Safety and efficacy of trastuzumab biosimilar plus irinotecan or gemcitabine in patients with previously treated HER2 (ERBB2)-positive non-breast/non-gastric solid tumors: a phase II basket trial with circulating tumor DNA analysis.

BACKGROUND: Human epidermal growth factor receptor 2 (HER2) (ERBB2)-directed agents are standard treatments for patients with HER2-positive breast and gastric cancer. Herein, we report the results of an open-label, single-center, phase II basket trial to investigate the efficacy and safety of trastuzumab biosimilar (Samfenet®) plus treatment of physician's choice for patients with previously treated HER2-positive advanced solid tumors, along with biomarker analysis employing circulating tumor DNA (ctDNA) sequencing. METHODS: Patients with HER2-positive unresectable or metastatic non-breast, non-gastric solid tumors who failed at least one prior treatment were included in this study conducted at Asan Medical Center, Seoul, Korea. Patients received trastuzumab combined with irinotecan or gemcitabine at the treating physicians' discretion. The primary endpoint was the objective response rate as per RECIST version 1.1. Plasma samples were collected at baseline and at the time of disease progression for ctDNA analysis. RESULTS: Twenty-three patients were screened from 31 December 2019 to 17 September 2021, and 20 were enrolled in this study. Their median age was 64 years (30-84 years), and 13 patients (65.0%) were male. The most common primary tumor was hepatobiliary cancer (seven patients, 35.0%), followed by colorectal cancer (six patients, 30.0%). Among 18 patients with an available response evaluation, the objective response rate was 11.1% (95% confidence interval 3.1% to 32.8%). ERBB2 amplification was detected from ctDNA analysis of baseline plasma samples in 85% of patients (n = 17), and the ERBB2 copy number from ctDNA analysis showed a significant correlation with the results from tissue sequencing. Among 16 patients with post-progression ctDNA analysis, 7 (43.8%) developed new alterations. None of the patients discontinued the study due to adverse events. CONCLUSIONS: Trastuzumab plus irinotecan or gemcitabine was safe and feasible for patients with previously treated HER2-positive advanced solid tumors with modest efficacy outcomes, and ctDNA analysis was useful for detecting HER2 amplification.

Management of Discolored Anterior Teeth with Pulp Canal Obliteration.

The purpose of this article is to present the effect and follow-up results of combined single-tooth vital bleaching when discoloration is due to pulp canal obliteration. In these cases, discoloration was managed successfully via home bleaching with a customized single-tooth tray and in-office bleaching without root canal treatment.

Stachydrine alleviates lipid-induced skeletal muscle insulin resistance via AMPK/HO-1-mediated suppression of inflammation and endoplasmic reticulum stress.

OBJECTIVE: Insulin resistance develops due to skeletal muscle inflammation and endoplasmic reticulum (ER) stress. Stachydrine (STA), extracted from Leonurus heterophyllus, has been shown to suppress proliferation and induce apoptosis in breast cancer cells and exert anti-inflammatory properties in the brain, heart, and liver. However, the roles of STA in insulin signaling in skeletal muscle remain unclear. Herein, we examined the impacts of STA on insulin signaling in skeletal muscle under hyperlipidemic conditions and its related molecular mechanisms. METHODS: Various protein expression levels were determined by Western blotting. Levels of mouse serum cytokines were measured by ELISA. RESULTS: We found that STA-ameliorated inflammation and ER stress, leading to attenuation of insulin resistance in palmitate-treated C2C12 myocytes. STA dose-dependently enhanced AMPK phosphorylation and HO-1 expression. Administration of STA attenuated not only insulin resistance but also inflammation and ER stress in the skeletal muscle of high-fat diet (HFD)-fed mice. Additionally, STA-ameliorated glucose tolerance and insulin sensitivity, as well as serum TNFα and MCP-1, in mice fed a HFD. Small interfering (si) RNA-associated suppression of AMPK or HO-1 expression abolished the effects of STA in C2C12 myocytes. CONCLUSIONS: These results suggest that STA activates AMPK/HO-1 signaling, resulting in reduced inflammation and ER stress, thereby improving skeletal muscle insulin resistance. Using STA as a natural ingredient, this research successfully treated insulin resistance and type 2 diabetes.

Tumor immune-gene expression profiles and peripheral immune phenotypes associated with clinical outcomes of locally advanced pancreatic cancer following FOLFIRINOX.

BACKGROUND: A comprehensive analysis of peripheral immune cell phenotypes and tumor immune-gene expression profiles in locally advanced pancreatic cancer patients treated with neoadjuvant chemotherapy in a phase II clinical trial was carried out. METHODS: Patients were treated with neoadjuvant modified folinic acid, fluorouracil, irinotecan hydrochloride, oxaliplatin (mFOLFIRINOX) followed by surgery and adjuvant gemcitabine at the Asan Medical Center. Correlations between survival outcomes and baseline peripheral immune cells and their changes during preoperative chemotherapy were analyzed. Patients who had surgery were divided into two groups according to achievement of disease-free survival >10 months (achieved versus failed). Differential expression and pathway analysis of immune-related genes were carried out using the Nanostring platform, and immune cells within the tumor microenvironment were compared by immunohistochemistry. RESULTS: Forty-four patients were treated in the phase II clinical trial. Higher baseline CD14+CD11c+HLA-DR+ monocytes (P = 0.044) and lower Foxp3+CD4+ T cells (P = 0.02) were associated with poor progression-free survival of neoadjuvant mFOLFIRINOX. During the preoperative chemotherapy, PD-1 T cells significantly decreased (P = 0.0110). Differential expression and pathway analysis of immune-genes from the resected tumor after neoadjuvant treatment revealed transforming growth factor-ß pathway enrichment and higher expression of MARCO (adjusted P < 0.05) associated with early recurrence. Enrichment of the Th1 pathway and higher peritumoral CD8+ T cells (P = 0.0103) were associated with durable disease-free survival from surgery (>10 months) following neoadjuvant mFOLFIRINOX. CONCLUSIONS: Our results identify potential immune biomarkers for locally advanced pancreatic cancer and provide insights into pancreatic cancer immunity.

Increased salivary syndecan-1 level is associated with salivary gland function and inflammation in patients with Sjögren's syndrome.

OBJECTIVE: Syndecan-1 (SDC-1), a transmembrane heparin sulphate proteoglycan predominantly expressed on epithelial cells, also exists in a soluble form through ectodomain shedding. SDC-1 expression and shedding may be modulated in the inflammatory milieu of primary Sjögren's syndrome (SS). We investigated SDC-1 expression in minor salivary glands (MSGs) and analysed the association between salivary or plasma levels of SDC-1 and clinical parameters in SS. METHOD: We measured salivary and plasma SDC-1 levels via an enzyme-linked immunosorbent assay and assessed the salivary flow rates (SFRs) in 70 patients with SS and 35 healthy subjects. Disease activity indices, serological markers, salivary gland scintigraphy, and MSG biopsy were evaluated in patients with SS. RESULTS: SDC-1 expression was upregulated on ductal epithelial cells in inflamed salivary glands. Salivary SDC-1 levels in patients significantly exceeded those in healthy subjects [median (interquartile range) 49.0 (20.7-79.1) vs 3.7 (1.7-6.3) ng/mL, p < 0.001] and inversely correlated with SFRs (r = -0.358, p = 0.032) and ejection fractions of the parotid (r = -0.363, p = 0.027) and submandibular (r = -0.485, p = 0.002) glands in salivary gland scintigraphy. Plasma SDC-1 levels were significantly correlated with the EULAR Sjögren's Syndrome Disease Activity Index (r = 0.507, p < 0.001) and EULAR Sjögren's Syndrome Patient Reported Index (r = 0.267, p = 0.033). Focus scores were correlated with salivary SDC-1 levels (r = 0.551, p = 0.004). CONCLUSIONS: Salivary and plasma SDC-1 levels may constitute potential biomarkers for salivary gland function and disease activity, respectively, in SS.

Capecitabine plus temozolomide in patients with grade 3 unresectable or metastatic gastroenteropancreatic neuroendocrine neoplasms with Ki-67 index <55%: single-arm phase II study.

BACKGROUND: Grade 3 neuroendocrine neoplasms (NENs) of gastroenteropancreatic (GEP) origin with Ki-67 indices <55% do not respond well to platinum-based chemotherapy. The combination of capecitabine and temozolomide (CAPTEM) has shown favorable responses in grade 1-2 NENs, but has rarely been studied in patients with grade 3 NENs. PATIENTS AND METHODS: This open-label, single-arm phase II trial included patients with unresectable or metastatic grade 3 NENs of GEP origin with Ki-67 indices <55% enrolled between June 2017 and July 2020. Patients received oral capecitabine 750 mg/m2 twice daily on days 1 to 14 and oral temozolomide 200 mg/m2 once daily on days 10 to 14 every 4 weeks. Histologic findings were centrally reviewed after the completion of enrollment. The primary endpoint was overall response rate, and the secondary endpoints were progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS: Of the 30 patients included in the full analysis set, 1 (3.3%) achieved complete response, 8 (26.7%) had partial responses, and 14 (46.7%) had stable disease, making the overall response rate 30.0%. At a median follow-up of 19.2 months, the median PFS was 5.9 months and the median OS was not reached. Patients with well-differentiated NENs showed significantly better median PFS (9.3 months versus 3.5 months, P = 0.005) and median OS (not reached versus 6.2 months, P = 0.004) than patients with poorly differentiated tumors. Expression of O6-methyl-guanine methyltransferase protein did not correlate with clinical outcomes. The most common grade 3-4 adverse events were thrombocytopenia (10%), anemia (6.7%), and nausea (6.7%). CONCLUSIONS: CAPTEM was effective and well tolerated in patients with grade 3 GEP-NENs with Ki-67 indices <55%, with superior efficacy outcomes compared with the historical controls receiving platinum-based chemotherapy.

Intramedullary pneumorrhachis following a cervical epidural steroid injection.

Pneumorrhachis (PR) is a rare radiological condition characterized by the presence of intraspinal air. PR is commonly classified as spontaneous (nontraumatic), traumatic, or iatrogenic, and iatrogenic PR is the most common and often occurs secondary to invasive procedures such as epidural anesthesia, lumbar puncture, or spinal surgery. PR is usually asymptomatic, but it can produce symptoms associated with its underlying pathology. Here, we report a rare case of intramedullary cervical PR following a cervical epidural steroid injection (ESI) and include pertinent discussion.

Safety and effectiveness of lumbar cerebrospinal fluid drainage to prevent delayed cerebral ischemia after Fisher grade 3 subarachnoid hemorrhage with minimal intraventricular hemorrhage.

OBJECTIVE: Lumbar drainage (LD) of cerebrospinal fluid (CSF) is a simple way of clearing subarachnoid hemorrhage (SAH) and reducing the risk of delayed cerebral ischemia (DCI). We focused on Fisher grade 3 SAH with or without minimal intraventricular hemorrhage (IVH; Graeb score ≤5), which has a lower risk of cerebellar tonsillar herniation during LD. The aim of this study was to test the efficacy of LD with respect to reducing the risk of DCI in this patient group. METHODS: The authors retrospectively reviewed the medical records of 107 patients with Fisher grade 3 SAH with or without minimal IVH, admitted to two hospitals from 2013 to 2019. Patients were retrospectively divided into two groups: study group receiving standard therapy plus LD, or control group receiving standard therapy alone. Primary outcome measures were efficient in preventing DCI. RESULTS: One hundred and seven subjects were allocated to the control (n=79) or study (n=28) groups. Incidence of DCI was 28% (n=22) and 18% (n=5), respectively (P=0.448). Subgroup analysis for HH grade 3+4 (n=68) showed incidence of DCI of 24% (n=19) in the control group (n=50) and 7% (n=2) in the study group (n=18) (P=0.040). There were no LD-related complications. CONCLUSIONS: This study could not draw a meaningful conclusion about the overall efficacy of LD on DCI reduction due to small sample size. However, there was a significant reduction of DCI by LD in the HH 3+4 subpopulation. Larger-scale studies are required to confirm our results.

Anion gap and base deficit are predictors of mortality in acute pesticide poisoning.

BACKGROUND:: Acute pesticide poisoning has long been a serious problem as a method of suicide worldwide. This poisoning is a highly fatal condition that requires a rapid and precise diagnosis for adequate treatment. However, various studies on mortality predictor factors have been insufficient for whole pesticide treatments. We hypothesized that the initial plasma anion gap (AG) and base deficit (BD) are reliable prognostic factors. METHODS:: A retrospective study analyzed 561 patients with a diagnosis of acute pesticide poisoning between January 1, 2014 and June 30, 2017. The initial AG and BD values were divided into quartiles according to the number of patients. Survival at 30 days from admission was estimated using the Kaplan-Meier survival analysis. Receiver-operator characteristic (ROC) curves were drawn, and the areas under the curve for AG and BD for mortality were calculated. RESULTS:: Fifty-eight (10.3%) of 561 patients died within 30 days. The highest AG quartile (>22 mEq/L) was associated with an increased risk of 30-day hospital mortality. Compared to patients with an AG less than 14.7 mEq/L, these patients had a 4.18-fold higher risk of 30-day hospital mortality and the highest BD quartile (>7.9 mEq/L) was associated with an increased risk of 30-day hospital mortality. Compared to patients with a BD less than 1.4 mEq/L, these patients had 2.23-fold higher risk of 30-day hospital mortality. The areas under the ROC for AG and BD curve were 0.699 and 0.744, respectively. CONCLUSIONS:: Initial high AG and BD values could predict mortality and require precise intensive care.

The effects of biodegradable poly(lactic-co-glycolic acid)-based microspheres loaded with quercetin on stemness, viability and osteogenic differentiation potential of stem cell spheroids.

OBJECTIVE: Quercetin has been reported to exert many beneficial effects on the protection against various diseases, such as diabetes, cancer, and inflammation. The aim of this study is to evaluate the potential osteogenic differentiation ability of mesenchymal stem cells in the presence of quercetin. MATERIAL AND METHODS: Quercetin-loaded poly(lactic-co-glycolic acid) microspheres were prepared using an electrospraying technique. Characterization of the microspheres was evaluated with a scanning electron microscope and release profile. Three-dimensional cell spheroids were fabricated using silicon elastomer-based concave microwells. Qualitative results of cellular viability were seen under a confocal microscope, and quantitative cellular viability was evaluated using the Cell Counting Kit-8 assay. The alkaline phosphatase activity and Alizarin Red S staining were performed. A quantitative real-time polymerase chain reaction and a western blot analysis were performed. RESULTS: Spheroids were well formed irrespective of quercetin concentration. Most of the cells in spheroids emitted green fluorescence, and the morphology was round without significant changes. The application of quercetin-loaded microspheres produced a significant increase in the alkaline phosphatase activity. The real-time polymerase chain reaction results showed a significant increase in Runx2, and western blot results showed higher expression of Runx2 protein expression. CONCLUSION: Biodegradable microspheres loaded with quercetin produced prolonged release profiles with increased mineralization. Microspheres loaded with quercetin can be used for the enhancement of osteoblastic differentiation in cell therapy.

Dicam promotes proliferation and maturation of chondrocyte through Indian hedgehog signaling in primary cilia.

OBJECTIVES: Primary cilium is required for mechano-biological signal transduction in chondrocytes, and its interaction with extracellular matrix is critical for cartilage homeostasis. However, the role of cilia-associated proteins that affect the function of cilia remains to be elucidated. Here, we show that Dicam has a novel function as a modulator of primary cilia-mediated Indian hedgehog (Ihh) signaling in chondrocytes. METHODS: Cartilage-specific Dicam transgenic mouse was constructed and the phenotype of growth plates at embryonic day 15.5 and 18.5 was analyzed. Primary chondrocytes and tibiae isolated from embryonic day 15.5 mice were used in vitro study. RESULTS: Dicam was mainly expressed in resting and proliferating chondrocytes of the growth plate and was increased by PTHrP and BMP2 in primary chondrocytes. Cartilage-specific Dicam gain-of-function demonstrated increased length of growth plate in long bones. Dicam enhanced both proliferation and maturation of growth plate chondrocytes in vivo and in vitro, and it was accompanied by enhanced Ihh and PTHrP signaling. Dicam was localized to primary cilia of chondrocytes, and increased the number of primary cilia and their assembly molecule, IFT88/Polaris as well. Dicam successfully rescued the knock-down phenotype of IFT88/Polaris and it was accompanied by increased number of cilia in tibia organ culture. CONCLUSION: These findings suggest that Dicam positively regulates primary cilia and Ihh signaling resulting in elongation of long bone.

Limited pathogenicity and transmissibility of Korean highly pathogenic avian influenza H5N6 clade 2.3.4.4 in ferrets.

The pathogenicity and transmissibility of a reassortant clade 2.3.4.4 avian influenza A (H5N6) virus were evaluated in ferrets. Virus excretion was detected in the upper respiratory tract, but the ferrets did not show any clinical signs of infection. Transmission did not occur between cohoused or respiratory droplet-contact ferrets.

Acetylcholine precursor, citicoline (cytidine 5'-diphosphocholine), reduces hypoglycaemia-induced neuronal death in rats.

Citicoline (cytidine 5'-diphosphocholine) is an important precursor for the synthesis of neuronal plasma membrane phospholipids, mainly phosphatidylcholine. The administration of citicoline serves as a choline donor for the synthesis of acetylcholine. Citicoline has been shown to reduce the neuronal injury in animal models with cerebral ischaemia and in clinical trials of stroke patients. Citicoline is currently being investigated in a multicentre clinical trial. However, citicoline has not yet been examined the context of hypoglycaemia-induced neuronal death. To clarify the therapeutic impact of citicoline in hypoglycaemia-induced neuronal death, we used a rat model with insulin-induced hypoglycaemia. Acute hypoglycaemia was induced by i.p. injection of regular insulin (10 U kg-1 ) after overnight fasting, after which iso-electricity was maintained for 30 minutes. Citicoline injections (500 mg/kg, i.p.) were started immediately after glucose reperfusion. We found that post-treatment of citicoline resulted in significantly reduced neuronal death, oxidative injury and microglial activation in the hippocampus compared to vehicle-treated control groups at 7 days after induced hypoglycaemia. Citicoline administration after hypoglycaemia decreased immunoglobulin leakage via blood-brain barrier disruption in the hippocampus compared to the vehicle group. Citicoline increased choline acetyltransferase expression for phosphatidylcholine synthesis after hypoglycaemia. Altogether, the present findings suggest that neuronal membrane stabilisation by citicoline administration can save neurones from the degeneration process after hypoglycaemia, as seen in several studies of ischaemia. Therefore, the results suggest that citicoline may have therapeutic potential to reduce hypoglycaemia-induced neuronal death.

Base deficit is a predictor of mortality in organophosphate insecticide poisoning.

OBJECTIVE: Organophosphate insecticide (OPI) self-poisoning is a major medical problem in many countries. Several studies have demonstrated that the base deficit (BD) is a prognostic tool that is correlated with the severity of injury and predicted mortality, particularly in trauma patients. Here, we aimed to investigate the prognostic significance of BD in OPI poisoning. METHODS: This retrospective observational study was conducted between January 1, 2006, and January 31, 2015, at a single emergency department (ED). The BD values were divided into quartiles according to the number of patients: 3 mEq/L or less, 3-5.9 mEq/L, 6-9.9 mEq/L, and 10 mEq/L or greater. Survival at 30 days from ED admission was estimated using the Kaplan-Meier survival analysis. RESULTS: Among 154 patients, 31 died, yielding a mortality of 20.1%. The highest BD quartile (≥ 10 mEq/L) and the 6-9.9 mEq/L group were associated with an increased risk of 30-day mortality. Patients with a BD of 10 mEq/L or greater had a 5.85-fold higher risk of 30-day mortality and patients with a BD of 6-9.9 mEq/L had a 5.40-fold higher risk of 30-day mortality compared to patients with a BD of 3 mEq/L or less. The area under the curves of the BD and the Acute Physiology and Chronic Health Evaluation II score for mortality were 0.748 (95% confidence interval (CI), 0.660-0.835) and 0.852 (95% CI, 0.789-0.915), respectively. CONCLUSIONS: This study showed that the BD is a predictor of 30-day mortality in patients with OPI poisoning.

Influence of various levels of milk by-products in weaner diets on growth performance, blood urea nitrogen, diarrhea incidence, and pork quality of weaning to finishing pigs.

OBJECTIVE: This study was conducted to evaluate various levels of milk by-product in weaning pig diet on growth performance, blood profiles, carcass characteristics and economic performance for weaning to finishing pigs. METHODS: A total of 160 weaning pigs ([Yorkshire×Landrace]×Duroc), average 7.01±1.32 kg body weight (BW), were allotted to four treatments by BW and sex in 10 replications with 4 pigs per pen in a randomized complete block design. Pigs were fed each treatment diet with various levels of milk by-product (Phase 1: 0%, 10%, 20%, and 30%, Phase 2: 0%, 5%, 10%, and 15%, respectively). During weaning period (0 to 5 week), weaning pigs were fed experimental diets and all pigs were fed the same commercial feed during growing-finishing period (6 to 14 week). RESULTS: In the growth trial, BW, average daily gain (ADG), and average daily feed intake (ADFI) in the nursery period (5 weeks) increased as the milk by-product level in the diet increased (linear, p<0.05). Linear increases of pig BW with increasing the milk product levels were observed until late growing period (linear, p = 0.01). However, there were no significant differences in BW at the finishing periods, ADG, ADFI, and gain:feed ratio during the entire growing-finishing periods. The blood urea nitrogen concentration had no significant difference among dietary treatments. High inclusion level of milk by-product in weaner diet decreased crude protein (quadratic, p = 0.05) and crude ash (Linear, p = 0.05) of Longissimus muscle. In addition, cooking loss and water holding capacity increased with increasing milk product levels in the weaner diets (linear, p<0.01; p = 0.05). High milk by-product treatment had higher feed cost per weight gain compared to non-milk by-products treatment (linear, p = 0.01). CONCLUSION: Supplementation of 10% to 5% milk by-products in weaning pig diet had results equivalent to the 30% to 15% milk treatment and 0% milk by-product supplementation in the diet had no negative influence on growth performance of finishing pigs.

Effect of rapeseed meal supplementation to gestation diet on reproductive performance, blood profiles and milk composition of sows.

OBJECTIVE: This experiment evaluated the effect of dietary supplementation levels of rapeseed meal (RSM) in gestation diets on reproductive performance, blood profiles, milk composition of sows, and growth of their progeny. METHODS: A total of 55 mixed-parity sows (Yorkshire×Landrace; average parity = 3.82) with an initial body weight (BW) of 193.0 kg were used in this experiment. Sows were allotted to one of 5 treatments at breeding based on BW and backfat thickness in a completely randomized design. Treatments consisted of dietary RSM supplementation levels (0%, 3%, 6%, 9%, and 12%) in gestation diets. During lactation all sows were fed a common lactation diet with no RSM supplementation. RESULTS: Body weight, backfat thickness, litter size, lactation feed intake, and milk composition of sows, and growth of their progeny were not different among dietary treatments. In blood profiles, a quadratic increase (Quadratic, p<0.05) in serum triiodothyronine (T3) concentration and a linear increase (Linear, p<0.01) in serum thyroxine (T4) concentration were observed at d 110 of gestation as dietary RSM supplementation levels increased. However, serum T3 and T4 concentrations in lactating sows and their piglets were not affected by RSM supplementation of gestation diets. Concentrations of serum total cholesterol and low density lipoprotein cholesterol in sows were not influenced by dietary treatments, whereas serum glucose level in sows decreased linearly at d 110 of gestation (Linear, p<0.05) by increasing dietary RSM supplementation in gestation diets. CONCLUSION: The RSM could be supplemented to gestation diets up to 12% with no detrimental effects on reproductive performance and growth of their progeny. However, increasing supplementation levels of RSM in gestation diets may increase serum T3 and T4 concentrations and decrease serum glucose concentration of sows in late gestation.

Various levels of copra meal supplementation with ß-Mannanase on growth performance, blood profile, nutrient digestibility, pork quality and economical analysis in growing-finishing pigs.

BACKGROUND: To reduce use of main feed ingredient like corn, soy bean meal (SBM) and wheat, alternative ingredients has been studied like copra meal (CM). Production amount of CM which has been high makes CM to be an alternative feed stuff. However, low digestibility on AA and low energy content by high fiber content can be an obstacle for using CM. This experiment was conducted to evaluate the effects of CM supplementation with ß-mannanase on growth performance, blood profile, nutrient digestibility, pork quality and economic analysis in growing-finishing pigs. METHODS: A total of 100 growing pigs ([Yorkshire × Landrace] × Duroc) averaging 31.22 ± 2.04 kg body weight were allotted to 5 different treatments by weight and sex in a randomized complete block (RCB) design in 5 replicate with 4 pigs per pen. Treatments were 1) Control (corn-SBM based diet + 0.1% of ß-mannanase (800 IU)), 2) CM10 (10% copra meal + 0.1% ß-mannanase (800 IU)), 3) CM15 (15% copra meal + 0.1% ß-mannanase (800 IU)), 4) CM20 (20% copra meal + 0.1% ß-mannanase (800 IU)) and 5) CM25 (25% copra meal + 0.1% ß-mannanase (800 IU)). Four phase feeding program was used: growing I (week 1-3), growing II (week 4-6), finishing I (week 7-9) and finishing II (week 10-12). RESULTS: In growth performance, there was no significant difference among treatments during whole experimental period. In growingI phase, G:F ratio tended to increase when CM was increased (P = 0.05), but ADG and ADFI tended to decrease in finishingII phase (linear, P = 0.08). Also, increasing CM reduced ADG (linear, P = 0.02) and feed efficiency (linear, P = 0.08) during the whole finishing period. In blood profiles, BUN was linearly increased as CM increased (linear, P = 0.02) at growingII period. In digestibility trial, there was no significant difference in dry matter, crude fat, crude ash and nitrogen digestibility. However, crude protein digestibility was decreased linearly (linear, P = 0.02). In economic analysis, feed cost per weight gain and total feed cost per pig were reduced in overall period when CM was provided by 25% (linear, P = 0.02). CONCLUSION: CM with 0.1% of ß-mannanase (800 IU) could be supplemented instead of corn and SBM up to 25% without detrimental effects on growth performance and pork quality of growing-finishing pigs.

IKKα-mediated biogenesis of miR-196a through interaction with Drosha regulates the sensitivity of cancer cells to radiotherapy.

Retraction to: Cell Death Differ 2016;23(9):1471­1482. doi:10.1038/cdd.2016.32

Effects of Dietary Energy Levels on the Physiological Parameters and Reproductive Performance of Gestating Gilts.

This experiment was conducted to investigate the effects of dietary energy levels on the physiological parameters and reproductive performance of gestating first parity sows. A total of 52 F1 gilts (Yorkshire×Landrace) were allocated to 4 dietary treatments using a completely randomized design. Each treatment contained diets with 3,100, 3,200, 3,300, or 3,400 kcal of metabolizable energy (ME)/kg, and the daily energy intake of the gestating gilts in each treatment were 6,200, 6,400, 6,600, and 6,800 kcal of ME, respectively. During gestation, the body weight (p = 0.04) and weight gain (p = 0.01) of gilts linearly increased with increasing dietary energy levels. Backfat thickness was not affected at d110 of gestation by dietary treatments, but increased linearly (p = 0.05) from breeding to d 110 of gestation. There were no significant differences on the litter size or litter birth weight. During lactation, the voluntary feed intake of sows tended to decrease when the dietary energy levels increased (p = 0.08). No difference was observed in backfat thickness of the sows within treatments; increasing energy levels linearly decreased the body weight of sows (p<0.05) at d 21 of lactation and body weight gain during lactation (p<0.01). No significant differences were observed in the chemical compositions of colostrum and milk. Therefore, these results indicated that high-energy diets influenced the bodyweight and backfat thickness of sows during gestation and lactation. NRC (2012) suggested that the energy requirement of the gestation gilt should be between 6,678 and 7,932 kcal of ME/d. Similarly, our results suggested that 3,100 kcal of ME/kg is not enough to maintain the reproductive performance for gilts during gestation with 2 kg feed daily. Gilts in the treatment 3,400 kcal of ME/kg have a higher weaning number of piglets, but bodyweight and backfat loss were higher than other treatments during lactation. But bodyweight and backfat loss were higher than other treatments during lactation. Consequently, an adequate energy requirement of gestating gilts is 6,400 kcal of ME/d.