Potential of Cellular Therapy for ALS: Current Strategies and Future Prospects

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive upper and lower motor neuron (MN) degeneration with unclear pathology. The worldwide prevalence of ALS is approximately 4.42 per 100,000 populations, and death occurs within 3–5 years after diagnosis. However, no effective therapeutic modality for ALS is currently available. In recent years, cellular therapy has shown considerable therapeutic potential because it exerts immunomodulatory effects and protects the MN circuit. However, the safety and efficacy of cellular therapy in ALS are still under debate. In this review, we summarize the current progress in cellular therapy for ALS. The underlying mechanism, current clinical trials, and the pros and cons of cellular therapy using different types of cell are discussed. In addition, clinical studies of mesenchymal stem cells (MSCs) in ALS are highlighted. The summarized findings of this review can facilitate the future clinical application of precision medicine using cellular therapy in ALS

Clinical features and outcome of sporadic serogroup W135 disease Taiwan

BACKGROUND: Few published reports have evaluated the clinical features and outcome of serogroup W135 meningococcal disease. In Taiwan, W135 is the second most prevalent meningococcal disease serogroup. METHOD: A nationwide study was conducted to retrospectively analyze epidemiologic data from 115 patients with laboratory confirmed meningococcal disease that occurred from 2001 through 2003. RESULTS: Serogroup W135 accounted for 26% of all cases and most (76.7%) were older than 20 years. There were no cases of serogroup W135 meningococcal disease associated with Hajj pilgrims, and all cases were sporadic. In 88 patients with complete case records, we compared the presenting symptoms, signs, laboratory data, and outcomes between W135 and non-W135 patients. There were no differences in presenting symptoms except for the higher prevalence of pneumonia found in W135 patients (23.8% vs. 1.5%; OR: 20.6; 95%CI: 2.3–189.0; p = 0.003). The distribution of inflammatory cells in CSF in patients with meningitis was also different between W135 and non-W135 patients. W135 patients had a trend toward more intubations and shock but it did not achieve statistical significance. In multivariate analysis of factors associated with death, three independent factors were found: bacteremia without meningitis, altered mental status, and petechiae or purpura on admission. CONCLUSION: Sporadic serogroup W135 meningococcal disease is an important component of the meningococcal disease burden in Taiwan, but it is not directly associated with Hajj pilgrims. Compared with patients infected by other serogroups of meningococci, patients with serogroup W135 were older and more likely to have extrameningeal involvement such as pneumonia

Extremity Exercise Program in Breast Cancer Survivors Suffering from Chemotherapy-Induced Peripheral Neuropathy: A Feasibility Pilot Study

Objectives: To evaluate the feasibility of implementation of an extremity exercise program and to examine its preliminary effects in breast cancer survivors suffering from chemotherapy-induced peripheral neuropathy (CIPN). Sample & Setting: Thirteen breast cancer survivors from one hospital in northern Taiwan. Methods and Variables: A single group with repeated measures, and a quasi-experimental design. The intervention program was a four week, home-based extremity exercise program that was comprised of 10 skilled hand exercises and Buerger-Allen exercises. The Total Neuropathy Scale (clinical version), Functional Assessment of Cancer Therapy/Gynecologic Oncology Group, Neurotoxicity (13-Item Version), Identification Pain Questionnaire, and pain Visual Analogue Scale were used to measure CIPN before exercise (T1), during (T2~T4), and after exercise (T5). Qualitative data were also collected at each time point. Data were analyzed by using descriptive statistics, generalized estimating equations, and directed content analysis. Results: None of the participants reported adverse events during the study period. The extremity exercise program significantly improved patient-reported CIPN after intervention at T4 or T5 but was insignificant on clinician-assessed CIPN. The qualitative data of participant experience indicated that this program is feasible and easy to follow. Conclusion: The extremity exercise program is feasible but needs to increase the sample size and prolong the intervention period for confirmation

Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+ cells remain unclear. Initially, HNSCC-ALDH1+ cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+ cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression property ALDH1− cells to that of ALDH1+ cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+ cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1− cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+ cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+ cells

Effects of and satisfaction with short message service reminders for patient medication adherence: a randomized controlled study

BACKGROUND: Medication adherence is critical for patient treatment. This study involved evaluating how implementing Short Message Service (SMS) reminders affected patient medication adherence and related factors. METHODS: We used a structured questionnaire to survey outpatients at three medical centers. Patients aged 20 years and older who were prescribed more than 7 days of a prescription medication were randomized into SMS intervention or control groups. The intervention group received daily messages reminding them of aspects regarding taking their medication; the control group received no messages. A phone follow-up was performed to assess outcomes after 8 days. Data were collected from 763 participants in the intervention group and 435 participants in the control group. RESULTS: After participants in the intervention group received SMS reminders to take medication or those in the control group received no messages, incidences of delayed doses were decreased by 46.4 and 78.8% for those in the control and intervention groups, respectively. The rate of missed doses was decreased by 90.1% for participants in the intervention group and 61.1% for those in the control group. We applied logistic regression analysis and determined that participants in the intervention group had a 3.2-fold higher probability of having a decrease in delayed doses compared with participants in the control group. Participants in the intervention group also showed a 2.2-fold higher probability of having a decrease in missed doses compared with participants in the control group. CONCLUSIONS: Use of SMS significantly affected the rates of taking medicine on schedule. Therefore, daily SMS could be useful for reminding patients to take their medicine on schedule

Induction of Apoptosis by Luteolin Involving Akt Inactivation in Human 786-O Renal Cell Carcinoma Cells

There is a growing interest in the health-promoting effects of natural substances obtained from plants. Although luteolin has been identified as a potential therapeutic and preventive agent for cancer because of its potent cancer cell-killing activity, the molecular mechanisms have not been well elucidated. This study provides evidence of an alternative target for luteolin and sheds light on the mechanism of its physiological benefits. Treatment of 786-O renal cell carcinoma (RCC) cells (as well as A498 and ACHN) with luteolin caused cell apoptosis and death. This cytotoxicity was caused by the downregulation of Akt and resultant upregulation of apoptosis signal-regulating kinase-1 (Ask1), p38, and c-Jun N-terminal kinase (JNK) activities, probably via protein phosphatase 2A (PP2A) activation. In addition to being a concurrent substrate of caspases and event of cell death, heat shock protein-90 (HSP90) cleavage might also play a role in driving further cellular alterations and cell death, at least in part, involving an Akt-related mechanism. Due to the high expression of HSP90 and Akt-related molecules in RCC and other cancer cells, our findings suggest that PP2A activation might work in concert with HSP90 cleavage to inactivate Akt and lead to a vicious caspase-dependent apoptotic cycle in luteolin-treated 786-O cells

Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis

BackgroundBreast cancer is the most common cancer type that affects women. In hormone receptor–positive (HR+), human epidermal growth factor receptor 2−negative (HER2–) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population.MethodologyThis is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment.ResultsPIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR−/HER2+ subtype and 42% of patients with HR+/HER2– postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2– premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort.ConclusionA high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes

Benchmarking of eight recurrent neural network variants for breath phase and adventitious sound detection on a self-developed open-access lung sound database-HF_Lung_V1

A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchi labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests for long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.Comment: 48 pages, 8 figures. To be submitte