Nutritional and physiological responses to dietary phosphorus levels and phytase in pullets and laying hens.

The objective of this study was to determine the effects of dietary available phosphorus (P) levels and dietary phytase added into the very low-P diet on the performance, mineral balance, odor emission, and stress responses in growing pullets and laying hens during 13 to 32 wk of age. One hundred sixty-eight pullets (Hy-Line Brown) were randomly assigned into 1 of 4 dietary treatments with 7 replicates of 6 birds each. Experimental diets were formulated to contain 3 graded P levels at 0.25, 0.35, and 0.45% during 13 to 15 wk (phase 1), 0.25, 0.35, and 0.45% during 16 to 18 wk (phase 2), and 0.20, 0.30, and 0.40% during 19 to 32 wk (phase 3). In addition, dietary phytase (500 FTU/kg matrix values) was added into the very low-P diets (0.20% during 13-15 wk, 0.25% during 16-18 wk, and 0.20% during 19-32 wk) to meet the nutritional adequacy with standard P diets. In all phases, decreasing dietary P levels did not affect (P > 0.05) growth, laying performance, and egg qualities. Decreasing dietary P levels linearly increased the relative duodenal and oviduct weights (P < 0.05), and quadratically increased the relative ovary weight in pullets (P = 0.016). Dietary phytase lowered (P = 0.021) the relative duodenal weight compared with the very low-P diet. Tibia breaking strength and tibia Mg contents in pullets were linearly lowered (P < 0.05) as dietary P levels decreased. Dietary phytase tended to increase (P = 0.091) tibia breaking strength and significantly increased (P = 0.025) tibia Mg content compared with the very low-P diet. Dietary P levels and dietary phytase affected (P < 0.05) ileal crypt depth and ileal villus height: crypt depth ratio in pullets. Decreasing dietary P levels linearly decreased (P < 0.01) crude fat digestibility and P excretion in both pullets and laying hens. Dietary phytase reversed (P < 0.05) the very low-P diet-mediated decrease of crude fat digestibility in pullets and laying hens. Dietary P levels and dietary phytase affected (P < 0.05) odor emission including ammonia in pullets and total volatile fatty acids in laying hens. Finally, lowering dietary P levels increased (P < 0.01) yolk corticosterone concentrations and the increased corticosterone concentration by the very low-P diet was reversed by dietary phytase. Collectively, our study shows that decreasing dietary P levels induced nutritional and physiological responses in pullets and laying hens and these P-mediated negative effects were mitigated by dietary phytase.

Alteration of Keratinized Mucosa Dimensions in the Early Healing Period after Implant Placement: A 6-month Prospective Study.

PURPOSE: This study aimed to assess the alteration in keratinized mucosa (KM) dimensions in the early healing period after implant placement, and the influence of variables obtained during implant surgery on KM alteration. MATERIALS AND METHODS: Study participants were consecutively recruited from patients who had received implants following a non-submerged surgical protocol. The implant had to be installed in the extraction socket that had healed for more than 6 months without any soft or hard tissue augmentation. Keratinized mucosa width (KMW), keratinized mucosa thickness (KMT), soft tissue level (STL), and probing pocket depth (PPD) were measured at implant placement and 3 and 6 months after implant surgery. The influence of variables obtained during implant surgery on the 6-month KMW alteration was assessed. RESULTS: A total of 66 implants in 55 patients who completed the follow-up examination after 6 months were included in this study. KMW, KMT, and STL significantly decreased at 3- and 6-months examination by 0.7-1.2 mm. KMW was reduced by 24.6%. Mesial PPD significantly increased between the 3- and 6-months follow-up. In the multivariate generalized estimating estimations analysis, the implant diameter negatively influenced the 6-month KMW alteration, but the KMW at implant surgery positively influenced the 6-month KMW alteration. CONCLUSIONS: The KMW decreased significantly at 3 and 6 months after implant placement. If the initial KMW was wider, the KMW was reduced more at 6 months after implant placement. Therefore, it is important to carefully monitor KMW alterations during the early healing period to ensure optimal esthetics and peri-implant tissue health.

Whole-Exome Sequencing and Analysis of the T Cell Receptor ß and γ Repertoires in Rheumatoid Arthritis.

This study investigated the potential genetic variants of rheumatoid arthritis (RA) using whole-exome sequencing (WES) and evaluated the disease course using T cell receptor (TCR) repertoire analysis. Fourteen patients with RA and five healthy controls (HCs) were enrolled. For the RA patient group, only treatment-naïve patients were recruited, and data were collected at baseline as well as at 6 and 12 months following the initiation of the disease-modifying antirheumatic drug (DMARD) treatment. Laboratory data and disease parameters were also collected. Genetic variants were detected using WES, and the diversity of the TCR repertoire was assessed using the Shannon-Wiener diversity index. While some variants were detected by WES, their clinical significance should be confirmed by further studies. The diversity of the TCR repertoire in the RA group was lower than that in the HCs; however, after DMARD treatment, it increased significantly. The diversity was negatively correlated with the laboratory findings and disease measures with statistical significance. Variants with a potential for RA pathogenesis were identified, and the clinical significance of the TCR repertoire was evaluated in Korean patients with RA. Further studies are required to confirm the findings of the present study.

Dietary probiotic Lacticaseibacillus paracasei NSMJ56 modulates gut immunity and microbiota in laying hens.

This study was performed to investigate supplementary effects of probiotic Lacticaseibacillus paracasei NSMJ56 strain on laying performance, egg quality, intestinal histology, antioxidant status, gut immunity and microbiota in laying hens. A total of ninety-six 21-wk-old Hy-Line Brown laying hens were randomly subjected to one of 2 dietary treatments: a control group fed a non-supplemented diet, or a probiotic group fed with a diet supplemented with 1 g of Lacticaseibacillus paracasei NSMJ56 (5 × 108 CFU/kg of diet). The trial lasted for 4 wk. Egg weight was increased (P < 0.05) in laying hens fed probiotic-fed diet compared with the control group. Dietary probiotics did not affect egg quality except for Haugh unit, which was improved (P < 0.05) in the probiotic-fed group. Neither jejunal histology nor cecal short-chain fatty acids were affected by dietary treatments. Dietary probiotics increased the activity of catalase compared with the control group. Flow cytometry analysis revealed that dietary probiotics elevated the CD4+ T cells, but not CD8+ T cells, in jejunal lamina propria. Based on the LEfSe analysis at the phylum and genus levels, Erysipelotrichales, Erysipelotrichia, Flintibater, Dielma, Hespellia, Coprobacter, Roseburia, Anaerotignum, and Coprococcus were enriched in the probiotic group compared with the control group. Taken together, our study showed that dietary probiotics could be used to improve some parameters associated with egg freshness and antioxidant capacity, and to partially alter T cell population and microbial community in laying hens.

16S rRNA Next-Generation Sequencing May Not Be Useful for Examining Suspected Cases of Spontaneous Bacterial Peritonitis.

Background and Objectives: Ascites, often associated with liver cirrhosis, poses diagnostic challenges, particularly in detecting bacterial infections. Traditional methods have limitations, prompting the exploration of advanced techniques such as 16S rDNA next-generation sequencing (NGS) for improved diagnostics in such low-biomass fluids. The aim of this study was to investigate whether the NGS method enhances detection sensitivity compared to a conventional ascites culture. Additionally, we aimed to explore the presence of a microbiome in the abdominal cavity and determine whether it has a sterile condition. Materials and Methods: Ten patients with clinically suspected spontaneous bacterial peritonitis (SBP) were included in this study. A traditional ascites culture was performed, and all ascites samples were subjected to 16S ribosomal RNA gene amplification and sequencing. 16S rRNA gene sequencing results were interpreted by comparing them to positive and negative controls for each sample. Results: Differential centrifugation was applied to all ascites samples, resulting in very small or no bacterial pellets being harvested. The examination of the 16S amplicon sequencing libraries indicated that the target amplicon products were either minimally visible or exhibited lower intensity than their corresponding negative controls. Contaminants present in the reagents were also identified in the ascites samples. Sequence analysis of the 16S rRNA gene of all samples showed microbial compositions that were akin to those found in the negative controls, without any bacteria isolated that were unique to the samples. Conclusions: The peritoneal cavity and ascites exhibit low bacterial biomass even in the presence of SBP, resulting in a very low positivity rate in 16S rRNA gene sequencing. Hence, the 16S RNA sequencing method does little to enhance the rate of positive samples compared to traditional culture methods, including in SBP cases.

Next-generation sequencing using tissue specimen collected with a 1.1 mm-diameter cryoprobe in patients with lung cancer.

BACKGROUND AND OBJECTIVE: Next-generation sequencing (NGS) analysis is considered standard for lung cancer diagnosis in clinical practice. Little is known about the feasibility of NGS using tumour tissue sampled with a 1.1 mm-diameter cryoprobe. We aimed to investigate the suitability of specimens obtained by transbronchial cryobiopsy (TBC) using a 1.1 mm-diameter cryoprobe for NGS analysis. METHODS: Patients with lung cancer who underwent TBC using a 1.1 mm-diameter cryoprobe for NGS testing between October 2020 and April 2023 were enrolled. A 4.0- or 3.0 mm-diameter bronchoscope with radial probe endobronchial ultrasound and virtual bronchoscopic navigation was used to detect peripheral lung lesions. All procedures were performed under fluoroscopic guidance. Data were analysed retrospectively. RESULTS: A total of 56 patients underwent TBC using a 1.1 mm cryoprobe for NGS testing, during the study period. Most patients (98%) were in the advanced stage of lung cancer (recurrent or inoperable disease of stages III or IV). The diagnostic yield of NGS for DNA and RNA sequencing was 95% each (53 of 56). Moderate bleeding was noted in three patients (5%) and none of the study patients developed life-threatening complications, such as pneumothorax or lung infection. CONCLUSION: TBC using a 1.1 mm-diameter cryoprobe is a useful and safe tool for NGS analysis, for both DNA and RNA sequencing.

Blood Lymphocytes as a Prognostic Factor for Stage III Non-Small Cell Lung Cancer with Concurrent Chemoradiation.

We aimed to identify blood lymphocytes as a prognostic factor for survival in patients with locally advanced stage III non-small cell lung cancer (NSCLC) treated with concurrent chemoradiotherapy (CCRT). This is a secondary study of 196 patients enrolled in the Korean Radiation Oncology Group 0903 phase III clinical trial to evaluate the prognostic significance of circulating blood lymphocyte levels. The median total lymphocyte count (TLC) reduction ratio during CCRT was 0.74 (range: 0.29-0.97). In multivariate analysis, patient age (p=0.014) and gross tumor volume (GTV, p=0.031) were significant factors associated with overall survival, while TLC reduction (p=0.018) and pretreatment neutrophil-to-lymphocyte ratio (NLR; p=0.010) were associated with progression-free survival (PFS). In multivariate logistic regression analysis, pretreatment NLR, GTV, and heart V20 were significantly associated with TLC reduction. Immunohistochemical analysis of programmed death ligand 1 and CD8 expression on T cells was performed on 84 patients. CD8 expression was not significantly associated with the pretreatment lymphocyte count (p=0.673), and PDL1 expression was not significantly associated with OS or PFS. Univariate analysis revealed that high CD8 expression in TILs was associated with favorable OS and was significantly associated with favorable PFS (p=0.032). TLC reduction during CCRT is a significant prognostic factor for PFS, and heart V20 is significantly associated with TLC reduction. Thus, in the era of immunotherapy, constraining the volume of the radiation dose to the whole heart must be prioritized for the better survival outcomes.

Minimization of preventable drug waste through use of a vial combination calculator tool.

PURPOSE: This project aimed to determine whether a supportive calculator that automates the vial selection process might offer a practical and efficient method of reducing pharmaceutical expenditures through minimizing preventable drug waste in outpatient pharmacy settings. SUMMARY: Drug waste is a substantial target of cost-saving efforts in the areas of oncology and autoimmune therapy, which involve use of a vast number of high-cost medications packaged in single-dose vials of varying strength. To facilitate selection of the optimal combination of medication vials and thereby minimize preventable drug waste, a Microsoft Excel-based calculator was developed for use by staff of a large oncology pharmacy network. Twenty-three high-cost chemotherapy and monoclonal antibody medications were identified as initial targets for the drug waste prevention initiative. After dissemination and implementation of the calculator and provision of monthly pharmacy staff education, the dollar value of preventable drug waste and the number of suboptimal vial combination selections were reduced by 51% ($412,300) and 54% (315 selections), respectively, in fiscal year 2022 and further reduced by 46% ($183,400) and 27% (71 selections), respectively, in fiscal year 2023. CONCLUSION: After implementation of an automated vial selection tool, preventable drug waste and the quantity of suboptimal vial combination selections were markedly reduced across 11 outpatient compounding pharmacies.

Trajectories of Wok Adjustment and Influencing Factors Among Newly Registered Nurses.

PURPOSE: This study explored the work adjustment trajectory and its predictors and characteristics among newly registered nurses. METHODS: A total of 245 newly registered nurses working in a university hospital provided general baseline characteristics and completed a work adjustment questionnaire along with self-report measures of clinical competency, psychological capital, preceptor exchange, social support, and role conflict when they started working independently (baseline) and at 7 and 12 months after employment. Data were collected from July 2020 to August 2022. The collected data were subjected to a group-based trajectory model, χ2 test, F test, one-way ANOVA, and multiple logistic regression using SAS 9.4, and SPSS 25.0. RESULTS: Group-based trajectory modeling classified three newly registered nurse groups: nurses with a high work adjustment level in all subscales from the beginning of employment (early adjustment group, 16.1%), nurses with a moderate level of adjustment from beginning to end (standard adjustment group, 60.6%), and nurses with a low level of work adjustment from early to mid-term, rising later (delayed adjustment group, 23.3%). Higher hope, optimism, and emotional support predicted early and standard adjustments. CONCLUSIONS: Based on the trajectory characteristics, newly registered nurses need to improve their work adjustment. The early and standard adjustment groups should continuously monitor their levels of work adjustment while monitoring their hopes, optimism, and emotional support. In particular, the delayed adjustment group required customized educational programs and strengthened peer support.

Corynoxine promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in Alzheimer's disease models.

Autophagy impairment is a key factor in Alzheimer's disease (AD) pathogenesis. TFEB (transcription factor EB) and TFE3 (transcription factor binding to IGHM enhancer 3) are nuclear transcription factors that regulate autophagy and lysosomal biogenesis. We previously showed that corynoxine (Cory), a Chinese medicine compound, protects neurons from Parkinson's disease (PD) by activating autophagy. In this study, we investigated the effect of Cory on AD models in vivo and in vitro. We found that Cory improved learning and memory function, increased neuronal autophagy and lysosomal biogenesis, and reduced pathogenic APP-CTFs levels in 5xFAD mice model. Cory activated TFEB/TFE3 by inhibiting AKT/mTOR signaling and stimulating lysosomal calcium release via transient receptor potential mucolipin 1 (TRPML1). Moreover, we demonstrated that TFEB/TFE3 knockdown abolished Cory-induced APP-CTFs degradation in N2aSwedAPP cells. Our findings suggest that Cory promotes TFEB/TFE3-mediated autophagy and alleviates Aß pathology in AD models.

Midterm Clinical and Radiological Outcomes of Revision Lateral Meniscal Allograft Transplantation.

Background: It is unknown whether the outcomes achieved in the early period after revision lateral meniscal allograft transplantation (RLMAT) are maintained through the midterm period. Purpose: To evaluate the midterm clinical and radiological results of patients who underwent RLMAT. Study Design: Case series; Level of evidence, 4. Methods: We reviewed the outcomes of 19 RLMATs in 18 patients with at least 5 years of follow-up data. The mean follow-up period was 6 ± 1.1 years (range, 5-8.5 years). Clinical outcomes were assessed using the modified Lysholm score, the International Knee Documentation Committee (IKDC) subjective score, and the Tegner activity level. Radiographic progression of arthritis was measured by the absolute and relative joint space widths on 45° of knee flexion posteroanterior radiographs preoperatively, 1 year postoperatively, and at the latest follow-up.Failure was defined as meniscocapsular separation, removal, or tear of more than half of the meniscal allograft on postoperative magnetic resonance imaging (MRI) or conversion to total knee arthroplasty. Of the 18 patients, 3 underwent ≥2 RLMATs. The survival rate was evaluated according to the number of revision surgeries. Results: For knees with an intact meniscus transplant at the final follow-up, the modified Lysholm and IKDC scores were significantly improved compared with preoperatively, but the Tegner activity level was unchanged. No significant differences were found in the absolute and relative joint space widths postoperatively. There were 6 failures within 3 years after RLMAT; the overall 5-year survival rate was 68.4% (13/19 knees). All failed knees showed bucket-handle tear patterns on MRI due to meniscocapsular healing failure. The survival rate decreased as the number of RLMATs increased-73.3% for a first RLMAT (n = 15 knees), 66.7% for a second RLMAT (n = 3 knees), and 0% for a third RLMAT (n = 1 knee). Midterm MRIs of 8 well-healed RLMATs showed evidence of meniscal degeneration; nonetheless, this did not affect clinical outcomes. Conclusion: The midterm results of RLMATs demonstrated a 5-year survival rate of 68.4% and positive clinical and radiological outcomes for failed MATs despite unimproved activity levels. Inadequate meniscocapsular healing was the leading cause of failure, and it needs to be carefully considered when performing RLMATs.

Research Note: Welfare and stress responses of broiler chickens raised in conventional and animal welfare-certified broiler farms.

The present study was conducted to assess the animal welfare status of broiler chickens raised in conventional and welfare-certified farms. One conventional farm (30,000 birds/house, 1,488 m2/house, 2 houses) and one animal welfare-certified farm (32,000 birds/house, 1,920 m2/house, 2 houses) were selected to measure productivity, stress responses, and animal welfare indicators in 3 broiler flocks (2 farms/season, n = 6 flocks/farm type) during summer, autumn, and spring. Upon farm visits, body weight, uniformity, and animal welfare indicators (i.e., fecal and feather corticosterone, footpad dermatitis, hock burn, feather dirtiness, and gait score) were measured at 26 d posthatch. Also, moisture, nitrogen, and pH of litter, light intensity, ammonia concentration, and body surface temperature of head, chest, and legs were measured. There was no difference in body weight and uniformity between farm types. Fecal corticosterone concentrations were higher (P = 0.021) in welfare-certified vs. conventional farm, but no significant difference was found in feather corticosterone. Welfare-certified vs. conventional farm had lower percentages of hock burn (P = 0.018), feather dirtiness scores (P = 0.009), and gait score (P = 0.040), and there was no difference in footpad dermatitis. Nitrogen content in litter samples tended to be higher in conventional vs. welfare-certified farms (P = 0.094), and there was no difference in moisture and pH between farm types. Ammonia concentration within the broiler houses was not different between 2 farms. However, animal welfare farm was found to be brighter than conventional farm (P < 0.001). The body surface temperature of head, chest, and legs was not different between farm types. In conclusion, the welfare-certified farm had higher welfare measures, including lower hock burn, feather dirtiness, and gait score, confirming an overall improvement in welfare indicators. However, the observation on the elevated feather corticosterone noted in welfare vs. conventionally raised chickens warrants further studies.

Effects of grain-based pecking blocks on productivity and welfare indicators in commercial broiler chickens.

OBJECTIVE: This experiment was conducted to investigate the effect of grain-based pecking blocks on productivity and welfare status at two commercial broiler welfare-certified farms. METHODS: Production and welfare indicators were assessed at two farms (designated Farm A and B). Both farms had two windowless houses with forced tunnel-type ventilation and housed broilers at stocking densities of approximately 16.7 birds/m2 (Farm A) and 16.8 birds/m2 (Farm B). Each house was divided into two or three equal sections and was provided with or without pecking blocks. Grain-based pecking blocks, measuring 25 × 25 × 25 cm, were given to broilers in both farms at 1 block per 1,000 birds. Various parameters including productivity (body weight and flock uniformity), corticosterone levels (in fecal droppings and feathers), footpad dermatitis, hock burn, feather dirtiness, gait score, litter quality, body surface temperature, and volatile fatty acids in fecal samples were assessed at 26 days of age, whereas litter quality was analyzed at 13 and 26 days of age. RESULTS: There were no significant effects of providing pecking blocks on productivity (body weight and uniformity), fecal and feather corticosterone, welfare indicators (i.e., footpad dermatitis, hock burn, feather cleanliness, and gait score), and litter quality (i.e., moisture, nitrogen, and pH). No differences in body surface temperature between the control and enrichment treatments were noted in Farm B, but body surface temperatures of the head (p = 0.029) and legs (p = 0.011) in the enrichment vs. control group were elevated in Farm A. Butyrate concentration in the enrichment vs control group was higher in Farm B (p = 0.023), but this effect was not detected in Farm A. CONCLUSION: It is concluded that grain-based pecking blocks did not affect performance and welfare indicators. Further studies are warranted to elucidate the potential impact of grain-based pecking blocks on gut health indicators.

Risk Factor for Clinical Failure of Medial Meniscal Allograft Transplant: Early vs Late Graft Tear.

BACKGROUND: Graft tears are common postoperative findings in meniscal allograft transplant (MAT). Graft tear in medial MAT may be different from that of lateral MAT, considering the difference between medial meniscal tears and lateral meniscal tears. Moreover, medial MAT is frequently accompanied by ligament reconstruction, which is associated with graft tear. The effect of graft tear on the long-term survivorship of medial MAT has not been investigated. HYPOTHESIS: Graft tear would adversely affect the survivorship of medial MAT and the effect would be different according to the timing of graft tear. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 55 patients undergoing medial MAT between June 2019 and March 2000 were retrospectively reviewed. Postoperative magnetic resonance imaging (MRI) scans were reviewed to identify graft tears, and the timing of their occurrence was investigated. Postoperative MRI was performed routinely during the first postoperative year and every 2 years thereafter. The patients were classified into a no graft tear (NT) group, early graft tear (occurring within 1 year; ET) group, and late graft tear (occurring 1 year after surgery; LT) group. The survival rate of medial MAT was estimated according to graft tear, with a failure being defined as (1) reoperations including arthroplasty, realignment osteotomy, revision MAT, and meniscectomy (>50% of the graft or to the zone of the meniscocapsular junction) or (2) Lysholm score <65. Clinical scores were compared between the groups. RESULTS: The mean follow-up duration was 8.6 ± 5.3 years. During that period, clinical failures occurred in 6 (10.9%) patients. The overall survival rate at 5 years was 94.0% (95% CI, 90.6%-97.4%). Graft tears were seen in 18 patients: 6 patients in the ET group and 12 patients in the LT group. The median time when the graft tear was noted on MRI scans was 5.5 months (range, 1-11 months) postoperatively in the ET group and 99.5 months (range, 19-264 months) postoperatively in the LT group. Five patients in the ET group had root tears, whereas 9 patients in the LT group had complex or horizontal tears. The 5-year survival rate of the ET group was 62.5% (95% CI, 41.2%-83.8%), which was significantly lower than that of the NT group (96.8%; 95% CI, 93.6%-99.9%) and the LT group (85.7%; 95% CI, 72.5%-98.9%; P = .002). The mean postoperative Lysholm scores were 85.6 ± 17.9 in the NT group, 93.0 ± 2.8 in the ET group, and 79.3 ± 11.6 in the LT group, showing no significant difference between the groups (Kruskal-Wallis test, P = .058). CONCLUSION: Clinical relevance of graft tear that occurred after medial MAT was dependent upon its timing. ET was a risk factor for clinical failure, whereas LT did not adversely affect graft survivorship. Lysholm scores did not differ according to graft tear.

Direct Tumor Irradiation Potentiates Adoptive NK Cell Targeting Against Parental and Stemlike Cancer in Human Liver Cancer Models.

PURPOSE: Radiation therapy (RT) has been shown to effectively induce the expression of intercellular adhesion molecule-1 (ICAM-1), which is recognized by lymphocyte function-associated antigen 1 (LFA-1) expressed on natural killer (NK) cells. However, the potential synergistic antitumor immune response of tumor irradiation and administered NK cells has not been explored in intractable human liver cancers. Furthermore, NK cell targeting against both parental and cancer stemness has never been investigated. METHODS AND MATERIALS: Highly activated ex vivo NK cells were administered into the human liver tumor-bearing mice. Tumor direct RT was optimized according to tumor bearing site. HepG2 and Hep3B ICAM-1 knockout cells were generated using CRISPR/CAS9. Stemness tumor spheres were generated. NK cell cytolysis against parental and tumor sphere was evaluated using flow cytometry and real-time cytotoxicity assay. RESULTS: A combination of adoptive NK cell therapy with RT significantly improved therapeutic efficacy over monotherapies against subcutaneous, orthotopic, and metastatic human liver tumor models. Direct tumor irradiation potentiated NK cell recognition and conjugation against liver cancer through the LFA-1/ICAM-1 axis. Suppression of immune synapse formation on NK cells using high-affinity LFA-1 inhibitors or ICAM-1 knockout liver cancer induced "outside-in" signal blocking in NK cells, resulting in failure to eliminate liver tumor despite the combination therapy. NK cells effectively recognized and targeted triple-high epithelial cell adhesion molecule+CD133+CD24+ liver cancer expressing upregulated ICAM-1 in the irradiated tumor microenvironment, which led to prevention of the initiation of metastasis, improving survival in a metastatic model. In addition, the LFA-1/ICAM-1 axis interruption between NK cells and stemness liver tumor spheres significantly diminished NK cell cytolysis. Consistent with our preclinical data, the LFA-1/ICAM-1 axis correlated with survival outcomes in patients with metastatic cancer from the The Cancer Genome Atlas databases. CONCLUSIONS: NK cells in combination with tumor irradiation can provide synergistic therapeutic effects for NK cell recognition and elimination against both parental and stemlike liver cancer through LFA-1/ICAM-1.

The Effect of Low Temperature on Laying Performance and Physiological Stress Responses in Laying Hens.

The present study investigated the effect of low temperature on laying performance, egg quality, body temperature, yolk malondialdehyde, yolk corticosterone, and serum biochemistry in laying hens. A total of 40 laying hens (Hy-Line Brown) aged 36 weeks were housed in one of two environmental chambers kept at 12 ± 4.5 °C (low temperature) or 24 ± 3 °C (normal temperature) for 4 weeks. Low vs. normal temperature significantly increased (p < 0.05) live body weight, feed intake, and feed conversion ratio in laying hens. Skin surface temperature, but not rectal temperature, was decreased in laying hens exposed to low vs. normal temperature. Hens exposed to low temperature laid an intense eggshell color compared with those raised in a normal temperature. Malondialdehyde concentrations in yolk were increased in low-temperature-exposed laying hens compared with those at normal temperature conditions, but this effect was only noted on day 7, post the low-temperature exposure (p = 0.04). Finally, low vs. normal temperature increased the concentrations of total cholesterol and triglyceride in serum. Collectively, this study indicates that exposure to low temperature in laying hens initially disrupted antioxidant system and altered lipid metabolism in laying hens without inducing stress responses.

Early Graft Tear As a Major Risk Factor for the Clinical Failure of Lateral Meniscal Allograft Transplantation.

BACKGROUND: Graft tears are often observed on magnetic resonance imaging after lateral meniscal allograft transplantation (MAT). Their characteristics, such as the location and configuration, are likely to be different depending on the timing of the injury. However, the clinical relevance of early and late graft tears has not been investigated. HYPOTHESIS: (1) Both early and late graft tears would be associated with the clinical failure of lateral MAT, and (2) an early graft tear (ET) would lead to worse outcomes than a late graft tear (LT) or an intact graft. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: A total of 261 patients who had undergone lateral MAT between March 2000 and June 2019 were retrospectively reviewed. The graft tear was investigated using magnetic resonance imaging, which was performed routinely during the first postoperative year and every 2 years thereafter. The patients were classified according to the timing of the graft tear: no graft tear (NT) group, ET (≤1 year after surgery) group, and LT (>1 year after surgery) group. Clinical failure was defined as (1) reoperations including arthroplasty, realignment osteotomy, revision MAT, and meniscectomy (>50% of the graft or to the zone of the meniscocapsular junction) or (2) a Lysholm score of <65. Risk factors for a low survival rate were investigated using Cox regression analysis. A comparison of the Lysholm scores for each group was also performed. RESULTS: There were 24 (9.2%) patients who had clinical failure at a mean follow-up of 7.5 ± 4.3 years. The overall survival rate at 5 years was 92.8% (95% CI, 91.1%-94.5%). A graft tear was noted in 80 patients: 23 patients in the ET group and 57 patients in the LT group. The most common tear pattern was a meniscocapsular tear in the ET group and a complex tear in the LT group. The hazard ratios for clinical failure in the ET and LT groups were 30.7 (95% CI, 9.4-76.4; P < .001) and 4.0 (95% CI, 1.3-12.9; P = .013), respectively. The Lysholm score of the ET group (82.7 ± 14.8) was significantly lower than that of the other 2 groups (NT: 87.6 ± 11.7; LT: 90.7 ± 9.0; P = .024). CONCLUSION: An ET was a major risk factor for the clinical failure of lateral MAT. An LT was associated with a lower survival rate. An ET was also associated with worse clinical outcomes.

Effect of White Noise on Pain Response, Heart Rate, and Oxygen Saturation During Heel Puncture in Premature Infants: A Randomized Controlled Trial.

OBJECTIVE: This study aimed to investigate the effect of white noise on pain response, heart rate, and oxygen saturation during heel puncture in premature infants. METHODS: A randomized, controlled, pretest-posttest design was used. The participants were premature infants admitted to the neonatal intensive care unit of a university hospital in Gyeonggi Province. Sixty premature infants were assigned to either an experimental (n = 30) or control (n = 30) group. The experimental group was exposed to white noise during heel puncture, and the measured variables were pain response, heart rate, and oxygen saturation. The data were analyzed using the independent t test, chi-squared test, and analysis of covariance. RESULTS: Premature infants in the experimental group had a lower pain response and heart rate than the control group (F = 81.26, P < .01; F = 7.05, P = .01), and higher oxygen saturation than the control group (F = 4.76, P = .03). CONCLUSION: These results demonstrated that the white noise intervention is an effective nursing intervention to reduce the pain response and stabilize heart rate and oxygen saturation in premature infants during heel puncture.

Postoperative change in the joint-line convergence angle is associated with inaccurate correction in open-wedge high tibial osteotomy.

OBJECTIVE: Accurate correction is a prerequisite for the favorable outcomes of open-wedge high tibial osteotomy (OWHTO). However, previous studies have reported disappointing results regarding correction accuracy despite the use of intra-operative navigation, which implies that a certain factor other than bony components is involved in the inaccurate correction (mainly overcorrection). The joint-line convergence angle (JLCA) can represent soft tissue effects in OWHTO. This study tried to determine whether the postoperative change in the JLCA (∆JLCA) led to inaccurate correction. METHODS: Medical records of 78 OWHTO patients from 2005 to 2021 were retrospectively reviewed. The hip-knee-ankle angle (HKA) was measured with a positive value indicating varus alignment. Inaccurate correction was defined as postoperative HKA < - 3°. The JLCA was measured before and 6 months after surgery on long-standing hip-to-ankle radiographs, and ∆JLCA was defined as the difference between the preoperative and 6-month postoperative JLCAs. ∆JLCA was compared between the accurate correction group and the inaccurate correction group, and a receiver operating characteristic (ROC) curve was used to obtain the cutoff ∆JLCA at which the sensitivity and the specificity for inaccurate correction were maximized. Clinical outcomes were also compared between the groups using the knee injury and osteoarthritis outcome score (KOOS) at final follow-up (60.9 ± 53.3 months postoperatively). RESULTS: Of the 78 patients, inaccurate correction was noted in 10 patients. The overall preoperative and postoperative HKAs were 7.0 ± 3.1° and - 0.4 ± 1.5°, respectively. The accurate correction group and the inaccurate correction group had a difference in ∆JLCA (p = 0.010). However, no significant difference was found in the preoperative HKA (p = 0.529). An ROC curve showed that the cutoff ∆JLCA was 1.9°. In the patients having ∆JLCA ≥ 1.9°, the mean JLCA was 4.9 ± 1.6° preoperatively and 1.7 ± 1.2° postoperatively. In the other patients having ∆JLCA < 1.9°, the mean preoperative and postoperative JLCA were 2.5 ± 1.8° and 2.3 ± 1.8°, respectively. The difference in the preoperative JLCA was significant (p < 0.001). The postoperative KOOS subscales did not differ according to correction accuracy. CONCLUSION: Inaccurate correction in OWHTO, specifically valgus overcorrection, is associated with large ∆JLCA which represents the postoperative change of soft tissue effects. Overcorrection should be checked in cases of large preoperative JLCAs.