Enhancing Cognitive Function in Older Adults through Processing Speed Training: Implications for Cognitive Health Awareness.

It may be possible to enhance adults' cognitive health and promote healthy aging through processing speed training using the Useful Field of View (UFOV) related activities and software. This study investigated the impact of utilizing UFOV on processing speed improvement in older adults in response to the growing global attention on cognitive health and aging issues. In this quasi-experimental study, 22 individuals (mean age ± SD = 71.9 ± 4.8) participated in the experimental group, and 20 community-based participants (mean age ± SD = 67.1 ± 4.8) were in the control group. The intervention involved ten sessions of UFOV training, each lasting 60 min, conducted twice a week for the experimental group while the control group engaged in volunteer service activities. Measurements of Counting Back, Fabrica, Double-Decision, and Hawkeye were administered to all participants before and after the intervention. The results showed significant improvements in the experimental group for the four measurements (p ≤ 0.01, 0.05, 0.001, 0.001) and non-significant gains in the control group (p ≥ 0.05) for all. Furthermore, mixed repeated-measures ANOVA analysis, with time 1 pre-test measures as the covariate, revealed significant interaction effects between time and group for all measurement indicators (p = 0.05, 0.01, 0.05) except for Fabrica (p > 0.05). In conclusion, these findings support the effectiveness of UFOV cognitive training interventions in enhancing specific cognitive abilities.

Efficacy and safety of pembrolizumab monotherapy in EGFR-mutant squamous cell lung cancer with PD-L1 over-expression: A case report.

BACKGROUND: Epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) patients are less likely to be programmed death-ligand 1 (PD-L1)-positive compared with wild-type EGFR mutant tumors. Given the rarity of actionable driver genes in squamous cell lung cancer (SQCC), the frequency of SQCC patients simultaneously carrying EGFR driver gene mutation and having PD-L1 over-expression is extremely low. Studies on the effectiveness and safety of EGFR-TKIs or immune-checkpoint inhibitors (ICIs) in this subset of patients are lacking. PATIENT CONCERNS: The patient suffered from coughing and chest pain for 1 month. A chest CT revealed a mass with a cavity in the right lung, enlarged mediastinal lymph nodes, diffuse pleural thickening in the right pleura, and pleural effusion of the right chest. DIAGNOSIS: A pleural biopsy was performed using a video-assisted thoracoscope. The pathological examination revealed a poorly differentiated squamous cell carcinoma of lung. Further genetic testing identified exon 19 deletion mutation in EGFR with abundance of 0.27%. Meanwhile, immunohistochemical PD-L1 analysis showed a TPS of 90%. INTERVENTIONS: The patient was initially resistant to EGFR-TKIs but exhibited a rapid and marked response to pembrolizumab. OUTCOMES: After 5 cycles of pembrolizumab monotherapy, the patient developed Grade 3 immune-related dermatitis, and ICI therapy was suspended. CONCLUSIONS: ICI monotherapy could be an effective therapy in SQCC patients with low-abundance of EGFR mutations and PD-L1 over-expression. However, close attention should be paid to immune-related adverse events.

Mediating effect of self-efficacy on the relationship between social support and self-management behaviors among patients with knee osteoarthritis: a cross-sectional study.

BACKGROUND: Good self-management behaviors in patients with knee osteoarthritis can improve disease awareness, treatment effectiveness, quality of life, and reduce medical costs. However, there is a paucity of studies focusing on patients with knee osteoarthritis. Therefore, the purpose of this study was to explore the mediating effect of self-efficacy on aspects of social support and self-management behaviors in this population. METHODS: This study employed a cross-sectional design and convenience sampling to survey patients with knee osteoarthritis in an outpatient department of a regional hospital in northern Taiwan from February 22, 2021, to April 15, 2021. The inclusion criteria for patients were (1) those diagnosed by a physician with knee osteoarthritis and (2) who could communicate in Chinese or Taiwanese. Participants were asked to complete a demographic questionnaire, the Arthritis Self-Efficacy Scale (ASE), the Inventory of Socially Supportive Behavior (including enacted support and perceived social support), and the Arthritis Self-Management Assessment Tool (ASMAT). In addition, the Kellgren-Lawrence Grading Scale was obtained from a chart review. Data were analyzed with descriptive statistics, t-test, one-way analysis of variance, Pearson product-moment correlation, and mediation analysis. RESULTS: A total of 140 patients met the inclusion criteria. The mean age of participants was 70.21 ± 10.84years; most (73.6%) were female. The mean total score of the ASMAT was 64.27 ± 14.84. Scores for the ASE, enacted support, and perceived social support were significantly positively correlated with ASMAT (all p < .001). The standardized coefficient for total effect and direct effect of perceived social support on ASMAT was 0.899 (p < .001) and 0.754 (p < .05), respectively. After introducing the ASE into the model, the indirect effect was 0.145 (p < .05), which indicated that ASE had a partial mediating effect on the relationship between perceived social support and ASMAT. CONCLUSION: Our findings might suggest that perceived social support indirectly affected ASMAT through ASE. Therefore, interventions designed to increase self-efficacy and social support could enhance self-management behaviors for patients with knee osteoarthritis.

Transplanted human neural precursor cells integrate into the host neural circuit and ameliorate neurological deficits in a mouse model of traumatic brain injury.

Traumatic brain injury (TBI) is to date one of the major critical conditions causing death and disability worldwide. Exogenous neural stem/precursor cells (NSCs/NPCs) hold great promise for improving neurological dysfunction, but their functional properties in vivo remain unknown. Human neural precursor cells (hNPCs) carrying one fluorescent reporter gene (DsRed) can be observed directly in vivo using two-photon laser-scanning microscope. Therefore, we evaluated the neural integration and potential therapeutic effect of hNPCs on mice with TBI. Behavioral tests were performed by rotarod task and Morris Water Maze task. Neural integration was detected by fluorometric Ca2+ imaging and nerve tracing. We found that motor and cognition functions were significantly improved in mice with hNPCs injection compared to mice with vehicle treatment, and hNPCs integrated into the host circuit and differentiated toward neuronal lineage. Our study provided reliable evidence for further hNPCs transplantation in clinical practice.

Optical coherence tomography angiography of optic disc perfusion in non-arteritic anterior ischemic optic neuropathy.

AIM: To compare the optic disc blood flow of non-arteritic ischemic optic neuropathy (NAION) eyes with normal eyes. METHODS: The optic disc blood flow densities of diagnosed non-acute phase NAION eyes (21 eyes, 14 individuals) and normal eyes (19 eyes, 12 individuals) were detected via Optovue optical coherence tomography angiography (OCTA). The optic disc blood flow was measured via Image J software. Correlations between optic disc perfusion and visual function variables were assessed by linear regression analysis. RESULTS: The average percentage of the optic disc non-perfusion areas in the non-acute phase NAION patients (17.84%±6.18%) was increased, when compared to the normal control eyes (8.61%±1.65%), and the difference was statistically significant (P<0.01). Moreover, there was a proportional correlation between the visual field mean defect (MD) and the optic disc non-perfusion area percentage, and the relationship was statistically significant (t=3.65, P<0.01, R2=0.4118). In addition, the critical correlation between the best corrected visual acuity (BCVA) and the optic disc non-perfusion area percentage was statistically significant (t=4.32, P<0.01, R2=0.4957). CONCLUSION: The optic disc non-perfusion area percentages detected via OCTA in NAION eyes were significantly increased when compared with the normal eyes. Both the BCVA and MD were correlated with the optic disc flow detected, revealing that OCTA may be valuable in the diagnosis and estimation of NAION.

The Pharmacological Heterogeneity of Nepenthone Analogs in Conferring Highly Selective and Potent κ-Opioid Agonistic Activities.

To develop novel analgesics with no side effects or less side effects than traditional opioids is highly demanded to treat opioid receptor mediated pain and addiction issues. Recently, κ-opioid receptor (KOR) has been established as an attractive target, although its selective agonists could bear heterogeneous pharmacological activities. In this study, we designed and synthesized two new series of nepenthone derivatives by inserting a spacer (carbonyl) between 6α,14α-endo-ethenylthebaine and the 7α-phenyl substitution of the skeleton and by substituting the 17-N-methyl group with a cyclopropylmethyl group. We performed in vitro tests (binding and functional assays) and molecular docking operations on our newly designed compounds. The results of wet-experimental measures and modeled binding structures demonstrate that these new compounds are selective KOR agonists with nanomolar level affinities. Compound 4 from these new derivatives showed the highest affinity (Ki = 0.4 ± 0.1 nM) and the highest selectivity (µ/κ = 339, δ/κ = 2034) toward KOR. The in vivo tests revealed that compound 4 is able to induce stronger (ED50 = 2.1 mg/kg) and much longer antinociceptive effect than that of the typical KOR agonist U50488H (ED50 = 4.4 mg/kg). Therefore, compound 4 can be used as a perfect lead compound for future design of potent analgesics acting through KOR.

Notch4 inhibition reduces migration and invasion and enhances sensitivity to docetaxel by inhibiting Akt/fascin in pancreatic cancer cells.

Overexpression of Notch4 is associated with a variety of tumor types. Only sparse information exists on Notch4 expression in pancreatic cancer (PC). The present study demonstrated that Notch4 expression was significantly upregulated in PC cell lines compared with a non-transformed pancreatic epithelial cell line, HPDE6c-7. To investigate the possible role of Notch4 in PC cells, an RNA interference approach was used to silence Notch4 expression. The results revealed that small interfering RNA (siRNA) targeting Notch4 significantly impeded the viability, migration and invasion abilities of PC cells in vitro. Downregulation of Notch4 with siRNA sensitized cells to the action of docetaxel. Furthermore, Notch4 downregulation enhanced the inhibition of Akt activation and the fascin expression induced by docetaxel in PC cells. Together, these data provide insight into the function of Notch4 and suggest that Notch4 may represent a new potential target for gene therapy in PC.

[Effects of interferon-alpha combined with saikosaponin on serum T lymphocyte subgroups and hepatic cytokines in mice with immune hepatic injury].

OBJECTIVE: To observe the effects of interferon-alpha combined with saikosaponin on serum T lymphocyte subgroups and hepatic cytokines in mice with immune hepatic injury. METHODS: The mice were randomly divided into five groups, i. e., the normal control group, the model group, the interferon group, the saikosaponin group, and the interferon combined saikosaponin group. Corresponding medication was given to mice in respective groups for two days. Peripheral blood was collected 8 and 24 h after concanavalin A (Con A) was injected. Serum lymphocyte subgroups, tumor necrosis factor alpha (TNF-alpha), levels of interleukin 18 (IL-18) and IL-10, activities of alanine aminotransferase (ALT) and aspartate transaminase (AST) were detected. Pathological changes of the liver tissue were observed. RESULTS: (1) Compared with the normal control group, serious inflammation and necrosis was significant in the liver tissue of the model group. The serum levels of ALT and AST obviously increased. Meanwhile, the 24-h peripheral blood CD4+ T cell and CD8+ T cell ratios and the hepatic IL-10 level obviously decreased (P < 0.01). The levels of IL-18 and TNF-alpha significantly increased (P < 0.05, P < 0.01). (2) Compared with the model group, dot and lamellar necrosis was dispersedly seen in the liver tissue in the three medication groups. The serum activities of ALT and AST significantly decreased (P < 0.01). Meanwhile, the peripheral blood CD4+ T cell and CD8+ T cell ratios, as well as the hepatic IL-10 level obviously increased (P < 0.01, P < 0.05). The levels of IL-18 and TNF-alpha significantly decreased (P < 0.05, P < 0.01). (3) In the interferon combined saikosaponin group, the 24-h peripheral blood CD4+ T cell and CD8+ T cell ratios increased more obviously than those of the interferon group. The 8- and 24-h IL-18 levels were obviously lower than those of the interferon group, while the 24-h TNF-alpha level significantly decreased more than that of the interferon group (P < 0.05). CONCLUSION: Interferon-alpha combined saikosaponin could effectively play a role in fighting against the immune hepatic injury.

Long-term results of bipolar radiofrequency needle ablation of the prostate for lower urinary tract symptoms.

PURPOSE: To report the first long-term experience on the efficacy of bipolar transurethral radiofrequency needle ablation (RFA) in patients with lower urinary tract symptoms that are secondary to benign prostatic hyperplasia. PATIENTS AND METHODS: A nonrandomized prospective cohort of 12 candidates for transurethral resection of the prostate underwent bipolar transurethral RFA in 2004 (mean age 63; prostate volume 34 cc). Patients were evaluated preoperatively and at 3, 12, 36, and 60 months postprocedure. International Prostate Symptom Score (IPSS), quality-of-life (QoL) index, peak urinary flow rate (Qmax), postvoid residual volume (PVR), and need for a second procedure were evaluated at each follow-up interval. RESULTS: Significant improvement in urinary symptoms and voiding parameters occurred at 1 year after the procedure. Mean improvements for IPSS, QoL, and Q(max) were 12 points, 3.5 points, and 8 mL/s, respectively. Improvement, however, was not sustained in the long term. Nine patients ultimately had treatment failure necessitating a secondary procedure, one at 2 months, five after 3 years, and three by 5 years. Two patients were lost to follow-up. Only one patient had long-term benefit from the procedure. CONCLUSION: In the short term, bipolar RFA produced clinically meaningful improvement in symptom scores and voiding parameters. The majority of patients, however, eventually experienced treatment failure and needed additional surgical procedures. Only 8% of patients had long-term (>5 years) benefit.

An outbreak of severe Clostridium difficile-associated disease possibly related to inappropriate antimicrobial therapy for community-acquired pneumonia.

We report a severe outbreak of Clostridium difficile infection. According to a chart review, half of the patients who received treatment for bacterial pneumonia before they developed C. difficile infection may not have had pneumonia. Excessive use of the hospital's new pneumonia care plan during the influenza season may have contributed to the intensity of this outbreak.

Applying Fong's CRS liver score in patients with colorectal liver metastases treated by cryotherapy.

BACKGROUND: A significant proportion of patients with liver metastases from colorectal cancer have unresectable disease and we have used cytoablative treatment such as cryotherapy in some of these patients. We retrospectively reviewed patients who underwent hepatic cryotherapy for colorectal metastases and studied the effect of the clinical risk score (CRS) reported by Fong et al, which can predict survival following liver resection. METHODS: A retrospective study was performed on patients who underwent hepatic cryotherapy between 1990 and 2000 in St George Hospital. There were 61 patients in this study and they were stratified into prognostic groups based on five preoperative CRS parameters: primary node positive, disease-free interval from primary to metastases < 12 months, number of hepatic tumours > 1, largest hepatic tumour > 5 cm and carcinoembryonic antigen level > 200 ng/mL. The median follow-up was 25 months. RESULTS: The median survival was 26 months and the 3-year survival rate was 37%. Median survivals for patients with CRS scores 1 (13%), 2 (25%), 3 (53%), 4 (6%) and 5 (4%) were 37, 25, 30, 21 and 15 months, respectively (R2 = 0.81). CONCLUSION: The CRS score can be used to predict outcome of hepatic cryotherapy, but the difference in survival between CRS 2, 3 and 4 is modest.

Epidemiology of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus in a rural state.

BACKGROUND: Most data on methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) isolates come from large tertiary care centers. Infection control personnel need to understand the epidemiology of MRSA and VRE across the continuum of care, including small rural hospitals, to develop effective control strategies. OBJECTIVE: To describe the epidemiology of MRSA and VRE in Iowa. SETTING: Fifteen hospitals in Iowa. Methods Between July 1998 and June 2001, a total of 1,968 S. aureus isolates and 1,845 Enterococcus isolates from patients infected with these pathogens were examined. Multivariate models were developed to evaluate patient and institutional risk factors for MRSA infection and VRE infection. RESULTS: The proportion of S. aureus isolates resistant to methicillin was 31%, and the proportion of Enterococcus isolates resistant to vancomycin was 6%. Independent risk factors for MRSA infection included residence in a long-term care facility, age of more than 60 years, hospitalization in a hospital with less than 200 short-term care beds, and acquiring the infection in the hospital. Independent risk factors for VRE infection included use of a central venous catheter, residence in a long-term care facility, acquisition of infection in the hospital, and hospitalization in a hospital with more than 200 short-term care beds. CONCLUSIONS: In Iowa, the epidemiology of MRSA differ from those of VRE. MRSA has become established in small rural hospitals. Effective MRSA control strategies may require inclusion of all hospitals in a state or region.

Risk factors for groin wound infection after femoral artery catheterization: a case-control study.

OBJECTIVE: Groin wound infection (GWI) after femoral artery catheterization is unusual. However, several reports of GWI associated with the use of a Perclose device appear in the surgical literature. DESIGN: A case-control study. SETTING: We pooled 23 cases and 83 controls from a university hospital and a community medical center. PATIENTS: A case was defined as a patient who developed a GWI after a femoral artery catheterization. At the university hospital, 3 controls were randomly selected from the at-risk population and matched to each case by time of procedure only (within 2 weeks). At the community medical center, 4 controls were selected and matched to each case by time of procedure (within 2 weeks), sex, and age (within 5 years). RESULTS: We considered several covariates, including age, sex, body mass index, medical conditions, Perclose use, hematoma formation, and antithrombotic therapy. In a multivariate model, only hematoma formation (odds ratio, 68.8; 95% confidence interval, 12.1-391.4) and glycoprotein IIb/IIIa platelet inhibitor therapy (odds ratio, 6.1; 95% confidence interval, 1.1-33.6) were statistically significant predictors of GWI; Perclose use (odds ratio, 0.9; 95% confidence interval, 0.2-3.7) was not a statistically significant predictor of GWI. However, most of the hematomas (15/17) formed after procedures during which a Perclose device was used. CONCLUSION: Perclose use did not have any additional effect on GWI risk beyond the effect that hematoma formation had.

Lipase and pancreatic amylase activities in diagnosis of acute pancreatitis in patients with hyperamylasemia.

BACKGROUND: Measurement of total serum amylase (AMY) is the most widely used biochemical test for the diagnosis of acute pancreatitis, but it is commonly considered a nonspecific marker. To improve the biochemical diagnosis of acute pancreatitis, lipase (LIP) and pancreatic amylase (PAMY) have been tested in recent years. The present study was designed to evaluate whether serum LIP and pancreatic PAMY tests could replace total amylase test to improve diagnostic efficiency in the evaluation of acute pancreatitis in patients with hyperamylasemia. METHODS: LIP and PAMY values were determined in serum samples from 92 patients with hyperamylasemia. Reference values for each enzyme were derived from serum samples of 147 healthy subjects. The activities of LIP and PAMY in patients with various diseases were shown directly by the boxplot graph. The diagnostic accuracy of LIP and PAMY was defined as the area under the receiver operating characteristic (ROC) curve. Their sensitivity and specificity in detecting acute pancreatitis at varying cutoff points were shown by the curve, and the best cutoff value for each enzyme was shown by the modified ROC curve. The diagnostic values of LIP, PAMY and LIP+AMY with each upper limit of reference range (ULR) were compared with the corresponding best cutoff values. RESULTS: The references values of LIP and PAMY were 12.2-47.6 U/L and 28-95 U/L, respectively. These values in patients with acute pancreatitis were higher than those patients with other diseases. The areas under the ROC curve (AUC) of LIP and PAMY were 0.799 and 0.792, respectively. With the best diagnostic cutoff point of maximum (sensitivity + specificity)-100%, we obtained values of 97.9 U/L (LIP(97.9)=2.06 X ULR) for LIP and 209 U/L (PAMY(209)=2.20 X ULR) for PAMY. The best cutoff values for LIP, PAMY and LIP+AMY demonstrated the specificity, positive predictive value, and diagnostic efficiency higher than the corresponding ULRs. CONCLUSIONS: Serum LIP and PAMY are specific for the pancreas and might replace total amylase for the diagnosis of acute pancreatitis in hyperamylasemia patients. LIP(97.9) is more efficient than PAMY(209) in the diagnosis of acute pancreatitis. A combined test of both enzymes is not superior to single test of either enzyme in diagnostic accuracy.