Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results.

GRN mutations cause progranulin haploinsufficiency, which eventually leads to frontotemporal dementia (FTD-GRN). PR006 is an investigational gene therapy delivering the granulin gene (GRN) using an adeno-associated virus serotype 9 (AAV9) vector. In non-clinical studies, PR006 transduced neurons derived from induced pluripotent stem cells of patients with FTD-GRN, resulted in progranulin expression and improvement of lipofuscin, lysosomal and neuroinflammation pathologies in Grn-knockout mice, and was well tolerated except for minimal, asymptomatic dorsal root ganglionopathy in non-human primates. We initiated a first-in-human phase 1/2 open-label trial. Here we report results of a pre-specified interim analysis triggered with the last treated patient of the low-dose cohort (n = 6) reaching the 12-month follow-up timepoint. We also include preliminary data from the mid-dose cohort (n = 7). Primary endpoints were safety, immunogenicity and change in progranulin levels in cerebrospinal fluid (CSF) and blood. Secondary endpoints were Clinical Dementia Rating (CDR) plus National Alzheimer's Disease Coordinating Center (NACC) Frontotemporal Lobar Degeneration (FTLD) rating scale and levels of neurofilament light chain (NfL). One-time administration of PR006 into the cisterna magna was generally safe and well tolerated. All patients developed treatment-emergent anti-AAV9 antibodies in the CSF, but none developed anti-progranulin antibodies. CSF pleocytosis was the most common PR006-related adverse event. Twelve serious adverse events occurred, mostly unrelated to PR006. Deep vein thrombosis developed in three patients. There was one death (unrelated) occurring 18 months after treatment. CSF progranulin increased after PR006 treatment in all patients; blood progranulin increased in most patients but only transiently. NfL levels transiently increased after PR006 treatment, likely reflecting dorsal root ganglia toxicity. Progression rates, based on the CDR scale, were within the broad ranges reported for patients with FTD. These data provide preliminary insights into the safety and bioactivity of PR006. Longer follow-up and additional studies are needed to confirm the safety and potential efficacy of PR006. ClinicalTrials.gov identifier: NCT04408625 .

Shock index to predict outcomes in patients with trauma following traffic collisions: a retrospective cohort study.

PURPOSE: Taiwan, which has a rate of high vehicle ownership, faces significant challenges in managing trauma caused by traffic collisions. In Taiwan, traffic collisions contribute significantly to morbidity and mortality, with a high incidence of severe bleeding trauma. The shock index (SI) and the modified shock index (MSI) have been proposed as early indicators of hemodynamic instability. In this study, we aimed to assess the efficacy of SI and MSI in predicting adverse outcomes in patients with trauma following traffic collisions. METHODS: This retrospective cohort study was conducted at Chi Mei Hospital from January 2015 to December 2020. The comprehensive analysis included 662 patients, with data collected on vital signs and outcomes such as mortality, blood transfusion, emergent surgical intervention (ESI), transarterial embolization (TAE), and intensive care unit (ICU) admission. Optimal cutoff points for SI and MSI were identified by calculating the Youden index. Logistic regression analysis was used to assess outcomes, adjusting for demographic and injury severity variables. RESULTS: An SI threshold of 1.11 was associated with an increased risk of mortality, while an SI of 0.84 predicted the need for blood transfusion in the context of traffic collisions. Both SI and MSI demonstrated high predictive power for mortality and blood transfusion, with acceptable accuracy for TAE, ESI, and ICU admission. Logistic regression analyses confirmed the independence of SI and MSI as risk factors for adverse outcomes, thus, providing valuable insights into their clinical utility. CONCLUSIONS: SI and MSI are valuable tools for predicting mortality and blood transfusion needs in patients with trauma due to traffic collisions. These findings advance the quality of care for patients with trauma during their transition from the emergency room to the ICU, facilitating prompt and reliable decision-making processes and improving the care of patients with trauma.

Linear interaction between replication and transcription shapes DNA break dynamics at recurrent DNA break Clusters.

Recurrent DNA break clusters (RDCs) are replication-transcription collision hotspots; many are unique to neural progenitor cells. Through high-resolution replication sequencing and a capture-ligation assay in mouse neural progenitor cells experiencing replication stress, we unravel the replication features dictating RDC location and orientation. Most RDCs occur at the replication forks traversing timing transition regions (TTRs), where sparse replication origins connect unidirectional forks. Leftward-moving forks generate telomere-connected DNA double-strand breaks (DSBs), while rightward-moving forks lead to centromere-connected DSBs. Strand-specific mapping for DNA-bound RNA reveals co-transcriptional dual-strand DNA:RNA hybrids present at a higher density in RDC than in other actively transcribed long genes. In addition, mapping RNA polymerase activity uncovers that head-to-head interactions between replication and transcription machinery result in 60% DSB contribution to the head-on compared to 40% for co-directional. Taken together we reveal TTR as a fragile class and show how the linear interaction between transcription and replication impacts genome stability.

Nattokinase attenuates endothelial inflammation through the activation of SRF and THBS1.

Natto contains a potent fibrinolytic enzyme called nattokinase (NK), which has thrombolytic, antihypertensive, antiatherosclerotic and lipid-lowering effects. Although NK has been recognized for its beneficial effect on humans with atherosclerotic cardiovascular disease (ASCVD), the underlying mechanisms involved in vascular inflammation-atherosclerosis development remain largely unknown. The current study aimed to explore the effects of NK on gene regulation, autophagy, necroptosis and inflammasome in vascular inflammation. The transcriptional profiles of NK in endothelial cells (ECs) by RNA sequencing (RNA-seq) revealed that NK affected THBS1, SRF and SREBF1 mRNA expression. In Q-PCR analysis, SRF and THBS1 were upregulated but SREBF1 was unaffected in ECs treated with NK. NK treatment induced autophagy and inhibited NLRP3 inflammasome and necroptosis in ECs. Furthermore, the inhibition of SRF or THBS1 by siRNA suppressed autophagy and enhanced the NLRP3 inflammasome and necroptosis. In a mouse model, NK reduced vascular inflammation by activating autophagy and inhibiting NLRP3 inflammasome and necroptosis. Our findings provide the first evidence that NK upregulates SRF and THBS1 genes, subsequently increasing autophagy and decreasing necroptosis and NLRP3 inflammasome formation to reduce vascular inflammation. Therefore, NK could serve as nutraceuticals or adjuvant therapies to reduce vascular inflammation and possible atherosclerosis progression.

Mitochondrial Dysfunction in Chronic Obstructive Pulmonary Disease: Unraveling the Molecular Nexus.

Chronic obstructive pulmonary disease (COPD) is a prevalent and debilitating respiratory disorder characterized by persistent airflow limitation and chronic inflammation. In recent years, the role of mitochondrial dysfunction in COPD pathogenesis has emerged as a focal point of investigation. This review endeavors to unravel the molecular nexus between mitochondrial dysfunction and COPD, delving into the intricate interplay of oxidative stress, bioenergetic impairment, mitochondrial genetics, and downstream cellular consequences. Oxidative stress, a consequence of mitochondrial dysfunction, is explored as a driving force behind inflammation, exacerbating the intricate cascade of events leading to COPD progression. Bioenergetic impairment sheds light on the systemic consequences of mitochondrial dysfunction, impacting cellular functions and contributing to the overall energy imbalance observed in COPD patients. This review navigates through the genetic landscape, elucidating the role of mitochondrial DNA mutations, variations, and haplogroups in COPD susceptibility and severity. Cellular consequences, including apoptosis, autophagy, and cellular senescence, are examined, providing insights into the intricate mechanisms by which mitochondrial dysfunction influences COPD pathology. Therapeutic implications, spanning antioxidant strategies, mitochondria-targeted compounds, and lifestyle modifications, are discussed in the context of translational research. Important future directions include identifying novel biomarkers, advancing mitochondria-targeted therapies, and embracing patient-centric approaches to redefine COPD management. This abstract provides a comprehensive overview of our review, offering a roadmap for understanding and addressing the molecular nexus between mitochondrial dysfunction and COPD, with potential implications for precision medicine and improved patient outcomes.

Sleep Quality and Associated Factors Among Survivors of Breast Cancer: From Diagnosis to One Year Postdiagnosis.

OBJECTIVES: To examine sleep quality and self-reported causes of sleep disturbance among patients with breast cancer at diagnosis and one year later. SAMPLE & SETTING: 486 of 606 patients with histologically confirmed breast cancer completed a Pittsburgh Quality Sleep Index (PSQI) survey at the time of diagnosis and again one year later. METHODS & VARIABLES: In this secondary data analysis, descriptive statistics were computed for seven PSQI components and its global score. Wilcoxon signed-rank tests and McNemar's tests were used. Self-reported reasons for sleep disturbances were summarized. RESULTS: PSQI scores significantly increased from baseline (mean = 6.75) to one-year follow-up (mean= 7.12), indicating worsened sleep. Sleep disturbance and onset latency scores increased, whereas sleep efficiency decreased. The two most frequently reported reasons for sleep disturbance were waking up late in the night or early in the morning (more than 50%) and needing to use the bathroom (49%). Feeling too hot and experiencing pain three or more times per week were reported by participants at baseline and one year later. IMPLICATIONS FOR NURSING: Results can aid in monitoring patient response to treatment methods and formulating benchmarks to manage sleep problems.

Investigation of organic contaminants in the blubber of a blue whale (Balaenoptera musculus) first stranded on the coast of Taiwan.

This study presents a comprehensive assessment of persistent organic pollutants (POPs) in the blubber of a stranded blue whale found on the coast of Taiwan. The analysis included polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane (DDT), Hexachlorobenzene (HCB), and polybrominated diphenyl ethers (PBDEs). The whale exhibited evident signs of emaciation, including low body weight, reduced blubber fat content, and thin blubber thickness. The dominant fatty acid type detected in the blubber was short-chain monounsaturated fatty acids (SC-MUFA), known to aid in thermoregulation. Stable isotope ratios indicated that the blue whale occupied a lower trophic position compared to a fin whale, suggesting its proximity to krill habitats in the Southern Ocean for feeding. The average concentrations of DDTs (1089.2 ± 4.7 ng/g lw; ΣDDT) and PCBs (1057.1 ± 49.8 ng/g lw) in the blubber were almost one order of magnitude higher than PAHs (41.7 ± 10.0 ng/g lw), HCB (70.6 ± 2. ng/g lw), and PBDEs (7.2 ± 1.2 ng/g lw). Pollutant concentrations in this individual blue whale were comparable to levels found in Norway, higher than those found in Chile, and notably lower than those found in Canada and Mexico. Calculating the biomagnification factor (BMF) for the POPs from krill (Euphausia superba) to the blue whale revealed significant bioaccumulation of pollutants in this particular whale. Additional research is imperative to achieve a thorough comprehension of bioaccumulation of POPs and their potential toxicological impacts on whale health.

Disease-modifying therapies for diabetic peripheral neuropathy: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Alpha-lipoic acid, epalrestat, and mecobalamin are widely used as monotherapies for diabetic peripheral neuropathy. However, whether a triple-combination therapy with these three drugs is superior to monotherapy or dual therapy remains debatable. METHODS: Nine randomized controlled trials were identified through a search on electronic databases such as PubMed, Web of Science, and Cochrane Library. The trial participants (N = 1153) were divided into the experimental group who received the triple-combination therapy and the control group who received conventional or dual therapy with the aforementioned drugs. RESULTS: Therapeutic outcomes were better in the experimental group than in the control group (odds ratio: 3.74; 95 % confidence interval: 2.57-5.45; I2 = 0 %; p < 0.00001). No statistic difference was noted in adverse effects. Compared with the control group, the experimental group exhibited significant improvements in median motor nerve conduction velocity (MNCV), sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and vibration perception thresholds (VPT) in the left and right lower limbs. In the control group, a subgroup analysis by treatment strategy revealed similar improvements in total efficacy, MNCV, and SNCV. CONCLUSIONS: For diabetic peripheral neuropathy, the triple-combination therapy may be more effective than monotherapy or dual therapy.

Nurse-led intervention to improve oral mucosal health of intubated patients in the intensive care unit: A prospective study.

BACKGROUND: This prospective study aimed to explore the effectiveness of an oral care intervention with Tegaderm on the oral mucosal health of intubated patients. METHODS: A total of 70 intubated patients were included and randomly assigned to 1 of 3 groups, clean water brushing teeth (n = 23), brushing teeth combined with mouthwash (BTM) (n = 23), and brushing teeth combined with mouthwash and Tegaderm (BTMT) (n = 24). The Oral Mucositis Assessment Scale (OMAS) was applied to evaluate the patient's oral mucosal health before and after oral care intervention. RESULTS: The BTMT group had lower OMAS scores in almost all regions of the oral cavity, compared to the brushing teeth and BTM groups. The general linear model for repeated measurement indicated the BTMT group had the lowest total OMAS scores from Day 2 to Day 4 after the initiation of baseline OMAS evaluation. Of the 3 intervention groups, the BTMT group had the shortest length of endotracheal intubation. The BTMT group had the lowest incidence rate of ventilator-associated pneumonia; however, no significant between-group differences were found. CONCLUSIONS: BTMT effectively reduced the decline in oral mucosal health that was caused by endotracheal intubation and shortened the length of endotracheal intubation.

Evaluating Social Determinants of Health Related to Cancer Survivorship and Quality of Care.

BACKGROUND: Social determinants of health posit that negative outcomes are influenced by individuals living in underserved and underresourced neighborhoods. OBJECTIVE: This study examines a cancer diagnosis, race/ethnicity, age, geographic location (residence), education, and social economic status factors at disease onset and treatment. METHODS: A multivariable PO regression analysis was run for quality of care at testing or diagnosis, and quality of care at treatment and the quality of received care compared with another person. RESULTS: Participants are representative of the Southern Community Cohort Study (SCCS) of adults diagnosed with breast (n = 263), prostate (n = 195), lung (n = 46), colorectal (n = 105), or other cancers (n = 526). This study includes cancer survivors who completed the SCCS Baseline and Cancer Navigation Surveys in urban (73.13%) and rural (26.87%) areas. White participants reported a higher quality of received care for testing or diagnosis and care for treatment compared with Black participants. Participants with high school or equivalent education (odds ratio, 1.662; 95% confidence interval, 1.172-2.356; P = .0044) or some college or junior college education (odds ratio, 1.970; 95% confidence interval, 1.348-2.879; P = .0005) were more likely to report a better level of quality of received care for treatment. CONCLUSIONS: The SCCS represents individuals who are historically underrepresented in cancer research. The results of this study will have broad implications across diverse communities to reduce disparities and inform models of care. IMPLICATIONS FOR PRACTICE: Nurses are positioned to evaluate the quality of population health and design and lead interventions that will benefit underserved and underresourced communities.

The Benefit of Hydrogen Gas as an Adjunctive Therapy for Chronic Obstructive Pulmonary Disease.

Background and Objectives: Recent studies suggest that hydrogen gas possesses anti-inflammatory, antioxidant, and anti-apoptotic properties. This study aimed to explore the therapeutic potential of hydrogen gas and assess its safety and tolerability in individuals with chronic obstructive pulmonary disease (COPD). Materials and Methods: Enrolled COPD patients received standard treatments along with additional hydrogen inhalation for 30 min in the morning, afternoon, and evening over a 30-day period. The assessment included changes in the COPD Assessment Test (CAT), the modified Medical Research Council (mMRC) Dyspnea Scale, lung function, sleep quality, inflammation markers, and oxidative stress markers before and after hydrogen inhalation. Results: Six patients participated in this study. Patients 2, 3, 4, 5, and 6 demonstrated improvements in CAT scores following hydrogen gas intervention, with patients 2, 4, 5, and 6 also showing improvements in mMRC scores. Statistically, this study revealed significant improvements in CAT [15.5 (10.5-19.75) vs. 8.5 (3-13.5); p = 0.043] and mMRC scores [2.5 (1-4) vs. 2 (0-3.25); p = 0.046] before and after intervention, respectively. However, no significant differences were observed in lung function, DLCO, sleep quality, and 6 MWT before and after hydrogen therapy. CBC examination showed a significant difference in platelet count before and after treatment [247 (209.75-298.75) vs. 260 (232.75-314.5); p = 0.043], respectively, while other blood tests, inflammation markers, and oxidative stress markers did not exhibit significant differences before and after hydrogen therapy. All patients experienced no obvious side-effects. Conclusions: Adjuvant therapy with hydrogen gas demonstrated symptom improvements in specific COPD patients, and no significant adverse effects were observed in any of the patients. Hydrogen gas may also exert a modulatory effect on platelet count.

How Long After Coronary Artery Bypass Surgery Can Patients Have Elective Safer Non-Cardiac Surgery?

Objective: To evaluate the complications and mortality after noncardiac surgeries in patients who underwent previous coronary artery bypass grafting (CABG). Methods: We used insurance data and identified patients aged ≥20 years undergoing noncardiac surgeries between 2010 and 2017 in Taiwan. Based on propensity-score matching, we selected an adequate number of patients with a previous history of CABG (within preoperative 24 months) and those who did not have a CABG history, and both groups had balanced baseline characteristics. The association of CABG with the risk of postoperative complications and mortality was estimated (odds ratio [OR] and 95% confidence interval [CI]) using multiple logistic regression analysis. Results: The matching procedure generated 2327 matched pairs for analyses. CABG significantly increased the risks of 30-day in-hospital mortality (OR 2.28, 95% CI 1.36-3.84), postoperative pneumonia (OR 1.49, 95% CI 1.12-1.98), sepsis (OR 1.49, 95% CI 1.17-1.89), stroke (OR 1.53, 95% CI 1.17-1.99) and admission to the intensive care unit (OR, 1.75, 95% CI 1.50-2.05). The findings were generally consistent across most of the evaluated subgroups. A noncardiac surgery performed within 1 month after CABG was associated with the highest risk for adverse events, which declined over time. Conclusion: Prior history of CABG was associated with postoperative pneumonia, sepsis, stroke, and mortality in patients undergoing noncardiac surgeries. Although we raised the possibility regarding deferral of non-critical elective noncardiac surgeries among patients had recent CABG when considering the risks, critical or emergency surgeries were not in the consideration of delay surgery, especially cancer surgery.

Use of consecutive transcutaneous oxygen measurement when assessing the need for revascularization and association with the outcomes of ischemic diabetic ulcers.

This study compared the ankle-brachial index (ABI) with transcutaneous oxygen pressure (TcPO2 ) in assessing peripheral vascular disease (PVD) prevalence in 100 diabetic foot ulcer (DFU) patients. Patients were categorized into vascular or nonvascular reconstruction groups and underwent both ABI and TcPO2 measurements four times over 6 months. Predictive validity for PVD diagnosis was analysed using the area under the receiver-operating characteristic curve (AUC). The study found TcPO2 to be a superior predictor of PVD than ABI. Among the DFU patients, 51 with abnormal TcPO2 values underwent vascular reconstruction. Only TcPO2 values showed significant pretreatment differences between the groups and increased post-reconstruction. These values declined over a 6-month follow-up, whereas ABI values rose. For those with end-stage renal disease (ESRD), TcPO2 values saw a sharp decrease within 3 months. Pre-reconstruction TcPO2 was notably lower in amputation patients versus limb salvage surgery patients. In conclusion, TcPO2 is more effective than ABI for evaluating ischemic limb perfusion and revascularization necessity. It should be prioritized as the primary follow-up tool, especially for ESRD patients.

Linear Interaction Between Replication and Transcription Shapes DNA Break Dynamics at Recurrent DNA Break Clusters.

Recurrent DNA break clusters (RDCs) are replication-transcription collision hotspots; many are unique to neural progenitor cells. Through high-resolution replication sequencing and a capture-ligation assay in mouse neural progenitor cells experiencing replication stress, we unraveled the replication features dictating RDC location and orientation. Most RDCs occur at the replication forks traversing timing transition regions (TTRs), where sparse replication origins connect unidirectional forks. Leftward-moving forks generate telomere-connected DNA double-strand breaks (DSBs), while rightward-moving forks lead to centromere-connected DSBs. Strand-specific mapping for DNA-bound RNA revealed co-transcriptional dual-strand DNA:RNA hybrids present at a higher density in RDC than in other actively transcribed long genes. In addition, mapping RNA polymerase activity revealed that head-to-head interactions between replication and transcription machinery resulted in 60% DSB contribution to the head-on compared to 40% for co-directional. Our findings revealed TTR as a novel fragile class and highlighted how the linear interaction between transcription and replication impacts genome stability.

Self-Supervised Learning-Based General Laboratory Progress Pretrained Model for Cardiovascular Event Detection.

OBJECTIVE: Leveraging patient data through machine learning techniques in disease care offers a multitude of substantial benefits. Nonetheless, the inherent nature of patient data poses several challenges. Prevalent cases amass substantial longitudinal data owing to their patient volume and consistent follow-ups, however, longitudinal laboratory data are renowned for their irregularity, temporality, absenteeism, and sparsity; In contrast, recruitment for rare or specific cases is often constrained due to their limited patient size and episodic observations. This study employed self-supervised learning (SSL) to pretrain a generalized laboratory progress (GLP) model that captures the overall progression of six common laboratory markers in prevalent cardiovascular cases, with the intention of transferring this knowledge to aid in the detection of specific cardiovascular event. METHODS AND PROCEDURES: GLP implemented a two-stage training approach, leveraging the information embedded within interpolated data and amplify the performance of SSL. After GLP pretraining, it is transferred for target vessel revascularization (TVR) detection. RESULTS: The proposed two-stage training improved the performance of pure SSL, and the transferability of GLP exhibited distinctiveness. After GLP processing, the classification exhibited a notable enhancement, with averaged accuracy rising from 0.63 to 0.90. All evaluated metrics demonstrated substantial superiority ([Formula: see text]) compared to prior GLP processing. CONCLUSION: Our study effectively engages in translational engineering by transferring patient progression of cardiovascular laboratory parameters from one patient group to another, transcending the limitations of data availability. The transferability of disease progression optimized the strategies of examinations and treatments, and improves patient prognosis while using commonly available laboratory parameters. The potential for expanding this approach to encompass other diseases holds great promise. CLINICAL IMPACT: Our study effectively transposes patient progression from one cohort to another, surpassing the constraints of episodic observation. The transferability of disease progression contributed to cardiovascular event assessment.

Predictors of Academic and Fieldwork Performance in Occupational Therapy Students: A Systematic Review.

Introduction: Occupational therapy (OT) educational programs are aimed at enrolling a diverse student population that is likely to succeed in the academic and fieldwork components of the program. Comprehending the array of factors that influence students' learning and academic and fieldwork success is important for university educators. This study investigated the existing literature on predictors of academic and fieldwork performance in OT students. Methods: The search process used in this review included screening, eligibility, and study quality. We searched the PubMed and Cochrane Library databases for literature published in the past 10 years (1 January 2012 to 30 March 2022). As a comprehensive search, the following keywords were used for abstract, title, and keywords sections: occupational therapy student, predictors, fieldwork, academic, academic success, academic performance, fieldwork success, and fieldwork performance. The Medical Education Research Study Quality Instrument was used to assess the quality of studies. Results: The systematic review retrieved 14 articles that met inclusion criteria. Most were cross-sectional studies, followed by cohort, retrospective analysis of secondary data, and exploratory studies. Four articles focused on academic success, eight focused on fieldwork success, and two explored both aspects. Promising predictors of academic performance included the admission grade point average and the student's approach to studying. Predictors of fieldwork performance included a graduate record examination score, emotional intelligence, and interpersonal relationships. Conclusion: This systematic review explores predictors of academic and fieldwork success in OT students, which provide opportunities to identify early the learning difficulties of students and assist educators to target modifiable predictors so they can provide high-quality education.

Punicalagin is cytotoxic to human colon cancer cells by modulating cell proliferation, apoptosis, and invasion.

Purpose: The purpose of this study was to explore the anticancer effect of punicalagin, an abundant bioactive tannin compound isolated from Punica granatum L., on three colon cancer cell lines, namely, HCT 116, HT-29, and LoVo.Research Design: Normal and colon cancer cells were treated with different concentrations of punicalagin for different periods. Data Collection and Analysis: Cell viability was measured with a CCK-8 assay. Programmed cell death and invasion were analyzed using an annexin V and cell death kit and a cell invasion analysis kit. The expression of active caspase-3, MMP-2, MMP-9, Snail, and Slug were measured by Western blot.Results: The results of the cell viability analysis showed that punicalagin was cytotoxic to colon cancer cells, but it was not to normal cells in a dose- and time-dependent manner. Additionally, punicalagin induced apoptosis in colon cancer cells (shown by the cumulative percentage of colorectal cancer cells in early and late apoptosis). It was found that caspase-3 activity increased following punicalagin treatment. Western blot results also showed that punicalagin increased the expression of activated caspase-3. In contrast, punicalagin inhibited the invasion of colon cancer cells. Further, treatment of colon cancer cells with punicalagin suppressed the expression of MMP-2, MMP-9, Snail, and Slug. Conclusions: These results showed that the activation of caspase-3 and the inhibition of MMP-2, MMP-9, Snail and Slug were involved in the effects of punicalagin on colon cancer cells.

A modified SELEX approach to identify DNA aptamers with binding specificity to the major histocompatibility complex presenting ovalbumin model antigen.

Aptamers have sparked significant interest in cell recognition because of their superior binding specificity and biocompatibility. Cell recognition can be mediated by targeting the major histocompatibility complex (MHC) that presents short peptides derived from intracellular antigens. Although numerous antibodies have demonstrated a specific affinity for the peptide-MHC complex, the number of aptamers that exhibit comparable characteristics is limited. Aptamers are usually selected from large libraries via the Systemic Evolution of Ligands by Exponential Enrichment (SELEX), an iterative process of selection and PCR amplification to enrich a pool of aptamers with high affinity. However, the success rate of aptamer identification is low, possibly due to the presence of complementary sequences or sequences rich in guanine and cytosine that are less accessible for primers. Here, we modified SELEX by employing systemic consecutive selections with minimal PCR amplification. We also modified the analysis by selecting aptamers that were identified in multiple selection rounds rather than those that are highly enriched. Using this approach, we were able to identify two aptamers with binding specificity to cells expressing the ovalbumin alloantigen as a proof of concept. These two aptamers were also discovered among the top 150 abundant candidates, despite not being highly enriched, by performing conventional SELEX. Additionally, we found that highly enriched aptamers tend to contain fractions of the primer sequence and have minimal target affinity. Candidate aptamers are easily missed in the conventional SELEX process. Therefore, our modification for SELEX may facilitate the identification of aptamers for more application in diverse biomedical fields. Significance: we modify the conventional method to improve the efficiency in the identification of the aptamer, a single strand of nucleic acid with binding specificity to the target molecule, showing as a proof of concept that this approach is particularly useful to select aptamers that can selectively bind to cells presenting a particular peptide by the major histocompatibility complex (MHC) on the cell surface. Given that cancer cells may express mutant peptide-MHC complexes that are distinct from those expressed by normal cells, this study sheds light on the potential application of aptamers to cancer cell targeting.

Undergraduate nurses' reflections on visual thinking learning to construct inductive reasoning through situated patient pictures: A mixed-method study.

BACKGROUND/OBJECTIVE: Deductive logic has often been used to develop critical thinking. However, inductive logical thinking, essential to care decision-making, has yet to be emphasized. This study aimed to explore visual thinking learning among undergraduate nursing students by asking them to draw situated patient pictures in order to integrate theoretical knowledge and promote inductive logical thinking. METHODS: A mixed-methods research design was used to obtain quantitative and qualitative data from a convenience sample of 100 students. The study was conducted in a Taiwanese university from September 2022 to January 2023. In the quantitative component, learners' views of situated patient pictures were captured based on 15 paired identifiers and two questions: (a) What word should be used in describing the situated patient's picture? (b) How strongly do you feel about the selection? Written feedback was analyzed using qualitative content analysis. RESULTS: Quantitative analysis identified specific, unpretentious, humorous, harmonious, conservative, realistic, rational, entire, image performance, professional performance, understandable, expressive, static performance, rigorous, and profuse with a reasonable degree of choice. Qualitative analysis identified four stages in participants' development of inductive reasoning through situated patient pictures and visual thinking learning. These were: exploration, intuition, theme, and logic and creation. CONCLUSIONS: The results suggest that visual thinking learning is a practical pedagogical approach to increasing learners' communication abilities, group cooperation, theoretical knowledge integration, and logical thinking. Neither educators nor learners required any artistic skills. Nonetheless, participants demonstrated creativity and innovation through continuous visual thinking learning.