Phosphorylation of EZH2 by AMPK Suppresses PRC2 Methyltransferase Activity and Oncogenic Function.

Sustained energy starvation leads to activation of AMP-activated protein kinase (AMPK), which coordinates energy status with numerous cellular processes including metabolism, protein synthesis, and autophagy. Here, we report that AMPK phosphorylates the histone methyltransferase EZH2 at T311 to disrupt the interaction between EZH2 and SUZ12, another core component of the polycomb repressive complex 2 (PRC2), leading to attenuated PRC2-dependent methylation of histone H3 at Lys27. As such, PRC2 target genes, many of which are known tumor suppressors, were upregulated upon T311-EZH2 phosphorylation, which suppressed tumor cell growth both in cell culture and mouse xenografts. Pathologically, immunohistochemical analyses uncovered a positive correlation between AMPK activity and pT311-EZH2, and higher pT311-EZH2 correlates with better survival in both ovarian and breast cancer patients. Our finding suggests that AMPK agonists might be promising sensitizers for EZH2-targeting cancer therapies.

Characterization of Mammary Tumors Arising from MMTV-PyVT Transgenic Mice.

Among genetically engineered mouse models of breast cancer, MMTV-PyVT is a mouse strain in which the oncogenic polyoma virus middle T antigen is driven by the mouse mammary tumor virus promoter. The aim of the present study was to perform morphologic and genetic analyses of mammary tumors arising from MMTV-PyVT mice. To this end, mammary tumors were obtained at 6, 9, 12, and 16 weeks of age for histology and whole-mount analyses. We conducted whole-exome sequencing to identify constitutional and tumor-specific mutations, and genetic variants were identified using the GRCm38/mm10 mouse reference genome. Using hematoxylin and eosin analysis and whole-mount carmine alum staining, we demonstrated the progressive proliferation and invasion of mammary tumors. Frameshift insertions/deletions (indels) were noted in the Muc4. Mammary tumors showed small indels and nonsynonymous single-nucleotide variants but no somatic structural alterations or copy number variations. In summary, we validated MMTV-PyVT transgenic mice as a multistage model for mammary carcinoma development and progression. Our characterization may be used as a reference for guidance in future research.

Factors associated with the intention to engage in care planning among persons with mild cognitive impairment and dementia.

This study examined factors associated with the intention to engage in advance care planning among persons with cognitive impairment. This cross-sectional study recruited 116 persons with cognitive impairment by convenience sampling from two teaching hospitals in Northern Taiwan from November 1, 2018, to December 31, 2020. Fewer than 50% of the participants intended to engage in advance care planning, and less than 10% signed the living will for hospice and palliative care. Multivariate linear regression determined factors influencing advance care planning intention included education level, a proxy signed do-not-resuscitate document, belief that family members would provide a signed do-not-resuscitate at their end-of-life, and necessity of explaining future care in advance. It is recommended to popularize advance care planning education and ensure the rights of persons with cognitive impairment to enable them to fully participate in their own care plans through family-centered advance care planning.

PCK1 regulates neuroendocrine differentiation in a positive feedback loop of LIF/ZBTB46 signalling in castration-resistant prostate cancer.

BACKGROUND: Castration-resistant prostate cancer (CRPC) patients frequently develop neuroendocrine differentiation, with high mortality and no effective treatment. However, the regulatory mechanism that connects neuroendocrine differentiation and metabolic adaptation in response to therapeutic resistance of prostate cancer remain to be unravelled. METHODS: By unbiased cross-correlation between RNA-sequencing, database signatures, and ChIP analysis, combining in vitro cell lines and in vivo animal models, we identified that PCK1 is a pivotal regulator in therapy-induced neuroendocrine differentiation of prostate cancer through a LIF/ZBTB46-driven glucose metabolism pathway. RESULTS: Upregulation of PCK1 supports cell proliferation and reciprocally increases ZBTB46 levels to promote the expression of neuroendocrine markers that are conducive to the development of neuroendocrine characteristic CRPC. PCK1 and neuroendocrine marker expressions are regulated by the ZBTB46 transcription factor upon activation of LIF signalling. Targeting PCK1 can reduce the neuroendocrine phenotype and decrease the growth of prostate cancer cells in vitro and in vivo. CONCLUSION: Our study uncovers LIF/ZBTB46 signalling activation as a key mechanism for upregulating PCK1-driven glucose metabolism and neuroendocrine differentiation of CRPC, which may yield significant improvements in prostate cancer treatment after ADT using PCK1 inhibitors.

Factors associated with positive aspects of caregiving experiences among family caregivers of persons living with dementia in Taiwan: A cross-sectional study.

This study examined the associated factors of positive aspects of caregiving experience among family caregivers of persons living with dementia in Taiwan. This cross-sectional correlational study recruited dyads of primary family caregivers of persons living with dementia by convenience sampling from dementia care centers in northern Taiwan from September 9, 2020, to June 20, 2021. A total of 100 dyads who met inclusions criteria agreed to participate in the study. Significant predictors of positive aspects of caregiving experience were scores of dementia behavior disturbance (t=-3.63, p =<.001), a spousal caregiver (t=2.83, p =.006), and the subscale score for satisfaction on the functional social support (t=2.62, p =.01). Our findings suggest prevention and treatment of dementia behavior disturbance for persons living with dementia, improving satisfaction with functional social support, and focusing on non-spousal caregivers could enhance experiences of positive caregiving for family caregivers.

Trilostane, a 3ß-hydroxysteroid dehydrogenase inhibitor, suppresses growth of hepatocellular carcinoma and enhances anti-cancer effects of sorafenib.

Background Human 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) is an enzyme associated with steroidogenesis, however its' role in hepatocellular carcinoma (HCC) biology is unknown. Trilostane is an inhibitor of HSD3B1 and has been tested as a treatment for patients with breast cancer but has not been studied in patients with HCC. Methods and Results The expression of HSD3B1 in HCC tumors in 57 patients were examined. A total of 44 out of 57 tumors (77.2%) showed increased HSD3B1 expression. The increased HSD3B1 in tumors was significantly associated with advanced HCC. In vitro, the knockdown of HSD3B1 expression in Mahlavu HCC cells by a short hairpin RNA (shRNA) led to significant decreases in colony formation and cell migration. The suppression of clonogenicity in the HSD3B1-knockdown HCC cells was reversed by testosterone and 17ß-estradiol. Trilostane-mediated inhibition of HSD3B1 in different HCC cells also caused significant inhibition of clonogenicity and cell migration. In subcutaneous HCC Mahlavu xenografts, trilostane (30 or 60 mg/kg, intraperitoneal injection) significantly inhibited tumor growth in a dose-dependent manner. Furthermore, the combination of trilostane and sorafenib significantly enhanced the inhibition of clonogenicity and xenograft growth, surpassing the effects of each drug used alone, with no documented additional toxicity to animals. HSD3B1 blockade was found to suppress the phosphorylation of extracellular signal-regulated kinase (ERK). The decreased ERK phosphorylation was reversed by testosterone or 17b-estradiol. Conclusions Trilostane significantly inhibited the growth of HCC by inhibiting HSD3B1 function and augmenting the efficacy of sorafenib.

Overexpression of chitinase-3-like protein 1 is associated with structural recurrence in patients with differentiated thyroid cancer.

We previously identified that the expression of chitinase-3-like protein 1 (CHI3L1) was upregulated during thyroid cancer progression. Here, we investigated the prognostic significance of CHI3L1 expression in thyroid neoplasms and examined the potential oncogenic roles. CHI3L1 immunochemical staining was performed on tissue microarrays of benign and malignant thyroid tumours. Compared with normal thyroid tissue and benign thyroid lesions that had low or no detectable CHI3L1 expression, CHI3L1 was overexpressed in both differentiated and undifferentiated thyroid cancer. High CHI3L1 expression was associated with extrathyroidal extension, lymph node metastasis, and shorter recurrence-free survival in differentiated thyroid cancer. The biological roles of CHI3L1 were further investigated by gain- and loss-of-function assays. CHI3L1 silencing suppressed clonogenicity, migration, invasion, anoikis resistance, and angiogenesis in thyroid cancer cells, although exogenous CHI3L1 treatment promoted these malignant phenotypes. Cysteine-rich angiogenic inducer 61 (CYR61) was identified as a downstream target of CHI3L1 by RNA-seq analysis. CYR61 silencing or treatment reversed the alterations induced by CHI3L1 modulation. Our results demonstrate that CHI3L1 is overexpressed in thyroid cancer and is associated with an increased risk of disease recurrence. Additionally, CYR61 may participate in CHI3L1-mediated tumour progression. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Learning curve analysis of radiofrequency ablation for benign thyroid nodules.

BACKGROUND: Radiofrequency ablation (RFA) has been increasingly accepted as an alternative to surgery in the treatment of symptomatic benign thyroid nodules. However, the learning curve of thyroid RFA has yet to be defined. We hypothesized a temporal relationship between proficiency of the skill and midterm volume reduction. METHODS: Consecutive patients who underwent RFA and had at least a six-month follow-up were identified from an institutional database. The cumulative sum (CUSUM) analysis was applied to visualize the learning curve on the adjusted volume reduction rate (VRR). RESULTS: A total of 102 nodules in 93 patients were included in the analysis. Linear regression revealed that nodule composition was the main predictor of the VRR. The composition-adjusted VRR increased with the chronological treatment order. The series was divided into three phases based on inflection points of the CUSUM analysis: the initial learning phase (case 1-20), consolidation phase (case 21-65), and proficiency phase (case 66-102). In the later phase, more solid nodules were treated, power output used by the operator was higher, and RFA treatment time was longer. CONCLUSION: The treatment efficiency of thyroid RFA was associated with technical proficiency, suggesting the presence of a learning curve effect.

[The Impact of Family-Centered Advance Care Planning for Persons With Dementia and Family Caregivers on Decision-Making Conflicts in End-of-Life Care].

BACKGROUND: Participating in advance care planning (ACP) discussions during the early stages of dementia is crucial to ensuring the quality of end-of-life (EoL) care. Inadequate discussions regarding ACP and EoL care between persons with dementia and family caregivers often lead to decisional conflicts when persons with dementia are in the later stages of their disease. PURPOSE: To explore the impact of a family-centered ACP information intervention on the EoL care decision-making conflicts between persons with dementia and their family caregivers. METHODS: A one-group, pretest-posttest, pre-experimental design was applied. Data were collected at outpatient clinics in regional teaching hospitals in northern Taiwan. Participants included 43 dyads of persons diagnosed with mild cognitive impairment or mild dementia and their family caregivers. The intervention was implemented by an ACP-trained senior registered nurse and was guided using ACP manuals and family-centered strategies. The decisional conflict scale was the main measure used. Paired t tests were used to compare differences between pre-intervention data and 4-weeks' post-intervention data. RESULTS: The ACP information intervention significantly reduced the decisional conflict score for end-of-life decision making in the participants with mild dementia (p < .001). In addition, significant declines were observed in all aspects of decision-making conflicts, including value clarification, uncertainty, and effective decision-making. The mean total conflict score of the family caregivers was also significantly reduced (p < .001), but no significant difference was found in the aspect of support. CONCLUSIONS: Family-centered care strategies provide knowledge about end-of-life care for persons with dementia. These strategies also facilitate regular and continuous communication between family caregivers, persons with dementia, and medical professionals, reducing decisional conflicts in EoL care.

Osteocalcin is an Independent Predictor for Hungry Bone Syndrome After Parathyroidectomy.

BACKGROUND: Hungry bone syndrome is characterized by prolonged and severe hypocalcemia following parathyroidectomy. Previously, we reported that preoperative alkaline phosphatase is a major factor predicting prolonged hospital stay. Nonetheless, some patients with low alkaline phosphatase levels presented with hungry bone syndrome, suggesting that additional factors may play a role. METHODS: From September 2010 to December 2017, consecutive dialysis patients who underwent parathyroidectomy for secondary hyperparathyroidism were analyzed. Length of hospital stay was used as a surrogate marker for postoperative bone hunger. RESULTS: A total of 260 patients were included in the study. The median postoperative hospital stay was 3 days, and 69 (27%) patients had a stay longer than 3 days. Multivariate logistic regression analysis revealed that alkaline phosphatase (odds ratio [OR] = 1.005), osteocalcin (OR = 1.001), and subtotal parathyroidectomy (OR = 0.061) were associated with prolonged hospital stay. Multivariate linear regression analysis indicated that age (ß = - 0.170), alkaline phosphatase (ß = 0.430), and osteocalcin (ß = 0.166) were correlated with the length of stay. After surgery, the median osteocalcin level increased from 264 to 478 ng/mL (P < 0.001). CONCLUSIONS: Alkaline phosphatase is the main predictor of hungry bone syndrome after parathyroidectomy, and preoperative osteocalcin is an additional independent predictor. Patients with a high osteocalcin level may prone to have a higher demand for calcium supplementation.

Machine Learning Model for Risk Prediction of Community-Acquired Acute Kidney Injury Hospitalization From Electronic Health Records: Development and Validation Study.

BACKGROUND: Community-acquired acute kidney injury (CA-AKI)-associated hospitalizations impose significant health care needs and contribute to in-hospital mortality. However, most risk prediction models developed to date have focused on AKI in a specific group of patients during hospitalization, and there is limited knowledge on the baseline risk in the general population for preventing CA-AKI-associated hospitalization. OBJECTIVE: To gain further insight into risk exploration, the aim of this study was to develop, validate, and establish a scoring system to facilitate health professionals in enabling early recognition and intervention of CA-AKI to prevent permanent kidney damage using different machine-learning techniques. METHODS: A nested case-control study design was employed using electronic health records derived from a group of Chang Gung Memorial Hospitals in Taiwan from 2010 to 2017 to identify 234,867 adults with at least two measures of serum creatinine at hospital admission. Patients were classified into a derivation cohort (2010-2016) and a temporal validation cohort (2017). Patients with the first episode of CA-AKI at hospital admission were classified into the case group and those without CA-AKI were classified in the control group. A total of 47 potential candidate variables, including age, gender, prior use of nephrotoxic medications, Charlson comorbid conditions, commonly measured laboratory results, and recent use of health services, were tested to develop a CA-AKI hospitalization risk model. Permutation-based selection with both the extreme gradient boost (XGBoost) and least absolute shrinkage and selection operator (LASSO) algorithms was performed to determine the top 10 important features for scoring function development. RESULTS: The discriminative ability of the risk model was assessed by the area under the receiver operating characteristic curve (AUC), and the predictive CA-AKI risk model derived by the logistic regression algorithm achieved an AUC of 0.767 (95% CI 0.764-0.770) on derivation and 0.761 on validation for any stage of AKI, with positive and negative predictive values of 19.2% and 96.1%, respectively. The risk model for prediction of CA-AKI stages 2 and 3 had an AUC value of 0.818 for the validation cohort with positive and negative predictive values of 13.3% and 98.4%, respectively. These metrics were evaluated at a cut-off value of 7.993, which was determined as the threshold to discriminate the risk of AKI. CONCLUSIONS: A machine learning-generated risk score model can identify patients at risk of developing CA-AKI-related hospitalization through a routine care data-driven approach. The validated multivariate risk assessment tool could help clinicians to stratify patients in primary care, and to provide monitoring and early intervention for preventing AKI while improving the quality of AKI care in the general population.

Inhibition of 3ß-Hydroxysteroid Dehydrogenase Type 1 Suppresses Interleukin-6 in Breast Cancer.

BACKGROUND: Recently, we demonstrated that the expression of 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) in breast cancer is associated with shorter recurrence-free survival, and genetic or pharmacologic inhibition of HSD3B1 reduced colony formation and xenograft growth. However, the mechanisms are unclear. METHODS: Triple-negative MDA-MB-231 and BT-20 breast cancer cells underwent HSD3B1 silencing. Microarray and bioinformatic analysis were performed. The interleukin-6 (IL-6) expression and secretion were evaluated using real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Clonogenic ability and cell viability were determined in the absence or presence of recombinant IL-6. RESULTS: Functional and pathway enrichment analyses showed that HSD3B1 silencing modulates the expression of several growth factors and cytokines. Cells transfected with HSD3B1-targeting small interfering RNA or treated with an HSD3B1 inhibitor (trilostane) had decreased IL-6 expression and secretion. HSD3B1 inhibition reduced colony formation, which was partially rescued by IL-6 supplementation. The HSD3B1 knockdown enhanced paclitaxel sensitivity, and IL-6 treatment partially reversed the augmented cytotoxicity. CONCLUSIONS: Our findings suggest that the therapeutic potential of targeting HSD3B1 is in part mediated by IL-6 suppression.

Dementia-friendly community indicators from the perspectives of people living with dementia and dementia-family caregivers.

AIMS: To identify dementia-friendly communities' indicators and their current conditions in Taiwan from the perspectives of people with dementia and dementia-family caregivers. DESIGN: This qualitative study explored the opinions and experiences of people with dementia and dementia-family caregivers regarding dementia-friendly communities. METHODS: Participants (16 people with dementia and 20 family caregivers) were recruited from neurological clinics, day care centres for people with dementia and support groups for family caregivers in the Taipei community from July - October, 2016. Data were collected in face-to-face interviews, which were tape recorded and transcribed verbatim. Transcripts were analysed by Miles and Huberman's (1994) guidelines. RESULTS: Similar indicators for dementia-friendly communities were identified in Taiwan as in other countries, including dementia-friendly care services, dementia-friendly hospitals, dementia-friendly community environment, dementia-friendly transportation, dementia-friendly stores and shops, dementia friendly people, integrated dementia-related information and community contribution- and -involvement opportunities for people with dementia. However, Taiwanese people with dementia and family caregivers described no emphasis on the potential of people with dementia to contribute to developing dementia-friendly communities and more top-down expectations for the government's role. CONCLUSION: These indicators can be a guide for developing and evaluating dementia-friendly communities in Taiwan. Differences between Taiwan and Western developed countries in indicators for dementia-friendly communities can be further explored. Community nursing assessment, interventions, and evaluation based on these dementia-friendly communities indicators can be further developed. IMPACT: This study developed indicators for dementia-friendly communities in an Asian country. These indicators can be used as a guide for developing and evaluating dementia-friendly communities.

Expression of serine peptidase inhibitor Kunitz type 1 in differentiated thyroid cancer.

SPINT1, also known as HAI-1, is a Kunitz-type serine protease inhibitor that inhibits multiple proteases including hepatocyte growth factor (HGF) activator and matriptase. SPINT1 has been shown to modulate HGF/MET activation in certain cancer types. In the present study, we analyzed microarray datasets and found that SPINT1 was consistently upregulated in differentiated thyroid cancer. SPINT1 protein expression was investigated using tissue microarrays and independent samples of our 143 patients. Strong SPINT1 expression was observed in 61-68% of papillary thyroid cancer and 41-50% of follicular thyroid cancer. The overexpression diminished in anaplastic thyroid cancer. The SPINT1 expression in normal thyroid tissues and benign thyroid lesions was low. Furthermore, we noted that the SPINT1 expression was associated with extrathyroidal invasion, lymphovascular invasion, lymph node metastasis, advanced TNM stage, and a higher risk of recurrence in differentiated thyroid cancer. The results were in accordance with our analysis of The Cancer Genome Atlas data. In conclusion, an overexpression of SPINT1 appears to be associated with an invasive phenotype in differentiated thyroid cancer.

Crystal orientation of PEO confined within the nanorod templated by AAO nanochannels.

The orientation of poly(ethylene oxide) (PEO) crystallites developed in the nanochannels of anodic aluminum oxide (AAO) membrane has been investigated. PEO was filled homogeneously into the nanochannels in the melt state, and the crystallization confined within the PEO nanorod thus formed was allowed to take place subsequently at different temperatures. The effects of PEO molecular weight (MPEO), crystallization temperature (Tc) and AAO channel diameter (DAAO) on the crystal orientation attained in the nanorod were revealed by 2-D wide angle X-ray scattering (WAXS) patterns. In the nanochannels with DAAO = 23 nm, the crystallites formed from PEO with the lowest MPEO (= 3400 g mol-1) were found to adopt a predominantly perpendicular orientation with the crystalline stems aligning normal to the channel axis irrespective of Tc (ranging from -40 to 20 °C). Increasing MPEO or decreasing Tc tended to induce the development of the tilt orientation characterized by the tilt of the (120) plane by 45° from the channel axis. In the case of the highest MPEO (= 95 000 g mol-1) studied, both perpendicular and tilt orientations coexisted irrespective of Tc. Coexistent orientation was always observed in the channels with a larger diameter (DAAO = 89 nm) irrespective of MPEO and Tc. Compared with the previous results of the crystal orientation attained in nanotubes templated by the preferential wetting of the channel walls by PEO, the window of the perpendicular crystal orientation in the nanorod was much narrower due to its weaker confinement effect imposed on the crystal growth than that set by the nanotube.

Parathyroidectomy decreases neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios.

BACKGROUND: Systemic inflammation has been implicated in complications and heightened mortality of patients with secondary hyperparathyroidism. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are widely available surrogate markers of inflammation. This study sought to delineate the changes in NLR and PLR after parathyroidectomy. METHODS: A total of 213 patients undergoing initial parathyroidectomy from 2010 to 2015 for secondary hyperparathyroidism were identified from a prospectively maintained clinical database. Among 183 patients free of persistent or recurrent disease, follow-up NLR and PLR were available for analysis in 85 patients. RESULTS: In the whole study population, the baseline NLR was positively correlated with male sex, total white blood cell count, height, serum phosphorus, and calcium-phosphorus product levels. The baseline PLR was positively correlated with platelet count, serum phosphorus, and calcium-phosphorus product levels and negatively associated with patient age. Postoperative parathyroid hormone levels were positively correlated with NLR and PLR at follow-up. For patients who had successful parathyroidectomy, there was a decrease in NLR (P = 0.0006), PLR (P = 0.0003), and platelet count (P = 0.033), whereas hemoglobin significantly increased (P = 0.0002) after surgery. Those with persistent or recurrent hyperparathyroidism had no change in NLR, PLR, hemoglobin, total white blood cell, or platelet count. CONCLUSIONS: Successful parathyroidectomy is associated with a decrease in NLR and PLR. The modulatory effects of parathyroidectomy on systemic inflammation may partially explain the benefits of surgery in secondary hyperparathyroidism.

Expression of 3ß-Hydroxysteroid Dehydrogenase Type 1 in Breast Cancer is Associated with Poor Prognosis Independent of Estrogen Receptor Status.

BACKGROUND: Human 3ß-hydroxysteroid dehydrogenase type 1 (HSD3B1) plays a vital role in steroidogenesis in breast tumors and may therefore be a suitable target for treatment of breast cancer. This study investigated the role of HSD3B1 in the pathogenesis of breast cancer in clinical and experimental settings. METHODS: Expression of HSD3B1 in primary tumors of 258 breast cancer patients was evaluated by immunohistochemistry. Screening of breast cancer cell lines indicated that triple-negative MDA-MB-231 cells expressed HSD3B1. The effects from genetic and pharmacologic inhibition of HSD3B1 were assessed in vitro and in vivo. RESULTS: The findings showed that 44% of the 258 breast cancers were HSD3B1-positive. The HSD3B1-positivity was associated with advanced-stage disease (p = 0.009) and reduced recurrence-free survival (p = 0.048) but not with tumor subtype or estrogen receptor status. Silencing of HSD3B1 or treatment with an HSD3B1 inhibitor (trilostane) reduced colony formation in breast cancer cells. Knockdown of HSD3B1 inhibited cell proliferation and migration. Analysis of a murine xenograft tumor model indicated that trilostane significantly slowed tumor growth. CONCLUSIONS: Expression of HSD3B1 in breast cancer is negatively associated with prognosis. The study found HSD3B1 to be a potential therapeutic target for breast cancer independent of estrogen receptor status.

Effect of Perioperative Intravenous Lidocaine Infusion on Acute and Chronic Pain after Breast Surgery: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Intravenous lidocaine infusion has been shown to reduce postoperative pain among patients undergoing abdominal surgery. This study aimed to evaluate the effects of perioperative lidocaine administration in breast surgery. METHODS: A meta-analysis of randomized controlled trials comparing lidocaine infusion vs. placebo/routine treatment was performed. Standardized mean difference (SMD) or risk ratio (RR) with 95% confidence intervals (CIs) was calculated from pooled data. Random-effects models were used, and heterogeneity was assessed. RESULTS: A total of 4 reports (3 primary studies and 1 extension) with 84 patients randomized to the lidocaine group and 83 patients randomized to the control group were included. There was no difference in pain scores at rest or during activity between the 2 groups from postoperative 2 hours to 3 days. At postoperative 72 hours, the lidocaine group had fewer analgesics consumed (SMD, -0.479; 95% CI, -0.914 to -0.043; P = 0.031). Chronic pain was assessed 3 to 6 months after breast surgery in 51 patients of the lidocaine group and 46 patients of the control group. Patients in the lidocaine group had significantly lower risk for the development of chronic pain (RR, 0.332; 95% CI, 0.141 to 0.781; P = 0.012). CONCLUSION: The results indicate no significant benefits of intravenous lidocaine infusion in terms of acute postoperative pain. Although lidocaine seems to attenuate the risk of chronic pain after breast surgery, there is insufficient evidence to conclude that lidocaine infusion is of proved benefit because the results were based on a limited number of small trials.

Crystallization behaviour of poly(ethylene oxide) under confinement in the electrospun nanofibers of polystyrene/poly(ethylene oxide) blends.

We have studied the confined crystallization behaviour of poly(ethylene oxide) (PEO) in the electrospun nanofibers of the phase-separated blends of polystyrene (PS) and PEO, where PS was present as the major component. The size and shape of PEO domains in the nanofibers were considerably different from those in the cast films, presumably because of the nano-dimensions of the nanofibers and the extensional forces experienced by the polymer solution during electrospinning. The phase-separated morphology in turn influenced the crystallization behaviour of PEO in the blend nanofibers. At a PEO weight fraction of ≥0.3, crystallization occurred through a heterogeneous nucleation mechanism similar to that in cast blend films. However, as the PEO weight fraction in the blend nanofibers was reduced from 0.3 to 0.2, an abrupt transformation of the nucleation mechanism from the heterogeneous to predominantly homogenous type was observed. The change in the nucleation mechanism implied a drastic reduction of the spatial continuity of PEO domains in the nanofibers, which was not encountered in the cast film. The melting temperature and crystallinity of the PEO crystallites developed in the nanofibers were also significantly lower than those in the corresponding cast films. The phenomena observed were reconciled by the morphological observation, which revealed that the phase separation under the radial constraint of the nanofibers led to the formation of small-sized fibrillar PEO domains with limited spatial connectivity. The thermal treatment of the PS/PEO blend nanofibers above the glass transition temperature of PS induced an even stronger confinement effect on PEO crystallization.

Aberrant expression of tumor-associated carbohydrate antigen Globo H in thyroid carcinoma.

BACKGROUND AND OBJECTIVES: The induction of tumor-associated carbohydrate antigen results from altered glycosylation in transformed cells. Globo H is a hexasaccharide glycosphingolipid overexpressed on malignancies of epithelial origin and has become an attractive vaccine target. We aimed to investigate the expression patterns and prognostic value of Globo H in thyroid neoplasms. METHODS: Globo H expression was examined by immunohistochemical analysis using commercial and in-house tissue microarrays. The expression was correlated with clinicopathologic characteristics in papillary thyroid cancer. RESULTS: Normal or benign thyroid lesions were negative for Globo H expression. Globo H was positive in 33% medullary, 24% papillary, 11% undifferentiated, and 8% follicular thyroid cancer. Globo H expression in papillary thyroid cancer was associated with extrathyroidal invasion (P = 0.017), BRAF mutation (P = 0.010), AMES high risk (P = 0.045), and increased ATA risk of recurrence (P = 0.022). CONCLUSIONS: Globo H is specifically expressed in a subset of thyroid malignancies. In papillary thyroid cancer, Globo H expression is associated with invasiveness and BRAF mutation. Immunotherapy targeting Globo H may have potential applications in thyroid cancer. J. Surg. Oncol. 2016;114:853-858. © 2016 2016 Wiley Periodicals, Inc.