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A fracture in the thoracolumbal junction may cause complete or incomplete damage to the spinal cord, conus medullaris or cauda equina and result in an isolated or mixed lesion of the upper and lower motor neurons causing leg weakness and urinary/bowel/sexual dysfunction. In this retrospective cross-sectional study, we aimed to describe electrodiagnostic and urodynamic findings after thoracolumbal fractures and determine potential discriminating factors. We identified 74 cases (mean age 42 years, range 16-79 years, 55 men) admitted to our institution between 2008 and 2018 for Th12, L1 or L2 vertebral fractures, and retrieved from their medical records available demographic, clinical, electrodiagnostic and urodynamic data. The most common electrodiagnostic findings in the lower limbs (n = 40) were moderate-to-severe L3-S1 (35%) and L5-S1 (40%) lesions. As to the external anal sphincter (n = 33), the most frequent findings were an incomplete cauda equina (39%) or conus medullaris (15%) lesion, followed by the combined upper and lower motor neuron lesion (12%). Only the fracture level (with peripheral damage) was statistically significantly associated with electromyography findings. Detrusor overactivity or underactivity was each present in 37 (50%) cases. Those with Th12 versus L1-L2 fractures had higher odds of exhibiting detrusor overactivity; men had higher odds of using clean intermittent catheterization for bladder emptying than women. In summary, detrusor overactivity is common after fractures at the thoracolumbal junction and urodynamic findings are essential for proper diagnosis and selection of therapeutic approach. Combining urodynamic and electrodiagnostic studies is especially valuable in the presence of L1 fracture and lower urinary tract symptoms.

Berg balance scale (BBS) is a widely used outcome measure in rehabilitation. We wanted to check if it can discriminate among levels of use of walking aid in patients with Guillain-Barré syndrome or polyneuropathy. A retrospective audit of 109 such patients (aged 16-85 years) who had completed inpatient rehabilitation in the period 2012-2017 was conducted. Receiver operating characteristic curve analysis was used to estimate the thresholds that optimise the prediction of the patient's walking aid. Statistically, significant threshold BBS score was estimated for the ability to walk without walking aid (≥49 points, yielding 88% sensitivity, 68% specificity and 83% classification accuracy) and the necessity to walk with a walker (≤37 points, yielding 62% sensitivity, 83% specificity and 78% classification accuracy). BBS score thresholds can therefore help clinicians choose the appropriate walking aid for patients with Guillain-Barré syndrome or polyneuropathy undergoing rehabilitation.

BACKGROUND Veterans Affairs is dedicated to providing a Whole Health approach to care, including offering complementary and integrative health (CIH) approaches to Veterans. OBJECTIVE The objective of this study was to examine the association of CIH participation with Veterans' patient-reported outcomes over time. RESEARCH DESIGN A survey of patient-reported outcomes at 5 timepoints: baseline, 2, 4, 6, and 12 months. SUBJECTS Veterans participating in any type of CIH approach at 2 Veterans Affairs medical centers. MEASURES Mixed hierarchical models with repeated variables were used to test the hypothesis that participating in any CIH approach would be associated with Veterans' overall physical/mental health [Patient-Reported Outcomes Measurement Information System 28 (PROMIS 28)], pain intensity, perceived stress (Perceived Stress Scale-4), and engagement in their care (Patient Activation Measure-13), controlling for age, male sex, site, participation in other CIH approaches, and surveys completed. RESULTS We received 401 surveys from 119 Veterans (72% male, age range: 29-85 y) across all timepoints. Yoga participation was related to decreases in perceived stress (P

Background Adrenal vein sampling (AVS) is essential for diagnostics of primary aldosteronism, distinguishing unilateral from bilateral disease and determining treatment options. We reviewed the performance of AVS for primary aldosteronism at our center during first 15 years, comparing the initial period to the period after the introduction of a dedicated radiologist. Additionally, AVS outcomes were checked against CT findings and the proportion of operated patients with proven unilateral disease was estimated. Patients and methods A retrospective cross-sectional study conducted at the national endocrine referral center included all patients with primary aldosteronism who underwent AVS after its introduction in 2004 until the end of 2018. AVS was performed sequentially during Synacthen infusion. When the ratio of cortisol concentrations from adrenal vein and inferior vena cava was at least 5, AVS was considered successful. Results Data from 235 patients were examined (168 men; age 32–73, median 56 years; BMI 18–48, median 30.4 kg/ m2). Average number of annual AVS procedures increased from 7 in the 2004–2011 period to 29 in the 2012–2018 period (p < 0.001). AVS had to be repeated in 10% of procedures; it was successful in 77% of procedures and 86% of patients. The proportion of patients with successful AVS (92% in 2012–2018 vs. 66% in 2004–2011, p < 0.001) and of successful AVS procedures (82% vs. 61%, p < 0.001) was statistically significantly higher in the recent period. Conclusions Number of AVS procedures and success rate at our center increased over time. Introduction of a dedicated radiologist and technical advance expanded and improved the AVS practice.

Background:Preoperative grade 3 pivot shift has been reported to be associated with higher rates of anterior cruciate ligament (ACL) failure, persistent instability, and inferior patient-reported outcomes. The etiology of a high-grade pivot shift is multifactorial, and numerous factors have been suggested to be responsible. More attention has recently been focused on injury to the anterolateral structures (ALS) as a risk factor for a grade 3 pivot shift.Purpose:To determine risk factors for grade 3 pivot shift, including soft tissue and osseous parameters.Study Design:Cross-sectional study; Level of evidence, 3.Methods:A prospective evaluation was undertaken of 200 consecutive patients undergoing acute ACL reconstruction (within 10 days of injury). An open exploration of the lateral side of the injured knee was performed at the time of the index procedure. Details regarding patient and injury characteristics were recorded, as were details of soft tissue injuries, including meniscal tears, ALS lesions, medial collateral ligament tears, and chondral injuries. Osseous parameters (tibial slope and condylar ratios) were determined per established magnetic resonance imaging protocols. A multivariate logistic regression with penalized maximum likelihood was used to identify risk factors associated with International Knee Documentation Committee (IKDC) grade 3 pivot shift.Results:The mean ± SD age of the population was 28.3 ± 9.8 years; 67.5% of patients were male. Among patients, 35 (17.5%) had a high-grade pivot shift (IKDC grade 3), and 165 (82.5%) had a low-grade pivot shift (IKDC grades 1 and 2). Univariate and multivariate logistic regression analysis demonstrated that injury to the ALS was the only significant risk factor for grade 3 pivot shift (odds ratio, 13.49; 95% CI, 1.80-1725.53).Conclusion:This comprehensive evaluation of soft tissue and osseous factors has identified that injury to the ALS is the most important risk factor for grade 3 pivot shift in acute ACL-injured knees.

World demography is changing as the population ages and there are more people with disabilities having problems to stay independently at home. Innovative technologies could help extend the independence of older people living at home. As part of a collaborative project, we investigated ownership and use of information and communication technologies (ICT) among older people with lower limb loss (LLL) using questionnaires and retrospective analysis. Our aim was to analyse factors associated with ICT use among people with LLL. We identified age as the main factor that limits ownership and use of ICT among older people with LLL in Slovenia. Cause of amputation also appears to be relevant, whereby those who had amputation because of peripheral vascular disease are more likely to use a personal or tablet computer, social networks, messaging apps, email and internet than those who had amputation because of diabetes. In addition, those living in the suburbs are more likely to use a health monitoring device than those living in the countryside.

The Measure of Processes of Care for professionals (MPOC-SP) is valid and reliable a self-administered questionnaire for paediatric service providers engaged in care for chronically ill children. Our aim was to evaluate internal consistency reliability, one-year stability and some aspects of validity of its Slovene translation. Sixty-seven service providers from seven professional groups of several hospitals and health centres participated in the study. MPOC-SP mean scores for all four subscales were high; their ranking order was the same as in other MPOC-SP studies. All subscales exhibited sufficient internal consistency (Cronbach alpha from 0.69 to 0.86, adequate corrected item-total correlations). None of the mean subscale scores changed significantly after one year (P values from 0.11 to 0.80). The Slovene translation of the MPOC-SP can therefore be considered a reliable instrument that shows good stability over a period of one year, and as such it can be adopted in clinical practice.

Rehabilitation programs after amputation often include fitting a prosthesis, but prescriptions vary under similar circumstances. The US Medicare Functional Classification Level (K-level) is a scale for describing functional abilities of persons after lower-limb amputation (from 0 = no ability or potential to ambulate, to 4 = prosthetic demands of a child/active adult/athlete). Different outcome measures are used to assess K-level, including six-minute walk test (6MWT). We attempted to predict the assigned K-level of unilateral transtibial prosthesis users from their results of 6MWT and one-leg standing test on prosthesis (OLSTP). Outpatients who had been rehabilitated and fitted with transtibial prosthesis at the University Rehabilitation Institute in Ljubljana in 2014 were included in a retrospective audit. The data were analysed using receiver-operating-characteristics curves, linear discriminant analysis, classification trees and ordinal logistic regression. Among the 120 patients (aged 39-90, mean 67 years; 79% men), eight belonged to K1 level, 94 to K2, and 18 to K3 or K4; 61 could not stand on the prosthesis, eight stood on it for 1 s, and 51 stood on it for 2 s or more. With a simple classification rule based only on 6MWT (130 m threshold for K2/K3/K4 vs. K1, 340 m for K3/K4 vs. K1/K2), we observed sensitivity and specificity close to 90%. The more sophisticated statistical approaches yielded substantially similar and comparably accurate results. 6MWT and OLST could therefore be used as predictors for transtibial prosthesis prescription in clinical practice.

Background: Brain health is one of the cornerstones of a long and full life. Active care for brain health and reduction of lifestyle-related risks for brain disorders may be a key strategy in tackling the growing prevalence of mental and neurological illnesses. Public knowledge, perception, and preventive behavior need to be considered in the planning of effective strategies for brain health promotion. Our research is the first effort aimed at assessing Slovenian lay public knowledge, search and use of scientific information about the brain, and care for brain health.Methods: An online survey was used to gather data for descriptive and associative statistical analyses of a sample of the Slovenian public (n = 2568) in August 2017. Participants with formal brain-related education were excluded, leaving the remaining sample of the lay public (n = 1012). Demographic characteristics and information regarding the perceived importance and knowledge of brain health and engagement in preventive behaviors of participants were collected, and key associative analyses were carried out.Results: The majority of respondents (89%) considered brain health to be important. Over one-third (39%) considered their knowledge of the brain as sufficient relative to their needs. Most of the respondents identified science-recommended practices to be important for brain health. No recommendation was followed daily by the majority of the respondents, primarily due to declared lack of time (59%), and lack of information (32%). Information was obtained primarily from television (38%), followed by newspapers and magazines (31%), the Internet (31%), and direct conversations (27%). However, the highest-rated, preferred source of information was lectured by experts. One-third of our sample struggled with the trustworthiness of information sources. Female gender and older age were associated with a higher frequency of healthy practices. Personal or familial diagnoses of brain disorders were not associated with a higher frequency of the behavior in favor of brain health, but did affect available time and perceived value of preventive practices.Conclusions: Our research provides an initial insight into the perceptions, knowledge, and brain health-promoting behavior of the Slovenian lay public. Our findings can inform future strategies for science communication, public education and engagement, and policy-making to improve lifelong active care for brain health.

We examined whether driving-related reaction times differ between 26 healthy adults (university students) and 26 patients after stroke, and how distractors and leg-dominance affect reaction time and correctness of reactions of healthy adults. Reaction times were measured with the Fiat Mediatester driving simulator using 18-lamps reaction test (simple reaction time measurement) and choice reaction test (scored as reaction time and number of correct reactions). There was no statistically significant difference between the groups in simple reaction time. As expected, choice reaction times of the healthy adults were shorter on average and their reactions more accurate than those of the patients. Under the influence of distractors, healthy adults had statistically significantly longer choice and simple reaction times and made fewer correct choices compared to normal conditions. Leg dominance statistically significantly affected choice reaction times and correctness of reactions, but not simple reaction times. Our results confirm validity and usefulness of the Fiat Mediatester driving simulator for research purposes.

Effects of rehabilitation on knee function, activity and health-related quality of life after soft-tissue knee injury have been widely studied in clinical trials, but there is still a lack of data on the relation between knee muscle strength and athlete's perceived performance to identify sports-risk modifiers. We performed a prospective observational clinical study of knee muscle strength and self-reported health during rehabilitation after unilateral knee soft-tissue injury in recreational sports. Forty-three patients performed isokinetic dynamometry and filled in the Short form Health Survey (SF-36) and the Oxford Knee Score questionnaires before and after 4 months of instructed home strengthening program. We observed significant improvement in peak torque deficit between two limbs during concentric extension (PTDE) and flexion, dynamic control ratio of the involved knee, most of the SF-36 subscales and the Oxford Knee Score values (P ≤ 0.001). Dynamic control ratio of the uninvolved knee values remained below referential values and unchanged. Improvement of PTDE correlated positively with improvement of the bodily pain subscale of SF-36 score (r = 0.51, P < 0.001). Receiver operating characteristic analysis indicated that reduction of pain by at least nine points predicts at least 10% reduction in PTDE, whereby the bodily pain change achieved poor (56%) sensitivity and good (86%) specificity as a rehabilitation success measure for recreational athletes after knee injury. Primary inferior eccentric strength of noninjured knee hamstrings might indicate increased risk of knee injury. Diminished perceived pain predicts strength improvement of the injured knee extensors with poor sensitivity and good specificity.

Preterm birth is defined as delivery before 37 completed weeks of pregnancy, and it is the leading cause of neonatal morbidity and mortality. Oxidative stress is recognized as an important factor in the pathogenesis of premature labor. We conducted this analysis to investigate the safety of administration of the tocolytic drug Atosiban—a reversible, competitive antagonist of the oxytocin receptor in the treatment of preterm birth and its impact on the level of oxidative stress in pregnant women after 48 hours of tocolytic treatment. This prospective study was conducted between March 2016 and August 2017 at the Obstetric Clinic of the Polish Mother’s Memorial Hospital Research Institute. Total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI) values as well as 3-nitrotyrosine, carbonyl, and thiol group levels were measured using an ELISA test in serum and plasma of 56 pregnant women before and after 48 hours of continuous administration of Atosiban. We found that TAS levels decreased almost twice after the 48-hour drug administration (0.936 ± 0.360 mmol/L vs. 0.582 ± 0.305 mmol/L, P<0.001) while TOS increased from 18.217 ± 16.093 μmol/L to 30.442 ± 30.578 μmol/L (P<0.001). We also found a significant increase in OSI index—almost a threefold increase from 0.022 ± 0.022 to 0.075 ± 0.085, P<0.001. In addition, statistically significant differences in the level of carbonyl groups were found. It increased from 65.358 ± 31.332 μmol/L to 97.982 ± 38.047 μmol/L (P<0.001), which indicates increased oxidation of plasma proteins. Furthermore, patients who gave birth prematurely had higher levels of TOS after a 48-hour drug administration than the second group with labor after 37 weeks of pregnancy (42.803 ± 34.683 μmol/L vs. 25.792 ± 27.821 μmol/L, P<0.031). The obtained results clearly indicate that pregnant women during tocolytic treatment with Atosiban are in a state of increased oxidative stress and occurrence of preterm birth can be associated with this phenomenon. This trial is registered with NCT03570294.

It is often difficult for the clinician to choose the most appropriate balance-assessment measure. We wanted to facilitate this decision based on the stroke patient's functional abilities. The aim of our study was to compare three established scales [Berg Balance Scale (BBS), mini-BESTest (MBT) and Functional Gait Assessment (FGA)] in terms of responsiveness, floor and ceiling effects at different levels of ambulation as defined by the Functional Ambulation Classification (FAC). The 18-month prospective study included 88 patients after cerebral stroke, who were able to walk independently or with assistance of one person (FAC 2-6). BBS showed the highest relative gain in the FAC 2-3 group (17% of maximum scale score); in the other two groups (FAC 4-5 and FAC 6), MBT showed the highest relative gain (16 and 13%, respectively), followed by FGA (11 and 10%, respectively). Among the patients with initial FAC 2-3, a floor effect occurred with FGA, while a ceiling effect occurred with BBS among patients with initial FAC 6. Gain in FGA correlated slightly more with improvement detected by MBT (r = 0.60) than with BBS (r = 0.50). We can conclude that BBS seems to be suitable for stroke patients with initial FAC 2-5, whereas MBT and FGA for those with FAC 4-6.

Background. There is a lack of studies on adjustment to upper limb prosthesis with large representative samples that would compare different prosthesis types and use standardised outcome measures. Hence, we wanted to assess satisfaction with, and level of adjustment to, an upper-limb prosthesis among people after an upper limb amputation in our country. Material and methods. We conducted a cross-sectional descriptive study. The TAPES-R questionnaire was mailed to 431 patients identified from electronic health records at national specialist outpatient clinics for rehabilitation of people after upper limb amputation. Results. 191 patients (44%) responded and were subsequently ascertained to be a representative sample of the population of upper limb amputees in our country. Univariate analyses and multiple regression models indicated that, on average, overall satisfaction is lower among those who have received their current prosthesis more recently, women might be more satisfied with prosthesis than men, above-elbow amputees experience more activity restrictions than those with amputation at a lower level, patients with amputated fingers or palm are more satisfied with the prosthesis than others, and so are those who had amputation following an accident as compared to other reasons. Conclusion. We reliably identified some systematic factors, but it is individual factors and experience that largely determine adjustment to and satisfaction with a prosthesis following an upper limb amputation.

Suprascapular neuropathy is more frequent in volleyball as compared to other overhead sports. This study aims to report the actual prevalence of suprascapular neuropathy among elite volleyball play...

BACKGROUND Different surgical techniques have been proposed for rectocele repair. However, controversial aspects exist on the best approach to use. The study aims to report the early and late outcomes of the sequential transfixed stich technique (STST) for the treatment of rectocele in the absence of mucosal prolapse. METHODS One hundred patients presenting a symptomatic rectocele were treated with STST from January 2010 through August 2015. Patients with mucosal prolapse were not considered eligible for STST. After a period of 24 months from surgery, all the patients were clinically evaluated with the intent to investigate the risk of recurrence of the preoperative symptoms. RESULTS All the patients were women (median age=54.7 years; ranges=37-75). Median discharge time was 1.5 days. One-month severe complications were: hemorrhoid thrombosis (6.0%), self-solved bleeding (6.0%), urinary retention (4.0%), anal secretion (4.0%) and urinary incontinence (1.0%). No post-operative cases of fecal incontinence were observed. Two years after surgery, 76.0% of patients reported a global improvement of the preoperative symptoms, with 73 and 35% of cases showing a reduced difficulty in the evacuation and need for digitation. Only 8.0% of patients showed a recurrence of the initial symptoms. CONCLUSIONS The STST is a feasible, safe, and cost-effective technique for the treatment of the rectocele without rectal mucosal prolapse. The method does not increase the risk of postoperative anal incontinence and presents a short hospital stay. STST presents long-term results in line with other transvaginal and transanal approaches.

The pathogenesis of hemorrhoids involves vascular congestion, fragmentation of supporting tissues and, in many cases, increased resting anal pressure. A new ointment (Hemolen®) has been devised to control hemorrhoids symptoms acting on all the pathophysiologic mechanisms involved.Pilot study on patients with grade I-III hemorrhoids. The ointment was applied twice daily for 30 days and follow-up visits were scheduled 7 days (T1), 14 days (T2) and 30 days (T3) after recruitment (T0). Signs and symptoms (bleeding, discomfort, itching, edema, thrombosis, congestion, inflammation, pain) were evaluated at each visit using dedicated scores and VAS scale. Resting anal pressure was measured at time T0, 1 hour after the first application and at T1. Use of painkiller was recorded.48 patients (25 females; mean age 47±15.8 years) were enrolled; 52.1% of them had II degree hemorrhoids and 27.1% had III degree hemorrhoids. The severity scores significantly dropped from T0 to each scheduled visit and a significant reduction of resting anal pressure was observed from T0 to 1 hour after application (z=13.5; p0.001) and from T0 to T1 (z=6; p0.001). The comparison of the resting pressure among whole time series showed a significant reduction (Fr=124.4; p=0.001). Use of pain-killers decreased significantly from T0 to T1 (p0.001) and from T1 to T2 (p=0.001).The new ointment tested in the present study is safe and effective for the management of hemorrhoid symptoms in the early stages hemorrhoids, during the acute phases and in patients with more severe hemorrhoids awaiting surgery. Prospective, randomized controlled trials are needed to confirm these encouraging results.

The objective of this study was to determine the concentration and the reference ranges of essential and toxic elements in amniotic fluid (AF) and maternal serum (MS) at birth. This study was conducted among 175 healthy pregnant Caucasian European women aged 18–42. AF and maternal blood samples were collected during delivery. An inductively coupled plasma mass spectrometry (ICP-MS) technique was used to determine the levels of Mg, Co, Cu, Zn, Sr, Cd, Ba, Pb, U, Ca, Cr, Al, Mn, V, Fe, As, Se and Sb in AF and MS. The range of reference values was calculated for all analyzed elements in the serum and AF. The mean concentrations of elements, except Pb, were generally higher in MS than in AF. Multiple regression analysis showed that the maternal/newborn body mass (MBM/NBM) ratio was a strong negative predictor (among maternal age and gravidity) of Mg concentration in amniotic fluid. In the serum, MBN/NBM ratio was a strong positive predictor of Cu concentration. Moreover, regression analysis showed that maternal age was an independent positive predictor of the Se level in maternal serum. The reference value ranges of 18 essential and toxic elements were established in AF and MS among a population of healthy pregnant Polish women at delivery. The level of Mg, Co, Cu, Ca and Se in AF and MS can be determined by maternal age and MBM/NBM ratio. These results can be useful in counseling individuals with pregnancies affected by exposure to one of the parameters under investigation. Electronic supplementary material The online version of this article (10.1007/s12011-018-1471-2) contains supplementary material, which is available to authorized users.

Purpose To evaluate the dietary intake of pregnant women and their nutritional status of Ca, Mg, Fe, Zn, and Cu, as the nutritional status of pregnant women is an important factor for the proper progression of a pregnancy and the development and health of the foetus. Methods The study was conducted on 108 pregnant women ages 18–42, at 6–32 weeks of gestation. We used a questionnaire and a 24-h recall nutrition interview. Hair samples were taken for testing and the level of each mineral was assessed using atomic absorption spectrometry. The results were analysed using the Dietetyk and Statistica 10 software. Results Low levels of Fe, Zn, Ca, Mg, vitamin D, and folic acid intake were seen in the pregnant women, with the use of dietary supplements significantly increasing their intake of Fe, Zn, and folic acid. The concentration of zinc and magnesium in the women’s hair was shown to be affected by their age and, in the case of magnesium, by the week of pregnancy. Conclusions It was observed that the diet of pregnant women is characterised by low levels of Fe, Zn, Ca, Mg, vitamin D, and folic acid. Dietary supplementation with vitamins and minerals significantly increases the daily Fe and folic acid intake in pregnant women. The concentration of Zn and Mg in hair depends on the age of pregnant women and Mg level in the hair of women decreases during pregnancy.

Gadolinium-enhancing lesions reflect active disease and are critical for in-patient monitoring in multiple sclerosis (MS). In this work, we have developed the first fully automated method to segment and count the gadolinium-enhancing lesions from routine clinical MRI of MS patients. The proposed method first segments the potential lesions using 2D-UNet from multi-channel scans (T1 post-contrast, T1 pre-contrast, FLAIR, T2, and proton-density) and classifies the lesions using a random forest classifier. The algorithm was trained and validated on 600 MRIs with manual segmentation. We compared the effect of loss functions (Dice, cross entropy, and bootstrapping cross entropy) and number of input contrasts. We compared the lesion counts with those by radiologists using 2,846 images. Dice, lesion-wise sensitivity, and false discovery rate with full 5 contrasts were 0.698, 0.844, and 0.307, which improved to 0.767, 0.969, and 0.00 in large lesions (>100 voxels). The model using bootstrapping loss function provided a statistically significant increase of 7.1% in sensitivity and of 2.3% in Dice compared with the model using cross entropy loss. T1 post/pre-contrast and FLAIR were the most important contrasts. For large lesions, the 2D-UNet model trained using T1 pre-contrast, FLAIR, T2, PD had a lesion-wise sensitivity of 0.688 and false discovery rate 0.083, even without T1 post-contrast. For counting lesions in 2846 routine MRI images, the model with 2D-UNet and random forest, which was trained with bootstrapping cross entropy, achieved accuracy of 87.7% using T1 pre-contrast, T1 post-contrast, and FLAIR when lesion counts were categorized as 0, 1, and 2 or more. The model performs well in routine non-standardized MRI datasets, allows large-scale analysis of clinical datasets, and may have clinical applications.

The aim of this study was to review the role of selected trace elements in pregnancy and fetal development. Citations related to the role of iron (Fe), zinc (Zn), manganese (Mn), copper (Cu) and selenium (Se) during pregnancy were searched in PubMed, Medline, Web of Science, using keywords and MeSH terms. Inadequate supply of trace elements can cause abnormalities of fetal development and predispose a child to disorders later on in life. Trace elements are the key elements of complex enzymes responsible for the modulation of the antioxidant defense system of the organism. It has been suggested that there is a correlation between reduced levels of trace elements essential for antioxidant function in the body of pregnant women, and an increased risk of developing preeclampsia. Trace elements are components of numerous regulatory enzymes and hormones essential to the division and differentiation of fetal cells and their further development. Mineral deficiencies in pregnant women can cause birth defects of the central nervous system, and growth disorders. Future research should be directed to explain the interaction between trace elements, and establish the optimum levels of macro and micronutrients supplementation, as well as determine the reference values for trace elements in the maternal serum, umbilical cord blood and amniotic fluid.

The mineral levels in maternal serum change during pregnancy and may be correlated with those of newborn cord blood. The aim of this study was to evaluate the concentrations of calcium (Ca), magnesium (Mg), zinc (Zn), iron (Fe), and copper (Cu) in maternal blood before and after delivery and in umbilical cord vein and artery serum. The study was carried out in 64 Caucasian pregnant women who delivered in a district hospital in Greater Poland region, aged 28.1 ± 5.4 years, with a mean gestational age of 39.2 ± 1.3 weeks. Blood samples were taken from women 2–8 h before delivery and immediately after childbirth. The umbilical cord artery and vein blood of newborns was obtained immediately after childbirth. The levels of minerals in serum were determined by flame atomic absorption spectrometry. A significant drop in the concentrations of Mg (17.71 ± 1.51 vs 17.07 ± 1.61 μg/ml; p

In traumatic brain injury (TBI) and stroke rehabilitation, the question of reintegration of the driver into traffic is faced very often. Driving is an important domain and for some patients, return to driving represents a crucial event for community inclusion. The aim of our study was to examine the utility of Glasgow Coma Scale within the first 24 h of injury and the Functional Independence Measure (FIM) at rehabilitation admission for predicting the return to driving. We included 72 patients after TBI or stroke. Driving outcome was assessed in terms of being allowed to drive without restrictions as opposed to failing the test or being allowed to drive with restrictions. We examined two samples: the TBI patients only and the entire sample including patients after stroke. The results indicate that for TBI patients, Glasgow Coma Scale and motor FIM could be predictors of driving outcome; in the entire sample, the unrestricted driving outcome was also associated with a high score on the FIM motor scale. Early prediction of return to driving after TBI and stroke is important for the patients, their families and the rehabilitation teams to set realistic goals that enable the best possible reintegration after rehabilitation.

Guillain-Barré syndrome (GBS) is an acute inflammatory demyelinating polyradiculopathy resulting in severe impairments of many body structures and functions with consequent limitations of activities and participation. The aim of our study was to evaluate rehabilitation outcome in these patients. Forty-five (20 women, 25 men) with GBS patients who had completed primary comprehensive rehabilitation were included in the study. Medical Research Council Scale for Muscle Strength was used for assessment of lower-limb function. Patients' activities were assessed using the Functional Independence Measure and two walking tests (6 min and 10 m). The patients were also described using an adapted International Classification of Functioning, Disability and Health checklist. Assessment was performed at admission and at discharge. Clinically important and statistically significant improvements were found in all outcome measures. Strong and significant correlations were found between the outcome measures. International Classification of Functioning, Disability and Health coding also clearly reflected the progress. Improvement in patients' activities increased statistically significantly with time for up to 3 months of rehabilitation. The outcome was not related to the time interval from establishing the diagnosis to the start of rehabilitation. Hence, multidisciplinary care for GBS patients is effective, because clinically important and statistically significant improvements regarding body functions and activities are achieved during relatively short inpatient rehabilitation.

We investigated metric properties of the Slovenian translation of de Morton Mobility Index in patients with musculoskeletal impairments during rehabilitation. The study included 30 inpatients, aged 22-84 years, with musculoskeletal impairments with or without impairment of peripheral nerves. They were assessed repeatedly with de Morton Mobility Index, Functional Ambulation Classification, Ten-metre Walk Test, Six-minute Walk Test, Berg Balance Scale and the motor subscale of the Functional Independence Measure. Convergent validity of de Morton Mobility Index was confirmed by good to very good correlations with the other measurements. Known-groups validity was demonstrated by significant differences in de Morton Mobility Index scores between patients who were not able to walk and those who were able to walk with or without waking aid, at admission and after 4 weeks. Predictive validity of de Morton Mobility Index for functional independence after 4 weeks of rehabilitation was moderate. Minimal clinically important difference of de Morton Mobility Index was estimated to be five points. De Morton Mobility Index was responsive after 2 and 4 weeks of rehabilitation (Cohen's d 1.15 and 0.95, respectively). No floor or ceiling effects were identified. Internal validity of de Morton Mobility Index was confirmed by Rasch analysis. Hence, de Morton Mobility Index is a valid, unidimensional, and responsive measure of mobility for patients with musculoskeletal impairments at rehabilitation regardless of age. Its use is recommended for adult patients at low and basic functioning level.

Tumor-driven immune suppression is a major barrier to successful immunotherapy in ovarian carcinomas (OvCa). Among various mechanisms responsible for immune suppression, arginase-1 (ARG1)-carrying small extracellular vesicles (EVs) emerge as important contributors to tumor growth and tumor escape from the host immune system. Here, we report that small EVs found in the ascites and plasma of OvCa patients contain ARG1. EVs suppress proliferation of CD4+ and CD8+ T-cells in vitro and in vivo in OvCa mouse models. In mice, ARG1-containing EVs are transported to draining lymph nodes, taken up by dendritic cells and inhibit antigen-specific T-cell proliferation. Increased expression of ARG1 in mouse OvCa cells is associated with accelerated tumor progression that can be blocked by an arginase inhibitor. Altogether, our studies show that tumor cells use EVs as vehicles to carry over long distances and deliver to immune cells a metabolic checkpoint molecule – ARG1, mitigating anti-tumor immune responses., Cancer cells employ a variety of ways to escape the immune system. Here, the authors show that ovarian cancer cells produce small extracellular vescicles containing arginase 1 that are taken up by dendritic cells in the draining lymph nodes, resulting in inhibition of antigen-specific T-cell proliferation.

Summary Background Low donor heart availability underscores the need to identify all potentially transplantable organs. We sought to determine whether pre-emptive administration of pangenotypic direct-acting antiviral therapy can safely prevent the development of chronic hepatitis C virus (HCV) infection in uninfected recipients of HCV-infected donor hearts. Methods Patients were recruited for this an open-label, single-centre, proof-of-concept study from Nov 1, 2017, to Nov 30, 2018. Following enrolment, the recipient's status on the heart transplantation waiting list was updated to reflect a willingness to accept either an HCV-positive or HCV-negative heart donor. Patients who underwent transplantation with a viraemic donor heart, as determined by nucleic acid testing (NAT), received pre-emptive oral glecaprevir-pibrentasvir before transport to the operating room followed by an 8-week course of glecaprevir-pibrentasvir after transplantation. Patients receiving HCV antibody-positive donor hearts without detectable circulating HCV RNA were followed using a reactive approach and started glecaprevir-pibrentasvir only if they developed viraemia. The primary outcome was achievement of sustained virological response 12 weeks after completion of glecaprevir-pibrentasvir therapy (SVR12). Patients were followed from study enrolment to 1 year after transplantation. This is an interim analysis, initiated after all enrolled patients reached the primary outcome. Results reflect data from Nov 1, 2017, to May 30, 2019. This trial is registered with ClinicalTrials.gov , number NCT03208244 . Findings 55 patients were assessed for eligibility and 52 consented to enrolment. 25 patients underwent heart transplantation with HCV-positive donor hearts (20 NAT-positive, five NAT-negative), three of whom underwent simultaneous heart–kidney transplantation. All 20 recipients of NAT-positive hearts tolerated glecaprevir-pibrentasvir and showed rapid viral suppression (median time to clearance 3·5 days, IQR 0·0–8·3), with the subsequent achievement of SVR12 by all 20. The five recipients of NAT-negative grafts did not become viraemic. Median pre-transplant waiting time for patients following enrolment in the HCV protocol was 20 days (IQR 8–57). Patient and allograft survival were 100% at a median follow-up of 10·7 months (range 6·5–18·0). Interpretation Pre-emptive administration of glecaprevir-pibrentasvir therapy results in expedited organ transplantation, rapid HCV suppression, prevention of chronic HCV infection, and excellent early allograft function in patients receiving HCV-infected donor hearts. Long-term outcomes are not yet known. Funding American Association for the Study of Liver Diseases, National Institutes of Health, and the Massachusetts General Hospital.

To compare the long-term effectiveness of non-operative treatment with immediate arthroscopic surgical stabilization in young, active patients after first-time anterior glenohumeral dislocation. Consecutive patients aged 15–25 years who suffered primary traumatic anterior glenohumeral dislocation were enrolled in this prospective, non-randomized investigation. In total, 160 patients were enrolled—64 opted for surgical stabilization (group A), while 96 opted for conservative treatment (group B). At final follow-up of over 6.5 years, 60 patients in group A (96.7% males, age 22.8 ± 3.2) and 70 patients in group B (90.0% males, age 20.8 ± 2.9) were evaluated with physical examination, patient-reported outcome measures (PROMs), and radiological studies. Recurrence and return to sport (RTS) data were collected, and variables were compared between groups. Recurrence rate in group A was 13.3% at mean latency of 3.3 ± 1.9 years, compared to 71.4% at mean latency of 2.1 ± 1.5 years in group B (P

Congenital birth defects may result in a critical condition affecting the baby, including severe fetal/neonatal handicap and mortality. Several studies have shown that genetic, nutritional, and environmental factors may have an impact on fetal development and neonatal health. The relevance of essential and toxic elements on fetal development has not yet been fully investigated, and the results of recent research indicate that these elements may be crucial in the assessment of the risk of malformations in neonates. We determined the association between essential and toxic elements and the level of folate in maternal serum (MS) and amniotic fluid (AF), along with neonatal abnormalities. A total of 258 pregnant Polish women in the age group of 17&ndash, 42 years participated in this study. AF and MS were collected during vaginal delivery or during cesarean section. An inductively coupled plasma mass spectrometry technique was used to determine the levels of various elements in AF and MS. The results of this exploratory study indicate that the levels of essential and toxic elements are associated with fetal and newborn anatomical abnormalities and growth disorders.

Adrenal venous sampling (AVS) is the only available method to distinguish bilateral from unilateral primary aldosteronism (PA). AVS has several drawbacks, so it is reasonable to avoid this procedure when the results would not affect clinical management. Our objective was to identify a clinical criterion that can reliably predict nonlateralized AVS as a surrogate for bilateral PA that is not treated surgically.A retrospective diagnostic cross-sectional study conducted at Slovenian national endocrine referral center included 69 consecutive patients (mean age 56 ± 8 years, 21 females) with PA who underwent AVS. PA was confirmed with the saline infusion test (SIT). AVS was performed sequentially during continuous adrenocorticotrophic hormone (ACTH) infusion. The main outcome measures were variables associated with nonlateralized AVS to derive a clinical prediction rule.Sixty-seven (97%) patients had a successful AVS and were included in the statistical analysis. A total of 39 (58%) patients had nonlateralized AVS. The combined criterion of serum potassium ≥3.5 mmol/L, post-SIT aldosterone18 ng/dL, and either no or bilateral tumor found on computed tomography (CT) imaging had perfect estimated specificity (and thus 100% positive predictive value) for bilateral PA, saving an estimated 16% of the patients (11/67) from unnecessary AVS. The best overall classification accuracy (50/67 = 75%) was achieved using the post-SIT aldosterone level18 ng/dL alone, which yielded 74% sensitivity and 75% specificity for predicting nonlateralized AVS.Our clinical prediction criterion appears to accurately determine a subset of patients with bilateral PA who could avoid unnecessary AVS and immediately commence with medical treatment.

To evaluate effectiveness of fall-risk-assessment-based fall prevention for stroke rehabilitation inpatients.A consecutive series of 232 patients admitted for the first time to a subacute stroke-rehabilitation ward during 2010-2011 was studied in detail. The Assessment Sheet for Fall Prediction in Stroke Inpatients (ASFPSI by Nakagawa et al.) was used to assess fall-risk upon admission. Association of ASFPSI score and patient characteristics with actual falls was statistically tested. Yearly incidence of falls per 1000 hospital days (HD) was retrospectively audited for the 2006-2014 period to evaluate effectiveness of fall-risk reduction measures.The observed incidence of falls over the detailed-study-period was 3.0/1000 HD; 39% of the fallers fell during the first week after admission. ASFPSI score was not significantly associated with falls. Longer hospital stay, left body-side affected and non-extreme FIM score (55-101) were associated with higher odds of fall. Introduction of fall-risk reduction measures followed by compulsory fall-risk assessment lead to incidence of falls dropping from 7.1/1000 HD in 2006 to 2.8/1000 HD in 2011 and remaining at that level until 2014.The fall-risk-assessment-based measures appear to have led to decreasing falls risk among post-stroke rehabilitation inpatients classified as being at high risk of falls. The fall prevention programme as a whole was successful. Patients with non-extreme level of functional independence should receive enhanced fall prevention. Implications for Rehabilitation Recognising the fall risk upon the patient's admission is essential for preventing falls in rehabilitation wards. Assessing the fall risk is a team tasks and combines information from various sources. Assessing fall risk in stroke patients using the assessment sheet by Nakagawa et al. immediately upon admission systematically draws attention to the risk of falls in each individual patient.

Objectives: Peroxiredoxins (PRDXs) constitute a family of antioxidant enzymes which are also involved in the process of carcinogenesis. They are composed of six identified isoforms (PRDX-1-6) and are supposed to play different roles in tumor progression, depending on type of cancer and member of the PRDX family. The aim of the study was to assess the prog- nostic value of PRDXs in ovarian cancer. Material and methods: a dataset of patients with ovarian cancer from The Cancer Genome Atlas was analyzed. Expression of PRDX-1 to 6 mRNA was evaluated in 260 samples. The prognostic value of PRDXs was assessed using the Cox regression model which included the following clinical and pathological data: age, clinical stage, tumor grade, and residual disease. Results: Within the PRDXs family, only higher expression of PRDX-5 was associated with worse overall survival both, in unselected patients and > 50-year-olds. PRDX-5 expression and residual disease were independent negative prognostic factors of patient survival. Conclusions: PRDX-5 is a negative predictor of survival in ovarian cancer.

The aim of the study was to determine the correlations between body mass index (BMI) values before pregnancy and the concentrations of selected elements (Mg, Co, Cu, Zn, Sr, Cd, Ba, Pb, U, Ca, Cr, Al, Mn, V, Fe) in blood serum and amniotic fluid (AF) in pregnant women. Elemental analysis of serum and amniotic fluid in 225 Polish women (Caucasian/white) showed a relationship between the concentration of minerals in the above-mentioned samples and the pre-pregnancy BMI. Analysis of blood serum was performed by using ICP-MS and it demonstrated that iron concentration was significantly lower in overweight and obese women. Being underweight in pregnant women was associated with a significantly lower concentration of magnesium and cobalt in the blood serum. Both underweight and overweight women were associated with significantly lower concentrations of calcium and strontium in the blood serum. The concentration of cobalt was significantly higher in underweight women. The concentration of lead in the blood serum of overweight and obese women was significantly higher than in other groups. Analysis of the AF showed that the concentration of copper was significantly lower in overweight and obese women, and the concentration of manganese and vanadium significantly higher than in other groups of women. A deficiency in essential minerals and an excess of heavy metals in women may be associated with abnormal body weight and this is important in the etiopathogenesis of pregnancy and fetal development disorders.

Purpose: To compare clinical outcomes and tunnel widening following anterior cruciate ligament reconstruction (ACLR) performed with an all-inside technique (Group A) or with a bioabsorbable tibial screw and suspensory femoral fixation (Group B).\ud \ud Methods: Tunnel widening was assessed using computed tomography (CT) and a previously validated analytical best fit cylinder technique at approximately 1-year following ACLR. Clinical follow-up comprised evaluation with IKDC, KSS, Tegner, Lysholm scores, and knee laxity assessment.\ud \ud Results: The study population comprised 22 patients in each group with a median clinical follow-up of 24 months (range 21–27 months). The median duration between ACLR and CT was 13 months (range 12–14 months). There were no significant differences in clinical outcome measures between groups. There were no differences between groups with respect to femoral tunnel widening. However, there was a significantly larger increase in tibial tunnel widening, at the middle portion, in Group B (2.4 ± 1.5 mm) compared to Group A (0.8 ± 0.4 mm) (p = 0.027), and also at the articular portion in Group B (1.5 ± 0.8 mm) compared to Group A (0.8 ± 0.8 mm) (p = 0.027).\ud \ud Conclusion: Tibial tunnel widening after ACLR using hamstring tendon autograft is significantly greater with suspensory femoral fixation and a bioabsorbable tibial interference screw when compared to an all-inside technique at a median follow-up of 2 years. The clinical relevance of this work lies in the rebuttal of concerns arising from biomechanical studies regarding the possibility of increased tunnel widening with an all-inside technique.\ud \ud Level of evidence: III.

A cute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines, we used a biotin affinity probe-labeling approach to identify potential molecular targets for the effects of SK053. Mass spectrometry of proteins precipitated from acute myeloid leukemia cells incubated with biotinylated SK053 used as a bait revealed protein disulfide isomerase as a potential binding partner for the compound. Biochemical, enzymatic and functional assays using fluorescence lifetime imaging confirmed that SK053 binds to and inhibits the activity of protein disulfide isomerase. Protein disulfide isomerase knockdown with short hairpin RNA was associated with inhibition of cell growth, increased CCAAT enhancer-binding protein α levels, and induction of differentiation of HL-60 cells. Molecular dynamics simulation followed by the covalent docking indicated that SK053 binds to the fourth thioredoxin-like domain of protein disulfide isomerase. Differentiation of myeloid precursor cells requires the activity of CCAAT enhancer-binding protein α, the function of which is impaired in acute myeloid leukemia cells through various mechanisms, including translational block by protein disulfide isomerase. SK053 increased the levels of CCAAT enhancer-binding protein α and upregulated mRNA levels for differentiation-associated genes. Finally, SK053 decreased the survival of blasts and increased the percentage of cells expressing the maturation-associated CD11b marker in primary cells isolated from bone marrow or peripheral blood of patients with acute myeloid leukemia. Collectively, these results provide a proof-of-concept that protein disulfide isomerase inhibition has potential as a therapeutic strategy for the treatment of acute myeloid leukemia and for the development of small-molecule inhibitors of protein disulfide isomerase.

Finger amputations are the most common amputations of upper limbs. They influence hand function, general functioning and quality of life. One of the possibilities for rehabilitation after finger amputation is fitting a silicone finger prosthesis. We wanted to evaluate the adjustment to amputation and prosthesis use in patients after finger amputation.We included 42 patients with partial or complete single or multiple finger amputation of one hand who visited the outpatient clinic for prosthetics and orthotics at our institute and received a silicone prosthesis. We assessed their adjustment to amputation and prosthesis with the Trinity Amputation and Prosthesis Experience Scales (TAPES).Most of the patients (28, 67%) had a single finger amputated. The average scores on all TAPES subscales (except adjustment to limitation) were above 50% of the maximum possible score. On average, the scores were the highest on the general adjustment and satisfaction with the prosthesis subscales.Silicone prostheses for finger amputation of upper limb play an important role in the process of adaptation to amputation. They offer aesthetically satisfying results and alleviate social interactions, which influences overall quality of life. Implications for Rehabilitation Silicone prostheses for finger amputation of upper limb offer an aesthetically satisfying result and alleviate problems with social interactions. Their influence on hand function is not optimal, but the prosthesis improves the amputee's quality of life.

Recently, a new minimally invasive single bundle technique for anatomic ACL reconstruction has been described, called the 'All-Inside graft-link technique'. One of the advantages of this procedure is the reduced morbidity at the donor site as the graft choice is the quadrupled semitendinosus, thus sparing the gracilis tendon. The aim of this study was to evaluate isokinetic flexion strength recovery in patients who underwent a gracilis sparing technique compared to those with a full-tibial tunnel technique using a doubled gracilis and semitendinosus tendons (DGST) graft.Patients were divided into two groups: Group A (22 patients) who underwent ACL reconstruction performed with an All-Inside graft-link technique; Group B (22 patients) who underwent ACL reconstruction with an Out-In technique and DGST graft. At a mean follow-up of 13 months, quadriceps and hamstring isokinetic peak torque deficits were recorded.In group A, the mean side to side peak torque flexion difference between the operated and non-operated limbs was -3% and the mean torque at 30° was -7.5% at high angular velocity (180°/sec); the mean peak flexion torque was 7.2% and the mean torque at 30° was 3.1% at low angular velocity (60°/sec). In group B, the mean side to side peak flexion torque was -3.5% and the mean torque at 30° was -7.6% at high angular velocity (180°/sec); the mean peak flexion torque was -7.2% and the mean torque at 30° was -11% at low angular velocity (60°/sec). A statistically significant difference was found between the two groups at lower angular velocity both for the mean peak flexion torque and the mean torque at 30° (p = 0.009), with better results in the study group.Gracilis sparing technique is a minimally invasive technique for ACL reconstruction and yielded a significantly better flexion strength recovery at lower angular velocity compared to a full tibial tunnel technique with DGST for ACL reconstruction.

The Human Body Posturizer (HBP) is an exoskeleton used in the neurorehabilitation. The HBP may improve motor control by stimulating the pre-frontal cortex, a brain region involved also in the inhibitory modulation of the amygdala whose hyperactivity is involved in the mechanisms of depression. The aim of the study was to investigate in institutionalized elderly patients the effects on depression of a physical training with the use of the HBP compared to a traditional training. Randomized controlled trial. 20 institutionalized patients (mean age = 88, ds = ± 5, 3 males) with moderate depression levels. The participants were randomly assigned to: a) HBP Group, which carried out physical training using the HBP; b) Excercise Group, which carried out a training without the use of the orthosis. The training was conducted for 6 months (3 sessions each week), with the same kind of exercises with or without the HBP according to the assignment group. Participants were evaluated at baseline using the Tinetti balance and Gait scale, the Mini Mental State Examination and the Geriatric Handicap Scale. The Geriatric Depression Scale was administered to the participants before and after the period of training. RESULTS: The two groups were homogeneous for age, baseline motor ability (risk falls), handicap score, cognitive functioning and depression levels. After 6 months of exercise training a significant reduction in depression levels was reported only in the HBP Group (p

CRISPR-Cas9–mediated genome editing can be used to treat ALS in an animal model of the disease., Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord and brain. In particular, autosomal dominant mutations in the superoxide dismutase 1 (SOD1) gene are responsible for ~20% of all familial ALS cases. The clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas9) genome editing system holds the potential to treat autosomal dominant disorders by facilitating the introduction of frameshift-induced mutations that can disable mutant gene function. We demonstrate that CRISPR-Cas9 can be harnessed to disrupt mutant SOD1 expression in the G93A-SOD1 mouse model of ALS following in vivo delivery using an adeno-associated virus vector. Genome editing reduced mutant SOD1 protein by >2.5-fold in the lumbar and thoracic spinal cord, resulting in improved motor function and reduced muscle atrophy. Crucially, ALS mice treated by CRISPR-mediated genome editing had ~50% more motor neurons at end stage and displayed a ~37% delay in disease onset and a ~25% increase in survival compared to control animals. Thus, this study illustrates the potential for CRISPR-Cas9 to treat SOD1-linked forms of ALS and other central nervous system disorders caused by autosomal dominant mutations.

The purpose of this investigation was the determination of the distribution of genotypes and alleles, residing within interleukin 6 (IL6) and interleukin 1 (IL1) polymorphisms, among fetuses and neonates, congenitally infected with Toxoplasma gondii, and among uninfected control cases. The study included 22 fetuses and newborns infected with T. gondii and 49 control cases. Screening for IgG and IgM antibodies against the parasite and IgG avidity was performed by enzyme-linked fluorescent assay (ELFA) tests. Quantitation of T. gondii DNA in amniotic fluids was assayed by the real-time Q PCR technique for the parasitic B1 gene. Genotypes at IL6 and IL1 single nucleotide polymorphisms (SNPs) were determined by a self-designed, nested polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. Representative genotypes at the studied loci were confirmed by sequencing. All the genotypes were estimated for Hardy–Weinberg equilibrium and IL1 genotypes were tested for linkage disequilibrium. Genotypes and haplotypes at the studied SNPs were investigated for their possible association with the occurrence of congenital T. gondii infection, using a logistic regression model. GC heterozygotes at the IL6 −174 G>C SNP were significantly associated with toxoplasmosis and increased the risk of T. gondii infection [odds ratio (OR) 4.24, 95 % confidence interval (CI) 1.24–14.50 in the codominant model, p ≤ 0.050]. In case of IL1 SNPs, similar prevalence rates were observed between T. gondii-infected and -uninfected offspring. Regarding allelic variability, the C alleles at both IL6 and IL1B SNPs were significantly more frequent in the infected than in the uninfected cases (p ≤ 0.050). It is concluded that IL6 −174 G>C and IL1B +3954 C>T SNPs might be involved in the development of congenital T. gondii infection.

The purpose of this investigation was the determination of the distribution of genotypes at single nucleotide polymorphisms (SNPs) of the toll-like receptor 4 (TLR4) and the toll-like receptor 9 (TLR9) in fetuses and newborns congenitally infected with Toxoplasma gondii and the identification of genetic changes predisposing to infection development. The study involved 20 fetuses and newborns with congenital toxoplasmosis and 50 uninfected controls. The levels of IgG and IgM antibodies against T. gondii, as well as IgG avidity, were estimated by enzyme-linked fluorescent assay (ELFA) tests. T. gondii DNA loads in amniotic fluids were assayed by the real-time (RT) quantitative polymerase chain reaction (Q PCR) technique for parasitic B1 gene. TLR4 and TLR9 SNPs were identified using a self-designed multiplex nested PCR-restriction fragment length polymorphism (RFLP) assay. Randomly selected genotypes at SNPs were confirmed by sequencing. All the genotypes were tested for Hardy-Weinberg equilibrium and TLR4 genotypes were analyzed for linkage disequilibrium. A correlation was studied between the genotypes or haplotypes and the development of congenital toxoplasmosis using a logistic regression model. Single SNP analysis showed no statistically significant differences in the distribution of distinct genotypes at the analyzed TLR4 and TLR9 SNPs between T. gondii-infected fetuses and newborns and the controls. Taking into account the prevalence of alleles residing within polymorphic sites, similar prevalence rates were observed in both of the studied groups. The multiple SNP analysis indicated GTG variants at the TLR4 and TLR9 SNPs to be significantly less frequent in offspring with congenital toxoplasmosis than in uninfected offspring (p ≤ 0.0001). TLR4 and TLR9 SNPs seem to be involved in protection against congenital toxoplasmosis.

Rapid eye movement (REM) and non-REM (NREM) sleep are controlled by specific neuronal circuits. Here we show that galanin-expressing GABAergic neurons in the dorsomedial hypothalamus (DMH) comprise separate subpopulations with opposing effects on REM versus NREM sleep. Microendoscopic calcium imaging revealed diverse sleep-wake activity of DMH GABAergic neurons, but the galanin-expressing subset falls into two distinct groups, either selectively activated (REM-on) or suppressed (REM-off) during REM sleep. Retrogradely labeled, preoptic area (POA)-projecting galaninergic neurons are REM-off, whereas the raphe pallidus (RPA)-projecting neurons are primarily REM-on. Bidirectional optogenetic manipulations showed that the POA-projecting neurons promote NREM sleep and suppress REM sleep, while the RPA-projecting neurons have the opposite effects. Thus, REM/NREM switch is regulated antagonistically by DMH galaninergic neurons with intermingled cell bodies but distinct axon projections.

Background The aim of this study was to determine how end-of-life decisions (EOLD) on limitations of life-sustaining treatment (LST) are made in three different types of intensive care units (ICUs) in Slovenia. Methods A national multicenter prospective study among 31 adult and three pediatric/neonatal ICUs (PICUs). The questionnaire form on EOLD was designed to assess the clinical practice. Data were collected between January 1, 2013, and March 31, 2013. For statistical analysis we used IBM® SPSS® Statistics 20 software package. Results Overall, of 4226 patients were admitted to ICUs, the EOLD on limitation of LST were performed in 112 patients (23.9%) out of 468 patients, which had died and/or had been subject to EOLD on limitation of LST. In 86.2% of the cases, patients had impaired competence. Advance directives were available only in 1.9% (2 out of 106 patients) of the cases. In the majority of cases, the EOLD was taken by the physicians (96.2%). In 61.8% of the cases, patient representatives were involved in the discussion about limitation of LST. The do-not-resuscitate order and withholding of inotropes/vasopressors were the most common measures to limit LST. Most commonly withdrawn were inotropes/vasopressors and antibiotics. Palliative care was included in 72.3% of the cases (80 out of 112 patients), however, palliative care team was only included in 4% of the cases. Conclusions No differences were found between the three different types of ICUs in EOLD on limitation of LST even though limitation of LST was provided regularly. The most commonly limited LST measures include mechanical ventilation, inotropes/vasopressors, hemodialysis, and antibiotics. Almost none of the patients had advance directives in place. Palliative care team was available in only few cases.