bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Electrosensory Feedback: Short-Term Plasticity and Inhibition in a Parallel Fiber Pathway
Authors: Lewis John E. , Maler Leonard
Published: December 2017

The dynamics of neuronal feedback pathways are generally not well understood. This is due to the complexity arising from the combined dynamics of closed-loop feedback systems and the synaptic plasticity of feedback connections. Here, we investigate the short-term synaptic dynamics underlying the parallel fiber feedback pathway to a primary electrosensory nucleus in the weakly electric fish, Apteronotus leptorhynchus. In open-loop conditions, the dynamics of this pathway arise from a monosynaptic excitatory connection and a disynaptic (feed-forward) inhibitory connection to pyramidal neurons in the electrosensory lateral line lobe (ELL). In a brain slice preparation of the ELL, we characterized the synaptic responses of pyramidal neurons to short trains of electrical stimuli delivered to the parallel fibers of the dorsal molecular layer. Stimulus trains consisted of 20 pulses, at either random intervals or constant intervals, with varying mean frequencies. With random trains, pyramidal neuron responses were well described by a single exponential function of the inter-stimulus interval—suggesting a single facilitation-like process underlies these synaptic dynamics. However, responses to periodic (constant interval) trains deviated from this simple description. Random and periodic stimulus trains delivered when the feed-forward inhibitory component of this pathway was pharmacologically blocked revealed that inhibition and depression also contribute to the observed dynamics. We formulated a simple model of the parallel fiber synaptic dynamics that provided an accurate description of our data. The model dynamics resulted from a combination of three distinct processes. Two of the processes are the classically-described synaptic facilitation and depression, and the third is a novel description of feed-forward inhibition. An analysis of this model suggests that synaptic pathways combining plasticity with feed-forward inhibition can be easily tuned to signal different types of transient stimuli and thus lead to diverse and nonintuitive filtering properties.
Discharge Characteristics of Neurons in the Red Nucleus During Voluntary Gait Modifications: A Comparison with the Motor Cortex
Authors: Lavoie Sylvain , Drew Trevor
Published: December 2017

We have examined the contribution of the red nucleus to the control of locomotion in the cat. Neuronal activity was recorded from 157 rubral neurons, including identified rubrospinal neurons, in three cats trained to walk on a treadmill and to step over obstacles attached to the moving belt. Of 72 neurons with a receptive field confined to the contralateral forelimb, 66 were phasically active during unobstructed locomotion. The maximal activity of the majority of neurons (59/66) was centered around the swing phase of locomotion. Slightly more than half of the neurons (36/66) were phasically activity during both swing and stance. In addition, some rubral neurons (14/66) showed multiple periods of phasic activity within the swing phase of the locomotor cycle. Periods of phasic discharge temporally coincident with the swing phase of the ipsilateral limb were observed in 7/66 neurons. During voluntary gait modifications, most forelimb-related neurons (70/72) showed a significant increase in their discharge activity when the contralateral limb was the first to step over the obstacle (lead condition). Maximal activity in nearly all cells (63/70) was observed during the swing phase, and 23/63 rubral neurons exhibited multiple increases of activity during the modified swing phase. A number of cells (18/70) showed multiple periods of increased activity during swing and stance. Many of the neurons (35/63, 56%) showed an increase in activity at the end of the swing phase; this period of activity was temporally coincident with the period of activity in wrist dorsiflexors, such as the extensor digitorum communis. A smaller proportion of neurons with receptive fields restricted to the hindlimbs showed similar characteristics to those observed in the population of forelimb-related neurons. The overall characteristics of these rubral neurons are similar to those that we obtained previously from pyramidal tract neurons recorded from the motor cortex during an identical task. However, in contrast to the results obtained in the rubral neurons, most motor cortical neurons showed only one period of increased activity during the step cycle. We suggest that both structures contribute to the modifications of the pattern of EMG activity that are required to produce the change in limb trajectory needed to step over an obstacle. However, the results suggest an additional role for the red nucleus in regulating intra- and interlimb coordination.
Common Inhibitory Mechanism for Saccades and Smooth-Pursuit Eye Movements
Authors: Missal M. , Keller E. L.
Published: December 2017

The premotor pathways subserving saccades and smooth-pursuit eye movements are usually thought to be different. Indeed, saccade and smooth-pursuit eye movements have different dynamics and functions. In particular, a group of midline cells in the pons called omnipause neurons (OPNs) are considered to be part of the saccadic system only. It has been established that OPNs keep premotor neurons for saccades under constant inhibition during fixation periods. Saccades occur only when the activity of OPNs has completely stopped or paused. Accordingly, electrical stimulation in the region of OPNs inhibits premotor neurons and interrupts saccades. The premotor relay for smooth pursuit is thought to be organized differently and omnipause neurons are not supposed to be involved in smooth-pursuit eye movements. To investigate this supposition, OPNs were recorded during saccades and during smooth pursuit in the monkey ( Macaca mulatta). Unexpectedly, we found that neuronal activity of OPNs decreased during smooth pursuit. The resulting activity reduction reached statistical significance in ∼50% of OPNs recorded during pursuit of a target moving at 40°/s. On average, activity was reduced by 34% but never completely stopped or paused. The onset of activity reduction coincided with the onset of smooth pursuit. The duration of activity reduction was correlated with pursuit duration and its intensity was correlated with eye velocity. Activity reduction was observed even in the absence of catch-up saccades that frequently occur during pursuit. Electrical microstimulation in the OPNs' area induced a strong deceleration of the eye during smooth pursuit. These results suggest that OPNs form an inhibitory mechanism that could control the time course of smooth pursuit. This inhibitory mechanism is part of the fixation system and is probably needed to avoid reflexive eye movements toward targets that are not purposefully selected. This study shows that saccades and smooth pursuit, although they are different kinds of eye movements, are controlled by the same inhibitory system.
Anticonvulsant Actions of Gap Junctional Blockers in an In Vitro Seizure Model
Authors: Jahromi Shokrollah S. , Wentlandt Kirsten , Piran Sanaz , Carlen Peter L.
Published: December 2017

Gap junctions (gjs) are increasingly recognized as playing a significant role in seizures. We demonstrate that different types of gap junctional blocking agents reduce the duration of evoked seizure-like primary afterdischarges (PADs) in the rat in vitro CA1 hippocampal pyramidal region, following repetitive tetanization of the Schaffer collaterals. Intracellular acidosis, which is known to block gap junctional communication, decreased the PADs, whereas alkalinization increased the PADs. Cellular excitability was not significantly depressed as determined by input/output relations recorded before and during perfusion of the gj blockers blockers carbenoxolone and sodium propionate. There was a small decrease following 1-octanol perfusion and a large decrease following NH4Cl application. Carbenoxolone diminished PAD duration, but increased neuronal excitability in whole-cell recordings. After robust PADs were established, the expression of several gj proteins including connexins (Cxs) 26, 32, 36, and 43, as measured by Western blotting, was unchanged, although the level of nonphosphorylated Cx43 was decreased. Our data support the concept that blocking gap junctional communication is an anticonvulsant mechanism.
Reassessment of the Effects of Cycloheximide on Mossy Fiber Sprouting and Epileptogenesis in the Pilocarpine Model of Temporal Lobe Epilepsy
Authors: Williams Philip A. , Wuarin Jean-Pierre , Dou Ping , Ferraro Damien J. , Dudek F. Edward
Published: December 2017

A feature of animal models of temporal lobe epilepsy and the human disorder is hippocampal sclerosis and Timm stain in the inner molecular layer (IML) of the dentate gyrus, which represents synaptic reorganization and may be important in epileptogenesis. We reassessed the hypothesis that pre-treatment with cycloheximide (CHX) prevents Timm staining in the IML following pilocarpine (PILO)-induced status epilepticus (a multifocal model of temporal lobe epilepsy), but allows epileptogenesis (i.e., chronic spontaneous seizures) after a latent period. Hippocampal slices from PILO-treated rats without Timm stain in the IML after CHX treatment were hypothesized to lack the electrophysiological abnormalities suggestive of recurrent excitation. The primary experimental groups were as follows: 1) CHX (1 mg/kg) 30–45 min prior to administration of PILO (320 mg/kg ip, 2) only PILO, and 3) only saline (0.5 ml, IP). The CHX pre-treatment significantly decreased the number of rats that responded to PILO with status epilepticus compared to rats that received only PILO. Pre-treatment with CHX did not significantly alter the spontaneous motor seizure rate post-treatment compared to treatment with PILO alone in those animals from each group that developed status epilepticus during PILO treatment. Timm stain in the IML was not significantly different between the PILO- and PILO+CHX-treated rats. Using quantitative methods, CHX did not prevent hilar, CA1, or CA3 neuronal loss compared to the PILO-treated rats. Extracellular responses to hilar stimulation in 30 μM bicuculline and 6 mM [K+]odemonstrated all-or-none bursting in both the CHX+PILO- and PILO-treated rats but not in control rats. Whole cell recordings from granule cells, using glutamate flash photolysis to activate other granule cells, showed that both the CHX+PILO- and PILO-treated rats had excitatory synaptic interactions in the granule cell layer, which were not found after saline treatment. Some rats responded to PILO (with or without CHX pre-treatment) with only one or a few seizures at treatment, and some of these animals ( n = 4) demonstrated spontaneous motor seizures within 2 mo after treatment. Timm staining and neuron loss in this group were not clearly different from saline-treated rats. These results suggest that in the PILO model, pre-treatment with CHX does not affect mossy fiber sprouting in the IML of epileptic rats and does not prevent the formation of recurrent excitatory circuits. However, the develoment of spontaneous motor seizures, in a small number of rats, could occur without detectable hippocampal neuron loss or mossy fiber sprouting, as assessed by the Timm stain method.
Mechanisms Influencing Acquisition and Recall of Motor Memories
Authors: Donchin Opher , Sawaki Lumy , Madupu Ghangadar , Cohen Leonardo G. , Shadmehr Reza
Published: December 2017

An internal model of the dynamics of a tool or an object is part of the motor memory acquired when learning to use the tool or to manipulate the object. Changes in synaptic efficacy may underlie acquisition and storage of memories. Here we studied the effect of pharmacological agents that interfere with synaptic plasticity on acquisition of new motor memories and on recall of a previously learned internal model. Forty-nine subjects, divided into six groups, made reaching movements while holding a robotic arm that applied forces to the hand. On day 1, all subjects learned to move in force field A. On day 2, each group of subjects was tested on their ability to recall field A and their ability to learn a new internal model in field B. Four groups participated in the experiments of day 2 under the effects of lorazepam (LZ; a GABA type A receptor-positive allosteric modulator), dextromethorphan [DM; an N-methyl-d-aspartate (NMDA) receptor blocker], lamotrigine (LG, a drug that blocks voltage-gated Na+ and Ca2+ channel), or scopolamine (SP; muscarinic receptor antagonist). Two control groups were tested in a drug-free condition: one group that was not exposed to additional experimental protocols (NP) and another group was tested under ∼24 h of sleep deprivation between completion of learning on day 1 and start of testing on day 2 (SD). Recall of field A was normal in all groups. Learning of field B was reduced by LZ and DM but not by SP, LG, SD or in the NP condition. These results suggest that a 24-h sleep-deprivation period may have little or no effect on consolidation of this motor memory and that NMDA receptor activation and GABAergic inhibition are mechanisms operating in the acquisition but not recall of new motor memories in humans.
Differential Distribution of Burst and Single-Spike Responses in Auditory Thalamus
Authors: He Jufang , Hu Bin
Published: December 2017

The medial geniculate body (MGB) of the auditory thalamus comprises lemniscal and nonlemniscal neurons that project to the primary auditory cortex and limbic structures, respectively. Here we show that in anesthetized guinea pigs, MGB responses to a noise-burst stimulus exhibit distinct and synaptic pathway-specific firing patterns. The majority of nonlemniscal MGB cells exhibited bursting responses, whereas lemniscal neurons discharged mainly single or spike doublets. The burst firing is delayed in nonlemniscal neurons and exhibited several features that are characteristics of those mediated by low-threshold Ca2+ spikes. Such a synaptic pathway-specific allocation of bursting and single-spike firing patterns is consistent with the notion of parallel processing of auditory information in thalamocortical system.
Measures of Adherence and Challenges in Using Glucometer Data in Youth with Type 1 Diabetes: Rethinking the Value of Self-Report
Authors: Datye Karishma A. , Patel Niral J. , Jaser Sarah S.
Published: December 2017

Purpose. The current study compares the relative strength of associations of different adherence measures with glycemic control in adolescents with type 1 diabetes, while highlighting the challenges in using more objective measures (i.e., glucometer data). Methods. Adolescents with type 1 diabetes (n=149) and their caregivers completed a questionnaire measure assessing adolescents’ adherence (Self-Care Inventory (SCI)) to the diabetes regimen. Adolescents’ glucometers were downloaded to determine average blood glucose checks per day, as an objective measure of adherence. A measure of glycemic control (hemoglobin A1c (HbA1c)) was obtained as part of adolescents’ regular clinic visits. Results. Adolescents’ self-reported adherence to the treatment regimen was more strongly correlated with HbA1c than caregivers’ reports of adherence. In multivariate analyses, both adolescents’ self-report of adherence and average blood glucose checks per day (obtained via a glucometer) were significant predictors of HbA1c. Challenges to obtaining glucometer data were identified. Conclusions. The findings highlight adolescents’ self-report of adherence using the SCI as a brief and meaningful measure to understand and improve adolescents’ glycemic control, particularly when glucometer data is difficult to obtain.
Regulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies
Authors: D’Arena Giovanni , Vitale Candida , Coscia Marta , Festa Agostino , Di Minno Nicola Matteo Dario , De Feo Vincenzo , Caraglia Michele , Calapai Gioacchino , Laurenti Luca , Musto Pellegrino , Di Minno Giovanni , Fenoglio Daniela
Published: December 2017

Regulatory T cells (Tregs) have a fundamental function in monitoring the immune homeostasis in healthy individuals. In cancer and, in particular, in hematological malignancies, Tregs exert a major immunosuppressive activity, thus playing a critical role in tumor cell growth, proliferation, and survival. Here, we summarize published data on the prognostic significance of Tregs in hematological malignancies and show that they are highly conflicting. The heterogeneity of the experimental approaches that were used explains—at least in part—the discordant results reported by different groups that have investigated the role of Tregs in cancer. In fact, different tissues have been studied (i.e., peripheral blood, bone marrow, and lymph node), applying different methods (i.e., flow cytometry versus immunohistochemistry, whole blood versus isolated peripheral blood mononuclear cells versus depletion of CD25+cells, various panels of monoclonal antibodies, techniques of fixation and permeabilization, and gating strategies). This is of relevance in order to stress the need to apply standardized approaches in the study of Tregs in hematological malignancies and in cancer in general.
A Pilot Study of Immune Activation and Rifampin Absorption in HIV-Infected Patients without Tuberculosis Infection: A Short Report
Authors: Vinnard Christopher , Manley Isabel , Scott Brittney , Bernui Mariana , Adams Joella , Varghese Sheryl , Zentner Isaac , Kutzler Michele A.
Published: December 2017

Background. Rifampin malabsorption is frequently observed in tuberculosis patients coinfected with human immunodeficiency virus (HIV) but cannot be predicted by patient factors such as CD4+ T cell count or HIV viral load. Methods. We sought to describe the relationship between HIV-associated immune activation, measures of gut absorptive capacity and permeability, and rifampin pharmacokinetic parameters in a pilot study of 6 HIV-infected, tuberculosis-uninfected patients who were naïve to antiretroviral therapy. Results. The median rifampin area under the concentration-versus-time curve during the 8-hour observation period was 42.8 mg·hr/L (range: 21.2 to 57.6), with a median peak concentration of 10.1 mg/L (range: 5.3 to 12.5). We observed delayed rifampin absorption, with a time to maximum concentration greater than 2 hours, in 2 of 6 participants. There was a trend towards increased plasma concentrations of sCD14, a marker of monocyte activation in response to bacterial translocation, among participants with delayed rifampin absorption compared to participants with rapid absorption (p=0.06). Conclusions. Delayed rifampin absorption may be associated with elevated markers of bacterial translocation among HIV-infected individuals naïve to antiretroviral therapy. This trial is registered with NCT01845298.
SSCM: An Unambiguous Acquisition Algorithm for CBOC Modulated Signal
Authors: Feng Yongxin , Fei Shunchao , Liu Fang , Qian Bo
Published: December 2017

Composite binary offset carrier (CBOC) signal has been widely researched in GNSS. The main ingredient of CBOC signal is BOC(1,1) signal. Usually, the acquisition method for BOC(1,1) signal is used to capture CBOC signal, while the research of special acquisition method for CBOC signal is rare. In this letter, according to the principle and characteristics of CBOC signal, a special side-peak cancellation method (SSCM) is proposed and simulated. In this method, two special auxiliary signals are introduced. And the local reference signals are obtained by multiplying the data channel signal and pilot channel signal by the auxiliary signals. The cross-correlation results from the received pilot signal and the two local pilot signals with different auxiliary signals will subtract from one another. Then, side peaks of correlation function and in-band noise of pilot channel are suppressed, while the data channel has the same operation results. At last the outputs of pilot channel and data channel will be added up to make full use of the received signal power. By this way, the acquisition efficiency, accuracy, and adaptability to low signal-to-noise ratio (SNR) conditions for CBOC signal have been improved, alongside possible solution when the GNSS receiver works in a critical environment.
Aging in HIV-Infected Subjects: A New Scenario and a New View
Authors: Negredo Eugenia , Back David , Blanco José-Ramón , Blanco Julià , Erlandson Kristine M. , Garolera Maite , Guaraldi Giovanni , Mallon Patrick , Moltó José , Serra José Antonio , Clotet Bonaventura
Published: December 2017

The prevalence of HIV-infected people aged 50 years or older is increasing rapidly; the proportion will increase from 28% to 73% in 2030. In addition, HIV-infected individuals may be more vulnerable to age-related condition. There is growing evidence that the prevalence of comorbidities and other age-related conditions (geriatric syndromes, functional or neurocognitive/mental problems, polypharmacy, and social difficulties) is higher in the HIV-infected population than in their uninfected counterparts. However, despite the potential impact of this situation on health care, little information exists about the optimal clinical management of older HIV-infected people. Here we examine the age-related conditions in older HIV-infected persons and address clinical management according to author expertise and published literature. Our aim is to advance the debate about the most appropriate management of this population, including less well-studied aspects, such as frequency of screening for psychological/mental and social and functional capabilities.
Audiovisual Biofeedback-Based Trunk Stabilization Training Using a Pressure Biofeedback System in Stroke Patients: A Randomized, Single-Blinded Study
Authors: Jung Sangwoo , Lee Kyeongjin , Kim Myungjoon , Song Changho
Published: December 2017

The purpose of this study was to assess the effects of audiovisual biofeedback-based trunk stabilization training using a pressure biofeedback system (PBS) in stroke patients. Forty-three chronic stroke patients, who had experienced a stroke more than 6 months ago and were able to sit and walk independently, participated in this study. The subjects were randomly allocated to an experimental group (n=21) or a control group (n=22). The experimental group participated in audiovisual biofeedback-based trunk stabilization training for 50 minutes/day, 5 days/week, for 6 weeks. The control group underwent trunk stabilization training without any biofeedback. The primary outcome of this study was the thickness of the trunk muscles. The secondary outcomes included static sitting balance ability and dynamic sitting balance ability. The thickness of the trunk muscles, static sitting balance ability, and dynamic sitting balance ability were significantly improved in the experimental group compared to the control group (p<0.05). The present study showed that trunk stabilization training using a PBS had a positive effect on the contracted ratio of trunk muscles and balance ability. By providing audiovisual feedback, the PBS enables accurate and effective training of the trunk muscles, and it is an effective method for trunk stabilization.
Associations between the Epithelial-Mesenchymal Transition Phenotypes of Circulating Tumor Cells and the Clinicopathological Features of Patients with Colorectal Cancer
Authors: Wu Fengjie , Zhu Jun , Mao Yongjiang , Li Xiaomei , Hu Baoguang , Zhang Dianliang
Published: December 2017

In this study, we identified CTCs using the previously reported CanPatrol CTC enrichment technique from peripheral blood samples of 126 patients with colorectal cancer (CRC) and found that CTCs could be classified into three subpopulations based on expression of epithelial cell adhesion molecule (EpCAM) (E-CTCs), the mesenchymal cell marker vimentin (M-CTCs), or both EpCAM and vimentin (biphenotypic E/M-CTCs). Circulating tumor microemboli (CTMs) were also identified in peripheral blood samples. Meanwhile, E-CTCs, M-CTCs, E/M-CTCs, and CTMs were detected in 76.98%, 42.06%, 56.35%, and 36.51% of the 126 patients, respectively. Interestingly, the presence of CTMs and each CTC subpopulation was significantly associated with blood lymphocyte counts and tumor-node-metastasis stage (P<0.001). Lymphocyte counts and the neutrophil-to-lymphocyte ratio (NLR) in patients lacking CTCs were significantly different from those in patients testing positive for CTMs and each CTC subpopulation (P<0.001). Our results indicate that tumor metastasis is more significantly associated with the presence of CTMs and M-CTCs than with other CTC subpopulations and suggest that EMT may be involved in CTC evasion of lymphocyte-mediated clearance.
Recurrent Stroke after Transcatheter PFO Closure in Cryptogenic Stroke or Tia: Long-Term Follow-Up
Authors: Mariucci Elisabetta , Donti Andrea , Salomone Luisa , Marcia Marta , Guidarini Marta , Formigari Roberto , Prandstraller Daniela , Balducci Anna , Bronzetti Gabriele , Bonvicini Marco
Published: December 2017

Background. There are few data on the mechanism of recurrent neurological events after transcatheter closure of patent foramen ovale (PFO) in cryptogenic stroke or TIA. Methods. We retrospectively reviewed PFO closure procedures for the secondary prevention of cryptogenic stroke/TIA performed between 1999 and 2014 in Bologna, Italy. Results. Written questionnaires were completed by 402 patients. Mean follow-up was 7 ± 3 years. Stroke recurred in 3.2% (0.5/100 patients-year) and TIA in 2.7% (0.4/100 patients-year). Ninety-two percent of recurrent strokes were not cryptogenic. Recurrent stroke was noncardioembolic in 69% of patients, AF related in 15% of patients, device related in 1 patient, and cryptogenic in 1 patient. AF was diagnosed after the procedure in 21 patients (5.2%). Multivariate Cox’s proportion hazard model identified age ≥ 55 years at the time of closure (OR 3.16, p=0.007) and RoPE score < 7 (OR 3.21, p=0.03) as predictors of recurrent neurological events. Conclusion. Recurrent neurological events after PFO closure are rare, usually noncryptogenic and associated with conventional vascular risk factors or AF related. Patients older than 55 years of age and those with a RoPE score < 7 are likely to get less benefit from PFO closure. After transcatheter PFO closure, lifelong strict vascular risk factor control is warranted.
Meeting the Iron Needs of Low and Very Low Birth Weight Infants
Authors: Domellöf Magnus
Published: December 2017

Low birth weight (LBW), defined as a birth weight of <2,500 g, affects 16% of all newborns and is a risk factor for impaired neurodevelopment as well as adverse cardiovascular and metabolic outcomes, including hypertension. LBW infants include both term, small for gestational age infants and preterm infants. Most LBW infants have only marginally LBW (2,000-2,500 g). Recent advances in neonatal care have significantly improved the survival of very LBW (VLBW) infants (<1,500 g). LBW infants are at high risk of iron deficiency due to low iron stores at birth and higher iron requirements due to rapid growth. Using a factorial approach, iron requirements of LBW infants have been estimated to be 1-2 mg/kg/day, which is much higher than the requirements of term, normal birth weight infants, who need almost no dietary iron during the first 6 months of life. In VLBW infants, blood losses and blood transfusions related to neonatal intensive care, as well as erythropoietin treatment, will greatly influence iron status and iron requirements. The timing of umbilical cord clamping at birth is of great importance for the amount of blood transfused from the placenta to the newborn and thereby total body iron. Delayed cord clamping of LBW infants is associated with less need for blood transfusion, less intraventricular hemorrhage, and less necrotizing enterocolitis. Randomized controlled trials have shown that an iron intake of 1-3 mg/kg/day (1-2 mg for marginally LBW and 2-3 mg for VLBW) is needed to effectively prevent iron deficiency. There is some recent evidence that these levels of iron intake will prevent some of the negative health consequences associated with LBW, especially behavioral problems and other neurodevelopmental outcomes and possibly even hypertension. However, it is also important to avoid excessive iron intakes which have been associated with adverse effects in LBW infants.
Clinical Implications of New Insights into Hepcidin-Mediated Regulation of Iron Absorption and Metabolism
Authors: Prentice Andrew M.
Published: December 2017

The fact that humans must balance their need for iron against its potential for causing harm has been known for several centuries, but the molecular mechanisms by which we achieve this feat have only been revealed in the last 2 decades. Chief amongst these is the discovery of the master-regulatory liver-derived hormone hepcidin. By switching off ferroportin in enterocytes and macrophages, hepcidin exerts fine control over both iron absorption and its distribution among tissues. Hepcidin expression is downregulated by low iron status and active erythropoiesis and upregulated by iron overload and infection and/or inflammation. The latter mechanism explains the etiology of the anemia of chronic infection. Pharmaceutical companies are actively developing hepcidin agonists and antagonists to combat iron overload and anemia, respectively. In a global health context the discovery of hepcidin shines a new light on the world's most prevalent micronutrient problem; iron deficiency and its consequent anemia. It is now apparent that humans are not poorly designed to absorb dietary iron, but rather are exerting a tonic downregulation of iron absorption to protect themselves against infection. These new insights suggest that interventions to reduce infections and inflammation will be at least as effective as dietary interventions and that the latter will not succeed without the former.
Difference between Methods for Estimation of Basal Metabolic Rate and Body Composition in Pediatric Patients with Osteogenesis Imperfecta
Authors: Zambrano Marina B. , Félix Têmis M. , de Mello Elza D.
Published: December 2017

Background/Aims: Osteogenesis Imperfecta (OI) is a bone disease characterized by bone fragility, deformities, and multiple fractures. The aim of this study was to compare the different methods of measuring the basal metabolic rate (BMR) and body composition (BC) in pediatric patients with OI. Methods: This cross-sectional study included 52 individuals with a median age of 9 (5.25–12.7) years. BMR was calculated by bioelectrical impedance analyses (BIA), predictive values according to age from the World Health Organization (WHO), a kcal/cm formula, and indirect calorimetry (IC). BC was assessed using the anthropometric calculation of percentage body fat (%BF) and lean mass (kg), BIA, and dual-energy X-ray absorptiometry (DEXA). Agreement among the methods was assessed using the Bland-Altman technique. Results: IC estimates of BMR were greater than BIA and lower than values obtained using the WHO and kcal/cm methods. Better agreement was observed using the WHO values for mild forms of OI and the kcal/cm formula for moderate-to-severe forms. For BC, DEXA estimates of %BF were higher and the lean mass was lower than the values obtained using BIA and anthropometry. Neither method agreed with the DEXA method results. Conclusions: Significant differences exist among the various methods used for measuring BMR and BC with regard to phenotypic differences between OI types.
Fatal Overdoses of Opioids in Israel 2005–2014
Authors: Feingold Daniel , Goldberger Nehama , Haklai Ziona , Lev-Ran Shaul
Published: December 2017

Aims: To explore previously unreported rates and trends in opioid-related mortality in Israel, 2005–2014. Methods: Data was obtained from the national database on causes of death. Drug poisoning deaths were divided into opioid-related deaths and deaths related to other drugs according to International Classification of Diseases (ICD)-10 code of underlying cause, and included drug poisoning of accidental, intentional or undetermined intent. Age-adjusted rates were calculated per 100,000 population. Rate ratios were calculated and a logistic model constructed to compare the risk of opioid-related deaths in both halves of the decade (2006–2009 and 2009–2013) and between various demographic groups. Results: While age-adjusted rates of deaths related to other drugs remained relatively stable, rates of opioid-related deaths significantly decreased during this period across all groups. During the study period, the number of opioid-related deaths in Israel declined from 1.3 to 0.3 per 100,000. Opioid-related deaths were more common among men, young adults and immigrants from the Former Soviet Union. Conclusions: Rates of opioid-related deaths in Israel were low compared to those reported in the United States and United Kingdom. In addition, the decline in opioid-related deaths in Israel is contrary to trends observed in the United States and United Kingdom. Factors that may contribute to these differences are discussed.
Nine-Year Outcome of Ranibizumab Monotherapy for Choroidal Neovascularization Secondary to Pathologic Myopia
Authors: Pastore Marco R. , Capuano Vittorio , Bruyère Elsa , Miere Alexandra , Corbelli Eleonora , Querques Lea , Tognetto Daniele , Bandello Francesco , Querques Giuseppe , Souied Eric H.
Published: December 2017

Purpose: The aim of this study was to evaluate the 9-year outcome of ranibizumab monotherapy for myopic choroidal neovascularization (mCNV). Methods: This was a retrospective, nonrandomized, multicentric study to evaluate the long-term outcomes of mCNV treated with ranibizumab monotherapy for at least 9 years according to a strict pro re nata regimen. Results: Seventeen eyes of 17 patients (12 women, mean age 57.9 ± 7.7 years) were included. The mean follow-up period was 112.4 ± 3.9 months (range 108–120). The mean difference in best-corrected visual acuity (BCVA) from baseline to the last follow-up was +1.2 ± 15.6 ETDRS letters (p = 0.004, between initial vs. 12 and 24 months). The mean total number of intravitreal injections for each patient was 1.24 ± 1.70 per year (range 2–25). No systemic adverse reactions related to the drug treatment were detected during the 9-year follow-up period. Conclusions: Long-term ranibizumab monotherapy treatment induces unchanged or better BCVA compared to baseline after a 9-year treatment in almost all eyes.
Prenatal Diagnosis of Trisomy 2p due to Terminal 2p Duplication including Interstitial Telomeric Sequences
Authors: Marlet Lyvia , Alix Eudeline , Till Marianne , Raskin-Champion Fabienne , Attia Jocelyne , Boggio Dominique , Sanlaville Damien , Schluth-Bolard Caroline
Published: December 2017

We report on a prenatally diagnosed unusual case of inverted terminal duplication of the short arm of chromosome 2, leading to interstitial telomeric sequences (ITSs) and partial trisomy 2p. To our knowledge, there are only 4 further cases of pure partial trisomy 2p reported prenatally. Here, the mother was referred at 22 weeks of gestation for isolated fetal congenital heart malformation at ultrasound. The karyotype of amniotic fluid cells displayed a large duplication of the short arm of chromosome 2 that was further investigated by array-CGH, which detected a 1-copy gain of 43.75 Mb in chromosome 2 at 2p21p25.3. FISH confirmed the presence of an inverted duplication in the short arm of chromosome 2 involving the region 2p21pter and revealed the presence of ITSs at the breakpoint in chromosome 2p21. This report contributes to the prenatal description of the syndrome. We also discuss the possible mechanisms leading to this duplication and the formation of ITSs which are rarely described in constitutional rearrangements.
Platinum-Based Neoadjuvant Chemotherapy versus Primary Surgery in Ovarian Carcinoma International Federation of Gynecology and Obstetrics Stages IIIc and IV: A Systematic Review and Meta-Analysis
Authors: Xiao Yunyun , Xie Shuang , Zhang Ningning , Wang Jiao , Lv Chao , Guo Jiao , Yang Qing
Published: December 2017

Background/Aim: This study aimed to compare neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS) with primary debulking surgery (PDS) followed by chemotherapy in patients with advanced ovarian carcinoma International Federation of Gynecology and Obstetrics (FIGO) stages IIIc and IV. Methods: PubMed, the Cochrane Library, and manual searches were applied to discriminate potentially eligible studies published before June 30, 2016. Results: A total of 12 comparative studies were finally included; 1,372 patients underwent NAC followed by IDS, and 2,680 patients underwent PDS followed by chemotherapy. For overall pooled estimates, significant between-trial differences were found in the optimal debulking rate, grade 3–5 postoperative adverse reactions, and median overall survival (OS), but no difference was found in the median progression-free survival (PFS). Moreover, a significantly higher incidence was identified in major infections, vascular events, and wound complications for patients in the PDS group. Conclusions: This study suggested that NAC followed by IDS could improve the optimal debulking rate and decrease the postoperative adverse reactions for the current studies, but whether it could improve the OS and PFS compared with PDS followed by chemotherapy in patients with ovarian carcinoma FIGO stages IIIc and IV were still needed to be verified by conducting more randomized controlled trials.
Expressions and Regulatory Effects of P38/ERK/JNK Mapks in the Adipogenic Trans-Differentiation of C2C12 Myoblasts
Authors: Qi Renli , Liu Hong , Wang Qi , Wang Jing , Yang Feiyun , Long Dingbiao , Huang Jinxiu
Published: December 2017

Background/Aims: Myoblasts and muscle satellite cells have the potential to transdifferentiate into adipocytes or adipocyte-like cells. Previous studies suggest that mitogen-activated protein kinase (MAPK) is critical to adipogenic trans-differentiation of muscle cells. ERK1/2, P38 and JNK are three major MAPK family members; their activation and regulatory functions during adipogenic trans-differentiation of myoblasts are investigated. Methods: C2C12 myoblasts were cultured and induced for adipogenic trans-differentiation. Activation patterns of MAPKs were assayed using protein microarray and Western blot. Three specific MAPK blockers, U0126, SB20358 and SP600125, were used to block ERK1/2, P38 and JNK during trans-differentiation. Cellular adipogenesis was measured using staining and morphological observations of cells and expression changes in adipogenic genes. Results: Inhibitors reduced phosphorylation of corresponding MAPK and produced unique cellular effects. Suppressing P38 promoted adipogenic trans-differentiation and intensified adipolytic metabolism in differentiated cells. However, inhibition of ERK1/2 had the opposite effects on adipogenesis and no effect on adipolysis. Blocking JNK weakly blocked trans-differentiation but stimulated adipolysis and induced apoptosis. Conclusion: Three MAPKs participate in the regulation of myoblast adipogenic trans-differentiation by controlling adipogenic and adipolysis metabolism.
A new species of Bryophryne (Anura: Strabomantidae) from the Cordillera de Vilcabamba, southeastern Peruvian Andes
Authors: Mamani Luis , Catenazzi Alessandro , Ttito Alex , Mallqui Sergio , Chaparro Juan C.
Published: December 2017

We describe a new species of Bryophryne from the Cordillera de Vilcabamba in Department Cusco, in the southeastern Peruvian Andes. The new species differs from all other congeneric taxa, except B. flammiventris and B. gymnotis, by possessing a weakly defined tympanic membrane and tympanic annulus, by the presence of vocal sac and vocal slits in males, and by producing advertisement calls. The new species is distinguished from B. flammiventris and B. gymnotis by skin texture, presence of small, oblique dentigerous processes on the vomer, ventral coloration ranging from bluish-gray to whitish-gray with irregular or reticulate dark brown spots, and call composed of two or three notes. The new species is further characterized by having dorsal skin shagreen with tubercles, discontinuous dorsolateral folds, skin smooth on ventral surfaces of the body, and lateral fringes on fingers and toes. This species was found at the transition from montane forest to high Andean puna, where it occurs in moist microhabitats under moss and rocks at elevations from 3519 to 3707 m a.s.l.
Redescription, geographic distribution and ecological niche modeling of Elapomorphus wuchereri (Serpentes: Dipsadidae)
Authors: Entiauspe-Neto Omar Machado , Renner Márcia Ferret , Mario-da-Rosa Conrado , Abegg Arthur Diesel , Loebmann Daniel , Lema Thales De
Published: December 2017

The original description of Elapomorphus wuchereri Günther, 1861 included a drawing and brief comments about the morphology of three specimens; two of the latter belong to another species and the holotype is lost. Based on the discovery of new specimens, we redescribe Elapomorphus wuchereri and designate a neotype. We discuss the variation and the taxonomic history of the species, and based on the results of a species distribution model analysis (SDM), we describe the distribution, extent of occurrence, and conservation status.
Revalidation of Apostolepis barrioi (Serpentes: Dipsadidae)
Authors: Cabral Hugo , Lema Thales De , Renner Márcia Ferret
Published: December 2017

With 32 species, Apostolepis is the most diverse genus in the tribe Elapomorphini. The description of Apostolepis barrioi is based on one specimen and the taxon later was synonymized with A. dimidiata. Based on a examination of new specimens, the taxon is resurrected to full species rank. Apostolepis barrioi differs from all congeners by having an immaculate white venter, narrow dorsolateral stripes not in contact with the ventrals, and a terminal black shield. With the addition of A. barrioi, the number of species of the genus increases to 33; however, more systematic research on the status of the species in the group is required, especially for those species that were described on the basis of only on few specimens.
Nesting in the lizard Phyllopezus pollicaris (Squamata: Phyllodactylidae) and a phylogenetic perspective on communal nesting in the family
Authors: Domingos Fabricius M. C. B. , Arantes Ísis C. , Bosque Renan J. , Santos Marcella G.
Published: December 2017

Communal nesting occurs in many reptile species. The hypotheses that explain the evolution of such behaviours are still controversial, but will be better understood as more communal nesting records are described in the literature. We report the findings of two communal nests of Phyllopezus pollicaris, including the largest known nest for the species. Our study is the first to provide a communal nesting record for squamate species in a Cerrado core area. We provide nest photographs and detailed neonate measurements and weight. Nests were found during the dry season, in contrast with the reproduction pattern previously described for the species in the Cerrado periphery. We also conducted an extensive literature review seeking all available information on communal nesting information in Phyllodactylidae, and present this information in the context of a phylogenetic tree of phyllodactylid genera. We suggest that studying the correlation between communal nesting evolution and reproductive investment will become a fertile field as more information on lizard nesting becomes available in the literature.
Marital Status and Outcomes in Patients With Cardiovascular Disease
Authors: Schultz William M. , Hayek Salim S. , Samman Tahhan Ayman , Ko Yi‐An , Sandesara Pratik , Awad Mosaab , Mohammed Kareem H. , Patel Keyur , Yuan Michael , Zheng Shuai , Topel Matthew L. , Hartsfield Joy , Bhimani Ravila , Varghese Tina , Kim Jonathan H. , Shaw Leslee , Wilson Peter , Vaccarino Viola , Quyyumi Arshed A.
Published: December 2017

Background

Being unmarried is associated with decreased survival in the general population. Whether married, divorced, separated, widowed, or never‐married status affects outcomes in patients with cardiovascular disease has not been well characterized.

Methods and Results

A prospective cohort (inception period 2003–2015) of 6051 patients (mean age 63 years, 64% male, 23% black) undergoing cardiac catheterization for suspected or confirmed coronary artery disease was followed for a median of 3.7 years (interquartile range: 1.7–6.7 years). Marital status was stratified as married (n=4088) versus unmarried (n=1963), which included those who were never married (n=451), divorced or separated (n=842), or widowed (n=670). The relationship between marital status and primary outcome of cardiovascular death and myocardial infarction was examined using Cox regression models adjusted for clinical characteristics. There were 1085 (18%) deaths from all causes, 688 (11%) cardiovascular‐related deaths, and 272 (4.5%) incident myocardial infarction events. Compared with married participants, being unmarried was associated with higher risk of all‐cause mortality (hazard ratio [HR]: 1.24; 95% confidence interval [
CI
], 1.06–1.47), cardiovascular death (
HR
: 1.45; 95%
CI
, 1.18–1.78), and cardiovascular death or myocardial infarction (
HR
: 1.52; 95% CI, 1.27–1.83). Compared with married participants, the increase in cardiovascular death or myocardial infarction was similar for the participants who were divorced or separated (HR: 1.41; 95%
CI
, 1.10–1.81), widowed (HR: 1.71; 95%
CI
, 1.32–2.20), or never married (HR: 1.40; 95%
CI
, 0.97–2.03). The findings persisted after adjustment for medications and other socioeconomic factors.

Conclusions

Marital status is independently associated with cardiovascular outcomes in patients with or at high risk of cardiovascular disease, with higher mortality in the unmarried population. The mechanisms responsible for this increased risk require further study.
The taxonomic revision of Asian Aristolochia (Aristolochiaceae) III: Two new taxa of Aristolochia and morphological revision for the flower character of A. obliqua from Yunnan, China
Authors: ZHU XIN-XIN , LIAO SHUAI , MA ZHENG-XU , XU BO , WANG ZHANG-HUA , WANG YUAN , MA JIN-SHUANG
Published: December 2017

In this paper, Aristolochia involuta and A. hainanensis subsp. yingjiangensis, two new taxa from Yunnan, China, are described and illustrated. The former is similar to A. bambusifolia in the calyx limb, but differs in the flower size and leaf shape. The latter differs from A. hainanensis by its leaf shape, fruit size and distribution. And we also clarify the flower character of Aristolochia obliqua.
First report of Limacella from Bangladesh, with a new species description
Authors: HOSEN MD. IQBAL , LI TAI-HUI
Published: December 2017

Limacella bangladeshana, a new species of well-known fungal family Amanitaceae from Bangladesh is described and illustrated based on morphology and molecular evidence. The species is mainly recognized by its medium-sized basidiomata, cream-white to off-white or buff-white pileus, the slightly uplifted pileal margin, globose basidiospores measuring 3.5–4 × 3.5–4 µm, an ixo-trichodermal pileipellis, and the common presence of clamp connections. Molecular phylogenetic analysis using sequence of the nuclear ribosomal large subunit (nrLSU) also supports the recognition of the new species in Limacella. This species represents the first generic record of Limacella for Bangladesh. Detailed description, color photos and illustration, and comparison with allied taxa are presented.