Feed restriction of lactating cows triggers acute downregulation of mammary mTOR signaling and chronic reduction of mammary epithelial mass.

While there is generally no consensus about how nutrients determine milk synthesis in the mammary gland, it is likely that the mechanistic target of rapamycin complex 1 (mTORC1) plays a role as a key integrator of nutritional and mitogenic signals that can influence a multitude of catabolic and anabolic pathways. The objectives of this study were to evaluate acute changes (<24 h) in translational signaling, in addition to chronic changes (14 d) in mammary gland structure and composition, in response to a severe feed restriction. Fourteen lactating Holstein dairy cows were assigned to either ad libitum feeding (n = 7), or a restricted feeding program (n = 7). Feed-restricted cows had feed removed after the evening milking on d 0. Mammary biopsies and blood samples were collected 16 h after feed removal, after which cows in the restricted group were fed 60% of their previously observed ad lib intake for the remainder of the study. On d 14, animals were sacrificed and mammary glands dissected. In response to feed removal, an acute increase in plasma nonesterified fatty acid concentration was observed, concurrent to a decrease in milk yield. In mammary tissue, we observed downregulation of the mTORC1-S6K1 signaling cascade, in addition to reductions in mRNA expression of markers of protein synthesis, endoplasmic reticulum biogenesis, and cell turnover (i.e., transcripts associated with apoptosis or cell proliferation). During the 14 d of restricted feeding, animals underwent homeorhetic adaptation to 40% lower nutrient intake, achieving a new setpoint of 14% reduced milk yield with 18% and 29% smaller mammary secretory tissue dry matter and crude protein masses, respectively. On d 14, no treatment differences were observed in markers of protein synthesis or mammary cell turnover evaluated using gene transcripts and immunohistochemical staining. These findings implicate mTORC1-S6K1 in the early phase of the adaptation of the mammary gland's capacity for milk synthesis in response to changes in nutrient supply. Additionally, changes in rates of mammary cell turnover may be transient in nature, returning to basal levels following brief alterations that have sustained effects.

Development and validation of a clinical prediction-score model for distant metastases in major salivary gland carcinoma.

BACKGROUND: The most common pattern of failure in major salivary gland carcinoma (SGC) is development of distant metastases (DMs). The objective of this study was to develop and validate a prediction score for DM in SGC. PATIENTS AND METHODS: Patients with SGC treated curatively at four tertiary cancer centers were divided into discovery (n = 619) and validation cohorts (n = 416). Multivariable analysis using competing risk regression was used to identify predictors of DM in the discovery cohort and create a prediction score of DM; the optimal score cut-off was determined using a minimal P value approach. The prediction score was subsequently evaluated in the validation cohort. The cumulative incidence and Kaplan-Meier methods were used to analyze DM and overall survival (OS), respectively. RESULTS: In the discovery cohort, DM predictors (risk coefficient) were: positive margin (0.6), pT3-4 (0.7), pN+ (0.7), lymphovascular invasion (0.8), and high-risk histology (1.2). High DM-risk SGC was defined by sum of coefficients greater than two. In the discovery cohort, the 5-year incidence of DM for high- versus low-risk SGC was 50% versus 8% (P < 0.01); this was similar in the validation cohort (44% versus 4%; P < 0.01). In the pooled cohorts, this model performed similarly in predicting distant-only failure (40% versus 6%, P < 0.01) and late (>2 years post surgery) DM (22% versus 4%; P < 0.01). Patients with high-risk SGC had an increased incidence of DM in the subgroup receiving postoperative radiation therapy (46% versus 8%; P < 0.01). The 5-year OS for high- versus low-risk SGC was 48% versus 92% (P < 0.01). CONCLUSION: This validated prediction-score model may be used to identify SGC patients at increased risk for DM and select those who may benefit from prospective evaluation of treatment intensification and/or surveillance strategies.

Large-scale pathway specific polygenic risk and transcriptomic community network analysis identifies novel functional pathways in Parkinson disease.

Polygenic inheritance plays a central role in Parkinson disease (PD). A priority in elucidating PD etiology lies in defining the biological basis of genetic risk. Unraveling how risk leads to disruption will yield disease-modifying therapeutic targets that may be effective. Here, we utilized a high-throughput and hypothesis-free approach to determine biological processes underlying PD using the largest currently available cohorts of genetic and gene expression data from International Parkinson's Disease Genetics Consortium (IPDGC) and the Accelerating Medicines Partnership-Parkinson's disease initiative (AMP-PD), among other sources. We applied large-scale gene-set specific polygenic risk score (PRS) analyses to assess the role of common variation on PD risk focusing on publicly annotated gene sets representative of curated pathways. We nominated specific molecular sub-processes underlying protein misfolding and aggregation, post-translational protein modification, immune response, membrane and intracellular trafficking, lipid and vitamin metabolism, synaptic transmission, endosomal-lysosomal dysfunction, chromatin remodeling and apoptosis mediated by caspases among the main contributors to PD etiology. We assessed the impact of rare variation on PD risk in an independent cohort of whole-genome sequencing data and found evidence for a burden of rare damaging alleles in a range of processes, including neuronal transmission-related pathways and immune response. We explored enrichment linked to expression cell specificity patterns using single-cell gene expression data and demonstrated a significant risk pattern for dopaminergic neurons, serotonergic neurons, hypothalamic GABAergic neurons, and neural progenitors. Subsequently, we created a novel way of building de novo pathways by constructing a network expression community map using transcriptomic data derived from the blood of PD patients, which revealed functional enrichment in inflammatory signaling pathways, cell death machinery related processes, and dysregulation of mitochondrial homeostasis. Our analyses highlight several specific promising pathways and genes for functional prioritization and provide a cellular context in which such work should be done.

Cooper Pair Density of Bi2Sr2CaCu2O8+ x in Atomic scale at 4.2 K.

In pursuit of the elusive mechanism of high- T C superconductors (HTSC), spectroscopic imaging scanning tunneling microscopy (SI-STM) is an indispensable tool for surveying local properties of HTSC. Since a conventional STM utilizes metal tips, which allow the examination of only quasiparticles and not superconducting (SC) pairs, Josephson tunneling using STM has been demonstrated by many authors in the past. An atomically resolved scanning Josephson tunneling microscopy (SJTM), however, was realized only recently on Bi2Sr2CaCu2O8+ x (Bi-2212) below 50 mK and on the Pb(110) surface at 20 mK. Here we report the atomically resolved SJTM on Bi2Sr2CaCu2O8+ x at 4.2 K using Bi-2212 tips created in situ. The I- V characteristics show clear zero bias conductance peaks following Ambegaokar-Baratoff (AB) theory. A gap map was produced for the first time using an atomically resolved Josephson critical current map I C( r) and AB theory. Surprisingly, we found that this new gap map is anticorrelated to the gap map produced by a conventional method relying on the coherence peaks. Quasiparticle resonance due to a single isolated zinc atom impurity was also observed by SJTM, indicating that atomically resolved SJTM was achieved at 4.2 K. Our result provides a starting point for realizing SJTM at even higher temperatures, rendering possible investigation of the existence of SC pairs in HTSC above the T C.

Gender difference in the impact of coexisting diabetes mellitus on long-term clinical outcome in people with heart failure: a report from the Korean Heart Failure Registry.

AIM: Few data are available on the gender-related differences in the prognostic impact of diabetes in people with heart failure. This study was performed to investigate whether there is a gender difference in the association between diabetes and long-term clinical outcomes in people hospitalized for heart failure. METHODS: A total of 3162 people hospitalized with heart failure (aged 67.4 ± 14.1 years, 50.4% females) from the data set of the nationwide registry were analysed. The primary endpoint was a composite of all-cause mortality and heart failure readmission. RESULTS: People with diabetes (30.5% for males vs. 31.1% for females, P = 0.740) were older and had more unfavourable risk factors and laboratory findings than those without diabetes in both genders. During a median follow-up period of 549 days, there were 1418 cases of composite events (44.8%). In univariable analysis, the coexistence of diabetes was significantly associated with a higher incidence of composite events in both genders (P < 0.05 each for males and females). In multivariable analysis, the prognostic impact of diabetes on the development of composite events remained significant in females even after controlling for potential confounders (hazard ratio 1.43, 95% confidence intervals 1.12-1.84; P = 0.004). However, an independent association between diabetes and composite events was not seen in males in the same multivariable analysis (P > 0.05). CONCLUSIONS: In people with heart failure, the impact of diabetes on long-term mortality and heart failure readmission seems to be stronger in females than in males. More careful and intensive management is needed especially in females with heart failure and diabetes.

Child abuse associates with an imbalance of oligodendrocyte-lineage cells in ventromedial prefrontal white matter.

Child abuse (CA) is a major risk factor for depression, and strongly associates with suicidal behavior during adulthood. Neuroimaging studies have reported widespread changes in white matter integrity and brain connectivity in subjects with a history of CA. Although such observations could reflect changes in myelin and oligodendrocyte function, their cellular underpinnings have never been addressed. Using postmortem brain samples from depressed suicides with or without history of CA and matched controls (18 per group), we aimed to characterize the effects of CA on oligodendrocyte-lineage (OL) cells in the ventromedial prefrontal white matter. Using immunoblotting, double-labeling immunofluorescence and stereological estimates of stage-specific markers, we found that CA is associated with increased numbers of mature myelinating oligodendrocytes, accompanied by decreased numbers of more immature OL cells. This was paralleled by an increased expression of transcription factor MASH1, which is involved in the terminal differentiation of the OL, suggesting that CA may trigger an increased maturation, or bias the populations of OL cells toward a more mature phenotype. Some of these effects, which were absent in the brain of depressed suicides with no history of CA, were also found to recover with age, suggesting that changes in the balance of the OL may reflect a transient adaptive mechanism triggered by early-life adversity. In conclusion, our results indicate that CA in depressed suicides is associated with an imbalance of the OL in the ventromedial prefrontal white matter, an effect that could lead to myelin remodeling and long-term connectivity changes within the limbic network.

Expression of genes related to energy metabolism and the unfolded protein response in dairy cow mammary cells is affected differently during dietary supplementation with energy from protein and fat.

Secretory capacity of bovine mammary glands is enabled by a high number of secretory cells and their ability to use a range of metabolites to produce milk components. We isolated RNA from milk fat to measure expression of genes involved in energy-yielding pathways and the unfolded protein response in mammary glands of lactating cows given supplemental energy from protein (PT) and fat (FT) tested in a 2 × 2 factorial arrangement. We hypothesized that PT and FT would affect expression of genes in the branched-chain AA catabolic pathway and tricarboxylic acid (TCA) cycle based on the different energy types (aminogenic versus lipogenic) used to synthesize milk components. We also hypothesized that the response of genes related to endoplasmic reticulum (ER) homeostasis via the unfolded protein response would reflect the increase in milk production stimulated by PT and FT. Fifty-six multiparous Holstein-Friesian dairy cows were fed a basal total mixed ration (34% grass silage, 33% corn silage, 5% grass hay, and 28% concentrate on a dry matter basis) for a 28-d control period. Experimental rations were then fed for 28 d, consisting of (1) low protein, low fat (LP/LF); (2) high protein, low fat (HP/LF); (3) low protein, high fat (LP/HF); or (4) high protein and high fat (HP/HF). To obtain the high-protein (HP) and high-fat (HF) diets, intake of the basal ration was restricted and supplemented isoenergetically (net energy basis) with 2.0 kg/d rumen-protected protein (soybean + rapeseed, 50:50 mixture on dry matter basis) and 0.68 kg/d hydrogenated palm fatty acids on a dry matter basis. RNA from milk fat samples collected on d 27 of each period underwent real-time quantitative PCR. Energy from protein increased expression of BCAT1 (branched-chain amino acid transferase 1) mRNA, but only at the LF level, and tended to decrease expression of mRNA encoding the main subunit of the branched-chain keto-acid dehydrogenase complex. mRNA expression of malic enzyme, a proposed channeling route for AA though the TCA cycle, was decreased by PT, but only at the LF level. Expression of genes associated with de novo fatty acid synthesis was not affected by PT or FT. Energy from fat had no independent effect on genes related to ER homeostasis. At the LF level, PT activated XBP1 (X-box binding protein 1) mRNA. At the HF level, PT increased mRNA expression of the gene encoding GADD34 (growth arrest and DNA damage-inducible 34). These findings support our hypothesis that mammary cells use aminogenic and lipogenic precursors differently for milk component production when dietary intervention alters AA and fatty acid supply. They also suggest that mammary cells respond to increased AA supply through mechanisms of ER homeostasis, dependent on the presence of FT.

In Vitro Models, Standards, and Experimental Methods for Tobacco Products.

Traditional tobacco products have well-known systemic and local oral effects, including inflammation, vasoconstriction, delayed wound healing, and increased severity of periodontal disease. Specifically in the oral cavity and the lung, cigarette smoking produces cancer, increased infectivity, acute and chronic inflammation, changes in gene expression in epithelial lining cells, and microbiome changes. In recent years, cigarette smoking has greatly decreased in the United States, but the use of new tobacco products has gained tremendous popularity. Without significant knowledge of the oral sequelae of products such as electronic cigarettes, researchers must evaluate current in vitro and in vivo methods to study these agents, as well as develop new tools to adequately study their effects. Some in vitro testing has been performed for electronic cigarettes, including toxicologic models and assays, but these mostly study the effect on the respiratory tract. Recently, direct exposure of the aerosol to in vitro 3-dimensional tissue constructs has been performed, demonstrating changes in cell viability and inflammatory cytokines. For in vivo studies, a universal e-cigarette testing machine or standard vaping regime is needed. A standard research electronic cigarette has recently been developed by the National Institute of Drug Abuse, and other devices delivering aerosols with different nicotine concentrations are becoming available. One of the biggest challenges in this research is keeping up with the new products and the rapidly changing technologies in the industry.

Clinicopathological features and outcome of type 3 gastric neuroendocrine tumours.

BACKGROUND: With the widespread use of endoscopy, small and low-grade type 3 gastric neuroendocrine tumours (NETs) are increasingly being detected. The clinicopathological features, biological behaviour and appropriate treatment strategy for these NETs remain unclear. METHODS: Patients with biopsy-proven gastric NET and a normal fasting serum gastrin level were identified from a prospectively maintained database. Clinicopathological features and long-term outcome of local resection for type 3 NETs were reviewed retrospectively and compared according to tumour grade. RESULTS: Some 32 patients with type 3 gastric NETs were included (25 patients with NET grade G1, 5 with G2 and 2 with G3). Pathological tumour size was 2·0 cm or less in 30 patients. All tumours were well differentiated, even G3 lesions, and all tumours but one were confined to the submucosal layer. G1 NETs were significantly smaller and had a significantly lower lymphovascular invasion rate than G2 and G3 NETs. Twenty-two patients with a G1 NET without lymphovascular invasion were treated with wedge or endoscopic resection. After a median follow-up of 59 (range 6-102) months, no patient with a G1 NET of 1·5 cm or smaller developed recurrence and one patient with a G1 NET larger than 1·5 cm had recurrence in a perigastric lymph node. Among seven patients with a G2 or G3 NET, two had lymph node metastasis and one had liver metastases. CONCLUSION: Low-grade type 3 gastric NET has non-aggressive features and a favourable prognosis. Wedge or endoscopic resection may be a valid option for patients with type 3 gastric G1 NET no larger than 1·5 cm without lymphovascular invasion.

Effective Condition for Whole Testis Cryopreservation of Endangered Miho Spine Loach (Cobitis choii) Through the Optimization of Mud Loach (Misgurnus mizolepis) Whole Testis Cryopreservation Condition.

　　BACKGROUND: Miho spine loach (Cobitis choii) is an endangered Korean endemic fish. Whole testis cryopreservation is a good way for species preservation, but needs to the sacrifice of a large number of fish to optimize the freezing condition. Considering this limitation, a surrogate fish species was used for the protocol development. OBJECTIVE: This study was to establish the effective condition for Miho spine loach whole testis cryopreservation by optimizing the conditions for whole testis cryopreservation in an allied species, mud loach (Misgurnus mizolepis). MATERIALS AND METHODS: The condition for whole testis cryopreservation was optimized in mud loach first, and then the optimal condition was applied to Miho spine loach testes. RESULTS: The optimal condition for mud loach testis cryopreservation consists of the freezing medium containing 1.3 M dimethyl sulfoxide, 6% fetal bovine serum and 0.3 M trehalose, -1 C/min cooling rate and 26 degree C thawing temperature, which also permits effective cryopreservation of Miho spine loach testes. CONCLUSION: An effective cryopreservation condition for whole testis of the endangered Miho spine loach has been established by using mud loach as a surrogate fish.

Influence of esophagectomy on the gastroesophageal reflux in patients with esophageal cancer.

This study aims to assess the influence of esophagectomy with gastric transposition on the gastroesophageal reflux (GER) and gastric acidity in patients with esophageal cancer. Data on 53 esophageal cancer patients who underwent 24-hour impedance-pH monitoring after esophagectomy were retrospectively analyzed. We used a solid-state esophageal pH probe in which the esophageal pH sensor is placed 1.5 cm distal to the upper esophageal sphincter and the gastric pH sensor is located 15 cm distal to the esophageal pH channel. 24-hour impedance-pH monitoring data and other clinical data including anastomosis site stricture and incidence of pneumonia were collected. We defined pathologic reflux with reference to known normative data. Stricture was defined when an intervention such as bougienage or balloon dilatation was required to relieve dysphagia. The esophageal and gastric mean pH were 5.47 ± 1.51 and 3.33 ± 1.64, respectively. The percent time of acidic pH (<4) was 6.66 ± 12.49% in the esophagus and 70.53 ± 32.19% in the stomach. Esophageal pathologic acid reflux was noticed in 32.1%, 20.8%, and 35.8% during total, upright, and recumbent time, respectively. Esophageal pathologic bolus reflux was noted in 83.0%, 77.4%, and 64.2% during total, upright, and recumbent time, respectively. Gastric acidity increased with time after esophagectomy. Esophageal acid exposure time correlated with intragastric pH. However, esophageal pathologic acid reflux was not associated with anastomosis site stricture or pneumonia. In conclusion, GER frequently occurs after esophagectomy. Thus, strict lifestyle modifications and acid suppression would be necessary in patients following esophagectomy.

Exogenous essential amino acids stimulate an adaptive unfolded protein response in the mammary glands of lactating cows.

The phosphorylation of mammalian target of rapamycin complex 1 (mTORC1) components and integrated stress response networks in the mammary glands of lactating cows have not accounted for the stimulation of milk protein yield by chronic supplementation with AA or glucose. Faster milk protein synthesis could be a consequence of increased milk protein mRNA per cell, the number of ribosomes per cell, the secretory capacity of cells, or the mammary cell number. To investigate these 4 possibilities using a translational and transcriptional approach, we performed protein and gene expression analyses of mammary and longissimus dorsi tissue collected from lactating dairy cows after 5 d of abomasal infusion with saline or 844 or 1,126 g/d of an essential AA (EAA) mixture, with and without 1,000 g/d glucose. Infusion with EAA increased milk protein yield but did not affect the phosphorylation of mTORC1-related proteins in the mammary gland. In skeletal muscle, phosphorylation of 4EBP1 (eIF4E-binding protein 1) increased in response to both EAA and glucose, and phosphorylated S6K1 (70-kDa ribosomal protein S6 kinase) increased with glucose. In response to EAA, mammary mRNA expression of the marker genes for milk proteins, ribosome biogenesis, and cell proliferation were not upregulated. Instead, reciprocal regulation of 2 arms of the unfolded protein response occurred. Infusion of EAA for 5 d activated XBP1 (X-box binding protein 1) mRNA, encoding a transcription factor for endoplasmic reticulum biogenesis, and it decreased the mRNA expression of genes encoding pro-apoptotic protein CHOP (C/EBP homologous protein) and downstream GADD34 (growth arrest and DNA damage-inducible 34). These findings implicate non-stress-related, adaptive capabilities of the unfolded protein response in the long-term nutritional regulation of milk protein yield in lactating dairy cows.

Addition of glycerol to lactating cow diets stimulates dry matter intake and milk protein yield to a greater extent than addition of corn grain.

The objective of this study was to determine if the addition of glycerol to the diet of dairy cows would stimulate milk protein yield in the same manner as the addition of corn grain. Twelve multiparous lactating dairy cows at 81 ± 5 d in milk were subjected to 3 dietary treatments in a replicated 3 × 3 Latin square design for 28-d periods. The diets were a 70% forage diet considered the basal diet, the basal diet with 19% ground and high-moisture corn replacing forages, and the basal diet with 15% refined glycerol and 4% added protein supplements to be isocaloric and isonitrogenous with the corn diet. Cows were milked twice a day and samples were collected on the last 7 d of each period for compositional analysis. Within each period, blood samples were collected on d 26 and 27, and mammary tissue was collected by biopsy on d 28 for Western blot analysis. Dry matter intake increased from 23.7 kg/d on the basal diet to 25.8 kg/d on the corn diet and 27.2 kg/d on the glycerol diet. Dry matter intake tended to be higher with glycerol than corn. Milk production increased from 39.2 kg/d on the basal diet to 43.8 kg/d on the corn diet and 44.2 kg/d on the glycerol diet. However, milk yield did not differ between corn and glycerol diets. Milk lactose yields were higher on the corn and glycerol diets than the basal diet. Milk fat yield significantly decreased on the glycerol diet compared with the basal diet and tended to decrease in comparison with the corn diet. Mean milk fat globule size was reduced by glycerol feeding. Milk protein yield increased 197 g/d with addition of corn to the basal diet and 263 g/d with addition of glycerol, and the glycerol effect was larger than the corn effect. The dietary treatments had no effects on plasma glucose concentration, but plasma acetate levels decreased 27% on the glycerol diet. Amino acid concentrations were not affected by dietary treatments, except for branched-chain amino acids, which decreased 22% on the glycerol diet compared with the corn diet. The decreases in plasma acetate and branched-chain amino acid concentrations with glycerol and the larger effects of glycerol than corn on milk protein and fat yields suggest that glycerol is more glucogenic for cows than corn grain.

Identifying the potential long-term survivors among breast cancer patients with distant metastasis.

BACKGROUND: We aimed to develop a prediction model to identify long-term survivors after developing distant metastasis from breast cancer. PATIENTS AND METHODS: From the institution's database, we collected data of 547 patients who developed distant metastasis during their follow-ups. We developed a model that predicts the post-metastasis overall survival (PMOS) based on the clinicopathologic factors of the primary tumors and the characteristics of the distant metastasis. For validation, the survival data of 254 patients from four independent institutions were used. RESULTS: The median duration of the PMOS was 31.0 months. The characteristics of the initial primary tumor, such as tumor stage, hormone receptor status, and Ki-67 expression level, and the characteristics of the distant metastasis presentation including the duration of disease-free interval, the site of metastasis, and the presence of metastasis-related symptoms were independent prognostic factors determining the PMOS. The association between tumor stage and the PMOS was only seen in tumors with early relapses. The PMOS score, which was developed based on the above six factors, successfully identified patients with superior survival after metastasis. The median PMOS for patients with a PMOS score of <2 and for patients with a PMOS score of >5 were 71.0 and 12 months, respectively. The clinical significance of the PMOS score was further validated using independent multicenter datasets. CONCLUSIONS: We have developed a novel prediction model that can classify breast cancer patients with distant metastasis according to their survival after metastasis. Our model can be a valuable tool to identify long-term survivors who can be potential candidates for more intensive multidisciplinary approaches. Furthermore, our model can provide a more reliable survival information for both physicians and patients during their informed decision-making process.

The value of male human papillomavirus vaccination in preventing cervical cancer and genital warts in a low-resource setting.

OBJECTIVE: To estimate health benefits and incremental cost-effectiveness of human papillomavirus (HPV) vaccination of pre-adolescent boys and girls compared with girls alone for preventing cervical cancer and genital warts. DESIGN: Model-based economic evaluation. SETTING: Southern Vietnam. POPULATION: Males and females aged ≥9 years. METHODS: We simulated dynamic HPV transmission to estimate cervical cancer and genital warts cases. Models were calibrated to epidemiological data from south Vietnam. MAIN OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs): cost per quality-adjusted life-year (QALY). RESULTS: Vaccinating girls alone was associated with reductions in lifetime cervical cancer risk ranging from 20 to 56.9% as coverage varied from 25 to 90%. Adding boys to the vaccination programme yielded marginal incremental benefits (≤3.6% higher absolute cervical cancer risk reduction), compared with vaccinating girls alone at all coverages. At ≤25 international dollars (I$) per vaccinated adolescent (I$5 per dose), HPV vaccination of boys was below the threshold of Vietnam's per-capita GDP (I$2800), with ICERs ranging from I$734 per QALY at 25% coverage to I$2064 per QALY for 90% coverage. Including health benefits from averting genital warts yielded more favourable ICERs, and vaccination of boys at I$10/dose became cost-effective at or below 75% coverage. Using a lower cost-effectiveness threshold of 50% of Vietnam's GDP (I$1400), vaccinating boys was no longer attractive at costs above I$5 per dose regardless of coverage. CONCLUSION: Vaccination of boys may be cost-effective at low vaccine costs, but provides little benefit over vaccinating girls only. Focusing on achieving high vaccine coverage of girls may be more efficient for southern Vietnam and similar low-resource settings. TWEETABLE ABSTRACT: Limited cervical cancer reduction from including boys in HPV vaccination of girls in low-resource settings.

Blue Emitters Based on Aryl End-Capped Pyrene Groups for OLEDs.

We have synthesized four pyrene-derived blue emitting materials using Suzuki cross coupling reactions. All OLED devices using these materials as emitting materials showed efficient blue electroluminescence (EL). Particularly, a device using 1,1'-(9,9-dimethyl-9H-fluorene-2,7-diyl)bis-pyrene (1) showed best EL properties with the luminous efficiency of 4.32 cd/A, the power efficiency of 3.98 lm/W and the external quantum efficiency of 2.48% at 500 cd/m2.

Glucose supplementation stimulates peripheral branched-chain amino acid catabolism in lactating dairy cows during essential amino acid infusions.

To determine how glucose modulates protein synthesis when essential AA are in abundant supply, 5 early-lactation, rumen-fistulated Holstein dairy cows were fed a diet containing 6.95 MJ/kg of net energy for lactation and 12.4% crude protein and abomasally infused for 5 d with saline, 844 or 1,126 g/d of a complete essential AA mix, with and without the inclusion of 1,000 g/d of glucose, in a 5×5 Latin square design. Infusion of essential AA increased milk yield by 4.1 kg/d, milk protein by 256 g/d, milk fat by 95 g/d, and milk urea nitrogen by 70% compared with saline, with no differences between the level of essential AA infusion. The addition of glucose to essential AA infusate did not stimulate milk protein yield or concentration, but reduced milk urea nitrogen by 17% and decreased milk fat yield. Arterial concentrations of total essential AA increased 3- to 4-fold, mammary clearance decreased 61%, and mammary uptake of essential AA increased 65% in response to essential AA infusion. Arterial branched-chain AA concentrations declined 29% in response to glucose and mammary clearance increased 48%, but mammary AA uptake was unchanged. Essential AA infusion increased plasma 3-methylhistidine by 50% and reduced muscle branched-chain α-keto acid dehydrogenase kinase abundance by 14%, indicating stimulation of muscle protein turnover and branched-chain AA catabolism, respectively. Glucose had no further effect on muscle branched-chain α-keto acid dehydrogenase kinase abundance but decreased mRNA expression of branched chain aminotransferase 1. Lack of further increases in plasma 3-methylhistidine or greater stimulation of muscle branched-chain AA catabolism indicates that muscle protein degradation was unchanged with glucose but that accretion may have been stimulated. The decrease in circulating branched-chain AA concentrations and nitrogen excretion in response to glucose suggests that surplus essential AA were redirected to peripheral, extra-mammary tissues.

Relationship between Single Nucleotide Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma Gene and Fatty Acid Composition in Korean Native Cattle.

The peroxisome proliferator-activated receptor gamma (PPARγ) gene plays an important role in the biosynthesis process controlled by a number of fatty acid transcription factors. This study investigates the relationships between 130 single-nucleotide polymorphisms (SNPs) in the PPARγ gene and the fatty acid composition of muscle fat in the commercial population of Korean native cattle. We identified 38 SNPs and verified relationships between 3 SNPs (g.1159-71208 A>G, g.42555-29812 G>A, and g.72362 G>T) and the fatty acid composition of commercial Korean native cattle (n = 513). Cattle with the AA genotype of g.1159-71208 A>G and the GG genotype of g.42555-29812 G>A and g.72362 G>T had higher levels of monounsaturated fatty acids and carcass traits (p<0.05). The results revealed that the 3 identified SNPs in the PPARγ gene affected fatty acid composition and carcass traits, suggesting that these 3 SNPs may improve the flavor and quality of beef in commercial Korean native cattle.

Effect of rescue surgery after non-curative endoscopic resection of early gastric cancer.

BACKGROUND: Whether rescue surgery confers a survival benefit in patients undergoing non-curative endoscopic resection of early gastric cancer remains controversial. METHODS: This was a retrospective review of patients who underwent non-curative endoscopic resection of at least one lesion of differentiated-type early gastric cancer between 2000 and 2011. Patients with a positive lateral resection margin as the only non-curative factor were excluded. Outcome was investigated by univariable (Kaplan-Meier) and multivariable (Cox proportional hazards) analysis. RESULTS: Some 341 patients underwent non-curative endoscopic resection for at least one lesion of differentiated-type early gastric cancer. Sixty-seven patients with a positive lateral resection margin as the only non-curative factor were excluded, leaving 274 patients for analysis; 194 had rescue surgery and 80 had no additional treatment. The median duration of follow-up was 60·5 months. Patients who had rescue surgery were younger, had a lower Charlson co-morbidity index score, smaller tumours and a higher lymphovascular invasion rate than patients with no treatment. Among 194 patients who had rescue surgery, intragastric local residual tumours were found in ten (5·2 per cent) and lymph node metastases in 11 (5·7 per cent). Patients with lymph node metastasis were significantly older than those without metastasis; no other significant differences were found. Univariable analysis showed that patients aged less than 65 years, those with a Charlson co-morbidity index score below 4 and patients undergoing rescue surgery had significantly longer overall survival. Five-year overall survival rates in the rescue surgery and no-treatment groups were 94·3 and 85 per cent respectively. In multivariable analysis, rescue surgery was identified as the only independent predictor of overall survival after non-curative endoscopic resection of early gastric cancer. CONCLUSION: Rescue surgery confers a survival benefit after non-curative endoscopic resection of early gastric cancer.