GH Group Research Articles

Evaluating the Effectiveness of a Family-Based Virtual Childhood Obesity Management Program Delivered During the COVID-19 Pandemic in Canada: Prospective Study.

Generation Health (GH) is a 10-week family-based lifestyle program designed to promote a healthy lifestyle for families with children who are off the healthy weight trajectory in British Columbia, Canada. GH uses a blended delivery format that involves 10 weekly in-person sessions, and self-guided lessons and activities on a web portal. The blended program was adapted to be delivered virtually due to the COVID-19 pandemic. Currently, the effectiveness of the virtual GH program compared with that of the blended GH program remains unclear. We aimed to (1) compare the effectiveness of the virtual GH program delivered during the COVID-19 pandemic with that of the blended GH program delivered prior to the pandemic for changing child physical activity, sedentary and dietary behaviors, screen time, and parental support-related behaviors for child physical activity and healthy eating, and (2) explore virtual GH program engagement and satisfaction. This study used a single-arm pre-post design. The blended GH program (n=102) was delivered from January 2019 to February 2020, and the virtual GH program (n=90) was delivered during the COVID-19 pandemic from April 2020 to March 2021. Families with children aged 8-12 years and considered overweight or obese (BMI ≥85th percentile according to age and sex) were recruited. Participants completed preintervention and postintervention questionnaires to assess the children's physical activity, dietary and sedentary behaviors, and screen time, and the parent's support behaviors. Intervention feedback was obtained by interviews. Repeated measures ANOVA was used to evaluate the difference between the virtual and blended GH programs over time. Qualitative interviews were analyzed using thematic analyses. Both the virtual and blended GH programs improved children's moderate-to-vigorous physical activity (F1,380=18.37; P<.001; ηp2=0.07) and reduced screen time (F1,380=9.17; P=.003; ηp2=0.06). However, vegetable intake was significantly greater in the virtual GH group than in the blended GH group at the 10-week follow-up (F1,380=15.19; P<.001; ηp2=0.004). Parents in both groups showed significant improvements in support behaviors for children's physical activity (F1,380=5.55; P=.02; ηp2=0.002) and healthy eating (F1,380=3.91; P<.001; ηp2=0.01), as well as self-regulation of parental support for children's physical activity (F1,380=49.20; P<.001; ηp2=0.16) and healthy eating (F1,380=91.13; P<.001; ηp2=0.28). Families in both groups were satisfied with program delivery. There were no significant differences in attendance for the weekly in-person or group video chat sessions; however, portal usage was significantly greater in the virtual GH group (mean 50, SD 55.82 minutes) than in the blended GH group (mean 17, SD 15.3 minutes; P<.001). The study findings suggested that the virtual GH program was as effective as the blended program for improving child lifestyle behaviors and parental support-related behaviors. The virtual program has the potential to improve the flexibility and scalability of family-based childhood obesity management interventions.

RF14 | LBMON195 Once-weekly Somapacitan Is Effective And Well Tolerated In Children With GH Deficiency: A Randomized Phase 3 Trial

Abstract Growth hormone (GH) replacement therapy usually requires daily subcutaneous (s.c.) injections that can be burdensome for patients and their caregivers. Somapacitan, a long-acting reversible albumin-binding GH derivative, is in development for once-weekly s.c. administration in children with GH deficiency (GHD). REAL4 is a randomised, multi-national, open labelled, and active-controlled parallel group phase 3 trial, comprising a 52-week main phase and three-year extension period (NCT03811535). Two-hundred GH-treatment-naïve, prepubertal children with GHD (74.5% male) were randomly assigned in a 2: 1 ratio to receive 0.16 mg/kg/week s.c. somapacitan (n=132) or daily s.c. GH (0.034 mg/kg/day Norditropin®; n=68). The 52-week main trial results are presented here. The primary endpoint was annualized height velocity (HV) after 52 weeks of treatment. At week 52, the estimated mean HV was 11.2 cm/year for somapacitan compared to 11.7 cm/year for daily GH. The estimated treatment difference was -0.5 [95% CI -1.1 to 0.2] cm/year, confirming non-inferiority (non-inferiority threshold: -1.8 cm/year). Secondary height-related endpoints supported the primary endpoint. Insulin-like growth factor-I standard deviation score (IGF-I SDS) showed consistent increases for both somapacitan and daily GH over the 52 weeks, with change differences from baseline not statistically significant between treatment groups. At week 52, mean IGF-I SDS levels were similar between somapacitan (+0.28) and daily GH (+0.10) and within normal range (-2 to +2). Somapacitan was well tolerated, with no safety or local tolerability issues identified. There were no clinically relevant findings with respect to changes in glucose metabolism, no neutralizing anti-somapacitan or anti-GH antibodies were detected, and a low number of patients reported injection-site reactions, with similar proportions for somapacitan (5.3%) and daily GH (5.9%). In both treatment groups, 1.5% of patients reported injection site pain. Adherence was high for both treatments. The mean and median adherence for somapacitan treatment were 95.8% and 100%, respectively. The mean and median adherence for the daily GH group were 88.3% and 96.9%, respectively. In conclusion, once-weekly somapacitan has a similar efficacy and safety profile as daily GH with similar mean IGF-I levels in treatment-naïve children with GHD. Presentation: Sunday, June 12, 2022 1:06 p.m. - 1:11 p.m., Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

An observational study of pro- and anti-angiogenic factors in hypertensive disorders of pregnancy in women of African ancestry

Hypertensive disorders in pregnancy (HDPs) are the leading cause of maternal and perinatal deaths worldwide. Despite the widely reported multisystemic pathophysiology of pre-eclampsia and other HDPs, it is unknown whether these disorders represent a continuum or separate entities making clinical diagnosis a challenge. This study aimed to investigate angiogenic, metabolic and immunoregulatory specific profiles of hypertensive and gestationally matched normotensive pregnancies. A total of 200 pregnancies from a regional hospital in South Africa, via convenience sampling, were quantitatively analysed for circulating sFlt-1; PlGF; VEGF; sENG; PAPP-A; PP13; ADAMTS 12; TGF-β1 in maternal serum samples using ELISA technique. Serum protein markers TGF-β1, sENG and PAPP-A were significantly increased (p < .05) in early-onset pre-eclampsia vs. NG1 groups. sFlt-1 was significantly higher in late-onset pre-eclampsia vs NG2 groups. The GH group showed a significant increase in TGF-β1 and PAPP-A vs. NG1 counterpart. ADAMTS12 and sENG were significantly lower in gestational hypertension vs. early-onset pre-eclampsia. No significant differences were seen in PlGF, VEGF and PP13 levels across the groups. These changes show the HDP spectrum has distinct characteristics on the angiogenic profile. Based on these results, further validation of diagnostic and prognostic biomarkers of pre-eclampsia and gestational hypertension is warranted. Impact statement What is already known on this subject? Hypertensive pregnancy disorders are a public health problem with adverse effects on both mother and neonate. The elusive pathogenesis of this syndrome combined with the late prevalence of symptoms leaves clinicians with a myriad of theories and indefinite treatments. The investigation into conventional anti-/angiogenic factors has been extensively studied in pre-eclampsia patients only. The overlapping clinical presentation of pre-eclampsia and gestational hypertension further complicates the diagnosis of disorders. What do the results of this study add? The investigation of novel angiogenic, metabolic and inflammatory markers will firstly contribute to generating a database for researchers both nationally and internationally. This combinatory triad of markers will assist in elucidating and differentiating between early- and late-onset preeclampsia versus gestational hypertension. The results of our cohort study suggest possible early diagnostic markers for pre-eclampsia and gestational hypertension. What are the implications of these findings for clinical practice and/or further research? Research in this area will contribute to an improvement in early disease management which will ultimately lead to a reduction in health care costs and mortality rate locally and globally. It will also enforce diagnostic and prognostic markers for hypertensive pregnancy diseases and warrant further investigation into the proteins primarily involved in the trophoblastic invasion. This will then clarify whether these two closely related hypertensive disorders represent a continuum or two separate entities.

Quantitative proteomic analysis of gingival crevicular fluids to identify novel biomarkers of gingival recession in orthodontic patients

ObjectiveTo identify gingival recession-related biomarkers in orthodontic patients, we compared the proteome of gingival crevicular fluids (GCF) from healthy gingiva without orthodontic treatment (GH), healthy gingiva undergoing orthodontic treatment (OGH), and recessed gingiva undergoing orthodontic treatment (OGR). MethodsGCF samples were obtained from the anterior teeth of 15 volunteers (n = 5/group). Quantitative proteomic analysis was performed using DIA-based liquid chromatography-tandem mass spectrometry (LC-MS/MS). Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were used to annotate differentially expressed proteins (DEPs). Receiver-operating characteristic (ROC) analysis was performed to detect and filter biomarker candidates, while Protein-Protein Interaction (PPI) Networks were utilized to determine the interactions between these DEPs. ResultsA total of 253, 238, and 101 DEPs were found in OGR vs. OGH, OGR vs. GH, and OGH vs. GH groups, respectively. Based on the Venn diagram of three groups, 128 DEPs in OGR vs. OGH group were identified as specific proteins associated with progressive gingival recession (GR) during orthodontic treatment. Molecular function analysis showed that 128 DEPs were enriched in “molecular binding”, including antigen binding, RNA binding, double-stranded RNA binding, cadherin binding involved in cell-cell adhesion, vinculin binding, S100 protein binding, and Ral GTPase binding. The majority of these DEPs were also involved in cytoskeletal regulation. In addition, biological process analysis showed an enrichment in translation, while cellular component analysis indicated that 128 DEPs were related to extracellular exosome. Furthermore, Ribosome and Phagosome were the top two terms in KEGG analysis. The results of ROC analysis demonstrated that 26 proteins could be potential biomarker candidates for GR. PPI networks analysis predicted that IQGAP1, ACTN1, TLN1, VASP, FN1, FERMT3, MYO1C, RALA, RPL35, SEC61G, KPNB1, and NPM1 could be involved in the development of GR via cytoskeletal regulation. ConclusionsIn summary, we identified several GCF proteins associated with GR after orthodontic treatment. These findings could contribute to the prevention of GR in susceptible patients before the initiation of orthodontic treatment. SignificanceOrthodontic patients with GR often report esthetic defects or root hypersensitivity during orthodontic treatment, especially at the anterior teeth site. GCF, rich in protein, is an easily accessible source of potential biomarkers for the diagnosis of periodontal diseases; however, little is known about the changes in GCF proteome associated with GR in orthodontic patients. In this study we firstly used DIA-based LC-MS/MS to evaluate the proteome and to identify the biomarker candidates for GR in orthodontic patients. These findings will improve our understanding of GR during orthodontic treatment, and could contribute to an earlier diagnosis, or even prevention, of GR in susceptible populations before orthodontic treatment.

Early patient-reported outcomes are a promising predictive factor of cancer progress and outcome in older patients: The EPROFECY study.

12045 Background: Contrary to commonly-held beliefs, older patients (OPs, aged 70 or more) in oncology are compliant with the use of a telemonitoring digital platform. Such a tool allows the medical team to gain detailed knowledge of the tolerance profile of patients, and help monitor and maintain their quality of life, which is a particularly important goal for older patients. The EPROFECY study assesses the predictive power of the patient health status in the first month of treatment, evaluated with the digital telemonitoring platform Cureety, on survival. Methods: This prospective study was conducted at the Military Hospital Bégin on OPs. Patients were allowed to respond to a symptomatology questionnaire based on CTCAE v.5.0, personalized to their pathology and treatment. An algorithm evaluated the patient status based on reported adverse events: correct (A), compromised (B), to be monitored (C) and critical state (D). For A/B (good health status), the patient received therapeutic advice to help manage each of the reported adverse events. For C/D (poor health status), the patient was invited to call the hospital. To assess the early tolerance of patience to their treatments, we determined the health status in the 1st month after initiation of treatment, which was classified as “Good health” (GH, majority of A/B reports) or “Poor health” (PH, majority of C/D reports). The primary endpoint was to assess if the first-month tolerance is a predictive factor of progression free-survival (PFS). The secondary endpoint was to assess if the first-month tolerance is a predictive factor of overall survival (OS). Results: Sixty-one patients were enrolled between July 1st, 2020 and September 30th, 2021. The median age was 78.0 years (range 70.0 – 99.0), with 81% presenting a metastatic stage, and the most represented cancer being prostate cancer. The median follow-up was 8.2 months. Overall, 2299 ePRO were completed, 89% (n= 2036) corresponding to a "correct" or a "compromised" state and only 11% (n=263) corresponding to a state "to be monitored" or "critical". Based on the first month of questionnaires, 62% of the patients were classified in the GH group, and 38% in the PH group. The PFS ratio at 6 months was 64.6 % in GH vs 23.4 % in PH (HR = 0.1980, 95% CI = 0.04431–0.8845, p = 0.0339). The OS ratio at 6 months was 100% in GH versus 95.5 % in PH (HR: 0.69, 95 % CI = 0.06 – 8.29, p = 0.77). Conclusions: This is the first study that assesses the use of PRO-based tolerance as a predictive factor of treatment response in older individuals. We demonstrated here a significant 80% reduction in the risk of progression in OPs that exhibited a good first-month tolerance. This suggests that e-PRO follow-up might be an effective predictor of response and a tool to treatment plan.

Guava seed polysaccharides ameliorate the inflammatory status in PC-3 xenograft mice

This work evaluates the effects of guava seed polysaccharide (GSPS) on inflammatory status in the experiment mice under PC-3 human prostate cancer stress for 4 weeks. Dietary control (DC group, 0 mg GSPS/kg BW/day), 50 (GL group), 250 (GM group) as well as 500 mg GSPS/kg BW/day (GH group) by gavage, positive control (PC group, 1 mg paclitaxel/week, i.p.) and non-treatment control (NTC group, normal mice without treatment) were designed in the experiment. Changes in tumor weights, serum non-specific antibody titers, Th1/Th2 cytokines secreted by splenocytes and pro-/anti-inflammatory cytokines secreted by peritoneal macrophages from the experiment mice were measured. As a result, GH group significantly (P < 0.05) decreased serum (IgM+IgA)/IgG ratio, but GL and GM groups slightly increased (IgM+IgA)/IgG ratios compared to that of DC group, demonstrating a differential effect on the serum antibody profile. Even though GSPS administration just slightly (P > 0.05) enhanced the effect to decrease tumor weights, there was a significantly (P < 0.05) negative correlation between tumor weights and (IgM+IgA)/IgG antibody titer ratios. GSPS administrations enhanced a Th2-inclined immune balance in splenocytes and anti-inflammatory responses in peritoneal macrophages in the experiment mice. Pro-inflammatory cytokine secretions by peritoneal macrophages were positively correlated with PC-3 tumor weights in vivo, inferring that anti-inflammatory cytokine secretions increased in vivo may decrease PC-3 tumor weight. Taken together, our results evidence that GSPS administrations ameliorated the inflammatory status in the experiment mice under PC-3 prostate cancer stress via regulating Th1/Th2 and pro-/anti-inflammatory cytokine secretion profiles toward Th2-inclined and anti-inflammatory immunity.

Effect of Gestational Diabetes on Postpartum Depression-like Behavior in Rats and Its Mechanism.

Recent studies have reported a strong association between gestational diabetes mellitus (GDM) and postpartum depression (PPD), but little is known about the underlying physiological mechanism. In this study, a GDM rat model was used to evaluate the direct effect of GDM on PPD and to explore the mechanism. After parturition, the GDM dams were divided into two groups: blood glucose not recovered group (GH group) and blood glucose recovered group (GL group). Fasting plasma glucose (FPG), cortisol (COR) and serotonin (5-hydroxytryptamine, 5-HT) metabolism were continuously monitored during the lactation period, until postnatal day 21. PPD was evaluated by behavioral tests. At the endpoint, the expression of the key enzymes of Trp metabolic pathway in colon and brain tissues was analyzed by immunohistochemistry and western blot. The microbe composition of colonic contents was determined by 16S rDNA gene sequencing. The results showed that GDM induced postpartum depression-like behavior in rats. The HPA axis hormone did not show the typical stress state of depression, but the level of 5-HT decreased significantly in serum, prefrontal cortex and hippocampus, and the Kyn/Trp ratio increased significantly in serum and prefrontal cortex, implying the switch of the tryptophan (Trp) metabolism from the 5-HT pathway to the kynurenine (Kyn) pathway. The expression of Indoleamine 2,3-dioxygenase (IDO), a key rate-limiting enzyme in Kyn metabolism, was up-regulated in the colon and brain, which was an important reason for this switch. This switch was accelerated by a decrease in the expression of tryptophan hydroxylase (TPH), a key enzyme of the 5-HT production pathway, in the colon. GDM dams displayed significant changes in gut microbiome profiles, which were correlated with depression. The ratio of Firmicutes to Bacteroidetes decreased. Lactobacillus and Bacteroides were negatively correlated with 5-HT level and positively correlated with Kyn level, whereas Clostridium XlVa and Ruminococcus were positively correlated with 5-HT level. These results suggest that GDM disrupts both the Trp pathway and the composition of the gut microbiota, which provide a putative physiological basis for PPD.

Ameliorating the efficacy of galacto-oligosaccharides on ovalumin-induced allergic dermatitis symptoms in Balb/c mice by regulating Th2 immune response and the ecosystem of gut microbiota.

In this study, we evaluated the effect of oral administration of galacto-oligosaccharide (GOS), famous biological molecules that are comprised of galactose and lactose, on ovalbumin (OVA)-induced allergic dermatitis. OVA-induced mice were divided into the OVA-administered group (OVA-C), promethazine hydrochloride-administered group (PC), and 100 and 200 mg kg-1 GOS-administered groups (GL and GH, respectively). GOS administration significantly improved epidermal thickness and decreased CD4+ cell numbers. The concentrations of IgE, OVA-specific IgE, and inflammatory cytokines (IL-4, IL-5, and INF-γ) in GH group mice were significantly lower than those in OVA-C group mice. Firmicutes and Bacteroidetes were identified as the major phyla in the intestinal microbiota in mice, and the relative abundance of Deferribacteres was significantly lower in the GH group than in the OVA-C group. Deferribacteraceae and Mucispirillum species were significantly lower in the GH group than in the OVA-C group. The relative abundance of Muribaculum species was significantly lower, but those of Lachnospira and Lactococcus species were significantly higher in the GH group than in the OVA-C group. Our results suggest that the alleviation effect of GOS on allergic dermatitis induced by OVA sensitization was achieved by regulating hypersensitive immune responses by improving the intestinal microbial ecosystem.

The relationship between ghrelin and inflammation in diabetic rat stomach

Ghrelin is a hormone that regulates the digestive system, as well as has immunomodulating effects. The aim of this study is to explain effects of ghrelin on inflammation and oxidative stress parameters in the stomach. Male Sprague Dawley rats 8-10 weeks old (n = 21) were randomly divided into three groups as control, type 2 diabetes (T2DM) and diabetes and given exogenous ghrelin (T2DM+Gh). The daily feed and water intake of the animals were measured. The levels of interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor (TNF-α), and interleukin-10 (IL-10) mRNA in tissues were analyzed using RT-PCR technique. Ghrelin and nuclear factor-κβ (NF-κβ) peptides were detected by immunohistochemistry. T2DM group had a significant increase in water intake when compared to control group. T2DM group had significantly higher levels of IL-6, IL-1, and IL-10 mRNA expression than control group. IL-1β and IL-10 mRNA expression were significantly lower in T2DM+Gh group than in T2DM group. In T2DM group, NF-κβ was higher than in control group, but it was lower in T2DM+Gh group. In terms of oxidative stress, there were non-significant changes. According to our findings, exogenous ghrelin intake was found to be highly effective in reducing inflammation in stomach tissue with type 2 diabetes (Tab. 1, Fig. 3, Ref. 33). Text in PDF www.elis.sk Keywords: ghrelin, rat, type 2 diabetes, stomach, inflammation.

Effect of Growth Hormone on Outcome of Pediatric Burn Patients

Abstract Background A burn is a thermal injury caused by biological, chemical, electrical and physical agents with local and systemic repercussions. There are several ways of classifying burns: Classification by mechanism or cause, Classification by the degree and depth of a burn, Classification by extent of burn the extent of burn. Objectives The objective of this study was to determine the safety and efficacy of using recombinant human growth hormone (rhGH) in the treatment of pediatric burn victims and their ICU length of stay, mortality and morbidity. Patients and Methods This study was an Interventional randomized controlled Double Blind Study in which Patients subdivided randomly into 2 groups: Group A received somatotropine hormone after their 3 days of resuscitation besides their conventional treatment during their stay in the Burn ICU. Group B received the conventional treatment only in the Burn ICU. Results The comparison between the GH group and the control group showed that the mean ICU stay in days in GH group was 10.88 while in the control group 13.59 with P value 0.018 as a significant result as the GH group showed a less ICU stay time than the control group with approximately 20%. Mortality in the GH group was 6.2% from the total number of the group while in control group 18.8% from the total number of the group with P value 0.033 as a significant result yet the mortality may also depend on other factors as the degree of burn and the area of burn and the associated events like inhalational injury or delay post burn or any other co-morbidity. Morbidity results seen was 0% in control group and 4.7% in GH group with P value 0.080 as a non-significant result, morbidity was in the form of hyperglycemia. Conclusion The use of recombinant Growth hormone with a dose of 0.2 mg/Kg SQ 2 days per week with 3 days time interval in pediatric burn patients after their primary resuscitation from the burn injury, shows a marvelous improvement concerning the ICU stay time as the patient received the growth hormone showed an approximately 20% time less ICU stay than the control group this may be accounted for the faster wound healing and readiness for grafting and even faster graft healing, also a decreased mortality in a significant way, although mortality may depend on many factors in burn patients like degree of burn and the area of burn and the associated events like inhalational injury or any other co-morbidity.

A Prospective Clinical Study of the Effect of Recombinant Human Growth Hormone in Wound Healing of Severely Burned Children

Abstract Background A burn is a thermal injury caused by biological, chemical, electrical and physical agents with local and systemic repercussions. There are several ways of classifying burns: Classification by mechanism or cause, depth and extent of burn . Objectives The objective of this study was to determine the safety and efficacy of using recombinant human growth hormone (rhGH) in the treatment of pediatric burn victims and their probable effect on accelerating burn wound healing. Patients and Methods This study was an Interventional randomized controlled Double Blind Study in which Patients subdivided randomly into 2 groups: Group A received somatotropine hormone after their 3 days of resuscitation besides their conventional treatment during their stay in the Burn ICU. Group B received the conventional treatment only in the Burn ICU. Results The comparison between the GH group and the control group showed that that there was statistically significant difference found between the two studied groups regarding TBSA of burn at 3rd week. The mean TBSA in GH group was ( 9.06 ± 7.47 ) while in the control group (13.94 ± 11.96) with P value (0.041). There was highly statistically significant difference found between the two studied groups regarding Insulin like growth factor .the mean Insulin like growth factor in GH group was (16.48 ± 11.40) while in the control group(2.77 ± 0.64) with P value(0.000). Conclusion The use of recombinant Growth hormone with a dose of 0.2 mg/Kg SQ 2 days per week with 3 days time interval in pediatric burn patients after their primary resuscitation from the burn injury, shows a marvelous improvement concerning the total body surface area of burn(TBSA) as the patient received the growth hormone showed a decrease total body surface area of burn(TBSA) than the control group. This may be accounted for the faster wound healing and readiness for grafting .

Characterisation of Rapid In Situ Forming Gelipin Hydrogel for Future Use in Irregular Deep Cutaneous Wound Healing.

The irregular deep chronic wound is a grand challenge to be healed due to multiple factors including slow angiogenesis that causing regenerated tissue failure. The narrow gap of deep wounds could hinder and slow down normal wound healing. Thus, the current study aimed to develop a polymerised genipin-crosslinked gelatin (gelipin) hydrogel (GNP_GH) as a potential biodegradable filler for the abovementioned limitations. Briefly, GNP_GH bioscaffolds have been developed successfully within three-minute polymerisation at room temperature (22–24 °C). The physicochemical and biocompatibility of GNP_GH bioscaffolds were respectively evaluated. Amongst GNP_GH groups, the 0.1%GNP_GH10% displayed the highest injectability (97.3 ± 0.6%). Meanwhile, the 0.5%GNP_GH15% degraded within more than two weeks with optimum swelling capacity (108.83 ± 15.7%) and higher mechanical strength (22.6 ± 3.9 kPa) than non-crosslinked gelatin hydrogel 15% (NC_GH15%). Furthermore, 0.1%GNP_GH15% offered higher porosity (>80%) and lower wettability (48.7 ± 0.3) than NC_GH15%. Surface and cross-section SEM photographs displayed an interconnected porous structure for all GNP_GH groups. The EDX spectra and maps represented no major changes after GNP modification. Moreover, no toxicity effect of GNP_GH against dermal fibroblasts was shown during the biocompatibility test. In conclusion, the abovementioned findings indicated that gelipin has excellent physicochemical properties and acceptable biocompatibility as an acellular rapid treatment for future use in irregular deep cutaneous wounds.

The Influence of Maternal Obesity on Cell-Free Fetal DNA and Blood Pressure Regulation in Pregnancies with Hypertensive Disorders.

Background and Objectives: obesity and blood pressure disorders are one of the main risk factors for antenatal, intra, postpartum, and neonatal complications. In preeclampsia (PE), the placental hypoxia leads to vascular endothelium dysfunction, cell necrosis, and apoptosis. This condition is associated with the release of free fetal DNA (cffDNA) circulating in plasma. The disturbance of the efficiency of vasodilatation and blood pressure regulation in PE can be confirmed by analyzing the apelin, salusin, and prosalusin. This study aimed to assess the influence of obesity on cffDNA, and the effectiveness of maintaining normal blood pressure in patients with preeclampsia and gestational hypertension. Material and Methods: the research material was blood serum and oral mucosa swabs, obtained from 168 patients. Pregnant women were divided into the following: a control group (C)—67 women; a gestational hypertension group (GH)—35 patients; a preeclampsia with obesity group (PE + O) (pre-gravid BMI > 30)—23 patients. The rest were lean preeclamptic women (PE)—66 patients—(pre-gravid BMI < 25 in 43 women). Results: the cffDNA was observed in 1.50% of women in the C group, in 2.45% in the GH group, but in 18.18% of lean patients with preeclampsia. The cffDNA was detected in 58% of obese pregnant women with PE. The greater the placental hypoxia was in preeclampsia, the less efficient the hypotensive mechanisms, according to an analysis of the studied adipokines. The prosalusin concentration was significantly lower in the PE group with cffDNA than in the PE group without it (p = 0.008). Apelin was higher in the PE group with cffDNA (p = 0.006) compared to other groups. The same results were also observed in the subgroup with obesity. Conclusion: in preeclamptic women, obesity seems to act as an additive factor of placental damage by means of the dysregulation of hypotensive mechanisms.

RNA-seq and nuclear proteomics provide insights into the lactation regulation mechanism of goat transfected IGF-I and GH recombinant vectors

There exists little available information on the mechanisms of lactation regulation until now. In order to explore the underlying mechanism, we injected IGF-I and GH recombinant vectors into the mammary gland, then RNA-seq analysis and nuclear proteomics were used for rapid high-throughput screening of DEGs and DEPs in the two groups linked to lactation regulation. KEGG analysis of 206 DEGs showed that the same 4 of top 10 enrichment pathways (ECM receptor interaction, protein digestion and absorption, focal adhesion and phagosome) involved in 4 co-expressed genes (IDO, BTG1, ITGB6 and keratin 83), the two groups enriched different metabolic pathways yet. Nuclear proteomics analysis showed 75 and 36 DEPs in the IGF-I and GH group respectively; Sixteen common proteins were identified between the IGF-I group and GH group, four of which (ALB, TPT1, CXXC-5 and ACTR2) significantly decreased and three of which (PRP1, PAG-9 and Hsp70) significantly increased. Similarly, DEPs in the two groups were enriched in same one of top 10 enrichment pathways (PI3K-Akt signaling pathway). Protein-protein interaction networks highlighted the contribution of glycosphingolipid biosynthesis, porphyrin and chlorophyll metabolism and the Jak-STAT signaling pathway to lactation regulation of GH and IGFI. GH and IGF-I improve milk yield, which may be linked to important nodal proteins (ALB and ACTB). Our research advances the understanding of the mammary gland transcriptome and nuclear proteomics during GH and IGF-I overexpression. Individual genes, proteins and pathways in this study point towards potential targets for lactation regulation.

Capacity of Japanese institutions to manage obstetrical disseminated intravascular coagulation in 2018: A national surveillance questionnaire and retrospective cohort study.

To investigate the management of obstetrical disseminated intravascular coagulation (DIC) in Japan. We sent a surveillance questionnaire to 2299 institutions to collect details about the deliveries they performed in 2018. We investigated differences in the management of obstetrical DIC among three types of institutions: perinatal medical centers (PMCs), general hospitals with obstetrical facilities (GHs), and maternal clinics with beds (MCs). We received responses from 703 institutions (30.6% of the total mailed) with results of 306 799 women who gave birth in 2018. In Japan, the potential to treat postpartum hemorrhage and obstetrical DIC was high in the PMC group, moderate in the GH group, and low in the MC group. The incidence of obstetrical DIC in the PMC group (0.44%) was significantly higher than that in the GH (0.21%) and MC (0.06%) groups. The mortality of women with obstetrical DIC in PMCs (1.3%) was similar to that in GHs (0.6%) and MCs (0.0%). The percentages of PMCs that always or sometimes transfused fresh frozen plasma or fibrinogen concentrates (100% and 42.2%, respectively) were significantly higher than those in the GH (88.2% and 29.5%, respectively) and MC groups (29.4% and 5.3%, respectively). Furthermore, institutions whose internal protocols mandated that replacement therapy be always administered in women with obstetrical DIC scores of ≥8 had similar protocols to those for women with fibrinogen levels of ≤1.5g/L. The capacity to provide therapy for postpartum hemorrhage and obstetrical DIC varied widely among the three groups of institutions.

Second trimester maternal serum D-dimer combined with alpha-fetoprotein and free \u03b2-subunit of human chorionic gonadotropin predict hypertensive disorders of pregnancy: a systematic review and retrospective case\u2013control study

BackgroundThis study investigated whether maternal serum D-dimer (DD) alone or DD combined with alpha-fetoprotein (AFP) and free β-subunit of human chorionic gonadotropin (free β-hCG) in the second trimester could be used to predict hypertensive disorders of pregnancy (HDP).Materials and methodsIn this retrospective case–control study, the data of gravidas patients who delivered at hospital were divided into the following groups: control (n = 136), gestational hypertension (GH, n = 126), preeclampsia (PE, n = 53), and severe preeclampsia (SPE, n = 41). Receiver operator characteristic (ROC) curves were used to evaluate the diagnostic value of maternal serum DD, AFP, and free β-hCG levels for HDP.ResultsDD levels of the GH, PE, and SPE groups were significantly higher than that of the control group (P < 0.001). The order of effectiveness for models predicting HDP was as follows: DD + AFP + free β-hCG > DD > DD + AFP > DD + free β-hCG > AFP + free β-hCG > AFP > free β-hCG. For predicting different types of HDP, DD alone had the best diagnostic value for SPE, followed by PE and GH. DD alone had a sensitivity of 100% with a 0% false negative rate and had the highest positive likelihood ratio (+ LR) for SPE. DD alone in combination with AFP alone, free β-hCG alone and AFP + free β-hCG could reduce false positive rate and improve + LR.ConclusionDD is possible the best individual predictive marker for predicting HDP. Levels of DD alone in the second trimester were positively correlated with the progression of elevated blood pressure in the third trimester, demonstrating the predicting the occurrence of HDP. The risk calculation model constructed with DD + free β-hCG + AFP had the greatest diagnostic value for SPE.

Molecular Mechanism of Aluminum-Induced Oxidative Damage and Apoptosis in Rat Cardiomyocytes.

Aluminum exposure can mediate either acute toxicity or chronic toxicity. Aluminum exerts toxic effects on the cardiovascular system, but there are few studies on its related mechanisms. In this study, we investigated the molecular mechanism of aluminum-induced oxidative damage and apoptosis in rat cardiomyocytes. Thirty-two male Wistar rats were randomly divided into four groups, including the control group (GC), low-dose group of aluminum exposure (GL), medium-dose group (GM), and high-dose group (GH), with eight rats in each group. The GL, GM, and GH groups were given 5, 10, and 20 mg/(kg·d) of AlCl3 solution by intraperitoneal injection, and the GC group received intraperitoneal injection of the same volume of normal saline (2 ml/rat/day), 5 times a week for 28 days. At the end of the experiment, the levels of aluminum, malondialdehyde (MDA), plasma lactate dehydrogenase (LDH), creatine kinase (CK), creatine kinase isoenzyme (CKMB), and alpha-hydroxybutyrate dehydrogenase (HBDH) were measured. The pathological changes of myocardium were observed by H&E staining. The apoptosis of cardiomyocytes was detected by TUNEL staining, and the expression of apoptosis-related proteins was determined by western blot. The results showed that the levels of CKMB and HBDH in the GM and GH groups were significantly higher than those in the GC group (P < 0.05). The content of aluminum in the myocardium and serum of the aluminum exposure groups was significantly higher than that of the GC group (P < 0.05). The level of MDA in the GM and GH groups was significantly higher than that in the GC group (P < 0.05). The pathological results showed that vacuolated and hypertrophied cardiomyocytes were found in aluminum exposure groups, especially in the GM and GH groups. The TUNEL staining showed that the apoptosis rate of the aluminum exposure groups was considerably higher than that of the GC group (P < 0.05). Western blot showed that the expression of Bcl-2, an anti-apoptotic protein, in cardiomyocytes of aluminum exposure groups was lower than that of the GC group (P < 0.05), while the levels of Bax and caspase-3 in the cardiomyocytes of the GM and GH groups were higher than those of the GC group (P < 0.05). The experimental results showed that aluminum could accumulate in myocardial tissues and cause damage to cardiomyocytes. It could induce oxidative stress damage by increasing the content of MDA in cardiomyocytes and trigger cardiomyocyte apoptosis by activating the pro-apoptotic proteins caspase-3 and Bax and reducing the anti-apoptotic protein Bcl-2.

MHC II-PI3K/Akt/mTOR Signaling Pathway Regulates Intestinal Immune Response Induced by Soy Glycinin in Hybrid Grouper: Protective Effects of Sodium Butyrate.

Soy glycinin (11S) is involved in immune regulation. As an additive, sodium butyrate (SB) can relieve inflammation caused by 11S. To further delve into the mechanisms. A diet containing 50% fishmeal was the control group (FM group), and the experimental groups consisted of the FM group baseline plus 2% glycinin (GL group), 8% glycinin (GH group), and 8% glycinin + 0.13% sodium butyrate (GH-SB group). The specific growth ratio (SGR), feed utilization, and density of distal intestinal (DI) type II mucous cells were increased in the GL group. In the serum, IFN-γ was significantly upregulated in the GL group, and IgG and IL-1β were upregulated in the GH group. IgG, IL-1β, and TNF-α in the GH-SB group were significantly downregulated compared to those in the GH group. The mRNA levels of mTOR C1, mTOR C2, and Deptor were upregulated in the GL, GH, and GH-SB groups in the DI compared with those in the FM group, while the mRNA levels of mTOR C1 and Deptor in the GH group were higher than those in the GL and GH-SB groups. 4E-BP1, RICTOR, PRR5, MHC II, and CD4 were upregulated in the GH group. TSC1, mLST8, and NFY mRNA levels in the GL and GH-SB groups were upregulated compared with those in the FM and GH groups. Western blotting showed P-PI3KSer294/T-PI3K, P-AktSer473/T-Akt, and P-mTORSer2448/T-mTOR were upregulated in the GH group. Collectively, our results demonstrate that low-dose 11S could improve serum immune by secreting IFN-γ. The overexpression of IgG and IL-1β is the reason that high-dose 11S reduces serum immune function, and supplementing SB can suppress this overexpression. Low-dose 11S can block the relationship between PI3K and mTOR C2. It can also inhibit the expression of 4E-BP1 through mTOR C1. High-dose 11S upregulates 4E-BP2 through mTOR C1, aggravating intestinal inflammation. SB could relieve inflammation by blocking PI3K/mTOR C2 and inhibiting 4E-BP2. Generally speaking, the hybrid grouper obtained different serum and DI immune responses under different doses of 11S, and these responses were ultimately manifested in growth performance. SB can effectively enhance serum immunity and relieve intestinal inflammation caused by high dose 11S.

Efficacy of growth hormone supplementation with ultrashort GnRH antagonist in IVF/ICSI for poor responders; randomized controlled trial

ObjectivesTo compare the ICSI-ET outcomes in poor responders who underwent ovarian stimulation by the ultrashort GnRH antagonist protocol with or without adjuvant GH injection. Material and methodsThis randomized controlled study was conducted at Al-Azhar University from December-2018 to June-2019 upon 156 participants. All patients received the same preparations. After randomization, in the study group, women have received GH 4 IU/day subcutaneous injection from the second day of the cycle stopped one day before ovum pickup. While in the control group, women have received subcutaneous saline in the same dosing as in the study group. After intervention, all procedures were the same in both groups. The main outcome measure was the clinical pregnancy rate. Statistical analysis was based on the intention-to-treat population. ResultsBoth groups were comparable with regard their baseline characteristics (p-values > 0.05). Ovulation characteristics were comparable (p-values > 0.05). The level of E2 is significantly (p-value = 0.003) higher in the GH group. The oocyte retrieved number was significantly (p-value < 0.001) higher in the GH group 4.94 ± 1.77 than in the control group 3.74 ± 1.82. The mean number of MII oocytes was significantly (p-value < 0.001) higher in the GH group 3.3 ± 1.36 than in the control group 2.29 ± 1.24. Fertilization characteristics, implantation rate, pregnancy rate were comparable (p-values > 0.05). ConclusionDespite the fact that this study showed no significant increase in the clinical and chemical pregnancy rates by the addition of GH to the ultrashort antagonist protocol in poor responders, the number of retrieved oocytes was significantly higher in the GH group. Clinical trial registrationClinicalTrials.gov Identifier: NCT03759301.

Comparative Evaluation of Surface Roughness of Resin- Modified Glass Ionomer and Glass Hybrid Restorative Materials Simulated by Tooth Brushing: An in-Vitro Study

Objective: To compare the effect of tooth brushing on surface roughness of Resin-Modified Glass Ionomer Cement (RMGIC; GC Gold label 2LC Light Cured Universal Restorative) and Glass Hybrid (GH; GC EQUIA SYSTEM- EQUIA Forte™ Fil and EQUIA Forte™ Coat) restorative material at 1- and 3-months interval simulated by tooth brushing . Material and Methods: RMGIC and GH material specimens (20 each) were prepared according to manufacturer instructions in 10 mm × 2 mm dimensions using a mylar strip. A specially designed toothbrush simulator was used along with Oral B Pro 2 2000N powered toothbrush and Colgate Total dentifrice (Colgate-Palmolive India limited; Relative dentin abrasivity - RDA: 70 - Low abrasive) to perform brushing strokes. Specimens were subjected to surface roughness analysis before and after simulated tooth brushing at baseline, 1, and 3 months. Results: The intragroup comparison was done using repeated-measures ANOVA. Intergroup comparisons were done using an independent sample t-test and General Linear Model (ANCOVA). Surface roughness increased from baseline through 3 months in both RMGIC and GH groups. The mean surface roughness in RMGIC group was significantly higher than GH group at baseline 1 and 3-months, respectively (p<0.001, <0.001, and <0.001). Interaction between group and baseline surface roughness was not significant (p=0.466). The estimated marginal means were significantly higher in RMGIC than GH group (p=0.008) . Conclusion: The surface roughness of both RMGIC and GH restorative increased from baseline to 1 month and 3 months after the simulated toothbrushing protocol. GH exhibited significantly lower surface roughness than RMGIC at all the tested intervals.