Restricted Subgroup Research Articles

Asociación del nivel de ácido úrico en suero con los beneficios del control intensivo de la presión arterial

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Association of serum uric acid with benefits of intensive blood pressure control

Introduction and objectivesIntensive systolic blood pressure (SBP) control improved outcomes in the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial. Whether the serum uric acid concentration at baseline alters the benefits of intensive SBP control is unknown. MethodsThe STEP trial was a randomized controlled trial that compared the effects of intensive (SBP target of 110 to<130mmHg) and standard (SBP target of 130 to <150mmHg) SBP control in Chinese patients aged 60 to 80 years with hypertension. The primary outcome was a composite of cardiovascular disease events. This post hoc analysis was performed to examine whether the effects of intensive SBP intervention differed by the baseline uric acid concentration using 2 models: restricted cubic spline curves and subgroup analyses, both based on the Fine-Gray subdistribution hazard model in the analysis of the primary outcome and secondary outcomes (excluding all-cause death). In the analysis of all-cause death, the Cox regression model was used. We also examined the change in the follow-up uric acid concentrations. ResultsOverall, the risk of the primary outcome rose as the cumulative uric acid concentration increased in both the intensive and standard treatment groups. Patients with intensive treatment had a lower multivariable-adjusted subdistribution hazard ratio for the primary outcome, but with a wide overlap of 95%CI. Next, we stratified patients according to their baseline uric acid concentration (tertile 1 [T1], <303.0μmol/L; tertile 2 [T2], 303.0 to <375.8μmol/L; and tertile 3 [T3], ≥375.8μmol/L). Subgroup analyses using tertiles provided HRs and 95%CI in T1 (HR, 0.55; 95%CI, 0.36–0.86; P=.008), T2 (HR, 0.80; 95%CI, 0.56–1.14; P=.22) and T3 (HR, 0.86; 95%CI, 0.60–1.21; P=.39), with an interaction P value of .29. The results for most of the secondary outcomes followed the same trends. ConclusionsThere was no evidence that the benefit of the intensive SBP control differed by baseline uric acid concentrations. This trial was registered at ClinicalTrial.gov (Identifier: NCT03015311).

Modified Myocardial Performance Index in Fetal Growth Disturbances as Diagnostic and Prognostic Adjunct.

Fetal growth disturbance can be associated with cardiac dysfunction. This study aimed to assess the modified myocardial performance index in growth-restricted and appropriate for gestational age fetuses and evaluate both its prognostic value in perinatal period and also its association with adverse perinatal outcomes. Totally 131 pregnant women were included in this prospective study. Of these, 56 cases were in study group with a diagnosis of small fetus and 75 cases were in control group with a diagnosis appropriately grown fetus. Fetal echocardiography was performed in all pregnant women to measure modified myocardial performance index. Umbilical, middle cerebral and uterine artery Doppler ultrasound parameters were measured in the study group. Small fetuses were categorized into 2 subgroups of late-onset fetal growth restriction and small for gestational age. Modified myocardial performance index was significantly higher in small fetuses compared to controls (0.45 vs. 0.37, P <.001). Newborn intensive care unit admission rates were significantly higher in small fetuses than in controls (chi-square test, P <.001). The highest mean modified myocardial performance index was recorded in the late-onset fetal growth restriction subgroup (0.45 vs. 0.41 vs. 0.37). The sensitivity and specificity of modified myocardial performance index in predicting adverse outcomes at a cut-off value of 0.41 were 63% and 75%, respectively. There was a significant negative correlation between modified myocardial performance index values and birth weights. We found higher left fetal heart modified myocardial performance index values in small fetuses indicating the presence of prenatal cardiac dysfunction. Fetal myocardial performance deteriorates in concordance with severity of growth restriction. Modified myocardial performance index can also be used to predict adverse perinatal outcomes among growth-restricted fetuses.

Is time-restricted eating (8/16) beneficial for body weight and metabolism of obese and overweight adults? A systematic review and meta-analysis of randomized controlled trials.

Time-restricted eating (TRE) is a new therapeutic strategy for the management of weight loss and dysmetabolic diseases. At present, TRE (8/16, 8h eating:16 h fasting) is the most common form of TRE. Therefore, this meta-analysis included randomized controlled trials (RCTs) on TRE (8/16) in overweight and obese adults to determine its impact on body weight and metabolism. Articles reviewed from PubMed, Ovid MEDLINE, Embase, and Cochrane Central Register for the relevant RCTs that compared TRE (8/16) to non-TRE in overweight and obese adults. Eight RCTs were included in this meta-analysis. Participants following TRE (8/16) showed significant body weight reduction (mean difference [MD]: -1.48 kg, 95% confidence interval [CI]: -2.53 to -0.44) and fat mass reduction (MD: -1.09 kg, 95% CI: -1.55 to -0.63). There was no significant difference in lean mass change with TRE intervention (MD: -0.48 kg, 95% CI: -1.02 to 0.05, p=.08, I 2=41%). The energy restriction and early TRE (eTRE) subgroups resulted in greater weight loss. TRE (8/16) showed beneficial effects on the homeostatic model assessment of insulin resistance (HOMA-IR, MD: -0.32, 95% CI: -0.59 to -0.06), but had no significant effect on other parameters of glucose metabolism and lipid profiles. In conclusion, TRE (8/16), especially eTRE, or in combination with caloric intake restriction, is a potential therapeutic strategy for weight control in overweight and obese adults. TRE (8/16) also reduced HOMA-IR; therefore, it may have a positive effect on glucose metabolism.

Plasma acylcarnitine and diabetic retinopathy: A study from Eastern China.

Acylcarnitines (ACars) are important for insulin resistance and type 2 diabetes (T2D). However, their roles in diabetic retinopathy (DR) remain controversial. In this study, we aimed to investigate the association of ACars with DR and their values in DR detection. This was a two-center case-control study based on the propensity score matching approach between August 2017 to June 2018 in Eastern China. Multivariable logistic regression models were applied to estimate the association of plasma ACars with DR. Differential ACars were screened by models of least absolute shrinkage and selection operator, elastic net, and weighted quantile sum regression, and their roles in DR identification were further evaluated by the area under the receiver operating curve (AUC). Eight of twenty plasma ACars (8:0, 12:0, 12:1, 14:1, 16:2, 18:0, 18:2 and 18:3) were associated with DR, while only ACar 8:0 was selected by three variable selection methods. As compared to those with the 1st tertile of ACar 8:0, the adjusted odds ratio (OR) and 95% confidence interval (CI) of DR were 0.22 (0.08, 0.59) and 0.12 (0.04, 0.36) for subjects in the 2nd and 3rd tertiles, respectively (P for trend < 0.001). Consistent associations were also observed in both restricted cubic spline regression models and subgroup analyses. AUC (95% CI) were 0.74 (0.66, 0.82) for ACar 8:0 alone and 0.77 (0.70, 0.85) for ACar 8:0 combined with covariates. Our findings suggest higher ACar 8:0 is significantly associated with a decreased risk of DR, which provides a unique window for early identification of DR.

Greater bone marrow fat and myosteatosis are associated with lower vBMD but not asymptomatic vertebral fracture.

Organ fat may affect bone metabolism and be associated with vertebral fracture (VF). This study aimed to explore relationships between VF, adiposity indexes measured by MRI, and volumetric BMD (vBMD) measured by quantitative CT (QCT). Four hundred volunteers, ranging in age from 22 to 83 years, were recruited and underwent same-day abdominal QCT and chemical shift-encoded (CSE) MRI. We used MRI to quantify the fat content of bone marrow (BMF), psoas major and paraspinal muscles, and the liver. Abdominal fat, VF, and vBMD of the lumbar spine were measured by QCT. For VF discrimination analysis, we examined both the whole cohort (60 VF cases in 30 men and 30 women) and a restricted subgroup of those aged over 50 years (50 VF cases in 23 men and 27 women). Amongst the men, a 1 SD increase in BMF was associated with a 27.67 (95% CI, -32.71 to -22.62) mg/cm3 decrease in vBMD after adjusting for age and BMI. Amongst women, all adiposity indexes except for liver fat were significantly associated with vBMD, with BMF having the strongest association (β, -24.00; 95% CI, -28.54 to -19.46 mg/cm3). Similar findings were also observed in participants aged over 50 years. The associations of adiposity indexes with vertebral fracture were not significant after adjusting for age in both sexes aged over 50 years. In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. However, marrow fat and other adipose tissues were not associated with radiographic-based prevalent vertebral fractures. • In both sexes, higher bone marrow fat was associated with lower vBMD at the spine. • Among women, all adiposity indexes except for liver fat content were significantly associated with vBMD, with bone marrow fat having the strongest association. • Marrow fat and other adipose tissues were not associated with radiographic-based asymptomatic vertebral fractures.

Association between tourniquet use and intraoperative blood loss during below-knee amputation.

BACKGROUNDDespite over 150000 amputations of lower limbs annually, there remains a wide variation in tourniquet practice patterns and no consensus on their necessity, especially among orthopedic patient populations. The purpose of this study was to determine whether tourniquet use in orthopedic patients undergoing below knee amputation (BKA) was associated with a difference in calculated blood loss relative to no tourniquet use.AIMTo determine if tourniquet use in orthopedic patients undergoing BKA was associated with a difference in calculated blood loss relative to no tourniquet use.METHODSWe performed a retrospective review of consecutive patients undergoing BKA by orthopedic surgeons at a tertiary care hospital from 2008 through 2018. Blood loss was calculated using a combination of the Nadler equation for preoperative blood volume and a novel formula utilizing preoperative and postoperative hemoglobin levels and transfusions. Univariate and forwards step-wise multivariate linear regressions were performed to determine the association between tourniquet use and blood loss. A Wilcoxon was used to determine the univariate relationship between tourniquet use and blood loss for in the restricted subgroups of patients who underwent BKA for trauma, tumor, and infection.RESULTSOf 97 eligible patients identified, 67 underwent surgery with a tourniquet and 30 did not. In multivariate regression, tourniquet use was associated with a 488 mL decrease in calculated blood loss (CI 119-857, P = 0.01). In subgroup analysis, no individual group showed a statistically significant decrease in blood loss with tourniquet use. There was no significant association between tourniquet use and either postoperative transfusions or reoperation at one year.CONCLUSIONWe found that tourniquet use during BKA is associated with decreased calculated intraoperative blood loss. We recommend that surgeons performing this procedure use a tourniquet to minimize blood loss.

Meta-analysis of Zinc Supplementation on Laying Performance, Egg Quality Characteristics, and Blood Zinc Concentrations in Laying Hens.

There are inconsistent results on the influence of zinc (Zn) supplementation levels on productive indices of laying hens. This study, therefore, uses meta-analysis to synthesis evidence on the effect of inclusion of Zn in chicken diets on performance, egg quality, and blood Zn status of laying hens. Eleven studies were identified and used to analyze the effect of diets with or without Zn supplementation on feed intake, feed conversion ratio (FCR), hen day egg production (HDEP), egg weight (EW), egg mass (EM), Haugh unit (HU) scores, eggshell thickness (EST), eggshell weight (ESW), and blood Zn concentrations in laying hens. Data extracted from the 11 studies included in the meta-analysis were pooled using a random-effects model and expressed as standardized mean differences (SMDs) at a 95% confidence interval (CI). Results indicate that dietary Zn supplementation reduced FCR (SMD = - 0.50g feed/g egg; 95% CI: - 0.68 to - 0.31) and increased HDEP (SMD = 0.33%; 95% CI: 0.18 to 0.48), EW (SMD = 0.14g; 95% CI: 0.03 to 0.25) and EM (SMD = 0.58g/hen/day; 95% CI: 0.22 to 0.95), HU (SMD = 0.64; 95% CI: 0.42 to 0.85), EST (SMD = 0.84mm; 95% CI: 0.45 to 1.23), and plasma Zn concentration (SMD = 4.20mg/dl; 95% CI: 2.99 to 5.40) compared with the controls. In contrast, feed intake and ESW were not significantly different from controls. Restricted subgroup analysis indicated that chosen moderators (age of hen, inclusion level, chicken breed/strain, and supplementation duration) influenced the results of this meta-analysis. There was evidence of significant heterogeneity, and meta-regression indicated that moderators explained most of the sources of heterogeneity. We conclude that dietary zinc supplementation had positive effect on feed conversion ratio, laying performance, aspects of egg quality traits, and blood zinc concentrations in laying hens. The findings from this meta-analysis will help in policy advancements and sustainable use of zinc in the egg production industry.

Cerebrospinal fluid proteomics targeted for central nervous system processes in bipolar disorder.

The etiopathology of bipolar disorder is largely unknown. We collected cerebrospinal fluid (CSF) samples from two independent case-control cohorts (total n = 351) to identify proteins associated with bipolar disorder. A panel of 92 proteins targeted towards central nervous system processes identified two proteins that replicated across the cohorts: the CSF concentrations of testican-1 were lower, and the CSF concentrations of C-type lectin domain family 1 member B (CLEC1B) were higher, in cases than controls. In a restricted subgroup analysis, we compared only bipolar type 1 with controls and identified two additional proteins that replicated in both cohorts: draxin and tumor necrosis factor receptor superfamily member 21 (TNFRSF21), both lower in cases than controls. This analysis additionally revealed several proteins significantly associated with bipolar type 1 in one cohort, falling just short of replicated statistical significance in the other (tenascin-R, disintegrin and metalloproteinase domain-containing protein 23, cell adhesion molecule 3, RGM domain family member B, plexin-B1, and brorin). Next, we conducted genome-wide association analyses of the case-control-associated proteins. In these analyses, we found associations with the voltage-gated calcium channel subunit CACNG4, and the lipid-droplet-associated gene PLIN5 with CSF concentrations of TNFRSF21 and CLEC1B, respectively. The reported proteins are involved in neuronal cell-cell and cell-matrix interactions, particularly in the developing brain, and in pathways of importance for lithium's mechanism of action. In summary, we report four novel CSF protein associations with bipolar disorder that replicated in two independent case-control cohorts, shedding new light on the central nervous system processes implicated in bipolar disorder.

The U-Shaped Association of Non-High-Density Lipoprotein Cholesterol Levels With All-Cause and Cardiovascular Mortality Among Patients With Hypertension.

Background: Non-high-density lipoprotein cholesterol (non-HDL-C) is a valuable indicator in routine blood lipid tests, but the associations of non-HDL-C with mortality in hypertensive population still remain uncertain.Methods: In the National Health and Nutrition Examination Surveys from 1999 to 2014, participants having hypertension were included and grouped by non-HDL-C levels (<130, 130–159, 160–189, 190–219, and ≥220 mg/dl). Multivariate Cox regression was conducted for calculation of hazard ratios (HR) and 95% confidence interval (CI). To reveal the relationship between non-HDL-C and mortality, Kaplan–Meier survival curves, restricted cubic spline, linear regression, and subgroup analysis were also applied.Results: A total of 12,169 participants (47.52% males, mean age 57.27 ± 15.79 years) were included. During average follow-up of 92.5 months, 1,946 (15.99%) all-cause deaths and 422 (3.47%) cardiovascular deaths occurred. After adjusting for confounders, the association of non-HDL-C with mortality was detected as U-shaped. Threshold values were observed at 158 mg/dl for all-cause mortality and 190 mg/dl as to cardiovascular mortality. Below the threshold, every 10 mg/dl increment in non-HDL-C attributed to relatively low all-cause mortality significantly (HR = 0.94, 95% CI: 0.92–0.96). Above the threshold, non-HDL-C has significant positive associations with both all-cause (HR = 1.03, 95% CI: 1.01–1.05) and cardiovascular mortality (HR = 1.09, 95% CI: 1.05–1.14). For subgroups analysis, similar results were found among participants age <65 years old, non-white population, those were not taking lipid-lowering drugs, and subjects with body mass index (BMI) ≥25 kg/m2.Conclusion: The U-shaped association was detected between non-HDL-C and mortality among hypertensive population.

The Traf2DNxBCL2-tg Mouse Model of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma Recapitulates the Biased IGHV Gene Usage, Stereotypy, and Antigen-Specific HCDR3 Selection of Its Human Counterpart.

Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma (SLL) is a heterogeneous disease consisting of at least two separate subtypes, based on the mutation status of the immunoglobulin heavy chain variable gene (IGHV) sequence. Exposure to antigens seems to play a role in malignant transformation and in the selection and expansion of more aggressive CLL clones. Furthermore, a biased usage of particular IGHV gene subgroups and the existence of stereotyped B-cell receptors (BCRs) are distinctive characteristics of human CLL. We have previously described that Traf2DN/BCL2 double-transgenic (tg, +/+) mice develop CLL/SLL with high incidence with aging. In this model, TNF-Receptor Associated Factor (TRAF)-2 deficiency cooperates with B cell lymphoma (BCL)-2 in promoting CLL/SLL in mice by specifically enforcing marginal zone (MZ) B cell differentiation and rendering B cells independent of BAFF for survival. In this report, we have performed the sequencing of the IGHV-D-J rearrangements of B cell clones from the Traf2DN/BCL2-tg+/+ mice with CLL/SLL. The results indicate that these mice develop oligoclonal and monoclonal B cell expansions. Allotransplantation of the oligoclonal populations into immunodeficient mice resulted in the preferential expansion of one of the parental clones. The analysis of the IGHV sequences indicated that 15% were mutated (M) and 85% unmutated (UM). Furthermore, while the Traf2DN/BCL2-tg-/- (wild-type), -/+ (BCL2 single-tg) and +/- (Traf2DNDN single-tg) littermates showed the expression of various IGHV gene subgroups, the CLL/SLL expanded clones from the Traf2DN/BCL2-tg+/+ (double-transgenic) mice showed a more restricted IGHV gene subgroup usage and an overrepresentation of particular IGHV genes. In addition, the HCDR3-encoded protein sequence indicates the existence of stereotyped immunoglobulin (Ig) in the BCRs and strong similarities with BCR recognizing autoantigens and pathogen-associated antigens. Altogether, these results highlight the remarkable similarities between the CLL/SLL developed by the Traf2DN/BCL2-tg+/+ mice and its human counterpart.

The potential association between a new angiogenic marker fractalkine and a placental vascularization in preeclampsia

PurposeImpaired angiogenesis is one of the most common findings in preeclamptic placentas. A new angiogenetic role of fractalkine (CX3CL1) is recently recognized apart from inflammatory activity. In this study, a link between CX3CL1 and the development of placental vasculature in preeclampsia was examined.MethodsThe study comprised 52 women allocated to Group 1 (normotensive, n = 23) and Group 2 (preeclampsia, n = 29). In each group Doppler parameters, serum levels of CX3CL1, soluble fms-like tyrosine kinase-1 (sFlt-1), and placental growth factor (PlGF) were assessed between 30 and 32 week of pregnancy. After the delivery, placental samples were taken and the vascularization and expression of CX3CR1 receptor were assessed after immunostaining.ResultsCX3CL1 and sFlt-1 serum levels were significantly higher levels in Group 2 vs Group 1, while PlGF serum levels was significantly lower in Group 2. Lower cerebroplacental ratio (CPR) was observed in Group 2. The vascular/extravascular tissue index (V/EVTI) was significantly lower in Group 2, while compared to Group 1, with the lowest value in the fetus growth restriction (FGR) subgroup (0.18 ± 0.02; 0.24 ± 0.03; 0.16 ± 0.02, respectively). The expression of examined CX3CR1 was higher in Group 2, while compared to Group 1, reaching the highest values in FGR subgroup. There was a moderate negative correlation between birth weight, V/EVTI and CX3CL1 serum level and CX3CR1 placental expression in the group of pregnancies complicated with preeclampsia.ConclusionThe significant underdevelopment of placental vascular network in preeclampsia is associated with the change in the CX3CL1/CX3CR1 system, especially in FGR complicated pregnancies.

The Long History of Vitamin C: From Prevention of the Common Cold to Potential Aid in the Treatment of COVID-19.

From Pauling’s theories to the present, considerable understanding has been acquired of both the physiological role of vitamin C and of the impact of vitamin C supplementation on the health. Although it is well known that a balanced diet which satisfies the daily intake of vitamin C positively affects the immune system and reduces susceptibility to infections, available data do not support the theory that oral vitamin C supplements boost immunity. No current clinical recommendations support the possibility of significantly decreasing the risk of respiratory infections by using high-dose supplements of vitamin C in a well-nourished general population. Only in restricted subgroups (e.g., athletes or the military) and in subjects with a low plasma vitamin C concentration a supplementation may be justified. Furthermore, in categories at high risk of infection (i.e., the obese, diabetics, the elderly, etc.), a vitamin C supplementation can modulate inflammation, with potential positive effects on immune response to infections. The impact of an extra oral intake of vitamin C on the duration of a cold and the prevention or treatment of pneumonia is still questioned, while, based on critical illness studies, vitamin C infusion has recently been hypothesized as a treatment for COVID-19 hospitalized patients. In this review, we focused on the effects of vitamin C on immune function, summarizing the most relevant studies from the prevention and treatment of common respiratory diseases to the use of vitamin C in critical illness conditions, with the aim of clarifying its potential application during an acute SARS-CoV2 infection.

Meta-analysis of the Effect of Ginger (Zingiber officinale) on Health Status, Production Indices and Semen Quality in Chickens

Nutritional strategies that improve growth performance indices in chickens without increasing feed consumption are desirable considering the escalating feed cost. The use of spices to maintain health and increase productivity in livestock and poultry has been documented. However, a consensus has not been attained whether ginger, one of such spices, improves productivity in poultry. Therefore, the aim of this meta-analysis was to ascertain the effect of ginger administration on chicken performance. We searched AGORA, Scopus, Science Direct and Google Scholar for papers published in English using Boolean operators, proximity searching, wildcard and alternate spelling. Selected criteria were randomized and control trials with chickens, studies published in peer-reviewed journals, reported at least one presentation form of ginger and outcomes of interest and a measure of dispersion (standard deviation or p value). Twenty-one papers that satisfy the selection criteria were employed to determine the impact of ginger on feed intake, body weight gain (BWG), feed conversion ratio (FCR), organ weight, semen parameters and total serum lipid (triglyceride and cholesterol) content using Open Meta-analyst for Ecology and Evolution software. A positive relationship was found between ginger and semen quality in chickens. Ginger administration improved BWG (Hedges’ d, d = 0.495; 95% confidence interval (CI) = 0.041–0.949; p = 0.033) and FCR (d = − 0.732; 95% CI − 1.195 to − 0.270; p = 0.002) taking cognizance of publication bias and heterogeneity. Restricted subgroup analysis showed there is a positive association between ginger powder and FCR (d = − 0.732; 95% CI = 1.195 to − 0.270; p = 0.002). Meta-regression revealed that covariates (duration of administration, dietary form, inclusion level and strain) explained most of the heterogeneity. The occurrence of variations and publication bias does not pose a major problem in this study since a relatively large number of unpublished studies will be needed to change significant impacts. In conclusion, meta-analytical results suggest enhanced performance in chickens on different levels of ginger administration.

A meta-analysis of iron-based additives on enhancements of biogas yields during anaerobic digestion of organic wastes

The profitability of biogas industries largely depends on substrate biodegradability. Most of the substrates for sustainable energy recovery via anaerobic digestion like lignocellulosic materials contains complex polymeric substances and requires some enhancements to achieve optimum biodegradability. Previous studies have reported that the use of iron additives improved both degradability of such substrates and biogas yield, but iron-based enhancements have shown variability in the input and yield results. This evidence-based study used meta-analysis in determining the performances of iron-based additives on biogas yield. Previously published articles on the subject were systematically identified and compiled based on set inclusion criteria. The database was used to analyze the influence of iron-based additives on the enhancement of biogas yield during anaerobic digestion of organic wastes. The pooled effect estimates at 95% confidence interval was generated with the use of Random-effects model. The overall result of the meta-analysis performed showed that iron-based additives supplementation significantly enhanced biogas yield at Standard mean difference = 1.451, 95% CI: 1.280–1.622, p < 0.001. Restricted subgroup analysis indicated that all the moderators had a significant influence on biogas yield of iron-based treated anaerobic digestion processes at p < 0.001. Evidence of heterogeneity was observed, while meta-regression analysis indicated that most of the sources of heterogeneity were explained by the additive-types, substrate-types, dosage range and research location at p < 0.05. The result of this study showed the potential of iron-based additives supplementation to improve biogas yield during anaerobic digestion of organic wastes. The information from this study avails important suggestions on policy advancements and sustainable usage of iron-based enhanced anaerobic digestion processes in biogas industries.

Groups with restricted non-permutable subgroups

A subgroup [Formula: see text] of a group [Formula: see text] is said to be permutable if [Formula: see text] for every subgroup [Formula: see text] of [Formula: see text] and the group [Formula: see text] is called metaquasihamiltonian if all subgroups of [Formula: see text] are either permutable or abelian. It is known that a locally graded metaquasihamiltonian group [Formula: see text] is soluble with derived length at most [Formula: see text] and contains a finite normal subgroup [Formula: see text] such that all subgroups of the factor [Formula: see text] are permutable. In this paper, we describe locally graded groups in which the set of all nonmetaquasihamiltonian subgroups satisfies the minimal condition and locally graded groups with the minimal condition on subgroups which are neither abelian nor permutable. Moreover, it is proved here that a finitely generated hyper-(abelian or finite) group whose finite homomorphic images are metaquasihamiltonian is itself metaquasihamiltonian.

Groups with no proper contranormal subgroups

We consider which groups G are nilpotent if they have a nilpotent normal subgroup N with G/N a restricted soluble group and if G is the only contranormal subgroup of G. This supplements Kurdachenko, Otal, and Subbotin work of 2009, where they consider the corresponding question but with G/N nilpotent and N a restricted soluble normal subgroup.

Meta-analysis of the influence of phytobiotic (pepper) supplementation in broiler chicken performance

The aim of the study is to use meta-analytical procedure to resolve uncertainty, identify knowledge gaps, and create new insights using published data on the phytobiotic effect of dietary pepper intervention on daily feed intake (DFI), average daily gain (ADG), and feed conversion ratio (FCR) in broiler chickens. The authors accessed AGORA, Scopus, ScienceDirect, and Google Scholar databases for primary studies published between 2011 and 2018 using combinations of different search terms. Fifteen studies were included to assess phytobiotic effect of pepper on DFI, FCR, and ADG in broiler chickens. Random-effects model (REM) was used to generate pooled effect estimates at 95% confidence intervals (CI). Analysis was performed using Open Meta-analyst for Ecology and Evolution (OpenMEE) software, while publication bias and source of heterogeneity were assessed using standard methods. Dietary pepper supplementation enhanced ADG (standardized mean difference (SMD) = 0.576, 95% CI 0.444 to 0.707, p < 0.001) and FCR (SMD = 0.325, 95% CI - 0.453 to - 0.196, p < 0.001) considering the presence of heterogeneity and publication bias. DFI (SMD = 0.052, 95%CI - 0.069 to 0.173, p = 0.403) was not significantly influenced by dietary pepper supplementation. Restricted subgroup analysis revealed that both black and red pepper increased ADG (p < 0.001). Broilers on black pepper intervention had better FCR (p = 0.002) than broilers on red pepper treatment. Higher (p < 0.05) DFI was obtained on broilers fed pepper-based diet at the rate of > 6 g/kg feed for 35 days. There was no association between DFI and explanatory variables (broiler strain used and number of broilers used), whereas study country influenced DFI (p < 0.001). Furthermore, there was an association between outcome of interests (ADG and FCR) and explanatory variables (supplementation level, study country, number of broilers used per treatment group, and broiler strain used). Broilers on dietary pepper intervention for 42 days had higher ADG (SMD = 62.2 g/bird/day, p < 0.001) than those on dietary pepper intervention for 56 days (SMD = 35.7 g/bird/day, p = 0.002). There is evidence of heterogeneity, and meta-regression analysis showed that study country, supplementation level, and broiler strain used explained most of the sources of heterogeneity. The results of the present study revealed the potential of dietary pepper intervention to improve production efficiency in broiler chickens. The current meta-analysis also set the steps for standardized experimental designs on the use of dietary pepper intervention in broiler feeding trials in the future.

1730P - Influence of eribulin on proliferation, migration and invasion properties of leiomyosarcoma cell line models

BackgroundEribulin has an effect on proliferation, migration and invasion of sarcoma and breast cancer in vitro assays. A phase III clinical trial in patients with advanced liposarcoma (LPS) or leiomyosarcoma (LMS) showed an improvement in overall survival (OS) for the eribulin arm compared to dacarbazine, although no benefit was observed in the LMS restricted subgroup. Based on these results, eribulin was approved only for advanced LPS patients. The aim of the current study is to evaluate the effect of eribulin on key cell properties, like proliferation, migration, and invasion in LMS cell lines, in conventional 2D, but also 3D culture models. MethodsEribulin was kindly provided by Eisai Inc. (Andover, USA) and tested on CP0024 and SK-UT-1 human LMS cell lines. Cellular proliferation was determined by SRB assay on 2D, and measured by spheroid diameter and by propidium iodide and calcein-AM double staining in 3D cultures by Celigo Platform (Nexcelom, Lawrence, USA).Cells were treated with increased concentrations of eribulin to determine IC50 values and its effect on proliferation. Chemotaxis and invasion were determined using transwell assay on 2D culture. Spheroids grown during 4 days were laid or embedded in matrigel for 3D assays and quantified over 3-7 additional days. ResultsBoth cell lines had a mesenchymal-like appearance on monolayer culture, although SK-UT-1 had a more compact spheroid pattern compared to CP0024. Proliferation, migration, and invasion were examined after exposure to eribulin. The results showed that eribulin is active on both cell lines inhibiting proliferation in 2 and 3D culture conditions at concentrations below the nanomolar range. Moreover, eribulin significantly inhibited migration and invasion. To our knowledge, these findings are the first to demonstrate the effect of eribulin in LMS cell line 3D models. ConclusionsOur results support the in vitro activity of eribulin in LMS cell lines and its further exploration as an agent with clinical benefit in patients with LMS. Legal entity responsible for the studyThe authors. FundingEisai. DisclosureM. Mendiola: Research grant / Funding (institution), Travel / Accommodation / Expenses: Eisai. A. Gallego Martínez: Travel / Accommodation / Expenses, Non-remunerated activity/ies, training courses: Eisai. A. Redondo: Honoraria (self), Research grant / Funding (institution): Eisai. All other authors have declared no conflicts of interest.

U-shaped association between low-density lipid cholesterol and diabetes mellitus in patients with hypertension

BackgroundThe magnitude and direction of association of low-density lipid cholesterol (LDL-C) with diabetes mellitus (DM) might differ by hypertensive status, but there is limited epidemiological evidence in China.MethodsWe examined the association between LDL-C levels and DM in 9892 participants with hypertension using logistic regression. Participants were stratified into three groups according to LDL-C levels (desirable, borderline high or high), then further divided into quartiles. Restricted cubic spline regression models, subgroup analysis and interaction tests were also conducted to evaluate the shape of association.ResultsAfter adjusting for covariates, lower LDL-C had a significant and inverse association with the likelihood of DM in all participants (OR: 0.944, 95% CI = 0.893, 0.998). In participants with desirable LDL-C concentrations (< 3.4 mmol/L), LDL-C protected against DM (OR = 1.240, 95% CI = 1.076, 1.429 per 1 mmol/L decrease). In participants with higher LDL-C concentrations (> 4.1 mmol/L), LDL-C increased the DM likelihood (OR = 1.536, 95% CI = 1.126, 2.096 per 1 mmol/L increase). Restricted cubic spline regression also found a U-shaped association between LDL-C levels and DM prevalence.ConclusionsThere was a U-shaped association between LDL-C levels and DM in Chinese patients with hypertension.