Development and external validation of a model to predict multidrug-resistant bacterial infections in patients with cirrhosis.

With the increasing rate of infections caused by multidrug-resistant organisms (MDRO), selecting appropriate empiric antibiotics has become challenging. We aimed to develop and externally validate a model for predicting the risk of MDRO infections in patients with cirrhosis. METHODS: We included patients with cirrhosis and bacterial infections from two prospective studies: a transcontinental study was used for model development and internal validation (n = 1302), and a study from Argentina and Uruguay was used for external validation (n = 472). All predictors were measured at the time of infection. Both culture-positive and culture-negative infections were included. The model was developed using logistic regression with backward stepwise predictor selection. We externally validated the optimism-adjusted model using calibration and discrimination statistics and evaluated its clinical utility. RESULTS: The prevalence of MDRO infections was 19% and 22% in the development and external validation datasets, respectively. The model's predictors were sex, prior antibiotic use, type and site of infection, MELD-Na, use of vasopressors, acute-on-chronic liver failure, and interaction terms. Upon external validation, the calibration slope was 77 (95% CI .48-1.05), and the area under the ROC curve was .68 (95% CI .61-.73). The application of the model significantly changed the post-test probability of having an MDRO infection, identifying patients with nosocomial infection at very low risk (8%) and patients with community-acquired infections at significant risk (36%). CONCLUSION: This model achieved adequate performance and could be used to improve the selection of empiric antibiotics, aligning with other antibiotic stewardship program strategies.

Autolyzed yeast and sodium butyrate supplemented alone to diets promoted improvements in performance, intestinal health and nutrient transporter in weaned piglets.

This study investigated the effects of supplemental nucleotides, autolyzed yeast (Saccharomyces cerevisiae), and sodium butyrate in diets for nursery pigs on growth performance, diarrhea incidence, blood profile, intestinal morphology, mRNA expression of nutrient transporters, inflammatory markers, antioxidant profile, and tight junction proteins in the small intestine. One hundred eighty 21-day-old pigs (5.17 ± 0.57 kg) were assigned in a randomized block design to 1 of 4 dietary treatments: (1) CON: control, basal diet, (2) NUC: CON + nucleotides, (3) YSC: CON + lysed yeast S. cerevisiae, (4) ASB: CON + acidifier sodium butyrate. Pigs were fed for 24 days, phase 1 (21-32 days) and 2 (32-45 days). During phase 1, YSC and ASB improved average daily gain (ADG) and feed conversion (FC) compared with CON. At the overall period, ASB improved ADG and YSC improved FC compared with CON. The NUC diet did not affect growth performance. The ASB increased ileal villus height compared to CON. The YSC and ASB reduced the number of Peyer's patches in the ileum compared with CON. The YSC increased mRNA expression of nutrient transporters (SMCT2, MCT1, and PepT1), tight junction proteins (OCL and ZO-1), antioxidants (GPX), and IL1-ß in the jejunum compared with CON. The ASB increased mRNA expression of nutrient transporters (SGLT1 and MCT1), tight junction proteins (OCL and ZO-1), and antioxidants (GPX and SOD) compared with CON. In conclusion, autolyzed yeast and sodium butyrate promoted growth performance by improving the integrity of the intestinal barrier, the mRNA expression of nutrient transporters, and antioxidant enzymes in the jejunum of nursery pigs whereas supplementation of nucleotides did not show such effects.

Carbohydrases and Phytase in Poultry and Pig Nutrition: A Review beyond the Nutrients and Energy Matrix.

This review aimed to clarify the mechanisms through which exogenous enzymes (carbohydrases and phytase) influence intestinal health, as well as their effects on the nutrients and energy matrix in diets fed to poultry and pigs reared under sanitary challenging conditions. Enzyme supplementation can positively affect intestinal microbiota, immune system, and enhance antioxidant status. Although enzymes have been shown to save energy and nutrients, their responses under sanitary challenging conditions are poorly documented. Immune system activation alters nutrient partitioning, which can affect the matrix values for exogenous enzymes on commercial farms. Notably, the carbohydrases and phytase supplementation under sanitary challenging conditions align with energy and nutritional valorization matrices. Studies conducted under commercial conditions have shown that matrices containing carbohydrases and phytase can maintain growth performance and health in poultry and pigs. However, these studies have predominantly focused on assessing a single level of reduction in energy and/or available phosphorus and total calcium, limiting our ability to quantify potential energy and nutrient savings in the diet. Future research should delve deeper into determining the extent of energy and nutrient savings and understanding the effects of alone or blended enzymes supplementation to achieve more specific insights.

Predictive value of radiologic studies for malignant otitis externa: a systematic review and meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of Necrotizing Otitis Externa (NOE) based on radiologic studies. METHODS: The PubMed, Cochrane, Embase, Web of Science, SCOPUS, and Google Scholar databases were searched. True-positive and false-negative results were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. RESULTS: The included studies contained data on 37 studies diagnosed with NOE. The sensitivity of gallium-67, technetium-99m, and Magnetic Resonance Imaging (MRI) was 0.9378 (0.7688-0.9856), 0.9699 (0.8839-0.9927), and 0.9417 (0.6968-0.9913), respectively. For Computed Tomography (CT), the positive criteria consisted of bony erosion alone and bony erosion plus any soft tissue abnormality. The sensitivity of CT based only on bony erosion was 0.7062 (0.5954-0.7971); it was higher 0.9572 (0.9000-0.9823) when based on bony erosion plus any soft tissue abnormality. CONCLUSION: The diagnostic sensitivity of technetium-99m, gallium-67, and MRI was favorable. On CT, the presence of bony erosion may be a useful diagnostic marker of NOE, but the diagnostic sensitivity will be even higher if the criterion of any soft tissue abnormality is also included; however, care should be taken when interpreting the results. Our study demonstrates the potential utility of radiology studies for diagnosing NOE, but their lack of specificity must be considered, and standardized anatomic criteria are still needed. LEVEL OF EVIDENCE: 2A.

Predictive value of radiologic studies for malignant otitis externa: a systematic review and meta-analysis

Abstract Objective: To determine the diagnostic accuracy of Necrotizing Otitis Externa (NOE) based on radiologic studies. Methods: The PubMed, Cochrane, Embase, Web of Science, SCOPUS, and Google Scholar databases were searched. True-positive and false-negative results were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Results: The included studies contained data on 37 studies diagnosed with NOE. The sensitivity of gallium-67, technetium-99m, and Magnetic Resonance Imaging (MRI) was 0.9378 (0.7688-0.9856), 0.9699 (0.8839-0.9927), and 0.9417 (0.6968-0.9913), respectively. For Computed Tomography (CT), the positive criteria consisted of bony erosion alone and bony erosion plus any soft tissue abnormality. The sensitivity of CT based only on bony erosion was 0.7062 (0.5954-0.7971); it was higher 0.9572 (0.9000-0.9823) when based on bony erosion plus any soft tissue abnormality. Conclusion: The diagnostic sensitivity of technetium-99m, gallium-67, and MRI was favorable. On CT, the presence of bony erosion may be a useful diagnostic marker of NOE, but the diagnostic sensitivity will be even higher if the criterion of any soft tissue abnormality is also included; however, care should be taken when interpreting the results. Our study demonstrates the potential utility of radiology studies for diagnosing NOE, but their lack of specificity must be considered, and standardized anatomic criteria are still needed. Level of evidence: 2A.

Advances, Implications, and Limitations of Low-Crude-Protein Diets in Pig Production.

Currently, five crystalline essential amino acids (Lys, Met, Thr, Trp, and Val) are generally used, allowing formulation of low-crude-protein (CP) diets. Moreover, Ile may also be used depending on its economic value and the specific feeding program. Experimentally, it has been shown that further reduced CP levels can be achieved by supplemental His, Leu, and Phe to the diets. However, decreasing the dietary CP level while maintaining optimal ratios of amino acids has shown contradictory effects on pigs' growth performance. Due to the divergence in the literature and the importance for practical formulation strategies in the swine industry, a literature review and a meta-analysis were performed to estimate the minimum CP level that would not compromise pig performance. Based on the present review, there is a minimum CP level after which the growth performance of pigs can be compromised, even though diets are balanced for essential amino acids. Considering average daily gain and gain to feed, respectively, these levels were estimated to be 18.4% CP (95% confidence interval [CI]: 16.3 to 18.4) and 18.3% CP (95% CI: 17.4 to 19.2) for nursery, 16.1% CP (95% CI: 16.0 to 16.2) and 16.3% CP (95% CI: 14.5 to 18.0) for growing, and 11.6% CP (95% CI: 10.8 to 12.3) and 11.4% CP (95% CI: 10.3 to 12.5) for finishing pigs.

Protective role of Caesalpinia sappan extract and its main component brazilin against blue light-induced damage in human fibroblasts.

BACKGROUND: Ultraviolet (UV) radiation is a well-known factor that causes skin aging. Recently, with the development of technology, the skin has been exposed to not only the UV radiation but also the blue light from electronic devices. Blue light is a high-energy visible light that penetrates deep into the dermal layer, producing reactive oxygen species (ROS) and resulting in skin aging. In this study, we searched for candidate materials that can inhibit blue light-induced skin aging and found Caesalpinia sappan extract (CSE) to be effective. METHODS: Human dermal fibroblasts (HDFs) were treated with various concentrations of CSE and brazilin and exposed to blue light. We measured that antioxidant activity, MMP-1 levels using MMP-1 ELISA, changes in collagen type 1, collagen type 3, MMP-1, and MMP-3 mRNA expressions, and ROS generation. RESULTS: We confirmed that CSE has high absorption of blue light and antioxidant activity. Blue light irradiation at 30 J/cm2 decreased the expression of collagen types 1 and 3, increased the expression of matrix metalloproteinase (MMP)-1 and 3, and decreased the production of ROS in human dermal fibroblasts as compared to those of the nonirradiated group. However, pretreatment with CSE protected against the damage caused by the blue light. Brazilin, a major constituent of C. sappan, had high absorbance in the blue light region and antioxidant activities. Pretreatment with brazilin also inhibited the damage caused by the blue light in the cells. CONCLUSION: CSE and brazilin are potential agents for inhibiting skin aging caused by blue light-induced damage.

Efficacy of chemiluminescence in the diagnosis and screening of oral cancer and precancer: a systematic review and meta-analysis / Eficácia da quimioluminescência no diagnóstico e rastreamento de câncer oral e pré-câncer: uma revisão sistemática e metanálise

Abstract Introduction Early detection of potentially malignant oral cavity disorders is critical for a good prognosis, and it is unclear whether the use of chemiluminescence as an adjunctive diagnostic screening method improves diagnostic accuracy. Objective This systematic review and meta-analysis was performed to assess the accuracy of chemiluminescence for diagnosis of oral cancer and precancerous lesions. Methods Sixteen prospective and retrospective studies from PubMed, Cochrane database, SCOPUS, Web of Science, Embase, and Google Scholar were reviewed. Oral mucosal disorder, as detected by chemiluminescence, was compared with oral mucosal disorder detected by toluidine blue or visual examination. True-positive, true-negative, false-positive, and false-negative rates were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool (ver. 2). Results Sensitivity, specificity, negative predictive value, and diagnostic odds ratio (DOR) of the use of toluidine blue were 0.832 (95% confidence interval [CI] 0.692-0.917), 0.429 (95% CI 0.217-0.672), 0.747 (95% CI 0.607-0.849), and 4.061 (95% CI 1.528-10.796; I2 = 9.128%), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.743. Compared with toluidine blue, as used in 12 studies, chemiluminescence had a higher sensitivity (0.831 vs. 0.694); it had a lower specificity (0.415 vs. 0.734), negative predictive value (0.674 vs. 0.729), and DOR (3.891 vs. 7.705). Compared with clinical examination, as used in three studies, chemiluminescence had lower DOR (4.576 vs. 5.499) and area under the curve (0.818 vs. 0.91). Conclusion Although chemiluminescence itself has good sensitivity for diagnostic work-up of oral cancer and precancer, the diagnostic accuracy of chemiluminescence is comparable to or worse than toluidine blue and clinical examination. Diagnostic accuracy was therefore insufficient for reliable use of chemiluminescence alone.

Resumo Introdução A detecção precoce de distúrbios orais potencialmente malignos é fundamental para um bom prognóstico e não está claro se o uso da quimioluminescência como método auxiliar de triagem diagnóstica melhora a eficácia do diagnóstico. Objetivo Avaliar a precisão da quimioluminescência para o diagnóstico de câncer oral e pré-câncer. Método Foram revisados 16 estudos prospectivos e retrospectivos dos bancos de dados PubMed, Cochrane, Scopus, Web of Science, Embase e Google Scholar. Os distúrbios da mucosa oral detectados por quimioluminescência foram comparados com os distúrbios da mucosa oral detectados pelo azul de toluidina ou pelo exame visual. Taxas de resultados verdadeiro-positivos, verdadeiro-negativos, falso-positivos e falso-negativos foram extraídas de cada estudo. A qualidade metodológica foi avaliada com a ferramenta Quality Assessment of Diagnostic Accuracy Studies-versão 2 (QUADAS-2). Resultados Sensibilidade, especificidade, valor preditivo negativo e odds ratio diagnóstico do uso do azul de toluidina foram 0,832 (intervalo de confiança de 95%: 0,692-0,917), 0,429 (IC95%: 0,217-0,672), 0,747 (IC95%: 0,607-0,849) e 4,061 (intervalo de confiança 95%: 1,528-10,796; I2 = 9,128%), respectivamente. A área sob a curva SROC, do inglês summary receiver operating characteristic, foi de 0,743. Comparada ao azul de toluidina, como usado em 12 estudos, a quimioluminescência apresentou uma sensibilidade mais alta (0,831 vs. 0,694) e especificidade (0,415 vs. 0,734), valor preditivo negativo (0,674 vs. 0,729) e odds ratio diagnóstico (3,889 vs. 7,705) mais baixos. Comparado com o exame clínico, como usado em três estudos, a quimioluminescência apresentou menor odds ratio diagnóstico (4.576 vs. 5.499) e área sob a curva (0,818 vs. 0,91). Conclusão Embora a quimioluminescência em si tenha boa sensibilidade para o diagnóstico de câncer oral e pré-câncer, sua precisão diagnóstica é comparável ou pior do que o azul de toluidina e o exame clínico. A precisão do diagnóstico foi, portanto, insuficiente para o uso isolado confiável da quimioluminescência.

High Healthcare Use at Age 5 Years in a European Cohort of Children Born Very Preterm.

OBJECTIVES: To describe parent-reported healthcare service use at age 5 years in children born very preterm and investigate whether perinatal and social factors and the use of very preterm follow-up services are associated with high service use. STUDY DESIGN: We used data from an area-based cohort of births at <32 weeks of gestation from 11 European countries, collected from birth records and parental questionnaires at 5 years of age. Using the published literature, we defined high use of outpatient/inpatient care (≥4 sick visits to general practitioners, pediatricians, or nurses, ≥3 emergency room visits, or ≥1 overnight hospitalization) and specialist care (≥2 different specialists or ≥3 visits). We also categorized countries as having either a high or a low rate of children using very preterm follow-up services at age 5 years. RESULTS: Overall, 43% of children had high outpatient/inpatient care use and 48% had high specialist care use during the previous year. Perinatal factors were associated with high outpatient/inpatient and specialist care use, with a more significant association with specialist services. Associations with intermediate parental educational level and unemployment were stronger for outpatient/inpatient services. Living in a country with higher rates of very preterm follow-up service use was associated with lower use of outpatient/inpatient services. CONCLUSIONS: Children born very preterm had high healthcare service use at age 5 years, with different patterns for outpatient/inpatient and specialist care by perinatal and social factors. Longer follow-up of children born very preterm may improve care coordination and help avoid undesirable health service use.

Efficacy of chemiluminescence in the diagnosis and screening of oral cancer and precancer: a systematic review and meta-analysis.

INTRODUCTION: Early detection of potentially malignant oral cavity disorders is critical for a good prognosis, and it is unclear whether the use of chemiluminescence as an adjunctive diagnostic screening method improves diagnostic accuracy. OBJECTIVE: This systematic review and meta-analysis was performed to assess the accuracy of chemiluminescence for diagnosis of oral cancer and precancerous lesions. METHODS: Sixteen prospective and retrospective studies from PubMed, Cochrane database, SCOPUS, Web of Science, Embase, and Google Scholar were reviewed. Oral mucosal disorder, as detected by chemiluminescence, was compared with oral mucosal disorder detected by toluidine blue or visual examination. True-positive, true-negative, false-positive, and false-negative rates were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool (ver. 2). RESULTS: Sensitivity, specificity, negative predictive value, and diagnostic odds ratio (DOR) of the use of toluidine blue were 0.832 (95% confidence interval [CI] 0.692-0.917), 0.429 (95% CI 0.217-0.672), 0.747 (95% CI 0.607-0.849), and 4.061 (95% CI 1.528-10.796; I2=9.128%), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.743. Compared with toluidine blue, as used in 12 studies, chemiluminescence had a higher sensitivity (0.831 vs. 0.694); it had a lower specificity (0.415 vs. 0.734), negative predictive value (0.674 vs. 0.729), and DOR (3.891 vs. 7.705). Compared with clinical examination, as used in three studies, chemiluminescence had lower DOR (4.576 vs. 5.499) and area under the curve (0.818 vs. 0.91). CONCLUSION: Although chemiluminescence itself has good sensitivity for diagnostic work-up of oral cancer and precancer, the diagnostic accuracy of chemiluminescence is comparable to or worse than toluidine blue and clinical examination. Diagnostic accuracy was therefore insufficient for reliable use of chemiluminescence alone.

Abemaciclib plus trastuzumab with or without fulvestrant versus trastuzumab plus standard-of-care chemotherapy in women with hormone receptor-positive, HER2-positive advanced breast cancer (monarcHER): a randomised, open-label, phase 2 trial.

BACKGROUND: Patients with HER2-positive breast cancer who have received two or more previous therapies for advanced disease have few effective treatment options. The monarcHER trial aimed to compare the efficacy of abemaciclib plus trastuzumab with or without fulvestrant with standard-of-care chemotherapy of physician's choice plus trastuzumab in women with advanced breast cancer. METHODS: This phase 2, three-group, open-label trial was done across 75 hospitals, clinics, and medical centres in 14 countries. Eligible patients were women aged 18 years or older, who had hormone receptor-positive, HER2-positive advanced breast cancer with unresectable, locally advanced, recurrent or metastatic disease, Eastern Cooperative Oncology Group performance status of 0 or 1, and who had previously received at least two HER2-targeted therapies for advanced disease. Patients were randomly assigned 1:1:1 to the abemaciclib, trastuzumab, and fulvestrant (group A), abemaciclib and trastuzumab (group B), or standard-of-care chemotherapy and trastuzumab (group C). Oral abemaciclib 150 mg 12 hourly was administered on days 1-21 of a 21-day cycle, intravenous trastuzumab 8 mg/kg on cycle 1 day 1, followed by 6 mg/kg on day 1 of each subsequent 21-day cycle, and intramuscular fulvestrant 500 mg on days 1, 15, and 29 and once every 4 weeks thereafter. Standard-of-care chemotherapy was administered as specified by the product label. Randomisation was by a computer-generated random sequence by means of an interactive web-response system and stratified by number of previous systemic therapies for advanced breast cancer and measurable versus non-measurable disease. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population, first testing group A versus group C and, if this result was significant, then group B versus group C. Safety was assessed in all patients who had received at least one dose of study treatment. This trial is registered at ClinicalTrials.gov (NCT02675231) and is ongoing for long-term survival follow-up. FINDINGS: Between May 31, 2016, and Feb 28, 2018, 325 patients were screened, of whom 237 eligible patients were enrolled and randomly assigned to groups A (n=79), B (n=79), and C (n=79). Median follow-up was 19·0 months (IQR 14·7-25·1). The study met its primary endpoint, showing a significant difference at the prespecified two-sided α of 0·2 in median progression-free survival between group A (8·3 months, 95% CI 5·9-12·6) and group C (5·7 months, 5·4-7·0; HR 0·67 [95% CI 0·45-1·00]; p=0·051). No difference was observed between median progression-free survival in group B (5·7 months, 95% CI 4·2-7·2) and group C (HR 0·94 [0·64-1·38]; p=0·77). The most common grade 3-4 treatment-emergent adverse event in groups A, B, and C was neutropenia (21 [27%] of 78 patients, 17 [22%] of 77, and 19 [26%] of 72). The most common serious adverse events were: in group A, pyrexia (three [4%]), diarrhoea (two [3%]), urinary tract infection (two [3%]), and acute kidney injury (two [3%]); in group B, diarrhoea (two [3%]) and pneumonitis (two [3%]); and in group C, neutropenia (four [6%]) and pleural effusion (two [3%]). Two deaths were attributed to treatment: one due to pulmonary fibrosis in group B and one due to febrile neutropenia in group C. INTERPRETATION: The combination of abemaciclib, fulvestrant, and trastuzumab significantly improved progression-free survival versus standard-of-care chemotherapy plus trastuzumab while showing a tolerable safety profile. Our results suggest that a chemotherapy-free regimen might potentially be an alternative treatment option for patients with hormone receptor-positive, HER2-positive advanced breast cancer. FUNDING: Eli Lilly and Company.

Evaluation of 2 techniques of epithelial removal in subepithelial connective tissue graft surgery: a comparative histological study.

PURPOSE: Subepithelial connective tissue grafts (SCTGs) are commonly performed for the treatment of gingival recession due to their high predictability. This study evaluated and histologically compared connective tissue grafts in terms of the presence of epithelial remnants and composition of the tissue types that were present (epithelium, lamina propria, and submucosa). METHODS: Ten patients underwent epithelium removal using 2 different techniques: the use of a blade (group B) and through abrasion (group A). Twenty samples were collected and each tissue type was analyzed histologically in terms of its area, thickness, and proportion of the total area of the graft. RESULTS: In 4 samples (40%) from group B (n=10) and 2 samples (20%) from group A (n=10), the presence of an epithelial remnant was observed, but the difference between the groups was not statistically significant (P>0.05). Likewise, no statistically significant differences were observed between the groups regarding the area, mean thickness, or proportion of the total area for any of the tissue types (P>0.05). CONCLUSIONS: Histologically, SCTGs did not show statistically significant differences in terms of their tissue composition depending on whether they were separated from the epithelial tissue by abrasion or by using a blade.

Comparison of Facial Proportions Between Eastern and Western Attractive Young Women.

The characteristics of what is considered a beautiful face differ between Eastern and Western countries.The authors of this study analyzed beauty pageant contestants using a three-dimensional (3D) photogrammetric analysis tool. All of the 3D photographs were taken between October and November 2016 in Seoul, Korea. The participants were 43 Miss Korea contestants (Group I) and 22 Miss Paraguay contestants (Group II).In absolute length, those in Group I had longer upper and middle faces. In the proportions of volume and length, Group I had larger upper and middle faces than Group II. Widths of the lower face and entire face were also wider in Group I. The lower facial index was larger in Group I. Group I had longer noses and wider intercanthal distance, not only in absolute length but also in proportion to the face. Group II showed thicker lips, longer chins, and wider noses relative to the face. Group II had wide eyes, in the absolute measurement and in proportion to the face. Group I participants appeared to have an increased height of eyes and had wider angles in their faces as well as wider nasofrontal, labiomental, and nasomental angles.The authors objectively established reference data for faces that are considered attractive in the East and the West. The data are expected to contribute to the clinical practice of plastic surgeons.

Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish.

Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish

ABSTRACT Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

Thermal change in a resin block during motorized and manual implant placement.

STATEMENT OF PROBLEM: Several studies have demonstrated the harmful role of heat generation during implant site drilling in subsequent bone healing. However, heat generation during implant placement should also be carefully considered. PURPOSE: The purpose of this in vitro study was to evaluate thermal change in a resin block during motorized and manual implant placement with and without saline irrigation. MATERIAL AND METHODS: Thermocouple probes were placed in resin blocks to measure the thermal change during forty 3.75x15-mm self-tapping cylindrical screw implant placements as follows: MtI group, 10 motorized implant placements with external saline irrigation; MtNI group, 10 motorized implant placements without irrigation; MI group, 10 manual implant placements with external saline irrigation; MNI group, 10 manual implant placements without irrigation. The temperature values were recorded with a data acquisition system with a 20-channel multiplexer module connected to a personal computer. The normality of data distribution was assessed with the Shapiro-Wilk test and the homogeneity of variances with the Levene test. The mean temperatures of the groups was assessed with the 3-way ANOVA test followed by the Tukey HSD test for normal distribution and the Games-Howell test for non-normal distribution (α=.05). RESULTS: The rate of temperature rise in the resin blocks was 1.1°C to 7.3°C. The highest mean temperature was present in the group for manual implant placement without irrigation (26.2 ±1.1°C), and the lowest thermal change was in the motorized implant placement group with external saline irrigation (23.6 ±1.0°C). CONCLUSIONS: The thermal change in resin blocks during motorized implant placement was lower than manual implant placement, especially with external saline irrigation.

VPAC1 Targeted (64)Cu-TP3805 Positron Emission Tomography Imaging of Prostate Cancer: Preliminary Evaluation in Man.

OBJECTIVE: To evaluate (64)Cu-TP3805 as a novel biomolecule, to positron emission tomography (PET) image prostate cancer (PC), at the onset of which VPAC1, the superfamily of G protein-coupled receptors, is expressed in high density on PC cells, but not on normal cells. MATERIALS AND METHODS: Twenty-five patients undergoing radical prostatectomy were PET/X-ray computerized tomography imaged preoperatively with (64)Cu-TP3805. Standardized maximum uptake (SUVmax) values were determined and malignant lesions (standardized uptake value > 1.0) counted, and compared with histologic findings. Whole-mount pathology slides from 6 VPAC1 PET imaged patients, 3 benign prostatic hyperplasia patients, 1 malignant and 1 benign lymph node underwent digital autoradiography (DAR) after (64)Cu-TP3805 incubation and were compared to hematoxylin- and eosin-stained slides. RESULTS: In 25 patients who underwent PET imaging, 212 prostate gland lesions had SUVmax > 1.0 vs 127 lesions identified by histology of biopsy tissues. The status of the additional 85 PET identified prostate lesions remains to be determined. In 68 histologic slides from 6 PET imaged patients, DAR identified 105 of 107 PC foci, 19 of 19 high-grade prostatic intraepithelial neoplasias, and ejaculatory ducts and verumontanum involved with cancer. Additionally, DAR found 9 PC lesions not previously identified histologically. The positive and negative lymph nodes were correctly identified, and in 3 of 3 benign prostatic hyperplasia patients and 5 of 5 cysts, DAR was negative. CONCLUSION: This feasibility study demonstrated that (64)Cu-TP3805 delineates PC in vivo and ex vivo, provided normal images for benign masses, and is worthy of further studies.

Amniotic fluid exerts a neurotrophic influence on fetal neurodevelopment via the ERK/GSK-3 pathway.

BACKGROUND: The fetus is surrounded by the amniotic fluid (AF) contained by the amniotic sac of the pregnant female. The AF is directly conveyed to the fetus during pregnancy. Although AF has recently been reported as an untapped resource containing various substances, it remains unclear whether the AF could influence fetal neurodevelopment. RESULTS: We used AF that was extracted from embryos at 16 days in pregnant SD rat and exposed the AF to the neural cells derived from the embryos of same rat. We found that the treatment of AF to cortical neurons increased the phosphorylation in ERK1/2 that is necessary for fetal neurodevelopment, which was inhibited by the treatment of MEK inhibitors. Moreover, we found the subsequent inhibition of glycogen synthase kinase-3 (GSK-3), which is an important determinant of cell fate in neural cells. Indeed, AF increased the neural clustering of cortical neurons, which revealed that the clustered cells were proliferating neural progenitor cells. Accordingly, we confirmed the ability of AF to increase the neural progenitor cells through neurosphere formation. Furthermore, we showed that the ERK/GSK-3 pathway was involved in AF-mediated neurosphere enlargement. CONCLUSIONS: Although the placenta mainly supplies oxygenated blood, nutrient substances for fetal development, these findings further suggest that circulating-AF into the fetus could affect fetal neurodevelopment via MAP kinases-derived GSK-3 pathway during pregnancy. Moreover, we suggest that AF could be utilized as a valuable resource in the field of regenerative medicine.

Tromboembolia arterial y amputación de una extremidad en un neonato posterior al síndrome de dificultad respiratoria: Caso clínico / Neonatal arterial thromboembolism and limb loss following respiratory distress syndrome: Case report

La tromboembolia en los recién nacidos es un problema grave. Los factores de riesgo más importantes son iatrogénicos, entre ellos, el uso de sondas umbilicales o vías centrales permanentes. Entre otros factores de riesgo, se incluyen la asfixia, la deshidratación, la septicemia, la cardiopatía, el síndrome de dificultad respiratoria, la coagulación intravascular diseminada, la trombofilia congénita (deficiencia de proteína C o proteína S), la diabetes mellitus materna y la transferencia pasiva de anticuerpos antifosfolípidos maternos. Los recién nacidos son más vulnerables que los adultos a presentar una trombosis debido a su menor capacidad fibrinolítica. Describimos el caso de una recién nacida de un día de vida con tromboembolia arterial en el miembro inferior; sin vía central. La tromboembolia en este caso estuvo asociada con un síndrome de dificultad respiratoria. Se realizó trombólisis; tratamiento anticoagulante y trombectomía quirúrgica. Posteriormente; se amputó el miembro inferior por debajo de la rodilla.

Thromboembolic disease in newborn infants is a serious problem. The most important risk factors are iatrogenic factors, including indwelling umbilical catheters or central catheters. Other risk factors include asphyxia, dehydration, sepsis, cardiac disease, respiratory distress syndrome (RDS), disseminated intravascular coagulation, congenital thrombophilia (i.e., protein C or protein S deficiency), maternal diabetes mellitus, and passive transfer of maternal antiphospholipid antibodies. Neonates are more vulnerable to thrombosis than adults due to their reduced fibrinolytic capability. We describe a case of a 1-day-old female newborn with arterial thromboembolism in the lower leg without a central line catheter. The thromboembolismin in this case was associated with RDS. The infant underwent thrombolysis, anticoagulation therapy, and surgical thrombectomy. The leg of the infant was subsequently amputated below the knee. The case is described here with a brief review of relevant literatures.

Tromboembolia arterial y amputación de una extremidad en un neonato posterior al síndrome de dificultad respiratoria: Caso clínico / Neonatal arterial thromboembolism and limb loss following respiratory distress syndrome: Case report

La tromboembolia en los recién nacidos es un problema grave. Los factores de riesgo más importantes son iatrogénicos, entre ellos, el uso de sondas umbilicales o vías centrales permanentes. Entre otros factores de riesgo, se incluyen la asfixia, la deshidratación, la septicemia, la cardiopatía, el síndrome de dificultad respiratoria, la coagulación intravascular diseminada, la trombofilia congénita (deficiencia de proteína C o proteína S), la diabetes mellitus materna y la transferencia pasiva de anticuerpos antifosfolípidos maternos. Los recién nacidos son más vulnerables que los adultos a presentar una trombosis debido a su menor capacidad fibrinolítica. Describimos el caso de una recién nacida de un día de vida con tromboembolia arterial en el miembro inferior; sin vía central. La tromboembolia en este caso estuvo asociada con un síndrome de dificultad respiratoria. Se realizó trombólisis; tratamiento anticoagulante y trombectomía quirúrgica. Posteriormente; se amputó el miembro inferior por debajo de la rodilla.(AU)

Thromboembolic disease in newborn infants is a serious problem. The most important risk factors are iatrogenic factors, including indwelling umbilical catheters or central catheters. Other risk factors include asphyxia, dehydration, sepsis, cardiac disease, respiratory distress syndrome (RDS), disseminated intravascular coagulation, congenital thrombophilia (i.e., protein C or protein S deficiency), maternal diabetes mellitus, and passive transfer of maternal antiphospholipid antibodies. Neonates are more vulnerable to thrombosis than adults due to their reduced fibrinolytic capability. We describe a case of a 1-day-old female newborn with arterial thromboembolism in the lower leg without a central line catheter. The thromboembolismin in this case was associated with RDS. The infant underwent thrombolysis, anticoagulation therapy, and surgical thrombectomy. The leg of the infant was subsequently amputated below the knee. The case is described here with a brief review of relevant literatures.(AU)