Chronic kidney disease stage affects small, dense low-density lipoprotein but not glycated low-density lipoprotein in younger chronic kidney disease patients: a cross-sectional study.

Background Small, dense low-density lipoprotein (sd-LDL) and glycated LDL (g-LDL) have been associated with cardiovascular disease (CVD) in chronic kidney disease (CKD) in patients \u3e60 years of age. Since young adult and paediatric patients have shorter exposure to Framingham-type risk factors, our study aims to determine whether younger CKD patients exhibit the same sd-LDL and g-LDL pattern. Methods After ethics board approval, this cross-sectional study was conducted at two universities with 44 patients (mean ± standard deviation age 12.6 ± 4.9, range 2-24 years) with CKD stage of 1-5. Laboratory parameters studied were Cystatin C (CysC), CysC estimated glomerular filtration rate (eGFR) (calculated from the Filler formula), sd-LDL, g-LDL and albumin. Lipid samples were measured for sd-LDL and g-LDL using ELISA. Non-linear correlation analysis was performed to determine the relationship between g-LDL, sd-LDL and eGFR. Clinical Trials Registration is at clinicaltrials.gov, NCT02126293, https://clinicaltrials.gov/ct2/show/NCT02126293. Results Triglycerides, but not total cholesterol and calculated LDL, were associated with CKD stages (ANOVA P = 0.0091). As in adults, sd-LDL was significantly associated with CKD stages (ANOVA P = 0.0133), CysC eGFR ( Conclusions Our study demonstrates that only triglycerides and sd-LDL were associated with CKD stages in this young cohort without confounding Framingham-type CVD risk factors. While larger studies are needed, this study suggests that lowering sd-LDL levels may be a potential target to ameliorate the long-term CVD risks in paediatric CKD patients

Neonatologie/Pädiatrie – Leitlinie Parenterale Ernährung, Kapitel 13

There are special challenges in implementing parenteral nutrition (PN) in paediatric patients, which arises from the wide range of patients, ranging from extremely premature infants up to teenagers weighing up to and over 100 kg, and their varying substrate requirements. Age and maturity-related changes of the metabolism and fluid and nutrient requirements must be taken into consideration along with the clinical situation during which PN is applied. The indication, the procedure as well as the intake of fluid and substrates are very different to that known in PN-practice in adult patients, e.g. the fluid, nutrient and energy needs of premature infants and newborns per kg body weight are markedly higher than of older paediatric and adult patients. Premature infants <35 weeks of pregnancy and most sick term infants usually require full or partial PN. In neonates the actual amount of PN administered must be calculated (not estimated). Enteral nutrition should be gradually introduced and should replace PN as quickly as possible in order to minimise any side-effects from exposure to PN. Inadequate substrate intake in early infancy can cause long-term detrimental effects in terms of metabolic programming of the risk of illness in later life. If energy and nutrient demands in children and adolescents cannot be met through enteral nutrition, partial or total PN should be considered within 7 days or less depending on the nutritional state and clinical conditions.Eine besondere Herausforderung bei der Durchführung parenteraler Ernährung (PE) bei pädiatrischen Patienten ergibt sich aus der großen Spannbreite zwischen den Patienten, die von extrem unreifen Frühgeborenen bis hin zu Jugendlichen mit einem Körpergewicht von mehr als 100 kg reicht, und ihrem unterschiedlichen Substratbedarf. Dabei sind alters- und reifeabhängige Veränderungen des Stoffwechsels sowie des Flüssigkeits- und Nährstoffbedarfs zu berücksichtigen sowie auch die klinische Situation, in der eine PE eingesetzt wird. Das Vorgehen unterscheidet sich deshalb ganz erheblich von der PE-Praxis bei erwachsenen Patienten, z.B. ist der Flüssigkeits-, Nährstoff- und Energiebedarf von Früh- und Neugeborenen pro kg Körpergewicht höher als bei älteren pädiatrischen und bei erwachsenen Patienten. In der Regel benötigen alle Frühgeborenen <35. SSW und alle kranken Reifgeborenen während der Phase des allmählichen Aufbaus der enteralen Nahrungszufuhr eine vollständige oder partielle PE. Die Zufuhrmengen der PE bei Neonaten müssen berechnet (nicht geschätzt) werden. Der Anteil der PE sollte zur Minimierung von Nebenwirkungen sobald wie möglich durch Einführung einer enteralen Ernährung vermindert (teilparenterale Ernährung) und schließlich komplett durch enterale Ernährung abgelöst werden. Eine unangemessene Substratzufuhr im frühen Säuglingsalter kann langfristig nachteilige Auswirkungen im Sinne einer metabolischen Programmierung des Krankheitsrisikos im späteren Lebensalter haben. Wenn bei älteren Kindern und Jugendlichen dagegen der Energie- und Nährstoffbedarf eines Patienten im Vorschul- oder Schulalter durch eine enterale Nährstoffzufuhr nicht gedeckt werden kann, ist abhängig von Ernährungszustand und klinischen Umständen spätestens innerhalb von 7 Tagen eine partielle oder totale PE zu erwägen

Norovirus infections in preterm infants: wide variety of clinical courses

<p>Abstract</p> <p>Background</p> <p>Norovirus is an important cause of nonbacterial acute gastroenteritis in all ages. Atypical courses are described. Clinical symptoms are diarrhea, vomiting, nausea, abdominal cramps, fever and malaise. Apart from three recent short reports we describe for the first time an outbreak of norovirus in a tertiary Neonatal Intensive Care Unit.</p> <p>Findings</p> <p>The typical symptoms of norovirus infection are in part also seen in premature born infants but with a different pattern and a huge variety of clinical courses. Vomiting is not the main symptom of norovirus infection in premature infants but distended abdomen and other symptoms such as apnea, gastric remainders or sepsis like appearance. The course in premature born patients could be explained by an immunocompromised mice model. Extensive hygienic measures were necessary to control the outbreak without closing the Neonatal Intensive Care Unit.</p> <p>Conclusion</p> <p>Norovirus infection in premature infants shows an impressive pattern of a wide variety of clinical courses. Only the consequent use of different hygienic pattern can lead to elimination of norovirus.</p

Стратегия развития организационной культуры как фактор эффективности деятельности организации

В работе были рассмотрены функции и элементы организационной культуры и её влияние на эффективность деятельности организации. В результате исследования были предложены рекомендации и мероприятия по совершенствованию организационной культуры.The word considered the functions and elements of organizational culture and its influence on the effectiveness of the organization. As a result of the study, recommendations and measures were proposed to improve the organizational culture

Identification of regulatory variants associated with genetic susceptibility to meningococcal disease.

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Target Fortification of Breast Milk: Predicting the Final Osmolality of the Feeds.

For preterm infants, it is common practice to add human milk fortifiers to native breast milk to enhance protein and calorie supply because the growth rates and nutritional requirements of preterm infants are considerably higher than those of term infants. However, macronutrient intake may still be inadequate because the composition of native breast milk has individual inter- and intra-sample variation. Target fortification (TFO) of breast milk is a new nutritional regime aiming to reduce such variations by individually measuring and adding deficient macronutrients. Added TFO components contribute to the final osmolality of milk feeds. It is important to predict the final osmolality of TFO breast milk to ensure current osmolality recommendations are followed to minimize feeding intolerance and necrotizing enterocolitis. This study aims to develop and validate equations to predict the osmolality of TFO milk batches. To establish prediction models, the osmolalities of either native or supplemented breast milk with known amounts of fat, protein, and carbohydrates were analyzed. To validate prediction models, the osmolalities of each macronutrient and combinations of macronutrients were measured in an independent sample set. Additionally, osmolality was measured in TFO milk samples obtained from a previous clinical study and compared with predicted osmolality using the prediction equations. Following the addition of 1 g of carbohydrates (glucose polymer), 1 g of hydrolyzed protein, or 1 g of whey protein per 100 mL breast milk, the average increase in osmolality was 20, 38, and 4 mOsm/kg respectively. Adding fat decreased osmolality only marginally due to dilution effect. Measured and predicted osmolality of combinations of macronutrients as well as single macronutrient (R2 = 0.93) were highly correlated. Using clinical data (n = 696), the average difference between the measured and predicted osmolality was 3 ± 11 mOsm/kg and was not statistically significant. In conclusion, the prediction model can be utilized to estimate osmolality values after fortification

Individualized Target Fortification of Breast Milk: Optimizing Macronutrient Content Using Different Fortifiers and Approaches

Background: Native breast milk composition displays significant inter- and intra-individual variation which persists after standard fortification with fixed doses and challenges target fortification. This study aims to analyze the macronutrient composition of different commercially available fortifiers and the effect of different fortification strategies on nutritional intake of preterm infants. Methods: In 103 preterm infants, native breast milk samples were collected from 24-h feeding batches (n = 3,338) and fat, protein and carbohydrate contents were analyzed. Nutrient content was compared for breast milk that had undergone either (i) standard fortification, (ii) targeted fortification, (iii) selective batching according to breast milk composition, or (iv) partial lyophilization. For (i) eight commercially available standard fortifiers were tested. Targeted fortification (ii) involved the addition of single component modulars of either protein, fat or carbohydrates to standard fortified breast milk. Using a mathematical growth model, the combined effect of protein, fat and carbohydrate intake on growth was assessed. The best composition of standard fortifiers as the initial step for target fortification was explored assuming three clinical scenarios for milk analysis. Results: Macronutrient content was highly variable between native breast milk samples, and this variation was still present after standard fortification, however at elevated macronutrient levels. Standard fortification, breast milk batching, as well as partial lyophilization of human milk resulted in deficient and imbalanced enteral intakes in a significant proportion of infants. Target fortification reduced this variation in a, respectively, higher percentage of samples. The effect size was dependent on the number of measurements per week. The optimum composition of standard fortifiers was dependent on the clinical scenario (measurement frequency) for target fortification. Conclusions: To provide precise and accurate intakes of macronutrients, breast milk should be target fortified. Standard fortified breast milk can result in excess above recommended intakes of some macronutrients which limits the efficiency of target fortification. Standard fortifiers with improved composition are needed for target fortification

Target Fortification of Breast Milk: How Often Should Milk Analysis Be Done?

Target fortification (TFO) reduces natural macronutrient variation in breast milk (BM). Daily BM analysis for TFO increases neonatal intensive care unit work load by 10–15 min/patient/day and may not be feasible in all nurseries. The variation of macronutrient intake when BM analysis is done for various schedules was studied. In an observational study, we analyzed 21 subsequent samples of native 24-h BM batches, which had been prepared for 10 healthy infants (gestational age 26.1 ± 1.3 weeks, birth weight: 890 ± 210 g). Levels of protein and fat (validated near-infrared milk analyzer), as well as lactose (UPLC-MS/MS) generated the database for modelling TFO to meet recommendations of European Society for Paediatric Gastroenterology Hepatology and Nutrition. Intake of macronutrients and energy were calculated for different schedules of BM measurements for TFO (n = 1/week; n = 2/week; n = 3/week; n = 5/week; n = 7/week) and compared to native and fixed dose fortified BM. Day-to-day variation of macronutrients (protein 20%, carbohydrate 13%, fat 17%, energy 10%) decreased as the frequency of milk analysis increased and was almost zero for protein and carbohydrate with daily measurements. Measurements two/week led to mean macronutrient intake within a range of ±5% of targeted levels. A reduced schedule for macronutrient measurement may increase the practical use of TFO. To what extent the day-to-day variation affects growth while mean intake is stable needs to be studied

Osmolality change on fortified breast milk with carbohydrates after 24 hours of storage at 4°C.

<p>Diamond symbol represents baseline osmolality that measured immediate when breast milk was fortified and round symbol represents osmolality that measured after 24 hours storage at 4°C.</p