bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary Hepatic Neuroendocrine Tumor
Authors: Bai Xia , Zhang Xia , Wang Xuemei
Published: November 2018

A 53-year-old man with tentative diagnosis of likely hepatocellular carcinoma underwent FDG PET/CT, which showed intense activity in both right lobe and caudate lobe of the liver. However, pathology examination from biopsy showed neuroendocrine tumor. He received transarterial chemoembolization and systemic chemotherapy. Posttherapy follow-up FDG PET/CT revealed no abnormal FDG activity in the liver.
Ectopic Papillary Thyroid Carcinoma Mimicking Esophageal Cancer in FDG PET
Authors: Gao Rui , Gao Shan , Jia Xi , Wang Hongyan , Zhang Guangjian
Published: November 2018

Ectopic papillary thyroid carcinoma (PTC) usually occurs along the cervical midline and was barely reported in FDG PET studies. We present a rare case of ectopic PTC within the esophagus with focal FDG activity on FDG PET in a 43-year-old woman who was previously diagnosed as having esophageal cancer based on the endoscopy and PET findings. Surgical pathology revealed the presence of PTC lesion within the muscular layer of the esophagus. Combining this with the negative imaging and laboratory results suggesting a normal thyroid gland led to a diagnosis of primary ectopic PTC.
Revisiting the Many Names of Freeman–Sheldon Syndrome
Authors: Poling Mikaela I. , Dufresne Craig R.
Published: November 2018

While officially designated as distal arthrogryposis type 2A, the condition commonly referred to as Freeman–Sheldon syndrome (FSS) also historically has been termed craniocarpotarsal dystrophy, whistling face syndrome, and craniocarpotarsal dysplasia and classified at different times as a skeletal dysplasia, nonprogressive myopathy, craniofacial syndrome, and distal arthrogryposis. Having previously provided evidence for FSS being a complex myopathic craniofacial syndrome with extra-craniofacial features in most patients, the rationale for revising the FSS eponym and supplanting the current official designation with a new one was based on considerations for educational usefulness, historical accuracy, communication fluency, and nosologic clarity underpinned by genetic, pathologic, and operative experience and outcomes.
Gridding Microsurgical Anatomy of Far Lateral Approach in the Three-Dimensional Model
Authors: Tang Ke , Qian Zeng-Hui , Feng Xu , Li Yang
Published: November 2018

Objective:

The far lateral craniotomy involves osteotomy of various portions of occipital condyle. Intracranial operation exposing clivus encounters complicated neurovascular anatomy. The aim of the present study was to make refinement for the anatomy of far lateral approach by gridding route in the 3-dimensional model.

Methods:

Computed tomography and magnetic resonance imaging data were used to construct 3-dimensional model containing osseous and neurovascular structures of skull base. Then, far lateral approach was simulated by triangular prism and divided into gridding surgical route. The relationship of surgical route and osseous and neurovascular structures was observed. Measurement of volume was performed to evaluate surgical exposure.

Results:

Observation of 3-dimensional model showed bony drilling of far lateral approach started with the occipital condyle and passed through the lateral edge of foramen magnum. The cerebellum and medulla oblongata were exempted from the surgical route exposing clivus. The anatomy variances of operative space, osseous, and neurovascular structures in the gridding route were displayed clearly and compared objectively.

Conclusion:

The gridding operative spaces for the far lateral approach are useful to disclose the detailed discrepancy in the different surgical region. The volumetric measurement provides quantified information to facilitate a better understanding of the anatomy variance.
Tranexamic Acid Decreases Blood Transfusion Burden in Open Craniosynostosis Surgery Without Operative Compromise
Authors: Lu Victor M. , Goyal Anshit , Daniels David J.
Published: November 2018

In the surgical management of craniosynostosis, there is a high red blood cell (RBC) transfusion burden due to the small blood volume of the patients combined with significant blood loss that can occur with open surgery (OS). Tranexamic acid (TXA) is an antifibrinolytic which has been shown to decrease such a burden in particular surgeries. The aim of this study was to compare the operative outcomes of craniosynostosis OS which did and did not utilize TXA. Searches of 7 electronic databases from inception to February 2018 were conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. There were 206 articles screened against selection criteria for inclusion. Relevant data were extracted and analyzed using meta-analysis of proportions. A total of 9 comparative studies were included for meta-analysis. Compared with the control cohort, craniosynostosis OS utilizing TXA demonstrated significantly lower intraoperative RBC transfusion volumes (mean difference, −8.25 mL/kg; P < 0.001), blood loss (mean difference, −10.96 mL/kg; P < 0.001) and postoperative RBC transfusion incidence (odds ratio, OR, 0.12; P = 0.005). Fresh frozen plasma and crystalloid transfusion, operation time, length of stay, and complications were not significantly different with TXA use. Based on the comparative evidence currently available, TXA significantly decreased RBC transfusion burden during craniosynostosis OS without operative compromise. There is significant heterogeneity in reported TXA regimes in the literature. Future studies that are larger, randomized, and account for these factors will further enhance the authors’ understanding.
Biological Aging Parameters Can Be Improved After Autologous Adipose-Derived Stem Cell Injection
Authors: Son Hye-Youn , Bae Hahn-Sol , Son Youngsook , Kim Sundong , Hong Hyun-Sook , Park Ji-Ung
Published: November 2018

Biological aging (BA) is a comprehensive assessment tool for elderly persons. The authors aimed to develop a rat model that can be used to assess BA by evaluating various blood, biochemical, and hormonal parameters and demonstrate that the intravenous administration of autologous adipose-derived stem cells (ADSCs) improves BA. Twelve elderly (aged 20 months) male Sprague–Dawley rats were used in this study and divided into 2 groups: autologous ADSC administration (n = 6) and saline administration (n = 6). The complete blood count, biochemical and hormonal parameters, and antioxidant potential were evaluated before harvesting the rat inguinal fat tissue and intravenous ADSC administration as well as at 1, 3, and 5 weeks after ADSC administration. Adipose-derived stem cells administration regulated blood content, biochemical parameters, renal function, and antioxidant enzymes in elderly rats. Furthermore, changes in several hormonal levels were identified in the ADSC administration group compared with the saline administration group. An assessment model of BA in elderly rats was successfully developed after the intravenous administration of autologous ADSCs. The authors suggest that intravenously injected ADSC treatment may be a valuable method to improve BA.
Trichoepithelioma Misdiagnosed as Basal Cell Carcinoma
Authors: Kang Kyo Joon , Seo Bomie Florence , Shin Jongweon , Kwon Ho , Byeon Jun Hee , Jung Sung-No
Published: November 2018

Trichoepithelioma is a benign tumor which can be easily confused with basal cell carcinoma. Since both tumors are histologically similar, it is important to distinguish them correctly as the courses for treatment are very different. Basal cell carcinoma is malignant; therefore, it requires total surgical excision, including a wide healthy margin. In contrast, trichoepithelioma requires only simple excision. A study involving a 69-year-old woman with a simple mass on the nasal tip was described in this study. On examination, a single skin-colored, round protruding mass (approximately 0.5 × 0.5 cm) was observed. Simple excision was performed and basal cell carcinoma was diagnosed at the initial biopsy. However, clinically, we considered it to be a benign tumor; therefore, we sought a histologic reconfirmation. Consequently, trichoepithelioma was diagnosed on histopathologic examination. When a small, round protruding simple mass is histologically diagnosed to be a basal cell carcinoma, it is important to suspect trichoepithelioma and seek histologic reconfirmation.
Cirrhotic Patients Admitted to the ICU With Septic Shock: Factors Predicting Short and Long-Term Outcome
Authors: Baudry Thomas , Hernu Romain , Valleix Baptiste , Jahandiez Vincent , Faucher Etienne , Simon Marie , Cour Martin , Argaud Laurent
Published: November 2018

Cirrhotic patients with septic shock have a poor prognosis in ICU compared to general population of critically ill patients. Little is known about long-term outcome in these patients. We performed a retrospective analysis of a prospective cohort of cirrhotic patients with septic shock. The aim of this study was to describe both short and long-term outcomes and to evaluate factors predicting mortality. Data from 149 patients were analyzed (mean age: 60 ± 11 years, sex ratio: 2.4). Mortality rate in the ICU was 54% and at 1 year it was 73%. Among factors associated with adverse outcome, independent factors predicting ICU mortality were early need for renal replacement therapy (odds ratios, OR 13.95, 95% confidence interval, CI 3.30; 59.03) and arterial lactate >5 mmol.L−1 (OR 7.27, 95% CI 2.92; 18.10), and early use of mechanical ventilation (OR 3.05, 95% CI 1.08; 8.58). For 1-year mortality, independent prognostic factors were the need for renal replacement therapy during ICU stay (OR 9.60, 95% CI 2.90; 31.82), prothrombin time ≤40% (OR 3.47, 95% CI 1.43; 8.43), and Charlson score (OR 1.36 per point, 95% CI 1.11; 1.67). The results emphasize the poor prognosis of cirrhotic patients with septic shock admitted to the ICU. The need for organ supports appears to be a better predictor of short-term outcome than the underlying hepatic disease. Renal replacement therapy is associated with both short and long-term outcomes.
Preparing the Next Generation of Code Blue Leaders Through Simulation: What's Missing?
Authors: Sachedina Ayaaz K. , Blissett Sarah , Remtulla Alliya , Sridhar Kumar , Morrison Deric
Published: November 2018

Introduction

Despite the increasing reliance on simulation to train residents as code blue leaders, the perceived role and effectiveness of code blue simulations from the learners' perspective have not been explored. A code blue Simulation Program (CBSP), developed based on evidence-based simulation principles, was implemented at our institution. We explored the role of simulation in code blue training and the differences between real and simulated code blues from the learner perspective.

Methods

Using a thematic analysis approach and a purposeful sampling strategy, residents who participated in the CBSP were invited to participate in one of the three focus groups. Data were collected through small group discussions guided by semistructured interviews. The interviews were audio-recorded and transcribed. Interview transcripts were coded to assess underlying themes.

Results

Thematic analysis revealed that participants believed that the CBSP enhanced preparedness by capturing aspects of real codes (eg, inclusion of precode scenarios with awake patients, lack of readily available information) and facilitating automatization of code blue processes. Despite efforts to develop a high-fidelity simulation, participants noted that they experienced more anxiety, observed more chaos in the environment, and encountered different communication challenges in real codes.

Conclusions

The CBSP enhanced resident preparedness to serve as code blue leaders. Learners highlighted that they valued the CBSP; however, differences remain between simulated and real codes that could be addressed to enhance the fidelity of future simulations.
Electroclinical Features of Generalized Paroxysmal Fast Activity in Typical Absence Seizures
Authors: Bansal Lalit , Vargas Collado Lines , Pawar Kailash , Nagesh Deepti , Ilyas Mohammed , Hall Ara , Kinnaman Brad , Abdelmoity Ahmed
Published: November 2018

Purpose:

Generalized paroxysmal fast activity (GPFA) is a diffuse, paroxysmal, frontal predominant activity described in patients with generalized epilepsies. Studies specifically focusing on electroclinical features of typical absence seizures in children have not reported any GPFA-like features. We sought to identify GPFA in children with typical absence seizures, study its incidence, characteristic electroclinical features, and effect on their epilepsy.

Methods:

We performed a retrospective review of electroencephalograms of children with diagnosis of absence epilepsy. A total of 173 subjects were identified. In subjects with GPFA on their electroencephalograms, GPFA characteristics were collected (i.e., predominant location, duration, amplitude, frequency, provocation factors, and if GPFA was followed by spike-wave discharges). In GPFA-positive subjects, further data sets were collected examining their demographics, duration of epilepsy, and pharmacoresponsiveness to epilepsy.

Results:

Generalized paroxysmal fast activity was identified in 10 subjects (5.78%) with female to male ratio of 9:1. Median age of subjects was 17 years, and median duration of illness was 9.5 years. Mean maximum GPFA amplitude was 88.3 μV with posterior predominance in 9/10 subjects. Generalized paroxysmal fast activity frequency ranged between 11 and 20 Hz with duration of 1 to 4 seconds. Generalized paroxysmal fast activity was provoked with eye closure, hyperventilation, and photic stimulation. Antiseizure medications had no effect on GPFA, and epilepsy was well controlled in most subjects.

Conclusions:

Generalized paroxysmal fast activity is uncommon in children with typical absence seizures and has medium voltage, posterior predominance, and marked female preponderance. Generalized paroxysmal fast activity is seen during both pharmacoresponsive and drug-resistant epilepsy, and is not affected by antiseizure medications. It may serve as an independent marker of lifelong epilepsy.
Point-of-Care Ultrasound Use in Neonatal Peripheral Intravenous Extravasation Injuries
Authors: Boyar Vita , Galiczewski Colleen , Kurepa Dalibor
Published: November 2018

PURPOSE:

The primary aim of this study was to examine and describe peripheral intravenous extravasation (PIVE) injuries using point-of-care ultrasound (POC-US). A secondary aim was to define skin tissue changes before and after hyaluronidase application using POC-US.

DESIGN:

Case series design.

SUBJECTS AND SETTING:

We report on 10 neonates with stage 3 or 4 PIVE who were studied clinically and with POC-US. All infants were studied during the December 2015 to September 2016 period in a large academic neonatal intensive care unit.

METHODS:

Initially, neonates with PIVE were staged using 3 criteria: physical findings, nature of the infusate, and the size of the injury. Next, we described different ultrasound appearances of the tissue injury in PIVE based on the type of the infusate (clear fluid, blood, or both). We then located the largest PIVE pocket and measured the skin elevation over it. Skin elevation ratio was measured at 3 time points: before hyaluronidase injection followed by 3 to 6 hours and 24 hours after hyaluronidase therapy. Each ultrasound examination of the skin injury was staged (severe, moderate, mild, or minimal) based on the skin elevation ratio obtained. In addition, we described changes in the skin using ultrasound before and after hyaluronidase treatment.

RESULTS:

Three types of ultrasound images based on the type of the extravasated fluid were described in detail. Based on the initial ultrasound measurements of the skin elevation ratio, 6 infants were staged with severe PIVE and 4 were staged as moderate PIVE. Finally, POC-US was used to describe the tissue changes before and after hyaluronidase injection.

CONCLUSIONS:

Point-of-care ultrasound may offer more structured and objective staging of PIVE injuries due to direct visualization of the skin tissue. This method needs to be further studied and introduced as a practical tool to complement physical examination of PIVE injuries.
Reducing Pressure Injuries in a Pediatric Cardiac Care Unit
Authors: Kriesberg (Lange) Chelsea P. , Little Jeanne Marie , Mohr Lynn , Kato Kimberly
Published: November 2018

The purpose of this quality improvement project was to develop an evidence-based protocol designed for pressure injury prevention for neonates and children in a pediatric cardiac care unit located in the Midwestern United States. The ultimate goal of the project was dissemination across all pediatric critical care and acute care inpatient arenas, but the focus of this initial iteration was neonates and children requiring cardiac surgery, extracorporeal support in the form of extracorporeal membranous oxygenation and ventricular assist devices in the cardiac care unit, or cardiac transplantation. A protocol based upon the National Pressure Ulcer Advisory Panel guidelines was developed and implemented in the pediatric cardiac care unit. Pediatric patients were monitored for pressure injury development for 6 months following protocol implementation. During the 40-month preintervention period, 60 hospital-acquired pressure injuries (HAPIs) were observed, 13 of which higher than stage 3. In the 6-month postintervention period, we observed zero HAPI greater than stage 2. We found that development and use of a standardized pressure injury prevention protocol reduced the incidence, prevalence, and severity of HAPIs among patients in our pediatric cardiac care unit.
Patients With Temporary Ostomies
Authors: Mohammed Ilyas Mohammed Iyoob , Haggstrom David A. , Maggard-Gibbons Melinda A. , Wendel Christopher S. , Rawl Susan , Schmidt Christian Max , Ko Clifford Y. , Krouse Robert S.
Published: November 2018

PURPOSE:

The purpose of this study was to describe clinical outcomes of patients with temporary ostomies in 3 Veterans Health Administration hospitals.

DESIGN:

Retrospective descriptive study, secondary analysis.

SAMPLE AND SETTING:

Veterans with temporary ostomies from 3 Veterans Health Administration hospitals who were enrolled in a previous study. The sample comprised 36 participants all were male. Their mean age was 67.05 ± 9.8 years (mean ± standard deviation). Twenty patients (55.6%) had ileostomies and 16 patients (44.4%) had colostomies.

METHODS:

This was a secondary analysis of data collected using medical record data. Variables examined included etiology for creation and type of ostomy, health-related quality of life, time to reversal, reasons for nonreversal, postoperative complications after reversal, and mortality in the follow-up period.

RESULTS:

Colorectal cancer and diverticular disease were the main reasons for temporary stoma formation. The reversal rate was 50%; the median time to reversal was 9 months in our sample; temporary ileostomies were reversed more often than temporary colostomies (P = .18). Comorbid conditions were identified as the main reason for nonreversal. Mortality was not significantly different between the reversal and nonreversal groups. No significant differences were reported with health-related quality-of-life parameters between reversal and nonreversal groups.

CONCLUSIONS:

This study identified that the proportion of temporary ostomies was limited to 50%. Complications during the index operation, medical comorbidities, and progression of cancer are the main reasons for nonreversal of temporary stomas. Study findings should be included in the counseling of patients who are likely to get intestinal stomas with temporary intention, and during consideration for later reversal of a stoma.
Rectal Trumpet–Associated Hemorrhage in the Intensive Care Unit
Authors: Glass Daniel , Huang David T. , Dugum Mohannad , Chintamaneni Preethi , Cua Sarah , Saul Melissa , Marsh Wallis , Al-Khafaji Ali
Published: November 2018

The rectal trumpet (RT) is a nasopharyngeal airway device that is inserted into the rectum for management of fecal incontinence. No published data exist on adverse events caused by the use of an RT. The purpose of this quality improvement project was to determine the rate of RT-associated hemorrhage among patients treated with an RT in our transplant intensive care unit (TICU). This quality improvement initiative and retrospective medical record review included all patients (N = 3933) cared for in a single specialty intensive care unit at a tertiary academic medical center between January 1, 2014, and May 31, 2016. We estimate that approximately 400 patients were treated with an RT. We found 3 possible and 9 probable cases of RT-associated hemorrhage, resulting in an estimated incident rate of 3% among RT-treated patients. All of these patients underwent invasive procedures for hemostasis. They received a mean of 4.9 units of packed red blood cell transfusions, and 9 experienced hypotension. Eight out of the 9 probable RT-associated hemorrhage patients experienced hemorrhage only after greater than 7 days of treatment with an RT. Following this initiative, RT use was banned in our TICU. The use of RTs can cause hemorrhage with clinically significant consequences.
Incontinence-Associated Dermatitis (IAD)
Authors: Johansen Edda , Bakken Linda N. , Duvaland Elisabeth , Faulstich Jürgen , Hoelstad Hanne L. , Moore Zena , Vestby Eva Marie , Beeckman Dimitri
Published: November 2018

PURPOSE:

The aim of this study was to investigate the prevalence and severity of incontinence-associated dermatitis (IAD) and associated factors in acute care settings in Southeast Norway.

DESIGN:

Descriptive, multisite epidemiologic survey.

SUBJECTS AND SETTING:

The study setting was 29 wards across 4 hospitals, in a hospital trust in the southeast of Norway. Data were collected from 340 patients (age ≥18 years). More than half (56.2%) were 70 years or older (median age category 70-79 years) and 53.3% were male.

METHODS:

Data collection was conducted in parallel with a pressure injury prevalence study undertaken in 2016. A modified Pressure Injury Prevalence Minimum Data Set, including documentation of fecal or urinary incontinence, use of indwelling fecal collection system or urinary catheter, and presence of IAD, was completed. RNs participating in the study were trained by the researchers on skin assessment and data extraction from the electronic medical record. Descriptive statistics were used for prevalence figures; the Kruskal-Wallis and χ2 tests were used to determine associated factors.

RESULTS:

Analysis revealed that 16.5% (56 out of 340) of the sample were incontinent. The prevalence of IAD in the total population was 7.6% (26 out of 340). The prevalence of IAD was 29% (16 out of 56) among patients with urinary or fecal incontinence. Of those identified with IAD, 5.2% (18 out of 340) had category 1 (red intact skin) and 2.4% (8 of 340) had category 2 (red skin with breakdown). Bivariate analysis revealed that fecal incontinence (P < .001), immobility (P < .01), and 70 years or older (P < .03) were associated with IAD.

CONCLUSIONS:

The overall prevalence (patients with and without incontinence) of IAD was lower than reported in prior studies; frequent use of indwelling urinary catheters and a relatively low prevalence of incontinence may explain this finding. Similar to prior studies, almost 1 in 3 patients who were incontinent suffered from IAD, showing a need for evidence-based guidelines to prevent IAD in hospitalized patients. Findings suggest that particular attention should be given to prevent IAD among patients with fecal incontinence patients, 70 years and older, and those with immobility.
Brain X chromosome inactivation is not random and can protect from paternally inherited neurodevelopmental disease
Authors: Szelenyi Eric R , Fisenne Danielle , Knox Joseph E , Harris Julie A , Gornet James A , Palaniswamy Ramesh , Kim Yongsoo , Venkataraju Kannan Umadevi , Osten Pavel
Published: November 2018

Non-random (skewed) X chromosome inactivation (XCI) in the female brain can ameliorate X-linked phenotypes, though clinical studies typically consider 80-90% skewing favoring the healthy allele as necessary for this effect1–10. Here we quantify for the first time whole-brain XCI at single-cell resolution and discover a preferential inactivation of paternal to maternal X at ∼60:40 ratio, which surprisingly impacts disease penetrance. In Fragile-X-syndrome mouse model, Fmr1-KO allele transmitted maternally in ∼60% brain cells causes phenotypes, but paternal transmission in ∼40% cells is unexpectedly tolerated. In the affected maternal Fmr1-KO(m)/+ mice, local XCI variability within distinct brain networks further determines sensory versus social manifestations, revealing a stochastic source of X-linked phenotypic diversity. Taken together, our data show that a modest ∼60% bias favoring the healthy allele is sufficient to ameliorate X-linked phenotypic penetrance, suggesting that conclusions of many clinical XCI studies using the 80-90% threshold should be re-evaluated. Furthermore, the paternal origin of the XCI bias points to a novel evolutionary mechanism acting to counter the higher rate of de novo mutations in male germiline11–16. Finally, the brain capacity to tolerate a major genetic lesion in ∼40% cells is also relevant for interpreting other neurodevelopmental genetic conditions, such as brain somatic mosaicism.
Stem cell differentiation trajectories inHydraresolved at single-cell resolution
Authors: Siebert Stefan , Farrell Jeffrey A. , Cazet Jack F. , Abeykoon Yashodara L. , Primack Abby S. , Schnitzler Christine E. , Juliano Celina E.
Published: November 2018

The adultHydrapolyp continuously renews all of its cells using three separate stem cell populations, but the genetic pathways enabling homeostatic tissue maintenance are not well understood. We used Drop-seq to sequence transcriptomes of 24,985 singleHydracells and identified the molecular signatures of a broad spectrum of cell states, from stem cells to terminally differentiated cells. We constructed differentiation trajectories for each cell lineage and identified the transcription factors expressed along these trajectories, thus creating a comprehensive molecular map of all developmental lineages in the adult animal. We unexpectedly found that neuron and gland cell differentiation transits through a common progenitor state, suggesting a shared evolutionary history for these secretory cell types. Finally, we have built the first gene expression map of theHydranervous system. By producing a comprehensive molecular description of the adultHydrapolyp, we have generated a resource for addressing fundamental questions regarding the evolution of developmental processes and nervous system function.
Dense connectomic reconstruction in layer 4 of the somatosensory cortex
Authors: Motta Alessandro , Berning Manuel , Boergens Kevin M. , Staffler Benedikt , Beining Marcel , Loomba Sahil , Schramm Christian , Hennig Philipp , Wissler Heiko , Helmstaedter Moritz
Published: November 2018

The dense circuit structure of the mammalian cerebral cortex is still unknown. With developments in 3-dimensional (3D) electron microscopy, the imaging of sizeable volumes of neuropil has become possible, but dense reconstruction of connectomes from such image data is the limiting step. Here, we report the dense reconstruction of a volume of about 500,000 μm3from layer 4 of mouse barrel cortex, about 300 times larger than previous dense reconstructions from the mammalian cerebral cortex. Using a novel reconstruction technique, FocusEM, we were able to reconstruct a total of 0.9 meters of dendrites and about 1.8 meters of axons investing only about 4,000 human work hours, about 10-25 times more efficient than previous dense circuit reconstructions. We find that connectomic data alone allows the definition of inhibitory axon types that show established principles of synaptic specificity for subcellular postsynaptic compartments. We find that also a fraction of excitatory axons exhibit such subcellular target specificity. Only about 35% of inhibitory and 55% of excitatory synaptic subcellular innervation can be predicted from the geometrical availability of membrane surface, revoking coarser models of random wiring for synaptic connections in cortical layer 4. We furthermore find evidence for enhanced variability of synaptic input composition between neurons at the level of primary dendrites in cortical layer 4. Finally, we obtain evidence for Hebbian synaptic weight adaptation in at least 24% of connections; at least 35% of connections show no sign of such previous plasticity. Together, these results establish an approach to connectomic phenotyping of local dense neuronal circuitry in the mammalian cortex.
Does batrachotoxin autoresistance co-evolve with toxicity inPhyllobatespoison-dart frogs?
Authors: Márquez Roberto , Ramírez-Castañeda Valeria , Amézquita Adolfo
Published: November 2018

Toxicity is widespread among living organisms, and evolves as a multimodal phenotype. Part of this phenotype is the ability to avoid self-intoxication (autoresistance). Evolving toxin resistance can involve fitness tradeoffs, so autoresistance is often expected to evolve gradually and in tandem with toxicity, resulting in a correlation between the degrees of toxicity and autoresistance among toxic populations. We investigate this correlation inPhyllobatespoison frogs, notorious for secreting batrachotoxin (BTX), a potent neurotoxin that targets sodium channels, using ancestral sequence reconstructions of BTX–sensing areas of the muscular voltage-gated sodium channel. Reconstructions suggest that BTX resistance arose at the root ofPhyllobates, coinciding with the evolution of BTX secretion. After this event little or no further evolution of autoresistance seems to have occurred, despite large increases in toxicity throughout the history of these frogs. Our results therefore provide no evidence in favor of an evolutionary correlation between toxicity and autoresistance, which conflicts with previous work. Future research on the functional costs and benefits of mutations putatively involved in BTX resistance, as well as their prevalence in natural populations should shed light on the evolutionary mechanisms driving the relationship between toxicity and autoresistance inPhyllobatesfrogs.
The human claustrum is functionally connected to cognitive networks and involved in cognitive control
Authors: Krimmel Samuel R. , White Michael G. , Panicker Matthew H. , Barrett Frederick S. , Mathur Brian N. , Seminowicz David A.
Published: November 2018

The claustrum is among the most highly connected structures in the mammalian brain. However, the function of the claustrum is unknown, which is due to its peculiar anatomical arrangement. Here, we use resting state and task functional magnetic resonance imaging (fMRI) to elucidate claustrum function in human subjects. We first describe a method to reveal claustrum signal with no linear relationship with adjacent regions. We applied this approach to resting state functional connectivity (RSFC) analysis of the claustrum at high resolution (1.5 mm isotropic voxels) using a 7T dataset (n=20) and a separate 3T dataset for replication (n=35). We then assessed claustrum activation during performance of a cognitive task, the multi-source interference task, at 3T (n=33). Extensive functional connectivity was observed between claustrum and cortical regions associated with cognitive control, including anterior cingulate, prefrontal and parietal cortices. Cognitive task performance was associated with widespread activation and deactivation that overlapped with the cortical areas showing functional connectivity to the claustrum. Furthermore, the claustrum was significantly activated at the onset of the difficult condition of the task, but not during the remainder of the difficult condition. These data suggest that the claustrum can be functionally isolated with fMRI, and that it is involved in cognitive control in humans independent of sensorimotor processing.

Highlights

Removing signal from neighboring structures isolates claustrum BOLD signal at 7T and 3T field strength

Claustrum is extensively functionally connected with cortex, including cognitive networks

Claustrum is activated at the onset of a cognitive conflict task

Claustrum may be involved in cognition independent of sensorimotor processing
Fast, multicolor 3-D imaging of brain organoids with a new single-objective two-photon virtual light-sheet microscope
Authors: Rakotoson Irina , Delhomme Brigitte , Djian Philippe , Deeg Andreas , Brunstein Maia , Seebacher Christian , Uhl Rainer , Ricard Clément , Oheim Martin
Published: November 2018

Human inducible pluripotent stem cells (hiPSCs) hold a large potential for disease modeling. hiPSC-derived human astrocyte and neuronal cultures permit investigations of neural signaling pathways with subcellular resolution. Combinatorial cultures, and three-dimensional (3-D) embryonic bodies enlarge the scope of investigations to multi-cellular phenomena. A the highest level of complexity, brain organoids that – in many aspects – recapitulate anatomical and functional features of the developing brain permit the study of developmental and morphological aspects of human disease. An ideal microscope for 3-D tissue imaging at these different scales would combine features from both confocal laser-scanning and light-sheet microscopes: a micrometric optical sectioning capacity and sub-micrometric spatial resolution, a large field of view and high frame rate, and a low degree of invasiveness, i.e., ideally, a better photon efficiency than that of a confocal microscope. In the present work, we describe such an instrument that belongs to the class of two-photon (2P) light-sheet microsocpes. Its particularity is that – unlike existing two- or three-lens designs – it is using a single, low-magnification, high-numerical aperture objective for the generation and scanning of a virtual light sheet. The microscope builds on a modified Nipkow-Petran spinning-disk scheme for achieving wide-field excitation. However, unlike the common Yokogawa design that uses a tandem disk, our concept combines micro lenses, dichroic mirrors and detection pinholes on a single disk. This design, advantageous for 2P excitation circumvents problems arising with the tandem disk from the large wavelength-difference between the infrared excitation light and visible fluorescence. 2P fluorescence excited in by the light sheet is collected by the same objective and imaged onto a fast sCMOS camera. We demonstrate three-dimensional imaging of TO-PRO3-stained embryonic bodies and of brain organoids, under control conditions and after rapid (partial) transparisation with triethanolamine and /ormamide (RTF) and compare the performance of our instrument to that of a confocal microscope having a similar numerical aperture. 2P-virtual light-sheet microscopy permits one order of magnitude faster imaging, affords less photobleaching and permits better depth penetration than a confocal microscope with similar spatial resolution.
Corporeal Commotions: St Faustina and the Transnational Evolution of her Cult across the Twentieth Century
Authors: Harris Alana
Published: November 2018

This article provides the first scholarly exploration of the hagiographical representations and modern mysticism of St Faustina — a Polish nun who from 1931 had a series of visions of Christ who instructed her to have a devotional image painted and to institute a series of rosary‐based prayers. It examines the visual, material, and corporeal practices associated with the transnational cult to the Merciful Heart of Jesus and excavates the ways in which the embodied and holistic intercessory strategies employed within this important strand of contemporary Catholic spirituality parallel, but also extend upon, the well‐established seventeenth‐century devotional to the Sacred Heart of Jesus. It argues that the cult's theological flexibility and practical malleability, alongside the premium on corporeality within contemporary religiosity, has ensured its delocalisation from its Polish genesis and adoption well beyond the Polish diaspora. Drawing upon the lived religious experiences of a number of St Faustina's clients, often centred on healing and the dying, and exploring the evolving devotion to the saint through shrines as well as online, this article illuminates the contemporaneous and traditional impulses at play within this new extra‐liturgical, which has been designated “the most dynamically developing devotion in the Christian world.”
Three‐dimensional navigation‐guided thoracoscopic combined subsegmentectomy for intersegmental pulmonary nodules
Authors: Wu Wei‐Bing , Xia Yang , Pan Xiang‐Long , Wang Jun , He Zhi‐Cheng , Xu Jing , Wen Wei , Xu Xin‐Feng , Zhu Quan , Chen Liang
Published: November 2018

Background

Extended or combined segmentectomies are usually adapted for intersegmental pulmonary nodules. This study explored precise combined subsegmentectomy (CSS) under the guidance of three‐dimensional computed tomography bronchography and angiography (3D‐CTBA).

Methods

The definition of a pulmonary intersegmental nodule was based on a minimum distance between the nodule and the involved intersegmental veins in the preoperative 3D‐CTBA being less than the size of the nodule. Centering on the involved intersegmental vein, two adjacent subsegments belonging to the different segments were combined as a resected unit.

Results

We retrospectively reviewed the records of 47 patients (mean age 53.6 ± 12.3, range: 26–81 years) who underwent CSS. Thirty‐nine (83.0%) nodules were involved in most intersegmental locations of the upper lobes; the remainder in the lower lobes. The mean nodule size was 0.86 ± 0.32 cm; the mean margin width was 2.20 ± 0.38 cm. Pathological stages included: Tis (8 cases), T1mi (16), IA1 (T1aN0M0, 13), and IA2 (T1bN0M0, 5). Pathological diagnoses included: invasive adenocarcinoma (18 cases), minimally invasive adenocarcinoma (16), adenocarcinoma in situ (8), atypical adenomatous hyperplasia (3), and benign (2). The average operative duration was 190.8 ± 54.9 minutes; operative hemorrhage was 42.7 ± 23.0 mL; 5.8 ± 2.8 lymph nodes dissected had not metastasized; the duration of postoperative chest tube drainage was 3.0 ± 1.8 days; and the postoperative hospital stay was 5.3 ± 2.4 days.

Conclusions

Under 3D navigation, thoracoscopic CSS is a safe technique for intersegmental nodules, sparing more pulmonary parenchyma and ensuring safe margins to achieve anatomical resection.
Does hypermethylation of CpG island in the promoter region of the E‐cadherin gene increase the risk of lung cancer? A meta‐analysis
Authors: Sun Zhenfeng , Liu Gongzhe , Xu Ning
Published: November 2018

Background

Hypermethylation of the CpG island in the promoter regions of tumor suppressor genes is common in the cancer tissue of non‐small cell lung cancer (NSCLC) patients. Epithelial cadherin (E‐cadherin) is a classic tumor suppressor gene of the cadherin superfamily and its promoter region is usually hypermethylated in malignant carcinomas. However, whether hypermethylation of the CpG island in the promoter region of E‐cadherin increases the risk of lung cancer is unknown. We conducted a meta‐analysis of E‐cadherin gene promoter methylation status in cancer tissue (CT) and autologous controls (AC).

Methods

Electronic databases were searched for E‐cadherin gene promoter methylation and NSCLC. The hypermethylation status between CT and AC of NSCLC patients were compared and pooled by random or fixed effect models according to statistical heterogeneity across the included studies.

Results

Eleven publications relevant to E‐cadherin gene promoter hypermethylation and lung cancer risk were identified and included. E‐cadherin gene promoter hypermethylation frequency in CT and AC was 0.32 (95% confidence interval [CI] 0.22–0.41) and 0.12 (95% CI 0.04–0.20), respectively, with statistical difference (P < 0.05). Significant statistical heterogeneity was found across the 11 studies (I2 = 54.5, P < 0.05). The data was pooled through a random effect model with an odds ratio of 4.21 (95% CI 2.33–7.58) in CT compared to AC.

Conclusion

The frequency of E‐cadherin promoter hypermethylation in CT is significantly higher than in AC, indicating that promoter hypermethylation of E‐cadherin plays an important role in NSCLC carcinogenesis.
Impacts of forest management type and season on soil carbon fluxes in Eastern Mau Forest, Kenya
Authors: Tarus George K. , Kirui Bernard K. , Obwoyere Gilbert
Published: November 2018

The value of ecosystems functions performed by forests in the climate change era has prompted increasing attention towards assessment of carbon stocks and fluxes in tropical forests. The aim of this study was to understand how forest management approaches and environmental controls impacted on soil CO2 efflux in a tropical Eastern Mau forest which is one of the blocks of the greater Mau complex in Kenya. Nested experimental design approach was employed where 32 plots were nested into four blocks (disturbed natural, undisturbed natural, plantation and glades). In 10 m2 plots, data were collected on soil CO2 efflux, soil temperature and soil moisture using soda lime methods, direct measurement and proxy techniques, respectively. There was significant forest management type effect (F3,127 = 3.01, p = 0.033) and seasonality effect (t test = 3.31, df = 1, p < 0.05) on mean soil CO2 efflux. The recorded mean soil CO2 efflux levels were as follows: plantation forest (9.219 ± 3.067 g C M−2 day−1), undisturbed natural forest (8.665 ± 4.818 g C M−2 day−1), glades (8.592 ± 3.253 g C M−2 day−1) and disturbed natural forest (7.198 ± 3.457 g C M−2 day−1). The study concludes that managing a forest in plantation form is primarily responsible for forest soil CO2 efflux levels due to aspects such as increased microbial activity and root respiration. However, further studies are required to understand the role and impact of soil CO2 efflux on the greater forest carbon budget.
BLT1 signaling in epithelial cells mediates allergic sensitization via promotion of IL‐33 production
Authors: Xiong Yingluo , Cui Xinyi , Li Wenjing , Lv Jiaoyan , Du Lixia , Mi Wenli , Li Huabin , Chen Zhengrong , Leng Qibin , Zhou Hong , He Rui
Published: November 2018

Background

Epithelial cells (ECs) play a crucial role in allergic sensitization to inhaled protease allergens by instructing type 2 innate lymphoid cells (ILC2) and dendritic cells (DCs) via release of pro‐type 2 cytokines, particularly interleukin‐33 (IL‐33). Leukotriene B4 (LTB4) is a well‐known leukocyte chemoattractant via engagement of its receptor 1 (BLT1). However, the role of LTB4‐BLT1 axis in allergic sensitization via activation of ECs is still unknown.

Methods

We evaluated the effect of LTB4‐BLT1 axis on IL‐33 expression and ILC2 activation in vivo and in vitro. Chimeric mice were established to evaluate the contribution of BLT1 expression in nonimmune cell to allergic sensitization.

Results

Genetical or pharmacological interruption of LTB4‐BLT1 axis during sensitization phase markedly reduced papain‐induced IL‐33 expression, decreased ILC2 activation and DC migration, thereby impairing the priming of allergic Th2 responses. Furthermore, papain inhalation induced a rapid release of LTB4 preceding IL‐33, and intranasal administration of LTB4 to naïve WT mice significantly increased IL‐33 expression and ILC2 activation in lung, which was absent in Il33−/− or Ltb4r1−/− mice. Furthermore, BLT1 was expressed in primary mouse ECs or normal human bronchial ECs (NHBE), and papain induced LTB4 release by NHBE, which in turn amplified IL‐33 production dependent on Akt activation via BLT1. Consequently, bone marrow chimeric mice lacking BLT1 in radio‐resistant structural cells failed to develop allergic lung inflammation to papain.

Conclusion

Our study reveals a functional role of LTB4‐BLT1 axis in nonimmune cells, most likely lung ECs, in controlling allergic sensitization as an upstream regulator of IL‐33.
Mast cell disorders: From infancy to maturity
Authors: Wilcock Amy , Bahri Rajia , Bulfone‐Paus Silvia , Arkwright Peter D.
Published: November 2018

Mast cells are typically linked to immediate hypersensitivity and anaphylaxis. This review looks beyond this narrow role, focusing on how these cells have evolved and diversified via natural selection promoting serine protease gene duplication, augmenting their innate host defense function against helminths and snake envenomation. Plasticity of mast cell genes has come at a price. Somatic activating mutations in the mast cell growth factor KIT gene cause cutaneous mastocytosis in young children and systemic mastocytosis with a more guarded prognosis in adults who may also harbor other gene mutations with oncogenic potential as they age. Allelic TPSAB1 gene duplication associated with higher basal mast cell tryptase is possibly one of the commonest autosomal dominantly inherited multi‐system diseases affecting the skin, gastrointestinal tract, circulation and musculoskeletal system. Mast cells are also establishing a new‐found importance in severe asthma, and in remodeling of blood vessels in cancer and atherosclerotic vascular disease. Furthermore, recent evidence suggests that mast cells sense changes in oxygen tension, particularly in neonates, and that subsequent degranulation may contribute to common lung, eye, and brain diseases of prematurity classically associated with hypoxic insults. One hundred and forty years since Paul Ehrlich's initial description of “mastzellen,” this review collates and highlights the complex and diverse roles that mast cells play in health and disease.
High levels of butyrate and propionate in early life are associated with protection against atopy
Authors: Roduit Caroline , Frei Remo , Ferstl Ruth , Loeliger Susanne , Westermann Patrick , Rhyner Claudio , Schiavi Elisa , Barcik Weronika , Rodriguez‐Perez Noelia , Wawrzyniak Marcin , Chassard Christophe , Lacroix Christophe , Schmausser‐Hechfellner Elisabeth , Depner Martin , von Mutius Erika , Braun‐Fahrländer Charlotte , Karvonen Anne M. , Kirjavainen Pirkka V. , Pekkanen Juha , Dalphin Jean‐Charles , Riedler Josef , Akdis Cezmi , Lauener Roger , O'Mahony Liam ,   the PASTURE/EFRAIM study group
Published: November 2018

Background

Dietary changes are suggested to play a role in the increasing prevalence of allergic diseases and asthma. Short‐chain fatty acids (SCFAs) are metabolites present in certain foods and are produced by microbes in the gut following fermentation of fibers. SCFAs have been shown to have anti‐inflammatory properties in animal models. Our objective was to investigate the potential role of SCFAs in the prevention of allergy and asthma.

Methods

We analyzed SCFA levels by high‐performance liquid chromatography (HPLC) in fecal samples from 301 one‐year‐old children from a birth cohort and examined their association with early life exposures, especially diet, and allergy and asthma later in life. Data on exposures and allergic diseases were collected by questionnaires. In addition, we treated mice with SCFAs to examine their effect on allergic airway inflammation.

Results

Significant associations between the levels of SCFAs and the infant's diet were identified. Children with the highest levels of butyrate and propionate (≥95th percentile) in feces at the age of one year had significantly less atopic sensitization and were less likely to have asthma between 3 and 6 years. Children with the highest levels of butyrate were also less likely to have a reported diagnosis of food allergy or allergic rhinitis. Oral administration of SCFAs to mice significantly reduced the severity of allergic airway inflammation.

Conclusion

Our results suggest that strategies to increase SCFA levels could be a new dietary preventive option for allergic diseases in children.