HA Treatments Research Articles

Unveiling differential impact of heat and microwave extraction treatments on the structure, functionality, and digestibility of jack bean proteins extracted under varying extraction pH

The poor extractability and digestibility of jack beans restrict their application in food systems. Thermal treatment could be a processing tool to disrupt the compact conformation of the plant matrix and inactivate inherent antinutrients. Therefore, this research investigated the impact of conventional heat-aided (HA-) and microwave-aided (MA-) extraction treatments on the structure, functional properties, and digestibility of jack bean protein concentrate (JBPC) under varying extraction pH. The novelty brought by the present study is establishing the thermal treatment/extraction pH combinations for improving techno-functionalities and digestibility of JBPC. Heat (50 °C for 1 h) and sequential microwave power (400 W, 600 W, and 800 W for 5 min) at three extraction pH (9.0, 10.0, and 11.0) were studied. Upon increasing extraction pH, a significant decrease in the protein content, and β-Sheet structure was observed, in the order of pH 11.0 > 10.0 > 9.0. JBPC extracted using HA treatments displayed the highest contents of surface hydrophobicity (90.02) and sulfhydryl groups. In functional properties, MA-extracted JBPC under 400 W showed significantly improved solubility (93.45 %), emulsifying activity index (45.23 m2/g), and foaming capacity (141.70 %) when compared to other thermal treatments. The degree of hydrolysis result revealed that MA treatment improved the JBPC in vitro digestibility at a low power level of 400 W. These findings suggest that MA extraction treatment can improve the functional and nutritional properties of JBPC regardless of the extraction pH, and thus, expand the potential application in food systems.

Sun exposure and high preharvest fruit temperatures increase antioxidants, heat shock proteins and thermotolerance of mango fruit (Mangifera indica L.)

ABSTRACT Preharvest sun-exposure can improve the tolerance of fruit during postharvest handling conditions and thus we examined the postharvest responses of mangos. Sun-exposed and shaded fruit of ‘Keitt’ and ‘Reynal’ mango were harvested and assessed for external and internal damage following postharvest hot water (HW 55°C/50min) and hot air (HA 47°C/20min; 49°C/90min) treatments used for fruit fly disinfestation. Heat shock proteins and antioxidant systems were examined as possible biochemical strategies for stress protection of fruit tissues. With maximum air temperatures <37°C, fruit exposed to direct sunlight reached temperatures up to 47°C. Following HW, sun-exposed ‘Reynal’ fruit had less external damage than shaded fruit, with damage mainly on the exposed surfaces. In contrast, sun-exposed and shaded ‘Keitt’ fruit had similar levels of damage following HW. For both cultivars, HA treatments of either sun-exposed or shaded fruit did not cause any significant external damage, but internal damage was observed. Both cultivars exhibited biochemical stress responses. Hsp17.4 in the flesh of sun-exposed ‘Reynal’ and ‘Keitt’ fruit were 2 and 6 times higher than in shaded fruit, respectively. Total polyphenols and anthocyanins were higher in tissues of sun-exposed than shaded fruit. Results are discussed in terms of the different biochemical defence strategies among these cultivars.

Organic Amendments promote saline-alkali soil desalinization and enhance maize growth.

Secondary soil salinization in arid and semi-arid regions is a serious problem that severely hampers local agricultural productivity and poses a threat to the long-term sustainability of food production. the utilization of organic soil amendments presents a promising approach to mitigate yield losses and promote sustainable agricultural production in saline-alkali soil. In this study, we established four distinct treatments, chemical fertilizer (CK), humic acid with chemical fertilizer (HA), carboxymethyl cellulose with chemical fertilizer (CMC), and amino acid with chemical fertilizer (AA), to elucidate their respective impacts on the reclamation of saline soil and the growth of maize. The findings of our study reveal notable variations in desalination rates within the 0-40 cm soil layer due to the application of distinct soil amendments, ranging from 11.66% to 37.17%. Moreover, application of amendments significantly increased the percentage of soil macro-aggregates as compared to the CK treatment. Furthermore, HA and AA treatments significantly augmented soil nutrient content (HA: 48.07%; AA: 39.50%), net photosynthetic rate (HA: 12.68%; AA: 13.94%), intercellular CO2 concentration (HA: 57.20%; AA: 35.93%) and maize yield (HA:18.32%; AA:16.81%). Correlation analysis and structural equation modeling unveiled diverse mechanisms of yield enhancement for HA, CMC, and AA treatments. HA enhanced yield by increasing organic matter and promoting soil aggregate formation, CMC improved soil water content and facilitated salt leaching due to its excellent water-holding properties, while AA increased yield by elevating soil organic matter and effective nitrogen content. Among the array of soil amendment materials scrutinized, HA treatment emerged as the most promising agent for enhancing soil conditions and is thus recommended as the preferred choice for treating local saline soils.

Local injection therapy in the complex treatment of musculoskeletal disorders: principles of application, evidence base, safety

Local injection therapy (LIT) is an important component of the complex treatment of musculoskeletal disorders (MSD), which is widely used in real clinical practice. Glucocorticoids, hyaluronic acid drugs (HA), autologous cell drugs, botulinum toxin type A, radioactive isotopes, etc. are used for LIT. LIT makes it possible to achieve a pronounced symptomatic effect, while in some cases, for example, repeated HA treatments in patients with osteoarthritis, the possibility of slowing the progression of the disease and reducing the need for surgical treatment is discussed.The performance of LIT requires special skills and abilities of the physician, careful compliance with the rules of asepsis and antisepsis, and instrumental visualization. LIT can be associated with serious complications and therefore must be performed according to strict indications.The Expert Council was devoted to defining the basic principles of LIT. The indications for the use of certain types of this therapies, the evidence base for its efficacy and safety, the order of application of different drugs, and the need to combine LIT with other drug and non-drug treatments of MSD were reviewed.

The Effect of Nitrogen and Humic Acid Treatments on Some Characteristics of Faba Bean (Vicia faba L.)

In addition to its agricultural characteristics, the faba bean plant is a remarkable plant due to its L-DOPA content. In this study, In this study, the effects of 3 different humic acid doses (HA0: control, HA1:2 l da-1, HA2:6 l da-1) and nitrogen fertilizer (5 kg da-1) treatments on some characteristics of Lara and Maçka genotypes and L-DOPA content in its flowers were investigated. The trial was carried out in the Strip Plots Trial Design in Samsun in one year. According to the findings, the effect of HA treatments on the amylose content in the seed was found to be statistically significant, and the values obtained from the treatments were equivalent to the control values in other examined properties. It has been determined that there are statistically significant differences between genotypes in many of the characteristics examined; It was determined that the flower yield and the amount of L-DOPA transferred to the tea water were higher in Maçka genotype.

Mim8 Clinical Development Program: An Overview of the Frontier Studies

Background Mim8 is a bispecific antibody, mimicking activated factor VIII (FVIIIa), currently in clinical development as a treatment for patients with hemophilia A (PwHA), independent of inhibitor status. Preclinical data demonstrate that Mim8 is highly potent with an efficacious hemostatic effect. The FRONTIER program aims to expedite Mim8 development, recruiting participants from >30 countries including women, previously untreated patients (PUPs), and patients with mild/moderate disease severity. FRONTIER 1 (NCT04204408; EudraCT:2019-000465-20), a phase 1/2 study of Mim8 in healthy participants and PwHA, provided proof of concept that Mim8 enables clinically relevant levels of thrombin generation with no safety concerns, and no occurrences of anti-Mim8 antibodies. The study also used biomarker bridging (in vitro and ex vivo) to benchmark against emicizumab. The outcomes from FRONTIER 1 support the further development of Mim8 in the ongoing phase 3 studies (FRONTIER 2 and 3). Methods & Study Design To allow for rapid clinical development, the observational run-in phases of both phase 3 studies were initiated prior to FRONTIER 1 completion (Figure 1A) and are running in parallel. FRONTIER 2 (NCT05053139; EudraCT:2020-001048-24) is an ongoing, open-label, randomized control study investigating the efficacy and safety of Mim8 dosed once-weekly (QW) and once-monthly (QM) in adult and adolescent PwHA (≥12 years of age). The study aims to recruit ~250 PwHA. The primary endpoint is the annualized bleeding rate. Prior to their first Mim8 dose, patients currently on FVIII or bypassing agent prophylaxis will remain on this treatment for ≥26-week observational run-in period (Figure 1B). Patients currently treated on demand with ≥5 bleeds in the 26 weeks prior to screening can join the main phase of the trial without a run-in period. Participants receiving emicizumab must discontinue use and switch to factor prophylaxis when entering the run-in period. Exclusion criteria include planned major surgery, ongoing/planned immune tolerance induction (ITI), and previous or current thromboembolic diseases/events. FRONTIER 3 (NCT05306418; EudraCT:2020-003467-26) is an ongoing, open-label, uncontrolled study investigating the safety of Mim8 in pediatric PwHA (aged 1-11 years). It is targeting recruitment of 70 children with HA with or without inhibitors, who will receive subcutaneous doses of Mim8 QW for 26 weeks. Thereafter, participants can choose between QW and QM prophylaxis regimen for the next 26 weeks (Figure 1B). The primary endpoint is the number of treatment-emergent adverse events during the 52-week treatment period. Key inclusion criteria for FRONTIER 3 include: previously treated patients prescribed FVIII, or by-passing agents, and PUPs with severe HA. Key exclusion criteria are the same as FRONTIER 2. ITI would need to be discontinued prior to joining the trial. To collect further data on the safety and efficacy of Mim8, FRONTIER 1-3 study participants will be invited to join the long-term, open-label extension FRONTIER 4 study. Additionally, plasma samples will be collected from participants with the aim of future exploratory analysis of further biomarkers. Conclusions The FRONTIER studies are a comprehensive clinical development program designed to evaluate Mim8 in PwHA, with or without inhibitors. The FRONTIER 2 and FRONTIER 3 studies initiated recruitment prior to the completion of FRONTIER 1 to accelerate the development of a novel alternative to current HA treatments. Moreover, Mim8 is being investigated in a broad patient population across many different countries and the inclusion criteria were designed to allow for the incorporation of female patients, PUPs, all disease severities, and all ages. This aims to ensure that the study population is as comparable to and representative as possible of the real-world population of PwHA. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Sedative and cardiopulmonary effects of intramuscular combinations of hydromorphone, acepromazine, dexmedetomidine, and glycopyrrolate followed by intravenous propofol and inhalant isoflurane anesthesia in healthy dogs.

To evaluate the sedative and cardiopulmonary effects of various combinations of acepromazine, dexmedetomidine, hydromorphone, and glycopyrrolate, followed by anesthetic induction with propofol and maintenance with isoflurane in healthy dogs. 6 healthy adult female Beagles. Dogs were instrumented for hemodynamic measurements while anesthetized with isoflurane. Two hours after recovery, dogs received 1 of 4 IM combinations in a crossover design with 1 week between treatments: hydromorphone (0.1 mg/kg) and acepromazine (0.005 mg/kg; HA); hydromorphone and dexmedetomidine (0.0025 mg/kg; HD); hydromorphone, acepromazine, and dexmedetomidine (HAD); and hydromorphone, acepromazine, dexmedetomidine, and glycopyrrolate (0.02 mg/kg; HADG). Sedation was scored after 30 minutes. Physiologic variables and cardiac index were measured after sedation, after anesthetic induction with propofol, and every 15 minutes during maintenance of anesthesia with isoflurane for 60 minutes (target expired concentration at 760 mm Hg, 1.3%). Sedation scores were not significantly different among treatments. Mean ± SD cardiac index was significantly higher for the HA (202 ± 45 mL/min/kg) and HADG (185 ± 59 mL/min/kg) treatments than for the HD (88 ± 31 mL/min/kg) and HAD (103 ± 25 mL/min/kg) treatments after sedation and through the first 15 minutes of isoflurane anesthesia. No ventricular arrhythmias were noted with any treatment. In healthy dogs, IM administration of HADG before propofol and isoflurane anesthesia provided acceptable cardiopulmonary function with no adverse effects. This combination should be considered for routine anesthetic premedication in healthy dogs.

Humic Acid Fertilizer Incorporation Increases Rice Radiation Use, Growth, and Yield: A Case Study on the Songnen Plain, China

Humic acid fertilizer (HA) incorporation is a common method for improving crop growth and soil fertility. However, the effects of HA incorporation on rice growth are still unknown. We conducted a two-year field experiment to determine the radiation use, growth, and yield of rice grown with five different HA rates: 110 kg∙ha−1 100% urea (pure nitrogen) (T1); 30% HA and 70% urea (T2); 50% HA and 50% urea (T3); 70% HA and 30% urea (T4), and 1500 kg∙ha−1 100% HA (T5). The results showed that the T2 treatment had the lowest values of photosynthetic efficiency of PSII (Fv/Fm), relative leaf chlorophyll content (SPAD), plant height and leaf area index (LAI) in both years, which were similar to the photosynthetically active radiation (IPAR), radiation use efficiency (RUE), yield, and biomass. In contrast, the highest harvest index (HI) value was found in the T2 treatment. In the two years, the T4 and T5 treatments showed no significant differences. However, the multivariate statistical method based on principal component analysis showed that in the first principal component, the LAI, biomass, yield, plant height, SPAD, Fv/Fm, IPAR, and RUE had a positive correlation, and the HI had a negative correlation. The LAI, yield, plant height, SPAD, HI, and RUE had a positive correlation, but biomass, Fv/Fm and IPAR had a negative correlation in the second principal component. Across the different HA treatments, the comprehensive scores were T5 &gt; T4 &gt; T3 &gt; T1 &gt; T2, with values of 2.13, 1.38, −0.17, −0.34, and −3.00, respectively. According to the principal component analysis results of each index, the T5 treatment was better than the T4 treatment.

Resource utilization and treatment costs of patients with severe hemophilia A: Real-world data from the ATHNdataset.

Hemophilia A is characterized by unpredictable spontaneous bleeds and chronic comorbidities. However, limited data exists at the national level into detailed management patterns related to patient clinical characteristics, representative real‐world dosing and treatment frequency, and costs. To assess and characterize the US severe hemophilia A (SHA) population, including subgroups of patients, in terms of clinical and demographic characteristics, healthcare resource utilization received at hemophilia treatment centers (HTCs), and projected annual costs of treatment utilizing data from the ATHNdataset of the American Thrombosis and Hemostasis Network (ATHN). Adult male people with SHA (PwSHA) (FVIII < 1%) were identified in the ATHNdataset between January 2013 and September 2019. This retrospective cohort study described patients’ demographic and clinical characteristics, clinical history, as well as the HTC‐related health resource utilization (HRU), treatment utilization, and projected annual treatment costs of US PwSHA received over the most recent year. Results are reported for the overall population and for three mutually exclusive subpopulations of patients: PwSHA with a history of and/or current inhibitors, PwSHA without a history of inhibitors but with (or a history of) one or more transfusion‐transmitted infections (hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV]), and PwSHA without a history of inhibitors or of transfusion‐transmitted infections (HBV, HCV, or HIV). Of the overall PwSHA cohort (N = 3677), there was a high prevalence of HCV (24.1%) and HIV (13.7%), while the prevalence of HBV (4.9%) was lower. Note that 20.5% of PwSHA overall currently or ever had FVIII inhibitors. On average, PwSHA had 2.8 total HTC visits per year, including 0.9 comprehensive care visits, 1.1 telephone contact visits, 0.5 office visits, and 0.1 surgeries or other procedures. However, 23.3% of PwSHA were not seen at an HTC, and 33.8% of PwSHA did not have a comprehensive care visit during their most recent year of data. HTC‐related HRU was similar between the overall cohort and across the patient subpopulations, although PwSHA and inhibitors had more frequent HTC visits (a mean of 3.6 visits annually vs. 2.5–2.8 in the other groups). Using reported treatment frequency and dosing, estimated mean annual hemophilia treatment costs varied by treatment and across the three subpopulations: extended half‐life factor product ($893,609–934,301 by subpopulation), standard half‐life factor product ($798,700–930,812), plasma‐derived factor product ($613,220–801,061), and non‐factor product treatment ($765,289—833,240). This study summarized recent sociodemographic and clinical characteristics, HTC‐related HRU, and HA treatments and projected costs among adult PwSHA, including among key subpopulations of PwSHA. PwSHA experience substantial clinical and resource burden on a chronic basis, despite the care coordination efforts of ATHN‐affiliated HTCs. These findings motivate further exploration of the drivers of resource utilization, observed differences across subpopulations and other disparities, and ongoing monitoring of clinical and treatment burden in the face of an evolving care landscape.

Integration of transcriptomics and metabolomics provides metabolic and functional insights into reduced insulin secretion in MIN6 β-cells exposed to deficient and excessive arginine.

Previous work demonstrated that arginine is one of the strongest insulin secretagogues. However, knowledge of the mechanisms linking chronic arginine metabolism with β-cell function and insulin secretion is relatively limited. After preliminary selection of concentration according to the cell proliferation, the MIN6 pancreatic β-cells were randomly assigned to culture in 0.04mM (low-arginine, LA), 0.4mM (standard-arginine, SA), or 8mM arginine (high-arginine, HA) for 24h. Following the treatment, a combination of transcriptomics and metabolomics, together with a series of molecular biological tests were performed to investigate the responses of β-cells to varied arginine availability. Our results showed that HA treatment reduced the chronic insulin releases, and LA and HA treatments decreased the glucose-stimulated insulin secretions (GSIS) of β-cells relative to the SA group (p<.05). Transcriptomics analysis indicated that LA administration significantly inhibited oxidative phosphorylation and ATP metabolic process but promoted DNA repair and mRNA processing in β-cells, while HA administration affected ammonium ion metabolic process and mRNA export (p<.05). Both LA and HA regulated the expressions of genes involved in DNA replication, cell-cycle phase transition, and response to oxidative stress (p<.05). Protein-protein interaction and transcription factor analyses suggested that Trp53 and Nr4a2genes may play key roles during arginine stimulation. On the contrary, metabolomics analysis demonstrated that the differentially expressed metabolites (DEM) of MIN6 β-cells induced by LA were mainly enriched in glycerophospholipid metabolism, linoleic acid metabolism, and purine metabolism, while most DEMs between LA vs. SA comparison belonged to amino acid metabolism. When combined the three groups, co-expression analysis suggested that insulin secretions had strong associations with L-pyroglutamic acid, L-glutamate, and creatine concentrations, while intracellular insulin contents were mainly correlated to L-arginine, argininosuccinic acid, and phosphorylcholine. At last, integrated analysis of transcriptomics and metabolomics showed that glycerophospholipid metabolism, biosynthesis of unsaturated fatty acids, and amino acid metabolism were the most relevant pathways in β-cells exposed to abnormal arginine supply. This descriptive bioinformatics analysis suggested that the disturbed carbohydrate, lipid, and amino acid metabolisms, as well as the increased apoptosis and elevated oxidative stress, contributed to the reduced insulin secretion and lower GSIS in β-cells induced by LA or HA treatments, while some underlying mechanisms need to be further explored.

Estimating the risk of thrombotic events in people with congenital hemophilia A using US claims data.

Aim: Compare thrombotic risk in people with congenital hemophilia A (PwcHA) to the general non-hemophilia A (HA) population. Patients & methods: USclaims databases were analyzed to identify PwcHA. Incidence rates of myocardial infarction, pulmonary embolism, ischemic stroke, deep vein thrombosisand device-related thrombosis were compared with a matched cohort without HA. Results: Over 3490 PwcHA were identified and 16,380 individuals matched. PwcHA had a similar incidence of myocardial infarction and pulmonary embolism compared with the non-HA population, but a slightly higher incidence of ischemic stroke and deep vein thrombosis. The incidence of device-related thrombosis was significantly higher in PwcHA. Conclusion: This analysis suggests that PwcHA are not protected against thrombosis, and provides context to evaluate thrombotic risk of HA treatments.

Costs and management of patients with hemophilia A in France: the Hemraude study

The Hemraude study was conducted to describe the profile of patients with HA, disease management, and economic burden in a collective perspective. This retrospective study was conducted using the French administrative healthcare claims database SNIIRAM/SNDS. Male patients treated for hemophilia A with a long-term illness (ALD) status or invalidity were included in the study between January 1, 2016 and December 31, 2017. Patients were classified in six treatment groups: no treatment, on-demand FVIII, prophylactic FVIII, FVIII in immune tolerance induction (ITI) protocol, on-demand bypassing agents, and prophylactic bypassing agents. Patients treated with FVIII in ITI protocol and those treated with bypassing agents are deemed to have developed inhibitors. HA patients were compared to a control population without coagulation disorder and matched (ratio 1:3) on age and sex. A total of 4172 patients were included in the analysis, aged on average 35.2years, 5.3% had HIV infection, and 8.8% had hepatitis B or C. In 2017, half of the patients received no treatment for HA, 46.7% were treated with FVIII (25% on demand, 20.6% with prophylaxis, and 1.1% ITI), 1.5% with bypassing agents. Patients treated with prophylactic treatments, either inhibitor or non-inhibitor, were less likely to be hospitalized for severe bleeding compared to patients receiving on-demand treatments. The average annual costs for HA management per patient were 72,209.60 €. The highest costs were observed in patients treated with FVIII in ITI protocol and those receiving prophylactic bypassing agents. Direct costs of HA treatments for HA may be very high especially in the small percentage of patients developing inhibitors or treated with ITI protocol.

Establishment of a framework for assessing mortality in persons with congenital hemophilia A and its application to an adverse event reporting database

BackgroundDespite recent therapeutic advances, life expectancy in persons with congenital hemophilia A (PwcHA) remains below that of the non‐HA population. As new therapies are introduced, a uniform approach to the assessment of mortality is required for comprehensive evaluation of risk–benefit profiles, timely identification of emerging safety signals, and comparisons between treatments. ObjectivesDevelop and test a framework for consistent reporting and analysis of mortality across past, current, and future therapies. Patients/MethodsWe identified known causes of mortality in PwcHA through literature review, analysis of the US Food and Drug Administration Adverse Event Reporting System (FAERS) database, and expert insights. Leading causes of death in general populations are those recognized by the Centers for Disease Control and Prevention and the World Health Organization. We developed an algorithm for assessing fatalities in PwcHA and used this to categorize FAERS data as a proof of concept. ResultsPwcHA share mortality causes with the non‐HA population including cardiovascular disease, malignancy, infections, pulmonary disease, dementias, and trauma/suicide. Causes associated with HA include hemorrhage, thrombosis, human immunodeficiency virus, hepatitis C virus, and liver dysfunction. We propose an algorithm employing these classes to categorize fatalities and use it to classify FAERS fatality data between 01/01/2000 and 03/31/2020; the most common causes were hemorrhage (22.2%) and thrombosis (10.4%). ConclusionsA conceptual framework for examining mortality in PwcHA receiving any hemophilia therapy is proposed to analyze and interpret fatalities, enabling consistent and objective assessment. Application of the framework using FAERS data suggests a generally consistent pattern of reported mortality across HA treatments, supporting the utility of this unified approach.

Oral supplementation of the diet of growing rabbits with a newly developed mixture of herbal plants and spices enriched with special extracts and essential oils affects their productive performance and immune status

This study aimed to evaluate the effect of feeding a mixture of herbal plants and spices enriched with special extracts and essential oils (phytogenic additives mixture) on feed intake, feed utilisation, blood chemistry, slaughter characteristics and caecal bacteria profile in rabbits. Ninety weaned unsexed V-Line rabbits, weighing 668.7 ± 8.2 g and aged 30 ± 1 days, were randomly allocated to three groups of 30 rabbits each and fed a basal diet without additives (Control rabbits) or supplemented with 0.5 mL (LA) or 1 mL (HA) of the additives mixture per litre of drinking water. Additives did not affect feed intake; however, the LA rabbits showed greater (P<0.001) feed conversion ratio compared to the other treatments. The LA treatment increased (P<0.01) final body weight and average daily gain compared to the control and HA treatments. Both the LA and HA treatments decreased (P<0.05) blood cholesterol, triglycerides and low-density lipoproteins; however, the LA treatment increased (P<0.05) high-density lipoproteins and total antioxidant capacity but decreased malondialdehyde (P<0.05) relative to the control treatment. Treatments did not affect carcass characteristics. The LA treatment followed by HA treatment increased (P<0.001) beneficial Lactobacillus spp. bacteria and decreased the concentrations of coliform bacteria and E. coli compared with the control treatment. It is concluded that additives mixture enhanced feed conversion and daily gain and positively altered caecal bacteria profile, with better effects of the low dose of the phytogenic additives mixture compared with the high dose.

Different Intra-articular Injections as Therapy for Hip Osteoarthritis: A Systematic Review and Network Meta-analysis

This systematic review and network meta-analysis aimed to compare the clinical outcomes between 4 intra-articular injections (platelet-rich plasma [PRP], hyaluronic acid [HA], corticosteroid [CS], and HA plus PRP) for hip osteoarthritis (OA). We performed a systematic literature search in PubMed, Embase, Web of Science, and the Cochrane database through April 2018 to identify any randomized controlled trials that evaluated the clinical efficacy of HA, PRP, CS, HA-plus-PRP, and control treatments for hip OA. Baseline information-country, mean age, number of patients, and Kellgren-Lawrence grade of hip OA in the treatment and control groups-was collected. The primary outcome was the visual analog scale (VAS) score at 1, 3, 6, and 12 months after injection. We included 11 randomized controlled trials with a total of 1,060 patients. The Kellgren-Lawrence grades of the treatment and control groups were similar in individual studies. The pair-wise meta-analysis indicated that CS and HA were superior to the control group in reducing the VAS score at 1 month and 3 months (P < .05) and that CS was superior to HA in reducing the VAS score at 1 month (P < .05). The network meta-analysis results indicated that HA and CS exhibited a beneficial role in reducing the VAS score at 1 month. CS achieved the lowest value for the surface under the cumulative ranking curve (SUCRA) for the VAS score at 1 month (0.23), and the SUCRA values of the 5 interventions showed that PRP achieved the lowest SUCRA value for the VAS score at 6 months (0.53). CS injections are recommended as the most efficient agent in hip OA patients in the short term. Moreover, PRP is reported to have the highest rank for pain relief for up to 6 months. Considering the limitations of this meta-analysis, future direct comparisons with more samples are needed. Level II, meta-analysis of Level I and II studies.

Effects of Allium mongolicum Regel supplementation on the digestibility, methane production, and antioxidant capacity of Simmental calves in northwest China.

This study evaluated the effects of Allium mongolicum Regel (AM) supplementation on nitrogen (N) balance, ruminal fermentation, and antioxidant properties. Sixteen male calves were assigned randomly to four groups, and the four were added with 0 (CON), 200mg/kg (body weight; BW) (Low AM; LA), 400mg/kg (BW) (Middle AM; MA), or 800mg/kg (BW) (High AM; HA) per day for each individual. AM was added on dry matter (DM) basis. The experiment lasted for 58days. Supplementation of AM could significantly increase average daily gain, DM digestibility, acid detergent fiber digestibility, and retained N/Intake N. N digestibility and molar proportion of propionate in the MA and HA treatments were higher than that in the CON treatment (p<.05), respectively. AM supplementation significantly increased the molar concentration of total volatile fatty acid in the rumen fluid (p<.05). The ratio of acetate to propionate in the MA and HA groups was lower than that in the CON treatment (p<.05). Furthermore, AM supplementation significantly reduced methane (CH4 ) (p<.05) emissions. AM supplementation significantly increased the activities of superoxide dismutase. The MA group could significantly increase the activities of glutathione peroxidase and decrease the content of malondialdehyde. Our results indicated that AM supplementation could affect the nutrient digestibility, CH4 emission, and antioxidant capacity of Simmental calves.

PSIII-5 Metabolic hormones, live weight, grazing behaviour and offspring distance of primiparous beef cows grazing grasslands at two herbage allowances

Abstract The objective of this study was to evaluate the effect of herbage allowance (HA; herbage mass in kg DM/ha: stocking rate in kg LW/ha ratio) during gestation and lactation on cow and calf LW, body condition score (BCS), insulin, IGF-1, and leptin concentrations, daily grazing, ruminating and idling proportion cow-calf distance in primiparous beef cows from -10 to 70 days from temporary suckling restriction (nose plates on calves during 12 days=TW; day 0=initiation of TW at 86 ± 10 postpartum) and flushing (2 kg FB/cow/day whole-rice bran for 22 days). Thirty-three cows were allocated to HA treatments during gestation and lactation (-150 to 195 days relative to calving), that annually averaged 2.5 (low HA) and 4 kg DM/kg LW (high HA). Data were analyzed using mixed models with repeated measures and general linear mixed models. Cows LW and BCS did not differ during the -10 to 50 day period but were greater in high HA at the end of the study. Concentrations of IGF-I were greater in high HA (80 vs 70 ± 3 ng/mL), but insulin and leptin did not differ. Daily grazing proportion was lower in high HA (0.64 vs 0.68 ± 0.06; P &amp;lt; 0.05), and the opposite occur with rumination and idling (P &amp;lt; 0.05). Cow-calf distance was greater in low HA cows (0.57 vs 0.75 ± 0.006; P &amp;lt; 0.05) and increased greatly in this group after flushing. Milk yield was greater (3.7 vs 3 ± 0.3; P &amp;gt; 0.05) and calf weight did not differ between treatments from -10 to 35 day and was greater after 45 days in high HA compared to low HA. Thus, increasing HA resulted in greater IGF-1 concentrations and milk yield, and induced changes in grazing and maternal behavior that were associated with increased cow and calf LW and BCS.

Characterization and Disease Management of Persons with Hemophilia A Treated with Emicizumab: A Survey Study of Hematologists in the US

Introduction Emicizumab (EMI) is a subcutaneously administered, bispecific, humanized monoclonal antibody that bridges activated factor IX (FIXa) and FX to restore the function of missing FVIIIa in persons with hemophilia A (PwHA). It was approved in the US for prophylaxis in PwHA with FVIII inhibitors in November 2017 and for PwHA without FVIII inhibitors in October 2018. In May 2019, an online survey of 50 board-certified hematologists (HEMs) was conducted with the objective of understanding the characteristics of PwHA who are being treated with EMI (PwHA-EMI) and assessing any changes in disease management of these individuals by HEMs. Methods Descriptive analysis was conducted on data collected from May 8 to May 20, 2019, through a 30-minute, online survey of 50 HEMs treating adult and pediatric PwHA with or without FVIII inhibitors in the US. These HEMs were required to have ≥2 years of experience post-residency and experience treating ≥3 PwHA per month with EMI. Results Of the 50 HEMs from 22 states who were surveyed in this study, 28% (n=14) primarily treated pediatric PwHA and 76% (n=38) practiced at federally funded hemophilia treatment centers. HEMs reported that the majority of their PwHA-EMI had severe HA, were previously treated, and did not have FVIII inhibitors. HEMs reported presence of inhibitors (40%, n=20) and high treatment burden with previous treatments (16%, n=8) as the top factors that were considered when initiating treatment with EMI. HEMs reported that they are testing less frequently for FVIII activity (52%, n=26) and inhibitors (28%, n=14) in PwHA-EMI. Most HEMs reported using multiple methods for breakthrough bleed recognition in their PwHA-EMI, such as advising them to call a healthcare provider (HCP) for diagnosis support (70%, n=35) and providing educational materials (68%, n=34). Further, 34% (n=17) reported a change in their guidance on bleed treatment in PwHA-EMI. Guidance varied by inhibitor status and type of bleed; these HEMs were more likely to recommend that their PwHA-EMI with FVIII inhibitors (65%, n=11/17) and without FVIII inhibitors (53%, n=9/17) call a HCP to discuss symptoms before treating the bleed. Also, 42% (n=21) of HEMs typically advised keeping 3-4 doses of bypassing agent or FVIII at hand in case of breakthrough bleed treatment in PwHA-EMI. A majority of HEMs (84%, n=42) reported that the recreational physical activity levels of their PwHA have remained the same or increased after starting EMI; 48% (n=24) of HEMs recommended that their patients have a gradual increase in these activities after starting EMI. Among HEMs who provided specific guidance on recreational physical activities (54%; n=27), most develop customized plans for their patients based on fitness goals (82%; n=22/27), disease severity (74%; n=20/27), and age (56%; n=15/27). For disease management support, 58% (n=29) of HEMs reported no change in the support they provide, even though EMI is a relatively new treatment. HEMs mainly attributed this to fewer bleeds in PwHA-EMI. For routine and follow-up care, 72% (n=36) and 56% (n=28) of HEMs, respectively, reported that their PwHA-EMI seek about the same levels of such care as they did prior to starting EMI, but 32% (n=16) of HEMs reported that their PwHA-EMI need less non-routine care after starting treatment with EMI. Breakthrough bleeds (22%, n=11) and trauma (20%, n=10) were reported as the top reasons for any non-routine care in PwHA-EMI. As for treatment adherence, 90% (n=45) of HEMs reported that their PwHA-EMI have similar or better adherence compared with those on other HA treatments. Lastly, 46% (n=23) of HEMs reported that their PwHA-EMI regularly experience insurance issues, including ones related to coverage for EMI and coverage for care and breakthrough bleed treatments while on EMI. Conclusions Based on the findings of this survey study, most HEMs have retained similar disease management support and practices for their PwHA-EMI. Although the frequency of routine care has not changed for most PwHA-EMI, HEMs indicated a reduction in the amount of non-routine care needed by these individuals. As EMI is prescribed and used over a longer period post approval, patient characteristics, treatment methods, and disease management practices should continue to be monitored to support HEMs' treatment and care of PwHA. Disclosures Owens: PRO Unlimited: Employment; Genentech, Inc.: Consultancy. Patel:Roche/Genentech: Equity Ownership; Genentech: Employment. Poulos:MedPanel, Inc.: Employment. Powers:MedPanel: Employment. Ko:Genentech, Inc.: Employment.

Water-soluble mercury induced by organic amendments affected microbial community assemblage in mercury-polluted paddy soil

Mercury (Hg) pollution or organic amendments (OA) may individually induce changes in the microbial community of paddy soils. However, little is known regarding the interaction of Hg and OA and the effect of different OA applications on the microbial community assemblage in Hg-polluted paddy soil. A soil incubation experiment was performed by applying three organic amendments (OA), namely a food-waste compost (FC), and its HA and FA, into an Hg-polluted paddy soil to examine the changes in the microbial community and merA/merB gene abundance. The results showed that the OA treatments promoted total (SOC) and dissolved organic carbon (DOC) in soils, which may harbor copiotrophic bacteria. The HA and FA treatments decreased microbial diversity and richness along with an increase of water-soluble Hg (WHg) through the complexation of DOC to Hg, which may be mainly attributed to the enhanced Hg biotoxicity to soil microbiome induced by the increased WHg under these two treatments. Additionally, the WHg enhancement also contributed to the increase of Hg-resistant bacteria and merA/merB gene abundance, and consequently, induced changes in the microbial community. These results indicated the interaction of Hg and different OA induced the variation of WHg fraction in paddy soil, which played a fundamental role in the distinct responses of the microbial community assemblage. Collectively, the application of FA and HA to Hg-polluted soil should be limited considering Hg risk to microbiome, and FC can be an alternative.

Chimeric peptide combining both growth hormone and somatostatin sequences (REG-O3) improves function and prevents cartilage degradation in rat model of osteoarthritis

Purpose: REG-O3 is an innovative chimeric peptide combining a short amino acid sequence derived from growth hormone (GH) and an analog of somatostatin (SST), both well-known molecules for their involvement in skeletal development and maintenance via their action on IGF-1-dependent pathways. This peptide was therefore thought to show disease modifying osteoarthritis drug (DMOAD) potential and protect articular structure from osteoarthritis (OA). The aim of this study was thus to investigate the protective effect of this peptide directly injected into the knee joint on pain and function, and on joint tissues structure. Methods: Mature male Lewis rats (n=12/group) were used for this study. OA was induced in the right knee by the surgical transection of the anterior cruciate ligament (ACLT) combined with the partial medial meniscectomy (pMMx). Treatments were administered intra-articularly (50μL) into the right operated knee from 14 days after surgery through 3 consecutive injections one week apart. The test item (REG-O3) was solubilized in a liposomal solution and was injected into the right operated knee at 10, 50 and 100μM final concentrations. It was compared to placebo (liposomal solution), and positive control items such as dexamethasone (0.5 mg/kg) and hyaluronic acid (HA, 1 mg/kg). The study endpoints were the pain and function measured throughout the entire study once a week and the structure of the knee joint evaluated 8 weeks after surgery using OARSI score. Results: ACLT+pMMx surgery induced a significant decrease of right operated paw weight bearing in all groups. Dexamethasone and HA treatments partially but significantly increased right paw weight bearing compared to placebo. REG-O3 displayed a similar effect to dexamethasone and higher effects than HA on weight bearing recovery after surgery. When looking at cartilage histology, REG-O3 (50μM) was the only treatment able to significantly improve cartilage OARSI global score and to significantly reduce total cartilage degeneration width, cartilage matrix loss width and cartilage degeneration. Conclusions: REG-O3 not only exhibited an interesting profile on function and pain in ACLT+pMMx model of OA in rat but was also able to significantly preserve cartilage from degeneration. REG-O3 might be a drug candidate for the treatment of OA.