HD Group Research Articles

Effect of the vision suppression on the graphomotor gesture in school aged children typically developed and with handwriting disorders

IntroductionThe knowledge aboutthe integration of letter motor programs during learning to write support the idea of an interdependence of visual and kinesthetic controls to direct the strokes.ObjectivesThe objective of our study is to analyze the effect of the vision suppression both on the postural-gestural organization and on the spatial/temporal/kinematic parameters in a prescriptural task.Methods35 school aged children with handwriting disorders (HD group) aged 6-11 years and 35 matched typical children were included in the study. They performed a prescriptural task of copying a cycloid line of loops, carried out under two conditions, with open eyes versus closed eyes. Postural-gestural measures were recorded with two video cameras allowing 2D reconstruction of the gesture. Spatial/temporal/kinematic measures were recorded with a digital pen.ResultsThe HD group showed a significantly poorer postural control and an improvement in the spatial/temporal/kinematic parameters of the loops when they closed their eyes compared to eyes open. In typical group, the postural-gestural organization became significantly more mature but with no significant influence on the spatial/temporal/kinematic parameters of the loops.ConclusionsHDs could be partly explained by a deficit in the processing of proprioceptive/kinesthetic feedback and a disruptive effect of the visual control on the quality of the prescriptural drawings. The ability to direct the strokes would remain dependent on sensory feedbacks, themselves insufficiently efficient, which would lead to difficulties in reaching a proactive control of handwriting. These results should be able to enhance clinical practices and to contribute to clinical decision making processes for handwriting disorders remediation.DisclosureNo significant relationships.

1221-P: Clinical Significance of Autoantibody Measurement for Glucose-Dependent Insulinotropic Polypeptide and Glucagon-Like Peptide-1 in the Plasma

Background: Polyclonal autoantibodies against various proteins that do not cause autoimmune diseases have been reportedly observed in the serum. The presence of polyclonal antibodies against glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) have been observed in the blood of patients who have not previously used the GLP-1 receptor agonist. Therefore, this study aimed to investigate the clinical significance of measuring anti-GIP and GLP-1 autoantibodies (Abs) in the plasma. Two groups consisted of 1healthy donors (HD) and 274 patients with diabetes mellitus (DM) were investigated. AlphaLISA was used to measure both GIP and GLP-1 Abs. This study was approved by the ethical review board of our university (approval number 21-Im-03) . Results: The serum concentration of anti-GIP Abs was significantly greater in the DM group than in the HD group (2697.6 ± 1998 vs. 2277.6 ± 821, p = 0.0001) , while the levels of anti-GLP-1 Abs were not different between the two groups. Since the concentration of anti-GIP Abs was significantly related to age, binary logistic regression analysis was perfomed for adjusting the age factor to reveal that anti-GIP Abs were greater with DM than without (OR: 1.0004; 95% CI 1.0001-1.001, p = 0.049) . Discussion: Several autoantibodies have been reportedly used as markers for various diseases, such as atherosclerosis, diabetes, and cancers. We found that the patients with DM had greater serum levels of anti-GIP Abs than those without it, indicating that the functions of GIP are inhibited in the presence of anti-GIP Abs in patients with DM. Since GIP is an insulinotropic intestinal hormone and the GLP-1/GIP dual agonist have been demonstrated to reduce both HbA1c and body weight, the functions of GIP inhibited by anti-GIP Abs may worse glucose metabolism. Conclusions: The patients with DM showed higher levels of anti-GIP autoantibodies. Disclosure H.Yamagata: None. S.Onishi: None. T.Yoshida: None. T.Hiwasa: None. M.Takemoto: None.

Treatment of GM2 Gangliosidosis in Adult Sandhoff Mice Using an Intravenous Self-Complementary Hexosaminidase Vector.

GM2 gangliosidosis is a neurodegenerative, lysosomal storage disease caused by the deficiency of β-hexosaminidase A enzyme (Hex A), an α/β-subunit heterodimer. A novel variant of the human hexosaminidase α-subunit, coded by HEX M, has previously been shown to form a stable homodimer, Hex M, that hydrolyzes GM2 gangliosides (GM2) in vivo. The current study assessed the efficacy of intravenous (IV) delivery of a self-complementary adeno-associated virus serotype 9 (scAAV9) vector incorporating the HEXM transgene, scAAV9/HEXM, including the outcomes based on the dosages provided to the Sandhoff (SD) mice. Six-week-old SD mice were injected with either 2.5E+12 vector genomes (low dose, LD) or 1.0E+13 vg (high dose, HD). We hypothesized that when examining the dosage comparison for scAAV9/HEXM in adult SD mice, the HD group would have more beneficial outcomes than the LD cohort. Assessments included survival, behavioral outcomes, vector biodistribution, and enzyme activity within the central nervous system. Toxicity was observed in the HD cohort, with 8 of 14 mice dying within one month of the injection. As compared to untreated SD mice, which have typical survival of 16 weeks, the LD cohort and the remaining HD mice had a significant survival benefit with an average/median survival of 40.6/34.5 and 55.9/56.7 weeks, respectively. Significant behavioral, biochemical and molecular benefits were also observed. The second aim of the study was to investigate the effects of IV mannitol infusions on the biodistribution of the LD scAAV9/HEXM vector and the survival of the SD mice. Increases in both the biodistribution of the vector as well as the survival benefit (average/median of 41.6/49.3 weeks) were observed. These results demonstrate the potential benefit and critical limitations of the treatment of GM2 gangliosidosis using IV delivered AAV vectors.

Traditional Sunchang Gochujang Attenuates Obesity in High-Fat Diet Induced Obese Mice

ObjectivesObesity is a major global health crisis. High fat diet (HFD) and salt intake have been linked to leptin resistance and obesity. Korea has lower obesity prevalence relative to other countries, although Koreans consume various fermented substances containing high salt, such as gochujang and doenjang amongst others. This phenomenon is defined as “the Korean paradox”. Gochujang is a Korean fermented pepper paste that contains high amount of salt. Therefore, we aimed to evaluate the anti-obesity potential of traditional gochujang on HFD-induced obese mice by comparing its effects with HFD and HFD containing same amount of salt from traditional gochujang.Methods4 weeks old C57BL/6J male mice were divided into 4 groups and fed a normal diet (ND), HFD (HD), HFD + salt (SALT) and HFD + traditional sunchang gochujang (TS) diets for 14 weeks. Biochemical analyses of serum, liver, and brown and epididymal fat tissues were performed to assess metabolic changes and obesity-related markers. The expressions of mRNA and protein involved in obesity, lipogenesis, adipogenesis and energy expenditure were evaluated from liver, brown and epididymal fat tissues by qPCR and western blot.ResultsTS supplementation significantly reduced obesity in HFD-induced obese mice. Compared to HD, TS had a lower body weight (24%), reduced serum leptin and insulin levels and improved serum and liver lipid profiles. Compared to HD and SALT groups, TS group had a significant reduction of mRNA and protein expressions associated with anabolic lipid metabolism including leptin, PPARγ, CEBPα, FAS, and ACC, while showing significant increase of adiponectin and energy expenditure-related mRNA, such as PPARα and CPT1.ConclusionsTS ameliorates obesity in HFD-induced obese mice by boosting leptin levels and inhibiting the adipogenesis and lipogenesis. Also, SALT group did not show any improvements compared with TS group. These observations imply that high salt content of TS is not a problematic feature. Our findings prove “the Korean paradox” of gochujang and anti-obesity effects of traditional gochujang, proposing the possibility of the traditional gochujang as a functional food against obesity.Funding SourcesMinistry of Agriculture, Food and Rural Affairs and partly Korea Agro-Fisheries and Food trade corporation.

Ventral Attention Network Correlates With High Traits of Emotion Dysregulation in Community Women - A Resting-State EEG Study.

In recent years, many studies have focused on resting-state brain activity, and especially on functional connectivity (FC), an approach that typically describes the statistical interdependence of activity in distant brain regions through specific networks. Our aim was to study the neurophysiological correlates of emotion dysregulation. Therefore, we expected that both the Default Mode Network (DMN), and the Ventral Attention Network (VAN) would have been involved. Indeed, the latter plays a role in the automatic orienting of attention towards biologically salient stimuli and includes key regions for emotion control and modulation. Starting from a community sample of 422 female students, we selected 25 women with high traits of emotion dysregulation (HD group) and 25 with low traits (LD group). They underwent a 64-channel EEG recording during a five-minute resting state with eyes open. Seed-based FC was computed on the EEG Alpha band (8–13 Hz) as a control band, and on EEG Gamma power (30–50 Hz) as the relevant measure. The power within each network and inter-network connectivity (Inter-NC) was also calculated. Analysis of the EEG Gamma band revealed, in the HD group, higher levels of Inter-NC between the VAN and all other resting-state networks as compared with the LD group, while no differences emerged in the Alpha band. Concerning correlations, Alpha power in the VAN was negatively correlated in the HD group with affective lability (ALS-18 questionnaire), both for total score (ρ = –0.52, pFDR < 0.01) and the Depression/Elation subscale) ρ = −0.45, pFDR < 0.05). Consistent with this, in the Gamma band, a positive correlation was found between VAN spectral power and the Depression/Elation subscale of ALS-18, again in the HD group only (ρ = 0.47, pFDR < 0.05). In conclusion, both resting state FC and network power in the VAN were found to be related to high emotion dysregulation, even in our non-clinical sample with high traits. Emotion dysregulation was characterized, in the EEG gamma band, by a VAN strongly connected to all other networks, a result that points, in women prone to emotion dysregulation, to a strong automatic orienting of attention towards their internal state, bodily sensations, and emotionally intense related thoughts.

Effects of Taraxacum mongolicum Hand.-Mazz. (dandelion) on growth performance, expression of genes coding for tight junction protein and mucin, microbiota composition and short chain fatty acids in ileum of broiler chickens

BackgroundDandelion is becoming an exploitable alternative to the widely prohibited antibiotics in the poultry production. This research aimed to investigate the effects of dandelion on the growth performance and intestinal barrier function of broiler chickens maintained under standard condition of management. One-hundred and sixty 1-day-old Arbor Acres (AA) male broiler chickens were randomly divided into four groups, with five replicates of eight birds each. The birds were fed a basal diet supplemented without (control group, [CON]) or with 500 (low dose [LD]) or 1000 (high dose [HD]) mg/kg dandelion or with 250 mg/kg chlortetracycline 20% premix (CTC) for 42 days, including the starter phase (d 1 to 21) and the grower phase (d 22 to 42). Body weight (BW) of each bird and feed consumption of each replicate were measured at d 21 and d 42. The ileal tissues were collected on day 21 and 42 to determine expression of genes coding for tight junction protein and mucin as well as ELISA analysis for immune factor. The ileal digesta was collected for microbiota and short chain fatty acids analysis.ResultsCompared with CON group, during day 1–21, the average daily feed intake (ADFI) and feed/gain ratio (F/G) of LD group were lower (P < 0.05); during day 22–42, the F/G of LD and CTC group tended to be lower (P = 0.07); during the overall phase, the ADFI of HD and CTC groups were decreased (P < 0.05), and the F/G of dandelion and CTC groups tended to be decreased (P = 0.07). On day 21, the relative mRNA expression of claudin, occludin-1 and mucin1 in dandelion groups were up-regulated (P < 0.05), and the ZO-1 mRNA expression in CTC group was increased (P < 0.05); on day 42, the claudin and mucin1 transcripts in LD group and ZO-1 transcripts in HD and CTC group were up-regulated (P < 0.05), while the occludin-1 and mucin1 transcripts in CTC group was significantly down-regulated (P < 0.05). In addition, the contents of TNF-α in dandelion groups were lower than that in CTC group (P < 0.05). In the analysis of ileal microbiota, on day 21, decreased α-diversity was observed in HD and CTC groups (P < 0.05). Meanwhile, on day 21, the relative abundance of Firmicutes in dandelion groups tended to be higher (P = 0.09), the relative abundance of Lactobacillus in LD and CTC group were increased (P < 0.05), while Bacteroidete, Bacteroides, and Alistipes relative abundance in dandelion and CTC groups were decreased (P < 0.05). On day 42, the Actinobacteriota relative abundance in CTC group tended to be higher (P = 0.05), and Lysinibacillus relative abundance of CTC group was higher (P = 0.02). Compared with CON group, on day 21, the propionic acid and butyric acid content in CTC group were higher, the butyric acid content in HD group was lower (P < 0.10).ConclusionIn summary, dietary dandelion supplementation at 500 mg/kg of diet enhanced growth performance of broilers by improving the intestinal barrier function. Dandelion can be supplemented in the diet as an antibiotics alternative to enhance production in poultry industry.

Kinetics of the inflammatory response during experimental Babesia rossi infection of beagle dogs

Babesia rossi causes severe morbidity and mortality in dogs in sub-Saharan Africa, and the complications associated with this disease are likely caused by an unfocused, excessive inflammatory response. During this experimental B. rossi study we investigated inflammatory marker and cytokine kinetics during infection and after treatment. We aimed to determine whether infectious dose and treatment would influence the progression of the inflammatory response and clinical disease. Six healthy male beagle dogs formed the study population, one was used to raise the infectious inoculum, three were administered a high B. rossi infectious dose (HD group) and two a low infectious dose (LD group). Clinical examination, complete blood count (CBC) and C-reactive protein (CRP) were determined daily. Cytokines were quantified on stored plasma collected during the study, using a canine specific cytokine magnetic bead panel (Milliplex©). The experiment was terminated and treatment administered when predetermined experimental or humane endpoints were reached. Parasitemia occurred on day 1 and 3 in the HD and LD groups respectively. The rate of increase in parasitemia in the HD group was significantly faster than that seen in the LD group. Significant differences were found in heart rate, blood pressure, interferon gamma (INFγ), keratinocyte chemoattractant (KC), INFγ-induced protein 10 (IP10), granulocyte-macrophage colony-stimulating factor (GM-CSF), monocyte chemoattractant protein 1 (MCP1), tumor necrosis factor alpha (TNFα), interleukin 2 (IL-2), IL-6, IL-7, IL-8, IL-10 IL-15, IL-18, CRP, neutrophils and monocytes between groups at multiple time points during the course of the infection. Our findings suggest that the initiation of inflammation occurs before the onset of clinical disease in B. rossi infection and infectious dose influences the onset of the inflammatory response. Treatment enhances the inflammatory response in the immediate post-treatment period which may contribute to disease associated complications. Finally, we found that there is an imbalance in pro/anti-inflammatory cytokine concentrations during infection which may promote parasite replication.

Topiramate and Acetazolamide Combination a Comparative Study between High and Low Dose Profile of Side Effects on Metabolism

Background: Topiramate, with multiple putative anticonvulsant pathways, is a relatively recent antiepileptic drug. The ability to inhibit carbonic anhydrase, a property common with the acetazolamide anticonvulsant, is among them. Aim: The study refers to compare between the use of combinations of topiramate and acetazolamide high and low doses of drugs and which one is safer for the patients. Methods: Twenty stable adult males wistar rats three weeks after acclimatization and uniformly split into two groups (10 rats in each group) and 60 days of treatment: 9 mg/kg/B.W of Topiramate and 30 mg/kg/B.W of Acetazolamide in the high dose (Hd) group and 5 mg/kg B.W of Topiramate and 30 mg/kg B.W of Acetazolamide in the low dose (Ld) group, orally/day in the high dose (Hd) group. Results: No major differences in mean Glutamate pyruvate transaminase, Glutamic oxaloacetic transaminase, Alkaline phosphatase concentration were found in the statistical analysis of the results in all experimental groups compared with each other at the pretreated period, also revealed that intubation of rats in the 60-days Hd induced a substantial (P&gt;0.05) rise in the mean Glutamate Pyruvate Transaminase and Glutamic Oxaloacetic Transaminase serum concentrations relative to the control and Ld classes. Treatment of low-dose rats showed a substantial (P&lt;0.05) decrease in serum alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen and creatinine enzyme concentrations at 30 and 60 days of the trial compared with the T1 group. Conclusion: The study showed that high-dose combinations of topiramate and acetazolamide had the same adverse effect somewhat in low-dose combinations.

The effect of density on sex differentiation, sexual dimorphism, stress, and related gene expression in yellow perch.

A 180-day experiment was conducted to evaluate the effects of density on sex differentiation, sexual dimorphism, cortisol level, and stress related gene expression. Yellow perch, Perca flavescens, with initial mean body weight of 0.03 ± 0.001 g were reared in three different stocking densities: 1, 2, and 4 fish/L, termed as low (LD), moderate (MD), and high (HD) density, respectively, in a flow-through tank system. Results showed no significant differences in sex ratio in all density groups compared to normal population 1:1, and sexual size dimorphism (SSD) appeared when male and female were as small as the mean size reaching 11.5 cm and 12.3 cm in total length (TL) or 13.2g and 16.9g in body weight (BW), respectively. This female-biased sexual growth dimorphism was more pronounced in LD, although it was observed across all density groups. A significantly higher condition factor (K) of females than males in the LD group, and significantly higher R values of LD and MD than HD with the length/weight (L/W) linear relationships in females, were observed. Parallelly, fish reared in LD showed significantly higher mean body weight than those in the MD and HD groups, but there were no significant differences between the MD and HD. Similar results were also observed in all the other parameters of weight gain, specific growth rate (SGR), condition factor (K), and survival. These findings suggested that high density not only affected growth itself, but also affected SSD, growth trajectory or body shape, and general wellbeing in fish, especially in females. There were no significant differences in gonadosomatic index (GSI) and viscerosomatic index (VSI) among all the density groups; however, the hepatosomatic index (HSI) of LD was significantly higher than MD and HD, suggesting high density affected liver reserves or functions. Physiologically, plasma cortisol level was significantly highest in the LD among all groups, followed by MD, and lowest in HD. At the molecular level, the expression of the 70-kDa heat shock protein (Hsp70), glutathione peroxidase (GPx), and superoxide dismutase (SOD) genes involved in cellular stress were significantly upregulated in the HD group. The most significantly downregulated expression of these genes was consistently observed in the MD when compared to the LD and HD groups. In conclusion, increasing density induced chronic stress in yellow perch without affecting sex differentiation, but negatively affected expression of stress-related genes and mobilization of liver reserve, resulting in poorer wellbeing and reduced SSD, growth, and survival.

MO641: Hemodiafiltration with Intermittent Infusion Reduces the Incidence of Dialysis Disequilibrium Syndrome in Hemodialysis Patients in the Initiation Phase

Abstract BACKGROUND AND AIMS The dialysis disequilibrium syndrome (DDS) is a major complication in hemodialysis patients in the initiation phase. Since urea removal restriction is an effective method to prevent DDS, a reduced dialysis dose is used in the initiation phase in hemodialysis patients. However, despite this, some patients still develop DDS in the initiation phase. Hemodiafiltration with intermittent infusion (I-HDF) provides intermittent infusion during dialysis, which can reduce the imbalance between the intravascular and interstitial concentrations, thus maintaining a high plasma osmolarity and potentially high plasma osmolarity, lowering the incidence of DDS. The aim of the present study was to clarify whether starting the treatment with I-HDF is useful for preventing DDS in hemodialysis patients in the initiation phase. METHOD Since January 2021, we have used I-HDF at the start of the treatment in patients being initiated on hemodialysis at our hospital. We conducted a retrospective review to examine if there were any changes in the incidence of clinical symptoms such as DDS or the mean blood pressure during dialysis with this mode change. The participants in this study included 11 patients who were started on treatment with conventional low-dose hemodialysis (HD group) (10 males/1 female; 5 diabetic, 6 non-diabetic; mean age, 73.7 years; SD 8.3) and 14 patients who were started on treatment with I-HDF (I-HDF group) (12 males/2 females; 12 diabetic, 2 non-diabetic; mean age, 66.8 years; SD 16.1). We compared the prevalence of symptoms of DDS (headache, nausea, vomiting, leg cramps, fatigue and hypotension), the normalized dialysis dose (spKt/V), the urea nitrogen (UN), serum albumin (Alb), fluid removal rate and mean blood pressure in the HD and I-HDF groups at first treatment. The treatment conditions were FA-150F membrane for the HD group and FIX-170E membrane for the I-HDF group, with a blood flow rate of 150 mL/min, dialysate flow rate of 500 mL/min and treatment time of 3-h in both groups. I-HDF was carried out with five infusions of 150–200 mL/min for one minute by back filtration of the dialysate every 30 minutes. RESULTS A significantly lower incidence of DDS was noted in the I-HDF group, with 3 events in the I-HDF group as compared with 17 events in the HD group (P &amp;lt; .01, chi-squared test). There was no significant difference in the spKt/V, UN, Alb, or fluid removal rate between the two groups (P = .80, P = .28, P = .96 and P = .20, respectively). The mean blood pressure was significantly lower in the HD group than in the I-HDF group (P &amp;lt; .05, t-test). These results indicated that the incidence of DDS could be reduced by starting treatment with I-HDF in patients being initiated on hemodialysis, because the intentional loading of fluid by intermittent infusion may enhance plasma refilling and have a positive effect on suppressing any rapid changes in the plasma osmolality. CONCLUSION I-HDF was useful for maintaining the blood pressure and reducing the incidence of dialysis disequilibrium syndrome in the initiation phase in hemodialysis patients.

MO1049: An Intradialytic Exercise at Start versus End of HD Session to Improve Strength with Non-Immersive Virtual Reality: A Randomized Controlled Trial

Abstract BACKGROUND AND AIMS Haemodialysis (HD) induces changes in addition to the kidney in other organs or systems so that patients usually present symptoms such as fatigue, generalized muscle weakness and low tolerance to exercise that result in functional impairment, decreased work capacity and dependence for activities of daily living. Intra-dialysis exercise programmes may help to partly reverse this situation. Exercise during the first 2-h of dialysis has proven to be safe. Our group showed that an acute session of virtual reality exercise during the last 30 min of HD was safe too. The aim of this study was to compare the impact of non-immersive virtual reality intra-dialysis during the first 2-h versus the last 2-h of dialysis on lower-limbs muscle strength. METHOD This was a randomized controlled trial. Participants were randomized in two groups: group A performed the exercise during the first and second hour of the HD session and group B performed it during the third and fourth hour. Strength was measured bilaterally with a hand-held Lafayette dynamometer in three movements of the lower limbs (hip flexion, hip abduction and plantar flexion) during the HD session. The intradialytic exercise consisted of a non-immersive virtual reality video game adapted to the dialysis session, in which the patient must catch treasures while avoiding bombs by moving the lower extremities, with a progressive duration of 25–45 min, over a 12-week period. RESULTS A total of 33 subjects were included in the analysis, 17 subjects (median age 71.8 years; 10 men) in group A and 16 subjects (median age 73.3 years, 9 men) in group B. At baseline the period analysed, there were no significant differences between the two groups in any of the movements analysed. The force analysed in the different movements showed that there was a significant increase in all the movements analysed in both groups. There was an increase in force in the movements of the lower right limb of 3.31 N in hip flexion, 2.01 N in hip abduction and 1.10 N in plantar flexion, as well as an increase in the outside in the lower left limb of 3.82 N in hip flexion, 2.47 N in hip abduction and 4.63 N in plantar flexion. There were no significant differences in the increase in strength in the movements analysed between both groups in the movements analysed after the 12-week period analysed. CONCLUSION There are no differences in the application of an intradialytic exercise at the beginning versus at the end of the HD session to improve strength with non-immersive virtual reality. An intradialytic exercise with non-immersive virtual reality improves limb strength in HD patients.

MO166: The Longitudinal Evolution of Covid-19 Outcomes Among Hemodialysis Patients: A Nationwide Multicentre Controlled Study

Abstract BACKGROUND AND AIMS Haemodialysis (HD) patients are at increased risk for adverse short-term consequences of COVID-19. In this study, we investigated the characteristics of chronic HD patients in the post-COVID-19 period and compared them with the control group. METHOD We conducted a national multicentre observational study involving adult chronic HD patients recovering from COVID-19. The control HD group was selected from patients with similar characteristics who did not have COVID-19 in the same center. SARS-CoV-2 RT-PCR negative patients and patients in the active period of COVID-19 were not included. RESULTS A total of 1223 patients (635 COVID-19 groups, 588 control groups) were included in the study from the data collected from 47 centres between 21 April 2021 and 11 June 2021. The patients' baseline demographics, comorbidities, medications, HD characteristics and basic laboratory tests were quite similar between the groups (Table 1). 28th-day mortality and between 28th day and 90th day mortality were higher in the COVID-19 group than in the control group [19 (3.0%) patients and 0 (0%) patients; 15 (2.4%) patients and 4 (0.7%) patients, respectively]. Presence of respiratory symptoms, rehospitalization, need for home oxygen therapy, lower respiratory tract infection and A-V fistula thrombosis were significantly higher in the COVID-19 group in the first 28 days of illness and between 28 and 90 days. Mortality was significantly associated with preexisting COVID-19, age, current smoking, use of tunneled HD catheter, persistence of respiratory symptoms, rehospitalization, need for home oxygen support, presence of lower respiratory tract infection within 28 days and persistence of respiratory symptoms. CONCLUSION In the post-COVID-19 period, mortality, rehospitalization, respiratory problems and vascular access problems are higher in maintenance HD patients who have had COVID-19 compared to control HD patients. Table 2. Comparative presentation of patients data on the 28th day and between 28 and 90 day COVID-19 groupN = 635 Control groupN = 588 28th-day results, n(%) Death* 19(3.0) 0(0) Any respiratory symptoms* 152(23.9) 11(1.9) Rehospitalization for any reason* 52(8.2) 24(4.1) Need for home oxygen support * 26(4.1) 2(0.3) Lower respiratory tract infection* 65(10.2) 8(1.4) AV fistula thrombosis* 13(2.0) 2(0.3) Other thromboembolic events * 15(2.4) 4(0.7) Need for HD catheter placement* 21(3.3) 9(1.5) 28th day-90. day resultsa n(%) N:616 N:588 Death* 15(2.4) 4(0.7) Any respiratory symptoms* 45(7.3) 10(1.7) Rehospitalization for any reason* 44(7.1) 18(3.1) Need for home oxygen support* 12(1.9) 2(0.3) AV fistula thrombosis* 9(1.5) 1(0.2) Other thromboembolic events* 9(1.5) 2(0.3) Need for HD catheter placement 13(2.1) 10(1.7) HD: haemodialysis, AV: arteriovenous. *P &amp;lt; .05. a Patients who died before 28 days were not included.

Acetyl-L-carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration

ABSTRACT Introduction Acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, has been proven to promote nerve repair and regeneration in a variety of neurodegenerative diseases. Neurogenic erectile dysfunction (NED) caused by CN injury is a common complication after radical prostatectomy, which lacks efficient curative treatments. Objective Although attempts have been made to apply ALCAR to treatment of peripheral neuropathy, the effects of ALCAR on NED remain unknown. Therefore, we intend to explore the potential role of ALCAR in the treatment of NED. Methods A rat model of bilateral cavernous nerve injury (BCNI) was established by crushing the CN 5 millimeters distal to the major pelvic ganglion (MPG). Twenty-four BCNI rats were randomly divided into BCNI group, BCNI+ALCAR-LD (50 mg/kg/day) group, and BCNI+ALCAR-HD (100 mg/kg/day) group, whereas the remaining eight age-matched rats were sham-operated as controls. Fourteen days after intraperitoneal injection of ALCAR, erectile function was evaluated by measuring intracavernosal pressure and mean arterial pressure. The penile tissues and CNs at the distal damage point were collected from each group of rats for subsequent histological and molecular biological analysis. Rat Schwann cell line S16 was used for CCK-8 and wound healing assay, and the expressions of SC markers Pmp22 and nerve growth factor (NGF) were verified by PCR. Results First, we found that the erectile function of rats in the BCNI model group was severely impaired, which was improved considerably in both BCNI+ALCAR-LD and BCNI+ALCAR-HD groups. Then, we observed that the penis was fibrotic after denervation in the BCNI group, which was manifested as decreased smooth muscle content and increased collagen content in the corpus cavernosum, and high expression of fibrosis indicators including TGF-beta, CTGF, and Smad 2/3. The above changes were alleviated after the administration of low and high-dose ALCAR. Meanwhile, our results also showed that after ALCAR treatment, the NO/cGMP pathway was promoted and the RhoA/ROCK pathway was inhibited in the corpus cavernosum of BCNI rats. Further, rats treated with ALCAR had high expression of ATF3 and S100 in the distal nerve tissues of the CN extrusion site, indicating the repairing effect of ALCAR on the CN. In vitro experiments showed that ALCAR promoted the proliferation and migration of SC, and increased the expression of Pmp22 and NGF. Conclusions ALCAR could boost CN repair and regeneration, thereby suppressing penile fibrosis and improving penile erection. ALCAR could inhibit penile fibrosis and improve penile erection by promoting proliferation and migration of SC and secretion of NGF to promote nerve repair and regeneration. Our study provides new insight into the therapeutic effect of ALCAR and preclinical evidence for a potential treatment strategy for NED. Disclosure Work supported by industry: no.

Lycium barbarum polysaccharides improves erectile function through suppression of inflammation and apoptosis in rats with bilateral cavernous nerve injury

ABSTRACT Introduction Neurogenic erectile dysfunction (NED) responds poorly to phosphodiesterase 5 (PDE5) inhibitors. Lycium barbarum polysaccharide (LBP) has broad-spectrum anti-inflammatory and anti-apoptotic effects, but whether it improves the erectile function of neuropathic ED through the above-mentioned mechanism is unclear. Objective We intend to explore the role of LBP in the treatment of NED. Methods A rat model of bilateral cavernous nerve injury (BCNI) was constructed by crushing the CN 5 mm distal to the major pelvic ganglion (MPG). Tweety-four BCNI rats were randomly divided into BCNI group, BCNI + LBP-LD (20 mg/kg/day) group and BCNI + LBP-HD (40 mg/kg/day) group, whereas another 8 age-matched rats formed the control group. Erectile function was evaluated by measuring intracavernosal pressure (ICP) and mean arterial pressure (MAP). The penile tissues, and MPG along with CN were collected from each group of rats for subsequent histological and molecular biological analysis. The rat Schwann cell line S16 was used for CCK-8 and wound healing assay, and the Schwann cell (SC) markers S100 and Pmp22, neuroinflammatory indicators IL-1β, TGF-β1, apoptosis-related proteins Caspase-3, Bax, Bcl-2 and nerve growth factor NGF were verified by PCR and WB. Results ICP/MAP indicated that the erectile function of rats in the BCNI model group was severely impaired, which was rescued in the BCNI+LBP-LD and BCNI+LBP-HD groups. Rats in the BCNI model group can highly express inflammatory indicators NF-kb, TNF-α and apoptosis-related proteins Bax, Caspase-3. TUNEL confirmed that the level of apoptosis in the penile tissue of BCNI rats increased. The above-mentioned penile inflammation and apoptosis changes can be inhibited by LBP. In addition, both immunofluorescence and WB confirmed that rats in the LBP-LD and LBP-HD groups highly expressed nNOS and down-regulated the expression of TH. In vitro experiments have shown that LBP can promote the proliferation and migration of SC, increase the expression of Pmp22 and NGF, and the inflammation and apoptosis-related proteins were down-regulated. Conclusion LBP can relieve the inflammation and apoptosis at the original site of nerve injury by promoting the proliferation and migration of SC, and secretion of NGF, thereby inhibiting the inflammation and apoptosis caused by hypoxia after denervation of penile tissue, and improving penile erection. Disclosure Work supported by industry: no.

Acetyl-L-carnitine improves erectile function in bilateral cavernous nerve injury rats via promoting cavernous nerve regeneration.

Neurogenic erectile dysfunction (NED) caused by cavernous nerve (CN) injury is a typical complication after pelvic surgery, which lacks efficient treatments. Acetyl-L-carnitine (ALCAR) has been proven to promote nerve repair. To investigate the effect and potential mechanism of ALCAR in the treatment of NED. Thirty-two rats were randomly divided into bilateral CN injury (BCNI) group, BCNI + lower-dose ALCAR (50mg/kg/day) group, BCNI + higher-dose (100mg/kg/day) group, and sham-operated group. Erectile function was assessed 14 days after daily intraperitoneal injection of ALCAR or placebo. The penile tissues were gathered for subsequent histological and molecular biological analysis. Rat Schwann cell (SC) line S16 was used to verify the mechanism of ALCAR in vitro. We found that the erectile function of the rats in the BCNI group was severely impaired, which was improved considerably in both BCNI+ALCAR-LD and BCNI+ALCAR-HD groups. Also, we observed decreased smooth muscle and increased collagen content in the corpus cavernosum in the BCNI group. The expressions of fibrosis markers transforming growth factor-beta (TGF-β), connective tissue growth factor (CTGF), and Smad 2/3 were significantly up-regulated in the BCNI group. The above changes were alleviated after the administration of lower and higher-dose ALCAR. Meanwhile, the nitric oxide (NO)/cyclic guanosine monophosphate pathway (cGMP) was promoted and the Ras homolog gene family member A (RhoA)/Rho-associated protein kinase (ROCK) pathway was inhibited in the corpus cavernosum of BCNI rats after ALCAR treatment, accompanied by increased neuronal nitric oxide synthase (nNOS) and down-regulated tyrosine hydroxylase (TH). In vitro, ALCAR promoted the migration and proliferation of SC and increased the expression of 22-kD peripheral myelin protein and nerve growth factor (NGF). Further, rats treated with ALCAR had high expression of ATF3 and S100 in the distal nerve tissues of the CN extrusion site. ALCAR could promote nerve repair and regeneration, inhibit penile fibrosis, and improve penile erection by promoting the proliferation and migration of SC and the secretion of NGF. Our study confirms that ALCAR may be a potential treatment strategy for NED.

Monascus vinegar alleviates high-fat-diet-induced inflammation in rats by regulating the NF-κB and PI3K/AKT/mTOR pathways

Monascus vinegar (MV) is a typical fermented food with various health-promoting effects. This study aimed to evaluate the role of MV in alleviating high-fat-diet-induced inflammation in rats with hyperlipidemia and elucidate the possible regulatory mechanisms. In the study, serum lipid profiles, liver pathology and liver inflammatory cytokines were analyzed in hyperlipidemia rats with MV (0.5 mL/kg mb, 2 mL/kg mb). Results showed that the administration of MV alleviated dyslipidemia by decreasing the serum and liver levels of triglyceride and total cholesterol. Increase in hepatic lipase and carnitine palmitoyl transferase 1 (CPT-1) levels and decrease in hepatocyte steatosis, nephritis, and intestinal tissue injury in the HD group showed that high-dose MV can significantly suppress hepatic lipid accumulation and steatosis. In addition, compared with the model (MOD) group, the HD group showed significantly down-regulated the level of serum or hepatic alanine aminotransferase (ALT), aspartate aminotransferase (AST), CPT-1, interleukin (IL)-2, IL-6, IL-12, and tumor necrosis factor α (TNF-α). Moreover, the HD group showed repressed hepatic nuclear factor κB (NF-κB) pathway and inactivated phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway mitigated liver inflammation. Similar results were obtained from cell experiments. Collectively, these findings revealed that MV might attenuate high-fat-diet-induced inflammation by inhibiting the NF-κB and PI3K/Akt/mTOR pathways.

Evaluation of eryptosis in patients with chronic kidney disease.

Anemia in patients with chronic kidney disease (CKD) is the result of reduced erythropoietin, disturbed erythropoiesis and decreased lifespan of circulating erythrocytes. Excessive eryptosis or premature suicidal erythrocyte death is characterized by cell shrinkage and phosphatidylserine externalization. This study aimed to explore accelerated eryptosis and accompanying biochemical alterations in CKD patients. A total of 106 CKD patients (59 predialysis [PreD] patients, 26 haemodialysis [HD] patients and 21 peritoneal dialysis [PD] patients) and a control group composed of 29 healthy volunteers were included in this study. Data on superoxide dismutase (SOD) activity (U/mL), annexin-V binding (mean fluorescent intensity, MFI) and intracellular calcium ([Ca2+]i; MFI) as well as the hematologic and biochemical parameters were recorded. The [Ca2+]i levels were 3.05 ± 1.66 MFI, 2.24 ± 0.99 MFI, 2.38 ± 0.87 MFI and 1.71 ± 0.46 MFI in the PreD, HD, PD and control groups, respectively. Other than significantly higher [Ca2+]i levels in the PreD group than in the control group (p < 0.001), no significant difference was noted between study groups in terms of [Ca2+]i. Annexin-V binding was 1.05 ± 0.99 MFI in PreD group, 1.15 ± 0.56 MFI in HD group, 1.06 ± 0.87 MFI in PD group, and 0.88 ± 0.86 MFI in controls. Annexin-V binding was significantly higher in PreD, HD and PD groups compared with the control group (p < 0.001 for each). SOD activity was 0.07 ± 0.07 in the PreD group, 0.13 ± 0.08 in the HD group, 0.14 ± 0.07 in the PD group, and 0.03 ± 0.01 in the control group. SOD activity in both HD and PD groups were significantly higher than control and PreD groups (p < 0.001 for each). Lower albumin, higher ferritin, and higher parathormon levels were found to be correlated with eryptosis biomarkers. Patients treated vs. non-treated with calcium channel blockers had significantly lower annexin-V binding levels (p = 0.013). Patients treated vs. non-treated with erythropoietin (EPO) had elevated annexin-V binding level (p < 0.001) and lower [Ca2+]i (p = 0.014). In conclusion, our findings revealed the presence accelerated eryptosis, as a potential contributing factor to development of anemia, in patients with CKD stages 3-5D. Inflamation and parathormon can also accelerate eryptosis. Favorable effect of CCB and EPO on eryptosis needs to be confirmed in larger scale studies.

Effects of stocking density on growth performance, digestive function and immune performance of Matou goats

The objective of this study was to examine the effects of different stocking densities on Matou goats. Thirty-six female Matou goats were randomly assigned into three experimental treatments including the low density (LD, 0.67 goat/m2), the medium density (MD, 1 goat/m2) and the high density (HD, 2 goats/m2) group. Compared with LD group, the average daily weight gain (ADG) of HD group decreased (p < .05). The length of duodenal and ileal villi in HD group was significantly lower than that in LD group (p < .05). The rumen pH and concentration of total volatile fatty acid (VFA), propionate butyrate and ammonia-nitrogen increased in HD group (p < .05). The acetate/propionate ratio was the highest in MD group (p < .05). The mRNA expression level of agouti-related protein gene (AgRP) in hypothalamus of LD was higher than that in HD group (p < 0.05). Proopiomelanocortin (POMC) mRNA expression level was the highest in MD group (p<.05) and the lowest in HD group (p < .05). An increase in growth hormone receptor (GHR), insulin-like growth factor 1 (IGF1) and claudin-1 mRNA expression level were noticed in HD group (p<.05). Compared with LD group, the serum total protein (TP), albumin (Alb), globulin (Glb) IgA and IgG levels in HD group decreased (p < .05). Glucocorticoid (GCS), β-endorphin (β-EP) and cortisol levels in serum were also significantly increased in HD group compared with LD group (p < .05). These results showed that stocking density affected rumen environment and high stocking density resulted in a decrease in growth, digestive and immune function of Matou goats.

Prospective randomized controlled trial on the effectiveness of low-dose and high-dose intravenous tranexamic acid in reducing perioperative blood loss in single-level minimally invasive transforaminal lumbar interbody fusion

A prospective randomized controlled trial was conducted to study the effectiveness and safety of intravenous different doses tranexamic acid (TXA) in single-level unilateral minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF). The patients treated with single-level unilateral MIS-TLIF between September 2019 and October 2020 were enrolled and randomly classified into low-dose TXA (LD) group (n=39), high-dose TXA (HD) group (n=39), and placebo-controlled (PC) group (n=38). The LD, HD, and PC groups received intravenous TXA 20 mg/kg, TXA 50 mg/kg, the same volume of normal saline at 30 minute before skin incision after general anesthesia, respectively. There was no significant difference on baseline characteristics and preoperative laboratory results among 3 groups (P>0.05), including age, gender, body mass index, surgical segments, hematocrit (HCT), hemoglobin (HGB), prothrombin time (PT), international normalized ratio (INR), D-dimer, fibrin degradation products (FDP), activated partial prothromboplastin time (APTT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (Cr), urea. The intraoperative blood loss (IBL), postoperative drainage volume, operation time, total blood loss (TBL), hidden blood loss (HBL), blood transfusion, hematological examination indexes on the first day after operation, and the incidence of complications within 1 month were compared among the 3 groups. There were 3, 2, and 4 patients in the LD, HD, and PC groups who underwent autologous blood transfusion, respectively, and there was no allogeneic blood transfusion patients in the 3 groups. There was no significant difference in IBL, postoperative drainage volume, and operation time between groups (P>0.05). The TBL, HBL, and the decreased value of HGB in LD and HD groups were significantly lower than those in PC group (P<0.05), and TBL and HBL in HD group were significantly lower than those in LD group (P<0.05); the decreased value of HGB between LD group and HD group showed no significant difference (P>0.05). On the first day after operation, D-dimer in LD and HD groups were significantly lower than that in PC group (P<0.05); there was no significant difference between LD and HD groups (P>0.05). There was no significant difference in other hematological indexes between groups (P>0.05). All patients were followed up 1 month, and there was no TXA-related complication such as deep venous thrombosis of lower extremity, pulmonary embolism, and epilepsy in the 3 groups. Intravenous administration of TXA in single-level unilateral MIS-TLIF is effective and safe in reducing postoperative TBL and HBL within 1 day in a dose-dependent manner. Also, TXA can reduce postoperative fibrinolysis markers and do not increase the risk of thrombotic events, including deep venous thrombosis and pulmonary embolism.

Characterization of microbiome and metabolite analyses in patients with metabolic associated fatty liver disease and type II diabetes mellitus

BackgroundState-of-the-art renewal has indicated the improvement of diagnostics of patients with metabolic associated fatty liver disease (MAFLD) and/or type II diabetes mellitus (T2DM) by dissecting the clinical characteristics as well as genomic analysis. However, the deficiency of the characterization of microbial and metabolite signatures largely impedes the symptomatic treatment.MethodsFor the purpose, we retrospectively analyzed the clinical data of 20 patients with MAFLD (short for “M”), 20 cases with MAFLD and T2DM (short for “MD”), together with 19 healthy donors (short for “Ctr”). Microbial and metabolite analyses were further conducted to explore the similarities and differences among the aforementioned populations based on feces and blood samples, respectively.ResultsCompared with those in the Ctr group, patients with M or MD revealed multifaceted similarities (e.g., Age, ALP, LDL, BUN) and distinctions in clinical indicators of liver (e.g., BMI, ALT, PCHE, CAP). With the aid of microbial and metabolite analyses as well as bioinformatic analyses, we found that the characteristics of gut microbiota (e.g., abundance, hierarchical clustering, cladogram, species) and lipid metabolism (e.g., metabolite, correlation coefficient and scatter plot) were distinct among the indicated groups.ConclusionsThe patients with MD revealed multifaceted similarities and distinctions in characteristics of microbiome and metabolites with those in the M and HD groups, and in particular, the significantly expressed microbes (e.g., Elusimicrobiota, Berkelbacteria, Cyanobacteria, Peregrinibacteria) and lipid metabolites (e.g., Lipid-Q-P-0765, Lipid-Q-P-0216, Lipid-Q-P-0034, Lipid-Q-P-0800), which would collectively benefit the clinical diagnosis of MAFLD and T2DM.