Neurog1-Derived Peptides RMNE1 and DualPep-Shine Penetrate the Skin and Inhibit Melanin Synthesis by Regulating MITF Transcription.

Anti-pigmentation peptides have been developed as alternative skin-lightening agents to replace conventional chemicals that have adverse effects on the skin. However, the maximum size of these peptides is often limited by their low skin and cell penetration. To address this issue, we used our intra-dermal delivery technology (IDDT) platform to identify peptides with hypo-pigmenting and high cell-penetrating activity. Using our cell-penetrating peptides (CPPs) from the IDDT platform, we identified RMNE1 and its derivative RMNE3, "DualPep-Shine", which showed levels of α-Melanocyte stimulating hormone (α-MSH)-induced melanin inhibition comparable to the conventional tyrosinase inhibitor, Kojic acid. In addition, DualPep-Shine was delivered into the nucleus and regulated the gene expression levels of melanogenic enzymes by inhibiting the promoter activity of microphthalmia-associated transcription factor-M (MITF-M). Using a 3D human skin model, we found that DualPep-Shine penetrated the lower region of the epidermis and reduced the melanin content in a dose-dependent manner. Furthermore, DualPep-Shine showed high safety with little immunogenicity, indicating its potential as a novel cosmeceutical ingredient and anti-pigmentation therapeutic agent.

Difference in Joint Stability Between Small Posterior Malleolar Fragments With Fixation and Those Without Fixation: A Biomechanical Cadaver Study.

The indication for the surgical treatment of ankle fractures that involve a posterior malleolar fragment remains controversial. This cadaver study assessed the biomechanical results of rotation stiffness of Haraguchi type 1 posterior malleolar fragments with or without cannulated screw fixation. Twelve anatomic lower-extremity specimens from 6 cadavers were tested. Six right legs were subjected to posterior malleolus osteotomy (Haraguchi type I) followed with (group A; n = 3) or without (group B; n = 3) fixation using a cannulated screw. Ankle joint stability was measured under both external rotation force and axial loading, and the passive resistive torque was measured in both groups. The mean torque value in group A was 0.1093 Nm/º, while that in group B was 0.0537 Nm/º. There was a significant intergroup difference (p = .004). In group B, the torque value was further increased in the latter rotation period (about 40-60 degrees). Group A proved more stable under experimental conditions than group B. Fixation in type I posterior malleolar fragments produced improved stability in ankle rotation, even for posterior malleolar fragments involving <25% of the articular surface, and has been considered an effective aid in treatment.

A Comparative Analysis of Pain Control Methods after Ankle Fracture Surgery with a Peripheral Nerve Block: A Single-Center Randomized Controlled Prospective Study.

Background and Objectives: Patients experience severe pain after surgical correction of ankle fractures. Although their exact mechanism is unknown, dexamethasone and epinephrine increase the analgesic effect of anesthetics in peripheral nerve blocks. This study aimed to compare the postoperative pain control efficacy of peripheral nerve blocks with ropivacaine combined with dexamethasone/epinephrine and peripheral nerve blocks with only ropivacaine and added patient-controlled analgesia in patients with ankle fractures. Materials and Methods: This randomized, controlled prospective study included patients aged 18-70 years surgically treated for ankle fractures between December 2021 and September 2022. The patients were divided into group A (n = 30), wherein pain was controlled using patient-controlled analgesia after lower extremity peripheral nerve block, and group B (n = 30), wherein dexamethasone/epinephrine was combined with the anesthetic solution during peripheral nerve block. In both groups, ropivacaine was used as the anesthetic solution for peripheral nerve block, and this peripheral nerve block was performed just before ankle surgery for the purpose of anesthesia for surgery. Pain (visual analog scale), patient satisfaction, and side effects were assessed and compared between the two groups. Results: The patients' demographic data were similar between groups. Pain scores were significantly lower in group B than in group A postoperatively. Satisfaction scores were significantly higher in group B (p = 0.003). There were no anesthesia-related complications in either group. Conclusions: Dexamethasone and epinephrine as adjuvant anesthetic solutions can effectively control pain when performing surgery using peripheral nerve blocks for patients with ankle fractures.

Risk factors for postoperative pneumonia in patients undergoing hip fracture surgery: a systematic review and meta-analysis.

BACKGROUND: Postoperative pneumonia (POP) is a devastating complication that can frequently occur after hip fracture surgery. This study aimed to quantitatively and comprehensively summarize the risk factors for POP following hip fracture surgery. METHODS: PubMed, Embase, and Cochrane Library were systematically searched for studies assessing risk factors for POP following hip fracture surgery. The pooled odds ratio (OR) and standardized mean difference (SMD) between patients with and without POP were calculated. Evidence was assessed using the Newcastle-Ottawa scale. RESULTS: Ten studies including 37,130 patients with hip fractures were selected. POP occurred in 1768 cases with an accumulated incidence of 7.8% (95% confidence interval [CI]: 0.061-0.094). Advanced age (SMD: 0.50, 95% CI: 0.10-0.90), male sex (OR: 1.50, 95% CI: 1.12-2.01), American Society of Anesthesiologists physical status scale ≥3 (OR: 3.17, 95% CI: 1.25-8.05), chronic obstructive pulmonary disease (OR: 2.05, 95% CI: 1.43-2.94), coronary heart disease (OR: 1.82, 95% CI: 1.27-2.60), arrhythmia (OR: 1.49, 95% CI: 1.04-2.15), congestive heart failure (OR: 1.41, 95% CI: 1.14-1.75), chronic kidney disease (OR: 2.09, 95% CI: 1.28-3.41), and cerebrovascular accident (OR: 2.14, 95% CI: 1.60-2.85) were risk factors for POP. Hemoglobin (SMD: -0.14, 95% CI: - 0.25 to - 0.03), albumin (SMD: -0.97, 95% CI: - 1.54--0.41), blood urea nitrogen (SMD: 0.20, 95% CI: 0.03-0.37), alanine aminotransferase (SMD: 0.27, 95% CI: 0.10-0.44), arterial oxygen pressure (SMD: -0.49, 95% CI: - 0.71--0.27), time from injury to surgery (SMD: 0.13, 95% CI: 0.08-0.17), and surgery within 48 h (OR: 3.74, 95% CI: 2.40-5.85) were associated with the development of POP. CONCLUSION: Patients with the aforementioned risk factors should be identified preoperatively, and related prophylaxis strategies should be implemented to prevent POP following hip fracture surgery.

Intramembrane proteolysis of an extracellular serine protease, epithin/PRSS14, enables its intracellular nuclear function.

BACKGROUND: Epithin/PRSS14, a type II transmembrane serine protease, is an emerging target of cancer therapy because of its critical roles in tumor progression and metastasis. In many circumstances, the protease, through its ectodomain shedding, exists as a soluble form and performs its proteolytic functions in extracellular environments increasing cellular invasiveness. The seemingly functional integrity of the soluble form raises the question of why the protease is initially made as a membrane-associated protein. RESULTS: In this report, we show that the epithin/PRSS14 intracellular domain (EICD) can be released from the membrane by the action of signal peptide peptidase-like 2b (SPPL2b) after ectodomain shedding. The EICD preferentially localizes in the nucleus and can enhance migration, invasion, and metastasis of epithelial cancer when heterologously expressed. Unbiased RNA-seq analysis and subsequent antibody arrays showed that EICD could control the gene expression of chemokines involved in cell motility, by increasing their promoter activities. Finally, bioinformatics analysis provided evidence for the clinical significance of the intramembrane proteolysis of epithin/PRSS14 by revealing that the poor survival of estrogen receptor (ER)-negative breast cancer patients with high epithin/PRSS14 expression is further worsened by high levels of SPPL2b. CONCLUSIONS: These results show that ectodomain shedding of epithin/PRSS14 can initiate a unique and synchronized bidirectional signal for cancer metastasis: extracellularly broadening proteolytic modification of the surrounding environment and intracellularly reprogramming the transcriptome for metastatic conversion. Clinically, this study also suggests that the intracellular function of epithin/PRSS14 should be considered for targeting this protease for anti-cancer treatment.

A phase 2 multicenter study of stereotactic body radiotherapy for hepatocellular carcinoma: Safety and efficacy.

BACKGROUND: Although several prospective studies have reported the efficacy of stereotactic body radiotherapy (SBRT) for hepatocellular carcinoma (HCC), treatment-related toxicity varies and has not been determined. Therefore, the authors evaluated the safety and efficacy of SBRT for patients with HCC in a hepatitis B virus-endemic area. METHODS: This multicenter phase 2 trial enrolled patients with unresectable HCC. Patients received SBRT with 45 to 60 Gy in 3 fractions. To evaluate gastroduodenal toxicity, esophagogastroduodenoscopy (EGD) was performed before and 2 months after SBRT. The primary endpoint was treatment-related severe toxicity at 1 year after SBRT. The secondary endpoints were the 2-year local control, progression-free survival, and overall survival rates. RESULTS: In total, 74 patients were enrolled between January 2012 and April 2015, and 65 eligible patients were analyzed. One patient experienced radiation-induced liver disease with acute grade ≥3 toxicity 1 month after SBRT. In addition, 1 patient had a grade 3 esophageal ulcer with stenosis 5 months after SBRT. The actuarial rate of treatment-related severe toxicity at 1 year was 3%. The pre-SBRT and post-SBRT EGD findings were not significantly different among the 57 evaluable patients who underwent EGD. The 2-year and 3-year local control rates were 97% and 95%, respectively. The progression-free and overall survival rates were 48% and 84% at 2 years, respectively, and 36% and 76% at 3 years, respectively. CONCLUSIONS: With a median follow-up of 41 months, this prospective multicenter study demonstrated that SBRT for patients with HCC is well tolerated and is an effective treatment modality.

Ionizing radiation attracts tumor targeting and apoptosis by radiotropic lysyl oxidase traceable nanoparticles.

Lysyl oxidase (LOX) is a cell-secreted amine oxidase that crosslinks collagen and elastin in extracellular microenvironment. LOX-traceable nanoparticles (LOXab-NPs) consisting of LOX antibodies (LOXab) and paclitaxel, can accumulate at high concentrations at radiation-treated target sites, as a tumor-targeting drug carrier for chemotherapy. Tumor-targeting and anticancer effects of PLGA based LOXab-NPs in vitro and in vivo were evaluated at radiation-targeted site. In the in vivo A549 lung carcinoma xenograft model, we showed highly specific tumor targeting (above 7.0 times higher) of LOXab-NPs on irradiated tumors. Notably, systemically administered NPs delayed tumor growth, reducing tumor volumes by more than 2 times compared with non-irradiated groups (222% vs. >500%) over 2 weeks. Radiotropic LOXab-NPs can serve as chemotherapeutic vehicles for combined targeted chemo-radiotherapy in clinical oncology.

Verification of the Necessity of the Tolyl Group of PF-543 for Sphingosine Kinase 1 Inhibitory Activity.

PF-543, the most potent sphingosine kinase (SK) inhibitor, does not demonstrate effective anticancer activity in some cancer cells, unlike other known SK1 inhibitors. PF-543 has a non-lipid structure with a unique toluene backbone; however, the importance of this structure remains unclear. Therefore, the purpose of this study was to investigate changes in SK inhibitory and anticancer activities and to explore the role of the tolyl group structure of PF-543 through various modifications. We transformed the methyl group of PF-543 into hydrogen, fluorine, and hydroxy. PF-543 derivatives in which the methyl group was substituted by hydrogen and fluorine (compound 5) demonstrated SK1 inhibitory and anticancer activities similar to PF-543. Moreover, we performed molecular modeling studies of PF-543 and compound 5. To assess the metabolic stability of PF-543 and compound 5, we determined their degree of degradation using the liver microsomes of four different animal species (human, dog, rat, and mouse). However, both PF-543 and compound 5 showed poor microsomal stability. Therefore, for the medical applications of PF-543, the structural modifications of its other parts may be necessary. Our results provide important information for the design of additional PF-543 analogs.

Preparation of Nanoemulsions of Vitamin A and C by Microfluidization: Efficacy on the Expression Pattern of Milk-Specific Proteins in MAC-T Cells.

In this study, we prepared stabilized vitamin A and C nanoemulsions, and investigated their efficacy on milk-specific proteins in bovine mammary epithelial cells (MAC-T). Emulsions of vitamin A (vit-A) and C (vit-C) were prepared using Lipoid S 75 and microfluidization. The particle size and polydispersity index (PDI) of nanoemulsified vit-A and vit-C were studied. The cytotoxic effect of nanoemulsion-free and nanoemulsified vit-A and vit-C was determined by an MTT assay. In addition, the efficacy of nanoemulsified vit-A and vit-C on the in vitro expression pattern of milk-specific proteins in MAC-T cells was investigated by quantitative RT-PCR. The results showed that the efficacies of stabilized nanoemulsions of vit-A and vit-C were 100% and 92.7%, respectively. The particle sizes were around 475.7 and 225.4 nm, and the zeta potentials were around -33.5 and -21.3 mV, respectively. The expression changes of αs2-, ß- and κ-casein were higher in the presence of a stabilized nanoemulsion of vit-A, compared with nanoemulsion-free vit-A. Furthermore, the expression changes of αs2- and ß-casein were lower and that of κ-casein was higher in the presence of a stabilized nanoemulsion of vit-C, compared with nanoemulsion-free vit-C. Thus, our findings demonstrate the efficacy of nanoemulsified vit-A and vit-C in changing the expression of milk-specific proteins in MAC-T cells.

Temperature and microbial changes of corn silage during aerobic exposure.

OBJECTIVE: This study was conducted to estimate the temperature and microbial changes of corn silages during aerobic exposure. METHODS: Kwangpyeongok (KW) and Pioneer 1543 (PI) corn hybrids were harvested at 29.7% of dry matter and chopped to 3 to 5 cm lengths. Homo (Lactobacillus plantarum; LP) or hetero (Lactobacillus buchneri; LB) fermentative inoculants at 1.2×105 colony forming unit/g of fresh forage was applied to the chopped corn forage which was then ensiled in quadruplicate with a 2×2 (hybrid×inoculant) treatment arrangement for 100 days. After the silo was opened, silage was sub-sampled for analysis of chemical compositions, in vitro digestibility, and fermentation indices. The fresh silage was continued to determine aerobic exposure qualities by recorded temperature and microbial changes. RESULTS: The KW silages had higher (p<0.01) in vitro digestibilities of dry matter and neutral detergent fiber than those of PI silages. Silages applied with LB had higher (p<0.001) acetate concentration, but lower (p<0.01) lactate concentration and lactate to acetate ratio than those of LP silages. The interaction effect among hybrid and inoculant was detected in acetate production (p = 0.008), aerobic stability (p = 0.006), and lactic acid bacteria count (p = 0.048). The yeast was lower (p = 0.018) in LB silages than that in LP silages. During the aerobic exposure, PI silages showed higher (p<0.05) temperature and mold than KW silages, while LP silages had higher (p<0.05) lactic acid bacteria and yeast than LB silages. CONCLUSION: The results indicated that the changes of silage temperature during aerobic exposure seems mainly affected by mold growth, while applied LB only enhanced aerobic stability of PI silages.

The effect of nanoemulsified methionine and cysteine on the in vitro expression of casein in bovine mammary epithelial cells.

OBJECTIVE: Dairy cattle nutrient requirement systems acknowledge amino acid (AAs) requirements in aggregate as metabolizable protein (MP) and assume fixed efficiencies of MP used for milk protein. Regulation of mammary protein synthesis may be associated with AA input and milk protein output. The aim of this study was to evaluate the effect of nanoemulsified methionine and cysteine on the in-vitro expression of milk protein (casein) in bovine mammary epithelial cells (MAC-T cells). METHODS: Methionine and cysteine were nonionized using Lipoid S 75 by high-speed homogenizer. The nanoemulsified AA particle size and polydispersity index were determined by dynamic light scattering correlation spectroscopy using a high-performance particle sizer instrument. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to determine the cytotoxicity effect of AAs with and without nanoionization at various concentrations (100 to 500 µg/mL) in mammary epithelial cells. MAC-T cells were subjected to 100% of free AA and nanoemulsified AA concentration in Dulbecco's modified Eagle medium/nutrient mixture F-12 (DMEM/F12) for the analysis of milk protein (casein) expression by the quantitative reverse transcription polymerase chain reaction method. RESULTS: The AA-treated cells showed that cell viability tended to decrease (80%) in proportion to the concentration before nanogenesis, but cell viability increased as much as 90% after nanogenesis. The analysis of the expression of genetic markers related to milk protein indicated that; αs2-casein increased 2-fold, κ-casein increased 5-fold, and the amount of unchanged ß-casein expression was nearly doubled in the nanoemulsified methionine-treated group when compared with the free-nanoemulsified methionine-supplemented group. On the contrary, the non-emulsified cysteine-administered group showed higher expression of genetic markers related to milk protein αs2-casein, κ-casein, and ß-casein, but all the genetic markers related to milk protein decreased significantly after nanoemulsification. CONCLUSION: Detailed knowledge of factors, such nanogenesis of methionine, associated with increasing cysteine and decreasing production of genetic markers related to milk protein (casein) will help guide future recommendations to producers for maximizing milk yield with a high level of milk protein casein.

The small molecule CA140 inhibits the neuroinflammatory response in wild-type mice and a mouse model of AD.

BACKGROUND: Neuroinflammation is associated with neurodegenerative diseases, including Alzheimer's disease (AD). Thus, modulating the neuroinflammatory response represents a potential therapeutic strategy for treating neurodegenerative diseases. Several recent studies have shown that dopamine (DA) and its receptors are expressed in immune cells and are involved in the neuroinflammatory response. Thus, we recently developed and synthesized a non-self-polymerizing analog of DA (CA140) and examined the effect of CA140 on neuroinflammation. METHODS: To determine the effects of CA140 on the neuroinflammatory response, BV2 microglial cells were pretreated with lipopolysaccharide (LPS, 1 µg/mL), followed by treatment with CA140 (10 µM) and analysis by reverse transcription-polymerase chain reaction (RT-PCR). To examine whether CA140 alters the neuroinflammatory response in vivo, wild-type mice were injected with both LPS (10 mg/kg, intraperitoneally (i.p.)) and CA140 (30 mg/kg, i.p.), and immunohistochemistry was performed. In addition, familial AD (5xFAD) mice were injected with CA140 or vehicle daily for 2 weeks and examined for microglial and astrocyte activation. RESULTS: Pre- or post-treatment with CA140 differentially regulated proinflammatory responses in LPS-stimulated microglia and astrocytes. Interestingly, CA140 regulated D1R levels to alter LPS-induced proinflammatory responses. CA140 significantly downregulated LPS-induced phosphorylation of ERK and STAT3 in BV2 microglia cells. In addition, CA140-injected wild-type mice exhibited significantly decreased LPS-induced microglial and astrocyte activation. Moreover, CA140-injected 5xFAD mice exhibited significantly reduced microglial and astrocyte activation. CONCLUSIONS: CA140 may be beneficial for preventing and treating neuroinflammatory-related diseases, including AD.

Measurement of Carpal Alignment Indices Using 3-Dimensional Computed Tomography.

PURPOSE: This study aimed to establish normal values for wrist carpal alignment measured by 3-dimensional computed tomography (CT) and to show the inter- and intraobserver reliability of this measurement compared with simple radiography. METHODS: The study utilized 3-dimensional CT and simple radiography of wrist joints in 30 asymptomatic volunteers. The wrist position was standardized using a custom-designed positioning device. Three independent observers measured carpal alignment parameters including distal radius articular angle, radiolunate angle, radioscaphoid angle, radiocapitate angle, radius-third metacarpal angle, scapholunate angle, lunocapitate angle, and lunate-third metacarpal angle. RESULTS: Based on 3-dimensional CT measurement, the mean values of these parameters were: 12.9° ± 1.8° for the distal radius articular angle; 1.2° ± 3.8° for the radiolunate angle; 54.2° ± 5.6° for the radioscaphoid angle; 1.9° ± 2.2° for the radiocapitate angle; -1.0° ± 2.5° for the radius-third metacarpal angle; 52.9° ± 6.9° for the scapholunate angle; 0.7° ± 4.1° for the lunocapitate angle; -2.3° ± 4.6° for the lunate-third metacarpal angle. All parameters showed high inter- and intraobserver reliability in the 2 modalities. CONCLUSIONS: The normal values and ranges for carpal alignment angles were evaluated by using 3-dimensional CT. We could obtain high reliability in 3-dimensional CT as well as plain radiograph for the measurement of carpal alignment. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

Modulation of Rat Hepatic CYP1A and 2C Activity by Honokiol and Magnolol: Differential Effects on Phenacetin and Diclofenac Pharmacokinetics In Vivo.

Honokiol (2-(4-hydroxy-3-prop-2-enyl-phenyl)-4-prop-2-enyl-phenol) and magnolol (4-Allyl-2-(5-allyl-2-hydroxy-phenyl)phenol) are the major active polyphenol constituents of Magnolia officinalis (Magnoliaceae) bark, which has been widely used in traditional Chinese medicine (Houpu Tang) for the treatment of various diseases, including anxiety, stress, gastrointestinal disorders, infection, and asthma. The aim of this study was to investigate the direct effects of honokiol and magnolol on hepatic CYP1A and 2C-mediated metabolism in vitro using rat liver microsomes and in vivo using the Sprague-Dawley rat model. Honokiol and magnolol inhibited in vitro CYP1A activity (probe substrate: phenacetin) more potently than CYP2C activity (probe substrate: diclofenac): The mean IC50 values of honokiol for the metabolism of phenacetin and diclofenac were 8.59 µM and 44.7 µM, while those of magnolol were 19.0 µM and 47.3 µM, respectively. Notably, the systemic exposure (AUC and Cmax) of phenacetin, but not of diclofenac, was markedly enhanced by the concurrent administration of intravenous honokiol or magnolol. The differential effects of the two phytochemicals on phenacetin and diclofenac in vivo pharmacokinetics could at least be partly attributed to their lower IC50 values for the inhibition of phenacetin metabolism than for diclofenac metabolism. In addition, the systemic exposure, CL, and Vss of honokiol and magnolol tended to be similar between the rat groups receiving phenacetin and diclofenac. These findings improve our understanding of CYP-mediated drug interactions with M. officinalis and its active constituents.

Effects of supplementing Barodon, Bacillus subtilis, and Ampbio on growth performance, biochemical metabolites, and hormone levels in Korean native heifers.

An experiment was conducted to evaluate the effects of supplementing feed additives of Barodon®, effective microorganism® (Bacillus (B.) subtilis), and Ampbio® on the growth performance, blood metabolites, stress, and reproductive hormone levels of Korean native heifers. A total of 48 Korean native heifers were assigned to four groups with 6 heifers in each group. The groups were control, Barodon (0.2%), beneficial microorganism (1%), and Ampbio (1%). Animals in all groups were fed a basal diet composed of selected feed additives and water ad libitum for 99 days. Results showed that there are significant changes in body weight and daily gain in the Ampbio-supplemented group as compared with the control and other feed additives groups (p < 0.05). The increased level of feed intake (7.30 ± 0.03 kg) and feed requirements (10.81 ± 0.52 kg) was observed in the Ampbio-fed group followed by the effective microorganism (EM), Barodon, and control groups. There were no significant changes in albumin, glucose, glutamic oxaloacetic transaminase (SGOT), serum pyruvic transaminase (SGPT), and total protein level, but the decreased levels of total cholesterol and triglycerides and the increased level of blood urea nitrogen were noted in the Ampbio-fed group as compared with the control and other feed additive groups. The reduced level of cortisol (p < 0.05) and elevated levels of progesterone and estradiol (p > 0.05) were noted in the Ampbio-fed group as compared to the other feed additive groups. It is therefore concluded that incorporation of Barodon, EM (B. subtilis), and Ampbio in the recommended diet improved the growth and health performance of Korean native heifers.

Effect of microbial inoculants on fermentation quality and aerobic stability of sweet potato vine silage.

OBJECTIVE: This study was conducted to evaluate the effect of homo or hetero fermentative inoculants on fermentation quality and aerobic stability of sweet potato vine (SPV) silage containing Italian ryegrass hay as moisture absorbent. METHODS: The SPV was harvested at 15% dry matter, mixed with Italian ryegrass hay at 1:1 ratio on a fresh weight basis, and chopped to 3 to 5 cm length. After then, the chopped forage mixture was ensiled into 20-L mini silos in quadruplicate for 7, 48, and 100 days after application of microbial inoculants at 1.2×105 colony forming units (cfu)/g of forage following: no inoculant (CON), Lactobacillus plantarum as a homo fermentative (LP), Lactobacillus buchneri as a hetero fermentative (LB), and mixture of LP and LB at 1:1 ratio as a combo fermentative (MIX). RESULTS: The LP and MIX silages had lowest pH (p<0.001) on 7 and 48 days, while MIX and CON silages had greatest lactate concentrations (p<0.05) on 7 and 48 days, respectively. Acetate concentrations were highest (p<0.01) in LB and MIX silages on 7 days, and in LB silage on 48 days, while lactate to acetate ratios were lowest (p<0.001) in LB silages. The chemical compositions and nutrient digestibility of silage ensiled for 100 days was not affected by inoculants. On 100 days of ensiling, LB silage had lowest (p<0.01) lactate concentration and lactate to acetate ratio, but highest acetate concentration. Aerobic stability was highest (p<0.001) in LB silage followed in MIX silage. On contrast, LB silage had lowest (p<0.05) lactic acid bacteria and mold. CONCLUSION: The results indicated that application of LB solely had a better effect on aerobic stability than not only LP, but also MIX. However, LP application did not show beneficial effects from the viewpoints of fermentation quality and aerobic stability compared to CON.

Effect of sodium stearoyl-2-lactylate supplementation on lactation performance, blood-biochemical profile, and economic efficacy of mid-lactation Holstein cows.

OBJECTIVE: This study was done to evaluate the effect of sodium stearoyl-2-lactylate (SSL) supplementation in a total mixed ration (TMR) on the lactation performance, blood parameters, and economic efficacy of mid-lactation Holstein cows. METHODS: Twenty-four cows (body weight 647±11.7 kg) were randomly divided into 4 treatment groups, with six cows per group. The dietary treatments were as follows: basal diet (CON); CON+17.5 g of top dressed SSL (treatment [TRT] 0.05); CON+35 g of SSL (TRT 0.1); and CON+70 g of SSL (TRT 0.2) per 35 kg TMR. RESULTS: The highest level of SSL supplementation (TRT 0.2) significantly improved milk yield during the second period compared to the TRT 0.05 group (5 to 8 wks; 33.28 vs 31.09 kg/d), during the third period compared to both the CON and TRT 0.05 groups (p<0.05) (9 to 13 wks; 32.59 vs 30.64 and 30.01 kg/d) and during the overall experimental period compared to both the CON and TRT 0.05 groups (p<0.05) (1 to 13 wks; 33.43 vs 32.06 and 31.40 kg/d), respectively. No negative effects on hematological or biochemical parameters were observed due to SSL supplementation. Considering both the milk fat and protein content, the total milk price was set at 1,073.60 (TRT 0.05), 1,085.60 (TRT 0.1), 1,086.10 (TRT 0.2), and 1,064.20 (CON) won/L, with consequent total milk profits of -1.7%, 5.4%, and 3.5% for the TRT 0.05, TRT 0.1, and TRT 0.2 diet, respectively, compared to those in the CON diet. CONCLUSION: The milk sales revenue related to SSL supplementation of the TRT 0.1 diet was increased by up to 5.4% compared to the milk sales revenue of the CON diet. Therefore, 0.1% SSL supplementation might be effective and profitable during the mid-lactation period of cows, without producing adverse effects.

Comparison of postoperative pain control methods after bony surgery in the foot and ankle.

BACKGROUND: We performed a prospective study to evaluate and compare the effectiveness of postoperative pain control methods after bone surgery in the foot and ankle. METHODS: Among the patients who underwent foot and ankle surgery from June 2014 to September 2015 with an ultrasound-guided nerve block, 84 patients who fully completed a postoperative pain survey were enrolled. An opioid patch (fentanyl patch, 25mg) was applied in group A (30 patients). Diluted anesthetic (0.2% ropivacaine, 30ml) was injected into the sciatic nerve once, about 12h after the preoperative nerve block, in group B (27 patients). Periodic intramuscular injection of an analgesic (ketorolac [Tarasyn], 30mg) was performed in group C (27 patients). The visual analogue scale (VAS) pain scores at 6, 12, 18, 24, and 48h after surgery were checked, and the complications of all methods were monitored. RESULTS: The mean VAS pain score was lower in group B, with a statistically significant difference (P<.05) between groups A, B, and C at 12 and 18h after surgery. Four patients in group A experienced nausea and vomiting; however, no other patients complained of any complications or adverse effects. CONCLUSION: The ultrasound-guided injection of a diluted anesthetic into the sciatic nerve seemed to be the most useful method for controlling pain in the acute phase after bone surgery in the foot and ankle. The injection of the diluted anesthetic once on the evening of the day of surgery resulted in less postoperative pain in the patients. LEVEL OF EVIDENCE: II.

Computer-assisted Patient-specific Prototype Template for Thoracolumbar Cortical Bone Trajectory Screw Placement: A Cadaveric Study.

The cortical bone trajectory (CBT) screw technique yields effective mechanical and clinical results, improving the holding screw strength with a less invasive exposure. Accurate and safe screw placement is crucial. A patient-specific drill template with a preplanned trajectory was considered a promising solution; however, it is critical to assess the efficacy and safety of this technique. This study aims to evaluate the accuracy of patient-specific computed tomography (CT)-based rapid prototype drill guide templates for the CBT technique. CT scanning was performed in 7 cadaveric thoracolumbar spines, and a 3-dimensional reconstruction model was generated. By using computer software, we constructed drill templates that fit onto the posterior surface of thoracolumbar vertebrae with drill guides to match the CBT. In total, 80 guide templates from T11 to L5 were created from the computer models by using rapid prototyping. The drill templates were used to guide the drilling of CBT screws without any fluoroscopic control, and CT images were obtained after fixation. The entry point and direction of the planned and inserted screws were measured and compared. In total, 80 screws were inserted from T11 to L5. No misplacement or bony perforation was observed on postoperative CT scan. The patient-specific prototype template system showed the advantage of safe and accurate cortical screw placement in the thoracolumbar spine. This method showed its ability to customize the patient-specific trajectory of the spine, based on the unique morphology of the spine. The potential use of drill templates to place CBT screws is promising.

Assessment of pharmacokinetics, bioavailability and protein binding of anacetrapib in rats by a simple high-performance liquid chromatography-tandem mass spectrometry method.

Anacetrapib is a potent and selective CETP inhibitor and is undergoing phase III clinical trials for the treatment of dyslipidemia. A simple and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for the quantification of anacetrapib in rat plasma was developed and validated using an easily purchasable compound, chlorpropamide, as an internal standard (IS). A minimal volume of rat plasma sample (20 µL) was prepared by a single-step deproteinization procedure with 80 µL of acetonitrile. Chromatographic separation was performed using Kinetex C18 column with a gradient mobile phase consisting of water and acetonitrile containing 0.1% formic acid at a flow rate of 0.3 mL/min. Mass spectrometric detection was performed using selected reaction monitoring modes at the mass/charge transitions m/z 638 → 283 for anacetrapib and m/z 277 → 175 for IS. The assay was validated to demonstrate the selectivity, linearity, precision, accuracy, recovery, matrix effect and stability. The lower limit of quantification was 5 ng/mL. This LC-MS/MS assay was successfully applied in the rat plasma protein binding and pharmacokinetic studies of anacetrapib. The fraction of unbound anacetrapib was determined to be low (ranging from 5.66 to 12.3%), and the absolute oral bioavailability of anacetrapib was 32.7%.