Cord-blood derived chemistry reference values in preterm infants for sodium, chloride, potassium, glucose, and creatinine

Objectives: Guidelines recommend preterm infants be supported to maintain their serum electrolytes within “normal” ranges. In term babies, cord blood values differed in pathological pregnancies from healthy ones. Study design: We examined cord blood sodium, chloride, potassium, glucose, and creatinine to derive maturity-related reference intervals. We examined associations with gestational age, delivery mode, singleton versus multiple, and prenatal maternal adverse conditions. We compared preterm cord values to term, and to adult reference ranges. Results: There were 591 infants, 537 preterm and 54 term. Preterm cord glucose levels were steady (3.7+/-1.1mmol/l), while sodium, chloride and creatinine increased over GA by 0.17, 0.14 and 1.07 micromol/week respectively (p<0.003). Average preterm cord potassium and chloride were higher than term (p<0.05). Compared to adult reference intervals, cord preterm reference intervals were higher for chloride (100-111 vs 98-106 mmol/l), lower for creatinine (29-84 vs 62-115 micromol/l), more variable for potassium (2.7-7.9 vs. 3.5-5.0 mmol/l) and sodium (130-141 vs. 136-145 mmol/l). Cesarean section was associated with higher potassium and lower glucose; multiple births with higher chloride and creatinine and lower glucose; SGA with lower glucose. Conclusions: Cord blood values vary across the GA range with increases in sodium, chloride and creatinine while glucose remained steady. Average preterm reference values were higher than term values for potassium and chloride. Preterm reference values differed from published adults’ reference values. The varies across GA and by delivery mode, SGA, and being a multiple, which may have direct implications for neonatal care and fluid management.

The Association Between Medicare Annual Wellness Visits and Detection and Management of Diabetes Among Older Adults

The rising prevalence of diabetes mellitus (DM) among older adults is an increasing concern in the U.S. and is expected to nearly triple within the next 40 years. The purpose of this study is to investigate the effectiveness of Medicare Annual Wellness Visits (AWV) utilization on the management of DM among Medicare beneficiaries using data from 26,703 Medicare beneficiaries seen at 13 primary care community clinics (clinic visits between 2017 and 2019). A total of 34% of Medicare beneficiaries participated in an AWV. The total sample was, on average, 72.6 years old (SD=7.0), 57% female, 84% White, and 91% non-Hispanic and had between zero and three co-morbid conditions. The AWV group was significantly younger (mean difference 2.0 years; p&lt;.001) and had fewer comorbid conditions (mean difference 0.1; p&lt;.001) than the non-AWV group at their initial visits. Comparing AWV and non-AWV groups at the first patient visit and last patient visit, there were significantly fewer patients with DM in the AWV group compared to the non-AWV groups (19.2% vs. 24.7%; p&lt;.001 and 53.5% vs. 59.2%; p&lt;.001). DM management was better in the AWV group compared to the non-AWV group at both the first and last patient visits, as exhibited by lower A1C levels (M= 5.9(SD=0.8) vs. M=6.2(SD=1.1); p&lt;.001 and M= 6.6(SD=0.8) vs. M=6.9(SD=1.4); p=.013), lower glucose levels (M=114.0(SD=34.0) vs. M=123.0(SD=51.0); p&lt;.001), and fewer DM medications (M=0.1(SD=.4) vs. M=0.2(SD=0.5); p&lt;.001 and M=0.2(SD=0.6) vs. M=0.3(SD=0.6); p&lt;.001). These results suggest that AWV are effective managing diabetes in older adults Medicare beneficiaries.

The dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide: a novel cardiometabolic therapeutic prospect

Incretin hormones are peptides released in the intestine in response to the presence of nutrients in its lumen. The main incretins are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 stimulates insulin secretion, inhibits glucagon secretion at pancreatic α cells and has also extrapancreatic influences as slowing of gastric emptying which increases the feeling of satiety. GIP is the main incretin hormone in healthy people, causative of most the incretin effects, but the insulin response after GIP secretion in type 2 diabetes mellitus (T2DM) is strongly reduced. Therefore, in the past GIP has been considered an unappealing therapeutic target for T2DM. This conception has been changing during recent years, since it has been reported that resistance to GIP can be reversed and its effectiveness restored by improving glycemic control. This fact paved the way for the development of a GIP receptor agonist-based therapy for T2DM, looking also for the possibility of finding a combined GLP-1/GIP receptor agonist. In this framework, the novel dual GIP and GLP-1 receptor agonist tirzepatide seems to be not just a new antidiabetic medication. Administered as a subcutaneous weekly injection, it is a manifold single pharmacological agent that has the ability to significantly lower glucose levels, as well as improve insulin sensitivity, reduce weight and amend dyslipidemia favorably modifying the lipid profile. Tirzepatide and additional dual GLP-1/GIP receptor agonists that could eventually be developed in the future seem to be a promising furthest advance for the management of several cardiometabolic settings. Obviously, it is too early to be overly hopeful since it is still necessary to determine the long-term effects of these compounds and properly verify the potential cardiovascular benefits. Anyway, we are currently facing a novel and very appealing therapeutic option.

PSXVI-21 The effect of enhancing the thermal environment of piglets on physiology, behavior and productivity

To determine if increasing the heated area provided to piglets may improve their welfare; Sows (n = 27) were assigned to stalls using a traditional heat lamp (Control), or stalls using 2, 0.4 x 2.4 m heated mats (Heat). The mat temperature was maintained at approximately 39 °C until the 3rd d post-farrowing when they were replaced with a traditional heat lamp. At 1 d of age, piglets’ temperature was recorded, and blood samples were taken from 4 piglets per litter to measure cortisol, lactate, and glucose. Of these piglets, 2 were females and 2 males, 1 each weighing above average (thrifty) and 1 each below average (unthrifty). ADG of all piglets and mortality were recorded on d 3, when the heated mats were replaced with heat lamps, as well as at weaning. There were no treatment differences (P &gt; 0.10) for cortisol (4.52 ± 0.22 ug/dL), glucose (102.84 ± 2.11 mg/dL), or lactate (2.42 ± 94.77 mmol/L). Unthrifty piglets had greater cortisol concentrations (5.45 ± 0.34 vs. 3.64 ± 0.24 ug/dL, P &lt; 0.0001) and lower glucose (97.3 ± 3.06 vs. 108.37 ± 2.76 mg/dL; P &lt; 0.0014) than thrifty. ADG was not different (P &gt; 0.10) on d 3 (0.12 ± 0.01 kg) or at weaning (0.24 ± 0.003 kg). There was no difference in body temperature between treatments (39.23 ± 0.03 °F, P &gt; 0.10). Day 3 mortality was lower in Heat crates than Control (0.04 ± 0.02 vs. 0.12 ± 0.03, P &lt; 0.02); however, mortality at weaning did not differ (11 ± 0.02%, P &gt; 0.10). In conclusion, increasing the warm area in farrowing crates with heated mats over the length of the piglet area may increase survivability while provided.

The utility of continuous glucose monitoring systems in the management of children with persistent hypoglycaemia

Objectives Glucose monitoring is vital in children with persistent hypoglycaemia to reduce the risk of adverse neuro-behavioural outcomes; especially in children with hyperinsulinism. The role of continuous glucose monitoring (CGM) systems in monitoring glucose levels in this cohort is limited. The objective of this study was to ascertain the effectiveness of CGM and to evaluate parents’ experience of using CGM for monitoring glucose levels in children with hypoglycaemia. Methods Retrospective analysis of sensor glucose (SG) values from Dexcom G4 CGM with paired finger-prick blood glucose (BG) values was performed to determine the accuracy of CGM. The parent experience of CGM was assessed using a questionnaire administered to families of children with congenital hyperinsulinism currently attending the clinic. Results SG data from 40 children (median age 6 months) with persistent hypoglycaemia (60% Hyperinsulinism) were analysed. The mean difference between 5,650 paired BG and SG values was 0.28 mmol/L. The sensitivity and specificity of CGM to identify severe hypoglycaemia (BG < 3.0 mmol/L) were 54.3% (95% CI: 39.0%, 69.1%) and 97.4% (95% CI: 96.9%, 97.8%) respectively. Parents (n=11) reported less anxiety (n=9), better sleep at night (n=7) and preferred to use CGM for monitoring (n=9). Conclusions Although the high number of false-positive readings precludes the routine use of CGM in the evaluation of hypoglycaemia, it avoids unnecessary BG testing during normoglycaemia. It is an acceptable tool for parents for monitoring their children who are at risk of hypoglycaemia. Newer CGM systems with improved accuracy at lower glucose levels have the potential to further improve monitoring.

Factors connected with anxiety and other neuropsychiatric symptoms in advanced gastric cancer

Objective: The aim of study was to determine factors connected with neuropsychiatric symptoms and anxiety in patients with terminal stomach cancer. Methods: We analyzed retrospectively 134 terminal stomach cancer patients admitted to Palliative Care Unit. Results: Patients with anxiety had greater chance for emergency admission, higher NRS result, occurrence of cachexia,occurrence of neuropsychiatric symptoms,longer duration of treatment, higher albumin concentration and lower glucose concentration. Patients with neuropsychiatric symptoms had greater chance for emergency admission, higher PS scale note, occurrence of dyselectrolytemia, lower albumin concentration. Patients with those symptoms had more than 7 times greater chance for death. Conclusion: It is important to know factors connected with neuropsychiatric symptoms and anxiety because thanks to that we could avoid those dangerous clinical symptoms.

Synthesis, Analytical Characterization and Anti-Diabetic Activity of Some Heterocycles of Quinazolin-4(3H)one

Aim: Novel quinazolin-4(3H)-one heterocycles were synthesized and assessed for their anti-diabetic activity. Non-enzymatic glycosylation of haemoglobin assay was carried out to identify their potential as anti-diabetic. The cyclization of quinazolinone-4(3H)-one heterocycles was achieved, whereas carbon-carbon cross coupling reactions were carried out using Sonogashira and Suzuki-Miyaura reaction conditions and characterized with analysis. This synthesis method afforded corresponding 2, 3 and 6 substituted quinazolin-4(3H)-ones (3a to 3m) with excellent yields. Methods: 2-Amino-6-bromobenzoic acid was used as a substrate which was converted to corresponding benzamide derivatives (1a-1b) by reaction with benzylamine or cyclohexylamine using acid-amine reaction, followed by cyclization and oxidation using suitable aldehyde in DMSO under microwave condition to give bromo substituted quinazolin-4(3H)-ones (2a-2c), which were cross coupled to suitable terminal alkyne with palladium catalyst as well as copper co-catalyst using Sonogashira condition to obtain desired (3a-3h) and suitable boronic acid with palladium catalyst using Suzuki-Miyaura condition to obtain desired (3i-3m). All synthesized compounds were characterized by FTIR, proton NMR, LC-MS analysis and evaluated for in vitro anti-diabetic activity using non-enzymatic glycosylation of haemoglobin assay. Results: Compounds 3m showed good inhibition of glycosylation of haemoglobin which in turn suggest good anti-oxidant potential on metabolism of glucose and hence lower glucose concentration. It showed IC50 value of 35.91±0.82 µg/mL which was comparable to the standard alpha tocopherol (34.47±0.87µg/mL). Conclusion: In-vitro non-enzymatic glycosylation of haemoglobin method is one of important assays to judge the control of diabetes. The haemoglobin present in RBCs has an affinity to bind with glucose. The greater the glucose level in blood, more amount of glucose-bound (called glycosylated) haemoglobin will be formed. Accordingly, presence of lower concentration of glycosylated haemoglobin is a sure guide to the lower concentration of glucose in the blood. Synthesized compounds (3a-3m) lower the blood glucose level and 3m has highest potential among those which can be further developed as potent anti-diabetic.

Production of Glucose 6-Phosphate From a Cellulosic Feedstock in a One Pot Multi-Enzyme Synthesis

Glucose 6-phosphate is the phosphorylated form of glucose and is used as a reagent in enzymatic assays. Current production occurs via a multi-step chemical synthesis. In this study we established a fully enzymatic route for the synthesis of glucose 6-phosphate from cellulose. As the enzymatic phosphorylation requires ATP as phosphoryl donor, the use of a cofactor regeneration system is required. We evaluated Escherichia coli glucokinase and Saccharomyces cerevisiae hexokinase (HK) for the phosphorylation reaction and Pseudomonas aeruginosa polyphosphate kinase 2 (PPK2) for ATP regeneration. All three enzymes were characterized in terms of temperature and pH optimum and the effects of substrates and products concentrations on enzymatic activities. After optimization of the conditions, we achieved a 85% conversion of glucose into glucose 6-phosphate using the HK/PPK2 activities within a 24 h reaction resulting in 12.56 g/l of glucose 6-phosphate. Finally, we demonstrated the glucose 6-phosphate formation from microcrystalline cellulose in a one-pot reaction comprising Aspergillus niger cellulase for glucose release and HK/PPK2 activities. We achieved a 77% conversion of released glucose into glucose 6-phosphate, however at the expense of a lower glucose 6-phosphate yield of 1.17 g/l. Overall, our study shows an alternative approach for synthesis of glucose 6-phosphate that can be used to valorize biomass derived cellulose.

Strategy For Cellulase Immobilization And Its Partial Purification And Characterization

Conversion of cellulose to glucose units by cellulases, called hydrolysis, is a very complex step in ethanol production. It requires the mixing of aqueous suspensions of cellulose/cellulases so that cellulases (majority composed of the active site domain and the binding site domain) can attach to cellulose chains, cut or hydrolyze ß(1-4) glycosidic bonds between glucose units, de-attach and move to another location. Mixing extent (insufficient or excessive agitation) might influence the attachment of cellulases and possibly lead to lower glucose yields. A long-term goal of this research is to determine the strength of mixing required to be applied during the cellulose-cellulase mixing cycle. For that purpose, one of the objectives was to purify CBH I exocellulase from the commercial cellulase mixture. A partial purification of the CBH I that was performed on a much smaller scale with uncontrolled flow rate was successful. Another objective was to propose a scheme that would covalently immobilize CBH I exoceullase via its active site domain (ASD) on an atomic force microscopy-compatible support, a silicon support. A theoretically-developed hypothetical scheme was constructed (with the provided detailed procedure). The approach of immobilizing the inhibitor specific to the ASD of CBH I enzyme led to the possibility that no purification of CBH I could be required. Skipping CBH I purification step would save time and hassle associated with purification step. Once the ASD of CBH I is immobilized on a silicon support, the AFM force profile between the free-floating CDB and substrate cellulose could be established.

Strategy For Cellulase Immobilization And Its Partial Purification And Characterization

Conversion of cellulose to glucose units by cellulases, called hydrolysis, is a very complex step in ethanol production. It requires the mixing of aqueous suspensions of cellulose/cellulases so that cellulases (majority composed of the active site domain and the binding site domain) can attach to cellulose chains, cut or hydrolyze ß(1-4) glycosidic bonds between glucose units, de-attach and move to another location. Mixing extent (insufficient or excessive agitation) might influence the attachment of cellulases and possibly lead to lower glucose yields. A long-term goal of this research is to determine the strength of mixing required to be applied during the cellulose-cellulase mixing cycle. For that purpose, one of the objectives was to purify CBH I exocellulase from the commercial cellulase mixture. A partial purification of the CBH I that was performed on a much smaller scale with uncontrolled flow rate was successful. Another objective was to propose a scheme that would covalently immobilize CBH I exoceullase via its active site domain (ASD) on an atomic force microscopy-compatible support, a silicon support. A theoretically-developed hypothetical scheme was constructed (with the provided detailed procedure). The approach of immobilizing the inhibitor specific to the ASD of CBH I enzyme led to the possibility that no purification of CBH I could be required. Skipping CBH I purification step would save time and hassle associated with purification step. Once the ASD of CBH I is immobilized on a silicon support, the AFM force profile between the free-floating CDB and substrate cellulose could be established.