Phospholipids with two polyunsaturated fatty acyl tails: an important driver of ferroptosis.

We highlight the latest work of Qiu et al. on the core mechanism of ferroptosis induced by rare phospholipids with two polyunsaturated fatty acyl tails (PL-PUFA2s), which has been published in Cell. It has long been acknowledged that PLs containing one PUFA tail (PL-PUFA1s) serve as substrates for phospholipid peroxidation during the process of ferroptosis, owing to their susceptibility to oxidation and prevalence in vivo. However, the authors note that PL-PUFA2s, rather than PL-PUFA1s, represent critical lipid classes involved in the pro-ferroptosis process. Exogenous phosphatidylcholine-PUFA2s accumulate in mitochondria and combine with Complex I within the electron transport chain, thereby potentially resulting in an elevation of mitochondrial reactive oxygen species levels. Then, these mitochondrial peroxides prompt the substantial accumulation of peroxides within the endoplasmic reticulum, ultimately culminating in ferroptosis. These findings shed light on the potential molecular mechanisms underlying the induction of ferroptosis by dietary PL-PUFA2s and offer novel insights for both the evaluation of cellular iron death sensitivity and the treatment of cancer. This article will provide a more comprehensive elucidation of the paper and facilitate an enhanced understanding of the underlying mechanisms for readers.

Efficacy and safety of an extended-release sebacoyl dinalbuphine ester for laparoscopic cholecystectomy: A randomized controlled trial.

BACKGROUND: A long-acting κreceptor agonist parenteral analgesic may theoretically improve acute pain and reduce incidence of chronic postsurgical pain (CPSP) after laparoscopic cholecystectomy with minimal drug-related side effects of the traditional µreceptor opioids. METHODS: Eighty adult patients undergoing elective laparoscopic cholecystectomy were randomly assigned to receive single intramuscular injection of an extended-release sebacoyl dinalbuphine ester (SDE, Naldebain 150 mg; n = 40) or placebo (n = 40) after anesthesia induction. Standard multimodal analgesia (MMA) was administered for postoperative pain control. The primary endpoint was pain intensity within 7 days after surgery. The secondary endpoints were incidence CPSP at 3 months and adverse reactions up to 7 days after surgery. RESULTS: The highest visual analogue scale (VAS) and area under the curve of VAS 0 to 48 hours after operation were not different between the two groups and a similar proportion of patients requested rescue parenteral analgesics. Average pain intensities were also not different at 72 hours and 7 days after surgery. Incidence of CPSP was 22.5% and 13.1% in patients who received placebo and SDE treatment, respectively (P = .379). Significantly higher incidence of drug-related adverse events, including dizziness, nausea and injection site reactions, were recorded in the SDE group. CONCLUSION: A single dose of extended-release analgesic SDE given intraoperatively did not provide sufficient add-on effect for acute and chronic pain management after laparoscopic cholecystectomies in patients who received standard postoperative MMA. Intramuscular injection of 150 mg SDE in patients with average body mass causes adverse events that could have been overlooked. More clinical studies are warranted to determine the target populations who may benefit from SDE injections for improvement of acute and chronic postsurgical pain management.

Pseudomonas aeruginosa Infections Are Associated with Infection Recurrence in Arteriovenous Grafts Treated with Revision.

Background and Objectives: This study was conducted to investigate whether Pseudomonas aeruginosa (PA) infections of arteriovenous grafts (AVGs) recur more frequently than other bacterial infections following treatment with revision. Materials and Methods: Operative procedures, including total excision, subtotal excision, and revision, were performed on 60 patients to treat 65 AVG infections. Final outcomes were classified as no infection recurrence, infection recurrence, and death without prior recurrence. In the competing risk setting, the cumulative incidence was estimated using the cumulative incidence function and Gray's test, and the associations between outcomes and different variables were estimated using a subdistribution hazard (SDH) model. Results: Comparing AVG infections with and without recurrence, PA infection was not associated with a higher risk of infection recurrence (p = 0.13); however, the first operative procedure type was associated with infection recurrence (p = 0.04). AVGs with PA infection were associated with a higher total number of surgical interventions (p < 0.05) than AVGs without PA infection. Regarding the cumulative incidences of outcomes, for AVGs treated with subtotal excision or revision, the cumulative incidence of recurrent infection was 3.3-fold higher for those with PA infection than without one year after the first surgery. However, when AVGs were treated with revision alone, the cumulative incidence was 4.1-fold. After excluding AVGs treated with total excision, the SDH model was applied, obtaining a hazard ratio for infection recurrence of 16.05 (p = 0.02) for AVGs with PA infection compared with AVGs without PA infection. No other variables were significantly associated with infection recurrence. Conclusions: For subtotal resection and revision, AVGs infected with PA had a higher recurrence rate than those infected with other species. However, revision surgery may aggravate the recurrence rate.

[Risk Factors of Rapidly Progressive Interstitial Lung Disease in Patients With Anti-Melanoma Differentiation-Associated Gene 5 Antibody-Positive Dermatomyositis].

Objective: To investigate the conditions of patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive dermatomyositis combined with rapidly progressive interstitial lung disease (RPILD), and to analyze the risk factors. Methods: A total of 145 patients diagnosed with anti-MDA5 antibody-positive dermatomyositis at West China Hospital, Sichuan University between January 2018 and September 2021 were selected, and their general and clinical data were collected. The patients were divided into two groups, a RPILD group of patients with comorbid RPILD and a non-RPILD group of those who did not have comorbid RPILD. Factors that might affect whether patients with anti-MDA5 antibody-positive dermatomyositis also had comorbid RPILD were screened out and binary logistic regression analysis was performed. Results: Among the 145 patients with anti-MDA5 antibody-positive dermatomyositis, 32 (22.07%) patients had comorbid RPILD, while the remaining 113 (77.93%) did not have comorbid RPILD. Binary logistic regression analysis showed that lactate dehydrogenase≥370 IU/L (compared with <370 IU/L, OR=4.066, 95% CI: 1.616-10.230) and carcinoembryo antigen≥5 ng/mL (compared with <5 ng/mL, OR=6.070, 95% CI: 2.013-18.303) were risk factors for comorbid RPILD in patients with anti-MDA5 antibody-positive dermatomyositis ( ß>0, OR>1, P<0.05). Conclusion: It is recommended that close attention be given to changes in high-resolution chest CT and pulmonary functions in patients with lactate dehydrogenase≥370 IU/L and carcinoembryo antigen≥5 ng/mL. If rapid progression of lung disease is detected, it is necessary to strengthen the treatment of the lung disease, thereby improving the prognosis of patients.

Social functioning, depression, and quality of life among breast cancer patients: A path analysis.

PURPOSE: To identify associations among social functioning, depression, and quality of life in breast cancer patients. METHOD: A cross-sectional study was conducted. A total of 180 breast cancer patients were recruited from the surgical units in southern Taiwan hospital in 2021. Path analysis was employed to analyze the relationships between background information and social functioning, depression, and quality of life. Structural equation modeling (SEM) was used for examining the path analysis in this study. RESULTS: The path model showed that respondents with a religious belief (ß = 0.18, p < .000) and less severe disease (ß = -0.29, p < .01) showed better social functioning. Income did not affect social functioning directly but was directly related to the social interaction dimension (ß = 0.30, p < .000). Moreover, younger age (ß = -0.29, p < .000, lower income (ß = -0.10, p < .05) and more severe disease (ß = 0.35, p < .000) increased the level of depression. Less severe disease would also result in a better quality of life (ß = -0.45, p < .000). Breast cancer patients with better social function levels have low levels of depression (ß = -0.82, p < .000) and better quality of life (ß = 0.76, p < .000). CONCLUSION: Age, religion, income, and severity are crucial predictors of social functioning, depression, and quality of life. Furthermore, severity variables which combined clinical variables to make this variable a stronger predictor for SF, depression, and QOL.

Cognitive Behavioral Therapy plus Coping Management for Depression and Anxiety on Improving Sleep Quality and Health for Patients with Breast Cancer.

Cancer-related treatments may lead to side effects that undermine a patients' quality of life (QOL). Although cognitive behavioral therapy plus coping management (CBTM) may appear to improve health-related QOL in cancer patients, limited documentation exists on the effectiveness of psychosocial interventions for patients with breast cancer (BC) during recovery. The purpose of this study was to examine the effectiveness of CBTM for sleep quality, anxiety, depression, and health among patients with BC. An experimental study was conducted to assess the efficacy of a CBTM intervention (experimental group = 36, control group = 34). The experimental group received a 12-week CBTM intervention focused on their identity, challenges, the replacement of dysfunctional beliefs, coping skills, relaxation, and rehabilitation exercises, while the control group received usual care. The follow-up evaluations were performed immediately after the intervention (T1), and at one (T2) and three months (T3). The generalized estimating equation (GEE) model showed significant effects from the CBTM intervention over time. The experimental group showed significant improvement in sleep quality, anxiety and depressive symptoms, and significant increases in their mental and physical QOL from baseline, T1, T2, and T3-except for the mental and physical QOL showing no significant change at T3-while the control group receiving usual care showed no changes over time. The results suggest that CBTM increases sleep quality, reduces anxiety and depressive symptoms, and enhances health-related QOL for participants. CBTM is efficacious and can be provided by nurses to enhance patients' coping skills and consequently improve their QOL.

Cold atmospheric plasma physically reinforced substances of platelets-laden photothermal-responsive methylcellulose complex restores burn wounds.

Patients with irregular, huge burn wounds require time-consuming healing. The skin has an epithelial barrier mechanism. Hence, the penetration and retention of therapeutics across the skin to deep lesion is generally quite difficult and these usually constrain the delivery/therapeutic efficacies for wound healing. Effective burn wound healing also necessitates proper circulation. Conventional polymeric dressing usually exhibits weak mechanical behaviors, obstructing their load-bearing applications. Cold atmospheric plasma (CAP) was used as an efficient, environmentally friendly, and biocompatible process to crosslink methylcellulose (MC) designed for topical administration such as therapeutic substances of platelets (SP) and polyethyleneimine-polypyrrole nanoparticle (PEI-PPy NP)-laden MC hydrogel carriers, and wound dressings. The roles of framework parameters for CAP-treated SP-PEI-PPy NP-MC polymeric complex system; chemical, physical, and photothermal effects; morphological, spectroscopical, mechanical, rheological, and surface properties; in vitro drug release; and hydrophobicity are discussed. Furthermore, CAP-treated SP-PEI-PPy NP-MC polymeric complex possessed augmented mechanical properties, biocompatibility, sustainable drug release, drug-retention effects, and near-infrared (NIR)-induced hyperthermia effects that drove heat-shock protein (HSP) expression with drug permeation to deep lesions. This work sheds light on the CAP crosslinking polymeric technology and the efficacy of combining sustained drug release with photothermal therapy in burn wound bioengineering carrier designs.

Psychometric and Linguistic Evaluation of a Coping Scale for Breast Cancer Survivors in Taiwan.

BACKGROUND: Coping strategies are essential in dealing with threatening situations or difficulties for better psychological adjustments and quality of life. A short-form modified Ways of Coping Questionnaire (MWCQ) would be useful to quickly assess the coping strategies used by breast cancer survivors. OBJECTIVES: The aim of this study was to evaluate the psychometric properties of a Chinese version of a brief version of the MWCQ in breast cancer survivors. METHODS: A methodological, cross-sectional design was used in this study. The study has internal consistency reliability, face/content, construct, and convergent/divergent validity. Factor analysis and confirmatory factor analysis were used to examine the psychometric properties of the MWCQ-brief in a convenience sample of 207 women with breast cancer from 2 general hospitals in Taiwan. RESULTS: From the initial 35-item coping scale, factor analysis results supported a 24-item questionnaire, and the following 4 factors were extracted: effective coping, optimistic coping, unpractical coping, and escape coping. Confirmatory factor analysis results revealed an 18-item questionnaire with 3 factors extracted: active coping, avoidance coping, and minimizing the situation. CONCLUSIONS: The 24- and 18-item MWCQ-brief versions demonstrate fair psychometric properties to measure adaptability among women with breast cancer in Taiwan. This scale is simple but contains 4 or 3 concepts for coping that can be appropriately used to assess underlying states of adaptation in women with breast cancer. IMPLICATIONS FOR PRACTICE: The MWCQ-brief is a valid and reliable tool to understand the adaptability states of female breast cancer survivors by exploring reactions to the disease. Healthcare professionals can provide appropriate psychosocial interventions based on assessment results.

Do the Paths of Sequential Vein Grafts Influence the Outcomes of Coronary Artery Bypass Surgeries?

BACKGROUND: The use of a sequential vein graft (SVG) in coronary artery bypass grafting (CABG) in multi-vessel coronary disease is common. This study aimed to investigate the influence of the paths of SVGs on the outcomes of CABG. METHODS: From January 2011 to June 2017, 126 patients underwent elective isolated CABG. If the path of the SVG was from the aorta to the right coronary artery (RCA)/ posterior descending artery (PDA) to the left circumflex artery (LCX)/obtuse marginal artery (OM), the patients were included in Group R. If the path was from the aorta to the LCX/OM to the RCA/PDA, the patients were included in Group L. The in-hospital and follow-up outcomes were analyzed. RESULTS: Group R had 69 patients, and Group L had 57 patients. Univariate analysis showed that Group L had a higher number of grafts (P < .001) and less aortic cross-clamping time (P < .001) and total bypass time (P = .001). Otherwise, Group L had 14 patients (19.3%), who received first diagonal branch (D1) bypass grafting, while Group R had none (P < .001). In the multivariate analysis, in- hospital mortality from heart failure, postoperative acute kidney injury, medium-term mortality, and readmission for cardiac incidents were not associated with the SVG path. CONCLUSION: The SVG path from the aorta to the LCX/OM to the RCA/PDA facilitated the additional D1 bypass grafting, but the outcomes for this approach were not significantly different from those for the other path.

A tumour-selective cascade activatable self-detained system for drug delivery and cancer imaging.

Achieving the activation of drugs within cellular systems may provide targeted therapies. Here we construct a tumour-selective cascade activatable self-detained system (TCASS) and incorporate imaging probes and therapeutics. We show in different mouse models that the TCASS system accumulates in solid tumours. The molecules show enhanced accumulation in tumour regions via the effect of recognition induced self-assembly. Analysis of the molecular penetration in tumour tissue shows that in vivo self-assembly increases the penetration capability compared to typical soft or hard nanomaterials. Importantly, the in vivo self-assembled molecules exhibit a comparable clearance pathway to that of small molecules, which are excreted from organs of the reticuloendothelial system (liver and kidney), while are relatively slowly eliminated from tumour tissues. Finally, this system, combined with the NIR probe, shows high specificity and sensitivity for detecting bladder cancer in isolated intact patient bladders.

Does Interhospital Transfer Influence the Outcomes of Patients Receiving Surgery for Acute Type A Aortic Dissection? Type A Aortic Dissection: Is Transfer Hazardous or Beneficial?

INTRODUCTION: The progression of acute type A aortic dissection may cause immediate death, such that, in the event of its diagnosis, emergency surgery is indicated. Relatedly, an interhospital transfer may prolong the time from diagnosis to surgery. This study therefore investigated how interhospital transfers impact surgical outcomes for acute type A aortic dissection. MATERIALS AND METHODS: After excluding those patients who received deferred surgery for acute type A aortic dissection, 112 patients who received emergency surgery for the condition at our hospital from January 2011 to January 2018 were enrolled. These patients were divided into two groups, one consisting of the patients who were sent directly to our emergency department (group 1) and the other consisting of the patients who were transferred from another hospital after first being diagnosed with type A aortic dissection (group 2). The collected data included the patient demographics, clinical characteristics, operative findings and methods, postoperative outcomes, latest follow-up time, and most recent status. RESULTS: There were 59 patients in group 1 and 53 patients in group 2. Univariate analysis revealed that group 1 had significantly more patients with a previous stroke (p = 0.007). Moreover, the average length of time from receiving a computed tomography (CT) scan to entering the operating room (OR) was shorter for the group 1 patients (p < 0.001). However, except for the incidence of postoperative acute kidney injury (14.5% versus 33.3%, p = 0.024), there was no statistical difference between the groups in terms of the operative findings and outcomes, such as hypotension before cardiopulmonary bypass, hemopericardium, other complications, and survival rate. Multivariate analysis showed that the independent predictors of hospital mortality included age > 61.5 years (p = 0.017), respiratory rate upon admission > 18.5 breaths/minute (p = 0.046), and total bypass time > 265.6 minutes (p = 0.015). For the patients who survived to discharge, log-rank analysis demonstrated similar cumulative survival rates for the two groups (p = 0.62). Further multivariate analysis showed that the risk of death after discharge was associated with the interval between the CT scan and OR entry (hazard ratio = 0.97 per minute; 95% confidence interval, 0.950-0.998; p = 0.037). CONCLUSION: In this study, it was found that interhospital transfer did not influence the surgical outcomes of patients with acute type A aortic dissection. As such, it can be concluded that the transfer of the patients with type A aortic dissection to tertiary hospitals with experienced cardiac surgical teams may not increase the surgical risk.

Relationships among personality, coping, and concurrent health-related quality of life in women with breast cancer.

BACKGROUND: Theory has suggested that personality plays an important role related to health behavior and results in health outcomes, but inconsistent with the findings exist. Moreover, limited research has focused on style of coping with personality traits and health-related quality of life (HRQOL) for patients with breast cancer. We tested how ways of coping and personality traits are associated with HRQOL in patients with breast cancer, after controlling for age, education, disease severity, and sleep disorders. METHODS: In a cross-sectional study of 207 patients with breast cancer, they completed a set of questionnaires at two general hospitals. The measures used were demographic and individual characteristics, personality traits, ways of coping, and health surveys. We used correlations and hierarchical regressions to determine all relationships among factors, sleep disorders, personality, coping, and HRQOL. RESULTS: Most participants were reported as having stage II (77, 37.2%) breast cancer. About 60% patients with breast cancer have poor sleep and sleep disorders having a negative association with HRQOL. Participants using more active coping, with lower neuroticism, and higher agreeableness traits are more likely to have a better physical quality of life (PQOL). In the PQOL regression model, clinical conditions (duration since cancer diagnosis; sleep disorders) and two personality traits (neuroticism and agreeableness) significantly explained 23% of variance. Moreover, fewer sleep disorders and two personality traits (neuroticism and conscientiousness) significantly explained 31% of variance in the mental quality-of-life (MQOL) regression model. CONCLUSIONS: A high prevalence of sleep disorders for patients with breast cancer has occurred and sleep disorders were negatively associated with PQOL and MQOL. In addition, neuroticism was positively related to sleep disorders and could be relevant to psycho-educational interventions.

Repurposing Cytarabine for Treating Primary Effusion Lymphoma by Targeting Kaposi's Sarcoma-Associated Herpesvirus Latent and Lytic Replications.

Oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) is etiologically linked to primary effusion lymphoma (PEL), an aggressive and nontreatable malignancy commonly found in AIDS patients. In this study, we performed a high-throughput screening of 3,731 characterized compounds and identified cytarabine, approved by the FDA for treating numerous types of cancer, as a potent inhibitor of KSHV-induced PEL. We showed the high efficacy of cytarabine in the growth inhibition of various PEL cells by inducing cell cycle arrest and apoptosis. Cytarabine inhibited host DNA and RNA syntheses and therefore induced cellular cytotoxicity. Furthermore, cytarabine inhibited viral DNA and RNA syntheses and induced the rapid degradation of KSHV major latent protein LANA (latency-associated nuclear antigen), leading to the suppression of KSHV latent replication. Importantly, cytarabine effectively inhibited active KSHV replication and virion production in PEL cells. Finally, cytarabine treatments not only effectively inhibited the initiation and progression of PEL tumors but also induced regression of grown PEL tumors in a xenograft mouse model. Altogether, our study has identified cytarabine as a novel therapeutic agent for treating PEL as well as eliminating KSHV persistent infection.IMPORTANCE Primary effusion lymphoma is an aggressive malignancy caused by Kaposi's sarcoma-associated herpesvirus. The outcome of primary effusion lymphoma is dismal without specific treatment. Through a high-throughput screening of characterized compounds, we identified an FDA-approved compound, cytarabine, as a potent inhibitor of primary effusion lymphoma. We showed that cytarabine induced regression of PEL tumors in a xenograft mouse model. Cytarabine inhibited host and viral DNA and RNA syntheses, resulting in the induction of cytotoxicity. Of interest, cytarabine induced the degradation of KSHV major latent protein LANA, hence suppressing KSHV latent replication, which is required for PEL cell survival. Furthermore, cytarabine inhibited KSHV lytic replication program, preventing virion production. Our findings identified cytarabine as a novel therapeutic agent for treating PEL as well as for eliminating KSHV persistent infection. Since cytarabine is already approved by the FDA, it might be an ideal candidate for repurposing for PEL therapy and for further evaluation in advanced clinical trials.

Structural basis of adaptor-mediated protein degradation by the tail-specific PDZ-protease Prc.

Peptidoglycan (PG) is a highly cross-linked, protective mesh-like sacculus that surrounds the bacterial cytoplasmic membrane. Expansion of PG is tightly coupled to growth of a bacterial cell and requires hydrolases to cleave the cross-links for insertion of nascent PG material. In Escherichia coli, a proteolytic system comprising the periplasmic PDZ-protease Prc and the lipoprotein adaptor NlpI contributes to PG enlargement by regulating cellular levels of MepS, a cross-link-specific hydrolase. Here, we demonstrate how NlpI binds Prc to facilitate the degradation of its substrate MepS by structural and mutational analyses. An NlpI homodimer binds two molecules of Prc and forms three-sided MepS-docking cradles using its tetratricopeptide repeats. Prc forms a monomeric bowl-shaped structure with a lid-like PDZ domain connected by a substrate-sensing hinge that recognizes the bound C terminus of the substrate. In summary, our study reveals mechanistic details of protein degradation by the PDZ-protease Prc bound to its cognate adaptor protein.

The Effects of Muscle Relaxation and Therapeutic Walking on Depression, Suicidal Ideation, and Quality of Life in Breast Cancer Patients Receiving Chemotherapy.

BACKGROUND: The suicide rate of cancer patients is high in Taiwan. Breast cancer has a high incidence rate and is the leading cause of cancer in women. There is a lack of research examining breast cancer-related depression, suicidal ideation, and quality of life. OBJECTIVES: This study evaluated the effects of muscle relaxation and therapeutic walking on depression, suicidal ideation, and quality of life in breast cancer patients receiving chemotherapy. METHODS: An experimental approach was adopted. A group of 87 breast cancer patients receiving chemotherapy were randomly assigned into an experimental group (n = 44) or a control group (n = 43). The subjects in the experimental group received 2 interventions for 3 months. This study used 3 instruments, including (1) the Center for Epidemiological Studies Depression Scale, (2) the Beck Scale for Suicidal Ideation, and (3) the World Health Organization Questionnaire on Quality of Life. RESULTS: The results showed no significant difference in any outcome variable in the pretest. The results of the posttest indicated that the 2 groups scored significantly differently only on the Center for Epidemiological Studies Depression Scale (U = 638.00, P < .05). The breast cancer patients who participated in the 3 month muscle relaxation and therapeutic walking interventions had a lower level of depression (RE¯ = 37.00) than those who did not (RC¯ = 51.16). CONCLUSION: The muscle relaxation and therapeutic walking program was effective in the reduction of breast cancer patients' depression. IMPLICATIONS FOR PRACTICE: Nursing staff could teach muscle relaxation and therapeutic walking to breast cancer patients to reduce their depression.

Neurodevelopmental Outcomes in Very Low Birth Weight Infants Using Aminophylline for the Treatment of Apnea.

BACKGROUND: Aminophylline has been widely used in the treatment of apneic episodes in premature infants. Animal models suggest caution in the use of aminophylline as it may increase the cerebral metabolic rate and decrease the rate of anoxic survival in neonates. This study aimed to evaluate the neurological outcomes in very low birth weight (VLBW) infants treated with aminophylline for apnea in our neonatal intensive care unit. METHODS: All VLBW infants (body birth weight < 1500 g) admitted to our neonatal intensive care unit between January 2000 and December 2011 were enrolled in this retrospective study. Clinical characteristics and outcomes of these infants were reviewed and recorded. Scores on the Bayley Scales of Infant Development at 6 months, 12 months, and 18 months of corrected age were also recorded. The controls (who did not receive aminophylline) were matched for gestational age with the aminophylline group. RESULTS: The baseline characteristics of the aminophylline group and the control group were similar. The neurodevelopmental outcomes as well as rates of patent ductus arteriosus, brain injury, severe retinopathy of prematurity, and necrotizing enterocolitis were not significantly different between the two groups. Only bronchopulmonary dysplasia remained significantly higher in the aminophylline group after adjusting for risk factors (48.08% vs. 21.15%; adjusted odds ratio: 12.50; p < 0.001). CONCLUSION: Aminophylline therapy for apnea of prematurity had no apparent and additional risk on the neurodevelopmental outcomes of VLBW infants at a corrected age of 18 months. Further studies with a larger sample size are needed to confirm the adverse neurological effects of aminophylline treatment.

Polysaccharides from Ganoderma formosanum function as a Th1 adjuvant and stimulate cytotoxic T cell response in vivo.

The fungus of Ganoderma is a basidiomycete that possesses a variety of pharmacological effects and has been used in traditional Asian medicine for centuries. Ganoderma formosanum is a native Ganoderma species isolated in Taiwan, and we have previously demonstrated that PS-F2, a polysaccharide fraction purified from the submerged culture broth of G. formosanum, exhibits immunostimulatory properties in macrophages. In this study, we further characterized the adjuvant functions of PS-F2. In vitro, PS-F2 stimulated dendritic cells (DCs) to produce proinflammatory cytokines, including TNF-α, interleukin (IL)-6, and IL-12/IL-23 p40. PS-F2 also stimulated DCs to express the maturation markers CD40, CD80, CD86, and MHC class II. In a murine splenocyte culture, PS-F2 treatment resulted in elevated expression of T-bet and interferon (IFN)-γ in T lymphocytes. When used as an adjuvant in vivo with the ovalbumin (OVA) antigen, PS-F2 stimulated OVA-specific antibody production and primed IFN-γ production in OVA-specific T lymphocytes. PS-F2-adjuvated immunization also induced OVA-specific CTLs, which protected mice from a challenge with tumor cells expressing OVA. Collectively, our data show that PS-F2 functions as an adjuvant capable of inducing a Th1-polarized adaptive immune response, which would be useful in vaccines against viruses and tumors.

Electrically tunable organic bioelectronics for spatial and temporal manipulation of neuron-like pheochromocytoma (PC-12) cells.

BACKGROUND: Organic bioelectronic devices consisting of alternating poly(3,4-ethylenedioxythiophene) (PEDOT) and reduced graphite oxide (rGO) striped microelectrode arrays were fabricated by lithography technology. It has been demonstrated that the organic bioelectronic devices can be used to spatially and temporally manipulate the location and proliferation of the neuron-like pheochromocytoma cells (PC-12 cells). METHODS: By coating an electrically labile contact repulsion layer of poly(l-lysine-graft-ethylene glycol) (PLL-g-PEG) on the PEDOT electrode, the location and polarity of the PC-12 cells were confined to the rGO electrodes. RESULTS: The outgrowth of spatially confined bipolar neurites was found to align along the direction of the 20µm wide electrode. The location of the PC-12 cells can also be manipulated temporally by applying electrical stimulation during the neurite differentiation of PC-12 cells, allowing the PC-12 cells to cross over the boundary between the PEDOT and the rGO regions and construct neurite networks in an unconfined manner where the contact repulsive coating of PLL-g-PEG was removed. CONCLUSIONS: This adsorption and desorption of the PLL-g-PEG without and with electrical stimulation can be attributed to the tunable surface properties of the PEDOT microelectrodes, whose surface charge can switch from being negative to positive under electrical stimulation. GENERAL SIGNIFICANCE: The electrically tunable organic bioelectronics reported here could potentially be applied to tissue engineering related to the development and regeneration of mammalian nervous systems. The spatial and temporal control in this device would also be used to study the synapse junctions of neuron-neuron contacts in both time and space domains. This article is part of a Special Issue entitled Organic Bioelectronics - Novel Applications in Biomedicine.

A strategy for reduction of antibiotic use in new patients admitted to a neonatal intensive care unit.

BACKGROUND: In order to reduce the unnecessary use of and provide appropriate guidance for the administration of antibiotics, the neonatal bacterial infections screening score (NBISS) was developed to assess each new patient that is admitted to the neonatal intensive care unit (NICU). METHODS: NBISS was designed based on maternal risk factors, clinical presentations, and laboratory data. The total score of each new patient is calculated at the time of admission. The first period of this study was an observational survey. Receiver operating characteristic (ROC) curves were used to determine the best cut-off NBISS for the diagnosis of bacterial infection (BI) and guide the use of antibiotics during the second period of this study. RESULTS: Of 250 neonates who were admitted to the NICU, 237 (94.8%) received antibiotics during the first period of study. The initial total scores were not statistically different between the BI and non-BI groups (p = 0.155). We weighted C-reaction protein (CRP) (by 8×), the presence of a bulging fontanelle, pus from the ear canal, redness around the umbilicus, reduced movement, and being unable to feed (each by 5×) as significantly different between the BI and non-BI groups (p = 0.015). Weighted scores >8 points demonstrated the best diagnostic accuracy for indicating BI. After introducing NBISS for predicting BI in new patients admitted to NICU, the rate of antibiotic use significantly decreased from 94.8% to 60.3% between the two periods. CONCLUSION: Using this simple screening strategy, we were able to clinically reduce the use of unnecessary antibiotics.

Ectopic pancreatic tissue presenting as an umbilcal mass in a newborn: a case report.

The case of an ectopic pancreatic mass at the umbilicus in an 8-day-old male neonate is reported, the youngest patient with this condition ever reported in an English-language journal. The patient was healthy except for a protruding mass with intermittent mucous discharge at the base of the umbilical stump. Surgical intervention was performed under the impression of the umbilical mass. Pathology diagnosed an ectopic pancreas with acute hemorrhage. To the best of our knowledge, only one case of ectopic pancreas presenting as an umbilical mass with intermittent mucous discharge has previously been reported.