Incidence and Risk Factors for Glucose Disturbances in Premature Infants.

Background and Objectives: There are limited data regarding the incidence and risk factors for hypoglycemia, hyperglycemia, and unstable glycemia in preterm infants. The aim of the present study was to determine the incidence and risk factors associated with neonatal hypoglycemia, hyperglycemia, and unstable glycemia in preterm infants during the first seven days of life. Materials and Methods: This prospective study included preterm infants <37 weeks of gestation, admitted to the Neonatal Intensive Care Unit between January 2018 and December 2020. Based on blood glucose levels in the first week of life, infants were divided into the following four groups: normoglycemic, hypoglycemic, hyperglycemic, and unstable. Blood glucose levels were measured from capillary blood at the 1st, 3rd, 6th, and 12th hour of life during the first 24 h, and at least once a day from days 2 to 7, prefeed. Results: Of 445 enrolled infants, 20.7% (92/445) were categorized as hypoglycemic, 9.9% (44/445) as hyperglycemic, and 2.9% (13/445) as unstable, respectively. Hypoglycemia was most commonly observed among infants ≥34 weeks (27.9%), and hyperglycemia was most common among preterm infants <28 weeks (50%). Female gender increased the chances of developing hypoglycemia by three times. The decrease in gestational age by one week increased the chance of developing hyperglycemia by 1.9 times. Sepsis increased the chance of developing hyperglycemia seven times, respiratory distress syndrome five times, and mechanical ventilation three times, respectively. Conclusions: Glucose disturbances in the early neonatal period in preterm infants are common and mostly asymptomatic. Therefore, careful blood glucose level monitoring is required in those infants, especially in late preterm infants, in order to prevent possible neurological complications.

Study of vitamin D receptor gene polymorphisms in a cohort of myocardial infarction patients with coronary artery disease.

BACKGROUND: Vitamin D deficiency is associated with cardiovascular diseases, including coronary artery diseases (CAD). As vitamin D manifests its biological function through its vitamin D receptor (VDR), VDR gene polymorphisms potentially affect VDR functionality and vitamin D activity. Therefore, the objective of this study was to analyze three well-studied VDR gene polymorphisms-Fok1 (rs2228570), BsmI (rs1544410) and Taq1 (rs731236)-in a cohort of CAD patients after acute myocardial infarction. METHODS: In the presented cross-sectional study, 155 participants with CAD after acute myocardial infarction and 104 participants in a control group without CAD were enrolled. The participants in both groups were Caucasians of European origin. The genotyping of VDR polymorphisms rs2228570, rs1544410 and rs731236 was assessed by RT-PCR. RESULTS: The results show an association between the T/T genotype of the BsmI (rs1544410) and the G/G genotype of the Taq1 (rs731236) VDR polymorphism and CAD patients after acute myocardial infarction. There was no association between the Fok1 (rs2228570) VDR polymorphism and CAD patients after acute myocardial infarction. CONCLUSION: The presented results suggest a potential association of the BsmI (rs1544410) and Taq1 (rs731236) VDR polymorphisms with CAD patients after myocardial infarction.

Clinical Parameters in Osteoporosis Patients Supplemented With PMA-Zeolite at the End of 5-Year Double-Blinded Clinical Trial.

Osteoporosis is among the most common pathologies. Associated complications in osteoporotic patients, in particular hip fractures and vertebral fractures, cause disabilities and significant quality of life deterioration. Standard treatment of osteoporosis, based on pharmacotherapy does still not yield adequate results, and the problem of osteoporosis remains incompletely solved. Additionally, adverse drug events and fractures after long-termed pharmacotherapy pose additional challenges within designing a proper therapy regimen. Improved clinical approach and new synergistic treatment modalities are consequently still needed. The rationale of the presented study was accordingly, to expand our preclinical animal study on human patients with osteoporosis, based on positive effects on bones observed in animals with osteopenia treated with PMA-zeolite. We specifically monitored effects of PMA-zeolite on the bone quality parameters, fracture risk and quality of life in a cohort of initially recruited 100 osteoporosis patients during a follow-up period of 5 years within a randomized, placebo-controlled and double blinded clinical study (TOP study). Obtained results provide evidence on the PMA-zeolite positive effects on the bone strength of osteoporotic patients as the risk of fractures was significantly decreased in PMA-zeolite-treated patients with respect to time before entering the study (p = 0.002). Statistical evidence point also to positive bone changes in the 5-years TOP study course as evidenced through osteocalcin and beta-cross laps values showing a prevalence of the bone-formation process (p < 0.05). BMD values were not significantly affected after the 5-years follow-up in PMA-zeolite-treated patients in comparison with the Placebo group. Results support the initial expectations based on our previously published preclinical studies on clinoptilolite product PMA-zeolite in animals that could be a new therapeutic option in osteoporosis patients.

Clinical Evaluation of a Defined Zeolite-Clinoptilolite Supplementation Effect on the Selected Blood Parameters of Patients.

The natural clinoptilolite material is an inorganic crystal mineral called zeolite. It has been extensively studied and used in industrial applications and veterinary and human medicine due to positive effects on health. Limited data is available in the scientific literature about its effects on the levels of physiologically relevant minerals in the human organism. Accordingly, we performed a comprehensive and controlled monitoring of the relevant mineral and contaminants levels in human subjects supplemented with a certified clinoptilolite material within three clinical trials with different supplementation regimens. Effects of a registered and certified clinoptilolite material PMA-zeolite on selected mineral and metal levels were determined by standard biochemical methods and inductively coupled plasma mass spectrometry (ICP-MS) in the blood of subjects enrolled in three clinical trials: short-term (28 days, Mineral Metabolism and selected Blood Parameters study MMBP), medium-term (12 weeks, Morbus Crohn study), and long-term (4 years, Osteoporosis TOP study) supplementation. Lower concentrations were observed for copper (Cu) in patients with osteoporosis, which normalized again in the long-term supplementation trial, whereas sodium (Na) and calcium (Ca) levels diminished below the reference values in patients with osteoporosis. In the short- and long-term supplementation trials, increased levels of lead (Pb) were observed in PMA-zeolite-supplemented subjects, which decreased in the continued long-term supplementation trial. Increased levels of aluminum (Al) or Pb attributable to eventual leakage from the material into the bloodstream were not detected 1 h after intake in the short-term supplementation trial. Nickel (Ni) and Al were statistically significantly decreased upon long-term 4-year supplementation within the long-term supplementation trial, and arsenic (As) was statistically significantly decreased upon 12-weeks supplementation in the medium-term trial. Alterations in the measured levels for Na and Ca, as well as for Pb, in the long-term trial are probably attributable to the bone remodeling process. Checking the balance of the minerals Cu, Ca, and Na after 1 year of supplementation might be prescribed for PMA-supplemented patients with osteoporosis. Clinical Trial Registration: [https://clinicaltrials.gov], identifiers [NCT03901989, NCT05178719, NCT04370535, NCT04607018].

Treatment of osteoporosis with a modified zeolite shows beneficial effects in an osteoporotic rat model and a human clinical trial.

The severity of osteoporosis in humans manifests in its high incidence and by its complications that diminish quality of life. A societal consequence of osteoporosis is the substantial burden that it inflicts upon patients and their families. Several bone-modifying drugs have been prescribed to patients with osteoporosis. However, evidence for their anti-fracture efficacy remains inconclusive. To the contrary, long-term use of anti-osteoporotic drugs such as bisphosphonates and Denosumab, an RANKL inhibitor, have resulted in adverse events. We now present an alternative and adjuvant approach for treatment of osteoporosis. The data derive from in vivo studies in an ovariectomized rat model and from a randomized double blind, placebo-controlled human clinical study. Both studies involved treatment with Panaceo Micro Activation (PMA)-zeolite-clinoptilolite, a defined cation exchange clinoptilolite, which clearly improved all bone histomorphometric parameters examined from ovariectomized animals, indicative for increased bone formation. Moreover, intervention with PMA-zeolite-clinoptilolite for one year proved safe in humans. Furthermore, patients treated with PMA-zeolite-clinoptilolite showed an increase in bone mineral density, an elevated level of markers indicative of bone formation, a significant reduction in pain, and significantly improved quality of life compared with patients in the control (placebo) group. These encouraging positive effects of PMA-zeolite-clinoptilolite on bone integrity and on osteoporosis warrant further evaluation of treatment with PMA-zeolite-clinoptilolite as a new alternative adjuvant therapy for osteoporosis.

Vitamin D-binding protein (rs4588) T/T genotype is associated with anteroseptal myocardial infarction in coronary artery disease patients.

BACKGROUND: Cardiovascular diseases (CVD) are among leading causes of death worldwide and amongst CVD, coronary artery disease (CAD) accounts for almost half of all cardiovascular deaths as the most common cause of death in the developed world. Vitamin D and the vitamin D-binding protein (VDBP) have been studied as possible CAD pathogenesis factors but literature data provide opposing evidence on their role in CAD. Herein we aimed to present novel evidence on the association of two VDBP polymorphisms (rs4588) and (rs7041) with CAD in patients after acute myocardial infarction and study possible correlations of these polymorphisms with 25-hydroxyvitamin D [25(OH)D] serum levels. METHODS: The cross-section genotyping study included 155 subjects with CAD upon acute myocardial infarct and 104 control subjects. All patients and control group were Caucasians of European descent. VDBP polymorphisms (rs4588) and (rs7041) were studied by use of RT-PCR. Liquid chromatography, tandem mass spectrometry (LC-MS/MS) method was used for measurement of vitamin D in the serum. RESULTS: Association of the VDBP (rs4588) T/T genotype with CAD patients after acute MI and correlation of VDBP (rs4588) genotype G/G with higher levels of total vitamin D were found. No correlation of 25(OH)D serum levels with CAD were established but the multivariate logistic regression modelling enabled association of total vitamin D level and VDBP (rs4588) T/T genotype with CAD and anteroseptal myocardial infarction (ASMI) CAD occurrence. CONCLUSIONS: Obtained data speak in favor to the VDBP (rs4588) T/T genotype as a susceptibility factor for anteroseptal myocardial infarction where the same genotype showed to be generally more prevalent in smokers.

Optimization of Ultrasonic-Assisted Extraction of Major Phenolic Compounds from Olive Leaves (Olea europaea L.) Using Response Surface Methodology.

The ultrasound-assisted extraction (UAE) of oleuropein (OLE), verbascoside (VER), and luteolin-4'-O-glucoside (L4OG), as the major phenolics from olive leaves, was optimized using response surface methodology (RSM). A Box⁻Behnken design (BBD) was used to monitor the effect of different modes of ultrasound operation (pulsed and continuous), liquid⁻solid (L⁻S) ratio, and sonication time on each phenolic yield. The yield of UAE and conventional solid extraction (CSE) was determined after performing ultrahigh-performance liquid chromatography with a diode-array detector (UHPLC-DAD) analysis on the extracts. The results suggested that, under optimal conditions, the concentrations of OLE, VER, and L4OG were 13.386, 0.363, and 0.527 mg/g of dry powdered olive leaves (DPOL), respectively. Verification of experiments was carried out under the modified optimal conditions and the relative errors between the predicted and experimental values were dependent on the examined phenolic compound (OLE 8.63%, VER 11.3%, and L4OG 22.48%). In comparison with CSE, UAE improved the yields of OLE, VER, and L4OG (32.6%, 41.8%, and 47.5%, respectively, after 1 min) at a temperature of 60 °C, an L⁻S ratio of 15 (v/w), and in the continuous mode of UAE. We demonstrated that the UAE technique is an efficient method for enhancing yields of OLE, VER, and L4OG in olive-leaf extracts, while the chosen model was adequate to optimize the extraction of major phenolic compounds from olive leaves.

Evaluation of nurses' workload in intensive care unit of a tertiary care university hospital in relation to the patients' severity of illness: A prospective study.

BACKGROUNDS: Costs of intensive care reach up to 30% of the hospital budget with workforce expenses being substantial. Determining proper nurse-patient ratio is necessary for optimizing patients' health related outcomes and hospitals' cost effective functioning. OBJECTIVES: To evaluate nurses' workload using Nine Equivalents of Nursing Manpower Use Score and Nursing Activities Score scoring systems while assessing correlation between both scores and the severity of illness measured by Simplified Acute Physiology Score II. DESIGN: A Prospective study SETTINGS: Cardiac Surgery Intensive Care Unit of the Clinical Hospital Centre Rijeka, Croatia, from October 2014 to February 2015. This Intensive Care Unit has 3 beds that can be expanded upon need. PARTICIPANTS: The study included 99 patients treated at this Unit during the study's period. The scores were obtained by 6 nurses, working in 12h shifts. METHODS: Measurements were obtained for each patient 24h after admission and subsequently twice a day, at the end of the day shift (7pm) and at the end of the night shift (7 am). The necessary data were obtained from the patient's medical records. RESULTS: Nursing Activities Score showed significantly higher number of nurses are required for one 12h shift (Z=3.76, p<0.001). Higher scores were obtained on day shifts vs. night shifts. (Nursing Manpower Use Score, z=3.25, p<0.001; Nursing Activities Score, z=4.16, p<0.001). When comparing Nursing Activities Score and Nursing Manpower Use Score during the week, we calculated higher required number of nurses on weekdays than on weekends and holidays, (Nursing Manpower Use Score, p<0.001; Nursing Activities Score, p<0.001). Correlation analysis of Nursing Activities Score and Nursing Manpower Use Score with Simplified Acute Physiology Score II has shown that Nursing Manpower Use Score positively associated with severity of disease, while Nursing Activities Score shows no association. CONCLUSION: Both scores can be used to estimate required number of nurses in 12-h shifts, although Nursing Activities Score seems more suitable for units with prolonged length of stay, while Nursing Manpower Use Score appears better for units with shorter duration of stay (up to four days). Higher workload measured by Nursing Manpower Use Score scale can be predicted with higher Simplified Acute Physiology Score II. However, with low Simplified Acute Physiology Score II scores it cannot be assumed that the nursing workload will also be low. Further research is needed to determine the best tool to asses nursing workload in intensive care units.