Associated anomalies in cases with anorectal anomalies

Anorectal anomalies (ARA) are common congenital anomalies. The etiology of ARA is unclear and its pathogenesis is controversial. Cases with ARA often have other non‐ARA‐associated congenital anomalies. The purpose of this study was to assess the prevalence and the types of these associated anomalies in a defined population. The associated anomalies in cases with ARA were collected in all live births, stillbirths, and terminations of pregnancy during 29 years in 387,067 consecutive births in the area covered by our population‐based registry of congenital malformations. Of the 202 cases with ARA, representing a prevalence of 5.21 per 10,000, 100 (49.5%) had associated anomalies. There were 7 (3.3%) cases with chromosomal abnormalities, and 31 (15.3%) nonchromosomal recognized dysmorphic conditions, including 17 cases with Vertebral defects, Anal atresia, Cardiac septal defects, esophageal atresia or TracheoEsophageal fistula, Renal anomalies and radial Limb defects association. Sixty two (30.7%) of the cases had nonsyndromic multiple congenital anomalies (MCA). Anomalies in the urogenital, the musculoskeletal, the cardiovascular, the digestive, and the central nervous systems were the most common other anomalies in the cases with MCA. The anomalies associated with ARA could be classified into a recognizable malformation syndrome or pattern in 38 out of the 100 cases (38%) with associated anomalies. This study included special strengths: each affected child was examined by a geneticist, all elective terminations were ascertained, and the surveillance for anomalies was continued until 2 years of age. In conclusion, the overall prevalence of associated anomalies, which was close to one in two cases, emphasizes the need for a routine screening for other anomalies in cases with ARA.

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Developmental Changes in NO-Containing Sympathetic Neurons in the Spinal Cord in Rats

Objectives. To determine the locations, percentage composition, and morphometric characteristics of sympathetic preganglionic neurons containing NO synthase (NOS) in the spinal cord of rats. Materials and methods. Experiments were performed on 35 white female Wistar rats aged 3, 10, 20, 30, and 60 days, 6 months, and 3 years. Immunohistochemical detection of NOS and the acetylcholine synthesis enzyme choline acetyltransferase (CAT) was performed on sections of spinal cord made at the level of segment T2. The areas of nerve cells and the proportions of immunoreactive neurons were determined. Results. Most sympathetic preganglionic neurons in the spinal cord of neonates and 10-day-old rats contained both NOS and CAT. At these age groups, rats also had a population of NOS-positive/CAT-negative neurons (26% in neonates and 8% in 10-day-old animals), this population was not seen in older animals. During the first 20 days, the proportion of NOS-immunopositive neurons decreased significantly, while the population of CAT-positive neurons increased. Conclusions. There was a reduction in the number of sympathetic preganglionic neurons expressing NOS during early postnatal ontogeny, which may influence the mechanisms of NO-ergic sympathetic transmission.

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Efficacy of Reslip (doxylamine) in Acute Insomnia: A Multicenter, Open, Comparative, Randomized Trial

Objectives. To assess the efficacy of Reslip (doxylamine) in acute insomnia in comparison with Donormyl. Materials and methods. A multicenter, open, randomized trial was conducted at six medical centers in the Russian Federation. The trial included 60 patients with acute insomnia aged 30–59 years, who were randomized into two groups. Patients of one group received Reslip and those of the other received Donormyl at the same dose and regime. Results. Most patients in both groups experienced improvements in the clinical signs of acute insomnia. The severity of insomnia, daytime drowsiness, and reductions in quality of sleep in both groups showed highly significant decreases. Side effects from the drugs were rare and in most cases did not require treatment termination. There were no significant differences in treatment results with Reslip and Donormyl. Conclusions. Short-term treatment with doxylamine formulations had marked positive clinical effects in acute insomnia, combined with satisfactory tolerance by the patients. The Russian doxylamine formulation Reslip had clinical efficacy and tolerance which were no different from those of Donormyl and can be used in clinical practice for the treatment of acute insomnia.

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Studies of the Efficacy of Cereton in Mild Cognitive Impairment of the Amnestic Type Based on Testing Lipid Markers

Objectives. To determine the efficacy and safety of treatment with Cereton (alfoscerate) in patients with mild cognitive impairment syndrome (MCI) and its effects during and after treatment on phosphatidyl-choline, sphingomyelin, and ceramide (a sphingolipids metabolite) contents and the activity of genes controlling the synthesis of enzymes (sphingomyelinase and ceramidase) involved in the sphingomyelin and ceramide metabolism. Materials and methods. A total of 20 patients (14 women, six men) aged 51–82 (mean 70.3 ± 9.1) years were studied. Patients' status corresponded to the criteria for diagnosis of MCI syndrome of the anamnestic type. Plasma phosphatidylcholine, sphingomyelin, and ceramide were estimated by thin layer chromatography, while expression of the sphingomyelinase and ceramidase genes was determined using the reverse transcriptase polymerase chain reaction. Results and conclusions. Sharp increases in the contents of phosphatidylcholine and ceramide – hydrolysis products of sphingomyelin – were seen. Expression of the genes (acid sphingomyelinase and ceramidase) controlling ceramide metabolism decreased in most patients during Cereton treatment. Increases in the levels of phosphatidylcholine and decreases in the expression of ceramide metabolism genes during treatment with Cereton and other agents affecting phosphatidylcholine and sphingomyelin metabolism can be used as markers for treatment efficacy.

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Characteristics of CART Peptide-Immunopositive Cells in the Subventricular Zone of the Brain

Objectives. To study the cytoarchitectonics of the neuronal organization and distribution of CART peptide-immunopositive cells in the subventricular zone of the brain. Materials and methods. Frontal sections of the rat brain (n = 18) were studied using the Nissl, Golgi, and immunohistochemical methods with antibodies to CART (55–102). Specimens were analyzed by light microscopy. Results. CART peptide-immunopositive cells were detected in the subventricular zone of the inferior horn of the lateral ventricle in the paleoamygdala. These had round-oval bodies, one or two short processes and, in terms of their neuronal organization, were neuroblastomorphic neurons. Conclusions. The data obtained here provide evidence that cells in the subventricular zone of the paleoamygdala express CART peptide in health. This determines the high efficacy of neuroregenerative treatment using this substance.

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Biomarkers for Cerebral Ischemia as a Novel Method for Validating the Efficacy of Neurocytoprotectors

Objectives. To assess the diagnostic value of NR2 peptide as a biomarker for cerebral ischemia by studying its plasma concentration in patients with ischemic stroke (IS) and to determine changes in levels due to treatment with the low molecular weight neuroprotector Cortexin. Materials and Methods. A total of 120 patients aged 18–70 years were studied, of which 36 were diagnosed with transient ischemic attacks (TIA) and 84 with IS – 70 in the carotid basin and 14 in the vertebrobasilar basin with Wallenberg–Zakharchenko syndrome. Determination of neurological status included assessment on the NIHSS stroke scale. Plasma NR2 concentrations were estimated in all patients on admission and after courses of treatment and results were compared with CT and MRI neuroimaging studies. Results and Conclusions. NR2 peptide fragment concentrations in all patients were above the normal value (>1.5 ng/ml, p < 0.0001). A direct correlation was found between the concentration of NR2 peptide (from 3.38 ng/ml to 15.6 ng/ml) and the size of the ischemia zone from a few mm to 80 mm (rs = 0.73). After 10-day courses of treatment with Cortexin, NR2 peptide fragment concentrations decreased (from 8.5 to 5.9 ng/ml, p < 0.0001). These data lead to the conclusion that this blood test for cerebral ischemia is valid and that Cortexin has significant therapeutic efficacy.

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Anxiolytic and Antidepressant Actions of Emoxypine, Reamberin, and Mexidol in Experimental Diabetes Mellitus

Objectives. To conduct a comparative study of the anxiolytic and antidepressant activities of derivatives of 3-hydroxypyridine and succinic acid (emoxypine, Reamberin, and Mexidol) in experimental diabetes mellitus (DM). Materials and methods. The effects of emoxypine, Reamberin, and Mexidol on the signs of anxiety in an elevated plus maze and the duration of "despair" behavior in the Porsolt test were assessed in rats with alloxan diabetes during courses of drug treatment. The reference agent was α-lipoic acid. An additional series of experiments was run to study the effects of emoxypine, Reamberin, Mexidol and α-lipoic acid on the severity of hyperglycemia in experimental DM. Results and conclusions. All study drugs were used at doses equivalent to the human therapeutic range for 14 days and significantly decreased the signs of anxiety and depression in rats with alloxan diabetes. The most marked anxiolytic potential was demonstrated for emoxypine, which was the only one of the study drugs decreasing the signs of anxiety not only in comparison with the alloxan diabetes control group, but also relative to the intact control group. Derivatives of 3-hydroxypyridine and succinic acid were no less effective than α-lipoic acid in terms of the level of tranquilizing activity and were more effective than α-lipoic acid in terms of thymoanaleptic activity when given at the maximal dose to rats with experimental DM. Emoxypine and Mexidol, and also α-lipoic acid, significantly decreased hyperglycemia in alloxan diabetes at all the doses tested. Reamberin displayed only minor trends in this direction.

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Diagnosis and Treatment of Cognitive Impairments in Attention Deficit Syndrome in Adults

Objectives. To clarify cognitive impairments in adults with attention deficit hyperactivity syndrome (ADHD) and to assess the efficacy of the formulation Memoplant in the treatment of this pathology. Materials and Methods. The results of clinical, psychological, and electroencephalographic studies of 40 patients aged 18–45 years with ADHD are presented. From recruitment into the study, all patients received Memoplant at a daily dose of 240 mg for eight weeks. Results and conclusions. Adult patients with ADHD had both subjective and objective impairments to memory and attention. EEG results suggested that patients showed dysfunction of the frontothalamic regulatory system and deficit of nonspecific activation by the reticular formation. Courses of Memoplant were followed by clinical improvements in 24 patients (60.0%). Repeat psychological and neurophysiological studies demonstrated decreases in attention deficit and improvements in memory measures.

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Immunohistochemical Characteristics of Neurons in the Substantia Nigra of the Human Brain

Objectives. To identify the cytochemical chromosomes of structurally unaltered neurons in the substantia nigra of the human brain using a wide spectrum of immunocytochemical markers, some of which (glutamate decarboxylase 65, PGP 9.5, unphosphorylated neurofilament proteins, α-tubulin) have not previously been used in studies of dopaminergic neurons in humans. Materials and methods. The study used fragments of human midbrain (17 men and women aged 28–78 years) obtained from the archive of the Department of General and Special Morphology, Institute of Experimental Medicine. Studies were performed using classical neurohistology and immunocytochemistry methods using antibodies to 15 different proteins. Results. Most neurons in the substantia nigra were characterized by decreased expression of general neuronal markers – nuclear protein NeuN, protein PGP 9.5, and neuron-specific enolase. The substantia nigra was not found to contain GABAergic (GAD65-immunopositive) neurons. The dorsal part of this area contained occasional cholinergic neurons not containing neuromelanin. Calcium-binding proteins calbindin and calretinin were absent from most nigral cells, though the dorsal part of the substantia nigra contained occasional calbindin-containing neurons, while the ventral part contained occasional calretinin-containing neurons. Nitric oxide synthase was present in both the neuropil and neuron bodies in the substantia nigra. Conclusions. The data obtained here provide evidence of the unique cytochemical properties of nigral neurons, which may be associated with their increased predisposition to degeneration.

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Morphological Changes and Characteristics of the Expression of Serine Racemase in the Hippocampus of Rats Exposed to Multiple Negative Gravitational Overloads

Objectives. To study the morphometric parameters and levels of expression of serine racemase in the hippocampus of rats repeatedly exposed to gravitational overloads in the caudocranial direction (–9 Gz). Materials and methods. Rat aged 12 months were subjected to 9-g forces for 5 min twice a day with 12-h intervals for 28 days (group 2, gravity group, n = 10); controls were not exposed to hypergravitation (group 1, controls, n = 10). Morphometric mean areas of the nuclei and perikarya of pyramidal cells were determined, along with the specific number of neurons with signs of damage, the relative areas of pyramidal neuron and neuroglial cell perikarya. Immunohistochemical studies addressed the level of expression of serine racemase in all zones of the hippocampus. Results. Signs of impaired blood supply in the microcirculatory component were seen in the form of spongiosis, thickening of capillary walls, and diapedesis of erythrocytes. All hippocampal zones in experimental rats showed sharp increases in the numbers of pyramidal neurons with signs of damage. Atrophic changes consisting of decreases in the mean and relative areas of neuron perikarya were identified. Immunohistochemical studies showed increased expression of serine racemase in field CA1, along with translocation of immunoreactive material into the processes of pyramidal neurons. Fields CA3 and CA4 showed a tendency to decreases in serine racemase content. Conclusions. Prolonged gravitational exposure in the caudocranial direction led to the appearance of signs of severe damage in all fields of the rat hippocampus, combined with increased expression and accumulation of serine racemase in the dendrites of pyramidal neurons in field CA1, which may be evidence that excitotoxicity is involved in the mechanisms of secondary damage in this zone.

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Structural and Histochemical Changes in Neurons in the Frontal Cortex of the Brain in Rats with Cholestasis

Objectives. To study structural and histochemical changes in neurons in the frontal cortex of the brain in rats after ligation of the common bile duct. Materials and methods. The cortex of the frontal lobe was studied in 72 mongrel adult white male rats weighing 200 ± 25 g. Ligation of the common bile duct and development of cholestasis (experimental group) and sham surgery (control group) was followed by histological and histochemical studies of microstructural changes in pyramidal neurons in all layers of the frontal cortex on days 2, 5, 10, 20, 45, and 90. Results. Ligation of the common bile duct in rats producing cholestasis led to profound histological and histochemical changes in neurons in the frontal cortex of the brain: changes in size and shape, and appearance of hyperchromic shrunken neurons and ghost cells. Impairments to energy and plastic metabolism in neurons led to the death of the experimental animals. The consequences of cholestasis in the brains of rats were apparent on days 2–5 and reached a maximum on days 10–20. In the later post-operative period (45–90 days), groups of survivors showed gradual reductions in these changes, though the consequences of cholestasis consisted of foci of neuron loss in all layers of the frontal cortex. Conclusions. It is suggested that survival of rats after ligation of the common bile duct is due to formation of bypass bile ducts, with elimination of cholestasis and the high adaptive potential of neurons.

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Complex Sleep Apnea

The term complex sleep apnea syndrome (Comp-SAS) refers to a specific variant of respiratory impairment during sleep characterized by the appearance or significant increases in the number of episodes of central apnea and hypopnea after starting CPAP therapy for obstructive sleep apnea syndrome (OSAS). The mechanisms producing Comp-SAS are not fully understood. It is possible that respiration with positive pressure and elimination of pharyngeal obstruction in some patients lead to increases in pulmonary ventilation and decreases in P_aCO₂ to below the individual threshold required for stimulating respiration. The prevalence of Comp-SAS is 5–20% of patients with OSAS receiving CPAP therapy. Significant clinical predictors for Comp-SAS have not been established, though this respiratory disorder is known to occur more frequently in male patients, older patients, those with severe OSAS, and those with cardiovascular diseases such as ischemic heart diseases, atrial fibrillation, or chronic heart failure (CHF). In most cases, Comp-SAS settles spontaneously after 1–2 months of regular CPAP therapy. If positive pressure treatment has no effect, other contemporary treatment methods can be used, such as adaptive servo ventilation or BPAP treatment with controlled respiratory frequency, though these are contraindicated in systolic heart failure. The question of whether treatment of patients with Comp-SAS is obligatory when the course of illness is straightforward and symptom-free remains open.

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Pharmacotherapy of Attention Deficit Hyperactivity Disorder in Children: Results of a Multicenter, Double-Blind, Placebo-Controlled Trial of Hopantenic Acid

Objectives. To assess the efficacy and safety of hopantenic acid (Pantogam) compared with placebo in the treatment of ADHD for four months in children aged 6–12 years during a prospective, multicenter, comparative, double-blind, placebo-controlled, parallel-group trial. Materials and methods. The study included 100 patients constituting the safety population (50 in the Pantogam group and 50 in the placebo group). A total of 89 patients completing the study in compliance with the protocol entered the efficacy evaluation population: 45 in the Pantogam group (group 1) and 44 in the placebo group (group 2). Pantogam was given as tablets containing 250 mg at the pediatric therapeutic dose of 30 mg/kg, divided into two split doses, for four months. Assessment of patients' statements at follow-up addressed the total points scores on the DSM-IV ADHD, the CGI-S Clinical Global Impression scale, the WFIRS-P functional impairments scale, and the results of a correction test (the Toulouse–Pieron test). Results and conclusions. The efficacy of Pantogam in ADHD in children aged 6–12 years as compared with placebo showed a marked tendency to an increase in the proportion of patients with improvements (decreases in total points scores on the DSM-IV ADHD scale by more than 25%) by the ends of the third and fourth months of treatment: treatment responses were achieved in 66.7% and 68.9%, respectively, compared with 52.3% and 61.4% in the placebo group. Pantogam therapy also produced a decrease in disease severity from the placebo level on the CGI-S scale. At four months of Pantogam treatment, there were decreases in the severity of functional impairments on sections 4 and 6 of the WFIRES-P "Family," "School and learning," "Child's self-concept," and "Risky activities" scales. Pantogam also improved the maintenance of attention in children with ADHD, as measured using the Toulouse–Pieron test (quality and rate of performance) as compared with placebo. Treatment with Pantogam at a mean daily dose of 30 mg/kg for four months demonstrated a favorable safety profile, no different from that of placebo.

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Methodological Features of the Morphometric Characterization of the Synaptoarchitectonics of the Human Neocortex by Immunofluorescent Detection of Neuromodulin

Objective. To study the possibility of using GAP-43 for morphometric characterization of synaptoarchitectonics. Materials and methods. Studies used immunofluorescent detection of neuromodulin (GAP-43) by confocal microscopy and automated computer image analysis of layer V (field 4) of the human brain (n = 4) using ImageJ 1.46. Results. Immunofluorescent detection of GAP-43 identified the distribution of axodendritic and axosomatic synapses, the total area of axon terminals, and the number densities of intermediate and large terminals. Conclusions. A necessary condition for obtaining accurate data is having digital images with sufficient resolution (600–900 pixels per inch). These results need to be considered in studies of the synaptoarchitectonics of the neocortex using immunohistochemical methods for investigating synapse structure.

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A Long and Difficult Path towards Understanding the Purpose of Sleep. The Period before Electrophysiology

We present a historical review of the concepts of Russian researchers regarding the mechanisms and functional roles of sleep – I. P. Pavlov and his predecessors (I. R. Tarkhanov and M. M. Manaseina) and students (N. A. Rozhanskii and K. M. Bykov). This analysis leads to the conclusion that sleep is linked with the realization of functional operations not previously associated with sleep and not addressed by current neuroscience. Thus, a real understanding of sleep functions can be expected to come only with a new neurophysiological paradigm.

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Standardized Cost Estimates for Home Visiting: Pilot Study of the Home Visiting Budget Assistance Tool (HV-BAT)

Abstract

Purpose Using a standardized approach and metrics to estimate home visiting costs across multiple evidence-based models and regions could improve the consistency and accuracy of cost estimates, allow stakeholders to observe trends in cost allocation, analyze how home visiting costs vary, and develop future program budgets. Between October 2015 and December 2018, we developed and pilot-tested the Home Visiting Budget Assistance Tool (HV-BAT) to standardize the collection of home visiting program costs and analyze costs for local implementing agencies (LIAs). Methods We recruited LIAs that implemented at least one of nine evidence-based home visiting models in 15 states implementing the Maternal, Infant, and Early Childhood Home Visiting (MIECHV) Program. LIAs reported their costs to implement a home visiting model using the HV-BAT and provided feedback on the tool. We estimated annual total cost and cost per family served for each LIA, examined cost summary statistics for the sample, and analyzed whether and how LIA characteristics affected home visiting costs using regression analyses. Results Of the 168 LIAs invited to participate in the HV-BAT pilot study, 75 agreed to participate, and 45 across 14 states completed the HV-BAT. We estimated home visiting costs of approximately $8500 per family per year, but costs varied across LIAs (range $1970–$39,770; standard deviation = $5794). The marginal cost of adding a family declined as the number of families served by an LIA increased. Feedback from LIAs indicated that users had difficulty providing some details on costs (e.g., mileage for specific services), needed more detailed instructions, and desired a summary of subtotals and total costs reported in the HV-BAT. Conclusions The HV-BAT provides an approach to standardize cost data collection for home visiting programs. Pilot study results indicate that there may be significant economies of scale for home visiting services. This study provides preliminary estimates of costs that can help in program planning and budgeting.

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Sleep Disturbances – an Important Factor in Combination with “Minor” Symptoms of Multiple Sclerosis

Objectives. To study the clinical and neurophysiological features of sleep disturbances in patients with different forms of multiple sclerosis (MS) and their effects on quality of life and the course and prognosis of illness; to identify the influences of sleep disturbances on the formation and maintenance of chronic fatigue syndrome in MS patients. Materials and methods. A total of 54 patients with different forms of MS and 54 healthy volunteers were studied. General clinical investigation methods were used, along with neuropsychological testing (detection of anxious-depressive states), subjective sleep quality assessment scales (assessment of the severity of daytime drowsiness, chronic fatigue syndrome, quality of life measures), and their subsequent relationship with neuroimaging and neurophysiological data. Results and discussion. Analysis of the data revealed a high frequency of sleep disturbances associated with anxiety disorders and other comorbid pathologies which occur significantly more frequently among MS patients.

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Determination of the Role of Subjective Investigation Methods in Assessment of Measures of Sleep Quality

Objectives. To assess the accuracy of questions for determining the quality and duration of sleep. Materials and methods. An in-depth study was performed with assessment of sleep parameters in 136 patients, 49 of these undergoing polysomnographic (PSG) investigations. Subjectively, sleep was assessed using the Sleep Quality Questionnaire and the Pittsburgh Sleep Quality Index; objective assessments were obtained from PSG recordings. Results. Sleep quality in the laboratory was assessed as "Worse than at home" by one third of respondents. Sleep duration in this group was 1.5 h shorter than in the group assessing sleep in the laboratory as "Just as good at home." Despite this, most respondents slept longer in the laboratory than they had averaged over the preceding month. Overall sleep evaluation showed that 59% of respondents noted sleep disturbance. Nocturnal sleep duration by PSG data was 6.6 [3; 9] h, compared with self-assessments of 7 [3; 10] h (p = 0.06); average sleep duration was 8 [5; 10] h (p = 0.005); assessments over the last month gave 7 [5; 9] h. Conclusions. Assessment of sleep quality in the laboratory as "worse than at home" was linked with subjectively shorter sleep durations. Subjective assessment of sleep duration and the time of falling asleep the evening before were quite accurate, in contrast to subjective assessments of the number of nocturnal wakings. Assessment of mean sleep duration depended on how the question was formulated.

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Interaction between Anxiety and Sleep in Experimental Studies and Clinical Practice

High anxiety is a personality features which is largely genetically determined and is due to the functioning of the limbic system and the activity of cerebral formations involved in maintaining waking and the development of sleep. Analysis of experiments on animals and clinical observations indicates that this feature, determining an individual's own responses, promotes the development of anxiety and anxiety disorders which, due to suppression of GABA-benzodiazepine inhibitory influences, has adverse effects on the duration and quality of nocturnal sleep. Phenazepam, acting via its anxiolytic properties, inactivates foci of arousal in the nervous system, countering the negative manifestations of anxiety, resulting in a somnogenic action which normalizes sleep impairments.

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A Comparative Study of the Efficacy of Cognitive Behavioral Therapy and Zopiclone in Chronic Insomnia

Objectives. To assess the efficacy of the cognitive behavioral therapy of insomnia (CBT-I) compared with pharmacotherapy in chronic insomnia in the Russian population. Materials and methods. A crossover trial was performed in 42 patients with chronic insomnia (14 men and 28 women) aged 29–80 years old, who received two courses of treatment: using zopiclone and using an educational method with elements of CBT-I. All patients underwent nocturnal polysomnography studies. Treatment efficacy was evaluated using the Insomnia Severity Index, the Pittsburgh Sleep Quality Index questionnaire, the Dysfunctional Beliefs about Sleep Scale, the Sleep Hygiene Index, and the Beck Depression Scale. The efficacy of medication and nonmedication treatment methods in insomnia were found to be comparable. The insomnia severity index after CBT-I decreased by 3.6 (from 17.7 ± 5.3 to 12.8 ± 5.1) points, compared with a decrease by 4.9 (from 16.5 ± 5.8 to 12.9 ± 6.2) points after courses of zopiclone (p < 0.05). However, after two weeks, treatment results persisted only after use of CBT (12.9 ± 6.2 points); scores increased to 15.5 ± 4.6 points by the end of zopiclone administration. In addition, CBT-I was followed by significant decreases in values on the Beck Depression Scale (from 11.8 ± 6.9 to 8.5 ± 7.0 points), the Sleep Hygiene Index (from 26.9 ± 7.5 to 23.9 ± 5.7 points), the Dysfunctional Beliefs about Sleep Scale, (from 104.9 ± 29.7 to 84.4 ± 34.2 points) (p < 0.05). Patients responding to CBT-I were younger than nonresponders (40.5 ± 12.9 and 57.2 ± 11.7 years, respectively, p < 0.05), such that young age can be regarded as a predictor for CBT-I being effective. Conclusions. Treatment of chronic insomnia using CBT was as effective as pharmacotherapy, its use was accompanied by additional improvements in emotional status, and its effects lasted longer.

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Association of Chronotype, Road Traffic Accidents, and Polymorphisms in Genes Linked with the Biological Clock and the Dopaminergic System

Objective. To study the association between single-nucleotide polymorphisms (SNP) of the RORA (rs1159814), CLOCK (rs12649507), PER3 (rs2640909), NPSR1 (rs324981), NPAS2 (rs4851377), DRD3 (rs6280), SLC6A3 (rs6347), and DBH (rs1611125) genes, chronotype parameters, and road traffic accident (RTA) driver statistics. Materials and methods. The study included 303 drivers of Moscow inter-city buses working rolling shifts. The study addressed associations between genotyping results for SNP and the Munich Chronotype Questionnaire (MCTQ) and the Shortened Sleep-Wake Pattern Assessment Questionnaire (SWPAQ), and official RTA statistics. Results and conclusions. The cohort was dominated by the mixed chronotype, with a tendency to go to bed late and able to get up early; there was a marked shift between sleep patterns between working days and rest days. The SNP of the PER3 gene showed an association with parameters of morning activity. The SNP of the CLOCK gene was associated with a change in the pattern and the risk of causing RTA, while the minor alleles of the NPSR1 and SLC6A3 genes were associated with a later chronotype and an increase in RTA risk. It is suggested that these polymorphism may be among the genetic factors linking the chronotype to the ability to work.

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Current Views on Chronic Pain and Its Relationship to the State of Sleep

Chronic pain is a unique pathophysiological state characterized by the formation of stable neurotransmitter, morphological, and behavioral patterns. Sleep has a facilitating influence on many pain syndromes by blocking signal conduction via the nociceptive pathways, the release of specific neurotransmitters, and the lack of conscious perception during this period. Restriction to the duration of sleep and impairment to its structure are accompanied by increased pain, while improvements in sleep in some cases allow pain to be decreased.

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Comprehensive genotyping reveals novel CFTR variants in cystic fibrosis patients from the Russian Federation

Single nucleotide variants are represented as lines. The height of the line corresponds to the allele frequency. Gross chromosomal copy number variations are shown as arrows. Color corresponds to the mutation type. Complex alleles represented with a clip. Previously reported variants are located above the schematic gene representation. Their names are presented in Table 1 in main text. Novel variants are depicted beneath the schematic gene representation.

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Determining the Genetic Architecture of Reproductive Stage Drought Tolerance in Wheat Using a Correlated Trait and Correlated Marker Effect Model

Water stress during reproductive growth is a major yield constraint for wheat (Triticum aestivum L). We previously established a controlled environment drought tolerance phenotyping method targeting the young microspore stage of pollen development. This method eliminates stress avoidance based on flowering time. We substituted soil drought treatments by a reproducible osmotic stress treatment using hydroponics and NaCl as osmolyte. Salt exclusion in hexaploid wheat avoids salt toxicity, causing osmotic stress. A Cranbrook x Halberd doubled haploid (DH) population was phenotyped by scoring spike grain numbers of unstressed (SGNCon) and osmotically stressed (SGNTrt) plants. Grain number data were analysed using a linear mixed model (LMM) that included genetic correlations between the SGNCon and SGNTrt traits. Viewing this as a genetic regression of SGNTrt on SGNCon allowed derivation of a stress tolerance trait (SGNTol). Importantly, and by definition of the trait, the genetic effects for SGNTol are statistically independent of those for SGNCon. Thus they represent non-pleiotropic effects associated with the stress treatment that are independent of the control treatment. QTL mapping was conducted using a whole genome approach in which the LMM included all traits and all markers simultaneously. The marker effects within chromosomes were assumed to follow a spatial correlation model. This resulted in smooth marker profiles that could be used to identify positions of putative QTL. The most influential QTL were located on chromosome 5A for SGNTol (126cM; contributed by Halberd), 5A for SGNCon (141cM; Cranbrook) and 2A for SGNTrt (116cM; Cranbrook). Sensitive and tolerant population tail lines all showed matching soil drought tolerance phenotypes, confirming that osmotic stress is a valid surrogate screening method.

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Complex Structural PPT1 Variant Associated with Non-syndromic Canine Retinal Degeneration

Rod and cone photoreceptors are specialized retinal neurons that have a fundamental role in visual perception, capturing light and transducing it into a neuronal signal. Aberrant functioning of rod and/or cone photoreceptors can ultimately lead to progressive degeneration and eventually blindness. In man, many rod and rod-cone degenerative diseases are classified as forms of retinitis pigmentosa (RP). Dogs also have a comparable disease grouping termed progressive retinal atrophy (PRA). These diseases are generally due to single gene defects and follow Mendelian inheritance. We collected 51 DNA samples from Miniature Schnauzers affected by PRA (average age of diagnosis ~3.9 ±1 years), as well as from 56 clinically normal controls of the same breed (average age ~6.6 ±2.8 years). Pedigree analysis suggested monogenic autosomal recessive inheritance of PRA. GWAS and homozygosity mapping defined a critical interval in the first 4,796,806 bp of CFA15. Whole genome sequencing of two affected cases, a carrier and a control identified two candidate variants within the critical interval. One was an intronic SNV in HIVEP3, and the other was a complex structural variant consisting of the duplication of exon 5 of the PPT1 gene along with a conversion and insertion (named PPT1_dci). PPT1_dci was confirmed homozygous in a cohort of 22 cases, and 12 more cases were homozygous for the CFA15 haplotype. Additionally, the variant was found homozygous in 6 non-affected dogs of age higher than the average age of onset. The HIVEP3 variant was found heterozygous (n=4) and homozygous wild-type (n=1) in cases either homozygous for PPT1_dci or for the mapped CFA15 haplotype. We detected the wildtype and three aberrant PPT1 transcripts in isolated white blood cell mRNA extracted from a PRA case homozygous for PPT1_dci, and the aberrant transcripts involved inclusion of the duplicated exon 5 and novel exons following the activation of cryptic splice sites. No neurological signs were detected among the dogs homozygous for the PPT1_dci variant. Therefore, we propose PPT1_dci as causative for a non-syndromic form of PRA (PRA_PPT1) that shows incomplete penetrance in Miniature Schnauzers, potentially related to the presence of the wild-type transcript. To our knowledge, this is the first case of isolated retinal degeneration associated with a PPT1 variant.

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A Statistical Procedure for Genome-Wide Detection of QTL Hotspots Using Public Databases with Application to Rice

Genome-wide detection of quantitative trait loci (QTL) hotspots underlying variation in many molecular and phenotypic traits has been a key step in various biological studies since the QTL hotspots are highly informative and can be linked to the genes for the quantitative traits. Several statistical methods have been proposed to detect QTL hotspots. These hotspot detection methods rely heavily on permutation tests performed on summarized QTL data or individual-level data (with genotypes and phenotypes) from the genetical genomics experiments. In this article, we propose a statistical procedure for QTL hotspot detection by using the summarized QTL (interval) data collected in public web-accessible databases. First, a simple statistical method based on the uniform distribution is derived to convert the QTL interval data into the expected QTL frequency (EQF) matrix. And then, to account for the correlation structure among traits, the QTLs for correlated traits are grouped together into the same categories to form a reduced EQF matrix. Furthermore, a permutation algorithm on the EQF elements or on the QTL intervals is developed to compute a sliding scale of EQF thresholds, ranging from strict to liberal, for assessing the significance of QTL hotspots. With grouping, much stricter thresholds can be obtained to avoid the detection of spurious hotspots. Real example analysis and simulation study are carried out to illustrate our procedure, evaluate the performances and compare with other methods. It shows that our procedure can control the genome-wide error rates at the target levels, provide appropriate thresholds for correlated data and is comparable to the methods using individual-level data in hotspot detection. Depending on the thresholds used, more than 100 hotspots are detected in GRAMENE rice database. We also perform a genome-wide comparative analysis of the detected hotspots and the known genes collected in the Rice Q-TARO database. The comparative analysis reveals that the hotspots and genes are conformable in the sense that they co-localize closely and are functionally related to relevant traits. Our statistical procedure can provide a framework for exploring the networks among QTL hotspots, genes and quantitative traits in biological studies. The R codes that produce both numerical and graphical outputs of QTL hotspot detection in the genome are available on the worldwide web https://ift.tt/2TKaS6a.

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Increased circulating microparticles in streptozotocin‐induced diabetes propagate inflammation contributing to microvascular dysfunction

Abstract

In various cardiovascular diseases, microparticles (MPs), the membrane‐derived vesicles released during cell activation, are markedly increased in the circulation. These MPs have been recognized to play diverse roles in the regulation of cellular functions. However, current knowledge of MP function has been largely concluded from in vitro studies. The precise impact of disease‐induced MPs on vascular inflammation and disease progression remain obscure. In this study we investigated the biogenesis, profile, and functional roles of circulating MPs using a streptozotocin‐induced diabetic rat model with well‐characterized microvascular functions. Our study revealed an over 130‐fold MP increase in plasma of diabetic rats compared to normal rats. Majority of these MPs originate from platelets, leukocytes, and endothelial cells and circulate as aggregates. Diabetic MPs show greater externalized phosphatidylserine (PS) than normal MPs. When diabetic plasma or isolated diabetic MPs were perfused into normal microvessels or systemically transfused into normal rats, MPs immediately adhered to endothelium and subsequently mediated leukocyte adhesion. These microvessels then exhibited augmented permeability responses to inflammatory mediators, replicating the microvascular manifestations observed in diabetic rats. These effects were abrogated when MPs were removed from diabetic plasma or when diabetic MPs were pre‐coated with a lipid‐binding protein, Annexin‐V, suggesting externalized PS to be key in mediating MP interactions with endothelium and leukocytes. Our study demonstrated that the elevated MPs in diabetic plasma are actively involved in the propagation of vascular inflammation through their adhesive surfaces, providing mechanistic insight into the pathogenesis of multi‐organ‐involved vascular dysfunction that commonly occurred in diabetic patients.

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Oral health‐related quality of life in patients with disorders of nutrition

Abstract

Background

Researchers demonstrated a correlation between nutrition and health‐related quality‐of‐life (HRQoL). Little is known about the correlation between disorders of nutrition (DON) and Oral HRQoL (OHRQoL).

Objectives

1) to measure OHRQoL in DON patients compared to patients attending nutritional counseling for other reasons (e.g. systemic diseases or general dietary counseling) (NCOR) and to healthy controls attending routine dental screenings.(2) analyze associations between OHRQoL and demographics, health‐related behaviors and nutritional practices. We hypothesized that OHRQoL is impaired in DON patients and correlates with poor health‐related behaviors and nutritional practices

Methods

Demographic, smoking, alcohol and physical activity habits, Verbal Pain Scale, Oral Health Impact Profile‐14 (OHIP‐14) and nutritional practice data were collected from 63 DON, 35 NCOR and 100 controls.

Results

Compared to controls, DON patients exhibited poorer OHIP‐14 global scores and had more: functional limitation, physical disability, psychological disability, social disability and handicap. OHIP‐14 global score was positively associated with: maternal origin, oral symptoms, eggs and eggplant consumption, avoiding seasoning, hot drinks and fibrous food and negatively associated with physical activity and fresh vegetable consumption. In the conceptual hierarchical multiple regression model, verbal pain scale, eggplant consumption and physical activity were mediators in the relationship between DON and OHIP‐14. DON, physical activity and eggplant consumption also directly associated with OHRQoL.

Conclusions

OHRQoL was impaired in DON patients and correlated with poor health‐related behaviors and nutritional practices. Routine work‐up of DON patients should include OHRQoL assessment.

This article is protected by copyright. All rights reserved.

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Outcomes of maxillary sinus floor augmentation without grafts in atrophic maxilla: a systematic review and meta‐analysis based on randomized controlled trials

Abstract

Background

Maxillary sinus floor augmentation without grafts has been more widely used, but the efficacy is still controversial.

Purpose

The aim of this review was to systematically evaluate the effectiveness of sinus floor augmentation without grafts in atrophic maxilla.

Methods

The electronic databases included PubMed, EMBASE and the Cochrane Central Register of Controlled Trials. The meta‐analysis was conducted by Review Manager 5.1. The quality of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE).

Results

The electronic database and manual search yield 707 studies. After critical selection, only 6 studies were eligible. Five studies with 336 implants were included in the meta‐analysis compared sinus augmentation with grafts to without grafts. No significant differences were found between the two groups in implant survivals (P=0.94), marginal bone loss (P=0.73) and new bone density (P=0.54). There was significantly more endo‐sinus bone gain in the grafting group (P=0.02). According to the GRADE, the levels of evidence were moderate (implant survival and marginal bone loss), low (endo‐sinus bone gain), and very low (new bone density).

Conclusion

There were no significant differences between maxillary sinus augmentation with and without grafts in short‐term implant survivals.

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A study in a Polish ataxia cohort indicates genetic heterogeneity and points to MTCL1 as a novel candidate gene

Inherited ataxias are a group of highly heterogeneous, complex neurological disorders representing a significant diagnostic challenge in clinical practice. We performed next generation sequencing analysis in 10 index cases with unexplained progressive cerebellar ataxia of suspected autosomal recessive inheritance. A definite molecular diagnosis was obtained in 5/10 families and included the following diseases: autosomal recessive spastic ataxia of Charlevoix‐Saguenay (ARSACS), POLR3B‐related hypomyelinating leukodystrophy, primary coenzyme Q10 deficiency type 4, Niemann‐Pick disease type C1 and SYNE1‐related ataxia. Additionally, we found a novel homozygous MTCL1 loss of function variant p.(Lys407fs) in a 23‐year‐old patient with slowly progressive cerebellar ataxia, mild intellectual disability (ID), seizures in childhood and episodic pain in the lower limbs. The identified variant is predicted to truncate the protein after first 444 of 1586 amino acids. MTCL1 encodes a microtubule‐associated protein highly expressed in cerebellar Purkinje cells; its knockout in a mouse model causes ataxia. We propose MTCL1 as a candidate gene for autosomal recessive cerebellar ataxia in humans. Additionally, our study confirms the high diagnostic yield of NGS in early‐onset cerebellar ataxias, with at least 50% detection rate in our ataxia cohort.

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Similar time courses for word form and meaning preactivation during sentence comprehension

Abstract

Current psycholinguistic research generally acknowledges that aspects of sentence comprehension benefit from neural preactivation of different types of information. However, despite strong support from a number of studies, routine specific word form preactivation has been challenged by Ito, Corley, Pickering, Martin, and Nieuwland (2016). They suggest that word form prediction is contingent upon having enough processing time and resources (afforded by slower input rates) to progress through unidirectional, productionlike stages of comprehension to arrive at word forms via semantic feature preactivation. This conclusion is based on findings from their ERP study, which used a related anomaly paradigm and reported form preactivation at a slow (700 ms) word presentation rate but not a faster one (500 ms). The present experimental design is a conceptual replication of Ito et al. (2016), testing young adults by measuring ERP amplitudes to unpredictable words related either semantically/associatively or orthographically to predictable sentence continuations, relative to unrelated continuations. Results showed that, at a visual presentation rate of two words per second, both types of related words show similarly reduced N400s, as well as varying degrees of increased posterior post‐N400 positivity. These findings indicate that word form preactivation during sentence comprehension is detectable along a similar time course as semantic feature preactivation, and such processing does not necessarily require additional time beyond that afforded by near‐normal reading rates.

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Heat acclimation does not affect maximal aerobic power in thermoneutral normoxic or hypoxic conditions

What is the central question of this study? Controlled‐hyperthermia heat acclimation protocols induce an array of thermoregulatory and cardiovascular adaptations that facilitate exercise in hot conditions. We investigated whether this ergogenic potential can be transferred to thermoneutral normoxic or hypoxic exercising conditions. What is the main finding and its importance? We show that heat acclimation did not affect maximal cardiac output or maximal aerobic power in thermoneutral normoxic/hypoxic conditions. Heat acclimation augmented the sweating response in thermoneutral normoxic conditions. The cross‐adaptation theory according to which heat acclimation could facilitate hypoxic exercise capacity is not supported by our data.

Abstract

Heat acclimation (HA) mitigates heat‐induced decrements in maximal aerobic power (V̇O_2peak) and augments exercise thermoregulatory responses in the heat. Whether this beneficial effect of HA is observed in hypoxic or thermoneutral conditions remains unresolved. We explored the effects of HA on exercise cardiorespiratory and thermoregulatory responses in normoxic, hypoxic, and hot conditions. Twelve males (V̇O _2peak 54.7(5.7) mL·kg⁻¹·min⁻¹) participated in a HA protocol comprising 10 daily 90‐min controlled‐hyperthermia (target rectal temperature, T_re = 38.5 °C) exercise sessions. Before and after HA, we determined V̇O_2peak in thermoneutral normoxic (NOR), thermoneutral hypoxic (13.5% F_iO₂; HYP) and hot (35 °C, 50% RH; HE) conditions in a randomized and counterbalanced order. Preceding each maximal cycling test, a 30‐min steady‐state exercise at 40% of the NOR peak power output (W_peak) was employed to evaluate thermoregulatory responses. HA induced the expected adaptations in HE: reduced T_re and submaximal heart rate (HR), enhanced sweating response and expanded plasma volume. However, HA did not affect V̇O_2peak or maximal cardiac output (CO_max) (P = 0.61). W_peak was increased post‐HA in NOR (P < 0.001) and HE (P < 0.001) by 41 ± 21 and 26 ± 22 W, respectively but not in HYP (P = 0.14). Gross mechanical efficiency was higher (P = 0.004) whereas resting T_re and sweating thresholds were lower (P < 0.01) post‐HA across environments. Nevertheless, the gain of the sweating response decreased (P = 0.05) in HYP. In conclusion, our data do not support a beneficial cross‐over effect of HA on V̇O_2peak in normoxic or hypoxic conditions.

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Postprandial augmentation index is reduced in adults with prediabetes following continuous and interval exercise training

Abstract

Background

People with prediabetes have elevated risk for cardiovascular disease (CVD) in part due to low insulin sensitivity mediated arterial stiffness. However, the effect of short‐term exercise training intensity, and/or amount (i.e. kcal/session), on fasting and postprandial arterial stiffness is unknown. We tested the hypothesis that increased exercise intensity and dose (i.e. amount) would correlate with reduced fasting and postprandial arterial stiffness in obese adults with prediabetes.

Methods

Following randomization, 31 adults (Age: 61.4 ± 8.3 y, BMI: 32.1 ± 5.4 kg/m2) with prediabetes performed supervised continuous (CONT; n = 17; 70% of HRpeak) or interval (INT; n = 14; 3 min at 50% HRpeak and 3 min at 90% HRpeak) cycling training for 60 min/d over 2‐wks. Exercise amount was calculated using VO2‐HR derived regression equations. Arterial stiffness (augmentation index; AI and cartoid‐femoral pulse wave velocity; caPWV), insulin and glucose were determined during a 75 g OGTT and analyzed by total area under the curve (tAUC) pre/post training. The simple index of insulin sensitivity (SIIS)OGTT was calculated; aerobic fitness (VO2peak) and body mass were also assessed.

Results

Short‐term training had no effect on weight, but did improve VO2peak (P = 0.003), glucose tAUC180min (P = 0.01) and insulin sensitivity (P = 0.002), independent of intensity. CONT and INT exercise significantly reduced AI 2‐hr postprandial (P = 0.008) and tAUC180min (P = 0.03). Reductions in fasted AI related to exercise dose (trend: r = ‐0.37, P = 0.055). Increased VO2peak was linked to reduced fasted (r = ‐0.47, P = 0.01) and tAUC180min AI (r = ‐0.39, P = 0.05). Decreased AI tAUC180min correlated with increased insulin sensitivity (r = ‐0.50, P = 0.009).

Conclusion

Short‐term CONT and INT training reduced postprandial arterial stiffness comparably in adults with prediabetes.

New Findings

What is the central question of this study?

We compared high intensity interval versus continuous training on fasting and postprandial arterial stiffness in people with prediabetes.

What is the main finding and its importance?

We show for the first time that exercise improves augmentation index during the postprandial, but not fasted state, in adults with prediabetes. However, fasted augmentation index improved in relation to exercise dose, as assessed by kilocalories per session. Collectively, these findings suggest that short‐term exercise can improve arterial compliance in adults with prediabetes. Therefore, lifestyle interventions designed to reduce arterial stiffness could have considerable clinical impact.

This article is protected by copyright. All rights reserved

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Evaluation of the Keeogo exoskeleton for assisting ambulatory activities in people with multiple sclerosis: an open-label, randomized, cross-over trial

Although physical activity and exercise is known to benefit people with multiple sclerosis (MS), the ability of these individuals to participate in such interventions is difficult due to the mobility impairmen...

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On the use of approximate entropy and sample entropy with centre of pressure time-series

Approximate entropy (ApEn) and sample entropy (SampEn) have been previously used to quantify the regularity in centre of pressure (COP) time-series in different experimental groups and/or conditions. ApEn and ...

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ACSM PRE-PARTICIPATION HEALTH SCREENING GUIDELINES: A UK UNIVERSITY COHORT PERSPECTIVE

Purpose Pre-participation health screening is recommended to detect individuals susceptible to serious adverse cardiovascular complications during exercise. Although expert opinion and best available scientific evidence have informed recent modifications, there remains limited experimental data to support or refute current practice. We therefore aimed to quantify the impact of change to the ACSM pre-participation health screening guidelines on risk classification and referral for medical clearance in a large cohort of undergraduate university students. Methods Participants attended the laboratory on a single occasion to undergo pre-participation health screening. Information concerning health status was obtained via self-report questionnaire and objective physiological assessment with all data recorded electronically and evaluated against ACSM screening guidelines (9th and 10th Edition). Results Five-hundred and fifty-three students completed the study. The 9th Edition screening guidance resulted in eighty-two (15%) subjects classified as high-risk, almost one quarter (24%) classified as moderate-risk, and almost two-thirds (61%) classified as low-risk. In comparison, the updated 10th Edition screening guidance resulted in a significant reduction in those previously classified as either high-risk (5%) or moderate risk (2%), respectively. The majority of subjects (93%) were therefore cleared to begin a structured exercise programme. Taken together, approximately one-third (32%) fewer medical referrals were required when applying the updated 10th Edition guidance (χ2 (4) = 247.7, P

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Bound Tree Medical partners with EMSGrantsHelp to offer free grant assistance for opioid response products

Bound Tree Medical, part of the Sarnova family of companies, and the leading national specialty distributor of emergency medical products in the emergency medical services (EMS) market, has partnered with EMSGrantsHelp to provide grants support to EMS agencies seeking grants for the purchase of opioid response products like naloxone and opioid overdose kits. Bound Tree is proud to offer 1:1...

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Logistics Coordinator - GAAA

**Galveston County Health District is seeking a new Logistics Coordinator! ** This position is responsible for successfully coordinating the ordering, stocking, and inventorying the medical supplies and pharmaceuticals utilized by the Galveston Area Ambulance Authority. Responsibility also includes coordination with Fleet Management for servicing of units. **We can offer you: ** • Excellent Benefits; ...

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Paramedic Team Captain - GAAA

**Make a Difference in your community and join our Emergency Medical Service Team! ** Galveston County Health District is seeking a new Team Captain (Paramedic)! The right candidate will be for performing responsible and technical medical work dealing with emergency or non-emergency and/or lifesaving treatment of patients who are transported via Mobile Intensive Care Unit or Basic Life Support ambulance ...

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EMS Training Captain - CyFair Volunteer Fire Department

The Cy-Fair Volunteer Fire Department (CFVFD) is accepting applications for the position of Emergency Medical Services (EMS) Training Captain. EMS Training Captain: The Department EMS Training Captain is responsible for advancing the quality of clinical practice through the management, provision and coordination of the training activities for new clinical providers of the Cy-Fair Volunteer Fire Department ...

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Lume Cube adds DJI Mavic 2 drone lighting kit to current lineup

Allows drone users to light up the sky for multiple applications, including search and rescue CARLSBAD, Calif. – Lume Cube, the world's most versatile light for content creators, announced today pre-orders for the Lume Cube Lighting Kit for the DJI Mavic 2 Drone. Dubbed as the go-to portable drone, the DJI Mavic 2, when paired with the Lume Cube Lighting Kit, provides pilots with a...

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Brain Death in Patients With “Isolated” Brainstem Lesions: A Case Against Controversy

No abstract available

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Marginal ulcer continues to be a major source of morbidity over time following gastric bypass

Abstract

Background

Marginal ulcerations (MU) are a common and concerning complication following Roux-en-Y gastric bypass (RYGB) surgery. The aim of the present study was to examine the progression of MU and identify risk factors for the need for surgical intervention in patients with MU following RYGB.

Methods

A New York state longitudinal administrative database was queried to identify patients who underwent RYGB between 2005 and 2010 and who were followed for at least 4 years for the development of MU using ICD-9 and CPT codes. Patients with perforation as their first presentation of MU were excluded. Multivariable Cox proportional hazard model was built to identify risk factors for surgical intervention. Hazard ratios (HR) with 95% confidence intervals (CI) were reported.

Results

We identified 35,075 patients who underwent RYGB. Mean age was 42.47 ± 10.90 years and most were female (81.08%). There were 2201 (6.28%) patients with MU, of which 204 (9.27% of MU; 0.58% of RYGB overall) required surgery. The estimated cumulative incidence of having surgical intervention 1, 2, 5, and 8 years after MU diagnosis was 6% (95% CI 5–7%), 8% (95% CI 7–9%), 13% (95% CI 11–14%), and 17% (95% CI 13–20%), respectively. At time of MU diagnosis, younger age (HR 0.93 every 5 years, 95% CI 0.87–0.99), white race (HR 1.60, 95% CI 1.15–2.23), and weight loss (HR 2.82, 95% CI 1.62–4.88) were independent risk factors for subsequent surgical intervention for MU. Estimated cumulative incidence of MU recurrence was 15% (95% CI 9–22%) and 24% (95 CI% 15–32%) at 6 and 12 months after surgical intervention.

Conclusions

The need for surgical intervention for MU after RYGB is uncommon. Young age, white race, and marked weight loss are risk factors for surgical intervention. Such patients may benefit from early intensive medical therapy at the time of MU diagnosis.

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Proximity-CLIP — close encounters of the RNA kind

Proximity-CLIP — close encounters of the RNA kind

Proximity-CLIP — close encounters of the RNA kind, Published online: 12 December 2018; doi:10.1038/s41576-018-0086-y

Proximity-CLIP, a method that combines proximity-based protein biotinylation and UV crosslinking, profiles the transcriptome and ribonucleoproteins in subcellular compartments.

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Training day: 3 Waveform capnography scenarios

Help student paramedics identify CHF, Curare cleft and ROSC in capnography waveforms, and develop a treatment plan

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Precise anesthesia in thoracoscopic operations

Purpose of review The current review focuses on precise anesthesia for video-assisted thoracoscopic surgery (VATS) with the goal of enhanced recovery. Recent findings VATS has become an established and widely used minimally invasive approach with broad implementation on a variety of thoracic operations. In the current environment of enhanced recovery protocols and cost containment, minimally invasive VATS operations suggest adoption of individualized tailored, precise anesthesia. In addition to a perfect lung collapse for surgical interventions with adequate oxygenation during one lung ventilation, anesthesia goals include a rapid, complete recovery with adequate postoperative analgesia leading to early discharge and minimized costs related to postoperative inpatient services. The components and decisions related to precise anesthesia are reviewed and discussed including: letting patients remain awake versus general anesthesia, whether the patient should be intubated or not, operating with or without muscle relaxation, whether to use different separation devises, operating with different local and regional blocks and monitors. Conclusion The determining factors in designing a precise anesthesic for VATS operations involve consensus on patients' tolerance of the associated side effects, the best practice or techniques for surgery and anesthesia, the required postoperative support, and the care team's experience. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://ift.tt/OBJ4xP Correspondence to Ya-Jung Cheng, MD, PhD, Department of Anesthesiology, National Taiwan University Hospital and National Taiwan University College of Medicine, Jen-Ai Road, Section 1, Taipei 10051, Taiwan. Tel: +88 62 23123456x65517; fax: +88 62 23415736; e-mail: chengyj@ntu.edu.tw Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Orthostatic intolerance following hip arthroplasty: Incidence, risk factors and effect on length of stay a prospective cohort study

BACKGROUND Early postoperative mobilisation is important for enhanced recovery, but can be hindered by orthostatic intolerance, characterised by dizziness, nausea, vomiting, feeling of heat, blurred vision and ultimately syncope. Although the incidence of orthostatic intolerance following total hip arthroplasty has been identified, few studies have yet investigated potential risk factors for developing orthostatic intolerance after hip arthroplasty. OBJECTIVES The aim of this study was to assess the incidence of orthostatic intolerance on the first postoperative day after total hip arthroplasty, potential predisposing risk factors for developing orthostatic intolerance and its effect on length of stay. DESIGN A prospective observational study. SETTING Tertiary hospital, Auckland, New Zealand, May to September 2015. PATIENTS One hundred and seventeen consecutive patients undergoing unilateral total hip arthroplasty. Patients were excluded if they had revision surgery. MAIN OUTCOME MEASURES Incidence of orthostatic intolerance during mobilisation on the first postoperative day. Significant peri-operative risk factors for developing orthostatic intolerance were identified using logistic regression. Length of stay was compared between orthostatic intolerant and orthostatic tolerant patients using the Mann–Whitney U-test. RESULTS On the first postoperative day, 22% of patients failed mobilisation due to orthostatic intolerance. Factors independently associated with orthostatic intolerance were female sex; OR (95% CI), 3.11 (1.01 to 9.57), postoperative use of gabapentin; OR 3.55 (1.24 to 10.15) and high peak pain levels (≥5/10) during mobilisation; OR 4.05 (1.30 to 12.61). Overall, 78% of patients were correctly identified. The model was more accurate at predicting those who would not get orthostatic intolerance (89% correct), compared with those who did have orthostatic intolerance (39% correct). Length of stay was longer in patients with orthostatic intolerance (P = 0.019). CONCLUSION Orthostatic intolerance is common after total hip arthroplasty. Optimising pain control prior to mobilisation and limiting gabapentin use may modify the risk of developing postoperative orthostatic intolerance. Although personalised recovery pathways appear attractive, at present, the ability to predict at-risk individuals is still limited. This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. https://ift.tt/OBJ4xP Correspondence to Dr David A. Rice, Health and Rehabilitation Research Institute, Auckland University of Technology, Private Bag 92006, Auckland 1142, New Zealand E-mail: david.rice@aut.ac.nz Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

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Comparison of rocuronium requirement in children with continuous infusion versus intermittent bolus: A randomised controlled trial

BACKGROUND Minimising rocuronium administration during paediatric surgery helps to reduce the incidence of residual muscular blockade. OBJECTIVE To determine whether intermittent bolus injection (Bolus group) or continuous infusion (group) requires the lesser amount of rocuronium. DESIGN A prospective, randomised, single-blind controlled trial. SETTING A single university hospital from March to June 2017. PATIENTS Sixty-six children undergoing general anaesthesia. INTERVENTIONS Dose of rocuronium for maintenance of muscle relaxation in either Bolus or continuous infusion group. Train-of-four (TOF) count of two was maintained during surgery. When TOF count reached three, 0.1 mg kg−1 of rocuronium was administered in Bolus group or infused at an increased rate of 0.1 mg kg−1 h−1 in continuous infusion group. MAIN OUTCOME MEASURES Primary outcome was the dose of rocuronium given (μg kg−1 min−1). The recovery time from the TOF count four to TOF 0.7 (RT0.7), and 0.9 (RT0.9) were recorded. All adverse events were recorded up to 30 min after extubation. RESULTS Mean (SD) rocuronium dose in the Bolus group was 6.1 (0.9), [95% confidence interval (95% CI) 5.7 to 6.4] μg kg−1 min−1 and 4.9 (1.0), (95% CI 4.6 to 5.3) μg kg−1 min−1 in the continuous infusion group (P = 0.001). RT0.7 was 24.0 (13.7), 95% CI 19.3 to 28.7) min in the Bolus group, and 25.7 (16.0), (95% CI 20.2 to 31.2) min in the continuous infusion group (P = 0.73). RT0.9 was 30.7 (17.1), (95% CI 24.9 to 36.5) min in the Bolus group, and 30.0 (17.6), (95% CI 24.0 to 36.0) min in the continuous infusion group (P  = 0.91). The incidence of adverse events was not significantly different between two groups. CONCLUSION In children undergoing general anaesthesia, the dose of rocuronium given by continuous administration was less than that with intermittent bolus. TRIAL REGISTRATION ClinicalTrials.gov (identifier: NCT03060707). Correspondence to Hee-Soo Kim, MD, PhD, Department of Anaesthesiology and Pain Medicine, College of Medicine, Seoul National University, #101 Daehak-ro, Jongno-gu, 03080, Seoul, Republic of Korea Tel: +82 2 2072 3659; fax: +82 2 747 5639; e-mail: dami0605@snu.ac.kr © 2018 European Society of Anaesthesiology

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Use of tracheal ultrasound combined with clinical parameters to select left double-lumen tube size: A prospective observational study

BACKGROUND Left double-lumen tubes (LDLTs) are used in thoracic surgery to allow one-lung ventilation. Their size is usually chosen on the basis of clinical parameters (height, sex). Double-lumen endobronchial tubes are frequently undersized/oversized, risking tube displacement or tracheal trauma. A correlation between ultrasound tracheal diameter and left main bronchus dimension has been demonstrated. OBJECTIVES We hypothesised that the insertion of undersized/oversized double-lumen tubes is frequent when the size is selected using standard criteria, and that the use of ultrasound to estimate tracheal diameter may help to reduce the frequency of insertion of oversized tubes. DESIGN Two-step prospective observational study. SETTING The operating room of a French University hospital from January 2016 to February 2017. PATIENTS We enrolled 102 and 50 consecutive patients undergoing elective thoracic surgery in Steps 1 and 2 (males 63.7 and 60.0%, age 63 (13) and 63 (11) years, height 170 (13) and 169 (9) cm, respectively). INTERVENTION In Step 1, the size of the LDLT inserted was selected on the basis of clinical parameters. Ultrasound data about tracheal diameter were collected to determine cut-off points associating height and tracheal diameter. Cut-off values for ultrasound tracheal diameter were applied retrospectively to test their capability to reduce the insertion rate of oversized tube. In Step 2, the LDLT size was chosen according to the determined combined cut-off values. MAIN OUTCOME MEASURE LDLT size was considered adequate if the bronchial cuff volume required for isolation of the lung (i.e. no difference between inspiratory and expiratory lung volumes) was 0.5 to 2.5 ml of air; undersized and oversized tubes required more than 2.5 ml and less than 0.5 ml, respectively. RESULTS In Step 1, LDLT size was appropriate/undersized/oversized in 40 (39.2%)/23 (22.6%)/39 (38.6%) of patients. Cut-off values derived from ultrasound measurements would have reduced the use of oversized tubes by 20.6% (P 

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Monitoring haemodynamic response to fluid-challenge in ICU: Comparison of pressure recording analytical method and oesophageal Doppler

BACKGROUND The ability of the pressure recording analytical method (PRAM) in tracking change in cardiac output (ΔCO) after a fluid challenge in ICU needs to be evaluated with the most contemporary comparison methods recommended by experts. OBJECTIVE Our objective was to report the trending ability of PRAM in tracking ΔCO after a fluid challenge in ICU and to compare this with oesophageal Doppler monitoring (ODM). DESIGN Prospective, observational study. SETTING Hôpital Lariboisière and Hôpital Européen George Pompidou, Paris, France, from April 2016 to December 2017. PATIENTS Critically ill patients admitted to ICU with monitoring of CO monitored by ODM and invasive arterial pressure. INTERVENTION ΔCO after fluid challenge was simultaneously registered with ODM and PRAM connected to the arterial line. MAIN OUTCOME MEASURE Polar statistics (mean angular bias, radial limits of agreement and polar concordance rate) and clinical concordance evaluation (error grid and clinical concordance rate). Predictors of bias were determined. RESULTS Sixty-eight fluid challenge were administered in 49 patients. At the time of fluid challenge, almost all were mechanically ventilated (99%), with 85% receiving norepinephrine. Admission diagnosis was septic shock in 70% of patients. Patients had a Sequential Organ Failure Assessment score of 10 [7 to 12] and a median Simplified Acute Physiology Score II of 61 [49 to 69]. Relative ΔCO bias was 7.8 (6.3°) with radial limits of agreement of ±41.7°, polar concordance rate 80% and clinical concordance rate 74%. ΔCO bias was associated with baseline bias (P = 0.007). Baseline bias was associated with radial location of the arterial line (P = 0.03). CONCLUSION When compared with ODM, PRAM has insufficient performance to track ΔCO induced by fluid challenge in ICU patients. Baseline bias is an independent predictor of trending bias. TRIAL REGISTRATION IRB 00010254-2016-033. Correspondence to Romain Barthélémy, MD, Department of Anaesthesia, Burn, and Critical Care, Saint-Louis Lariboisière University Hospital, AP-HP, 2 Rue Ambroise Paré, 75475 Paris Cedex 10, France E-mail: romain.barthelemy@aphp.fr Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (https://ift.tt/2ylyqmW). © 2018 European Society of Anaesthesiology

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The Frequency of Lysosomal Acid Lipase Deficiency in Children With Unexplained Liver Disease

Objectives: Evidence suggests that lysosomal acid lipase deficiency (LAL-D) is often underdiagnosed because symptoms may be nonspecific. We aimed to investigate the prevalence of LAL-D in children with unexplained liver disease and to identify demographic and clinical features with a prospective, multicenter, cross-sectional study. Methods: Patients (aged 3 months–18 years) who had unexplained transaminase elevation, unexplained hepatomegaly or hepatosplenomegaly, obesity-unrelated liver steatosis, biopsy-proven cryptogenic fibrosis and cirrhosis, or liver transplantation for cryptogenic cirrhosis were enrolled. A Web-based electronic data collection system was used. LAL activity (nmol/punch/h) was measured using the dried blood spot method and classified as LAL-D ( 0.37). A second dried blood spot sample was obtained from patients with intermediate LAL activity for confirmation of the result. Results: A total of 810 children (median age 5.6 years) from 795 families were enrolled. The reasons for enrollment were unexplained transaminase elevation (62%), unexplained organomegaly (45%), obesity-unrelated liver steatosis (26%), cryptogenic fibrosis and cirrhosis (6%), and liver transplantation for cryptogenic cirrhosis (

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Social Stress Affects Colonic Inflammation, the Gut Microbiome, and Short Chain Fatty Acid Levels and Receptors

Objectives: Gastrointestinal disorders, such as inflammatory bowel diseases (IBD) and functional gastrointestinal disorders (FGID), involve disrupted homeostatic interactions between the microbiota and the host. Both disorders are worsened during stress, and in laboratory mice, stress exposure has been shown to change the composition of the gut microbiome. Stress-induced changes to the microbiome exacerbate intestinal inflammation and alter intestinal motility in mice. However, it is not yet known whether microbiota-derived short chain fatty acids (butyrate, propionate, and acetate) and their receptors contribute to this effect. Methods: Mice were exposed to a social disruption (SDR) stress, or left undisturbed as a control. After the first stress exposure, mice were orally challenged with Citrobacter rodentium or with vehicle. The levels of SCFAs were measured using gas chromatography-mass spectrometry. SCFA receptors were measured via real time PCR. Microbial community composition was assessed using 16S rRNA gene sequencing. Results: Stress exposure reduced colonic SCFA levels. However, stress exposure and C. rodentium significantly increased SCFA levels and changed the expression of SCFA receptors. The levels of SCFAs did not correlate with the severity of colonic inflammation, but the colonic expression of the SCFA receptor GPR41 was positively associated with inflammatory cytokines and colonic histopathology scores. The relative abundances of several taxa of colonic bacteria were significantly changed by stress exposure, including SCFA producers. Conclusions: Social stress can have a significant effect on infection-induced colonic inflammation, and stress-induced changes in microbial-produced metabolites and their receptors may be involved. Address correspondence and reprint requests to Ross M. Maltz, M.D., Pediatric Gastroenterology, Nationwide Children's Hospital, 700 Children's Drive, Columbus, OH 43205 (e-mail: Ross.Maltz@nationwidechildrens.org). Received 24 April, 2018 Accepted 5 November, 2018 Jeremy Keirsey, jeremy.keirsey@thermofisher.com, 4120 Kilbannon Way Dublin, OH 43016 Sandra C. Kim, Sandra.Kim@chp.edu, 4401 Penn Avenue Pittsburgh, PA 15224 Amy R. Mackos, mackos.3@osu.edu, 034H Newton Hall, 1585 Neil Ave, Columbus, OH 43210 Raad Z. Gharaibeh, rgharaibeh@gmail.com, 2033 Mowry Rd. PO Box 103633 Gainesville, Florida 32610 Cathy C. Moore, CathyMoore@uncc.edu, 9201 University City Blvd Charlotte, NC 28223 Jinyu Xu, Jinyu.Xu@nationwidechildrens.org, 700 Children's Drive Columbus, OH 43205 Arpad Somogyi, somogyi.16@osu.edu, 281 Biomedical Research Tower (BRT), 460 W. 12th Street, Columbus, OH 43210 Michael T. Bailey, Michael.Bailey2@nationwidechildrens.org, 700 Children's Drive Columbus, OH 43205 Conflicts of Interest and Source of Funding: This works was supported by the National Center for Complementary & Integrative Health of the National Institutes of Health under Award Number R01AT006552 (to M.T.B.). The author(s) report no conflict of interests or competing financial interests. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Esophageal IgG4: Clinical, Endoscopic, and Histologic Correlations in Eosinophilic Esophagitis

Objective: Recent studies show increased serum and esophageal IgG4 in patients with eosinophilic esophagitis (EoE), suggesting a possible IgG4-involved process. The role of IgG4 in pediatric EoE has not been extensively investigated. Our aim was to analyze IgG4 in esophageal tissue in children in parallel to that in adults with EoE. Methods: In a retrospective institutional review board–approved study, we performed immunohistochemical staining of IgG4 in esophageal biopsy specimens from 39 subjects: children with EoE (n = 16), adults with EoE (n = 15), children with reflux esophagitis (n = 4), and pediatric controls (n = 4). We assessed the relationships between IgG4 staining and clinical, endoscopic, and histopathologic characteristics. Results: Patients with EoE were significantly more likely to stain positively for IgG4 than children with reflux esophagitis or controls (P = 0.015). Fifteen of 31 (48%) EoE cases stained positively for IgG4. None of the reflux esophagitis or control cases stained positively. IgG4 staining had 48% sensitivity and 100% specificity for EoE. There was a trend toward IgG4 staining being associated with foreign body/food impaction (P = 0.153). There was a strong association between distal IgG4 staining and basal zone hyperplasia (P = 0.003). Conclusions: Our study suggests IgG4 is not a consistent finding of EoE at disease diagnosis. Although IgG4 staining was specific for EoE, it had a poor sensitivity with positive staining in only 48% of EoE patients. Further studies are warranted to fully elucidate the role of IgG4 in EoE. Address correspondence and reprint requests to Amanda E. Pope, MD, Department of Pediatrics, Division of Pediatric Gastroenterology, Hepatology and Nutrition, University of California Los Angeles, 10833 Le Conte Ave, MDCC 12-383, Los Angeles, CA 90095 (e-mail: APope@mednet.ucla.edu). Received 5 June, 2018 Accepted 27 October, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). The authors report no conflicts of interest. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Validation of Lipase and SIRS as Prognostic Indicators in Pediatric Acute Pancreatitis: A Retrospective Analysis

Introduction: Acute pancreatitis (AP) is understudied in the pediatric population despite increasing incidence. Although many cases are mild and resolve with supportive care, severe acute pancreatitis (SAP) can be associated with significant morbidity and mortality. There is a lack of pediatric-specific predictive tools to help stratify risk of SAP in children. Methods: A retrospective cohort study of patients with AP or recurrent AP at Cohen Children's Medical Center between 2011 and 2016 was performed. Lipase level and the presence of pediatric systemic inflammatory response syndrome (SIRS) on admission were examined as potential predictors of SAP and length of stay (LOS). A multivariate logistic regression or analysis of covariance was used to conduct the multivariate analysis. Results: Seventy-nine pediatric patients met inclusion criteria. Approximately 37% (29/79) had SIRS on admission, 22% (17/79) developed SAP, and there were no mortalities. In both the univariate and multivariate models, SIRS was a predictor of SAP. Mean (SD) LOS for patients with SIRS compared with without SIRS was 9.6 ± 8.3 compared with 6.3 ± 6.9 days (P 

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Decreased Fecal Bacterial Diversity and Altered Microbiome in Children Colonized With Clostridium difficile

Objectives: The gut microbiome is believed to play a role in the susceptibility to and treatment of Clostridium difficile infections (CDIs). It is, however, unknown whether the gut microbiome is also affected by asymptomatic C difficile colonization. Our study aimed to evaluate the fecal microbiome of children based on C difficile colonization, and CDI risk factors, including antibiotic use and comorbid inflammatory bowel disease (IBD). Methods: Subjects with IBD and non-IBD controls were prospectively enrolled from pediatric clinics for a biobanking project (n = 113). A fecal sample was collected from each subject for research purposes only and was evaluated for asymptomatic toxigenic C difficile colonization. Fecal microbiome composition was determined by 16S rRNA sequencing. Results: We found reduced bacterial diversity and altered microbiome composition in subjects with C difficile colonization, concurrent antibiotic use, and/or concomitant IBD (all P 

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Association of Maternal Secretor Status and Human Milk Oligosaccharides With Milk Microbiota: An Observational Pilot Study

Background and Objectives: Breast milk contains several bioactive factors including human milk oligosaccharides (HMOs) and microbes that shape the infant gut microbiota. HMO profile is determined by secretor status; however, their influence on milk microbiota is still uncovered. This study is aimed to determine the impact of the FUT2 genotype on the milk microbiota during the first month of lactation and the association with HMO. Methods: Milk microbiota from 25 healthy lactating women was determined by quantitative polymerase chain reaction and 16S gene pyrosequencing. Secretor genotype was obtained by polymerase chain reaction-RFLPs and by HMO identification and quantification. Results: The most abundant bacteria were Staphylococcus and Streptococcus, followed by Enterobacteriaceae-related bacteria. The predominant HMO in secretor milk samples were 2FL and lacto-N-fucopentaose I, whereas nonsecretor milk was characterized by lacto-N-fucopentaose II and lacto-N-neodifucohexaose II. Differences in microbiota composition and quantity were found depending on secretor/nonsecretor status. Lactobacillus spp, Enterococcus spp, and Streptococcus spp were lower in nonsecretor than in secretor samples. Bifidobacterium genus and species were less prevalent in nonsecretor samples. Despite no differences on diversity and richness, nonsecretor samples had lower Actinobacteria and higher relative abundance of Enterobacteriaceae, Lactobacillaceae, and Staphylococcaceae. Conclusions: Maternal secretor status is associated with the human milk microbiota composition and is maintained during the first 4 weeks. Specific associations between milk microbiota, HMO, and secretor status were observed, although the potential biological impact on the neonate remains elusive. Future studies are needed to reveal the early nutrition influence on the reduction of risk of disease. Address correspondence and reprint requests to Maria C. Collado, PhD, Institute of Agrochemistry and Food Technology, National Research Council (IATA-CSIC), Av. Agustin Escardino 7, 46980 Paterna, Valencia, Spain (e-mail: mcolam@iata.csic.es). Received 2 July, 2018 Accepted 13 November, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). I.G.M. and M.C.C. would like to acknowledge the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (ERC Starting grant, project no. 639226).The authors report no conflicts of interest. Raul Cabrera-Rubio, Actual address: Food Biosciences Department, Teagasc Food Research Centre, Moorepark, Fermoy, County Cork, Ireland and APC Microbiome Institute, University College Cork, Cork, Ireland. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Clinical Management of Pediatric Achalasia: A Survey of Current Practice

Objectives: Pediatric achalasia is a rare neurodegenerative disorder of the esophagus that requires treatment. Different diagnostic and treatment modalities are available, but there are no data that show how children can best be diagnosed and treated. We aimed to identify current practices regarding the diagnostic and therapeutic approach toward children with achalasia. Methods: Information on the current practice regarding the management of pediatric achalasia was collected by an online-based survey sent to members of the European and North American Societies for Pediatric Gastroenterology Hepatology and Nutrition involved in pediatric achalasia care. Results: The survey was completed by 38 centers from 24 countries. Within these centers, 108 children were diagnosed with achalasia in the last year (median 2, range 0–15). Achalasia was primarily managed by a pediatric gastroenterologist (76%) and involved a multidisciplinary team in 84% of centers, also including a surgeon (87%), radiologist (61%), dietician (37%), speech pathologist (8%), and psychologist (5%). Medical history taking and physical examination were considered most important to establish the diagnosis (50%), followed by (a combination of) manometry (45%) or contrast swallow (21%). Treatment of first choice was Heller myotomy (58%), followed by pneumatic dilation (46%) and peroral endoscopic myotomy (29%). Conclusion: This study shows a great heterogeneity in the management of pediatric achalasia amongst different centers worldwide. These findings stress the need for well-designed intervention trials in children with achalasia. Given the rarity of this disease, we recommend that achalasia care should be managed in centers with access to appropriate diagnostic and treatment modalities. Address correspondence and reprint requests to Maartje M.J. Singendonk, MD, PhD, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, C2-312, PO Box 22700, 1100 DD Amsterdam, The Netherlands (e-mail: m.m.j.singendonk@amc.uva.nl). Received 24 July, 2018 Accepted 30 October, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Although this article is produced by the ESPGHAN Motility Working Group it does not necessarily represent ESPGHAN policy and is not endorsed by ESPGHAN. The authors report no conflicts of interest. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Pediatric Eosinophilic Esophagitis: Results of the European Retrospective Pediatric Eosinophilic Esophagitis Registry (RetroPEER)

Objectives: Recommendations for diagnosing and treating eosinophilic esophagitis (EoE) are evolving; however, information on real world clinical practice is lacking. To assess the practices of pediatric gastroenterologists diagnosing and treating EoE and to identify the triggering allergens in European children. Methods: Retrospective anonymized data were collected from 26 European pediatric gastroenterology centers in 13 countries. Inclusion criteria were patients diagnosis with EoE, completed investigations prescribed by the treating physician, and were on stable medical or dietary interventions. Results: In total, 410 patients diagnosed between December 1999 and June 2016 were analyzed, 76.3% boys. The time from symptoms to diagnosis was 12 ± 33.5 months and age at diagnosis was 8.9 ± 4.75 years. The most frequent indications for endoscopy were: dysphagia (38%), gastroesophageal reflux (31.2%), bolus impaction (24.4%), and failure to thrive (10.5%). Approximately 70.3% had failed proton pump inhibitor treatment. The foods found to be causative of EoE by elimination and rechallenge were milk (42%), egg (21.5%), wheat/gluten (10.9%), and peanut (9.9%). Elimination diets were used exclusively in 154 of 410 (37.5%), topical steroids without elimination diets in 52 of 410 (12.6%), both diet and steroids in 183 of 410 (44.6%), systemic steroids in 22 of 410 (5.3%), and esophageal dilation in 7 of 410 (1.7%). Patient refusal, shortage of endoscopy time, and reluctance to perform multiple endoscopies per patient were noted as factors justifying deviation from guidelines. Conclusions: In this "real world" pediatric European cohort, milk and egg were the most common allergens triggering EoE. Although high-dose proton pump inhibitor trials have increased, attempted PPI treatment is not universal. Address correspondence and reprint requests to Noam Zevit, MD, Institute of Gastroenterology, Nutrition, and Liver Disease, Schneider Children's Medical Center of Israel, 14 Kaplan St, Petah-Tikva 4920235, Israel (e-mail: nzevit@gmail.com);AssafHoofien,MD,SchneiderChildren'sMedicalCenterofIsrael,Petah-Tikva,Israel(e-mail:Laerites@gmail.com). Received 15 August, 2018 Accepted 22 October, 2018 This study was supported by a networking research grant from the European Society of Pediatric Gastroenterology, Hepatology, and Nutrition. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). N.Z. reports consultant fees from Adare Pharmaceuticals. The remaining authors report no conflicts of interests. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Antiemetic Drug Use in Children: What the Clinician Needs to Know

Vomiting is not only unpleasant for both children and families, but can lead to frequent hospital admission. The persistent vomiting hampers oral intake and increases the risk of dehydration so the proper use of antiemetic drugs can be useful. The pharmacological treatment of vomiting in children remains a challenge for the pediatrician because several antiemetics are prescribed as "off-label", outside their authorized drug label. Domperidone and ondansetron are the most commonly known antiemetic drugs. A single oral dose of ondansetron has been shown to reduce the risk of recurrent vomiting, the need for intravenous fluids and hospital admissions in children with acute gastroenteritis. There is enough evidence to support ondansetron administration in children, so the clinical use can be defined as "off-label/on evidence". This review aims to provide an overview of therapeutic use, safety and main pharmacological properties of antiemetic drugs in children. A comprehensive search of published literature using the PubMed MEDLINE database was carried out to identify all papers published in English from 1998 to February 2018. At present time, the "off-label/on-evidence" use of some antiemetics could improve the success rate of oral rehydration therapy in pediatric emergency settings and to change the management of vomiting with the prevention of the complications. Address correspondence and reprint requests to Claudio Romano, MD, PharmD, Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124, Messina, Italy (e-mail: romanoc@unime.it). Received 21 August, 2018 Accepted 22 November, 2018 Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). Conflicts of Interest and Source of Funding: The authors have no conflict of interest to declare. This study was not supported by any governmental or private grant. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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