Growth restriction induced by chronic prenatal hypoxia affects the breathing rhythm and its pontine catecholaminergic modulation

Impaired transplacental supply of oxygen leads to intra uterine growth restriction, one of the most important causes of perinatal mortality and respiratory morbidity. The breathing rhythm depends on the central respiratory network modulated by catecholamines. We investigated the impact of growth restriction, using prenatal hypoxia, on respiratory frequency, on the central respiratory-like rhythm and on its catecholaminergic modulation after birth. At birth the respiratory frequency was increased and confirmed in, en bloc medullary preparations where the frequency of the fourth cervical (C4) ventral root discharge was increased, and in slice preparations containing the prebötzinger complex with an increased inspiratory rhythm. The inhibition of the C4 burst discharge observed in ponto-medullary preparation was stronger in the growth restricted group. These results cannot be directly linked by the tyrosine hydroxylase (TH) activity increase of A₁/C₁ and A₂/C₂ cell groups in the medulla since blocking the α-adrenergic receptors 1 and 2 does not abolish the difference between both groups. However in ponto-medullary preparation, the stronger inhibition of C4 burst discharge is probably supported by an increased inhibition of A5, a respiratory rhythm inhibitor pontine group of neurons, displaying an increased TH activity because blocking α2 adrenergic receptors abolished the difference between the two groups. Altogether, these results indicate that growth restriction leads to a perturbation of the breathing frequency, which finds, at least in part, its origin in the modification of the catecholaminergic modulation of the central breathing network.

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Sensitivities of Biopsy Sites in the Endoscopic Evaluation of Graft-Versus-Host Disease: Retrospective Review from a Tertiary Center

Abstract

Background

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation that frequently affects the gastrointestinal (GI) tract. The best biopsy sites to establish the diagnosis have not been clearly established.

Aims

To determine the best sites for obtaining biopsies in evaluating GI GVHD.

Methods

All cases of biopsy-proven GI GVHD (GVHD+) were isolated from a pathology database over a 2-year period at a single tertiary center (n = 46). Demographic, clinical, and endoscopic data were extracted. For comparison, 46 consecutive GVHD-negative cases (GVHD−) were obtained. Sensitivities in diagnosing GVHD in the upper and lower GI tract were calculated.

Results

In the GVHD− group, they were commonly investigated with an esophagogastroduodenoscopy (EGD) (60 vs. 22 % in the GVHD+ group, p < 0.01), while a colonoscopy (CLN) was commonly performed in the GVHD+ group (33 vs. 12 %, p = 0.02). Among the GVHD + patients, for EGDs, the sensitivity was highest for duodenal biopsies at 89 %. For flexible sigmoidoscopies (FSs) and CLNs, the sensitivities among all sites were similar (85 % agreement, kappa 0.58, p = 0.01). There were no cases in which GVHD was diagnosed in the right side of the colon without a positive biopsy in the left side of the colon.

Conclusions

In this cohort of GI GVHD patients, duodenum biopsies produced the highest yield in diagnosing GVHD when compared to other sites of the upper GI tract. Sensitivities were similar among all sites on lower endoscopies, suggesting that a FS is sufficient for diagnosing GVHD in suspected patients with diarrhea.

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The firing characteristics of deep dorsal horn neurons following acute spinal transection during administration of agonists for 5-HT1B/1D and NMDA receptors

Spinal cord injury (SCI) results in a loss of serotonin (5-HT) to the spinal cord and a loss of inhibition to deep dorsal horn (DDH) neurons, which produces an exaggerated excitatory drive to motoneurons. The mechanism of this excitatory drive could involve the DDH neurons triggering long excitatory postsynaptic potentials (EPSPs) in motoneurons, which may ultimately drive muscle spasms. Modifying the activity of DDH neurons with drugs such as NMDA or the 5-HT_1B/1D receptor agonist zolmitriptan could have a large effect on motoneuron activity and, therefore, on muscle spasms. In this study, we characterize the firing properties of DDH neurons following acute spinal transection in adult mice during administration of zolmitriptan and NMDA, using the in vitro sacral cord preparation and extracellular electrophysiology. DDH neurons can be categorized into three major types with distinct evoked and spontaneous firing characteristics: burst (bursting), simple (single-spiking), and tonic (spontaneously tonic-firing) neurons. The burst neurons likely contribute to muscle spasm mechanisms due to their bursting behavior. Only the burst neurons show significant changes in their firing characteristics during zolmitriptan and NMDA administration. Zolmitriptan suppresses the burst neurons by reducing their evoked spikes, burst duration, and spontaneous firing rate. Conversely, NMDA facilitates them by enhancing their burst duration and spontaneous firing rate. These results suggest that zolmitriptan may exert its anti-spastic effect on the burst neurons via activation of 5-HT_1B/1D receptors, whereas activation of NMDA receptors may facilitate the burst neurons in contributing to muscle spasm mechanisms following SCI.

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Resolution of Isolated, Aspergillus Colonization in a Deep Esophageal Ulcer in an Immunocompetent Patient with Ulcer Healing Without Specific Antifungal Therapy

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Air-Track: A real-world floating environment for active sensing in head-fixed mice

Natural behavior occurs in multiple sensory and motor modalities and in particular is dependent on sensory feedback that constantly adjusts behavior. To investigate the underlying neuronal correlates of natural behavior, it is useful to have access to state-of-the-art recording equipment (e.g. 2-photon imaging, patch recordings, etc.) that frequently requires head-fixation. This limitation has been addressed with various approaches such as virtual reality/air ball or treadmill systems. However, achieving multimodal, realistic behavior in these systems can be challenging. These systems are often also complex and expensive to implement. Here we present "Air-Track", an easy to build, head-fixed behavioral environment that requires only minimal computational processing. The Air-Track is a lightweight, physical maze floating on an air table that has all the properties of the "real" world, including multiple sensory modalities tightly coupled to motor actions. To test this system, we trained mice in Go/No-Go and two-alternative forced choice tasks in a plus maze. Mice chose lanes, and discriminated apertures or textures by moving the Air-Track back and forth, and rotating it around themselves. Mice rapidly adapted to moving the track, and utilized visual, auditory and tactile cues to guide them in performing the tasks. A custom-controlled camera system monitored animal location, and generated data that could be used to calculate reaction times in the visual and somatosensory discrimination tasks. We conclude that the Air-Track system is ideal for eliciting natural behavior in concert with virtually any system for monitoring or manipulating brain activity.

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Helicobacter pylori Clarithromycin Resistance and Treatment Failure Are Common in the USA

Abstract

Background

Helicobacter pylori antibiotic resistance leads to frequent treatment failure. However, the current US prevalence of H. pylori clarithromycin resistance and treatment failure is unknown.

Aims

To determine the prevalence of clarithromycin-resistant H. pylori and its impact on treatment failure in the USA.

Methods

A multicenter, retrospective, cohort study for clarithromycin-resistant H. pylori was conducted over four academic medical centers in different geographic regions of the USA. Gastric biopsy material, residual from standard clinical pathologic examination, was examined for clarithromycin resistance by DNA sequencing of H. pylori 23S rRNA.

Results

One hundred and twenty-four cases of H. pylori gastritis were examined from medical centers in four different geographic regions of the USA. The overall prevalence of clarithromycin resistance was 32.3 % (range 23.1–45.8 %). There was no significant difference in the prevalence of clarithromycin resistance by study site, gender, age, or race/ethnicity. In a subset of 67 patients that had clinical follow-up data, the overall prevalence of clarithromycin resistance was 31.3 %. There was a 2.9-fold increase (p = 0.002) in treatment failure for cases with clarithromycin resistance (57.1 %) compared to wildtype H. pylori (19.6 %).

Conclusions

H. pylori clarithromycin resistance in the USA exceeds the estimated 20 % prevalence compatible with successful empiric antibiotic therapy. This resistance resulted in a significant rate of treatment failure in all sites surveyed. Empiric therapy in the USA should be used with caution until there is better regional or local determination of H. pylori antibiotic resistance.

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Live Interaction Distinctively Shapes Social Gaze Dynamics in Rhesus Macaques

The dynamic interaction of gaze between individuals is a hallmark of social cognition. However, very few studies have examined social gaze dynamics following mutual eye contact during real-time interactions. We used a highly quantifiable paradigm to assess social gaze dynamics between pairs of monkeys and modeled these dynamics using an exponential decay function to investigate sustained attention following mutual eye contact. When interacting with real partners compared to static images and movies of the same monkeys, we found a significant increase in the proportion of fixations to the eyes and a smaller dispersion of fixations around the eyes, indicating enhanced focal attention to the eye region. Notably, dominance and familiarity between the interacting pairs induced separable components of gaze dynamics that were unique to live interactions. Gaze dynamics of dominant monkeys following mutual eye contact were associated with a greater number of fixations to the eyes, whereas those of familiar pairs were associated with a faster rate of decrease in this eye-directed attention. Our findings endorse the notion that certain key aspects of social cognition are only captured during interactive social contexts and dependent on the elapsed time relative to socially meaningful events.

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Gastric Enterovirus Infection: A Possible Causative Etiology of Gastroparesis

Abstract

Background

Gastroparesis (GP) is a disabling chronic gastroenterologic disorder with high morbidity that severely impacts patients' quality of life. GP can present acutely after a viral-like gastrointestinal illness resulting in speculation that in some patients, neurologic damage caused by the infection might underlie the pathogenesis of idiopathic gastroparesis (IGP).

Aims

The aim of this study is to document case reports of Enterovirus (EV) infection as a possible cause of IGP.

Methods

Eleven patients referred with a diagnosis of GP underwent workup to exclude known causes of GP. Those with a history of flu-like symptoms or gastroenteritis prior to onset of GP symptoms had gastric biopsies taken during upper endoscopy to assess for the presence of gastric mucosal EV infection. Data on presenting symptoms, extra-intestinal symptoms and conditions, prior nutritional support requirements, upper endoscopy findings, and response to therapy were cataloged.

Results

Eleven patients were diagnosed as IGP. Nine had active EV infection on gastric biopsies and were included (7/9 female, mean age 43 years). Eight out of nine received EV treatment with antivirals and/or immune therapies, with a wide degree of variability in treatment regimens. Four out of eight who received EV treatment had symptomatic improvement. One patient had stable symptoms. Three patients are currently undergoing therapy.

Conclusions

Gastric EV infection was frequently detected (82 %) in patients undergoing investigation for IGP. Antiviral and/or immune therapies against EV seem to be favorable, as most of our patients had resolution of their GP symptoms after treatment. This is the first study to identify EV as a possible infectious etiology of IGP.

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Savings for visuomotor adaptation requires prior history of error, not prior repetition of successful actions

When we move, perturbations to our body or the environment can elicit discrepancies between predicted and actual outcomes. We readily adapt movements to compensate for such discrepancies. The retention of this learning is evident as savings; or faster re-adaptation to a previously encountered perturbation. The mechanistic processes contributing to savings, or even the necessary conditions for savings, is not fully understood. One theory suggests that savings requires increased sensitivity to previously experienced errors: when perturbations evoke a sequence of correlated errors, we increase our sensitivity to the errors experienced, which subsequently improves error correction (Herzfeld et al. 2014). An alternative theory suggests that savings requires a memory of actions: when an action becomes associated with success through repetition, that action is more rapidly retrieved at subsequent learning (Huang et al. 2011). Here, to better understand the necessary conditions for savings, we tested how savings is affected by prior experience of similar errors and prior repetition of the action required to eliminate errors. Prior experience of errors induced by a visuomotor rotation in the savings block was either prevented at initial learning by gradually removing an oppositely signed perturbation, or enforced by abruptly removing the perturbation. Prior repetition of the action required to eliminate errors in the savings block was deprived or enforced by manipulating target location in preceding trials. The data suggest that prior experience of errors is both necessary and sufficient for savings, whereas prior repetition of a successful action is neither necessary nor sufficient for savings.

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A Case Series: Outcomes of Endoscopic Biliary Self-Expandable Metal Stent for Malignant Biliary Obstruction with Surgically Altered Anatomy

Abstract

Background

Few studies have reported the outcomes of self-expandable metal stent (SEMS) placement for malignant biliary obstruction in patients with surgically altered anatomy.

Aims

To evaluate the outcomes of biliary metal stent placement with the use of a short-type single-balloon enteroscope (working length, 1520 mm; channel diameter, 3.2 mm) in such patients.

Methods

We retrospectively studied 13 malignant biliary obstructions treated by SEMS placement. Technical success rate, functional success rate, time to recurrent biliary obstruction (RBO), and complications were evaluated.

Results

Technical success rate was 100 % (13/13), functional success rate was 92 % (12/13), and the median time to RBO was 247 days (95 % CI 205.6–285.5). Complications comprised mild pancreatitis in one patient. Uncovered SEMSs were placed in three obstructions, partially covered SEMS in five obstructions, and fully covered SEMSs in five obstructions. Three stents occluded (two ingrowths and one mucosal hyperplasia), and one symptomatic distal stent migration occurred after more than 30 days from placement.

Conclusions

A short-type single-balloon enteroscope was useful for the placement of various SEMS in this patient population with satisfactory outcomes.

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Peri-movement decrease of alpha-/beta-oscillations in the human nucleus accumbens

The human nucleus accumbens is thought to play an important role in guiding future action selection via an evaluation of current action outcomes. Here, we provide electrophysiological evidence for a more direct, i.e., on-line, role during action preparation. We recorded local field potentials from the nucleus accumbens in patients with epilepsy undergoing surgery for deep brain stimulation. We found a consistent decrease in the power of alpha-/beta-oscillations (10 to 30 Hz) before and around the time of movements. This peri-movement alpha-/beta-desynchronization was observed in seven of eight patients and was present both before instructed movements in a serial reaction time task as well as before self-paced, deliberate, choices in a decision-making task. A similar beta-decrease over sensorimotor cortex and in the subthalamic nucleus has been directly related to movement preparation and execution. Our results support the idea of a direct role of the human nucleus accumbens in action preparation and execution.

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Velocity-dependence of Vestibular Information for Postural Control on Tilting Surfaces

Vestibular information is known to be important for postural stability on tilting surfaces, but the relative importance of vestibular information across a wide range of surface tilt velocities is less clear. We compared how tilt velocity influences postural orientation and stability in 9 subjects with bilateral vestibular loss and 9 age-matched, control subjects. Subjects stood on a force platform that tilted 6 degrees, toes-up at eight velocities (0.25-32 deg/s), with and without vision. Results showed that visual information effectively compensated for lack of vestibular information at all tilt velocities. However, with eyes closed, vestibular loss subjects were most unstable within a critical tilt velocity range of 2-8 deg/s. Vestibular-deficient subjects lost their balance in over 90% of trials during the 4 deg/s condition, but never fell during slower tilts (0.25-1 deg/s) and fell only very rarely during faster tilts (16-32 deg/s). At the critical velocity range in which falls occurred, the body CoM stayed aligned with respect to the surface, onset of ankle dorsiflexion was delayed, and there was delayed or absent gastrocnemius inhibition, suggesting that subjects were attempting to actively align their upper bodies with respect to the moving surface instead of to gravity. Vestibular information may be critical for stability at velocities of 2-8 deg/s because the associated postural sway above 8 deg/s may be too fast to elicit stabilizing responses through the graviceptive somatosensory system and postural sway below 2 deg/sec may be too slow for somatosensory-triggered responses or passive stabilization from trunk inertia.

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GI-Safer Aspirin: Sometimes Sugar Coating Helps

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Spike Synchrony Generated by Modulatory Common Input through NMDA-type Synapses

Common excitatory input to neurons increases their firing rates and the strength of the spike correlation (synchrony) between them. Little is known, however, about the synchronizing effects of modulatory common input. Here we show that modulatory common input with the slow synaptic kinetics of NMDA receptors enhances firing rates and also produces synchrony. Tight synchrony (correlations on the order of milliseconds) always increases with modulatory strength. Unexpectedly, the relationship between strength of modulation and strength of loose synchrony (tens of milliseconds) is not monotonic: The strongest loose synchrony is obtained for intermediate modulatory amplitudes. This finding explains recent neurophysiological results showing that in cortical areas V1 and V2, presumed modulatory top-down input due to contour grouping increases (loose and tight) synchrony, but that additional modulatory input due to top-down attention does not change tight synchrony, and actually decreases loose synchrony. These neurophysiological findings are understood from our model of integrate-and-fire neurons under the assumption that contour grouping as well as attention lead to additive modulatory common input through NMDA-type synapses. In contrast, circuits with common projections through model AMPA receptors did not exhibit the paradoxical decrease of synchrony with increased input. Our results suggest that NMDA receptors play a critical role in top-down response modulation in visual cortex.

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Differential effect of treadmill exercise on histone deacetylase activity in rat striatum at different stages of development

Abstract

The study described herein aimed to evaluate the impact of exercise on histone acetylation markers in striatum from Wistar rats at different stages of development. Male Wistar rats were submitted to two different exercise protocols: a single session of treadmill (running 20 min) or a moderate daily exercise protocol (running 20 min for 2 weeks). Striata of rats aged 39 days postnatal (adolescents), 3 months (young adults), and 20 months (aged) were used. The single exercise session induced persistent effects on global HDAC activity only in the adolescent group, given that exercised rats showed decreased HDAC activity 1 and 18 h after training, without effect on histone H4 acetylation levels. However, the moderate daily exercise did not alter any histone acetylation marker in adolescent and mature groups in any time point evaluated after training. In sum, our data suggest that exercise impacts striatal HDAC activity in an age- and protocol-dependent manner. Specifically, this response seems to be more evident during the adolescent period and might suffer a molecular adaptation in response to chronic training.

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Energetics of muscle contraction: further trials

Abstract

Knowledge accumulated in the field of energetics of muscle contraction has been reviewed in this article. Active muscle converts chemical energy into heat and work. Therefore, measurements of heat production and mechanical work provide the framework for understanding the process of energy conversion in contraction. In the 1970s, precise comparison between energy output and the associated chemical reactions was performed. It has been found that the two do not match in several situations, resulting in an energy balance discrepancy. More recently, efforts in resolving these discrepancies in the energy balance have been made involving chemical analysis, phosphorus nuclear magnetic resonance spectroscopy, and microcalorimetry. Through reviewing the evidence from these studies, the energy balance discrepancy developed early during isometric contraction has become well understood on a quantitative basis. In this situation energy balance is established when we take into account the binding of Ca to sarcoplasmic proteins such as troponin and parvalbumin, and also the shift of cross-bridge states. On the other hand, the energy balance discrepancy observed during rapid shortening still remains to be clarified. The problem may be related to the essential mechanism of cross-bridge action.

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Promoter Identification and Transcription Analysis of Penicillin-Binding Protein Genes in Streptococcus pneumoniae R6

Microbial Drug Resistance , Vol. 0, No. 0.


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Primary and Secondary Stroke Prevention in Children With Sickle Cell Disease

Children with sickle cell disease (SCD) have numerous acute and chronic complications, including central nervous system (CNS) disease, which can be debilitating over their life span. Recognition of risk factors for CNS disease and overt CNS disease should be properly identified by primary care providers, including physicians, physician assistants, and nurse practitioners. Here, we discuss an emerging and important early indicator of CNS disease in the form of silent cerebral infarcts and review overt stroke in patients with SCD.

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Development and genetics of brain temporal stability related to attention problems in adolescent twins

Publication date: Available online 12 July 2016
Source:International Journal of Psychophysiology
Author(s): Dirk J.A. Smit, Andrey P. Anokhin
The brain continuously develops and reorganizes to support an expanding repertoire of behaviors and increasingly complex cognition. These processes may, however, also result in the appearance or disappearance of specific neurodevelopmental disorders such as attention problems. To investigate whether brain activity changed during adolescence, how genetics shape this change, and how these changes were related to attention problems, we measured EEG activity in 759 twins and siblings, assessed longitudinally in four waves (12, 14, 16, and 18years of age). Attention problems were assessed with the SWAN at waves 12, 14, and 16. To characterize functional brain development, we used a measure of temporal stability (TS) of brain oscillations over the recording time of 5min reflecting the tendency of a brain to maintain the same oscillatory state for longer or shorter periods. Increased TS may reflect the brain's tendency to maintain stability, achieve focused attention, and thus reduce "mind wandering" and attention problems. The results indicate that brain TS is increased across the scalp from 12 to 18. TS showed large individual differences that were heritable. Change in TS (alpha oscillations) was heritable between 12 and 14 and between 14 and 16 for the frontal brain areas. Absolute levels of brain TS at each wave were positively correlated with attention problems but not significantly. High and low attention problems subjects showed different developmental trajectories in TS, which was significant in a cluster of frontal leads. These results indicate that trajectories in brain TS development are a biomarker for the developing brain. TS in brain oscillations is highly heritable, and age-related change in TS is also heritable in selected brain areas. These results suggest that high and low attention problems subjects are at different stages of brain development.



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Dexmedetomidine protects against lung ischemia–reperfusion injury by the PI3K/Akt/HIF-1α signaling pathway

Abstract

Purpose

To evaluate the role of the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor 1α (HIF-1α) signaling pathway in the protection by dexmedetomidine against lung ischemia–reperfusion injury (IRI) in rats.

Methods

Forty-eight male Sprague–Dawley rats weighing 250–350 g were randomly divided into six groups (n = 8 each group): sham group, IRI group, low-dose dexmedetomidine group (LD group), high-dose dexmedetomidine group (HD group), combined low-dose dexmedetomidine and LY294002 group (LDL group), and combined high-dose dexmedetomidine and LY294002 group (HDL group). A 30-min ischemia was induced by occluding the hilum of the left lung, followed by a 120-min reperfusion by removing occlusion of the hilum. After the left lung was removed, the wet/dry weight ratio (W/D) of the lung tissues was determined. Pathological changes of lung tissues were evaluated by light and electron microscopes and the expression of p-Akt and HIF-1α in the lung tissues was determined by western blotting.

Results

Compared with the sham group, both the W/D ratio and lung injury were significantly increased, the p-Akt expression was down-regulated and HIF-1α expression was up-regulated in the five experimental groups. Compared with the LD and LDL groups, both the W/D ratio and lung injury were decreased, but the expression of p-Akt and HIF-1α was increased in the HD and HDL groups.

Conclusions

Administration of dexmedetomidine before ischemia can provide a protection against lung IRI by re-installing the PI3K/Akt/HIF-1α signaling pathway.

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Concurrent Validity of Caffeine Problems and Diagnostic Criteria for Substance Use Disorders

Journal of Caffeine Research , Vol. 0, No. 0.


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Clinical features of negative pathologic results after gastric endoscopic submucosal dissection

Abstract

Background

Endoscopic submucosal dissection (ESD) is widely used for the treatment of gastric superficial neoplasms. Negative pathologic results after ESD can confuse the endoscopists and patients. The aim of this study was to evaluate the reasons for and the factors associated with negative pathologic results after ESD.

Patients and methods

From December 2008 to July 2015, a total of 1379 lesions diagnosed as definite dysplasia or adenocarcinoma by endoscopic forceps biopsy (EFB) were removed with an ESD procedure. The initial endoscopic and pathologic findings were analyzed.

Results

The incidence of negative pathology after ESD was 2.0 % (28/1379). Compared with positive pathologic lesions, negative pathologic lesions were smaller and had less surface area (P < 0.001). The reasons for negative pathologic lesions after ESD were complete removal by EFB (n = 20), over-estimations of the EFB specimen (n = 5), and different ESD site (n = 3).

Conclusion

Small tumor size and surface area are associated with negative pathologic results after ESD. When negative pathologic results are reported after ESD, we should review the previous endoscopic biopsy tissue specimen and compare the previous EFB site to the ESD site. Thereafter, regular endoscopic examination of the lesion is needed.

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Laparoscopic duodenojejunostomy for superior mesenteric artery syndrome: intermediate follow-up results and a review of the literature

Abstract

Background

Superior mesenteric artery syndrome (SMAS) is a rare condition caused by partial obstruction of the third portion of the duodenum by the SMA anteriorly and aorta posteriorly. Laparoscopic duodenojejunostomy has been described as a safe and feasible surgical intervention with favorable short-term outcomes. However, descriptions of intermediate outcomes are lacking in the literature.

Methods

A retrospective chart review was performed on patients who underwent minimally invasive duodenojejunostomy from March 2005 to August 2015 at our healthcare system with greater than 6-month follow-up.

Results

Eighteen patients with mean age of 31.2 were identified. There were 4 men and 14 women. Patients' diagnosis was made by clinical presentation with radiographic confirmation. Mean weight loss preoperatively was 13.9 kg, representing 24.1 % total body weight loss. There were no intraoperative complications. Postoperatively, 2 patients developed prolonged ileus. One underwent exploratory laparotomy and washout for presumed leak, but none was identified. Three patients were readmitted within 30 days; 2 for intolerance to enteral intake with dehydration, and 1 for closed-loop obstruction requiring laparoscopic lysis of adhesions. The average and median length of follow-up were 27.7 and 26.0 months, respectively. Patients gained an average of 2.2 kg with an increase in body mass index of from 19.6 to 20.4 m/kg². Although 14 of 18 patients reported initial symptom improvement, at latest follow-up, only 6 patients reported symptomatic improvement or resolution. Three were diagnosed with global dysmotility, and 1 underwent intestinal transplant. Two were diagnosed with gastroparesis, and 1 underwent a laparoscopic gastric electric stimulator placement and pyloroplasty. There were no mortalities.

Conclusion

Duodenojejunostomy is the most common surgical intervention in management of SMAS. Our intermediate follow-up reveals infrequent improvement and rare resolution of preoperative symptomatology. Patients had a modest average weight gain postoperatively. This may suggest that different preoperative workup and treatment is indicated.

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A combined thoracoscopic and laparoscopic approach for high epiphrenic diverticula and the importance of complete myotomy

Abstract

Background

The traditional approach to epiphrenic diverticula is thoracotomy and diverticulectomy, together with myotomy ± partial fundoplication to address underlying dysmotility. A laparoscopic approach has been advocated but access to more proximal diverticula is problematic. We propose the selective addition of a thoracoscopic approach to overcome these challenges and reviewed our results.

Methods

A retrospective review from 2004 to 2015 identified 17 patients with an epiphrenic diverticulum who underwent surgery. Patients were grouped according to height of the diverticular neck (HDN) above the GEJ: group A < 5 cm, group B > 5 cm. Preoperative evaluation and type of surgery performed were recorded. Postoperative complications, mortality, and clinical outcomes using quality of life metrics and objective testing were assessed.

Results

The mean size of the diverticulum was 3.3 cm (2–6 cm) with a mean height above the GEJ of 5.5 cm (0–12 cm). A motility disorder was identified in 15/17. Group A, 9 patients, underwent laparoscopic diverticulectomy, myotomy, and partial fundoplication. For group B, 8 patients, the intended procedure was thoracoscopic diverticulectomy followed by laparoscopic myotomy and partial fundoplication, but this was only completed in 5. In 3 the myotomy was aborted or incomplete with subsequent staple line leaks resulting in 1 death. At a mean follow-up of 21 months, improvement of median QOLRAD scores from 3.42 to 6.2 (p = 0.18); GERD-HRQL from 23 to 1 (p = 0.05), swallowing score from 17.5 to 30 (p = 0.22), and Eckardt scores from 5 to 0 (p < 0.05) were observed.

Conclusions

A minimally invasive strategy for epiphrenic diverticula based HDN above the GEJ and selective thoracoscopy for higher diverticula is feasible and appropriate, and resulted in improved quality of life. Incomplete myotomy was associated with a substantially higher complication rate. Laparoscopic myotomy should precede diverticulectomy for all cases, especially for high diverticula.

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Erratum to: A feasibility study of the use of computed virtual chromoendoscopy for laparoscopic evaluation of peritoneal metastases

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Video-assisted thoracoscopic surgery is a safe option for benign lung diseases requiring lobectomy

Abstract

Background

Lobectomy for benign lung disease is renowned to be technically complex and to be subjected to an increased complication rate. The objective of this study was to evaluate whether the results obtained with video-assisted surgery (VATS) in benign disease are comparable to those obtained in oncologic surgery, where VATS has been validated.

Methods

We have reviewed the files of 246 consecutive patients who underwent VATS lobectomy from January 2012 to August 2015. The cohort was divided into two groups according to pathology (benign or malignant). Outcome parameters on scrutiny were demographics, pathology, duration of air leak, drainage and hospital stay, conversion, and perioperative complication rate. Comparisons were made with the χ ² test and Student's t test; any p value ≤0.05 was considered as significant.

Results

Group 1 (36 patients) included patients who underwent lobectomy for benign disease and group 2 (210 patients) patients affected by lung cancer or pulmonary metastases. The two groups differed with reference to age (p < 0.001), history of cancer (p < 0.001), history of stroke (p = 0.05), and the presence of pleural adhesions (p = 0.03). There was no difference for duration of air leaks, chest tube drainage and hospital stay, conversion rate, and perioperative complication rate.

Conclusions

We conclude that pathology did not impact on outcomes after VATS lobectomy. This study suggests that VATS is as a safe option in selected patients with benign disease requiring lobectomy, despite a more complex technical context.

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Characteristics of learning curve in minimally invasive ileal pouch-anal anastomosis in a single institution

Abstract

Background

Previous work from our institution has characterized the learning curve for open ileal pouch-anal anastomosis (IPAA). The purpose of the present study was to assess the learning curve of minimally invasive IPAA.

Methods

Perioperative outcomes of 372 minimally invasive IPAA by 20 surgeons (10 high-volume vs. 10 low-volume surgeons) during 2002–2013, included in a prospectively maintained database, were assessed. Predicted outcome models were constructed using perioperative variables selected by stepwise logistic regression, using Akaike's information criterion. Cumulative sums (CUSUM) of differences between observed and predicted outcomes were graphed over time to identify possible improvement patterns.

Results

Institutional pelvic sepsis and other pouch morbidity rates (hemorrhage, anastomotic separation, pouch failure, fistula) significantly decreased (18.2 vs. 7.0 %, CUSUM peak after 143 cases, p = 0.001; 18.4 vs. 5.3 %, CUSUM peak after 239 cases, respectively, p < 0.001). Institutional total proctocolectomy mean operative times significantly decreased (307 min vs. 253 min, CUSUM peak after 84 cases, p < 0.001), unlike completion proctectomy (p = 0.093) or conversion rates (10 vs. 5.4 %, p = 0.235). Similar learning curves were identified among high-volume surgeons but not among low-volume surgeons. Learning curves were identified in the two busiest individual surgeons for pelvic sepsis (peaks at 47 and 9 cases, p = 0.045 and p = 0.002) and in one surgeon for operative times (CUSUM peak after 16 and 13 cases for both total proctocolectomy and completion proctectomy (p < 0.001 and p = 0.006) but not for other pouch complications (peak at 49 and 41 cases, p = 0.199 and p = 0.094).

Conclusion

Pouch complications, particularly pelvic sepsis, are the most consistent and relevant learning curve end points in laparoscopic IPAA.

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Multiple colonic ulcers associated with trisomy 8: serial changes in colonoscopic findings

Abstract

We report a 54-year-old female patient with myelodysplastic syndrome (MDS) associated with trisomy 8, who had multiple colonic ulcers. The patient had been diagnosed as having MDS of refractory cytopenia with trisomy 8 10 years previously. She underwent colonoscopy for abdominal pain, which revealed severe circumferential stenosis with multiple ulcers in the ileocecal region and a discrete excavating ulcer in the transverse colon. The patient had been free from any dermatological, oral, genital or ocular symptoms suggestive of Behçet's disease (BD). A diagnosis of multiple colonic ulcers associated with MDS with trisomy 8 was thus suggested. Follow-up colonoscopies 5 and 6 years later revealed progression of the ileocecal stenosis to a circumferential ulcer, while the ulcer in the transverse colon had not changed. Because our patient lacked extraintestinal symptoms of BD, trisomy 8 was presumed to be responsible for her colonic ulcers.

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Evaluation of esophageal intramural pseudo-diverticulosis using high-resolution manometry

Abstract

Esophageal intramural pseudo-diverticulosis (EIPD) is a rare disease characterized by multiple small flask-shaped pouches in the esophageal wall, with the predominant symptom of chronic progressive or intermittent dysphagia. However, its etiology and pathogenesis remain unknown. We present a case of EIPD evaluated with high-resolution manometry in a 75-year-old man with food impaction after eating beef, who came to our emergency department. The patient experienced similar episodes three times previously, though the cause was unknown. Computed tomography (CT) findings revealed diffuse wall thickness in the upper intrathoracic esophagus, while esophagogastroduodenoscopy showed multiple small depressions and several white plaque patches, and a barium meal esophagogram showed characteristic multiple small outpouching areas. From these findings, we diagnosed the patient with EIPD. In addition, high-resolution manometry revealed strong contractions in the distal esophagus. We started an administration of isosorbide dinitrate, because abnormal esophageal motility may have been causative of the condition and development of pseudo-diverticulosis. Thereafter, the patient had a good clinical course without food impaction. Elevated intra-esophageal luminal pressure caused by abnormal esophageal motility seems to be an important factor in the pathogenesis of EIPD in some cases.

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Concurrent Validity of Caffeine Problems and Diagnostic Criteria for Substance Use Disorders

Journal of Caffeine Research , Vol. 0, No. 0.


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Family burden in alcohol dependence: A study in north-eastern India

2016-07-13T08-31-58Z
Source: International Journal of Medical Science and Public Health
Surajit Kumar Sen, Robin Victor, Kaveri Saxena.
Background: Substance abuse and dependence besides affecting the individual also has substantial impact upon the family. It puts the whole family through a physical, psychological, emotional and financial stress. Objectives: The aim of the present study was to assess the various socio-demographic variables of alcohol-dependent patients as well as their primary care givers and evaluate the severity and pattern of family burden among them. Material and Methods: A cross-sectional single interview case study done at Silchar Medical College and Hospital Assam after obtaining permission from ethics committee. Briefly, 50 cases were selected serially from the Psychiatry Outpatient department fulfilling the ICD-10 criteria of alcohol dependence syndrome and the primary care givers of these cases were assessed to evaluate the pattern and severity of family burden which was assessed via family burden interview scale. Results: Majority of alcohol dependence cases were from the age range of 35 to 44 years (44%) while their primary care givers from 30 to 39 years (44%). Most of cases had their spouses (74%) as the primary care givers and 1014 years of alcohol dependence (34%). Majority the primary care givers suffered from moderate type of family burden especially in area such as disruption of routine family activity, recreation and family interaction. Higher family burden was associated with equal to or more than 15 years of alcohol dependence which was statistically significant in most of the areas. Higher subjective burden was also observed when the primary care givers were spouse, cases were from rural areas, having nuclear family type with being illiterate/primary educated, belonging to lower/lower socio-economic group, and were financially dependent on others (unemployed/housewives). Conclusion: The severity of family burden is greatly influenced by the socio-demographic variables of the families as well as the duration of the substance dependence of the cases.


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QT and corrected QT parameters in non-obese young Indian women with polycystic ovary syndrome

2016-07-13T08-31-58Z
Source: International Journal of Medical Science and Public Health
Malathi Balamurugan, Balamurugan Maruthamuthu, Gomathi Ramanathan.
Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age group. The QTc interval duration, which is related to cardiac arrhythmia, sudden death and a sign of cardiac autonomic neuropathy, has not been investigated thoroughly in PCOS population. Objectives: The aim of the present study was to investigate the potential alterations in electrocardiographic (ECG) QT parameters in lean and ideal weight young Indian patients with PCOS. Materials and Methods: 24 classical PCOS diagnosed by Rotterdam 2003 Diagnostic criteria and were lean or ideal weight as per WHO criteria and 24 BMI matched, age matched normally menstruating women served as study participants. All of them underwent assessments clinically and by appropriate laboratory tests. We assessed metabolic pattern and performed ECG analysis for evaluating QT interval, minimum and maximum QT interval (QT Max and QT Min), QT dispersion (QTd), minimum and maximum QT interval corrected for heart rate (QTcmin and QTcmax, respectively), corrected QT dispersion (QTcd) and QT/QTc ratio. Results: QT (388 ± 35 vs 431 ± 53 ms , P value

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Study of clinical manifestations of dengue cases in a tertiary care hospital, Bangalore, Karnataka

2016-07-13T08-31-58Z
Source: International Journal of Medical Science and Public Health
CN Tejaswi, Savita S Patil, Kanavi Roopa Shekharappa.
Background: Symptomatic dengue virus infections can present with a wide range of clinical manifestations, from mild febrile illness to a life-threatening shock syndrome or organ dysfunction. Objectives: To study the clinical manifestations and laboratory findings of dengue cases, which is important for patient management and crucial for saving life. Material and Methods: Hospital-based cross-sectional study conducted from July to December 2015, included suspected dengue cases aged 16 years and above admitted in the medical wards of the hospital. Detailed epidemiological, clinical, and laboratory parameters recorded. Chi-square (χ2) test and descriptive statistics were analyzed using SPSS (17.0). Results: Of the total 114 patients, 64 (56.1%) males and 50 (43.8%) were females. Majority of the affected patients were in the age group of 3140 years (6 (31.5%)). Commonest symptom and sign observed was fever in 103 (90.3%). Signs of quadrant/epigastric tenderness, tachycardia, flushing were observed in more than > 50% of the patients and bradycardia, right upper shifting dullness, evidence of pleural effusion, shortness of breath, low blood pressure, low urine output, cold extremities were observed in less than 30% of patients. The commonest complication was severe abdominal bloating (8 (7.0%)), major bleeding and hepatitis in 5 (4.3%) of the patients. Briefly, 13 (11.4%) required the ICU treatment. In total, 107 (93.8%) had thrombocytopenia, raised AST and ALT in 89 (78.0%), leucopania in 74 (64.9%), ascites in 71 (62.2%), gall bladder wall edema in 64 (56.1%), and hematocrit in 28 (24.5%) of the patients. Also, 92 (80.7%) patients were NS1 positive. Conclusion: Manifestations of dengue cases are acute and varied. Proper confirmation of diagnosis, early institution of therapy helps in dengue prevention and management.


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Platelet dysfunction in pre-eclamptic mothers

2016-07-13T08-31-58Z
Source: International Journal of Medical Science and Public Health
Purnima Meher, Sunil Kumar Jena, Sitanshu Kumar Meher.
Background: Pre-eclampsia (PE) is a pregnancy-specific hypertensive disorder leading to a high proportion of hospital admission, labor induction, maternal as well as fetal morbidity and mortality. However it is fortunate that with timely detection and prompt management, this disease can often be ameliorated and eclampsia can be prevented. Objective: The objective of this study is to find out the changes in total platelet count (TPC), bleeding time (BT), and clotting time (CT) in pre-eclamptic pregnant women as compared with normal pregnant women. Material and Methods: This was a casecontrol study which included 60 pregnant women of more than 20 weeks of gestation. Out of these, 30 subjects were normotensive and 30 subjects were diagnosed with pre-eclamptic women. Patients having a past history of hypertension, renal diseases, diabetes during non-pregnant state, drug administration altering hematological profile, and autoimmune disorder were excluded from the study. Blood pressure was measured in all the cases and control subjects and three blood tests, i.e., BT, CT, and TPC were performed for each. Results: There was a significant fall in TPC in PE cases as compared with normal (P

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Perception and aspiration of final year B.Sc. nursing students towards their professional life

2016-07-13T08-31-58Z
Source: International Journal of Medical Science and Public Health
Sayed Kashif Mustafa Momin, Syed Jawwad Hashmi, Hrishikesh A Khadilkar.
Background: Nurses are the backbone of the healthcare sector and are fundamental in the delivery of quality care. The perception and image of both nurses and nursing as a profession are vital in the successful recruitment and retention of staff in the health care industry. Objective: To study the perception and aspirations of B.Sc. final year nursing students towards their professional life. Material and Methods: This cross-sectional study was conducted in Urban Health Care and training Center Shahaganj, Aurangabad. A total 70 B.Sc. final year nursing students were interviewed through self-administered questionnaire containing three major parts: the first part is the socio-demographic characteristics; the second part is perception of nursing profession; the third part is aspirations of nursing students. Results: Approximately 80% of students source of awareness was from nearly people, i.e., parents, relatives, and friends. And most (85%) of students were interested in their field. Most of the students choose this field mainly because of more job opportunities. The other significant reason to choose this field is their own interest in health care system and also their passion to serve the community. Majority (81.4%) of the students preferred the urban area while there was a small group (18.6%) of students even willing to work in the rural area. Majority of the students feel that both males and females are equally compassionate and dedicated to nursing profession. Maximum students want to be a doctor if they had opportunity but the majority of students (85.7%) were satisfied. Conclusion: The perception of nursing profession among nursing students is changing towards positive side. The guidance by family and friends were important factors in joining nursing profession. Providing more career opportunities and projecting the nursing profession as a respectable and high demanding profession will help to boost admission and improve perceptions further.


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17q12 deletion and duplication syndrome in Denmark—A clinical cohort of 38 patients and review of the literature

17q12 deletions and duplications are two distinct, recurrent chromosomal aberrations usually diagnosed by chromosomal microarray analysis (CMA). The aberrations encompass the genes, HNF1B, LHX1, and ACACA, among others. We here describe a large national cohort of 12 phenotyped patients with 17q12 deletions and 26 phenotyped patients with 17q12 duplications. The total cohort includes 19 index patients and 19 family members. We also reviewed the literature in order to further improve the basis for the counseling. We emphasize that renal disease, learning disability, behavioral abnormalities, epilepsy, autism, schizophrenia, structural brain abnormalities, facial dysmorphism, and joint laxity are features seen in both the 17q12 deletion syndrome and the reciprocal 17q12 duplication syndrome; and we extend the list of features seen in both patient categories to include strabismus, esophageal defects, and duodenal atresia. Delayed language development, learning disability, kidney involvement, and eye dysmorphism and strabismus were the most consistently shared features among patients with 17q12 deletion. Patients with 17q12 duplications were characterized by an extremely wide phenotypic spectrum, including a variable degree of learning disabilities, delayed language development, delayed motor milestones, and a broad range of psychiatric and neurological features. This patient group also included adults achieving an academic degree. Assessing index patients and non-index patients separately, our observations illustrate that an overall milder disease burden is seen, in particular in patients with 17q12 duplications who are ascertained on the duplication rather than the phenotype. This evidence may be useful in prenatal counseling. © 2016 Wiley Periodicals, Inc.

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Increased bone turnover, osteoporosis, progressive tibial bowing, fractures, and scoliosis in a patient with a final-exon SATB2 frameshift mutation

Haploinsufficiency of SATB2 causes cleft palate, intellectual disability with deficient speech, facial and dental abnormalities, and other variable features known collectively as SATB2-associated syndrome. This phenotype was accompanied by osteoporosis, fractures, and tibial bowing in two previously reported adult patients; each possessed SATB2 mutations either predicted or demonstrated to escape nonsense-mediated decay, suggesting that the additional bone defects result from a dominant negative effect and/or age-dependent penetrance. These hypotheses remain to be confirmed, as do the specific downstream defects causing bone abnormalities. We report a SATB2 mutation (c.2018dupA; p.(H673fs)) in a 15-year-old patient whose SATB2-associated syndrome phenotype is accompanied by osteoporosis, fractures, progressive tibial bowing, and scoliosis. As this homeodomain-disrupting and predicted truncating mutation resides within the final exon of SATB2, escape from nonsense-mediated decay is likely. Thus, we provide further evidence of bone phenotypes beyond those typically associated with SATB2-associated syndrome in individuals with potential dominant-negative SATB2 alleles, as well as evidence for age-dependence of bone features. Elevations in alkaline phosphatase, urinary N-telopeptide/creatinine ratio, and osteocalcin in the patient indicate increased bone turnover. We propose surveillance and treatment with osteoclast inhibitors to prevent fractures and to slow progressive bone deformities. © 2016 Wiley Periodicals, Inc.

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Atypical presentation of infantile-onset farber disease with novel ASAH1 mutations

Farber disease is a very rare autosomal recessive disease caused by mutation of ASAH1 that results in the accumulation of ceramide in various tissues. Clinical symptoms of classic Farber disease comprise painful joint deformity, hoarseness of voice, and subcutaneous nodules. Here, we describe a patient with Farber disease with atypical presentation of early onset hypotonia, sacral mass, congenital heart disease, and dysmorphic face since birth. Severe cognitive disability, failure to gain motor skills, failure to thrive, and joint contractures developed. Using whole-exome sequencing, we identified the compound heterozygote missense mutations of ASAH1 (p.R333C and p.G235R). Because of the diagnostic delay, she underwent sacral mass excision, which revealed enlarged lysosomes and zebra bodies. We report an atypical presentation of Farber disease with her pathology and associated genetic defect. This case expands the phenotypic spectrum of Farber disease to include novel mutations of ASAH1, which pose a diagnostic challenge. We also discuss the clinical utility of whole-exome sequencing for diagnosis of ultra-rare diseases. © 2016 Wiley Periodicals, Inc.

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Failure of ossification of the occipital bone in mandibuloacral dysplasia type B

Mandibuloacral dysplasia with type B lipodystrophy is a rare autosomal recessive disease characterized by atrophic skin, lipodystrophy, and skeletal features. It is caused by mutations in ZMPSTE24, a gene encoding a zinc metalloproteinase involved in the post-translational modification of lamin. Nine distinct pathogenic variants have been identified in 11 patients from nine unrelated families with this disorder. We report a 12-year-old boy with mandibuloacral dysplasia with type B lipodystrophy and a novel homozygous c.1196A>G; p.(Tyr399Cys) mutation in ZMPSTE24. The patient had typical dermatological and skeletal features of mandibuloacral dysplasia with type B lipodystrophy, sparse hair, short stature, mild microcephaly, facial dysmorphism, and a striking failure of ossification of the interparietal region of the occipital bone, up to the position where transverse occipital suture can be observed. Newly recognized signs for mandibuloacral dysplasia with type B lipodystrophy were gaze palsy and ptosis. Delayed closure of cranial sutures and Wormian bones have been described in three patients, but an ossification failure strictly limited to the occipital bone, as seen in the present patient, appears to be unique for mandibuloacral dysplasia with type B lipodystrophy. This observation illustrates that ZMPSTE24 could play a specific role in membranous ossification in the interparietal part of the squama (Inca bone) but not in the intracartilaginous ossification of the supraoccipital. This failure of ossification in the squama appears to be a useful feature for the radiological diagnosis of mandibuloacral dysplasia with type B lipodystrophy. © 2016 Wiley Periodicals, Inc.

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16p11.2 deletion and duplication: Characterizing neurologic phenotypes in a large clinically ascertained cohort

Chromosome 16p11.2 deletions and duplications are among the most frequent genetic etiologies of autism spectrum disorder (ASD) and other neurodevelopmental disorders, but detailed descriptions of their neurologic phenotypes have not yet been completed. We utilized standardized examination and history methods to characterize a neurologic phenotype in 136 carriers of 16p11.2 deletion and 110 carriers of 16p11.2 duplication—the largest cohort to date of uniformly and comprehensively characterized individuals with the same 16p copy number variants (CNVs). The 16p11.2 deletion neurologic phenotype is characterized by highly prevalent speech articulation abnormalities, limb and trunk hypotonia with hyporeflexia, abnormalities of agility, sacral dimples, seizures/epilepsy, large head size/macrocephaly, and Chiari I/cerebellar tonsillar ectopia. Speech articulation abnormalities, hypotonia, abnormal agility, sacral dimples, and seizures/epilepsy are also seen in duplication carriers, along with more prominent hyperreflexia; less, though still prevalent, hyporeflexia; highly prevalent action tremor; small head size/microcephaly; and cerebral white matter/corpus callosum abnormalities and ventricular enlargement. The neurologic phenotypes of these reciprocal 16p11.2 CNVs include both shared and distinct features. Reciprocal phenotypic characteristics of predominant hypo- versus hyperreflexia and macro- versus microcephaly may reflect opposite neurobiological abnormalities with converging effects causing the functional impairments shared between 16p11.2 deletion and duplication carriers (i.e., abnormal motor agility and articulation). While the phenotypes exhibit overlap with other genetically-caused neurodevelopmental disorders, clinicians should be aware of the more striking features—such as the speech and motor impairments, growth abnormalities, tremor, and sacral dimples—when evaluating individuals with developmental delay, intellectual disability, ASD, and/or language disorders. © 2016 Wiley Periodicals, Inc.

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Neonatal McCune–Albright syndrome with survival beyond two years

McCune–Albright syndrome (MAS) is a rare disease resulting from a somatic, mosaic mutation of GNAS1 encoding the G_sα subunit of the G-protein coupled membrane receptor responsible for multiple hormonal signaling cascades. We present a patient with neonatal MAS who initially presented with neonatal diabetes and concern for congenital cardiac disease, and subsequently was found to have significant ACTH-independent neonatal Cushing syndrome. Her course included multi-system organ involvement, although she initially did not have obvious findings consistent with the MAS classic triad of café-au-lait macules, fibrous dysplasia, or peripheral precocious puberty. After medical and surgical treatment, she remains the only reported survivor of neonatal MAS. This clinical report alerts clinicians to the possibility of this disease in neonates with non-classical endocrine and non-endocrine manifestations of MAS, and demonstrates that this very early presentation is potentially survivable. © 2016 Wiley Periodicals, Inc.

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Biallelic mutations in CYP26B1: A differential diagnosis for Pfeiffer and Antley–Bixler syndromes

Recently, a newly identified autosomal recessive skeletal dysplasia was described characterized by calvarial abnormalities (including cranium bifidum, coronal, and lambdoid synostosis), oligodactyly, femoral bowing, narrow thorax, small pelvic bones, and radiohumeral synostosis. In the two families described, a more severe phenotype led to in utero lethality in three siblings while in a single patient in a second family the phenotype was sufficiently mild to allow survival to 5 months of age. The disorder is caused by biallelic missense mutations in CYP26B1, which encodes for a cytochrome P450 enzyme responsible for the catabolism of retinoic acid in a temporally and spatially restricted fashion during embryonic development. Here, we provide the third family affected by the disorder and the first affected individual to survive beyond infancy. This woman homozygous for c.1303G>A; p.(Gly435Ser) in CYP26B1, which was associated with multisutural synostosis, radiohumeral synostosis, normal bone mineral density, and apparent intellectual disability, a phenotype with significant similarities to Antley–Bixler and Pfeiffer syndromes. © 2016 Wiley Periodicals, Inc.

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“It wasn't a disaster or anything”: Parents’ experiences of their child's uncertain chromosomal microarray result

Chromosomal microarray is an increasingly utilized diagnostic test, particularly in the pediatric setting. However, the clinical significance of copy number variants detected by this technology is not always understood, creating uncertainties in interpreting and communicating results. The aim of this study was to explore parents' experiences of an uncertain microarray result for their child. This research utilized a qualitative approach with a phenomenological methodology. Semi-structured interviews were conducted with nine parents of eight children who received an uncertain microarray result for their child, either a 16p11.2 microdeletion or 15q13.3 microdeletion. Interviews were transcribed verbatim and thematic analysis was used to identify themes within the data. Participants were unprepared for the abnormal test result. They had a complex perception of the extent of their child's condition and a mixed understanding of the clinical relevance of the result, but were accepting of the limitations of medical knowledge, and appeared to have adapted to the result. The test result was empowering for parents in terms of access to medical and educational services; however, they articulated significant unmet support needs. Participants expressed hope for the future, in particular that more information would become available over time. This research has demonstrated that parents of children who have an uncertain microarray result appeared to adapt to uncertainty and limited availability of information and valued honesty and empathic ongoing support from health professionals. Genetic health professionals are well positioned to provide such support and aid patients' and families' adaptation to their situation as well as promote empowerment. © 2016 Wiley Periodicals, Inc.

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In this issue

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Cover Image, Volume 170A, Number 8, August 2016

The cover image, by Lihadh Al Gazali et al., is based on the Original Article A recessive syndrome of intellectual disability, moderate overgrowth, and renal dysplasia predisposing to Wilms tumor is caused by a mutation in FIBP gene, DOI:10.1002/ajmg.a.37741.

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Gene therapy for severe combined immune deficiency poised for European approval

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Publication schedule for 2016

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Table of Contents, Volume 170A, Number 8, August 2016

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Facial malformation atlas aims to aid diagnosis of genetic disorders in patients of non-European descent

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Erythropoietin does not have effects on the ventilatory and pulmonary vascular response to acute hypoxia in men and women

Sustained and chronic hypoxia lead to a rise in pulmonary ventilation (hypoxic ventilatory response, HVR) and to an increase in pulmonary vascular resistance (hypoxic pulmonary vasoconstriction, HPV). In this study, we examined the effect of a clinical intravenous dose of recombinant human erythropoietin (rHuEPO,50 IU kg⁻¹) on the isocapnic HVR and HPV in 7 male and 7 female subjects by exposing them to hypoxia for 20 min (end-tidal PO₂ ∼ 50 mmHg) while measuring their ventilation and estimating pulmonary arterial pressure from the maximal velocity of the regurgitant jet over the tricuspid valve during systole (ΔPmax) with echocardiography. In placebo, after 5 and 20 min, men responded with a rise in ventilation by 0.0056 and 0.0023 l/min/kg/%SpO₂, respectively, indicating the presence of hypoxic ventilatory depression. In women, the rise in ventilation was 0.0067 and 0.0047 l/min/kg/%SpO₂, respectively. In both sexes, EPO did not alter these responses significantl . In placebo, mean ΔPmax rose by 6.1 ± 0.7 mmHg in men P = 0.035) and by 8.4 ± 1.4 mmHg in women (P = 0.020) during the hypoxic exposure whereby women had a ∼5 mmHg lower end-tidal PCO₂. EPO did not alter these responses: in men a rise in ΔPmax by 7.5 ± 1.1 mmHg (NS vs. placebo) and in women by 9.7 ± 2.2 mmHg (NS vs. placebo). We conclude that women tended to have a greater HPV in placebo and that a clinical dose of EPO has no effect on the HVR and HPV in either sex

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