Search

Jung Hee Lee,1,* Hyun-Jong Lee,1,* Sang Ha Woo,1 Yu-Kyeong Park,1 Ji Hoon Han,1 Ga-Young Choi,1 Eun Sil Heo,1 Jae Soo Kim,1 Chung A Park,2 Woo Dong Lee,3 Chang Sop Yang,4 Ae-Ran Kim,5 Chang-Hyun Han4,6 1Department of Acupuncture & Moxibustion, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 2Department of Diagnostics, College of Korean Medicine, Daegu Haany University, Daegu, Republic of Korea; 3Pre-Major of Cosmetics and Pharmaceutics, College of Herbal Bio-Industry, Daegu Haany University, Daegu, Republic of Korea; 4KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 5Clinical Research Coordinating Team, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 6Korean Convergence Medicine, University of Science & Technology (UST), Campus of Korea Institute of Oriental Medicine, Daejeon, Republic of Korea*These authors contributed equally to this workCorrespondence: Chang-Hyun Han, KM Science Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, Republic of Korea, Tel +82 42 868 9498, Fax +82 42 869 2775, Email chhan@kiom.re.krPurpose: In Korea, complex treatments such as acupotomy, acupuncture, and physical therapy are performed for lumbar spinal stenosis (LSS). Although there are reports of acupotomy as monotherapy or acupuncture treatment for LSS, pragmatic studies are lacking. Therefore, this study aimed to determine the effectiveness and safety of acupotomy for LSS to provide baseline evidence for a large-scale study.Materials and Methods: This pragmatic randomized controlled pilot study enrolled 34 participants and randomly assigned them to two groups (n=17/group). The intervention was conducted for 8 weeks. Acupotomy plus and usual care groups received acupuncture (17 acupoints) and interferential current therapy (ICT) twice weekly; however, the acupotomy plus group received an additional acupotomy (7 acupoints) for treatment of the usual care group. The primary outcome was measured using visual analog scales (VAS), and secondary outcomes were assessed using the self-rated walking distance, short-form McGill Pain Questionnaire (SF-MPQ), and the Oswestry Disability Index (ODI). Outcome measurements were conducted at baseline and 4, 8, and 12 weeks after the commencement of the intervention. Adverse events were assessed at each visit. Hematological and biochemical examinations were performed at screening and week 8.Results: Overall, 33 of the 34 participants completed the study, and one participant in the usual care group dropped out. In both groups, VAS scores at weeks 4, 8, and 12 significantly improved compared to baseline. Also, self-rated walking distance, SF-MPQ, and ODI scores were significantly improved at weeks 4, 8, and 12 than at baseline. However, there were no significant differences in the time-dependent and group-to-time interactions between the two groups. In addition, no severe adverse reactions were reported, and there were no significant differences in hematological and biochemical results.Conclusion: This study provides baseline data for large-scale studies on the effectiveness and safety of acupotomy in LSS.Clinical Trial Number: KCT0006234.Keywords: complementary therapy, pragmatic clinical trial, low back pain, acupuncture therapy

Despite the known metabolic benefits of exercise, an integrated metabolic understanding of exercise is lacking. Here, we use in vivo steady-state isotope-labeled infusions to quantify fuel flux and oxidation during exercise in fasted, fed, and exhausted female mice, revealing several novel findings. Exercise strongly promoted glucose fluxes from liver glycogen, lactate, and glycerol, distinct from humans. Several organs spared glucose, a process that broke down in exhausted mice despite concomitant hypoglycemia. Proteolysis increased markedly, also divergent from humans. Fatty acid oxidation dominated during fasted exercise. Ketone production and oxidation rose rapidly, seemingly driven by a hepatic bottleneck caused by gluconeogenesis-induced cataplerotic stress. Altered fuel consumption was observed in organs not directly involved in muscle contraction, including the pancreas and brown fat. Several futile cycles surprisingly persisted during exercise, despite their energy cost. In sum, we provide a comprehensive, integrated, holistic, and quantitative accounting of metabolism during exercise in an intact organism., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Nicotinamide adenine dinucleotide (NAD + ) is an essential co-factor in metabolic reactions and co-substrate for signaling enzymes. Failing human hearts display decreased expression of the major NAD + biosynthetic enzyme nicotinamide phosphoribosyltransferase (Nampt) and lower NAD + levels, and supplementation with NAD + precursors is protective in preclinical models. Here we show that Nampt loss in adult cardiomyocytes caused depletion of NAD + along with marked metabolic derangements, hypertrophic remodeling and sudden cardiac deaths, despite unchanged ejection fraction, endurance and mitochondrial respiratory capacity. These effects were directly attributable to NAD + loss as all were ameliorated by restoring cardiac NAD + levels with the NAD + precursor nicotinamide riboside (NR). Electrocardiograms revealed that loss of myocardial Nampt caused a shortening of QT intervals with spontaneous lethal arrhythmias causing sudden cardiac death. Thus, changes in NAD + concentration can have a profound influence on cardiac physiology even at levels sufficient to maintain energetics., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Friedreich's ataxia (FRDA) is a progressive disorder caused by insufficient expression of frataxin, which plays a critical role in assembly of iron-sulfur centers in mitochondria. Individuals are cognitively normal but display a loss of motor coordination and cardiac abnormalities. Many ultimately develop heart failure. Administration of nicotinamide adenine dinucleotide-positive (NAD+) precursors has shown promise in human mitochondrial myopathy and rodent models of heart failure, including mice lacking frataxin in cardiomyocytes. We studied mice with systemic knockdown of frataxin (shFxn), which display motor deficits and early mortality with cardiac hypertrophy. Hearts in these mice do not "fail" per se but become hyperdynamic with small chamber sizes. Data from an ongoing natural history study indicate that hyperdynamic hearts are observed in young individuals with FRDA, suggesting that the mouse model could reflect early pathology. Administering nicotinamide mononucleotide or riboside to shFxn mice increases survival, modestly improves cardiac hypertrophy, and limits increases in ejection fraction. Mechanistically, most of the transcriptional and metabolic changes induced by frataxin knockdown are insensitive to NAD+ precursor administration, but glutathione levels are increased, suggesting improved antioxidant capacity. Overall, our findings indicate that NAD+ precursors are modestly cardioprotective in this model of FRDA and warrant further investigation.

Background/aims: Gastric subepithelial tumors (SETs) are often encountered during the upper gastrointestinal endoscopic screening. We assessed the prevalence of gastric SETs and the risk factors for their progression., Methods: We reviewed the electronic medical records of 30,754 patients who underwent upper gastrointestinal endoscopic screening at our medical center between January 2013 and December 2016., Results: Among the 30,754 patients examined, 599 (1.94%) had gastric SETs. The prevalence increased with age and was 9.56% in patients aged ≥70 years. In total, 262 patients underwent serial endoscopy for more than 6 months. The median age was 68 years (interquartile range [IQR], 61-74), and the number of females was 167 (63.7%). During a median follow-up of 58 months (IQR, 38-75), 22 patients (8.4%) showed significant changes in tumor size. An irregular border (odds ratio, 4.623; 95% confidence interval, 1.093-19.558; p=0.037) was a significant risk factor for progression. Seven patients underwent surgical or endoscopic resections. The pathologies of gastric SETs included leiomyomas (n=3), gastrointestinal stromal tumors (n=2), and lipomas (n=2)., Conclusions: The prevalence of gastric SETs increases with age. Most gastric SETs do not progress during long-term endoscopic examinations, and the risk of an increase in size is low in asymptomatic small SETs without irregular borders.

Orbitrap mass spectrometry in full scan mode enables the simultaneous detection of hundreds of metabolites and their isotope-labeled forms. Yet, sensitivity remains limiting for many metabolites, including low-concentration species, poor ionizers, and low-fractional-abundance isotope-labeled forms in isotope-tracing studies. Here, we explore selected ion monitoring (SIM) as a means of sensitivity enhancement. The analytes of interest are enriched in the orbitrap analyzer by using the quadrupole as a mass filter to select particular ions. In tissue extracts, SIM significantly enhances the detection of ions of low intensity, as indicated by improved signal-to-noise (S/N) ratios and measurement precision. In addition, SIM improves the accuracy of isotope-ratio measurements. SIM, however, must be deployed with care, as excessive accumulation in the orbitrap of similar m / z ions can lead, via space-charge effects, to decreased performance (signal loss, mass shift, and ion coalescence). Ion accumulation can be controlled by adjusting settings including injection time and target ion quantity. Overall, we suggest using a full scan to ensure broad metabolic coverage, in tandem with SIM, for the accurate quantitation of targeted low-intensity ions, and provide methods deploying this approach to enhance metabolome coverage.

In response to a meal, insulin drives hepatic glycogen synthesis to help regulate systemic glucose homeostasis. The mechanistic target of rapamycin complex 1 (mTORC1) is a well-established insulin target and contributes to the postprandial control of liver lipid metabolism, autophagy, and protein synthesis. However, its role in hepatic glucose metabolism is less understood. Here, we used metabolomics, isotope tracing, and mouse genetics to define a role for liver mTORC1 signaling in the control of postprandial glycolytic intermediates and glycogen deposition. We show that mTORC1 is required for glycogen synthase activity and glycogenesis. Mechanistically, hepatic mTORC1 activity promotes the feeding-dependent induction of Ppp1r3b, a gene encoding a phosphatase important for glycogen synthase activity whose polymorphisms are linked to human diabetes. Reexpression of Ppp1r3b in livers lacking mTORC1 signaling enhances glycogen synthase activity and restores postprandial glycogen content. mTORC1-dependent transcriptional control of Ppp1r3b is facilitated by FOXO1, a well characterized transcriptional regulator involved in the hepatic response to nutrient intake. Collectively, we identify a role for mTORC1 signaling in the transcriptional regulation of Ppp1r3b and the subsequent induction of postprandial hepatic glycogen synthesis.

Extensive endoscopic submucosal dissection (ESD) for gastric adenoma or early cancer can lead to post-ESD stenosis. This may cause a decrease in quality of life and an increase in medical issues. Therefore, this study examined the safety and effectiveness of gastric open peroral endoscopic myotomy (GO-POEM) in preventing stenosis following ESD. A retrospective investigation was carried out on 31 patients who underwent gastric ESD for > 75% of the lumen in the antrum or pylorus at the Presbyterian Medical Center in Korea between December 2004 and October 2022. The patients were divided into GO-POEM (n = 11) and non-GO-POEM groups (n = 20). The average age of the 31 patients was 73.23 years, and 18 were male. There were no differences in age, sex, location, gross findings, or procedure time between the 2 groups. In the GO-POEM group, only 1 patient (9 %) developed stenosis, compared to 11 patients (55 %) in the control group (P = .02). Multivariate analysis showed that the GO-POEM group had a significantly lower risk of post-ESD stenosis (P < .05). Stenosis symptoms resolved with a single endoscopic balloon dilatation (EBD) in 1 patient in the GO-POEM group. In contrast, 5 of 11 patients with stenosis in the non-GO-POEM group required a median of 2 EBD sessions (range, 1-8). GO-POEM may be an effective and reliable method for preventing stenosis post extensive gastric ESD. Further investigations are necessary to establish its efficacy and safety., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The gastrointestinal tract microbiome is essential for regulating nutrient absorption, gut immune function, and host growth and development. In the present study, we characterized the development of ileum and cecum microbiota in pullets throughout the rearing period, encompassing a period from the day of hatching to 18 weeks of age. The growth performance and intestinal microbiome (ileum and cecum) of pullets were analyzed at 1, 5, 11, and 18 weeks of age. The richness of the ileum and cecum bacterial communities (alpha diversity) was higher in pullets at 18 weeks of age than in those at 1 and 5 weeks of age. Microbiota from weeks 1, 5, 11, and 18 were distinctly grouped in a NMDS plot, representing beta diversity within the ileum. However, the results for cecum microbiota did not reveal evident separation among the different age groups in the weighted UniFrac. In conclusion, our findings demonstrate variations and diversification in ileum and cecum microbiota across different rearing stages in pullets. These insights have the potential to inform the development of nutritional strategies that promote gut health and contribute to the improved development of pullets.

The inability to inspect metabolic activities within distinct subcellular compartments has been a major barrier to our understanding of eukaryotic cell metabolism. Previous work addressed this challenge by analyzing metabolism in isolated organelles, which grossly bias metabolic activity. Here, we describe a method for inferring physiological metabolic fluxes and metabolite concentrations in mitochondria and cytosol based on isotope tracing experiments performed with intact cells. This is made possible by computational deconvolution of metabolite isotopic labeling patterns and concentrations into cytosolic and mitochondrial counterparts, coupled with metabolic and thermodynamic modelling. Our approach lowers the uncertainty regarding compartmentalized fluxes and concentrations by one and three orders of magnitude compared to existing modelling approaches, respectively. We derive a quantitative view of mitochondrial and cytosolic metabolic activities in central carbon metabolism across cultured cell lines without performing cell fractionation, finding major variability in compartmentalized malate-aspartate shuttle fluxes. We expect our approach for inferring metabolism at a subcellular resolution to be instrumental for a variety of studies of metabolic dysfunction in human disease and for bioengineering., (© 2023. The Author(s).)

Cancer-related fatigue (CRF) is one of the most common complications in patients with multiple cancer types and severely affects patients' quality of life. However, there have only been single symptom-relieving adjuvant therapies but no effective pharmaceutical treatment for the CRF syndrome. Dichloroacetate (DCA), a small molecule inhibitor of pyruvate dehydrogenase kinase, has been tested as a potential therapy to slow tumor growth, based largely on its effects in vitro to halt cell division. We found that although DCA did not affect rates of tumor growth or the efficacy of standard cancer treatment (immunotherapy and chemotherapy) in two murine cancer models, DCA preserved physical function in mice with late-stage tumors by reducing circulating lactate concentrations. In vivo liquid chromatography-mass spectrometry/mass spectrometry studies suggest that DCA treatment may preserve membrane potential, postpone proteolysis, and relieve oxidative stress in muscles of tumor-bearing mice. In all, this study provides evidence for DCA as a novel pharmaceutical treatment to maintain physical function and motivation in murine models of CRF. NEW & NOTEWORTHY We identify a new metabolic target for cancer-related fatigue, dichloroacetate (DCA). They demonstrate that in mice, DCA preserves physical function and protects against the detrimental effects of cancer treatment by reducing cancer-induced increases in circulating lactate. As DCA is already FDA approved for another indication, these results could be rapidly translated to clinical trials for this condition for which no pharmaceutical therapies exist beyond symptom management.

Competing Interests: The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Reprogramming metabolism is of great therapeutic interest for reducing morbidity and mortality during sepsis-induced critical illness. Disappointing results from randomized controlled trials targeting glutamine and antioxidant metabolism in patients with sepsis have begged a deeper understanding of the tissue-specific metabolic response to sepsis. The current study sought to fill this gap. We analyzed skeletal muscle transcriptomics of critically ill patients, versus elective surgical controls, which revealed reduced expression of genes involved in mitochondrial metabolism and electron transport, with increases in glutathione cycling, glutamine, branched chain, and aromatic amino acid transport. We then performed untargeted metabolomics and 13C isotope tracing to analyze systemic and tissue specific metabolic phenotyping in a murine polymicrobial sepsis model. We found an increased number of correlations between the metabolomes of liver, kidney, and spleen, with loss of correlations between the heart and quadriceps and all other organs, pointing to a shared metabolic signature within vital abdominal organs, and unique metabolic signatures for muscles during sepsis. A lowered GSH:GSSG and elevated AMP:ATP ratio in the liver underlie the significant upregulation of isotopically labeled glutamine's contribution to TCA cycle anaplerosis and glutamine-derived glutathione biosynthesis; meanwhile, the skeletal muscle and spleen were the only organs where glutamine's contribution to the TCA cycle was significantly suppressed. These results highlight tissue-specific mitochondrial reprogramming to support liver energetic demands and antioxidant synthesis, rather than global mitochondrial dysfunction, as a metabolic consequence of sepsis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Leitner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Plasma metabolite concentrations and labeling enrichments are common measures of organismal metabolism. In mice, blood is often collected by tail snip sampling. Here, we systematically examined the effect of such sampling, relative to gold-standard sampling from an in-dwelling arterial catheter, on plasma metabolomics and stable isotope tracing. We find marked differences between the arterial and tail circulating metabolome, which arise from two major factors: handling stress and sampling site, whose effects were deconvoluted by taking a second arterial sample immediately after tail snip. Pyruvate and lactate were the most stress-sensitive plasma metabolites, rising ~14 and ~5-fold. Both acute handling stress and adrenergic agonists induce extensive, immediate production of lactate, and modest production of many other circulating metabolites, and we provide a reference set of mouse circulatory turnover fluxes with noninvasive arterial sampling to avoid such artifacts. Even in the absence of stress, lactate remains the highest flux circulating metabolite on a molar basis, and most glucose flux into the TCA cycle in fasted mice flows through circulating lactate. Thus, lactate is both a central player in unstressed mammalian metabolism and strongly produced in response to acute stress.

Skeletal fragility is associated with type 2 diabetes mellitus (T2D), but the underlying mechanism is not well understood. Here, in a mouse model for youth-onset T2D, we show that both trabecular and cortical bone mass is reduced due to diminished osteoblast activity. Stable isotope tracing in vivo with 13 C-glucose demonstrates that both glycolysis and glucose fueling of the TCA cycle are impaired in diabetic bones. Similarly, Seahorse assays show suppression of both glycolysis and oxidative phosphorylation by diabetes in bone marrow mesenchymal cells as a whole, whereas single-cell RNA sequencing reveals distinct modes of metabolic dysregulation among the subpopulations. Metformin not only promotes glycolysis and osteoblast differentiation in vitro, but also improves bone mass in diabetic mice. Finally, osteoblast-specific overexpression of either Hif1a, a general inducer of glycolysis, or Pfkfb3 which stimulates a specific step in glycolysis, averts bone loss in T2D mice. The study identifies osteoblast-intrinsic defects in glucose metabolism as an underlying cause of diabetic osteopenia, which may be targeted therapeutically., Competing Interests: FS, WL, TM, XJ, CS, XL, RS, LY, HL, FL No competing interests declared, (© 2023, Song et al.)

The poultry industry, which produces excellent sources of protein, suffers enormous economic damage from diseases. To solve this problem, research is being conducted on the early detection of infection according to the behavioral characteristics of poultry. The purpose of this study was to evaluate the potential of a non-movement behavior observation method to detect sick chickens. Forty 1-day-old Ross 308 males were used in the experiments, and an isolator equipped with an Internet Protocol (IP) camera was fabricated for observation. The chickens were inoculated with Salmonella enterica serovar Gallinarum A18-GCVP-014, the causative agent of fowl typhoid (FT), at 14 days of age, which is a vulnerable period for FT infection. The chickens were continuously observed with an IP camera for 2 weeks after inoculation, chickens that did not move for more than 30 minutes were detected and marked according to the algorithm. FT infection was confirmed based on clinical symptoms, analysis of cardiac, spleen and liver lesion scores, pathogen re-isolation, and serological analysis. As a result, clinical symptoms were first observed four days after inoculation, and dead chickens were observed on day six. Eleven days after inoculation, the number of clinical symptoms gradually decreased, indicating a state of recovery. For lesion scores, dead chickens scored 3.57 and live chickens scored 2.38. Pathogens were re-isolated in 37 out of 40 chickens, and hemagglutination test was positive in seven out of 26 chickens. The IP camera applied with the algorithm detected about 83% of the chickens that died in advance through non-movement behavior observation. Therefore, observation of non-movement behavior is one of the ways to detect infected chickens in advance, and it appears to have potential for the development of remote broiler management system., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2023 Korean Society of Animal Science and Technology.)

Tissues derive ATP from two pathways-glycolysis and the tricarboxylic acid (TCA) cycle coupled to the electron transport chain. Most energy in mammals is produced via TCA metabolism 1 . In tumours, however, the absolute rates of these pathways remain unclear. Here we optimize tracer infusion approaches to measure the rates of glycolysis and the TCA cycle in healthy mouse tissues, Kras-mutant solid tumours, metastases and leukaemia. Then, given the rates of these two pathways, we calculate total ATP synthesis rates. We find that TCA cycle flux is suppressed in all five primary solid tumour models examined and is increased in lung metastases of breast cancer relative to primary orthotopic tumours. As expected, glycolysis flux is increased in tumours compared with healthy tissues (the Warburg effect 2,3 ), but this increase is insufficient to compensate for low TCA flux in terms of ATP production. Thus, instead of being hypermetabolic, as commonly assumed, solid tumours generally produce ATP at a slower than normal rate. In mouse pancreatic cancer, this is accommodated by the downregulation of protein synthesis, one of this tissue's major energy costs. We propose that, as solid tumours develop, cancer cells shed energetically expensive tissue-specific functions, enabling uncontrolled growth despite a limited ability to produce ATP., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Antioxidants such as vitamin C (VC) and green tea extract (GTE) have been reported to have various antioxidant functions and are used as one of the nutritional approaches to alleviate heat stress (HS) in chickens. However, studies on the feeding timing that can produce optimal effects have not been reported. In this study, the stress-relieving effect of VC and GTE addition timing was investigated in high-temperature broiler chickens. A total of 880 1-d-old male chickens were used, and the treatments were as follows: no feed additives provided, CON; VC 250 mg/kg added from 1 d, VC1; GTE 600 mg/kg added from 1 d, GTE1; VC 250 mg/kg added from 22 d, VC22; GTE 600 mg/kg added from 22 d, GTE22. The HS environment was provided for 2 wk from the 22 d and was set at 33 ± 1 °C, 55 ± 10% for 24 h. Feed and water were provided ad libitum. Broiler production was similar in all treatments. In chicken meat quality, the addition of VC and GTE had an effect on meat color and pH (P < 0.05). In particular, GTE had a positive effect on the antioxidant capacity and quality preservation of breast meat (P < 0.05). In blood characteristics, GTE1 significantly lowered the level of total cholesterol, and VC1 affected AST and IgM (P < 0.05). Interestingly, the VC1 group had a positive effect on the maintenance and development of intestinal morphology, a lower rectal temperature, and showed to relieve stress. In conclusion, the addition of VC and GTE has been shown to alleviate the high-temperature stress of broilers, and in the case of VC in particular, feeding from 1 d appeared to alleviate stress more effectively. This study suggests that it is important to determine the appropriate timing of addition of functional substances in order to effectively reduce various stresses that occur in livestock rearing., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Society of Animal Science.)

The present study explores the application of CC juice as a suitable feed additive and alternative to conventional antibiotics. We performed a comparative study to investigate the effects of non-fermented and fermented CC juice on broiler productivity, meat quality, blood characteristics, intestinal characteristics, and microbiota associated with intestinal characteristics. A total of 800 one-day-old Ross 308 broiler chickens were randomly assigned to one of the four dietary treatment groups: (1) basal diet (negative control; NC); (2) basal diet + 0.01% enramycin (positive control; PC); (3) basal diet + 3% non-fermented CC juice (NCC; CC juice 10%, water 90%); and (4) basal diet + 3% fermented CC juice (FCC; CC juice 10%, water 90%, Lactobacillus plantarum SK4719). Feed and water were provided ad libitum. Intriguingly, all treatments showed similar results in terms of broiler productivity and chicken meat quality. Considering organ characteristics, the FCC group showed a low spleen weight and lower (p < 0.05) blood levels of AST and total cholesterol (TCHO). Regarding intestinal characteristics, the CC feed additive (NCC and FCC) resulted in a heavier intestinal weight (p < 0.05) without affecting the length ratio of the villi or the crypt compared to the control (NC or PC). NCC and FCC lowered the growth of intestinal pathogens (p < 0.01). In summary, the addition of FCC can maintain poultry health by improving blood compositions and inhibiting the growth of intestinal pathogens, leading to a productivity comparable to that of poultry treated with growth-promoting antibiotics.

Background: Thread embedding acupuncture (TEA) is a widely used clinical procedure for the treatment of musculoskeletal pain. However, few clinical studies have been conducted on the efficacy and safety of TEA for knee osteoarthritis (KOA), and data from randomized controlled trials are lacking. This randomized controlled pilot study aimed to assess the feasibility of conducting large-scale studies on the efficacy and safety of TEA for KOA., Methods: Forty participants were included in the study and randomly divided into 2 groups (TEA and acupuncture) of 20 each. The intervention period was 6 weeks. The experimental group received TEA once a week (total of 6 sessions) on 14 defined knee areas, and the control group received acupuncture twice a week (total of 12 sessions) on 9 defined acupuncture points. The primary outcome measure was the visual analogue scale score, and the secondary outcome measures were the short-form McGill pain questionnaire, and Western Ontario and McMaster Universities Osteoarthritis Index scores. Participants were assessed prior to the intervention (baseline) and at 3, 6, and 10 weeks (4 weeks after the end of intervention). The adverse effects of TEA and acupuncture were documented. Hematological examination and biochemical tests were performed at the screening and at 6 weeks., Results: Of the 40 participants, 37 completed the study and 3 participants dropped out. Both the TEA and acupuncture groups showed a significant improvement in the visual analogue scale, short-form McGill Pain Questionnaire, and Western Ontario and McMaster Universities Osteoarthritis Index scores in a time-dependent manner. However, there was no significant interaction between group and time. No serious adverse events were reported in the groups, and no clinically significant changes were observed in the hematological and biochemical parameters., Conclusion: This pilot study suggests that TEA is a safe and effective procedure for relieving pain in patients with KOA. The results of this study provide basic data and indicate the feasibility of large-scale clinical studies to evaluate the efficacy and safety of TEA for KOA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study evaluates the in vitro probiotic characteristics of P. konkukensis sp. nov. SK-3146, which was isolated from animal feed, and its dietary effects on growth performance, intestinal characteristics, intestinal microbiota, and meat quality in broilers. In vitro experiments revealed that P. konkukensis was non-hemolytic with variable antibiotic susceptibility, and acid as well as bile tolerance. To assess the effect of P. konkukensis on broilers, a total of four hundred eighty 1-day-old Ross 308 broiler chicks were allocated to 3 treatment groups with 4 replicates of 40 birds each; the negative control group was fed a basal diet without any feed additives (NC), the positive control group was fed a basal diet containing 0.01% enramycin (PC), and the experimental group was fed a basal diet containing P. konkukensis bacterial culture (PK) at 104 CFU/g of the diet based on bacterial count. The experiment lasted for 35 days. Results indicated that there were no significant differences in any growth performance parameters among the dietary treatments (p > 0.05). In addition, the inclusion of P. konkukensis in the broilers’ diet did not affect meat cooking loss, color, and pH but increased the relative weight of breast meat (p < 0.05). The PK group showed heavier intestinal weight and shorter intestinal length than the NC group (p < 0.05). The ratio of the intestinal weight to length of jejunum was the highest in the PK group (p < 0.05). The PK group showed increased counts of Streptococcus thermophilus (p < 0.05) with no adverse effects of P. konkukensis on other intestinal microbiota in the jejunum. This study implies that P. konkukensis might have the potential to be applied as a probiotic feed additive in poultry.

Significance: Nonhealing wounds are an ever-growing global pandemic, with mortality rates and management costs exceeding many common cancers. Although our understanding of the molecular and cellular factors driving wound healing continues to grow, standards for diagnosing and evaluating wounds remain largely subjective and experiential, whereas therapeutic strategies fail to consistently achieve closure and clinicians are challenged to deliver individualized care protocols. There is a need to apply precision medicine practices to wound care by developing evidence-based approaches, which are predictive, prescriptive, and personalized. Recent Advances: Recent developments in "advanced" wound diagnostics, namely biomarkers (proteases, acute phase reactants, volatile emissions, and more) and imaging systems (ultrasound, autofluorescence, spectral imaging, and optical coherence tomography), have begun to revolutionize our understanding of the molecular wound landscape and usher in a modern age of therapeutic strategies. Herein, biomarkers and imaging systems with the greatest evidence to support their potential clinical utility are reviewed. Critical Issues: Although many potential biomarkers have been identified and several imaging systems have been or are being developed, more high-quality randomized controlled trials are necessary to elucidate the currently questionable role that these tools are playing in altering healing dynamics or predicting wound closure within the clinical setting. Future Directions: The literature supports the need for the development of effective point-of-care wound assessment tools, such as a platform diagnostic array that is capable of measuring multiple biomarkers at once. These, along with advances in telemedicine, synthetic biology, and "smart" wearables, will pave the way for the transformation of wound care into a precision medicine. Clinical Trial Registration number: NCT03148977.

This study aimed to determine the effects of providing environmental enrichment materials—pumice stone and alfalfa hay—to laying hens in the aviary system. A total of 2196 40-week-old Hy-Line Brown laying hens were randomly allotted to three treatment groups: (1) no enrichment (control; CON), (2) enrichment with pumice stone (PS), and (3) enrichment with alfalfa hay (HAY). Each treatment comprised four replicates of 183 hens each, and four of the same materials were provided per replicate. The experiment lasted for 26 weeks. Feed and water were provided ad libitum. As a result, the PS and HAY groups demonstrated increased egg production (p < 0.001). The HAY group showed a reduced rate of mislaid eggs (p < 0.01) and produced low egg weight and pale-yellow yolk (p < 0.05). Both enrichment materials decreased blood creatinine (CRE) or lactate dehydrogenase (LDH) in the blood and resulted in a significantly lower corticosterone (CORT) level (p < 0.05). However, the feather condition scores for the laying hens were similar across all treatments (p > 0.05). In summary, although pumice stone and alfalfa hay are effective in alleviating stress and improving the production of laying hens, additional environmental improvement studies are needed to contribute to reducing pecking behaviors in poultry farming.

Background: Fractal analyses quantify self-similarities in stride-to-stride fluctuations over different time scales. Fractal exponents can be measured with adaptive fractal analysis (AFA) or detrended fluctuation analysis (DFA), though measurements obtained with the algorithms have not been directly compared., Research Question: Are stride time fractal exponents measured with AFA and DFA algorithms equivalent?, Methods: Data from 50 participants with Parkinson's Disease (n = 15), age-similar healthy adults (n = 15) and healthy young adults (n = 20) were analyzed in this cross-sectional, observational study. Participants completed 6-min walks at self-selected speeds overground on a straight walkway and on a treadmill. Stride times were measured with inertial measurement units. Fractal exponents in stride time data were processed using AFA and DFA algorithms and compared with two one-sided tests of equivalence. Mixed ANOVAs were used to compare exponents between groups and conditions., Results: Fractal exponents computed with AFA and DFA were equivalent neither in the overground (0.796 & 0.830, respectively, p = .587) nor treadmill conditions (0.806 & 0.882, respectively, p = .122). Fractal exponents measured with DFA were higher than when measured with AFA. Standard errors were 22% lower when measured with AFA. Additionally, a group × condition interaction was statistically significant when fractal exponents were processed with the AFA algorithm (F(2,47) = 11.696, p < .001), whereas the group × condition interaction was not statistically significant when DFA exponents were compared (F(2, 47) = 2.144, p = .129)., Significance: AFA and DFA do not produce equivalent estimates of the fractal exponent α in stride time dynamics. Estimates of the fractal exponent α obtained with AFA or DFA algorithms therefore should not be used interchangeably. Standard errors were lower when derived with AFA. Fractal exponents calculated with AFA may be more sensitive to conditions that influence stride time fractal dynamics than are measures calculated with DFA., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Endoscopic resection of over 3/4 of the lumen of the antrum or pylorus is a known risk factor for post-endoscopic submucosal dissection (ESD) stenosis. Local or systemic steroids may reduce the risk of stenosis, but their overall role in stenosis prevention remains controversial. We aimed to evaluate the efficacy and safety of prophylactic gastric open peroral endoscopic myotomy (GO-POEM) in preventing post-ESD stenosis., Methods: Ten patients who underwent GO-POEM during or immediately after ESD in the Presbyterian Medical Center between June 2017 and November 2020 were included. All patients underwent excision of over 3/4 of the lumen of the antrum or pylorus. GO-POEM was performed without submucosal tunneling., Results: Well-differentiated tubular adenocarcinoma, tubulovillous adenoma with high-grade dysplasia, and tubular adenoma with low-grade dysplasia were diagnosed in three, one, and six patients, respectively. GO-POEM was performed successfully in all the 10 patients. Stenosis could not be evaluated in one patient, whereas one of the remaining nine patients developed post-ESD stenosis. GO-POEM decreased the risk of post-ESD stenosis in the other eight patients. Two patients presented with intraprocedural bleeding, both of whom were managed endoscopically successfully., Conclusions: Prophylactic GO-POEM may be a novel, effective and safe treatment modality for preventing post-ESD stenosis in the stomach. Well-designed, multicenter studies with large sample sizes are needed to confirm our results., (© 2022 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Homeostasis maintains serum metabolites within physiological ranges. For glucose, this requires insulin, which suppresses glucose production while accelerating its consumption. For other circulating metabolites, a comparable master regulator has yet to be discovered. Here we show that, in mice, many circulating metabolites are cleared via the tricarboxylic acid cycle (TCA) cycle in linear proportionality to their circulating concentration. Abundant circulating metabolites (essential amino acids, serine, alanine, citrate, 3-hydroxybutyrate) were administered intravenously in perturbative amounts and their fluxes were measured using isotope labelling. The increased circulating concentrations induced by the perturbative infusions hardly altered production fluxes while linearly enhancing consumption fluxes and TCA contributions. The same mass action relationship between concentration and consumption flux largely held across feeding, fasting and high- and low-protein diets, with amino acid homeostasis during fasting further supported by enhanced endogenous protein catabolism. Thus, despite the copious regulatory machinery in mammals, circulating metabolite homeostasis is achieved substantially through mass action-driven oxidation., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Lumbar spinal stenosis (LSS) is a pathological condition that causes a variety of neurological symptoms due to narrowing of the anatomical structures; usually, conservative treatment is recommended, rather than surgical treatment. Acupotomy combines conventional acupuncture with small scalpels; the procedure can be considered minimally invasive, and has recently received considerable attention in clinical practice. Still, there is a lack of data and randomized controlled trials regarding acupotomy related to LSS. Additional studies are necessary, considering the low methodological quality and small size of the study., Methods and Analysis: This is a pragmatic, pilot, randomized controlled trial. The trial comprises 8 weeks of treatment, with 16 visits and a 4-week follow-up period. Forty participants diagnosed with LSS will be randomly assigned to either the experimental or control groups; both groups will receive acupuncture and interferential current therapy twice a week for 8 weeks, while the experimental group will receive an additional acupotomy intervention once a week for 8 weeks. The primary outcome will be assessed using the visual analog scale; the secondary outcome will be measured by self-rated walking distance, Oswestry Disability Index, and short-form McGill Pain Questionnaire. Measurements will be obtained prior to the start of the clinical trial, 4 weeks after the interventional procedure, 8 weeks after the procedure, and 4 weeks after the end of the interventional procedure. Blood tests and adverse reactions will be performed to ensure safety of the treatments., Conclusion: We expect that this study will provide basic data for future large-scale acupotomy studies regarding LSS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

The objective of this study was to evaluate in vitro antimicrobial and anti-biofilm activity of sodium long chain polyphosphate (SLCPP) and effect of dietary supplementation of SLCPP on growth performance, organ characteristics, blood metabolites, and intestinal microflora of broilers. Antimicrobial activities of SLCPP were observed against Escherichia coli O157:H7, Listeria monocytogenes , Salmonella enterica ser. Pullorum, Shigella sonnei , Klebsiella pneumonia , Pseudomonas aeruginosa in agar well diffusion assay. In addition, SLCPP demonstrated good anti-biofilm activity against K. pneumonia and P. aeruginosa . Furthermore, to investigate the dietary effect of SLCPP, a total of 480 1-day-old male Ross 308 broiler chicks were randomly allotted to three dietary treatment groups (4 replicates per group, 40 birds in each replicate): an antibiotic-free corn-soybean meal basal diet (NC); basal diet + enramycin 0.01% (PC); and basal diet + 0.1% SLCPP (SPP). The experiment lasted for 35 days. Results showed that birds fed with SLCPP had higher body weight (BW) and average daily gain (ADG), and lower feed conversion ratio (FCR) during the grower phase (days 7 to 21) ( p < 0.05). Except for blood urea nitrogen, all other blood biochemical parameters remained unaffected by the dietary supplementation of SLCPP. Compared to the control group, lengths of the duodenum and ileum in the SPP group were significantly shorter ( p < 0.05). Moreover, counts of lactic acid bacteria (LAB), total aerobes, and Streptococcus spp. in jejunum as well as LAB in cecum were increased in the SPP group than in the PC group ( p < 0.05). These results suggest that dietary supplementation of SLCPP might promote the growth of broilers in their early growth phase., Competing Interests: No potential conflict of interest relevant to this article was reported., (© Copyright 2021 Korean Society of Animal Science and Technology.)

Trp8Arg polymorphism of the LH beta gene has decreased bioactivity in vivo and previous studies showed conflicting data on the effect of LH beta gene polymorphism on the IVF outcome. In this study, 591 IVF patients were recruited. Patients with the variant allele(s) were the carrier group. In GnRH antagonist cycles, the clinical pregnancy rate was significantly lower in the carrier group (18.9%) than in the noncarrier group (37.1%). In long GnRH agonist cycles, the clinical pregnancy rate was comparable between both groups. To clarify the effect of COH protocols, IVF outcomes in the GnRH antagonist and long GnRH agonist protocol groups in carriers were analysed. Among carriers, the clinical pregnancy rate was significantly lower in the GnRH antagonist protocol group (18.9%) than in the long GnRH agonist protocol group (45.2%). Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.Impact Statement What is already known on this subject? Trp8Arg polymorphism of the LH beta gene is known to have decreased bioactivity in vivo . Previous studies have demonstrated hypo-sensitivity in the patients with the variant LH beta protein, while other study showed similar carrier frequency between the poor and the normal response group. What the results of this study add? The variant LH beta gene was associated with a lower clinical pregnancy rate in GnRH antagonist cycles but not in long GnRH agonist cycles. What the implications are of these findings for clinical practice and/or further research? Single nucleotide polymorphism analysis may contribute to the individualisation of COH protocols for each patient in the future.

In recent years, considerable and growing attention has been given to the application of host-associated microorganisms as a more suitable source of probiotics in aquaculture sector. Herein, we isolated and screened the olive flounder gut microbiota for beneficial bacterial strains that might serve as potential probiotics in a low fishmeal extruded aquafeed. Among the ten identified isolates, Bacillus amyloliquefaciens SK4079 and B. subtilis SK4082 were screened out based on their heat-resistant ability as well as enzymatic and non-hemolytic activities. Although both strains were well able to utilize carboxymethyl cellulose (CMC), xylan, and soybean meal (SBM) as a single carbon source in the minimal nutrient M9 medium, B. subtilis exhibited significantly higher cellulase, xylanase, and protease activities than B. amyloliquefaciens. The two selected strains were well able to degrade the undesirable anti-nutritional component of the SBM, which would limit its utilization as protein source in aquafeed industry. Significantly higher biofilm formation capacity and notably stronger adhesive interactions with the flounder's skin mucus were detected in B. subtilis than B. amyloliquefaciens. Immobilization of the spores from the selected strains, in a SBM complex carrier, remarkably enhances their thermal resistance at 120 °C for 5 min and different drying conditions. It was also interesting to learn that the B. subtilis spores could survive and remain viable after being sprayed onto extruded low-fish meal feed pellets for as long as 6 months. Overall, the findings of the present study could help the food/feed industries achieve their goal of developing cost-effective yet efficient products., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chicken eggshell (ES) waste is a rich source of calcium carbonate (CaCO 3 ); however, the potential of ES as dietary calcium (Ca) in old laying hens has not been explored. This study compared the effects of feeding limestone, cockle shell, oyster shell, fine ES, and coarse ES as the sole Ca source on production performance, egg quality, blood biochemical constituents, and tibia characteristics in old laying hens. A total of 450 ISA-Brown laying hens at 73 wk of age with similar egg production rate (EPR) were randomly assigned to 5 treatment groups (90 hens/group, 9 hens/replicate) for 7 wk. Dietary treatment groups comprised a corn-soybean meal based diet containing different Ca sources: (i) limestone (LS; < 2 mm and 2-4 mm mixed in the ratio of 3:7) as control, (ii) cockle shell (CS; 1-4 mm), (iii) oyster shell (OS; 3-16 mm), (iv) ES fine particles (ESF; < 1 mm), and (v) ES coarse particles (ESC; 3-5 mm). Results indicated that dietary inclusion of coarse ES particles significantly increased average egg weight (P < 0.001) and daily egg mass (P < 0.05), and decreased feed conversion ratio (P < 0.001) as compared with the other treatments. However, no significant differences in EPR, feed intake, cracked egg proportion, and mortality were observed among the dietary treatments (P > 0.05). Notably, the use of ESF led to a lower proportion of cracked eggs than ESC (P < 0.05). ESC fed hens produced the heaviest eggs whereas CS fed hens produced the lightest (P < 0.001); the particle size of ES also affected the egg weight (P < 0.05). The eggs from OS and ESC fed hens showed a greater albumen height in comparison to eggs from CS group (P < 0.05); but no significant difference was observed among the LS, OS, ESF, and ESC groups (P > 0.05). The yolk color was darker in the eggs of group ESF as compared with other dietary groups (P < 0.01). However, no significant effects on Haugh units and shell properties were observed among the treatments (P > 0.05). The blood biochemistry results were not affected by the dietary Ca (P > 0.05) except for lower levels of high-density lipoprotein percentage (HDL %) in OS and ESC fed hens (P < 0.05). The tibia characteristics including weight, length, width, and breaking strength did not differ among the dietary groups (P > 0.05). However, the ESC and OS fed hens showed higher tibia bone mineral density (BMD) than the other groups (P < 0.001). In conclusion, coarse ES as a sole Ca source had beneficial effects on the production performance, egg quality, and tibia BMD in old laying hens.

This study aimed to investigate the supplemental effects of fermented pine ( Pinus densiflora ) needle extract (FPNE) in laying hen diets on productive performance, egg quality, and serum lipid metabolites. A total of 108 40-week-old Hy-line brown laying hens were randomly assigned to one of the three dietary treatment groups: (1) basal diet + 0 mL FPNE/kg diet (CON), (2) basal diet + 2.5 mL FPNE/kg diet (T1), or (3) basal diet + 5 mL FPNE/kg diet (T2) for 6 weeks. Each group consisted of four replicates of nine hens each. Feed and water provided ad libitum. Results showed that dietary supplementation of FPNE increased egg production percentage (linear, p < 0.01 and quadratic, p < 0.05), egg mass (linear, p < 0.05), and feed intake (linear, p < 0.05) during the entire experimental period. In addition, dietary inclusion of FPNE significantly increased the eggshell color (linear, p < 0.01), egg yolk color (quadratic, p < 0.01), and eggshell breaking strength (linear, p < 0.05 and quadratic, p < 0.05) while the Haugh unit decreased (quadratic, p < 0.05). However, serum lipid profile did not differ among the dietary treatments ( p > 0.05). Notably, antioxidant activity of egg yolk was improved by significantly decreasing the malondialdehyde content in egg yolks after 6 weeks of storage (linear, p < 0.001 and quadratic, p < 0.05). In summary, dietary inclusion of FPNE could improve laying performance and the antioxidant capacity of eggs.

This study uses mobile phone data to examine how socioeconomic status was associated with the extent of mobility reduction during the spring 2020 lockdown in England in a manner that considers both potentially confounding effects and spatial dependency and heterogeneity. It shows that socioeconomic status as approximated through income and occupation was strongly correlated with the extent of mobility reduction. It also demonstrates that the specific nature of the association of socioeconomic status with mobility reduction varied markedly across England. Finally, the analysis suggests that the spatial differentiation in the ability to restrict everyday mobility in response to a national lockdown is an important topic for future research., (Crown Copyright © 2021. Published by Elsevier Ltd. All rights reserved.)