Plasma isoprostanoids assessment as Alzheimer's disease progression biomarkers.

Alzheimer's Disease (AD) is the most common neurodegenerative disease worldwide. So, there is a need to identify AD early diagnosis and monitoring biomarkers in blood samples. The aim of this study was to analyse the utility of lipid peroxidation biomarkers in AD progression evaluation. Participants (n = 19) were diagnosed with AD at early stages (Time 0, T0), and they were re-evaluated 2 years later (Time 1, T1). Plasma biomarkers from AD patients were determined at both times. Some analytes, such as dihomo-isoprostanes (17-epi-17-F2t-dihomo-IsoP, 17-F2t-dihomo-IsoP, Ent-7(RS)-7-F2t-dihomo-IsoP), and neuroprostanes (10-epi-10-F4t-NeuroP) showed very high probability of showing an increasing trend over time. Baseline values allowed to develop an affordable preliminary regression model to predict long-term cognitive status. So, some lipid peroxidation biomarkers would deserve consideration as useful progression AD biomarkers. The developed prediction model would constitute an important minimally invasive approach in AD personalized prognosis and perhaps could have some interest also in experimental treatments evaluation.

Diagnostic accuracy of C-reactive protein, procalcitonin and neutrophils for the early detection of anastomotic leakage after colorectal resection: a multicentric, prospective study.

AIM: The aim was to determine the accuracy of C-reactive protein (CRP), procalcitonin and neutrophils in the early detection (fourth postoperative day) of anastomotic leakage (AL) after colorectal surgery. METHODS: We conducted a multicentre, prospective study that included a consecutive series of patients who underwent colorectal resection with anastomosis without ostomy (September 2015 to December 2017). CRP, procalcitonin and neutrophil values on the fourth postoperative day after colorectal resection along with the postoperative outcome (60-day AL, morbidity and mortality) were prospectively included in an online, anonymous database. RESULTS: The analysis ultimately included 2501 cases. The overall morbidity and mortality was 30.1% and 1.6%, respectively, and the AL rate was 8.6%. The area under the receiver operating characteristic curve values (95% CI) for detecting AL were 0.84 (0.81-0.87), 0.75 (0.72-0.79) and 0.70 (0.66-0.74) for CRP, procalcitonin and neutrophils, respectively. The best cut-off level for CRP was 119 mg/l, resulting in 70% sensitivity, 81% specificity and 97% negative predictive value. After laparoscopic resection, the accuracy for CRP and procalcitonin was increased, compared with open resection. The combination of two or three of these biomarkers did not significantly increase their accuracy. CONCLUSION: On the fourth postoperative day, CRP was the most reliable marker for excluding AL. Its high negative predictive value, especially after laparoscopic resection, allows for safe hospital discharge on the fourth postoperative day. The routine use of procalcitonin or neutrophil counts does not seem to increase the diagnostic accuracy.

The Effectiveness of an Oral Sensorimotor Stimulation Protocol for the Early Achievement of Exclusive Oral Feeding in Premature Infants. A Randomized, Controlled Trial.

Aims: This study is aimed to investigate the effectiveness of an oral stimulation protocol in preterm infants compared to usual care, to reduce the time for achieving safe full oral feeding.Methods: 47 preterm infants (25- 30 weeks of gestational age) were randomized into two groups. Babies of the EG (n = 24) received a 10-minute oral stimulation protocol while the CG (n = 23) received the standard care. The primary outcome were the days from the initiation of the intervention until the achievement of full oral feeding. Secondary outcomes were: days from the first day the intervention started until achieving a first oral intake of 30% in the first 5 minutes, days from the first day the intervention started until achieving a first oral intake of 100%, and days of hospitalization. A parametric survival model with Gaussian distribution was used.Results: The EG achieved full oral feeding 8.3 days before the CG (p = 0.013). EG also achieved the first oral intake of 30% in the first five minutes, 6.03 days before (p = 0.019) and of 100%, 5.88 days before (p = 0.040). EG also spent 6.9 days less hospitalized than CG (p = 0.028).Conclusion: Oral stimulation in preterm infants significantly shortens the time to achieve full oral feeding and reduces the length of hospitalization.

Maternal telomere length is shorter in intrauterine growth restriction versus uncomplicated pregnancies, but not in the offspring or in IVF-conceived newborns.

RESEARCH QUESTION: The study aimed to determine whether IVF or intrauterine growth restriction (IUGR) result in short neonatal telomeres, which could explain the higher risk of cardiovascular and metabolic disease described in these populations. DESIGN: This was an observational, analytical, cross-sectional, prospective study with controls in a tertiary hospital. The main outcome was to determine the leukocyte telomere length in 126 newborns and their mothers (n = 109). Newborns were conceived spontaneously or by IVF, and uncomplicated and IUGR pregnancies were studied. Telomere lengths were measured using high-throughput telomere quantitative fluorescent in-situ hybridization. RESULTS: There was no difference in average telomere length between newborns conceived by IVF or those with IUGR and spontaneously conceived healthy newborns (P = 0.466 and P = 0.732, respectively); this remained after controlling for confounders (P = 0.218 and P = 0.991, respectively). Mothers of newborns with IUGR had a shorter average telomere length than women with uncomplicated pregnancies (P = 0.023), which was confirmed after controlling for age, body mass index and smoking habit (P = 0.034). CONCLUSIONS: The results support the safety of IVF and IUGR in terms of the postnatal health of the newborns. The shorter telomeres of IUGR mothers may represent a higher cardiovascular risk, which would have clinical implications under the stress of pregnancy in otherwise healthy adults.

Antiepileptic drug reduction and increased risk of stimulation-evoked focal to bilateral tonic-clonic seizure during cortical stimulation in patients with focal epilepsy.

INTRODUCTION: Stimulation-evoked focal to bilateral tonic-clonic seizure (FBTCS) can be a stressful and possibly harmful adverse event for patients during cortical stimulation (CS). We evaluated if drug load reduction of antiepileptic drugs (AEDs) during CS increases the risk of stimulation-evoked FBTCS. MATERIAL AND METHODS: In this retrospective cohort study, we searched our local database for patients with drug-resistant epilepsy who underwent invasive video-EEG monitoring and CS in the University Hospital la Fe Valencia from January 2006 to November 2016. The AED drug load was calculated with the defined daily dose. We applied a uni- and multivariate logistic regression model to estimate the risk of stimulation-evoked FBTCS and evaluate possible influencing factors. Furthermore, we compared patients whose AEDs were completely withdrawn with those whose AEDs were not. RESULTS: Fifty-eight patients met the inclusion criteria and were included in the analysis. Stimulating 3806 electrode contact pairs, 152 seizures were evoked in 28 patients (48.3%). Ten seizures (6.6%) in seven patients (12.1%) evolved to FBTCS. In the univariate and multivariate analysis, a 10% reduction in drug load was associated with an increase of the odds ratio (OR) of stimulation-evoked FBTCS by 1.9 (95%-CI 1.2, 4.0, p-value=0.04) and 1.9 (95%-CI 1.2, 4.6, p-value=0.04), respectively. In patients, whose AEDs were completely withdrawn the OR of FBTCS increased by 9.1 (95%CI 1.7, 69.9, p-value=0.01) compared with patients whose AEDs were not completely withdrawn. No other factor (implantation type, maximum stimulus intensity, number of stimulated contacts, history of FBTCS, age, gender, or epilepsy type) appears to have a significant effect on the risk of stimulation-evoked FBTCS. CONCLUSIONS: The overall risk of stimulation-evoked FBTCS during CS is relatively low. However, a stronger reduction and, especially, a complete withdrawal of AEDs are associated with an increased risk of stimulation-evoked FBTCS.

Cardiovascular risk reduction over time in patients with diabetes or pre-diabetes undergoing bariatric surgery: data from a single-center retrospective observational study.

BACKGROUND: Bariatric surgery is effective in remission of obesity comorbidities. This study was aimed at comparing CVD risk between morbidly obese patients with type 2 diabetes and pre-diabetes before and after bariatric surgery as well as assessing comorbidities. METHODS: This is a retrospective observational study with 105 patients with type 2 diabetes (DMbaseline) and prediabetes (preDMbaseline) who underwent Roux-en-Y gastric bypass. Data were collected preoperative and then at 3,6,12,18,24,36,48, and 60 months after surgery. Anthropometric, cardiovascular and glycemic parameters were assessed. CVD risk was calculated using the Framingham Risk Score. RESULTS: Prior to surgery, 48 patients had type 2 diabetes, while 57 had pre-diabetes. Mean age was 48 (9.2) and mean BMI was 52 (7.4). 26.1% of patients had a high CVD risk. CVD risk decreased in patients with type 2 diabetes and prediabetes at month 12 after surgery compared to the baseline risk (p < 0.001). BMI, body fat percentage, fasting plasma glucose, HbA1c, c-peptide, HOMA-IR, LDL-c, systolic blood pressure, and diastolic blood pressure decreased during the first year after surgery. From the 12th month until the 60th, they showed a flat trend, or a very mild increase in some cases. 3.2% of patients maintained high CVD risk at 60 months. Type 2 diabetes remission was 92%. No patient of the preDMbaseline group developed type 2 diabetes. CONCLUSION: Bariatric surgery reduces CVD risk in type 2 diabetes and pre-diabetes. Given that patients with type 2 diabetes benefit the most, more studies are necessary to consider pre-diabetes as a criterion for metabolic surgery in patients with BMI ≥ 35 kg/m2.

Psychiatric symptoms after temporal epilepsy surgery. A one-year follow-up study.

Psychiatric symptoms must be considered in patients with refractory temporal lobe epilepsy after epilepsy surgery. The main objectives of our study were to describe clinical and socio-demographical characteristics of a cohort of patients with pharmacoresistant temporal lobe epilepsy who underwent temporal lobe epilepsy surgery, and moreover, to evaluate possible risk factors for developing psychiatric symptoms. In order to achieve those goals, we conducted a prospective evaluation of psychopathology throughout the first year after surgery in a clinical sample of 72 patients, by means of three clinical rated measures; the Hamilton Anxiety Rating Scale (HARS), the Hamilton Depression Rating Scale (HDRS), and the Brief Psychiatric Rating Scale (BPRS). The psychopathological evaluations were performed by an experienced psychiatrist. A presurgical evaluation was done by a multidisciplinary team (that includes neurologist, psychiatrist, neurosurgeon, neurophysiologist, radiologists, and nuclear medicine specialist) in all patients. The decision to proceed to surgery was taken after a surgical meeting of all members of the Multidisciplinary Epilepsy Unit team. The psychiatrist conducted two postoperative assessments at 6months and 12months after surgery. The main finding was that past history of mental illness (patients who were receiving psychiatric treatment prior to the baseline evaluation) was a risk factor for anxiety, depression, and psychosis after temporal lobe epilepsy surgery.

Neonatal Acid-Base Status in Term Fetuses: Mathematical Models Investigating Cerebroplacental Ratio and Birth Weight.

OBJECTIVE: Cerebroplacental ratio (CPR) is emerging as a marker of fetal hypoxia at term. The aim of this study was to demonstrate graphically the interrelationships among CPR, birthweight (BW), and neonatal pH, and construct 2D and 3D representations of the areas with potential low pH. METHODS: This was a retrospective study of 2,927 term fetuses evaluated according to BW and CPR. The outcome was the acid-base status at birth. Multivariate relationships among CPR, BW, and arterial and venous pH were depicted in 3D scattergrams. Subsequently, trend surfaces were calculated and represented in 2D contour graphs. Finally, 3D representations were constructed by smothering pH data using moving average filters. RESULTS: The trend surfaces and the 2D and 3D contour graphs showed the complex association among the three variables. Although pH changed with CPR and BW, the influence of the BW was smaller than the influence of the CPR, with this effect being more evident in the venous than in the arterial pH. CONCLUSIONS: Two scenarios threaten fetal well-being at term: a very low birth weight and a very low fetal CPR. Our findings suggest that the importance of fetal hemodynamics in determining the acid-base status at birth surpasses that of fetal weight.

The vertebral artery Doppler might be an alternative to the middle cerebral artery Doppler in the follow-up of the early onset growth-restricted fetus.

OBJECTIVE: The objective of this article is to show the clinical utility of the vertebral artery Doppler as an alternative to the middle cerebral artery Doppler in the follow-up of fetuses affected with early-onset growth restriction [fetal growth restriction (FGR)]. METHODS: We present a group of fetuses with early-onset FGR in which the vertebral artery resistance index (VA RI) and pulsatility index (VA PI) were measured and plotted along with their references earlier calculated using 1980 Doppler examinations. In addition, the VA and middle cerebral artery (MCA) performance was compared using values converted into multiples of the median. RESULTS: Similar to that of the MCA, VA RI and VA PI percentiles showed curve shapes with higher values at the beginning of the third trimester. The majority of growth-restricted fetuses showed a notorious decrease in the VA impedance, which was not statistically different to that of the MCA. CONCLUSION: Vertebral artery Doppler values can be obtained throughout the second half of pregnancy. Preliminary data suggest a clinical application in the management of early-onset FGR.

Virtual Screening of Small Molecules Targeting BCL2 with Machine Learning, Molecular Docking, and MD Simulation.

This study aimed to identify potential BCL-2 small molecule inhibitors using deep neural networks (DNN) and random forest (RF), algorithms as well as molecular docking and molecular dynamics (MD) simulations to screen a library of small molecules. The RF model classified 61% (2355/3867) of molecules as 'Active'. Further analysis through molecular docking with Vina identified CHEMBL3940231, CHEMBL3938023, and CHEMBL3947358 as top-scored small molecules with docking scores of -11, -10.9, and 10.8 kcal/mol, respectively. MD simulations validated these compounds' stability and binding affinity to the BCL2 protein.

Doppler study of the fetal vertebral and middle cerebral arteries in fetuses with normal and increased umbilical artery resistance indices.

OBJECTIVE: To compare the brain sparing mechanism of the fetal vertebral artery (VA), with the one of the middle cerebral artery (MCA) in fetuses with increased umbilical artery (UA) Doppler impedance. METHOD: We retrospectively studied 1084 Doppler examinations of the VA, MCA and UA performed in 1084 fetuses between 19 and 41 week of gestation. These were divided into 3 groups according to the UA resistance index (UA RI): group 1: UA RI < 95(th) percentile (N = 965), group 2: UA RI > 95(th) percentile (N = 111) and group 3: absent UA diastolic flow (N = 8). Afterwards, values were converted into multiples of the median (MoM), and means and standard deviations were calculated. Finally, Kruskal-Wallis tests and box and whiskers charts were applied to evaluate differences. RESULTS: For both, the VA RI and MCA RI, no differences were seen among the groups of fetuses who maintained diastolic flow in the UA. However, the VA RI and MCA RI were lower when the UA diastolic flow was absent. CONCLUSION: The VA and MCA work in unison, decreasing impedances only when UA flow is severely affected.

Low-Dose Gamma Radiation Sterilization for Decellularized Tracheal Grafts.

One of the main key aspects in ensuring that a transplant evolves correctly is the sterility of the medium. Decellularized tracheal transplantation involves implanting an organ that was originally in contact with the environment, thus not being sterile from the outset. While the decellularization protocol (through detergent exposition [2% sodium dodecyl sulfate], continuous stirring, and osmotic shocks) is conducted in line with aseptic measures, it does not provide sterilization. Therefore, one of the main challenges is ensuring sterility prior to in vivo implantation. Although there are established gamma radiation sterilization protocols for inorganic materials, there are no such measures for organic materials. Additionally, the protocols in place for inorganic materials cannot be applied to organic materials, as the established radiation dose (25 kGy) would completely destroy the implant. This paper studies the effect of an escalated radiation dose in a decellularized rabbit trachea. We maintained the dose range (kGy) and tested escalated doses until finding the minimal dose at which sterilization is achieved. After determining the dose, we studied effects of it on the organ, both histologically and biomechanically. We determined that while 0.5 kGy did not achieve sterility, doses of both 1 kGy and 2 kGy did, with 1 kGy, therefore, being the minimal dose necessary to achieve sterilization. Microscopic studies showed no relevant changes compared to non-sterilized organs. Axial biomechanical characteristics were not altered at all, and only a slight reduction in the force per unit of length that the organ can radially tolerate was observed. We can therefore conclude that 1 kGy achieves complete sterilization of decellularized rabbit trachea with a minimal, if any, effects on the organ.

Doppler changes in the vertebral, middle cerebral, and umbilical arteries in fetuses delivered after 34 weeks: relationship to severity of growth restriction.

OBJECTIVE: To determine the association between Doppler changes in the fetal vertebral (VA), middle cerebral (MCA), and umbilical arteries (UA) and severity of growth restriction (FGR) in fetuses delivered after 34 weeks. METHOD: Five hundred seventy-one Doppler examinations of the VA, MCA, and UA were performed between 26 and 41 weeks of gestation. Values were converted into multiples of the median and divided into birth weight (BW) categories: BW>P10(th) , BW

Affective temperaments and sexual functioning in euthymic patients with bipolar disorder.

Sexual functioning in bipolar disorder (BD) is dependent on multiple clinical and demographic determinants that can eventually lead to sexual dysfunction. However, the contribution of affective temperaments remains unstudied in this population. In this cross-sectional multicentric work, we studied the impact of temperament traits on sexual functioning in 100 euthymic BD outpatients treated only with mood stabilizers with or without benzodiazepines. Temperament was evaluated using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego - Autoquestionnaire (TEMPS-A) and sexual functioning with the Changes on Sexual Functioning Questionnaire (CSFQ-14). The effect of temperament on sexual functioning was analyzed using Bayesian ordinal regression models, which included age, gender, BD type, dominant polarity, metabolic syndrome, marital status, and affective symptomatology. Our results showed that hyperthymic traits predicted a significantly higher CSFQ-14 score for global sexual functioning (OR = 1.222; 95% CI [1.073, 1.431]), desire (OR = 1.164; 95% CI [1.025, 1.357]), arousal (OR = 1.278; 95% CI: [1.083, 1.551]), and orgasm (OR = 1.182; 95% CI [1.037, 1.365]). We did not find a significant contribution for other types of temperaments. Better sexual functioning was also associated with a better quality of life. Our findings highlight the importance of temperament traits in sexual functioning in euthymic BD, which may have implications in sexual dysfunction prevention.

Hemodynamic Tolerance of Virtual Reality Intradialysis Exercise Performed during the Last 30 Minutes versus the Beginning of the Hemodialysis Session.

Background: Exercise improves the physical function of people suffering from chronic kidney disease on hemodialysis (HD). Virtual reality is a new type of intradialysis exercise that has a positive impact on physical function. Intradialysis exercise is recommended during the first 2 h, but its safety in the last part of the dialysis session is unknown. Methods: This was a pilot sub-study of a clinical trial. Several hemodynamic control variables were recorded, including blood pressure, heart rate, and intradialytic hypotensive events. These variables were recorded during three different HD sessions, one HD session at rest, another HD session with exercise during the first two hours, and one HD session with exercise during the last 30 min of dialysis. The intradialysis virtual reality exercise was performed for a maximum of 30 min. Results: During exercise sessions, there was a significant increase in heart rate (6.65 (4.92, 8.39) bpm; p < 0.001) and systolic blood pressure (6.25 (0.04,12.47) mmHg; p < 0.05). There was no difference in hemodynamic control between the sessions with exercise during the first two hours and the sessions with exercise during the last 30 min. There was no association between intra-dialytic hypotensive events at rest (five events) or exercise at any point (two vs. one event(s), respectively). Conclusion: performing exercise with virtual reality at the end of a hemodialysis session is not associated with hemodynamic instability.

Mathematical simulation of Doppler changes in late-onset smallness; progression patterns of cerebral and umbilical anomalies define two types of late-onset fetal growth restriction.

OBJECTIVE: To evaluate the progression of Doppler abnormalities in fetuses with late-onset fetal smallness (SGA) that become growth restricted (FGR). METHODS: 524 Doppler examinations of the umbilical and cerebral arteries systems, belonging to 442 late-onset SGA fetuses after week 34, were studied, evaluating by means of the statistical difference with the respective abnormal centiles, the pattern of progression into abnormal Doppler values and the distribution and cumulative sum of Doppler anomalies according to the interval to delivery. RESULTS: Only one third (33.5%, N = 148) of late-onset SGA fetuses presented Doppler anomalies, suggesting that most were of constitutional origin. The most frequent progression pattern into abnormal Doppler (N = 127, 85.81%) was that in which only one system (umbilical or cerebral) became abnormal. Half of fetuses debuted with abnormal umbilical flow (52%, N = 77) and half with cerebral anomalies (47.97%, N = 71), which were more likely to appear later and at shorter intervals to delivery (p = .007). These progression patters defined two varieties of late-onset FGR (type I and II) with similar outcome but different birth weight centiles (BW centile = 2.51, SD 2.91 versus 3.97, SD 3.17, p < .01). CONCLUSION: Two thirds of late-onset fetal smallness occurs without hemodynamic changes. In half of the remaining cases an initial cerebral vasodilation defines a group of fetuses with similar outcome but higher BW centile.

Expired Tidal Volume and Respiratory Rate During Postnatal Stabilization of Newborn Infants Born at Term via Cesarean Delivery.

Objective: To retrieve evolving respiratory measures in the first minutes after birth in normal neonates born at term using a respiratory function monitor. Study design: We evaluated newborn babies delivered at term via cesarean after uncomplicated pregnancies. Immediately after birth, a respiratory function monitor with an adapted flowmeter and a face mask were applied at 2, 5, and 10 minutes after birth for 90 seconds in each period. We analyzed expired and inspired tidal volume, respiratory rate (RR), percentage of leakage, and number of analyzed breaths in each individual infant's recording using a respiratory research software. Results: A total of 243 infants completed the study. The final data set included 59 058 (48.35%) valid observations for each of the variables representing the analysis of 32 801 breaths. With these data, we constructed a reference range with 10th, 25th, 50th, 75th, and 90th percentiles for expired tidal volume and RR. Tidal volumes plateaued earlier in female than in male infants. No correlation with delayed cord clamping, gestational age, maternal morbidity, or indication for cesarean delivery were established. Conclusions: We have constructed a reference range with percentiles for inspired and expired tidal volumes and RR in newborn babies born at term for the first 10 minutes after birth. Reference ranges can be employed for research and can be useful in the clinical setting to guide positive pressure ventilation in the delivery room.

Relationship between Skin Temperature, Electrical Manifestations of Muscle Fatigue, and Exercise-Induced Delayed Onset Muscle Soreness for Dynamic Contractions: A Preliminary Study.

Delayed onset muscle soreness (DOMS) indicates the presence of muscle damage and impairs force production and control. Monitorization of DOMS is useful to improving recovery intervention plans. The magnitude of DOMS may relate to muscle fatigue, which can be monitored by surface electromyography (EMG). Additionally, growing interest has been expressed in determining whether the skin temperature over a muscle group during exercise to fatigue could be a non-invasive marker for DOMS. Here we determine whether skin temperature and manifestations of muscle fatigue during exercise are correlated and can predict DOMS after concentric-eccentric bicep curl exercises. We tested 10 young adults who performed concentric-eccentric bicep curl exercises to induce muscle damage in the biceps brachialis to investigate the relationship between skin temperature and fatigue during exercise and DOMS after exercise. Muscle activation and skin temperature were recorded during exercise. DOMS was evaluated 24 h after exercise. Data analysis was performed using Bayesian regression models with regularizing priors. We found significant muscle fatigue and an increase in skin temperature during exercise. DOMS was observed 24 h after exercise. The regression models showed no correlation of changes in skin temperature and muscle fatigue during exercise with DOMS 24 h after exercise. In conclusion, our preliminary results do not support a relationship between skin temperature measured during exercise and either muscle fatigue during exercise or the ability to predict DOMS 24 h after exercise.