNF-α expression in the perilesioned cortex were investigated using an immunofluorescence assay. Bacterial evaluation was performed by Brown and Brenn's Gram staining. These parameters above were measured at 72 h after TBI. RESULTS: Compared with the TBI + vehicle group, the TBI + ceftriaxone 250 mg/kg group showed significantly lower ICP, improved motor dysfunction, reduced body weight loss, decreased infarct volume and neuronal apoptosis, decreased TBI-induced microglial activation and TNF-α expression in microglia, and increased GLT-1 expression in neurons and microglia. However, the grades of histopathological changes of antibacterial effects are zero. CONCLUSIONS: The intraperitoneal injection of ceftriaxone with 250 mg/kg/day for three days may attenuate TBI by increasing GLT-1 expression and reducing neuroinflammation and neuronal apoptosis, thereby resulting in an improvement in functional outcomes, and this neuroprotective effect is not related to its antibacterial effects.

Neuroinflammation and Neurogenesis in Alzheimer's Disease and Potential Therapeutic Approaches.

In adult brain, new neurons are generated throughout adulthood in the subventricular zone and the dentate gyrus; this process is commonly known as adult neurogenesis. The regulation or modulation of adult neurogenesis includes various intrinsic pathways (signal transduction pathway and epigenetic or genetic modulation pathways) or extrinsic pathways (metabolic growth factor modulation, vascular, and immune system pathways). Altered neurogenesis has been identified in Alzheimer's disease (AD), in both human AD brains and AD rodent models. The exact mechanism of the dysregulation of adult neurogenesis in AD has not been completely elucidated. However, neuroinflammation has been demonstrated to alter adult neurogenesis. The presence of various inflammatory components, such as immune cells, cytokines, or chemokines, plays a role in regulating the survival, proliferation, and maturation of neural stem cells. Neuroinflammation has also been considered as a hallmark neuropathological feature of AD. In this review, we summarize current, state-of-the art perspectives on adult neurogenesis, neuroinflammation, and the relationship between these two phenomena in AD. Furthermore, we discuss the potential therapeutic approaches, focusing on the anti-inflammatory and proneurogenic interventions that have been reported in this field.

Prophylactic management for taxane-induced nail toxicity: A systematic review and meta-analysis.

OBJECTIVE: This meta-analysis was performed to assess the efficacy of cryotherapy and nail solution (NS) use in preventing nail toxicity (NT) induced by taxane-based chemotherapy. METHODS: PubMed, EMBASE, Cochrane Library and ClinicalTrials.gov registry databases were searched for relevant studies published up to December 2018. The primary outcome was taxane-induced NT. Secondary outcomes were skin toxicity (ST), time to toxicity and patient comfort. RESULTS: We reviewed three randomised control trials and six prospective studies with 708 patients. For meta-analysis, taxane-induced NT grading was compared. NT and ST were significantly lower in the cryotherapy patients than in the controls (grade 1 NT: risk ratio [RR] = 0.51, 95% confidence interval [CI] = 0.30-0.89; grade 2-3 NT: RR = 0.36, 95% CI = 0.11-1.12; total NT: RR = 0.49; 95% CI = 0.30-0.79; ST: RR = 0.46, 95% CI = 0.33-0.64). The NS-treated patients exhibited significantly lower NT than the controls. CONCLUSIONS: Nail solution-treated or cryotherapy patients exhibited lower NT incidence and severity associated with taxane-based chemotherapy than the controls. For patients who can afford and comply with NS use or cryotherapy, these measures represent effective prophylactic management for taxane-induced NT and improve their quality of life and functional statuses. Further studies are needed to establish the routine usage protocols, long-term efficacy and safety for these interventions.

Delayed Endovascular Thrombectomy in a Patient Suffering from Stroke in Progression after Intravenous Thrombolytic Therapy.

PURPOSE: Significant improvement of stroke symptoms may occur in acute stroke patients due to large artery occlusion (LAO) treated with intravenous thrombolysis (IVT). Directly proceeding with endovascular thrombectomy (EVT) would be a clinical dilemma. CASE REPORT: A 55-year-old male suddenly suffered from global aphasia and right side hemiplegia at work. Left proximal middle cerebral artery (MCA) occlusion was shown on CT angiography. After IVT, NIHSS significantly improved from 11 to 4 points. EVT was withheld due to rapidly improving symptoms and low NIHSS scores. However, stroke in progression occurred 7 hours after onset with NIHSS scores increasing from 4 to 13 points. A follow-up brain CT scan showed an Alberta Stroke Program Early CT score of 9 and no hemorrhage. Successful recanalization of the left MCA by EVT was performed at 10.5 hours after onset. The patient was discharged with a NIHSS score of 3 and his modified Rankin Scale score was 0 at 3 months. CONCLUSION: In LAO patients, directly proceeding EVT following IVT may not be hesitated. In addition, while LAO patients with incomplete IV-tPA treatment responses result in transient improvement of neurological symptoms but later reversed, EVT may be a potential rescue therapy in carefully selected patients.

Diffusion-weighted imaging as an aid in the diagnosis of the etiology of medial longitudinal fasciculus syndrome.

PURPOSE: Internuclear ophthalmoplegia is caused by a lesion; stroke, multiple sclerosis, brain metastases, or trauma may produce lesions of the medial longitudinal fasciculus (MLF). Imaging techniques, such as DWI, can help identify the site of the lesion in order to speed diagnosis and lead to appropriate treatment. METHODS: Over an 8-month period, eight consecutive patients with suspected MLF syndrome (most secondary to ischemic stroke) underwent MRI examinations, including DWI sequencing, at an academic center in Taiwan. RESULTS: In all eight patients, abnormal high-signal lesions were found close to the floor of the fourth ventricle on the dorsal side of the pons. A neuroanatomical comparison showed that the location of the lesions was identical to the anatomical position of the MLF. CONCLUSION: Using DWI, good clinico-radiological correlation was found in all eight ischemic stroke patients diagnosed with MLF syndrome. DWI may broaden the application of MRI in the diagnosis of MLF syndrome.

[Developing and testing the validity and reliability of the Chinese version attitudes toward mental illness scale in a sample of senior high school students].

BACKGROUND: Public attitudes toward mental illness influence the success with which patients reenter the community. An attitude instrument suitable to the Chinese cultural setting with good reliability and validity is essential to examining public attitudes toward mental illness. Exploring the perspectives of adolescents is relevant because most mental illness occurs during adolescence. PURPOSE: This study developed and tested the psychometric quality of the Chinese-version Attitudes Toward Mental Illness (CAMI) scale among senior high school students. METHODS: The original AMI was translated into Chinese using a back and forth translation method and its content validity was examined. A cross-sectional survey of 479 senior high school students was conducted to assess the construct validity, cross validity, and internal consistency of the CAMI. RESULTS: The CAMI showed adequate content validity. The confirmatory factor analysis support: the appropriateness of CAMI's original two-factor structure of negative attitude and recovery outcomes after deleting items 9 and 11; the measurement of the negative perceptions of mentally ill patients and their risks to community; and the perceptions of recovery of mentally ill patients. The construct validity and cross validity are appropriate and the internal consistency of the total scale and two subscales are acceptable (Cronbach's α: .76, .75, .81). CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The reliability and validity of the CAMI is appropriate for the sample of senior high students in this study. Future studies should target a broader range of people in order to establish the reliability and validity of the scale in different groups and to build up empirical knowledge on public attitudes toward mental illness. The application of this scale is expected to contribute to the development of anti-stigma interventions and to the creation of friendly communities for mentally ill patients.

Efficacy and safety of adjuvant therapies in older patients with breast cancer: a systematic review and meta-analysis of real-world data.

BACKGROUND: Insufficient data available for older patients with breast cancer complicates decision-making regarding optimal treatment. A systematic review that uses real-world data is required for assessing the effectiveness and potential adverse effects of various therapies for this age group of patients. METHODS: Databases of PubMed, Embase, and Cochrane Library were searched. We included clinical studies that evaluated various treatments for geriatric breast cancer, including adjuvant radiation therapy, hypofractionated radiation therapy (hypo-RT) and accelerated and partial breast irradiation (APBI), endocrine therapy, chemotherapy, and targeted therapy. RESULTS: A total of 71 studies were retrieved. Adjuvant radiation therapy significantly improved overall survival (OS) compared with no radiation [hazard ratio (HR) = 0.60, 95% confidence interval (CI) 0.54-0.67]. The pooled estimates of OS for hypo-RT and APBI demonstrated no inferiority compared with conventional radiation. Both endocrine treatment (HR = 0.63, 95% CI 0.43-0.92) and chemotherapy (HR = 0.76, 95% CI 0.65-0.88) significantly increased OS compared with no treatment. Trastuzumab monotherapy significantly enhanced OS compared with no trastuzumab use (HR = 0.23, 95% CI 0.07-0.73). CONCLUSION: Despite concerns about potential complications during treatment in older patients, proactive therapies significantly increase their survival rates. For patients who are frailer, hypo-RT and APBI offer survival rates comparable to traditional modalities. Additionally, targeted therapy as a monotherapy holds promise as a viable option for patients with HER2-positive breast cancer who cannot undergo chemotherapy. Therefore, by conducting thorough general assessments and clinical evaluations, the side effects of postoperative treatments can be effectively managed.

Association of intrinsic capacity and medication non-adherence among older adults with non-communicable diseases in Taiwan.

OBJECTIVES: Medication non-adherence among older adults with non-communicable diseases (NCDs) remains prevalent worldwide, which causes hospitalization and mortality. Our study aimed to examine the association of medication non-adherence with level of overall intrinsic capacity (IC), pattern of IC, and specific IC component among older adults with NCDs. METHODS: A cross-sectional questionnaire-based survey of 1268 older adults aged 60 years and above was conducted in 2022 in southern Taiwan. Among them, 894 suffered from 1 more NCD were included in this study. The Integrated Care for Older People Screening Tool for Taiwanese and the Adherence to Refills and Medication Scale were used to assess IC and medication non-adherence, respectively. Latent class analysis (LCA) was used to identify patterns of IC impairment, and binary logistic regression was used to assess the association between medication non-adherence and IC. RESULTS: Older adults in the moderate (score: 1-2) or low (score≧3) overall IC groups were more likely to experience medication non-adherence (moderate: adjusted odds ratio (aOR) 1.57 [95% CI: 1.05-2.36]; low: 2.26 [1.40-3.67]). The "physical and nutritional impairments accompanied by depressive symptoms" group was associated with statistically higher odds of medication non-adherence (aOR 1.66 [1.01-2.73]). Older adults with cognitive impairment, hearing loss, or depressive symptoms showed greater likelihood of medication non-adherence (cognitive impairment: aOR 1.53 [1.03-2.27]; hearing loss: aOR 1.57 [1.03-2.37]; depressive symptoms: aOR 1.81 [1.17-2.80]). CONCLUSIONS: Intervention for improving medication non-adherence among older adults with NCDs should consider IC.

Blockade of reactive oxygen species and Akt activation is critical for anti-inflammation and growth inhibition of metformin in phosphatase and tensin homolog-deficient RAW264.7 cells.

CONTEXT: Metformin is widely used for treatment of type 2 diabetes and has a potential application on the treatment of inflammation and cancer. Phosphatase and tensin homolog (PTEN) plays a critical role in cancer cell growth and inflammation; however, precise mechanisms remain unclear. OBJECTIVE: We aimed to investigate the possible mechanisms of how PTEN regulates metformin against cell growth and inflammation. MATERIALS AND METHODS: We established PTEN knockdown in RAW264.7 murine macrophages (shPTEN cells) to detect inflammatory mediators using commercial kits, production of reactive oxygen species (ROS) by flow cytometry, cell growth by MTT assay and phosphorylated levels of signal molecules by western blot. RESULTS: The shPTEN cells had a significant large amount of inflammatory mediators, such as inducible nitric oxide synthase (iNOS)/nitric oxide (NO) and cyclooxygenase-2 (COX-2)/prostaglandin E(2) (PGE(2)); and also elevated the production of ROS and increased cell proliferation. These effects were accompanied with the activation of Akt and p38 mitogen-activated protein kinase (MAPK), and the inactivation of an AMP-activated protein kinase (AMPK) activator and extracellular signal-regulated kinase 1/2. Pretreatment with metformin not only blocked these inflammatory mediators, but also caused growth inhibition induced by significant apoptosis. Furthermore, inactivation of Akt, blockade of ROS generation and independence of activations of AMPK and MAPK by metformin were also observed. CONCLUSION: Macrophages with PTEN deficiency developed a continuous inflammatory microenvironment, which further aggravated tumor cell growth. Moreover, metformin affected PTEN-deficient cells dependent of inhibition of ROS production and Akt activation against enlarged inflammatory mediators and/or cell growth in shPTEN cells.

The Association between Ankle-Brachial Index/Pulse Wave Velocity and Cerebral Large and Small Vessel Diseases in Stroke Patients.

(1) Background: The study investigated whether the ankle-brachial index (ABI) and pulse wave velocity (baPWV) could reflect the severity of small vessel disease (SVD) and large artery atherosclerosis (LAA). (2) Methods: A total of 956 consecutive patients diagnosed with ischemic stroke were prospectively enrolled from July 2016 to December 2017. SVD severity and LAA stenosis grades were evaluated via magnetic resonance imaging and carotid duplex ultrasonography. Correlation coefficients were calculated between the ABI/baPWV and measurement values. Multinomial logistic regression analysis was performed to determine predictive potential. (3) Results: Among the 820 patients included in the final analysis, the stenosis grade of extracranial and intracranial vessels was inversely correlated with the ABI (p < 0.001, respectively) and positively correlated with the baPWV (p < 0.001 and p = 0.004, respectively). Abnormal ABI, not baPWV, independently predicted the presence of moderate (adjusted odds ratio, aOR: 2.18, 95% CI: 1.31-3.63) to severe (aOR: 5.59, 95% CI: 2.21-14.13) extracranial vessel stenosis and intracranial vessel stenosis (aOR: 1.89, 95% CI: 1.15-3.11). Neither the ABI nor baPWV was independently associated with SVD severity. (4) Conclusions: ABI is better than baPWV in screening for and identifying the existence of cerebral large vessel disease, but neither test is a good predictor of cerebral SVD severity.

Association between sleep health and intrinsic capacity among older adults in Taiwan.

Although the association between poor sleep quality and frailty has been previously reported, the relationship between sleep health and intrinsic capacity (IC) remains largely unknown. We aimed to examine the association between sleep health and IC among older adults. This was a cross-sectional study, and 1268 eligible participants completed a questionnaire collecting information on demographic, socioeconomic, lifestyle, sleep health, and IC. Sleep health was measured by the RU-SATED V2.0 scale. High, moderate, and low levels of IC were defined using the Integrated Care for Older People Screening Tool for Taiwanese. The ordinal logistic regression model estimated the odds ratio and corresponding 95% confidence interval. Low IC was significantly associated with age of 80 years or above, female, currently unmarried, uneducated, currently not working, financially dependent, and having emotional disorders. A one-point increase in sleep health was significantly associated with a 9% reduction in the odds of poor IC. An increase in daytime alertness was related to the greatest reduction in poor IC (aOR, 0.64; 95% CI, 0.52-0.79). In addition, the subitems sleep regularity (aOR, 0.77; 95% CI, 0.60-0.99), sleep timing (aOR, 0.80; 95% CI, 0.65-0.99), and sleep duration (aOR, 0.77; 95% CI, 0.61-0.96) were associated with a reduced OR of poor IC but with marginal statistical significance. Our findings showed that sleep health across multiple dimensions is related to IC, particularly daytime alertness in older adults. We suggest developing interventions to improve sleep health and prevent IC decline, which is crucial in causing poor health outcomes.