Colloid coload versus crystalloid coload to prevent maternal hypotension in women receiving prophylactic phenylephrine infusion during caesarean delivery: a randomised controlled trial.

BACKGROUND: The optimal fluid strategy to prevent maternal hypotension during caesarean delivery remains unclear. This study aim was to compare the incidence of post-spinal anaesthesia hypotension in women receiving either colloid or crystalloid coload in the setting of prophylactic phenylephrine infusion during caesarean delivery. METHODS: Healthy mothers undergoing elective caesarean delivery under spinal anaesthesia were randomised to receive a rapid intravenous coload with 6% hydroxyethyl starch 130/0.4 10 mL/kg (colloid group) or balanced crystalloid solution (Plasma Solution A) 10 mL/kg (crystalloid group) during spinal anaesthesia. All women had a prophylactic phenylephrine infusion initiated at 25 µg/min immediately after the subarachnoid block and titrated to systolic blood pressure using a standardised protocol. The primary outcome was the incidence of hypotension (systolic blood pressure <80% of baseline) until delivery. RESULTS: The incidence of hypotension was 50% in the colloid group and 62% in the crystalloid group (absolute difference, -12% [95% CI -33% to 9%]; relative risk, 0.8 [95% CI 0.56 to 1.14]; P=0.314). No significant difference between groups was found in the number of hypotensive episodes (median 0.5 [IQR 0 to 1] vs 1 [0 to 2], P=0.132) or phenylephrine dose (675 [IQR 425 to 975] µg vs 750 [625 to 950] µg, P=0.109). The incidence of severe hypotension, symptomatic hypotension, bradycardia, nausea, and the neonatal outcomes were not significantly different. CONCLUSIONS: This study found no benefit of colloid coload compared with crystalloid coload for preventing maternal hypotension in the presence of prophylactic phenylephrine infusion during caesarean delivery.

Automated Skeletal Classification with Lateral Cephalometry Based on Artificial Intelligence.

Lateral cephalometry has been widely used for skeletal classification in orthodontic diagnosis and treatment planning. However, this conventional system, requiring manual tracing of individual landmarks, contains possible errors of inter- and intravariability and is highly time-consuming. This study aims to provide an accurate and robust skeletal diagnostic system by incorporating a convolutional neural network (CNN) into a 1-step, end-to-end diagnostic system with lateral cephalograms. A multimodal CNN model was constructed on the basis of 5,890 lateral cephalograms and demographic data as an input. The model was optimized with transfer learning and data augmentation techniques. Diagnostic performance was evaluated with statistical analysis. The proposed system exhibited >90% sensitivity, specificity, and accuracy for vertical and sagittal skeletal diagnosis. Clinical performance of the vertical classification showed the highest accuracy at 96.40 (95% CI, 93.06 to 98.39; model III). The receiver operating characteristic curve and the area under the curve both demonstrated the excellent performance of the system, with a mean area under the curve >95%. The heat maps of cephalograms were also provided for deeper understanding of the quality of the learned model by visually representing the region of the cephalogram that is most informative in distinguishing skeletal classes. In addition, we present broad applicability of this system through subtasks. The proposed CNN-incorporated system showed potential for skeletal orthodontic diagnosis without the need for intermediary steps requiring complicated diagnostic procedures.

Relationship of serum leptin concentration with pituitary-dependent hyperadrenocorticism and cholestatic disease in dogs.

OBJECTIVES: To measure serum leptin concentration in dogs with pituitary-dependent hyperadrenocorticism and varying degrees of cholestatic disease and determine whether serum levels differed between dogs with pituitary-dependent hyperadrenocorticism and those with gall bladder mucocoele. MATERIALS AND METHODS: Client-owned healthy dogs (n=20), dogs diagnosed with gall bladder mucocoele (n=20) and dogs diagnosed with pituitary-dependent hyperadrenocorticism (n=60) were enrolled. Only dogs of normal body condition score were included. Dogs with pituitary-dependent hyperadrenocorticism were divided into three groups according to the severity of cholestatic disease: normal gall bladder (n=20), cholestasis (n=20) and gall bladder mucocoele (n=20). Serum leptin levels were measured using sandwich enzyme-linked immunosorbent assay. RESULTS: Serum concentrations of leptin were similar between dogs with gall bladder mucocoele and those with pituitary-dependent hyperadrenocorticism accompanied by gall bladder mucocoele; these concentrations were significantly higher than those in healthy control dogs. In dogs with pituitary-dependent hyperadrenocorticism, circulating leptin concentration significantly increased with the severity of cholestasis: higher in the cholestasis group than the normal gall bladder group and higher in the gall bladder mucocoele group than the cholestasis group. CLINICAL SIGNIFICANCE: Elevated circulating leptin concentration was associated with canine pituitary-dependent hyperadrenocorticism and gall bladder mucocoele. Homeostatic imbalance of leptin concentration might be associated with severity of cholestatic disease in pituitary-dependent hyperadrenocorticism.

Comparison between general, spinal, epidural, and combined spinal-epidural anesthesia for cesarean delivery: a network meta-analysis.

BACKGROUND: This study is a network meta-analysis to compare maternal and fetal outcomes associated with four different anesthetic techniques for cesarean delivery. METHODS: An arm-based, random-effects frequentist network meta-analysis was performed. A random effect model was selected considering deviance information criteria. Randomized trials reporting the following outcomes were included: Apgar score at 1- or 5-min; umbilical arterial and venous pH; umbilical arterial pH <7.2; and neonatal score at 2-4 hours. Loop-specific heterogeneity was evaluated by risk of odds ratio and τ2. Quality of evidence was assessed using the GRADE approach. RESULTS: Data from 46 randomized trials including 3689 women contributed to the study. There were significant differences in Apgar score ≤6 at 1 min between spinal versus general anesthesia (odds ratio 0.27, 95% confidence interval [CI] 0.13 to 0.55: moderate quality evidence) and Apgar scores at 1- and 5-min, favoring spinal anesthesia. Umbilical venous pH associated with epidural anesthesia was significantly higher than that with general anesthesia (mean difference 0.010, 95% CI 0.001 to 0.020: moderate quality evidence) or spinal anesthesia. Spinal anesthesia was ranked best for Apgar score ≤6 at 1-min (SUCRA=89.8), Apgar score at 1-min (SUCRA=80.4) and 5-min (SUCRA=90.5). Epidural anesthesia was ranked highest for umbilical venous pH (SUCRA=87.4) and neonatal score (SUCRA=79.3). CONCLUSIONS: Spinal and epidural anesthesia were ranked high regarding Apgar scores and epidural anesthesia was ranked high regarding umbilical venous pH, but the results were based on small heterogeneous studies with high or unclear risks of bias.

Effect of prolonged inspiratory time on gas exchange during robot-assisted laparoscopic urologic surgery.

BACKGROUND: Gas exchange disturbance may develop during urologic robotic laparoscopic surgery with the patient in a steep Trendelenburg position. This study investigated whether prolonged inspiratory time could mitigate gas exchange disturbances including hypercapnia. METHODS: In this randomized cross-over trial, 32 patients scheduled for robot-assisted urologic surgery were randomized to receive an inspiratory to expiratory time ratio (I:E) of 1:1 for the first hour of pneumoperitoneum followed by 1:2 for last period of surgery (group A, n = 17) or I:E of 1:2 followed by 1:1 (group B, n = 15). Arterial blood gas analysis, airway pressure and hemodynamic variables were assessed at four time points (T1: 10 min after induction of general anesthesia, T2: 1 h after the initiation of pneumoperitoneum, T3: 1 h after T2 and T4: at skin closure). The carry over effect of initial I:E was also evaluated over the next hour through arterial blood gas analysis. RESULTS: There was a significant decrease in partial pressure of oxygen in arterial blood (PaO2) for both groups at T2 and T3 compared to T1 but in group B the PaO2 at T4 was not decreased from the baseline. Partial pressure of carbon dioxide in arterial blood (PaCO2) increased with I:E of 1:2 but did not significantly increase with I:E of 1:1; however, there were no differences in PaO2 and PaCO2 between the groups. CONCLUSION: Decreased oxygenation by pneumoperitoneum was improved and PaCO2 did not increase after 1 h of I:E of 1:1; however, the effect of equal ratio ventilation longer than 1 h remains to be determined. There was no carryover effect of the two different I:E ratios.

Risk factors associated with highly pathogenic avian influenza subtype H5N8 outbreaks on broiler duck farms in South Korea.

Highly Pathogenic Avian Influenza (HPAI) subtype H5N8 outbreaks occurred in poultry farms in South Korea in 2014 resulting in significant damage to the poultry industry. Between 2014 and 2016, the pandemic disease caused significant economic loss and social disruption. To evaluate the risk factors for HPAI infection in broiler duck farms, we conducted a retrospective case-control study on broiler duck farms. Forty-three farms with confirmed laboratories on premises were selected as the case group, and 43 HPAI-negative farms were designated as the control group. Control farms were matched based on farm location and were within a 3-km radius from the case premises. Spatial and environmental factors were characterized by site visit and plotted through a geographic information system (GIS). Univariable and multivariable logistic regression models were developed to assess possible risk factors associated with HPAI broiler duck farm infection. Four final variables were identified as risk factors in a final multivariable logistic model: "Farms with ≥7 flocks" (odds ratio [OR] = 6.99, 95% confidence interval [CI] 1.34-37.04), "Farm owner with ≥15 years of raising poultry career" (OR = 7.91, 95% CI 1.69-37.14), "Presence of any poultry farms located within 500 m of the farm" (OR = 6.30, 95% CI 1.08-36.93) and "Not using a faecal removal service" (OR = 27.78, 95% CI 3.89-198.80). This highlights that the HPAI H5N8 outbreaks in South Korea were associated with farm owner education, number of flocks and facilities and farm biosecurity. Awareness of these factors may help to reduce the spread of HPAI H5N8 across broiler duck farms in Korea during epidemics. Greater understanding of the risk factors for H5N8 may improve farm vulnerability to HPAI and other subtypes and help to establish policies to prevent re-occurrence. These findings are relevant to global prevention recommendations and intervention protocols.

Pharmacological interventions for protecting renal function after cardiac surgery: a Bayesian network meta-analysis of comparative effectiveness.

Many drugs have been investigated as potentially protective of renal function after cardiac surgery. However, their comparative effectiveness has not been established. We performed an arm-based hierarchical Bayesian network meta-analysis including 95 randomised controlled trials with 28,833 participants, which allowed us to compare some agents not previously compared directly. Renal outcomes, including: the incidence of postoperative renal dysfunction and haemodialysis; serum creatinine level at 24 hours postoperatively; all-cause mortality; and length of hospital and ICU stay, were compared. Exploratory meta-regression was conducted for potential effect modifiers. A random effects model was selected according to the evaluation of model fit by deviance information criteria. Atrial natriuretic peptide (odds ratio (95%CrI) 0.28 (0.17-0.48); moderate-quality evidence), B-type natriuretic peptide, dexmedetomidine, levosimendan and N-acetyl cysteine significantly decreased the rate of postoperative renal dysfunction compared with placebo. Atrial natriuretic peptide (OR (95%CrI) 0.24 (0.10-0.58); low-quality evidence), B-type natriuretic peptide, and dexamethasone significantly decreased the need for haemodialysis. Levosimendan significantly decreased mortality, OR (95%CrI) 0.49 (0.27-0.91); low-quality evidence). The benefit of atrial natriuretic peptide was still apparent when baseline renal function was normal. None of the potential effect modifiers were significantly correlated with our renal outcomes. Atrial natriuretic peptide was ranked best regarding renal dysfunction, haemodialysis and length of hospital stay. Levosimendan was ranked best regarding mortality and ICU stay. However, our results should be interpreted cautiously given the assumptions made about transitivity and consistency.

Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: a review.

With the increase in regulations regarding the use of antibiotic growth promoters and the rise in consumer demand for poultry products from 'Raised Without Antibiotics' or 'No Antibiotics Ever' flocks, the quest for alternative products or approaches has intensified in recent years. A great deal of research has focused on the development of antibiotic alternatives to maintain or improve poultry health and performance. This review describes the potential for the various alternatives available to increase animal productivity and help poultry perform to their genetic potential under existing commercial conditions. The classes of alternatives described include probiotics, prebiotics, synbiotics, organic acids, enzymes, phytogenics, antimicrobial peptides, hyperimmune egg antibodies, bacteriophages, clay, and metals. A brief description of the mechanism of action, efficacy, and advantages and disadvantages of their uses are also presented. Though the beneficial effects of many of the alternatives developed have been well demonstrated, the general consensus is that these products lack consistency and the results vary greatly from farm to farm. Furthermore, their mode of action needs to be better defined. Optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximize performance and maintain animal productivity, while we move forward with the ultimate goal of reducing antibiotic use in the animal industry.

Quantitative proteomic analysis of HER2 expression in the selection of gastric cancer patients for trastuzumab treatment.

Background: A wide range of response rates have been reported in HER2-positive gastric cancer (GC) patients treated with trastuzumab. Other HER2-targeted therapies for GC have yet to show efficacy in clinical trials. These findings raise question about the ability of standard HER2 diagnostics to accurately distinguish between GC patients who would and would not benefit from anti-HER2 therapies. Patients and methods: GC patients (n = 237), including a subset from the Trastuzumab in GC (ToGA) trial were divided into three groups based on HER2 status and history of treatment with standard chemotherapy or chemotherapy plus trastuzumab. We applied mass spectrometry-based proteomic analysis to quantify HER2 protein expression in formalin-fixed tumor samples. Using HER2 expression as a continuous variable, we defined a predictive protein level cutoff to identify which patients would benefit from trastuzumab. We compared quantitated protein level with clinical outcome and HER2 status as determined by conventional HER2 diagnostics. Results: Quantitative proteomics detected a 115-fold range of HER2 protein expression among patients diagnosed as HER2 positive by standard methods. A protein level of 1825 amol/µg was predicted to determine benefit from the addition of trastuzumab to chemotherapy. Trastuzumab treated patients with HER2 protein levels above this cutoff had twice the median overall survival (OS) of their counterparts below the cutoff (35.0 versus 17.5 months, P = 0.011). Conversely, trastuzumab-treated patients with HER2 levels below the cutoff had outcomes similar to HER2-positive patients treated with chemotherapy. (Progression-free survival = 7.0 versus 6.5 months: P = 0.504; OS = 17.5 versus 12.6 months: P = 0.520). HER2 levels were not prognostic for response to chemotherapy. Conclusions: Proteomic analysis of HER2 expression demonstrated a quantitative cutoff that improves selection of GC patients for trastuzumab as compared with current diagnostic methods.

Increased Leptin and Leptin Receptor Expression in Dogs With Gallbladder Mucocele.

BACKGROUND: Leptin and its receptor play a role in several disease processes such as pancreatitis and heart disease. However, their association with gallbladder mucocele (GBM) in dogs has not been reported. HYPOTHESIS/OBJECTIVES: To evaluate differences in the expression of leptin and leptin receptor between dogs with and without GBM. ANIMALS: Twenty-five healthy dogs, including 9 laboratory beagle dogs, and 22 client-owned dogs with GBM. METHODS: Serum leptin concentration was determined in blood samples of all dogs by ELISA. Canine gallbladder samples were collected from 9 dogs with GBM that underwent surgery for therapeutic purposes and from 9 healthy laboratory beagle dogs as a normal control group. Samples were analyzed for leptin and leptin receptor mRNA by real-time polymerase chain reaction. RESULTS: Serum leptin concentration was significantly higher in dogs with GBM than in healthy dogs (medians of 7.03 and 2.18 ng/mL, respectively; P < .001). Patients with GBM that had undergone surgery had significantly higher serum leptin concentrations than those that had not (medians of 12.2 and 4.09 ng/mL, respectively; P = .001). However, no difference in serum leptin concentration was found between dogs with GBM with or without endocrinopathies. The mRNA expression levels of leptin and its receptor were significantly increased in the gallbladder tissues of dogs with GBM. CONCLUSIONS AND CLINICAL IMPORTANCE: Dysregulation of leptin might be involved in the pathophysiology of GBM, and leptin concentrations might be associated with GBM severity.

Elevated Microsatellite Alterations at Selected Tetranucleotide Repeats (EMAST) and Microsatellite Instability in Patients with Colorectal Cancer and Its Clinical Features.

PURPOSE: Recently, a different type of microsatellite instability (MSI) instability designated 'elevated microsatellite alterations at selected tetranucleotide repeats' (EMAST) has been reported in several neoplasms, but its clinical implications remain unclear. We aimed to determine the relationships among EMAST, MSI and clinicopathologic characteristics, including oncologic outcomes, in colorectal cancer (CRC). MATERIALS AND METHODS: We evaluated 100 sporadic CRC cases subjected to surgery using five markers (MYCL1, D9S242, D20S85, D8S321, and D20S82) for EMAST and the Bethesda panel for MSI status. Immunohistochemical detection of hMSH3, c-erbB2, EGFR and thymidylate synthase was performed. Clinical characteristics and prognostic relevance were assessed. RESULTS: We identified 22 EMAST-positive tumors (22.0%) and 32 MSI-high (MSI-H) tumors (32.0%). EMAST was more frequent in colon cancer than rectal cancer (p=0.033), and associated with MSI-H phenotype (p<0.001), low expression of hMSH3 (p=0.004), and overexpression of thymidylate synthase (p=0.006). Among the 38 MSI-L tumors, only one (4.5%) showed EMAST. Long-term oncologic results in terms of overall and disease-free survival were similar between EMAST and non-EMAST tumors. CONCLUSION: EMAST is more closely related to MSI-H than MSI-L or MSS status. The clinical and molecular characteristics of EMAST were distinct in terms of tumor location, thymidylate synthase expression, MSI status and hMSH3 expression. Our preliminary findings support the utility of EMAST as a new potential classifier in CRC.

Using genomics to identify novel antimicrobials.

There is a critical need in animal agriculture to develop novel antimicrobials and alternative strategies that will help to reduce the use of antibiotics and address the challenges of antimicrobial resistance. High-throughput gene expression analysis is providing new tools that are enabling the discovery of host-derived antimicrobial peptides. Examples of gene-encoded natural antibiotics that have gained attention include antimicrobial peptides such as human granulysin and its multi-species homolog, namely NK-lysin, which provide a protective response against a broad range of microbes and are a principal component of innate immunity in vertebrates. Both granulysin and NK-lysin are localised in cytolytic granules in natural killer and cytotoxic T lymphocytes. Host-derived NK-lysins that were first described in mammals are also found in avian species, and they have been shown to have antimicrobial activities that could potentially be used to control important poultry pathogens. Morphological alterations observed following chicken NK-lysin binding to Eimeria sporozoites and Escherichia coli membranes indicate damage and disruption of cell membranes, suggesting that NK-lysin kills pathogenic protozoans and bacteria by direct interaction. Genotype analysis revealed that chicken NK-lysin peptides derived from certain alleles were more effective at killing pathogens than those derived from others, which could potentially affect susceptibility to diseases. Although the host-derived antimicrobial peptides described in this paper may not, by themselves, be able to replace the antibiotics currently used in animal production, their use as specific treatments based on their known mechanisms of action is showing promising results.

Il est devenu impératif de développer de nouveaux agents antimicrobiens utilisables en production animale et de mettre au point des stratégies alternatives permettant de réduire l'utilisation des antibiotiques et de faire face aux enjeux de la résistance aux agents antimicrobiens. Les nouveaux outils rendus possibles par l'analyse à haut débit de l'expression génique permettent de découvrir les peptides antimicrobiens synthétisés par l'hôte. Parmi les antibiotiques naturels codés par des gènes qui suscitent actuellement le plus d'intérêt figurent les peptides antimicrobiens tels que la granulysine humaine et son homologue pluriespèces, la NK-lysine, qui déclenchent une réponse protectrice contre un large éventail d'agents microbiens et constituent l'une des principales composantes de l'immunité innée chez les vertébrés. La granulysine et la NK-lysine sont toutes deux localisées dans les granules cytolytiques des lymphocytes cytotoxiques T et des cellules NK (natural killer). Décrites dans un premier temps chez des mammifères, les NK-lysines synthétisées par l'hôte sont également présentes chez les oiseaux et il a été démontré qu'elles présentent des propriétés antimicrobiennes qui pourraient être utilisées pour contrôler d'importants agents pathogènes affectant les volailles. Les modifications morphologiques observées suite à la fixation de la NK-lysine du poulet aux sporozoïtes d'Eimeria et aux membranes d'Escherichia coli sont le signe d'un endommagement et d'une rupture des membranes cellulaires qui semblent indiquer que la NK-lysine tue les protozoaires et bactéries pathogènes par interaction directe. L'analyse génotypique a révélé que les peptides des NK-lysines de poulet encodés par certains allèles sont plus efficaces pour tuer les agents pathogènes que ceux encodés par d'autres allèles, ce qui pourrait avoir une influence sur la sensibilité aux maladies. Bien que les peptides antimicrobiens synthétisés par l'hôte décrits dans cet article ne puissent remplacer à eux seuls les antibiotiques utilisés actuellement en production animale, leur utilisation en tant que traitements spécifiques basés sur leurs propres mécanismes d'action connus, donne déjà des résultats prometteurs.

En el ámbito de la producción animal es ahora imperativo no solo dar con nuevos antimicrobianos, sino también concebir estrategias alternativas que ayuden a reducir el uso de antibióticos y a afrontar los problemas derivados de la resistencia a los antimicrobianos. El análisis de alto rendimiento de la expresión génica proporciona nuevas herramientas que están propiciando el descubrimiento de péptidos antimicrobianos sintetizados por los organismos anfitriones. Entre los ejemplos de antibióticos naturales codificados por genes que vienen suscitando interés están péptidos antimicrobianos como la granulisina humana y su homólogo multiespecífico, la NK-lisina, que inducen una respuesta protectora contra muy diversos microbios y son un componente básico de la inmunidad innata de los vertebrados. Tanto la granulisina como la NK-lisina están localizadas en el interior de los gránulos citolíticos de las células NK (natural killer) y los linfocitos T citotóxicos. Las NK-lisinas sintetizadas por el anfitrión, descritas en un principio en mamíferos, también se encuentran en especies aviares, y se ha demostrado que presentan propiedades antimicrobianas que podrían ser útiles para luchar contra importantes patógenos de las aves de corral. Las alteraciones morfológicas observadas después de que la NK-lisina de pollo se uniera a esporozoítos de Eimeria y a membranas de Escherichia coli son indicativas de deterioro y desorganización de la membrana celular, de donde se infiere que la NK-lisina mata a los patógenos protozoarios y bacterianos por interacción directa. El análisis genotípico en pollos reveló que ciertos alelos codificaban NK-lisinas que mataban a los patógenos con más eficacia que los péptidos codificados por otros alelos, lo que podría tener influencia en la sensibilidad a las enfermedades. Aunque tal vez los péptidos antimicrobianos sintetizados por el anfitrión que los autores describen en estas líneas no puedan, por sí solos, sustituir a los antibióticos actualmente utilizados en producción animal, su utilización en tratamientos específicos basados en sus mecanismos de acción conocidos está deparando resultados prometedores.

Allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease: a pilot clinical trial.

AIM: Many perianal fistulae in Crohn's disease do not respond to conventional surgical and medical management and recurrence rates are high. The study evaluated the safety and feasibility of allogeneic adipose-derived stem cells for the treatment of perianal fistula in Crohn's disease. METHOD: A multicentre, open-label, dose escalation pilot study was performed. The first three patients (group 1) were administered 1 × 10(7) cells/ml based on the size of the fistula tract. Four weeks later, after which time this dose had been confirmed to be safe, the next three patients (group 2) were administered 3 × 10(7) cells/ml. The end-point was complete closure at 8 weeks after the injection. Patients who attended for the 8 week assessment were followed for an additional 6 months. RESULTS: There were no adverse events of Grade 3 or 4 severity and no adverse events related to the treatment with allogeneic adipose-derived stem cells. Two patients in group 1 achieved complete closure of the fistula at month 4 and month 6, and one patient in group 2 achieved complete closure at 8 weeks. The closure was sustained up to month 8 in all three of those patients. CONCLUSION: These data suggest that allogeneic adipose-derived stem cells may be a feasible treatment option for perianal fistula in Crohn's disease.

PHF2 histone demethylase acts as a tumor suppressor in association with p53 in cancer.

Plant homeodomain finger 2 (PHF2) has a role in epigenetic regulation of gene expression by demethylating H3K9-Me2. Several genome-wide studies have demonstrated that the chromosomal region including the PHF2 gene is often deleted in some cancers including colorectal cancer, and this finding encouraged us to investigate the tumor suppressive role of PHF2. As p53 is a critical tumor suppressor in colon cancer, we tested the possibility that PHF2 is an epigenetic regulator of p53. PHF2 was associated with p53, and thereby, promoted p53-driven gene expression in cancer cells under genotoxic stress. PHF2 converted the chromatin that is favorable for transcription by demethylating the repressive H3K9-Me2 mark. In an HCT116 xenograft model, PHF2 was found to be required for the anticancer effects of oxaliplatin and doxorubicin. In PHF2-deficient xenografts, p53 expression was profoundly induced by both drugs, but its downstream product p21 was not, suggesting that p53 cannot be activated in the absence of PHF2. To find clinical evidence about the role of PHF2, we analyzed the expressions of PHF2, p53 and p21 in human colon cancer tissues and adjacent normal tissues from patients. PHF2 was downregulated in cancer tissues and PHF2 correlated with p21 in cancers expressing functional p53. Colon and stomach cancer tissue arrays showed a positive correlation between PHF2 and p21 expressions. Informatics analyses using the Oncomine database also supported our notion that PHF2 is downregulated in colon and stomach cancers. On the basis of these findings, we propose that PHF2 acts as a tumor suppressor in association with p53 in cancer development and ensures p53-mediated cell death in response to chemotherapy.

Lateral spread response monitoring during microvascular decompression for hemifacial spasm. Comparison of two targets of partial neuromuscular blockade.

AIM: The aim of the present study was to determine (1) whether successful intraoperative electromyography monitoring for lateral spread response (LSR) is possible with partial neuromuscular blockade (NMB) in subjects undergoing microvascular decompression (MVD) for hemifacial spasm and (2) the adequate level of NMB to achieve that goal. MATERIAL AND METHODS: A total of 61 patients in whom LSR was monitored during MVD were enrolled in the study. Patients were randomly allocated to two groups: group TOF in which the NMB target was maintenance of two train-of-four (TOF) counts and group T1 in which the NMB target was maintenance of a T1/Tc ratio of 50 % (T1: first twitch height of TOF and Tc: control twitch height). The adductor pollicis brevis muscle was used to monitor TOF responses. The frequency of successful LSR monitoring, defined as successful baseline establishment and maintenance of LSR until surgical decompression, was compared between the two groups. RESULTS: Of the 61 patients 2 were excluded from the study so that 30 patients in group TOF and 29 patients in group T1 were analyzed. The success rate of LSR monitoring was clinically acceptable and significantly higher in group T1 than in group TOF, i.e. n = 15 (50.0 %) in group TOF versus n = 24 (82.8 %) in group T1 (P = 0.008), corresponding to a 32.8 % higher success rate in group T1 than group TOF (95 % CI: 13.9-51.7 %). Mean vecuronium infusion dose was smaller and mean TOF count was higher in group T1 than group TOF with a TOF count = 2 (1) in group TOF versus 3 (1) in group T1 (P = 0.003). Mean sevoflurane and remifentanil infusion doses were not different between groups. There was no incidence of spontaneous movement during microscopy in either group. CONCLUSION: Maintenance of partial NMB with a target T1/Tc ratio of 50 % resulted in a clinically acceptable success rate of LSR monitoring and surgical condition during MVD. Maintenance of partial NMB with a target T1/Tc ratio of 50 % rather than TOF count of two during LSR monitoring for MVD can therefore be recommended.

Acute gastroenteritis outbreaks associated with ground-waterborne norovirus in South Korea during 2008-2012.

Epidemiological and virological studies indicate that noroviruses-contaminated groundwater was the primary source of four acute gastroenteritis outbreaks in South Korea between 2008 and 2012. Furthermore, cabbage kimchi was first identified as the vehicle of transmission between groundwater and infected patients in an outbreak in 2011. The proper treatment of groundwater sources prior to use for drinking or in food preparation is necessary to prevent further outbreaks.