Preeclamptic serum and soluble fms-like tyrosine kinase-1 suppress endothelial inward rectifier potassium currents.

INTRODUCTION: Inward rectifier K+ (Kir) channel, a major factor determining endothelial membrane potential, regulates Ca2+ influx and vasodilator release, which is impaired in preeclamptic blood vessels. Previously, human umbilical vein endothelial cell (HUVEC) Kir currents were shown to decrease after incubating in preeclamptic plasma. We aimed to demonstrate whether sFlt-1, which is high in preeclamptic blood, could inhibit Kir channel function and expression. METHODS: HUVECs were cultured in regular medium, regular medium with added sFlt-1, or serum from preeclampsia patients or normal pregnant women (Control, sFlt-1, PE, or NP, respectively). Using whole-cell patch clamp technique, we identified Kir currents with the Kir blocker 2 mM BaCl2 and compared the currents among groups. The expression of Kir 2.1 and 2.2 channels were determined using immunofluorescent staining. RESULTS: sFlt-1 and PE groups exhibited similar Kir currents, while NP group possessed significantly larger currents, similar to Control group currents. Moreover, sFlt-1 and sFlt-1/PlGF ratio showed strong negative correlation with Kir currents (r = -0.71 and -0.70, respectively; P < 0.05). There were no significant differences in mean fluorescence intensity representing Kir 2.1 and 2.2 channels expression in all four groups. DISCUSSION: This is the first report to demonstrate sFlt-1 inhibition against Kir currents, which could lead to maternal endothelial dysfunction and hypertension seen in preeclampsia. However, channel expression was unaffected by sFlt-1 incubation, suggesting dysfunctions of channel or other processes (e.g., membrane translocation). The present data could pave the way for novel therapies targeting sFlt-1 or Kir to alleviate hypertension in preeclampsia.

Intrapartum prediction of birth weight with a simplified algorithmic approach derived from maternal characteristics.

Objective To derive and validate a population-specific multivariate approach for birth weight (BW) prediction based on quantitative intrapartum assessment of maternal characteristics by means of an algorithmic method in low-risk women. Methods The derivation part (n = 200) prospectively explored 10 variables to create the best-fit algorithms (70% correct estimates within ±10% of actual BW) for prediction of BW at term; vertex presentation with engagement. The algorithm was then cross validated with samples of unrelated cases (n = 280) to compare the accuracy with the routine abdominal palpation method. Results The best-fit algorithms were parity-specific. The derived simplified algorithms were (1) BW (g) = 100 [(0.42 × symphysis-fundal height (SFH; cm)) + gestational age at delivery (GA; weeks) - 25] in nulliparous, and (2) BW (g) = 100 [(0.42 × SFH (cm)) + GA - 23] in multiparous. Cross validation showed an overall 69.3% accuracy within ±10% of actual BW, which exceeded routine abdominal palpation (60.4%) (P = 0.019). The algorithmic BW prediction was significantly more accurate than routine abdominal palpation in women with the following characteristics: BW 2500-4000 g, multiparous, pre-pregnancy weight <50 kg, current weight <60 kg, height <155 cm, body mass index (BMI) <18.5 kg/m2, cervical dilatation 3-5 cm, station <0, intact membranes, SFH 30-39 cm, maternal abdominal circumference (mAC) <90 cm, mid-upper arm circumference (MUAC) <25 cm and female gender of the neonates (P < 0.05). Conclusion An overall accuracy of term BW prediction by our simplified algorithms exceeded that of routine abdominal palpation.

Redefining Health: The Evolution of Health Ideas from Antiquity to the Era of Value-Based Care.

The current healthcare system in the United States (US) is characterized by high costs and poor patient outcomes. A value-based healthcare system, centered on providing the highest quality of care for the lowest cost, is the country's chosen solution for its healthcare crisis. As the US transitions to a value-based model, a new definition of health is necessary to clearly define what constitutes a healthy state. However, such a definition is impossible to develop without a proper understanding of what "health" actually means. To truly understand its meaning, one must have a thorough historical understanding of the changes in the concept of health and how it has evolved to reflect the beliefs and scientific understanding of each time period. Thus, this review summarizes the changes in the definition of health over time in order to provide a context for the definition needed today. We then propose a new definition of health that is specifically tailored to providers working in the era of value-based care.

Accuracy of administrative billing codes to detect urinary tract infection hospitalizations.

BACKGROUND: Hospital billing data are frequently used for quality measures and research, but the accuracy of the use of discharge codes to identify urinary tract infections (UTIs) is unknown. OBJECTIVE: To determine the accuracy of International Classification of Diseases, 9th revision (ICD-9) discharge codes to identify children hospitalized with UTIs. METHODS: This multicenter study conducted in 5 children's hospitals included children aged 3 days to 18 years who had been admitted to the hospital, undergone a urinalysis or urine culture, and discharged from the hospital. Data were obtained from the pediatric health information system database and medical record review. With the use of 2 gold-standard methods, the positive predictive value (PPV) was calculated for individual and combined UTI codes and for common UTI identification strategies. PPV was measured for all groupings for which the UTI code was the principal discharge diagnosis. RESULTS: There were 833 patients in the study. The PPV was 50.3% with the use of the gold standard of laboratory-confirmed UTIs but increased to 85% with provider confirmation. Restriction of the study cohort to patients with a principle diagnosis of UTI improved the PPV for laboratory-confirmed UTI (61.2%) and provider-confirmed UTI (93.2%), as well as the ability to benchmark performance. Other common identification strategies did not markedly affect the PPV. CONCLUSIONS: ICD-9 codes can be used to identify patients with UTIs but are most accurate when UTI is the principal discharge diagnosis. The identification strategies reported in this study can be used to improve the accuracy and applicability of benchmarking measures.

Modulating the effects of diabetes on osseointegration with aminoguanidine and doxycycline.

BACKGROUND: The current knowledge of wound healing around implant surfaces is quite limited, particularly as it relates to the effects of systemic diseases such as diabetes. The purpose of our research is to histologically evaluate the effects of aminoguanidine and doxycycline in the modification of peri-implant wound healing around endosseous implants in diabetic rats. METHODS: Thirty-two Sprague-Dawley rats were randomly assigned to four different treatment groups. One group served as the non-diabetic control, while diabetes was induced in other groups. Titanium plasma-sprayed (TPS) implants were placed in the femora of each animal 2 weeks following diabetic induction. One group of diabetic rats was given aminoguanidine via intraperitoneal injection, and another given doxycycline via oral gavage for 28 days beginning on the day of implantation. The third group of diabetic rats received no medication (controls). All animals were sacrificed following 28 days of healing. RESULTS: The results were measured by marrow bone-to implant contact (MBIC) between the groups. Values for MBIC were greater for the non-diabetic control group than the diabetic control group (P < 0.001). Aminoguanidine-treated diabetic animals had a significantly greater MBIC than the diabetic control group (P < 0.01). Diabetic animals receiving doxycycline did not differ significantly from the diabetic control group (P > 0.05). CONCLUSIONS: The results of this study using a rat model con- firm previous reports that diabetes inhibits osseointegration, as defined by MBIC. In addition, this study demonstrates that the detrimental effects of diabetes on osseointegration can be modified using aminoguanidine systemically. However, systemic administration of doxycycline only slightly enhances osseointegration.

Maintenance of osseointegration utilizing insulin therapy in a diabetic rat model.

BACKGROUND: Normal wound healing processes have been shown to be altered in diabetes, and the effect of the diabetes on bone-to-implant contact (BIC) once osseointegration has been established is still unknown. The purpose of this study was to histologically evaluate the bone-to-implant contact in uncontrolled and insulin-controlled rats in which diabetes was induced following the establishment of osseointegration. METHODS: Thirty-two rats were assigned to eight different treatment groups of four each. Titanium plasma-sprayed (TPS) implants were placed in the femora of each animal, and allowed to osseointegrate for 28 days before diabetic induction. Daily insulin injections were given to four groups of rats and the other four groups received no insulin (uncontrolled). The rats were sacrificed at 1, 2, 3, and 4 months following diabetic induction. RESULTS: The results indicated that at 1, 2, 3, and 4 months, there was more BIC in the insulin-controlled groups compared to the uncontrolled groups. The differences were significantly greater at 2, 3, and 4 months (P < or =0.001). CONCLUSIONS: This study demonstrated that osseointegrated dental implants in insulin-controlled diabetic rats maintained bone-to-implant contacts over a 4-month period. However, boneto- implant contact appears to decrease with time in uncontrolled diabetic rats.