HL Groups Research Articles

Effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet

IntroductionThe aim of this study was to investigate effect of energy levels on liver oxidative state and gut microbiota of laying hens fed a low-protein diet.MethodsA total of 216 laying hens (57-week-old with similar body weight) were randomly divided into 3 groups: low-energy and low-protein diet (LL: 10.73 MJ/kg), middle-energy and low-protein diet (ML: 11.15 MJ/kg), and high-energy and low-protein diet (HL: 11.57 MJ/kg) groups. The experiment lasted for 10 weeks.ResultsResults showed that the liver MDA level was higher, while the liver T-AOC level was lower in the HL group compared with LL and ML groups. The dominant phyla in LL group, ML group, and HL group were Bacteroidetes (38.08%, 39.69%, and 40.93%) and Firmicutes (16.78%, 18.37%, and 17.44%). At the genus level, Alistipes (9.45%) was abundant in the LL group. Bacteroides (14.46%), Phocaeicola (4.48%) and Precotella (2.95%) were highest in the ML group. Parabacteroides (1.78%) and Desulfovibrio (1.02%) were highest in the HL group. At the species level, Bacteroides fragilis (0.42%) is lowest in LL group, Desulfovibrio piger increased with the increase of energy. MDA was significantly and positively correlated with Methanobrevibacter woesei between ML group and HL groups (p < 0.05). T-AOC was highly significantly and positively correlated with Phocaeicola sp. Sa1YUN3 (p < 0.01) .DiscussionThis study found that high-energy and low-protein diets might cause liver oxidative stress by gut microbes in the laying hens.

Biochemical and chemosensory characterization of doubanjiang fermented via two-stage controlled temperature

This study aimed to elaborate the biochemical and chemosensory characteristics of doubanjiang fermentation via a two-stage controlled temperature. HL group with variable temperature (40 °C → 30 °C) and NTF group fermented following traditional technique were prepared and their volatile and non-volatile metabolites were compared through multivariate statistical analysis. HL group favored the accumulation of amino acid nitrogen, free amino acids and organic acids in the early stage and maintained adequate total acids and biogenic amines in the mid-late stage. HL group also had preferred jiang and fruity flavor through sensory evaluation. A total of 116 volatile metabolites were identified in HL or NTF groups and 22 marker volatile metabolites were screened through the combinational use of OPLS-DA and Random Forest analysis. Stronger anti-oxidant ability was observed in HL group while adequate number of acidic compounds and biogenic amines were ensured. This indicated that the two-stage controlled temperature fermentation was beneficial for doubanjiang fermentation.

Effect of Crushed Flaxseed Consumption on Cardiovascular Risk Indicators in Menopausal Women.

Flaxseed is known for its numerous health benefits and is often used in the prevention and treatment of civilizational diseases. This study aimed to evaluate the impact of consuming crushed flaxseed on cardiovascular risk in 51 menopausal women. The intervention lasted for 8 weeks, during which participants received a daily dose of 40 g of crushed flaxseed from two varieties with differing lignan contents. Participants were divided into three subgroups based on the variety of flaxseed consumed: (1) high-lignan group (HL), (2) low-lignan group (LL), and (3) control group (no flaxseed consumption). Biochemical blood parameters were measured using a BiOLis 24i Premium automatic analyzer. Body composition was assessed using an InBody 720 device. In the lipid profile, we observed a significant increase in total cholesterol (T-C) and high-density lipoprotein cholesterol (HDL-C) levels, along with a significant decrease in low-density lipoprotein cholesterol (LDL-C) levels in both the HL and LL groups. Triglyceride (TG) levels exhibited no significant change, whereas high-sensitivity C-reactive protein (hs-CRP) levels were significantly reduced in both the HL (p < 0.01) and LL (p < 0.01) groups. Visceral fat area (VFA) and percent body fat (PBF) showed a slight decreasing trend in the HL group, whereas in the LL group, VFA showed a slight increase. Body mass index (BMI) remained stable across all groups. These findings suggest that for the modulation of cardiovascular disease (CVD) risk factors, the daily dosage, duration of consumption, form of intake, and the specific variety of flaxseed (based on lignan content) are crucial factors.

Transcriptome and metabolome analysis reveals mechanism of light intensity modulating iridoid biosynthesis in Gentiana macrophylla Pall.

Light intensity is a key factor affecting the synthesis of secondary metabolites in plants. However, the response mechanisms of metabolites and genes in Gentiana macrophylla under different light intensities have not been determined. In the present study, G. macrophylla seedlings were treated with LED light intensities of 15 µmol/m2/s (low light, LL), 90 µmol/m2/s (medium light, ML), and 200 µmol/m2/s (high light, HL), and leaves were collected on the 5th day for further investigation. A total of 2162 metabolites were detected, in which, the most abundant metabolites were identified as flavonoids, carbohydrates, terpenoids and amino acids. A total of 3313 and 613 differentially expressed genes (DEGs) were identified in the LL and HL groups compared with the ML group, respectively, mainly enriched in KEGG pathways such as carotenoid biosynthesis, carbon metabolism, glycolysis/gluconeogenesis, amino acids biosynthesis, plant MAPK pathway and plant hormone signaling. Besides, the transcription factors of GmMYB5 and GmbHLH20 were determined to be significantly correlated with loganic acid biosynthesis; the expression of photosystem-related enzyme genes was altered under different light intensities, regulating the expression of enzyme genes involved in the carotenoid, chlorophyll, glycolysis and amino acids pathway, then affecting their metabolic biosynthesis. As a result, low light inhibited photosynthesis, delayed glycolysis, thus, increased certain amino acids and decreased loganic acid production, while high light got an opposite trend. Our research contributed significantly to understand the molecular mechanism of light intensity in controlling metabolic accumulation in G. macrophylla.

PSI-5 Potential Involvement of Ferroptosis in Lipopolysaccharide-Induced Intestinal Inflammation in Broilers

Abstract Ferroptosis is a recently discovered form of programmed cell death that is characterized by iron-dependent lipid peroxidation. Several studies have indicated that ferroptosis might be involved in various intestinal disease, including intestinal ischemia/reperfusion injury, Crohn’s disease and ulcerative colitis. In poultry, inflammatory bowel diseases (IBDs) resulting from pathogen invasion, nutritional deficiencies or environmental factors, might significantly reduce productivity and feed conversion rates of broilers, leading to economic losses for the industry. However, it is unclear whether ferroptosis contributes to the development of IBDs in broilers. In the present study, we aimed to investigate the potential involvement of ferroptosis in the development of intestinal inflammation in broilers. A total of 192 one-day-old Ross308 broilers were randomly divided into four treatments, with 4 pens per treatment and 12 birds per pen. The treatments consisted of intraperitoneal injections of 0.9% sterile saline as control (CON) and 0.5, 1.0, 5.0mg/kg lipopolysaccharide (LPS), respectively (LL, ML, HL). The results showed that the administration of LPS decreased body weight of broilers compared with CON group at 21d of age (P &amp;lt; 0.05). Additionally, at 1 to 21 d of age, the average daily gain of broilers was significantly decreased relative to CON group (P &amp;lt; 0.05). Histological examination revealed that treatment with LPS decreased the villi lengths while increased the crypt depths of ileum in HL group compared with CON group (P &amp;lt; 0.05). Furthermore, the relative mRNA expression of lipid peroxidation and iron accumulation-associated genes were significantly increased in jejunum and ileum in HL group (P &amp;lt; 0.05). Importantly, the untargeted metabolomics analysis of serum samples showed that cysteine and methionine metabolism was the most significant pathway differences between HL and CON groups, indicating that the key antioxidant in ferroptosis mechanism, glutathione, might be affected after the administration of LPS. The results suggested that ferroptosis might be involved in LPS-induced intestinal inflammation in broilers. Further investigations are required to elucidate the underlying mechanisms of how ferroptosis contributes to inflammatory bowel disease in broilers.

3 Emotional Expression in Infants with Agenesis of the Corpus Callosum: The Role of Callosal Connectivity in Early Temperament

Objective:Accumulating evidence suggests that corpus callosum development is critically involved in the emergence of behavioral and cognitive skills during the first two years of life and that structural abnormalities of the corpus callosum are associated with a variety of neurodevelopmental disorders. Indeed by adulthood ∼30% of individuals with agenesis of the corpus callosum (ACC), a congenital condition resulting in a partial or fully absent corpus callosum, exhibit phenotypic features consistent with autism spectrum disorder (ASD). However, very little is known about developmental similarities and/or differences among infants with ACC and infants who develop ASD. This study describes temperament in infants with ACC during the first year of life in comparison with a neurotypical control group. Additionally, it examines the potential contribution of disrupted callosal connectivity to early expression of temperament in ASD through comparison to children with high familial likelihood of ASD.Participants and Methods:Longitudinal ratings of positive and negative emotionality were acquired at 6 and 12 months on the Infant Behavior Questionnaire-Revised across four groups of infants: isolated complete and partial ACC (n=104), high familial likelihood of ASD who do and do not have a confirmed ASD diagnosis (HL+ n=81, HL- n=282), and low-likelihood controls (LL- n=152).Results:Overall, the ACC group demonstrated blunted affect, with significantly lower positive and negative emotionality than LL controls at both timepoints. Specifically, the ACC group exhibited lower activity and approach dimensions of positive emotionality at both timepoints, with lower high-intensity pleasure at 6 months and lower vocal reactivity at 12 months. On negative emotionality subscales, the ACC group exhibited lower distress to limitations and sadness at both timepoints, as well as lower falling reactivity at 6 months. The ACC and HL groups did not differ significantly on positive emotionality at either timepoint. However, negative emotionality was lower in the ACC group than the HL- group at both timepoints and lower than the HL+ group at 12 months, with lower distress to limitations and sadness ratings than both HL groups at both timepoints.Conclusions:These findings highlight the importance of interhemispheric connections in facilitating active engagement and pursuit of pleasurable activities during the first year of life, as well as expression of sadness and distress to limitations. Notably, similarities between infants with ACC and infants at elevated familial risk of ASD suggest that disrupted callosal connectivity may specifically contribute to reductions in positive emotionality.

Self-fertilization in a gonochoristic fish yellow catfish

Sex control techniques are in great demand for aquaculture because of the huge benefits of mono-sex production. In a previous study on yellow catfish (Tachysurus fulvidraco), intersex individuals were produced by administrating 17α-methyltestosterone (MT) or aromatase inhibitor letrozole (LZ). The ovarian and testicular portions of intersexual gonads developed well and were completely separated, arousing our interest in producing self-fertilizable fish and clone-like fish populations. In this study, yellow catfish fry were treated with a combination of MT and LZ at a low dose (5 mg kg−1 MT, 300 mg kg−1 LZ) at a low water temperature (27.0 °C, mixed sex-producing temperature, LL group) and a high temperature (33.5 °C, male-producing temperature, HL group), and with a high dose (10 mg kg−1 MT, 600 mg kg−1 LZ) at a low water temperature (LH group), during 12–65 days post-hatching, the critical period of sex differentiation. Both XX and XY intersex were produced with different percentages at the same time through co-treatment with MT and LZ, with or without the help of male-producing temperature. The highest percentage of XY intersex (53% in XY, 36% in XX and XY) and XX intersex (47% in XX, 25% in XX and XY) was produced in LH and HL groups, respectively. Results of gonadal morphology, histology, and sperm dynamic analysis indicate that some XX and XY intersex individuals were capable of self-fertilization through artificial insemination. The reproductive performance of these intersex individuals was then investigated by injecting spawning agents, dissecting gonads, and artificially fertilizing eggs with their own sperm. The XX, XY, and YY genotypic individuals were produced by the self-fertilization of XY intersex individuals. The present study successfully produced high percentages of XX and XY intersex and conducted self-fertilization by mating the eggs and sperm of a single intersex individual. Self-fertilization in fish will show great potential in aquaculture genetics and breeding, for example, generating highly homozygous (or ‘‘clonal’’) genetic material, producing mono-sex populations, and identifying unknown sex determination modes. In particular, the cloning method of producing genetic materials will be greatly beneficial for maintaining advantageous traits through self-fertilization generation after generation.

The physical, mechanical and fire performance of bamboo scrimber processed with thermal-treated bamboo bundles

Thermal treatment is gaining increasing attention for bamboo modification in practical production due to its advantages of simplicity, effectiveness and environmental friendliness, particularly in the production of bamboo scrimber. The objective of this study is to investigate the effects of two typical thermal modification methods on the physical, mechanical and fire performance of bamboo scrimber, as well as the related physicochemical properties of bamboo bundles for production purpose. The results indicated that the two types of bamboo scrimber processed distinct advantages in terms of physical and mechanical performances. Specifically, the one processed with bamboo bundles treated by superheated steam at a temperature of 200 ℃ (referred to as the “HL group”), exhibited exceptional dimensional stability and fire resistance, while exhibiting slightly lower mechanical properties. Notably, the HL group exhibited a significantly more pronounced hue compared to the LS group, which was treated with saturated vapor at a temperature of 140 ℃. Both demonstrated exceptional water resistance, with the HL group surpassing that of the LS group in either 24-hour room temperature or a combination of boiling-drying cycling treatments. The MORs of the LS group were determined to be 152.3 MPa and 108.5 MPa under dry and wet conditions, respectively, exhibiting significantly higher values than those observed in the HL group. Conversely, the variation of MOEs was found to be opposite. Both MORs and MOEs of the two groups exhibited a significant decrease in wet condition compared to those in dry condition, with reductions linearly correlated to water absorption of the samples. The failure mode of the LS group demonstrated elastoplastic failure characterized by a “Z-shaped”, while the HL group exhibited with a relatively flat cross-section. Furthermore, the HL group demonstrated superior fire performance in comparison to the LS group, and as evidenced by a significantly denser char residue surface with fewer and wider cracks than that of the LS group. The variations of chemical components and microstructures in bamboo can be attributed to variances in the extent of degradation of hemicellulose, lignin, and even cellulose during the thermal modification processes. The water resistance, dimensional stability and fire performance of bamboo scrimber can be significantly improved through thermal treatment, while resulting in a decrease in MOR, particularly for the HL group. The HL and LS groups of bamboo scrimber both exhibited excellent performances, making them suitable for application as structural engineering materials. The work we conducted offers experimental and theoretical support for improve the pre-treatment procedures of bamboo in the manufacturing of bamboo scrimber for structural utilizations.

Age‐related hearing loss and neural correlates of visual short‐term memory

AbstractBackgroundAge‐related hearing loss (ARHL) may be a potential modifiable risk factor for neurocognitive decline and dementia. Previous studies have reported HL is associated with decline in visual memory function. Evidence also suggests that following ARHL, there is neural reorganization in regions critical for memory. The aim of this pilot was to explore the association of ARHL with neural correlates of visual short‐term memory binding (VSTMB).MethodParticipants over the age of 65 were recruited and divided into three groups (controls (n = 14), mild HL (n = 21), and moderate or greater HL (n = 23)) based on results from a tablet‐based hearing measure. Volunteers completed the VSTMB task (shapes and binding conditions) while electroencephalography (EEG) data was synchronously recorded using a high‐density EEG array (128 scalp electrodes). Analysis was focused on comparing 5 different components (P1, N1, P2, P3, and late positive potential (LPP)) between both HL groups to controls for the memory encoding and testing phases on both shapes and binding conditions. Statistical analysis of source reconstructions (sLORETA) was also performed to explore neural regions underlying VSTMB.ResultThere was no difference between groups in behavioral performance on the VSTMB task. There were a limited number of differences in electrophysiological activity, primarily in P1, P2, P3 and LPP which increased from mild to moderate or greater HL. Analyses of source reconstructions suggested there were bilateral differences in frontal, central, parietal, temporal, and occipital neural regions between groups.ConclusionThere were no differences in behavioral outcomes in VSTMB with HL. There may be underlying differences in neural activity on this task with greater HL which is in accordance with prior research. Further investigation into differences in neural processes underlying episodic memory with HL would be informative, particularly to examine if such differences are associated with future memory function.

Serum Metabolites Associated with Muscle Hypertrophy after 8 Weeks of High- and Low-Load Resistance Training.

The mechanisms responsible for the similar muscle growth attained with high- and low-load resistance training (RT) have not yet been fully elucidated. One mechanism is related to the mechanical stimulus and the level of motor unit recruitment; another mechanism is related to the metabolic response. We investigated the electromyographic signal amplitude (sEMG) and the general metabolic response to high-load RT (HL) and low-load resistance training (LL). We measured muscle thickness by ultrasound, sEMG amplitude by electromyography, and analysis of metabolites expressed through metabolomics. No differences were observed between the HL and LL groups for metabolic response and muscle thickness. A greater amplitude of sEMG was observed in the HL group. In addition, a correlation was observed between changes in muscle thickness of the vastus lateralis muscle in the HL group and levels of the metabolites carnitine, creatine, 3-hydroxyisovalerate, phenylalanine, asparagine, creatine phosphate, and methionine. In the LL group, a correlation was observed between changes in muscle thickness of the vastus lateralis muscle and levels of the metabolites acetoacetate, creatine phosphate, and oxypurinol. These correlations seem to be related to the characteristics of activated muscle fibers, the metabolic demand of the training protocols used, and the process of protein synthesis.

Low-Load Resistance Exercise with Blood Flow Restriction Increases Hypoxia-Induced Angiogenic Genes Expression.

The aim of the study was to determine whether low-load exercise (LL) with blood flow restriction (LL-BFR) would induce similar changes in expression of genes involved in hypoxia and angiogenesis compared to LL and high-load exercise (HL). Twenty-four males (age: 21.3 ± 1.9 years, body height: 1.74 ± 0.8 m, body mass: 73 ± 1.8 kg) were allocated into three groups: low-load exercise (LL), low-load exercise with blood-flow restriction (LL-BFR), and high-load exercise (HL). For the LL-BFR group a pneumatic cuff was inflated at 80% of the arterial occlusion pressure. All participants performed bilateral knee extension exercise, twice a week, for 8 weeks. LL and LL-BFR groups performed 3-4 sets of 15 reps at 20% 1RM, whilst the HL group performed 3-4 sets of 8-10 reps at 80% 1RM with a 60-s rest interval between sets. The hypoxia-inducible factor-1 alpha (HIF-1α) and beta (HIF-1β), vascular endothelial growth factor (VEGF), neuronal (nNOS), and inducible nitric oxide synthase (iNOS) genes expression were assessed before and after training. HIF-1α and HIF-1β mRNA levels significantly increased in the LL-BFR group and exceeded those elicited by HL and LL groups (p < .0001). VEGF gene expression was increased in both LL-BFR and HL groups, however, LL-BFR elicited a greater increase than LL (p < .0001). nNOS and iNOS genes expression significantly increased in all groups with greatest increases being observed in the LL-BFR group (p < .0001). The findings suggest that LL-BFR induces greater increases in genes expression related to hypoxia and angiogenesis than traditional resistance training.

Effect of 1st line treatment on aortic inflammation as assessed by 18 FDG PET/CT in patients with Hodgkin and non-Hodgkin lymphoma

Abstract Background Despite advances in the treatment of oncology patients, therapy-related side effects may lead to premature morbidity among cancer survivors. Inflammatory activation that has been linked to cardiovascular disease is particularly crucial for the pathogenesis of both Hodgkin (HL) and non-Hodgkin lymphoma (NHL). Objectives To assess the vascular effects of chemotherapy in patients with HL and NHL by 18-Fluorodeoxyglucose (FDG PET/CT) and to investigate possible interactions with systemic inflammation as assessed by circulating inflammatory markers. Methods Between July 2015 and July 2019, sixty-five consecutive patients (37 males, mean age 56±17.8 years) with histologically confirmed new diagnosis of either HL (n=33) or NHL (n=32), were prospectively studied. PET/CT imaging was performed at baseline, at an interim phase and after 1st line treatment. Aortic FDG uptake was assessed by measuring global aortic TBR. Serum interleukin-6 (IL6) and interleukin-1b (IL1b) were measured at each phase for all patients and served as circulating inflammatory markers. Results Patients with HL demonstrated significant reduction in aortic TBR after 1st line treatment (aortic TBRbaseline=1.98, aorticTBR3rdscan=1.75, p=0.001, F=8.335), which remained significant after adjustment for 10-year cardiovascular risk (Framingham risk score), dyslipidemia, hypertension and diabetes (p=0.002, F=7.664). In contrast, patients with NHL did not demonstrate a significant aortic inflammation response (aortic TBRbaseline = 2.13, aorticTBR3rd scan=2.015, p=0.596, F=0.527), Figure 1. Regarding inflammatory markers, after 1st line treatment IL6 levels were reduced significantly in both HL and NHL groups (IL6baseline HL=3.25, IL6 post 1st line treatment HL=0.448, p=0.00; IL6baseline NHL=0.475, IL6 post 1st line treatment NHL=0.144, p=0.001); IL1b levels did not change significantly in either group, Table 1. Conclusions We demonstrate for the first time that aortic inflammation as assessed by 18-FDG PET-CT is reduced in HL patients after 1st line treatment but not in NHL patients. These findings imply that different pathophysiological pathways and different therapies might affect the arterial bed in different ways in lymphoma patients. Further, a strong potential role of molecular imaging in cardio-oncology emerges, offering valuable information on disease prognosis and progression with a single examination. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): Hellenic Society of Hypertension

Leveraging genomic diversity for discovery in an electronic health record linked biobank: the UCLA ATLAS Community Health Initiative

BackgroundLarge medical centers in urban areas, like Los Angeles, care for a diverse patient population and offer the potential to study the interplay between genetic ancestry and social determinants of health. Here, we explore the implications of genetic ancestry within the University of California, Los Angeles (UCLA) ATLAS Community Health Initiative—an ancestrally diverse biobank of genomic data linked with de-identified electronic health records (EHRs) of UCLA Health patients (N=36,736).MethodsWe quantify the extensive continental and subcontinental genetic diversity within the ATLAS data through principal component analysis, identity-by-descent, and genetic admixture. We assess the relationship between genetically inferred ancestry (GIA) and >1500 EHR-derived phenotypes (phecodes). Finally, we demonstrate the utility of genetic data linked with EHR to perform ancestry-specific and multi-ancestry genome and phenome-wide scans across a broad set of disease phenotypes.ResultsWe identify 5 continental-scale GIA clusters including European American (EA), African American (AA), Hispanic Latino American (HL), South Asian American (SAA) and East Asian American (EAA) individuals and 7 subcontinental GIA clusters within the EAA GIA corresponding to Chinese American, Vietnamese American, and Japanese American individuals. Although we broadly find that self-identified race/ethnicity (SIRE) is highly correlated with GIA, we still observe marked differences between the two, emphasizing that the populations defined by these two criteria are not analogous. We find a total of 259 significant associations between continental GIA and phecodes even after accounting for individuals’ SIRE, demonstrating that for some phenotypes, GIA provides information not already captured by SIRE. GWAS identifies significant associations for liver disease in the 22q13.31 locus across the HL and EAA GIA groups (HL p-value=2.32×10−16, EAA p-value=6.73×10−11). A subsequent PheWAS at the top SNP reveals significant associations with neurologic and neoplastic phenotypes specifically within the HL GIA group.ConclusionsOverall, our results explore the interplay between SIRE and GIA within a disease context and underscore the utility of studying the genomes of diverse individuals through biobank-scale genotyping linked with EHR-based phenotyping.

Blood-Flow-Restriction-Training-Induced Hormonal Response is not Associated with Gains in Muscle Size and Strength.

The aim of this study was to determine whether increases in post-exercise endocrine response to low-load resistance exercise with blood flow restriction and high-load resistance exercise would have association with increases in muscle size and strength after an 8-week training period. Twenty-nine untrained men were randomly allocated into three groups: low-load resistance exercise with (LL-BFR) or without blood flow restriction (LL), and high-load resistance exercise (HL). Participants from LL-BFR and LL groups performed leg extension exercise at 20% of one repetition maximum (1RM), four sets of 15 repetitions and the HL group performed four sets of eight repetitions at 80% 1RM. Before the first training session, growth hormone (GH), insulin-like growth factor 1 (IGF-1), testosterone, cortisol, and lactate concentration were measured at rest and 15 min after the exercise. Quadriceps CSA and 1RM knee extension were assessed at baseline and after an 8-week training period. GH increased 15 min after exercise in the LL-BFR (p = 0.032) and HL (p < 0.001) groups, with GH concentration in the HL group being higher than in the LL group (p = 0.010). There was a time effect for a decrease in testosterone (p = 0.042) and an increase in cortisol (p = 0.005), while IGF-1 remained unchanged (p = 0.346). Both muscle size and strength were increased after training in LL-BFR and HL groups, however, these changes were not associated with the acute post-exercise hormone levels (p > 0.05). Our data suggest that other mechanisms than the acute post-exercise increase in systemic hormones induced by LL-BFR and HL produce changes in muscle size and strength.

Health Economic Evaluation of a High and Low Molecular Weight Hyaluronic Acid Formulation for the Treatment of Knee Osteoarthritis. Post Hoc Analyses from a Randomized Clinical Trial.

IntroductionIn a recent randomized placebo-controlled trial, a single intra-articular injection of a high and low molecular weight hyaluronic acid formulation (HA–HL) was shown to be effective in providing a clinically meaningful reduction in pain and functional limitation up to 24 weeks in subjects with painful knee osteoarthritis (OA). The objective of this post hoc analyses is to assess the cost-effectiveness of HA–HL compared with placebo using individual patient data from this clinical trial in a Swiss health care perspective.MethodsA total of 692 patients fulfilling the inclusion criteria were randomly allocated to HA–HL or placebo groups. Each patient received one intra-articular injection of HA–HL or placebo at baseline and was then followed-up for a total duration of 24 weeks with five follow-up visits (i.e., after weeks 1, 6, 12, 18, and 24). The EQ-5D-5L five-point verbal Likert scale was used to calculate the health utility and the related quality-adjusted life-years (QALYs) using the area-under-the-curve (AUC) method. For the costs, the price of HA-HL in Switzerland was used. The primary threshold for the incremental cost/effectiveness ratio (ICER) below which HA-HL was considered as cost-effective was 91,540 Swiss francs (CHF) per QALY (i.e., US $100,000).ResultsNo significant difference between the baseline characteristics of the HA–HL group and the placebo group was observed. With a mean ICER of 27,212 CHF per QALY (95% CI 20,135–34,289), HA–HL was considered as cost-effective compared to placebo. Sensitivity analyses (e.g., using lower or upper limit prices or using other threshold values) gave similar results, i.e., ICERs far below the threshold values of cost-effectiveness.ConclusionsThese results confirm the role of HA–HL as a cost-effective therapeutic option in the management of OA. However, more studies taking into account the utilization of other health care resources are needed.

Frequency and natural course of congenital cytomegalovirus-associated hearing loss in children

Background Congenital cytomegalovirus-associated hearing loss (cCMV-associated HL) is a common cause of congenital or early-onset deafness. Although cCMV infection has been reported to lead to various types of HL, the natural course of cCMV-associated HL over a long period is not yet known. Objectives To investigate the clinical phenotype of cCMV-associated HL in the largest study to date. Methods Thirty-one CMV-positive children, diagnosed by examining CMV DNA extracted from their dried umbilical cords retrospectively, were divided into unilateral and bilateral HL groups, and their hearing ability was evaluated using pure-tone audiometry and auditory steady-state response over time. Results Thirteen patients (41.9%) had unilateral HL and 18 (58.1%) had bilateral HL. In most cases of unilateral cCMV-associated HL, the ear with better hearing maintained a normal hearing threshold. Notably, in most cases of both unilateral and bilateral HL, the ear with worse hearing ultimately showed severe to profound HL. Conclusion Our findings revealed that the natural course of cCMV-associated HL was different between the cases of unilateral and bilateral HL, as well as between the ears with better or worse hearing in all cases. These findings indicate that accurate diagnosis could enable proper follow-up and management of cCMV-associated HL in children.

Metabolic response of Mercenaria mercenaria under heat and hypoxia stress by widely targeted metabolomic approach

In the context of global climatic changes, marine organisms have been exposed to environmental stressors including heat and hypoxia. This calls for the design of multi-stressors to uncover the impact of oceanic factors on aquatic organisms. So far, little is known about the metabolic response of marine organisms, especially bivalves, to the combined effects of heat and hypoxia. In this study, we employed widely targeted metabolomic analysis to study the metabolic response of gills in hard clam, a heat- and hypoxia-tolerant bivalve. A total of 810 metabolites were identified. Results showed that the heat group (HT) and heat plus hypoxia group (HL) had a higher number of differential metabolites than the hypoxia group (LO). Glycolysis was affected by the heat and heat plus hypoxia stress. Moreover, anaerobic metabolic biomarkers were accumulated marking the onset of anaerobic metabolism. Environmental stresses may affect Tricarboxylic acid (TCA) cycle. Accumulation of carnitine and glycerophospholipid may promote fatty acid β oxidation and maintain cell membrane stability, respectively. The high content of oxidized lipids (i.e., Leukotriene) in HL and HT groups implied that the organisms were under ROS stress. The significantly differential metabolites of organic osmolytes and vitamins might relieve ROS stress. Moreover, accumulation of thermoprotective osmolytes (monosaccharide, Trimethylamine N-oxide (TMAO)) accumulation was helpful to maintain protein homeostasis. This investigation provided new insights into the adaptation mechanisms of hard clam to heat, hypoxia and combined stress at the metabolite level and highlighted the roles of molecules and protectants.

Heat and Hypoxia Exposure Mediates Circadian Rhythms Response via Methylation Modification in Apostichopus japonicas

As global warming progresses, heat and hypoxia are gradually becoming important factors threatening the survival, reproduction, and development of marine organisms. To determine the effect of heat and hypoxia on Apostichopus japonicus, whole genome methylation of the respiratory tree was determined under heat, hypoxia, and heat-hypoxia conditions [designed as heat stress treatment (HT), hypoxia treatment (LO), and heat-hypoxia combined treatment (HL) groups]. The number of differentially methylated regions (DMRs) under three treatments was determined based on the Venn diagram. The network of the DMRs associated with promoters that were co-existed under the three conditions showed that circadian rhythm was involved based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Circadian rhythm-related genes, CRY1a, CRY1b, CLC, and TIM, decreased in LO and HL groups, while CRY1a, CRY1b, and BMAL1 increased in the HT group. Bisulfite sequencing PCR (BSP) showed that the methylation levels of CpG island regions in the promoters of CRY1a and CRY1b were upregulated in HT, LO, and HL groups, leading to the decreased promoter activity of CRY1a and CRY1b. RNAi of CRY1a and CRY1b led to increased enzyme activities of two energy-related enzymes, pyruvate kinase (PK) catalyzing the rate-limiting step in glycolysis, and ATPase hydrolyzing ATP to ADP, which were also increased under the three tested conditions. Thus, it was concluded that A. japonicus may respond to the heat, hypoxia, and heat-hypoxia stresses via the DNA methylation of heat, hypoxia, and heat-hypoxia stresses via the DNA methylation of CpG islands of circadian rhythm-related genes, which increased the activity of energy-related enzymes.

Low-intensity pulsed ultrasound attenuates replacement root resorption of avulsed teeth stored in dry condition in dogs

This study aimed to investigate the effects of low-intensity pulsed ultrasound (LIPUS) on replacement root resorption after replantation of avulsed teeth stored in a dry condition in dogs. A total of 73 premolar roots from four male mongrel dogs were intentionally avulsed with forceps and divided into four groups—HN, HL, DN, and DL—according to storage conditions and whether or not they received LIPUS treatment. Thirty-eight roots were kept in Hanks’ Balanced Salt Solution for 30 min (HN and HL groups), whereas the remaining 35 roots were left to dry in the air for an hour (DN and DL groups) prior to replantation. Following replantation, the roots in the HL and DL groups (21 and 18 roots, respectively) received a 20-min daily LIPUS treatment for 2 weeks. The animals were euthanized 4 weeks after the operation. Micro-computed tomography images were acquired for each root and the amount of replacement root resorption was measured three-dimensionally. Histological assessments were also carried out. There was significantly less replacement root resorption for the roots in the DL group compared to the DN group (p < 0.01). Histological findings in the DN group demonstrated evident replacement root resorption, whereas the DL group revealed less severe resorption compared to the DN group. Within the limitations, these results suggest that LIPUS could attenuate the replacement resorption of avulsed teeth stored in a dry condition, thereby improving their prognosis.

Regulatory effects of Lactobacillus fermented black barley on intestinal microbiota of NAFLD rats

Gut microbiota dysbiosis and oxidative stress may play important roles in the progression of nonalcoholic fatty liver disease (NAFLD). Fermented foods contain probiotics and other bioactive components that may improve gastrointestinal health and provide other health benefits. Here, we investigated the effect of Lactobacillus-fermented black barley on NAFLD rats. Adult Sprague Dawley rats were randomized into four groups: normal chow diet (NC), high-fat diet (HF), HF + fermented black barley treatment (HB) and HF + Lactobacillus treatment (HL). The rats in the HB and HL groups were continuously administered fermented black barley or Lactobacillus, respectively, for 12 weeks (1 mL/100 g·BW, containing 1 × 108 CFU/mL Lactobacillus). Compared with the HF treatment, HB treatment effectively inhibited the increase in body weight, liver and abdominal fat indexes and hepatic lipids (p < 0.01), increased hepatic SOD activity (p < 0.05), decreased thiobarbituric acid reactive substances (TBARSs) (p < 0.01) and improved liver function. Moreover, Lactobacillus-fermented black barley exhibited regulatory effect on high-fat diet-induced intestinal microbiota dysbiosis by increasing the relative microbiota abundance and diversity, increasing the relative abundance of Bacteroidetes, decreasing the Firmicutes/Bacteroidetes ratio, increasing the abundances of some intestinal probiotics (such as Akkermansia and Lactococcus), and influencing some of the fecal metabolites related to hormones and lipid metabolism. The supplementation of fermented cereal food might be a new effective and safe preventive dietary strategy against NAFLD.