bluuebunny/crossref_metadata_2025 huggingface dataset:
58 Case Report: Clinical Challenges in the Diagnoses and Management of Delirious Mania in a US Veteran with a Mental Health History of Bipolar Disorder
Authors: Zaidi Muhammad , Brown Kurt , Brown Aquanette , Neptune Dominique , Perkins Vicenzio-Holder
Published: March 2019

A 46 year old Caucasian male veteran with a mental health history of Bipolar Disorder was admitted to the inpatient psychiatric unit following an episode of mania. He was re-started on his outpatient medication regimen for mood stabilization with Quetiapine, Lamotrigine, and Clonazepam. He improved initially, however, on hospital Day 3, the veteran was noted to have acute worsening of manic and psychotic symptoms including, decreased need for sleep, excess energy and responding to internal stimuli. Additionally, he developed symptoms which were atypical for mania, including unprovoked agitation, depersonalization, difficulty sustaining attention, and visual hallucinations. These mental status changes were associated with, excessive motor movement, walking with bizarre postures, squatting, laying taut on the ground, and standing still for several minutes in uncomfortable positions. At this time, Seroquel was switched with Olanzapine for management of mania and psychosis. On physical exam, his vital signs were notable for tachycardia and fever, his extremities were noted to have a normal range of motion; he also experienced loss of bowel continence. The treatment team initiated a medical work up for delirium which revealed no infectious, neurological, or metabolic cause. Of note, there was concern for benzodiazepine withdrawal; however, adequate management did not relieve the symptoms. The veteran was transferred to medicine and neurology was consulted to assist with medical workup. His neuroleptic and benzodiazepine medications were discontinued at that time, except for Lamotrigine. The veteran was then transferred back to psychiatry after medical stabilization, Lamotrigine was discontinued at that time. He was started on Haloperidol, Benztropine and restarted on Clonazepam. At this time, veteran experienced improvement on his mental status exam, with resolution of mania, psychosis, and delirium. However, after two days of treatment, he developed acute rigidity in his extremities. Intramuscular Benztropine and Lorazepam improved his rigidity. Haloperidol was discontinued because of side effects and the veteran was managed with Risperidone and Ativan. He continued to show improvement in his mental status examination and was discharged on a medication regimen of Risperidone, Clonazepam, and Benztropine. The veteran experienced signs and symptoms which were atypical in nature for Bipolar Mania, such as fever, movement disorder, and delirium. This presentation is consistent with a rare medical condition, Delirious Mania for which limited research is available. Delirious mania meets the criteria for mania and delirium with out an underlying medical disorder. Delirious mania is a potentially life threatening but under-recognized neuropsychiatric syndrome. Early recognition and aggressive treatment can significantly reduce morbidity and mortality.
59 “Lithium Damaged My Spine” Might not Be a Delusion After All
Authors: Zaidi Muhammad , Prabhu Anurag , Martell Jose Perez , Dhir Sakshi
Published: March 2019

Background

Lithium remains to be the drug of choice for treating BPAD for the past few decades. There is extensive literature showing the effectiveness of Lithium when used as a mood stabilizing agent in bipolar spectrum disorders. However significant number of articles show that a third of the patients who receive lithium for their symptomology not only do not show any response but also may show deterioration of their clinical symptoms. (However, research shows that Lithium may negatively affect a third of the patients depending on various factors). The side effect profile of Lithium and especially its neurotoxic effects were discussed in depth in literature over the last decade. Although Lithium remains first choice as maintenance treatment for bipolar affective disorder, about half of all individuals may stop their treatment at some point, despite its proven benefits concerning the prevention of severe affective episodes and suicide.

Methods

The authors performed a systematic literature review to recognize the significance of negative effects of Lithium in a minority of patient population and also comment on the factors influencing patient compliance. We ran a literature search on Pubmed using the following terms: “Lithium” AND (“schizoaffective disorder [MeSH terms]” OR “Bipolar Affective disorder [MeSH terms]” ). Our inclusion criteria were studies which have observed effects of Lithium in schizoaffective patient population or bipolar affective patient population. Studies with other concurrent diagnoses were excluded.

Case presentation

We discuss a fifty nine year old male with a history of multiple admissions to a forensic hospital care setting. He initially endorsed a diagnosis of Psychotic disorder NOS which was later changed to schizoaffective disorder during his subsequent admissions. He presented with affective psychotic features where his mood was labile shifting from melancholic to euphoric and a concurrent history of auditory verbal hallucinations. He displayed paranoid non-bizarre persecutory delusions and also alleged that one of his doctors had hated him and put him on Lithium as a form of punishment. He claims that Lithium, as a result, has significantly affected him negatively and also damaged his nerves. This led the authors to explore the significance of use of Lithiumin people with schizoaffective disorders and also bipolar affective disorders. We also discuss the disease course in the patient and his clinical response to use of various psychotropic medications.

Conclusions

The case exemplifies the negative effects of Lithium when used as a mood stabilizer in patient population that is susceptible to its adverse effects due to various factors.
74 Alpha Lipoic Acid Responsive Hypergeusia
Authors: Cormie Sarah E. , Hirsch Alan R.
Published: March 2019

Introduction

Improvement in hypergeusia in response to alpha lipoic acid treatment has not heretofore been described. Such a case is presented.

Methods

Case Study: A 64 year old right handed nasute female noted the sudden onset of salty hypergeusia, about 200% saltier than foods should be. Concurrently she experienced a constant phantogeusia of salt involving the front half of her tongue, lips, and inside her mouth. She denied any smell problems, cacogeusia, or palinageusia. This persisted for five months until treatment with 1800mg/day of alpha lipoic acid, whereupon, over a one month duration, the salty hypergeusia gradually resolved. Suppression of the salty hypergeusia continued until she developed an upper respiratory infection, whereupon, despite the continuation of alpha lipoic acid, the salty hypergeusia returned to 250% of normal. During the cold, her ability to taste dropped down from 100% to 80%, and ability to smell dropped from 100% to 50% and upon resolution of the cold, the senses returned to normal and the salty hypergeusia remitted.

Results

Abnormalities in Neurologic Examination: Reflexes: 3+ bilateral quadriceps femoris and pendular. Chemosensory testing: Olfaction: Alcohol Sniff Test: 12 (hyposmia), Phenylethyl Alcohol Threshold: greater than –2 (anosmia). Suprathreshold Amyl Acetate Odor Intensity Testing: parallel pattern (normosmia). Pocket Smell Test: 4(normosmia). Retronasal Olfactory Testing: Retronasal Smell Index: 8(normosmia). Gustatory testing: Propylthiouracil Disc Taste Test: 5(normogeusia). Taste Super threshold Testing: normogeusia to sodium chloride, sucrose, and phenylthiocarbamol: hypogeusia(10–30%) to urea; ageusia(0%) to hydrochloric acid. Taste Quadrant Testing: taste weakness to sodium chloride for the entire mouth.

Discussion

The alpha lipoic acid may have acted to improve smell and associated enhanced retro nasal smell, inhibiting savory gustatory discharge, and thus, effectively reducing salt perception. Such a mechanism would also explain the recurrence of hypergeusia with the upper respiratory infection; the infection presumably transiently reducing the olfactory ability, overcoming any olfactory enhancing effects of alpha lipoic acid. On the other hand, this agent could have acted to improve smell as well as taste. With such enhanced chemosensory capacity, the normal olfactory and gustatory components of food would have inhibited competing pathologically discharging gustatory receptors for salt, reducing dysgeusia and hypergeusia. Moreover, the alpha lipoic acidmay have acted to focus the patient’s attention on the gustatory stimulation which may have caused her to perceive not just the predominant salt sensation but enhanced perception of the other gustatory sensations which acted to competitively inhibit the perception of salt. Further investigation of alpha lipoic acid in the management of dysgeusia and hypergeusia is warranted.
80 Misdiagnosis as a Cause of Treatment Failure in Repetitive Transcranial Magnetic Stimulation Therapy (rTMS) for MDD
Authors: Malik Sitwat , Malik Azfar , Mercille Kimberly
Published: March 2019

Background and Objective

Research suggests that repetitive Transcranial Magnetic Stimulation (rTMS) is effective, safe, and proven treatment option for patients with treatment resistant major depressive disorder (MDD). Success rate is high, around 65–70% nationwide. Around 30% patients are still not responding to the treatment. Objective of this study is to evaluate the cause of treatment failure or non-responsiveness of TMS treatment despite high efficacy of the therapy. This is the first study to evaluate the cause of treatment failure of TMS therapy.

Method

Retrospective, 16months, post- TMS treatment, Clinical rating scales PHQ-9 and GAD-7.

68 patients who got treatment over 16months were included in the study, inclusion criteria for thisstudy

includes patients with primary diagnosis of MDD, have previously received at least 20 TMS treatments

and must be evaluated with at least two clinical rating scales that were entered each day during treatment.

Result

Number of treated patients:68

Patients responded to treatment: 50 (73.5%)

Patients not responded: 18 (26.4%)

Mean # of treatments received:37

Mean Baseline PHQ-9 Score:19

Mean Outcome PHQ-9 Score:7

To evaluate the cause of treatment failure in 18 non-responsive patients, patient charts were reviewed in detail. Patients were interviewed near the end of treatment, during follow-ups, and over the phone. It was established that they were either misdiagnosed, have symptoms of other psychiatric disorders such as bipolar depression, have dual diagnoses (e.g: MDD with anxiety, OCD, PTSD) or unclear diagnoses and in need of further psychiatric evaluations. The variety of these diagnostic scenarios mentioned are not typically treated with TMS therapy or treated differently with TMS as compared to MDD, hence the explanation of therapy failure.

Conclusion

Number one cause of TMS treatment failure is misdiagnosis due to various reasons. That includes failure to be accurately diagnosed by a primary psychiatrist, as those patients did not have primary psychiatrist and were referred by primary care physicians and were getting treated for MDD without a proper psychiatric evaluation and diagnosis. However, due to the limitations of the study due to small sample size, we propose that further investigations are needed to be replicated in larger patient population.
82 Ice Melts Phantogeusia: Cold Inhibition of Gustatory Hallucinations
Authors: Mutti Suhanna , Hirsch Alan R.
Published: March 2019

Introduction

Relief of phantogeusia through ice cube stimulation has not heretofore been noted.

Methods

This 70-year-old left handed (familial) female noted the onset, three and a half years ago, of reduced taste 80 percent of normal, distorted taste, hallucinated metallic taste, and BMS. Upon application of an ice cube to the tongue, both the metallic taste and the BMS resolved for a few seconds, without impairing her true taste ability. With repeat application, the alleviation effect persists.

Results

Abnormalities in Neurologic Examination: Sensory Examination: Decreased pinprick and temperature bilateral lower extremities. Reflexes: 3+ throughout. Bilateral positive Hoffman’s reflexes. Chemosensory testing: Olfaction: Brief Smell Identification Test: 9 (normosmia). Retronasal Smell Index: 10 (normosmia). Gustation: Propylthiouracil Disc Taste Test: 5 (normogeusia).

Discussion

Transient Receptor Potential 5, is expressed in tongue taste buds, facilitating sweet perception, and is temperature dependent (Fujiyama, 2010). Ice may act to reduce such sweet taste receptor discharge, causing an imbalance in taste fiber discharge thus inhibiting the perceived metallic taste. In those who suffer from intractable phantogeusia, a trial of ice cubes or mechanisms to reduce temperature of the tongue is warranted.
93 Practical Outpatient Pharmacotherapy for Alcohol Use Disorder
Authors: Kim Youngjung , Hack Laura M , Ahn Elizabeth S , Kim Jungjin
Published: March 2019

Alcohol use disorder (AUD) is commonly encountered in clinical practice. A combination of psychosocial intervention and pharmacotherapy is the cornerstone of AUD treatment. Despite their efficacy, safety and cost-effectiveness, clinicians are reluctant to prescribe medications to treat individuals with AUD. Given the high rate of relapse with psychosocial intervention alone, increasing patient access to this underutilized treatment has the potential to improve clinical outcome in this difficult-to-treat population. Herein, we provide practical pharmacotherapy strategies to improve treatment outcome for AUD. We review the efficacy and side effects of both on- and off-label agents with a particular focus on clinical applicability. Recommendations are supported by findings from randomized controlled trials (RCT) and meta-analyses selected to be representative, where possible, of current treatment guidelines. The goal of this paper is to help readers use pharmacotherapy with greater confidence when treating patients with AUD.
97 My Inner Blizzard: Effect of Weather on Multiple Sclerosis Exacerbation
Authors: Winchester Chevelle R. , Batta Priya , Davinder Dhillon , Hirsch Alan R.
Published: March 2019

Study Objective

Exacerbation of Multiple Sclerosis (MS) symptoms prior to weather change has not heretofore been described.

Methods

Case Study: A 60 year old right handed female with lifelong anxiety and four years of depression presented with a 20 year history of MS manifested by bilateral lower extremity pain and weakness and urinary incontinence. Since the onset, she observed that approaching storms or weather changes cause her symptoms to worsen. This manifests one day prior to the meteorological shifts of rain or snow. This occurs whether she is at home or on vacation and unlike the weatherman, “she is never wrong.” The aggravation of symptomatology would consist of worsening leg pain and weakness of both lower extremities so that her functional status changes from using a cane to a wheelchair. These symptoms begin one day prior to the storm and gradually worsen to the point of maximum intensity as the storm arrives. The baseline pain is usually 5/10 in severity but with the storm it increases to 8/10. The pain, which progressively worsens as the storm advances, is a vice-like numbness in her shins and spasm in her legs. The pain and weakness will persist for as long as the storm lasts. The pain diminishes and the motor symptoms improve six hours after the storm is over. She can differentiate approaching snow or rain such that snow causes more intense symptoms. She denies change in symptomatology on airplanes or when she is present at high altitude such as Las Vegas or Colorado. She also affirms that her symptoms are worse when she is in a hot tub and better in a cold-water bath. She reports that there is a family history of similar ability to predict the weather in a cousin and nephew, both who also suffer from MS.

Results

Abnormalities in Neurological Examination: BP 159/115. Pulse 100. Mental Status Examination: disheveled. Depressed mood with congruent affect. Short-term memory: 5 digits forwards, 2 digits backwards. Recent memory: able to recall none of 4 objects in 3minutes without improvement with reinforcement. Unable to interpret similarities or proverbs. Poor ability to calculate. Reflexes: 3+ bilateral lower extremities. Clock Drawing Test: 1 (abnormal).

Conclusions

Uhthoff’s phenomena (hot bath test) is well described in MS (Humm, 2004), however the worsening of symptoms prior to weather change has not been reported. Possible mechanisms include meteorological induced anxiety and depression with associated exacerbation (Ackerman, 1998). Other possible mechanisms include misattribution, selective recall, or a misreporting due to psychological needs for acceptance by examiner, similar to the Hawthorne effect (observer effect) (Adair, 1984). With the approaching storms there could be a change in internal temperature, which then preferentially affects areas of demyelination (Kudo, 2014). It is worth querying those with epoch associated neurological disorders as to linkage with meteorological events.
Psychopharmaka – ja oder nein?
Authors: Kleeberg Annette
Published: March 2019

Zusammenfassung. Was gibt es aus meiner Perspektive der Psychiatrie-Erfahrenen zum Thema Psychopharmaka zu sagen? Sind Psychopharmaka gut oder schlecht? Wie gehen die skandinavischen Nachbarn mit dem Einsatz von Psychopharmaka um? Können Medikamente helfen? Das sind die Fragen, mit denen ich mich in den nachfolgenden Ausführungen befasse. Gleichzeitig ist es ein Rückblick auf meine persönliche Geschichte – beginnend Mitte der 1980er-Jahre in Hessen bis heute. Es ermöglicht mir, das Erlebte neu zu betrachten und zu bewerten.
Lebendiges Konzept
Authors: Gödecke Simon
Published: March 2019

Zusammenfassung. Kommt man mit anderen professionellen Akteuren über Recovery als individuelle Entwicklungsmöglichkeit für psychisch erkrankte Menschen ins Gespräch, landet man schnell beim Thema Psychopharmaka. Die Gedanken an Hoffnung auf Genesung, Sinnhaftigkeit, Empowerment sind dabei für die meisten einleuchtend und als etwas Erstrebenswertes, etwas, das man unterstützen und worauf man gerne hinarbeiten möchte. Wenn es jedoch um die Frage der Medikamente geht, wird man schnell feststellen, dass die meisten professionellen Helfer, aber auch manche Angehörige und weite Teile der Gesellschaft, sich ein Genesen ohne Medikamente nicht vorstellen können und die Sichtweise der Recovery-Bewegung mit Skepsis betrachten. Im Artikel wird versucht herauszufinden, wie die Haltung der Recovery-Bewegung gegenüber Medikamenten ist und welche Möglichkeiten und Konzepte sich für die psychiatrische Praxis im Alltag ergeben.
Psychopharmaka als Hoffnungsträger
Authors: Heim Susanne
Published: March 2019

Zusammenfassung. Die medikamentöse Behandlung ist wohl nirgends so umstritten wie in der Psychiatrie. Erkrankte lehnen oftmals jegliche „Chemie“ vehement ab und setzen allenfalls auf Homöopathie oder Naturheilmittel. Angehörige sind eher überzeugt, dass psychischen Erkrankungen nur mit Psychopharmaka zu heilen sind. Eine nüchtern abwägende Betrachtungsweise stößt bei beiden Parteien bestenfalls auf widerwillige Skepsis. So bleibt das Ringen um die Medikation auch in den betroffenen Familien ein Dauerbrenner.
Coherence‐Based Approaches for Estimating the Composition of the Seismic Wavefield
Authors: Coughlin M. , Harms J. , Bowden D. C. , Meyers P. , Tsai V. C. , Mandic V. , Pavlis G. , Prestegard T.
Published: March 2019

As new techniques exploiting the Earth's ambient seismic noise field are developed and applied, such as for the observation of temporal changes in seismic velocity structure, it is crucial to quantify the precision with which wave‐type measurements can be made. This work uses array data at the Homestake mine in Lead, South Dakota, and an array at Sweetwater, Texas, to consider two aspects that control this precision: the types of seismic wave contributing to the ambient noise field at microseism frequencies and the effect of array geometry. Both are quantified using measurements of wavefield coherence between stations in combination with Wiener filters. We find a strong seasonal change between body‐wave and surface‐wave content. Regarding the inclusion of underground stations, we quantify the lower limit to which the ambient noise field can be characterized and reproduced; the applications of the Wiener filters are about 4 times more successful in reproducing ambient noise waveforms when underground stations are included in the array, resulting in predictions of seismic time series with less than a 1% residual, and are ultimately limited by the geometry and aperture of the array, as well as by temporal variations in the seismic field. We discuss the implications of these results for the geophysics community performing ambient seismic noise studies, as well as for the cancellation of seismic Newtonian gravity noise in ground‐based, sub‐Hertz, gravitational‐wave detectors.
Lithospheric Thickness of Volcanic Rifting Margins: Constraints From Seaward Dipping Reflectors
Authors: Tian Xiaochuan , Buck W. Roger
Published: March 2019

Seaward dipping reflectors (SDRs) are large piles of seaward thickening volcanic wedges imaged seismically along most rifted continental margins. Despite their global ubiquity, it is still debated whether the primary cause of SDR formation is tectonic faulting or magmatic loading. To study how SDRs might form, we developed the first two‐dimensional thermomechanical model that can account for both tectonics and magmatism development of SDRs during rifting. We focus here on the magmatic loading mechanism and show that the shape of SDRs may provide unprecedented constraints on lithospheric strength at volcanic rifting margins. For mapping SDRs geometries to lithospheric strength, a sequence of model lithospheric rheologies are treated, ranging from analytic thin elastic plates to numerical thick elasto‐visco‐plastic crust and mantle layers with temperature and stress‐dependent viscosity. We then analyzed multichannel seismic depth‐converted images of SDRs from Vøring and Argentinian rifted margins in terms of geometric parameters that can be compared to our model results. This results in estimates for the lithospheric thickness during rifting at the two margins of 3.4 and 5.7 km. The plate thickness correlates inversely with mantle potential temperature at these margins during rifting, as estimated by independent studies.
Roles of the Tropical/Extratropical Intraseasonal Oscillations on Generating the Heat Wave Over Yangtze River Valley: A Numerical Study
Authors: Qi Xin , Yang Jing , Gao Miaoni , Yang Hongwei , Liu Hongbo
Published: March 2019

Yangtze River Valley (YRV) is the core region for the occurrence of heat wave (HW) in China. HW over YRV has been reported to be associated with intraseasonal oscillations (ISOs) from tropical/extratropical regions. However, the specific roles of these ISOs on the generation of HW cannot be separated in the observational analysis. This study identified the impact of ISOs from tropic/extratropic on the period of HW development through partial lateral forcing (PLF) experiments using the Weather Research and Forecasting model for a typical ISO‐related HW event over YRV in 2012. The observations show that a remarkable eastward/westward extension of South Asian high/western North Pacific subtropical high accompanied the HW occurrence. Accordingly, this anomalous strong high pressure produced the HW through horizontal warm advection and adiabatic heating, which was related to a lower‐level westward propagating meridional dipole anomaly and an upper‐level eastward migrating wave train from the extratropical region. The PLF experiments confirmed that this HW event was caused by the propagation of intraseasonal perturbations from the surrounding regions. The tropical westward propagating meridional dipole anomaly directly generated a lower‐level anomalous anticyclone in the early period of HW development, whereas extratropical intraseasonal forcing primarily contributed to the eastward extension of the South Asian high in the late, which jointly established the strong high pressure and caused the HW. The PLF experiments also indicate plausible tropical–extratropical interaction of intraseasonal perturbations over YRV. Improving the prediction skills of the tropical/extratropical ISOs may facilitate the subseasonal forecast of the local HW events.
Sea Surface Temperatures and Paleoenvironmental Variability in the Central Mediterranean During Historical Times Reconstructed Using Planktonic Foraminifera
Authors: Incarbona Alessandro , Jonkers Lukas , Ferraro Serena , Sprovieri Rodolfo , Tranchida Giorgio
Published: March 2019

The ongoing anthropogenic‐induced warming assessment requires a robust background from regional sea surface temperature (SST) reconstructions. Planktonic foraminifera have yielded valuable insights into late Quaternary SST dynamics, but the techniques to estimate SST from fossil assemblages have only rarely been used in very recent sedimentary records (the last 2,000 years). Here we use two transfer function methods, modern analog technique and artificial neural networks, to reconstruct SST variability in two cores from the Central Mediterranean Sea that span the last five centuries. Both cores show similar and considerable changes in the planktonic foraminifera assemblages. However, the inferred mean annual SSTs only varied in a narrow range, in agreement with instrumental data that go back to 1850 CE. Our reconstructions extend this time frame and indicate that SST variability did not exceed 1.5 °C over the past three centuries. Rather than temperature, we suggest that the changes in the assemblages reflect switches between sea surface winter/spring productivity and a deep winter mixed layer, due to the atmosphere/ocean interplay that governs different productivity modes in neighboring mesoscale gyres.
Making the First National Seafloor Habitat Map
Authors: Lucieer Vanessa , Johnson Craig , Barrett Neville
Published: March 2019

Seamap Australia integrates seafloor maps with information on plant and animal habitats, environmental stressors, and resource management to create a first-of-its-kind resource.
Magnetic Anomalies on the Pacific Plate Reveal True Polar Wander
Authors: Sidder Aaron
Published: March 2019

A new study rebuffs the standard approach to paleomagnetism and offers an updated methodology and new locations of paleomagnetic poles.
Genome Analysis of A Novel Recombinant Human Adenovirus Type 1 in China
Authors: Zhang Wanju , Huang Lisu
Published: March 2019

Human adenovirus (HAdV) group C are the common etiologic in infants with severe acute respiratory infections (SARI). In the study, we report that a novel recombinant HAdV-C group strain (SH2016) was isolated from an infant with SARI in Shanghai in Feb. 4, 2016. The whole-genome sequence of SH2016 strain was generated and compared to other HAdV genomes publicly available. The strain SH2016 genome contains 35,946 nucleotides and coded 40 putative proteins, which was divided into 11 regions. RDP and phylogenetic analyses of the complete genome showed that the SH2016 strain was arranged into a novel subtype and might be recombined with HAdV-1 and HAdV-2. Our finding indicated that the frequent recombination among the HAdV-C group played an important role in driving force for polymorphism of human HAdV-C group prevalent in Shanghai, China. Further epidemiological surveillance of HAdV-C group is necessary to explore whether the novel HAdV-C group will maintain long-term stability. And the pathogenicity and clinical characteristics of the novel HAdV-C group member should be done more.
Glatiramer Acetate modulates ion channels expression and calcium homeostasis in B cell of patients with relapsing-remitting multiple sclerosis
Authors: Criscuolo C. , Cianflone A. , Lanzillo R. , Carrella D. , Carissimo A. , Napolitano F. , de Cegli R. , de Candia P. , La Rocca C. , Petrozziello T. , Matarese G. , Boscia F. , Secondo A. , Di Bernardo D. , Brescia Morra V.
Published: March 2019

To investigate the effects of Glatiramer Acetate (GA) on B cells by an integrated computational and experimental approach. GA is an immunomodulatory drug approved for the treatment of multiple sclerosis (MS). GA effect on B cells is yet to be fully elucidated. We compared transcriptional profiles of B cells from treatment-naïve relapsing remitting MS patients, treated or not with GA for 6 hours in vitro, and of B cells before and after six months of GA administration in vivo. Microarrays were analyzed with two different computational approaches, one for functional analysis of pathways (Gene Set Enrichment Analysis) and one for the identification of new drug targets (Mode-of-action by Network Analysis). GA modulates the expression of genes involved in immune response and apoptosis. A differential expression of genes encoding ion channels, mostly regulating Ca2+ homeostasis in endoplasmic reticulum (ER) was also observed. Microfluorimetric analysis confirmed this finding, showing a specific GA effect on ER Ca2+ concentration. Our findings unveils a GA regulatory effect on the immune response by influencing B cell phenotype and function. In particular, our results highlight a new functional role for GA in modulating Ca2+ homeostasis in these cells.
Ectopic expression of Snord115 in choroid plexus interferes with editing but not splicing of 5-Ht2c receptor pre-mRNA in mice
Authors: Raabe Carsten A. , Voss Reinhard , Kummerfeld Delf-Magnus , Brosius Juergen , Galiveti Chenna R. , Wolters Anna , Seggewiss Jochen , Huge Andreas , Skryabin Boris V. , Rozhdestvensky Timofey S.
Published: March 2019

Serotonin 5-HT2C receptor is a G-protein coupled excitatory receptor that regulates several biochemical pathways and has been implicated in obesity, mental state, sleep cycles, autism, neuropsychiatric disorders and neurodegenerative diseases. The activity of 5-HT2CR is regulatedviaalternative splicing and A to I editing of exon Vb of its pre-mRNA. Snord115 is a small nucleolar RNA that is expressed in mouse neurons and displays an 18-nucleotide base complementary to exon Vb of 5-HT2CR pre-mRNA. For almost two decades this putative guide element of Snord115 has wandered like a ghost through the literature in attempts to elucidate the biological significance of this complementarity. In mice, Snord115 is expressed in neurons and absent in the choroid plexus where, in contrast, 5-Ht2cr mRNA is highly abundant. Here we report the analysis of 5-Ht2cr pre-mRNA posttranscriptional processingviaRNA deep sequencing in a mouse model that ectopically expresses Snord115 in the choroid plexus. In contrast to previous reports, our analysis demonstrated that Snord115 does not control alternative splicing of 5-Ht2cr pre-mRNAin vivo. We identified a modest, yet statistically significant reduction of 5-Ht2cr pre-mRNA A to I editing at the major A, B, C and D sites. We suggest that Snord115 and exon Vb of 5Ht2cr pre-mRNA form a double-stranded structure that is subject to ADAR-mediated A to I editing. To the best of our knowledge, this is the first comprehensive Snord115 gain-of-function analysis based onin vivomouse models.
Engulfment, persistence and fate of Bdellovibrio bacteriovorus predators inside human phagocytic cells informs their future therapeutic potential
Authors: Raghunathan Dhaarini , Radford Paul M. , Gell Christopher , Negus David , Moore Christopher , Till Rob , Tighe Patrick J. , Wheatley Sally P. , Martinez-Pomares Luisa , Sockett R. Elizabeth , Tyson Jess
Published: March 2019

In assessing the potential of predatory bacteria, such as Bdellovibrio bacteriovorus, to become live therapeutic agents against bacterial infections, it is crucial to understand and quantify Bdellovibrio host cell interactions at a molecular level. Here, we quantify the interactions of live B. bacteriovorus with human phagocytic cells, determining the uptake mechanisms, persistence, associated cytokine responses and intracellular trafficking of the non-growing B. bacteriovorus in PMA-differentiated U937 cells. B. bacteriovorus are engulfed by U937 cells and persist for 24 h without affecting host cell viability and can be observed microscopically and recovered and cultured post-uptake. The uptake of predators is passive and depends on the dynamics of the host cell cytoskeleton; the engulfed predators are eventually trafficked through the phagolysosomal pathway of degradation. We have also studied the prevalence of B. bacteriovorus specific antibodies in the general human population. Together, these results quantify a period of viable persistence and the ultimate fate of B. bacteriovorus inside phagocytic cells. They provide new knowledge on predator availability inside hosts, plus potential longevity and therefore potential efficacy as a treatment in humans and open up future fields of work testing if predators can prey on host-engulfed pathogenic bacteria.
Author Correction: Density functional theory study of the role of benzylic hydrogen atoms in the antioxidant properties of lignans
Authors: Vo Quan V. , Nam Pham Cam , Van Bay Mai , Thong Nguyen Minh , Cuong Nguyen Duc , Mechler Adam
Published: March 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Two-tailed RT-qPCR panel for quality control of circulating microRNA studies
Authors: Androvic Peter , Romanyuk Nataliya , Urdzikova-Machova Lucia , Rohlova Eva , Kubista Mikael , Valihrach Lukas
Published: March 2019

Circulating cell-free microRNAs are promising candidates for minimally invasive clinical biomarkers for the diagnosis, prognosis and monitoring of many human diseases. Despite substantial efforts invested in the field, the research so far has failed to deliver expected results. One of the contributing factors is general lack of agreement between various studies, partly due to the considerable technical challenges accompanying the workflow. Pre-analytical variables including sample collection, RNA isolation, and quantification are sources of bias that may hamper biological interpretation of the results. Here, we present a Two-tailed RT-qPCR panel for quality control, monitoring of technical performance, and optimization of microRNA profiling experiments from biofluid samples. The Two-tailed QC (quality control) panel is based on two sets of synthetic spike-in molecules and three endogenous microRNAs that are quantified with the highly specific Two-tailed RT-qPCR technology. The QC panel is a cost-effective way to assess quality of isolated microRNA, degree of inhibition, and erythrocyte contamination to ensure technical soundness of the obtained results. We provide assay sequences, detailed experimental protocol and guide to data interpretation. The application of the QC panel is demonstrated on the optimization of RNA isolation from biofluids with the miRNeasy Serum/Plasma Advanced Kit (Qiagen).
Primary lung cancer samples cultured under microenvironment-mimetic conditions enrich for mesenchymal stem-like cells that promote metastasis
Authors: Saforo Douglas , Omer Linda , Smolenkov Andrei , Barve Aditya , Casson Lavona , Boyd Nolan , Clark Geoffrey , Siskind Leah , Beverly Levi
Published: March 2019

The tumor microenvironment (TME) is composed of a heterogeneous biological ecosystem of cellular and non-cellular elements including transformed tumor cells, endothelial cells, immune cells, activated fibroblasts or myofibroblasts, stem and progenitor cells, as well as the cytokines and matrix that they produce. The constituents of the TME stroma are multiple and varied, however cancer associated fibroblasts (CAF) and their contribution to the TME are important in tumor progression. CAF are hypothesized to arise from multiple progenitor cell types, including mesenchymal stem cells. Currently, isolation of TME stroma from patients is complicated by issues such as limited availability of biopsy material and cell stress incurred during lengthy adaptation to atmospheric oxygen (20% O2) in cell culture, limiting pre-clinical studies of patient tumor stromal interactions. Here we describe a microenvironment mimetic in vitro cell culturing system that incorporates elements of the in vivo lung environment, including lung fibroblast derived extracellular matrix and physiological hypoxia (5% O2). Using this system, we easily isolated and rapidly expanded stromal progenitors from patient lung tumor resections without complex sorting methods or growth supplements. These progenitor populations retained expression of pluripotency markers, secreted factors associated with cancer progression, and enhanced tumor cell growth and metastasis. An understanding of the biology of these progenitor cell populations in a TME-like environment may advance our ability to target these cells and limit their effects on promoting cancer metastasis.
Intestine specific regulation of pig cytidine-5′-monophospho-N-acetylneuraminic acid hydroxylase gene for N-glycolylneuraminic acid biosynthesis
Authors: Song Kwon-Ho , Kwak Choong-Hwan , Chung Tae-Wook , Ha Sun-Hyung , Park Jun-Young , Ha Ki-Tae , Cho Seung-Hak , Lee Young-Choon , Kim Cheorl-Ho
Published: March 2019

N-glycolylneuraminic acid (Neu5Gc), a generic form of sialic acid, is enzymatically synthesized by cytidine-5′-monophospho-N-acetylneuraminic acid hydroxylase (CMAH). Although expression of pig CMAH gene pcmah encoding CMAH has been reported to be regulated by pathogenic infection and developmental processes, little is known about the mechanisms underlying the regulation of pcmah gene expression. The objective of this study was to determine mechanism(s) involved in intestine specific regulation of pcmah gene by identifying several cis-acting elements and nuclear transcription factors that could directly interact with these cis-acting elements. We identified intestine specific promoter region (Pi) of pcmah gene located at upstream regions of the 5′flanking region of exon 1a and found that the promoter region is responsible for the transcriptional regulation of 5′pcmah-1. Based on reporter assays using serially constructed luciferase genes with each deleted promoter, we demonstrated that the Pi promoter activity was more active in intestinal IPI-2I cells than that in kidney PK15 cells, corresponding to both mRNA expression patterns in the two cell lines. In addition, we found that Sp1 transcription factor was necessary for basal activity of Pi promoter and that Ets-1 contributed to intestine-specific activity of Pi promoter. This study helps us understand transcriptional regulation of pcmah in the intestine of pig tissues. It also allows us to consider potential roles of Neu5Gc in interaction with environmental factors present in the intestinal tissue during pathogenic infection and developmental process.
Limited freshwater cap in the Eocene Arctic Ocean
Authors: Neville Lisa A. , Grasby Stephen E. , McNeil David H.
Published: March 2019

Remains of the freshwater fern Azolla, found in Eocene (~50 Ma ago) sediments in the modern central Arctic Ocean, have been used to suggest that seasonal freshwater caps covered the entire Arctic Ocean during that time, with significant impact on global ocean circulation and climate. However, these records are located on the Lomonosov Ridge, which during the Eocene was a continental fragment barely rifted from Eurasia, separating the smaller Eurasian Basin from the much larger Amerasian Basin to the west. As such, the Lomonosov Ridge does not necessarily record environmental conditions of the broader Arctic Ocean. We tested the hypothesis of freshwater caps by examining sediment records from the western Amerasian Basin. Here we show that in the larger Amerasian Basin the Azolla event is associated with marine microfauna along with allochthonous (terrestrially sourced) organic matter. We propose that Azolla events are related to an increased hydrologic cycle washing terrestrially sourced Azolla, and other organics, into the Arctic Ocean. If freshwater caps did occur, then they were at best restricted to the small Eurasian Basin and would have had a limited impact on Eocene global climate, contrary to current models.
Three-dimensional geometry of human tibial anterior curvature in chronologically distinct population samples of Central Europeans (2900 BC – 21st century AD)
Authors: Brzobohatá Hana , Krajíček Václav , Velemínský Petr , Velemínská Jana
Published: March 2019

Several lines of bioarchaeological research have confirmed the gradual decline in lower limb loading among past human populations, beginning with the transition to agriculture. The goal of this study was to assess whether human tibial curvature reflects this decline, with a special emphasis on the time-span during which the pace of technological change has been the most rapid. Our study is the first (1) to apply longitudinal curvature analysis in the antero-posterior (A–P) and medio-lateral (M–L) planes to the human tibia, and (2) that incorporates a broad temporal population sample including the periods of intensification of agriculture, urbanization and industrialization (from 2900 BC to the 21stcentury AD; N = 435) within Czech territories. Using three-dimensional geometric morphometrics, we investigated whether anterior tibial curvature mirrors assumed diminishing lower limb loading between prehistoric and industrialized societies and explored its shape in all three dimensions. Results showed the continuous trend of A–P straightening of the shaft. This straightening was associated with a relative sigmoidal curve accentuation in the M-L plane. Given the timescale involved and the known phenomenon of declining mobility, such adaptive changes in bone geometry can be interpreted in terms of the diminishing biomechanical demands on the tibia under different living conditions.
Focus Tracking System for Femtosecond Laser Machining using Low Coherence Interferometry
Authors: Raele Marcus Paulo , De Pretto Lucas Ramos , de Rossi Wagner , Vieira Nilson Dias , Samad Ricardo Elgul
Published: March 2019

We designed a real time, single-laser focus tracking system using low coherence properties of the machining femtosecond laser itself in order to monitor and correct the sample position relative to the focal plane. Using a Michelson Interferometer, the system collects data arising from part of the beam backscattered at the ablation spot. The data is analyzed by a custom software for position correction (employing an XYZ automated translation stage). With the focus tracking enabled we were able to etch channels with a stable cross-section profile on a bovine tooth with relief amplitude tens of times greater than the Rayleigh length of the system, keeping the sample inside the confocal parameter during most of the processing time. Moreover, the system is also capable of monitoring crater depth evolution during the ablation process, allowing for material removal assessment.
Effects of species traits and environmental predictors on performance and transferability of ecological niche models
Authors: Regos Adrián , Gagne Laura , Alcaraz-Segura Domingo , Honrado João P. , Domínguez Jesús
Published: March 2019

The ability of ecological niche models (ENMs) to produce robust predictions for different time frames (i.e. temporal transferability) may be hindered by a lack of ecologically relevant predictors. Model performance may also be affected by species traits, which may reflect different responses to processes controlling species distribution. In this study, we tested four primary hypotheses involving the role of species traits and environmental predictors in ENM performance and transferability. We compared the predictive accuracy of ENMs based upon (1) climate, (2) land-use/cover (LULC) and (3) ecosystem functional attributes (EFAs), and (4) the combination of these factors for 27 bird species within and beyond the time frame of model calibration. The combination of these factors significantly increased both model performance and transferability, highlighting the need to integrate climate, LULC and EFAs to improve biodiversity projections. However, the overall model transferability was low (being only acceptable for less than 25% of species), even under a hierarchical modelling approach, which calls for great caution in the use of ENMs to predict bird distributions under global change scenarios. Our findings also indicate that positive effects of species traits on predictive accuracy within model calibration are not necessarily translated into higher temporal transferability.
Facile synthesis of graphene-tin oxide nanocomposite derived from agricultural waste for enhanced antibacterial activity against Pseudomonas aeruginosa
Authors: Mohan Anu N. , B Manoj , Panicker Sandhya
Published: March 2019

Antibacterial screening of graphene-tin oxide nanocomposites synthesized from carbonized wood and coconut shell is investigated against Pseudomonas aeruginosa for the first time. Efficient and facile one step hydrothermal process adopted in the present work for the synthesis of graphene-tin oxide nanoparticles provides an ideal method for the economic large-scale production of the same. Graphene-tin oxide nanocomposites derived from wood charcoal possess a spherical morphology whereas rod like structures are seen in the case of coconut shell derivatives. An excitation independent fluorescence response is observed in graphene-tin oxide nanohybrids while graphene oxide nanostructures exhibited an excitation dependent behavior. These hydrophilic nanostructures are highly stable and exhibited no sign of luminescence quenching or particle aggregation even after a storage of 30 months. Bactericidal effects of the nanostructures obtained from coconut shell is found to be relatively higher compared to those procured from wood. This variation in antibacterial performance of the samples is directly related to their morphological difference which in turn is heavily influenced by the precursor material used. MIC assay revealed that coconut shell derived graphene-tin oxide composite is able to inhibit the bacterial growth at a lower concentration (250 μg/mL) than the other nanostructures. Nanocomposites synthesized from agro-waste displayed significantly higher antimicrobial activity compared to the precursor and graphene oxide nanostructures thereby making them excellent candidates for various bactericidal applications such as disinfectants, sanitary agents etc.
Proposal of a rhombohedral-tetragonal phase composition for maximizing piezoelectricity of (K,Na)NbO3 ceramics
Authors: Lee Min-Ku , Yang Sun-A , Park Jin-Ju , Lee Gyoung-Ja
Published: March 2019

Great progress in the field of piezoelectricity of (K,Na)NbO3 (KNN) lead-free ceramics, driven by emerging rhombohedral-tetragonal (R-T) phase boundary, has instigated research activity regarding elaborate controls of the phase boundary structure. Through phase-microstructure-property mapping in KNN ceramics doped with Bi-containing perovskite oxides, in this study we for the first time report the existence of a certain R-T phase boundary state by which to create maximum piezoelectric response in KNN systems. This phase boundary condition is usually comprised of approximately 15% R phase and 85% T phase, regardless of the choice of dopant material. Any deviation from this phase composition, either by inclusion of orthorhombic (O) phase or by enrichment of R phase, has a negative effect on the value of d33. These findings can provide useful guidance for chemical doping control associated with the type of phase boundary and the phase composition for advanced KNN-based materials.