bluuebunny/crossref_metadata_2025 huggingface dataset:
Depression and Cognitive Impairment in Parkinson's Disease: A Role for Inflammation and Immunomodulation?
Authors: Pessoa Rocha Natália , Reis Helton José , Vanden Berghe Pieter , Cirillo Carla
Published: April 2017

The etiology of Parkinson's disease (PD) is complex and not fully understood, most probably because of the multiplicity of factors involved. Inflammatory and abnormal immune responses have been hypothesized to play a crucial role in PD. Not only in the brain, but also peripherally, inflammation is believed to contribute to the onset and progression of the neurodegenerative process seen in PD. Furthermore, increased inflammatory responses have been described both in the brain and peripheral blood of PD subjects. Although PD is considered a motor disorder, nonmotor symptoms are extremely frequent and disabling. Cognitive impairment and mood alterations are such symptoms that deserve increased attention since on the one hand they can appear even before typical motor disturbances are recognized, and on the other hand they are associated with high morbidity and mortality. A growing body of evidence suggests the existence of a link between inflammatory-immune responses and the occurrence of depression and cognitive impairment in PD patients. However, not all data are equally conclusive and are sometimes even conflicting. The aim of this brief review is to give an overview of the possible role that inflammation and immunomodulation may play in PD together with their putative impact on mood and cognitive alterations. What clearly emerges from this work is the fact that studies performed until now lack standardized and comparable methods to analyze both clinical and biological parameters. It is thus difficult to conclusively link mood and cognitive changes to underlying pathological mechanisms. Additional studies in this direction are warranted to convincingly establish or refute any causative relation.
High-Throughput Gene Expression and Mutation Profiling: Current Methods and Future Perspectives
Authors: Karn Thomas
Published: April 2017

Following the completion of the human genome sequence at the beginning of the new millennium, a series of high-throughput methods have changed cancer research. Using these techniques, global analysis such as expression profiling could be carried out on a genomic scale. In breast cancer they led to the classification of the intrinsic subtypes, and the development of several prognostic and predictive ‘genomic tests' for patient stratification. During the last 2 years we have faced a similar dramatic revolution with the introduction of next generation sequencing (NGS). These techniques allow sequencing of the complete human exome or whole genome with a cost reduction in the order of 10,000-100,000 fold. Consequently, the number of known cancer genome sequences exploded with more than 6,000 samples, published between 2011 and 2013. These studies have led to important and surprising discoveries both for basic cancer research and clinical applications. They relate to understanding the development of cancer as well as the heterogeneity of the disease, and how to use this information to guide the development and application of therapies. Although it is foreseeable that the sequencing surveys of neoplasms will soon conclude, their introduction into clinical practice is just beginning.
Brainstem Circuits Underlying the Prey-Catching Behavior of the Frog
Authors: Matesz Klara , Kecskes Szilvia , Bácskai Tímea , Rácz Éva , Birinyi András
Published: April 2017

Prey-catching behavior (PCB) of the frog consists of a sequence of movements as a stimulus-response chain of the behavioral pattern in which each action presents a signal for the subsequent event. The transformation of visual information into appropriate spatiotemporal patterns of motor activity is carried out by the motor pattern generators located in the brainstem reticular formation. The motor pattern generators provide input to the motoneurons either directly or via the last-order premotor interneurons (LOPI). Although the feeding program is predetermined in this way, various sensory mechanisms control the motor activity. By using neuronal labeling methods, we have studied the morphological details of sensorimotor integration related to the hypoglossal motoneurons to provide further insight into the neuronal circuits underlying the PCB in ranid frogs. Our major findings are as follows. (1) Dendrodendritic and dendrosomatic contacts established by the crossing dendrites of hypoglossal (XII) motoneurons may serve as a morphological option for co-activation, synchronization and proper timing of the bilateral activity of tongue muscles. The crossing dendrites may also provide a feedforward amplification of various signals to the XII motoneurons. The overlapping dendritic territories of the motoneurons innervating protractor and retractor muscles may facilitate the coordinated activities of the agonistic and antagonistic muscles. (2) The musculotopic organization of the XII motoneurons is reflected in the distribution of LOPI for the protractor and retractor muscles of the tongue. (3) Direct sensory inputs from the trigeminal, vestibular, glossopharyngeal-vagal, hypoglossal and spinal afferent fibers to the XII motoneurons may modulate the basic motor pattern and contribute to the plasticity of neuronal circuits. (4) The electrical couplings observed in the vestibulocerebellar neuronal circuits may synchronize and amplify the afferent signals. The combination of chemical and electrical impulse transmission provides a mechanism by which motoneurons can be activated sequentially.
Evolution and Development of Hair Cell Polarity and Efferent Function in the Inner Ear
Authors: Sienknecht Ulrike J. , Köppl Christine , Fritzsch Bernd
Published: April 2017

The function of the inner ear critically depends on mechanoelectrically transducing hair cells and their afferent and efferent innervation. The first part of this review presents data on the evolution and development of polarized vertebrate hair cells that generate a sensitive axis for mechanical stimulation, an essential part of the function of hair cells. Beyond the cellular level, a coordinated alignment of polarized hair cells across a sensory epithelium, a phenomenon called planar cell polarity (PCP), is essential for the organ's function. The coordinated alignment of hair cells leads to hair cell orientation patterns that are characteristic of the different sensory epithelia of the vertebrate inner ear. Here, we review the developmental mechanisms that potentially generate molecular and morphological asymmetries necessary for the control of PCP. In the second part, this review concentrates on the evolution, development and function of the enigmatic efferent neurons terminating on hair cells. We present evidence suggestive of efferents being derived from motoneurons and synapsing predominantly onto a unique but ancient cholinergic receptor. A review of functional data shows that the plesiomorphic role of the efferent system likely was to globally shut down and protect the peripheral sensors, be they vestibular, lateral line or auditory hair cells, from desensitization and damage during situations of self-induced sensory overload. The addition of a dedicated auditory papilla in land vertebrates appears to have favored the separation of vestibular and auditory efferents and specializations for more sophisticated and more diverse functions.
Correlation between Histologic and Radiographic Reconstruction of Intracochlear Electrode Position in Human Temporal Bones
Authors: O'Malley Jennifer T. , Burgess Barbara J. , Zhu Meng-Yu , Curtin Hugh D. , Nadol Jr. Joseph B.
Published: April 2017

In our laboratory, human temporal bone specimens from patients who in life have undergone cochlear implantation are routinely processed with the implant in situ, embedded in Araldite, sectioned at 20 µm and serially photographed during cutting, stained with toluidine blue and mounted on glass slides. From the images, two-dimensional and three-dimensional reconstructions can be made and a very accurate implant insertion depth can be calculated from the three-dimensional reconstructions. However, this method precludes subsequent special stains and further molecular investigations of the tissue including proteomics and immunostaining, which is now possible with celloidin-embedded tissue. In this study, we correlated measurement of the implant array insertion depth calculated from histologic three-dimensional reconstruction with that measured from three-dimensional radiologic multiplanar reconstruction. Four human temporal bones with cochlear implants underwent postfixation preprocessing CT imaging with a Siemens Somatom Sensation Scanner. The CT scans from these four bones were downloaded into the Voxar software application, reformatted using the multiplanar reconstruction tool, viewed in three dimensions and measurements of intracochlear insertion lengths of the implants were obtained. The bones were processed routinely for in situ Araldite embedding, serial images were made of the block during sectioning, postprocessed using PV-Wave® software, aligned with Amira® software, and used to create histologic three-dimensional reconstructions. From these three-dimensional reconstructions, the insertion depth of the electrode array was mathematically calculated. The range of insertion depths was 15.9 mm (case 1) to 26.6 mm (case 4). The two methods, radiographic multiplanar reconstruction and three-dimensional reconstruction, differed by 0.4-0.9%. This provides confidence that important localization information about the electrode in situ can be gleaned from CT scans, thereby allowing us to extract the implants prior to processing for celloidin embedment and allow further techniques such as special stains and immunostaining to be accomplished in order to evaluate molecular mechanisms involved in cochlear implantation.
Single Immunoglobulin Interleukin-1 Receptor-Related Molecule Impairs Host Defense during Pneumonia and Sepsis Caused by Streptococcus Pneumoniae
Authors: Blok Dana C. , van Lieshout Miriam H.P. , Hoogendijk Arie J. , Florquin Sandrine , de Boer Onno J. , Garlanda Cecilia , Mantovani Alberto , van't Veer Cornelis , de Vos Alex F. , van der Poll Tom
Published: April 2017

Streptococcus pneumoniae is a common cause of pneumonia and sepsis. Toll-like receptors (TLRs) play a pivotal role in the host defense against infection. In this study, we sought to determine the role of single immunoglobulin interleukin-1 receptor-related molecule (SIGIRR a.k.a. TIR8), a negative regulator of TLR signaling, in pneumococcal pneumonia and sepsis. Wild-type and SIGIRR-deficient (sigirr-/-) mice were infected intranasally (to induce pneumonia) or intravenously (to induce primary sepsis) with S. pneumoniae and euthanized after 6, 24, or 48 h for analyses. Additionally, survival studies were performed. sigirr-/- mice showed delayed mortality during lethal pneumococcal pneumonia. Accordingly, sigirr-/- mice displayed lower bacterial loads in lungs and less dissemination of the infection 24 h after the induction of pneumonia. SIGIRR deficiency was associated with increased interstitial and perivascular inflammation in lung tissue early after infection, with no impact on neutrophil recruitment or cytokine production. sigirr-/- mice also demonstrated reduced bacterial burdens at multiple body sites during S. pneumoniae sepsis. sigirr-/- alveolar macrophages and neutrophils exhibited an increased capacity to phagocytose viable pneumococci. These results suggest that SIGIRR impairs the antibacterial host defense during pneumonia and sepsis caused by S. pneumoniae.
Sudden Coma from Acute Bilateral M1 Occlusion: Successful Treatment with Mechanical Thrombectomy
Authors: Dietrich Uwe , Graf Tilmann , Schäbitz Wolf-Rüdiger
Published: April 2017

We report a case with acute small infarct of the left middle cerebral artery in a 72-year-old man with atrial fibrillation documented by MRI and MR angiography. One hour later, he lost consciousness and CT with CT angiography revealed bilateral hyperdense middle cerebral arteries due to occlusion of the M1 segments. Mechanical thrombectomy of the right middle cerebral artery was successfully performed. During that time, thrombosis on the left side had progressed to carotid T occlusion, which was recanalized as well. The patient had a good outcome with slight aphasia and mild paresis of the left hand and could be transferred to rehabilitation 2 weeks later.
Participant Anxiety and Presence of Hyperfunction in Stroboscopy
Authors: Kelkar Amit S. , Cox Kathleen T. , Hough Monica , Ball Laura , OʼBrien Kevin
Published: April 2017

Objective: Excessive supraglottic and abnormal fine vibratory characteristics associated with vocal hyperfunction are identified even in individuals with normal laryngeal structure, function and vocal quality when they undergo stroboscopy, possibly due to anxiety. The purpose of this study is to (a) test for vocal hyperfunction in individuals with normal laryngeal structure and function and if present, (b) to track changes in vocal hyperfunction associated with anxiety when stroboscopy is repeated within 24-48 h. Participants and Methods: Thirty participants, naïve to stroboscopy, underwent the procedure and completed the State-Trait Anxiety Inventory 3 times over 24-48 h. Results: 41.4% of participants demonstrated vocal hyperfunction in supraglottic and fine vibratory characteristics after the first trial. Vocal hyperfunction decreased to 27.6% after the third trial. Results showed a significant main effect of time indicating that vocal hyperfunction decreased as participants repeated stroboscopy. Although the average anxiety score decreased across trials, state (anxiety) had no significant effect on change in vocal hyperfunction. Conclusions: In the real world, true representation of vocal function can be achieved by getting a patient acquainted to the presence of strobe in the oral cavity and practice the tasks that will be attempted during the procedure without introducing vocal hyperfunction and most importantly, without the use of a topical anesthetic.
Trigeminal Neuralgia Related to Megadolichobasilar Artery Compression: A Prospective Series of Twenty-Nine Patients Treated with Gamma Knife Surgery, with More Than One Year of Follow-Up
Authors: Tuleasca Constantin , Carron Romain , Resseguier Noémie , Donnet Anne , Roussel Philippe , Gaudart Jean , Levivier Marc , Régis Jean
Published: April 2017

Background: Trigeminal neuralgia (TN) secondary to megadolichobasilar artery (MBA) compression is considerably difficult to manage surgically. Objective: This study aims to evaluate the safety/efficacy of Gamma Knife surgery (GKS) in this special group of patients. Methods: Between July 1992 and November 2010, 29 patients with >1 year of follow-up presenting with MBA compression were treated with GKS at Timone University Hospital. Radiosurgery was performed using a Gamma Knife (model B, C or Perfexion). A single 4-mm isocenter was positioned in the cisternal portion of the trigeminal nerve at a median distance of 9.1 mm (range: 6-18.2 mm) from the emergence. Results: The median follow-up period was 46.1 months (range: 12.9-157.9 months). Initially, all patients (100%) were pain free; the average time to complete pain relief was 13.5 days (range: 0-240 days). Their actuarial probability of remaining pain free without medication at 0.5, 1 and 2 years was 93.1, 79.3 and 75.7%, respectively, and remained stable until 13 years after treatment. The actuarial probability of hypoesthesia onset at 6 months was 4.3%; at 1 year it reached 13% and remained stable until 13 years after treatment. Conclusions: GKS proved to be reasonably safe and effective on a long-term basis as a first- and/or second-line surgical treatment for TN due to MBA compression.
Recommendations for Promoting Physical Activity for Children and Adolescents in Germany. A Consensus Statement
Authors: Graf Christine , Beneke Ralph , Bloch Wilhelm , Bucksch Jens , Dordel Sigrid , Eiser Stefanie , Ferrari Nina , Koch Benjamin , Krug Susanne , Lawrenz Wolfgang , Manz Kristin , Naul Roland , Oberhoffer Renate , Quilling Eike , Schulz Henry , Stemper Theo , Stibbe Günter , Tokarski Walter , Völker Klaus , Woll Alexander
Published: April 2017

Increasing physical activity and reduction of sedentary behaviour play important roles in health promotion and prevention of lifestyle-related diseases in children and adolescents. However, the question of how much physical activity is useful for which target group is still a matter of debate. International guidelines (World Health Organization; European Association for the Study of Obesity), which are mainly based on expert opinions, recommend 60 min of physical activity every day. Age- and sex-specific features and regional differences are not taken into account. Therefore, expert consensus recommendations for promoting physical activity of children and adolescents in Germany were developed with special respect to national data, but also with respect to aspects of specific target groups, e.g., children with a lower socio-economic status (SES) or with migration background. They propose 90 min/day of physical activity, or at least 12,000 steps daily. Additionally, lifestyle factors, especially restriction of media consumption, were integrated. The recommendations provide orientation for parents and caregivers, for institutions such as schools and kindergartens as well as for communities and stakeholders.
A Rare Case of Parkinson's Disease with Severe Neck Pain Owing to Crowned Dens Syndrome
Authors: Takahashi Teruyuki , Tamura Masato , Osabe Keiichi , Tamiya Takashi , Miki Kenji , Yamaguchi Mai , Akira Kanno , Kamei Satoshi , Takasu Toshiaki
Published: April 2017

Background: Pain is regarded as one of the most common nonmotor symptoms in Parkinson's disease (PD). In particular, musculoskeletal pain has been reported as the most common type of PD-associated pain. Crowned dens syndrome (CDS), related to microcrystalline deposition in the periodontoid process, is the main cause of acute or chronic cervical pain. Case Presentation: This report describes the case of an 87-year-old woman who had severe bradykinesia, muscle rigidity, gait disturbance and neck pain. Laboratory examination revealed marked elevations of white blood cells (10,100/µl) and C-reactive protein (CRP; 8.63 mg/dl). She was primarily diagnosed with severe and untreated PD, corresponding to Hoehn and Yahr scale score IV, with musculoskeletal pain and urinary tract infection. The patient was treated with antiparkinsonism drugs, antibiotic agents and nonsteroidal anti-inflammatory drugs, but they had only limited effects. Cervical plain computed tomography (CT) scanning detected remarkable crown-like calcification surrounding the odontoid process. Based on CT findings, the patient was diagnosed as having CDS with PD, and was immediately treated with corticosteroid. The severe neck rigidity with pain and the serum CRP level (0.83 mg/dl) of the patient were drastically improved within a week by the additional corticosteroid therapy. Conclusion: Severe neck rigidity and bradykinesia in this patient might have strengthened the chondrocalcinosis around the odontoid process. Cervical plain CT scan is necessary and useful for the definitive diagnosis of CDS. CDS should be considered as a differential diagnosis of a possible etiology for musculoskeletal pain related to rigidity and bradykinesia in PD.
Renal Sodium Transporters Are Increased in Urinary Exosomes of Cyclosporine-Treated Kidney Transplant Patients
Authors: Esteva-Font Cristina , Guillén-Gómez Elena , Diaz Joan Manuel , Guirado Luís , Facundo Carmen , Ars Elisabet , Ballarin Jose A. , Fernández-Llama Patricia
Published: April 2017

Background/Aims: Cyclosporine (CsA) is a calcineurin inhibitor widely used as an immunosuppressant in organ transplantation. Previous studies demonstrated the relationship between CsA and renal sodium transporters such as the Na-K-2Cl cotransporter in the loop of Henle (NKCC2). Experimental models of CsA-induced hypertension have shown an increase in renal NKCC2. Methods: Using immunoblotting of urinary exosomes, we investigated in CsA-treated kidney transplant patients (n = 39) the excretion of NKCC2 and Na-Cl cotransporter (NCC) and its association with blood pressure (BP) level. We included 8 non-CsA-treated kidney transplant patients as a control group. Clinical data, immunosuppression and hypertension treatments, blood and 24-hour urine tests, and 24-hour ambulatory BP monitoring were recorded. Results: CsA-treated patients tended to excrete a higher amount of NKCC2 than non-CsA-treated patients (mean ± SD, 175 ± 98 DU and 90 ± 70.3 DU, respectively; p = 0.05) and showed higher BP values (24-hour systolic BP 138 ± 17 mm Hg and 112 ± 12 mm Hg, p = 0.003; 24-hour diastolic BP, 83.8 ± 9.8 mm Hg and 72.4 ± 5.2 mm Hg, p = 0.015, respectively). Within the CsA-treated group, there was no correlation between either NKCC2 or NCC excretion and BP levels. This was confirmed by a further analysis including potential confounding factors. On the other hand, a significant positive correlation was observed between CsA blood levels and the excretion of NKCC2 and NCC. Conclusion: Overall, these results support the hypothesis that CsA induces an increase in NKCC2 and NCC in urinary exosomes of renal transplant patients. The fact that the increase in sodium transporters in urine did not correlate with the BP level suggests that in kidney transplant patients, other mechanisms could be implicated in CsA-induced hypertension.
Manganese Superoxide Dismutase Gene Expression and Cognitive Functions in Recurrent Depressive Disorder
Authors: Talarowska Monika , Orzechowska Agata , Szemraj Janusz , Su Kuan-Pin , Maes Michael , Gałecki Piotr
Published: April 2017

Background: Recent studies have revealed that recurrent depressive disorders (rDD) are linked with dysregulation of the immune system. Previous studies have found that manganese superoxide dismutase (MnSOD, SOD2) may be a key inflammatory enzyme involved in this disorder. The purpose of this study was to determine the mRNA and protein levels of MnSOD in patients with rDD and to define the relationship between serum MnSOD levels and cognitive performance. Methods: The study comprised 236 subjects, which included patients with rDD (n = 131) and healthy subjects (n = 105, healthy control group, HC). Assessment of cognitive function was based on performance on the Trail Making test (TMT), the Stroop test, the Verbal Fluency test (VFT) and the Auditory Verbal Learning test (AVLT). Results: MnSOD gene expression at mRNA and protein level was significantly lower in rDD patients than in the HC group (p < 0.01). In the rDD and HC groups separately, there were no statistically significant associations between mRNA and protein expression levels of the MnSOD and psychological tests. In the total study group (n = 236), there was a statistically significant correlation between both MnSOD gene levels and the following tests (p < 0.01): the TMT parts A and B (negative correlation), the Stroop test parts RCNb (reading color names in black) and NCWd (naming color of word - different; negative correlation), the VFT (positive correlation) and the AVLT (positive correlation). Conclusions: Our study provides evidence that the MnSOD enzyme-coding gene and MnSOD expression are important for the regulation of cognitive functioning.
Effectiveness of Three Different Walking Prescription Durations on Total Physical Activity in Normal- and Overweight Women
Authors: Schutz Yves , Nguyen Dac Min Tuan , Byrne Nuala M. , Hills Andrew P.
Published: April 2017

Objective: While there is a dose-response relationship between physical activity (PA) and health benefit, little is known about the effectiveness of different PA prescriptions on total daily PA. Aim: To test, under real-life conditions and using an objective, non-invasive measurement technique (accelerometry), the effect of prescribing additional physical activity (walking only) of different durations (30, 60 and 90 min/day) on compliance (to the activity prescribed) and compensation (to total daily PA). Participants in each group were prescribed 5 sessions of walking per week over 4 weeks. Methods: 55 normal-weight and overweight women (mean BMI 25 ± 5 kg/m2, height 165 ± 1 cm, weight 68 ± 2 kg and mean age 27 ± 1 years) were randomly assigned to 3 prescription groups: 30, 60 or 90 min/day PA. Results: Walking duration resulted in an almost linear increase in the number of steps per day during the prescription period from an average of about 10,000 steps per day for the 30-min prescription to about 14,000 for the 90-min prescription. Compliance was excellent for the 30-min prescription but decreased significantly with 60-min and 90-min prescriptions. In parallel, degree of compensation subsequent to exercise increased progressively as length of prescription increased. Conclusion: A 30-min prescription of extra walking 5 times per week was well tolerated. However, in order to increase total PA further, much more than 60 min of walking may need to be prescribed in the majority of individuals. While total exercise ‘volume' increased with prescriptions longer than 30 min, compliance to the prescription decreased and greater compensation was evident.
Choroidal Neovascularization in a Patient with Crohn's Disease
Authors: Casalino Giuseppe , Querques Giuseppe , Corvi Federico , Borrelli Enrico , Triolo Giacinto , Ramirez Giuseppe Alvise , Bandello Francesco
Published: April 2017

Purpose: To report a case of subfoveal choroidal neovascularization (CNV) in a patient with Crohn's disease (CD) and to discuss a possible association between these two conditions. Methods: This is an observational case report. Results: A 69-year-old male affected by CD was referred to our department because of sudden visual acuity drop in the left eye. A subfoveal CNV was diagnosed based on slit-lamp fundus biomicroscopy and fluorescein angiography. Color fundus photography, infrared autofluorescence and spectral-domain optical coherence tomography imaging of both eyes were also performed. Following six intravitreal ranibizumab injections, visual improvement was obtained with no related adverse events. Conclusion: We report a case of CNV as a possible rare extraintestinal manifestation of CD. The use of ranibizumab successfully impacted on CNV, while not affecting CD, which remained quiescent.
Intravitreal Injection of Dexamethasone Implant and Ranibizumab in Cystoid Macular Edema in the Course of Irvine-Gass Syndrome
Authors: Fenicia Vito , Balestrieri Marco , Perdicchi Andrea , Maurizi Enrici Maurizio , Delle Fave Martina , Recupero Santi Maria
Published: April 2017

Purpose: To evaluate the efficacy of 2 dexamethasone intravitreal implants and 1 ranibizumab intravitreal injection after a bilateral postoperative complication of cataract surgery as pseudophakic cystoid macular edema. Patients and Methods: A 70-year-old male patient with systemic hypertension developed a progressive cystoid macular edema (CME) in both eyes starting between 10 and 20 days after cataract surgery. Two intravitreal dexamethasone implants and 1 ranibizumab injection were administered; first in the right eye (RE) and then in the left eye (LE). The patient was checked for 1 whole week and then once a month for 5 months after the injections. Results: One month after the first dexamethasone implant in his RE, the spectral domain optical coherence tomography (SD-OCT) showed a progressive reduction of the foveal thickness until a complete resolution of the CME occurred, which was associated with an improvement of visual acuity. After 3 months, the SD-OCT showed a relapse of the CME, which was then treated with 1 injection of ranibizumab. One month after this injection, there was a complete resolution of the CME. A new CME in his RE was diagnosed 2 months after the last ranibizumab injection; it was treated with a new dexamethasone implant. A complete resolution of the CME was obtained; a normal foveal profile was still present 5 months after the last injection, and the best-corrected visual acuity was 20/20. His LE developed a CME 40 days after surgery. One intravitreal injection of ranibizumab was first administered in his LE, with a complete resolution of the CME at SD-OCT 2 weeks later. As observed in his RE, 40 days after the ranibizumab injection, there was a relapse of the CME that was treated with 1 intravitreal injection of dexamethasone implant. Five months later, the patient showed a worsening of the CME, but it was completely resolved with a second dexamethasone injection. After 3 months, the foveal thickness was back to normal with a BCVA of 20/20. Conclusion: Treatment with dexamethasone implants (Ozurdex®) and ranibizumab injections (Lucentis®) induced a progressive reduction of our patient's CME after cataract surgery (Irvine-Gass syndrome) until a complete normal foveal thickness was restored and his visual function was improved despite the order of injections.
Acute Kidney Injury after Valvular Heart Surgery and Early Changes in Cardiac Function and Structure
Authors: Olsson Daniel P. , Eck Arvstrand Christopher , Sartipy Ulrik , Holzmann Martin J.
Published: April 2017

Background: Acute kidney injury (AKI) following heart surgery is associated with long-term risk of heart failure. It is not known if AKI following valvular heart surgery is associated with early changes in cardiac function or structure. Methods: A cohort study was conducted on 201 patients with AKI and 201 patients without AKI after valvular heart surgery, who were matched for age, sex, left ventricular function, and estimated glomerular filtration rate. AKI was defined as an increase in postoperative serum creatinine of ≥26 Vmol/l (≥0.3 mg/dl) or a relative increase of ≥50%. The two primary outcomes were changes in post- compared with preoperative left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) assessed by echocardiography. Results: The mean age was 72 years, and 33% were female. Aortic valve surgery was the most frequent procedure. The mean time from surgery to the postoperative echocardiographic examination was 4.9 days (SD 3.7). There was no significant change in postoperative mean LVEF (-3.6 vs. -4.3%; p = 0.58) or mean LVEDD (-4.7 vs. -3.9 mm; p = 0.31) in patients with AKI compared to those without AKI. Conclusion: We found no acute changes in cardiac function or structure assessed by echocardiography in patients with AKI compared to those without AKI after valvular heart surgery. i 2014 S. Karger AG, Basel
Association between the Hemoglobin Level and Cardiothoracic Ratio in Patients on Incident Dialysis
Authors: Asakawa Takasuke , Joki Nobuhiko , Tanaka Yuri , Hayashi Toshihide , Hase Hiroki , Komatsu Yasuhiro , Ando Ryoichi , Ikeda Masato , Inaguma Daijo , Sakaguchi Toshifumi , Shinoda Toshio , Koiwa Fumihiko , Negi Shigeo , Yamaka Toshihiko , Shigematsu Takashi
Published: April 2017

Background/Aim: The present study explores associations between hemoglobin (Hb) levels and patients with cardiac enlargement in end-stage kidney disease (ESKD) to help prevent cardiac remodeling during the predialysis phase of chronic kidney disease (CKD). Methods: This cross-sectional study included 2,249 patients with ESKD (age, 67 w 13 years; male, 67%; diabetic kidney disease, 41%) who started hemodialysis (HD) between January 2006 and October 2013 at eight participating hospitals. We examined associations between Hb levels immediately before the first HD session and cardiothoracic ratios (CTRs). Clinical factors associated with the CTR were also assessed. Results: The mean Hb level was 8.7 w 1.6 g/dl, and the mean and median CTRs were 55.0 and 54.7%, respectively. The correlation between the Hb level and the CTR was linear and negative (r = -0.129, p < 0.001). The mean CTR and the prevalence of patients with a CTR >50% obviously decreased with increasing Hb levels (both p < 0.001 for trend). Univariate logistic regression analysis revealed an approximately 20% reduction in the odds ratio for complicating CTRs >50% per 1 g/dl increase in Hb. Hb levels of <9 g/dl were significantly associated with CTRs >50%. Numerical and categorical Hb remained significantly associated with CTRs >50% after adjusting for confounding variables. Conclusions: Lower Hb levels participate in progressive CTR enlargement in patients with ESKD, and maintaining Hb levels of >9 g/dl might help prevent cardiac remodeling during the predialysis phase of CKD. i 2014 S. Karger AG, Basel
Surgical Trauma Leads to a Shorter Survival in a Murine Orthotopic Pancreatic Cancer Model
Authors: Menges Pia , Klöcker Christian , Diedrich Stephan , Sendler Matthias , Maier Stefan , Weiss Frank-Ulrich , Heidecke Claus-Dieter , von Bernstorff Wolfram , Partecke Lars Ivo
Published: April 2017

Background: Abdominal surgery is frequently followed by immune dysfunction usually lasting for several days. This is especially important in cases with tumour diseases as an intact immune function is essential in this situation. Therefore, we analysed the outcome of tumour-bearing mice in a mouse model of surgically induced immune dysfunction (SID). Methods: In male C57BL/6 mice, a pancreatic tumour was implanted orthotopically. Following tumour implantation, the model of SID was applied. The control groups were either laparotomised or underwent no surgical procedure. The survival rate was determined by observation for >60 days. The tumour growth progress was imaged by a 7-tesla small animal MRI. Results: On day 60 after tumour implantation, the survival rate in SID mice was reduced to 41%. In the laparotomised group, 81% of mice survived, while the control group had a survival rate of 75%. These differences were significant (SID vs. control: p < 0.02, and SID vs. laparotomy: p < 0.002). The tumour volume was not influenced by the degree of surgical trauma. Conclusion: In pancreatic cancer, the SID model is ideally suited to investigate the influence of SID on this tumour entity.
Acute Kidney Injury Care Bundles
Authors: Bagshaw Sean M.
Published: April 2017

Acute kidney injury (AKI) is a common complication that occurs in hospitalized patients and appears susceptible to a wide variability in practice. This may lead to suboptimal quality of care. The concept of a ‘care bundle' for AKI has been proposed to improve the reliability and quality of care. A bundle is designed to be a structured method of improving care processes and outcomes. It contains a small set of evidence-based practices intended for a defined population and care setting. The Institute for Healthcare Improvement has developed guidelines for the design of care bundles. Care bundles for critically ill patients focusing on mechanical ventilation, central venous catheters, and sepsis have been widely implemented with modest success in terms of compliance and impact on care processes and outcomes. A care bundle for AKI is highly desired, given the observed practice variation and indication of poor care for AKI patients; however, existing proposals are too comprehensive and have not been focused on a defined population at-risk, clinical context or setting. They have also not engaged local stakeholders in the process.
Admission Low Magnesium Level Is Associated with In-Hospital Mortality in Acute Ischemic Stroke Patients
Authors: You Shoujiang , Zhong Chongke , Du Huaping , Zhang Yu , Zheng Danni , Wang Xia , Qiu Chenhong , Zhao Hongru , Cao Yongjun , Liu Chun-Feng
Published: April 2017

Background: Low magnesium levels are associated with an elevated risk of stroke. In this study, we investigated the association between magnesium levels on hospital admission and in-hospital mortality in acute ischemic stroke (AIS) patients. Methods: A total of 2,485 AIS patients, enrolled from December 2013 to May 2014 across 22 hospitals in Suzhou city, were included in this study. The patients were divided into 4 groups according to their level of admission magnesium: Q1 (<0.82 mmol/L), Q2 (0.82-0.89 mmol/L), Q3 (0.89-0.98 mmol/L), and Q4 (≥0.98 mmol/L). Cox proportional hazard model was used to estimate the effect of magnesium on all-cause in-hospital mortality in AIS patients. Results: During hospitalization, 92 patients (3.7%) died from all causes. The lowest serum magnesium level (Q1) was associated with a 2.66-fold increase in the risk of in-hospital mortality in comparison to Q4 (hazard ratio [HR] 2.66; 95% CI 1.55-4.56; p-trend < 0.001). After adjusting for age, sex, time from onset to hospital admission, baseline National Institutes of Health Stroke Scale score, and other potential covariates, HR for Q1 was 2.03 (95% CI 1.11-3.70; p-trend = 0.014). Sensitivity and subgroup analyses further confirmed a significant association between lower magnesium levels and a high risk of in-hospital mortality. Conclusions: Decreased serum magnesium levels at admission were independently associated with in-hospital mortality in AIS patients.
Erythropoietin-Derived Peptide Protects Against Acute Lung Injury After Rat Traumatic Brain Injury
Authors: Liu Yuan , Lu Junyu , Wang Xiaoya , Chen Liu , Liu Su , Zhang Zhiren , Yao Wei
Published: April 2017

Background: Traumatic brain injury (TBI) can be complicated by TBI-triggered acute lung injury (ALI), in which inflammation plays a central role. It has been reported that an Erythropoietin-derived peptide (pHBSP) was able to ameliorate TBI; however, its function in TBI-caused ALI has not been reported yet. Methods: In this study, we studied the effect of pHBSP on TBI-caused ALI by using a weight-drop induced TBI model. At 8 h and 24 h post-TBI, pulmonary edema (PE) and bronchoalveolar lavage fluid (BALF) proteins were measured, and haematoxylin and eosin (H&E) staining of lung sections was carried out. At 24 h following TBI, the lungs were harvested for immunofluorescence staining and qRT-PCR analysis. Results: At 8 h and 24 h post-TBI, pHBSP treatment significantly decreased wet/dry ratios, decreased total BALF protein, and attenuated the histological signs of pulmonary injury. At 24 h post-TBI, pHBSP treatment decreased the accumulation of CD68+ macrophages in the lung and reduced the mRNA levels of TNF-α, IL-6, IL-1β and iNOS in the lung. Conclusions: We identified the protective role that pHBSP played in TBI-caused ALI, suggesting that pHBSP is a potent candidate for systemic therapy in TBI patients.
Reduction in Peripheral CD19+CD24hCD27+ B Cell Frequency Predicts Favourable Clinical Course in XELOX-Treated Patients with Advanced Gastric Cancer
Authors: Li Wei , Song Dongli , Li Hong , Liang Li , Zhao Naiqing , Liu Tianshu
Published: April 2017

Background: Accumulating evidence suggests that regulatory B cells (Bregs) play an important role in modulating the immune response to tumours. Our previous study indicated that a small percentage of peripheral CD19+CD24hCD27+ Breg cells slowed gastric cancer progression in XELOX-treated patients. Here, we further investigated the relationship between dynamic changes in circulating Breg cells and the clinical course in XELOX-treated gastric cancer patients. Methods: A total of 52 patients with advanced gastric cancer were enrolled in this study. The frequencies of CD19+CD24hCD27+ cells in peripheral blood were tested before (as a baseline) and 9 weeks after administration of oxaliplatin and capecitabine (XELOX). The primary endpoint of the study was progression-free survival time (PFS) of the patients. The overall survival (OS) and adverse events of chemotherapy were also recorded. Results: The median PFS of patients was 6 months (95% CI, 5.27-6.73) with effective rate of 46.2%. The percentage of CD19+CD24hCD27+ cells in lymphocytes ranged from 0.007% to 1.94%, with a median value of 0.45%. The median percentage of CD19+CD24hCD27+ lymphocytes was 0.59% (0.01%-6.02%) 9 weeks after treatment. There were no significant differences for this index. However, the patients with decreased Breg frequencies after XELOX treatment had a longer PFS time (7.0 months vs. 5.0 months, p=0.01) than those with increased Breg frequencies. Conclusion: Patients with downtrend of CD19+CD24hCD27+ B lymphocytes during early stages of chemotherapy relative to their initial values had longer PFS times, and this could be used to predict the efficacy of chemotherapy and help physicians adjust treatments accordingly.
Degradation of Mcl-1 through GSK-3β Activation Regulates Apoptosis Induced by Bufalin in Non-Small Cell Lung Cancer H1975 Cells
Authors: Kang Xiao-hong , Zhang Jing-hang , Zhang Qing-qin , Cui Yan-hui , Wang Ying , Kou Wei-zheng , Miao Zhan-hui , Lu Ping , Wang Li-Fang , Xu Zhen-ye , Cao Fei
Published: April 2017

Background/Aims: Mcl-1, an anti-apoptotic Bcl-2 family member, is often overexpressed in non-small cell lung cancer (NSCLC). Bufalin has been reported to induce apoptosis in various tumor cells. However, there is no report showing that bufalin could downregulate Mcl-1 expression in NSCLC. Methods: Cell proliferation was analyzed by cell counting kit-8 (CCK-8) assay in H1975 cells. Cell apoptosis was detected by flow cytometry. Mcl-1 mRNA was detected by RT-PCR. The expression of apoptosis-associated proteins in H1975 cells was detected by western blotting. The levels of Mcl-1 ubiquitination and NOXA were analyzed by Immunoprecipitation assay. Results: Cell growth was inhibited by bufalin in a time and dose-dependent manner. Bufalin induced apoptosis in NSCLC cells by activating caspase cascades and downregulating Mcl-1 expression. However, overexpression of Mcl-1 diminished bufalin-induced apoptosis. Furthermore, bufalin did not reduce Mcl-1 mRNA expression in H1975 cells, but strongly promoted Mcl-1 protein degradation. Proteasome inhibitor MG132 markedly prevented the degradation of Mcl-1 and blocked bufalin-induced Mcl-1 reduction. Bufalin did not significantly affect NOXA protein levels, but downregulated the expression of p-GSK-3β. GSK-3 inhibitor and GSK-3β siRNA resulted in increased levels of Mcl-1 and reversed the bufalin-induced Mcl-1 degradation. Conclusion: Bufalin induced cell apoptosis in H1975 cells may be through downregulation of Mcl-1. Proteasomal degradation of Mcl-1 via GSK-3β activation was involved in bufalin-induced apoptosis.
Investigating the Genetic Architecture of the PR Interval Using Clinical Phenotypes
Authors: Mosley Jonathan D. , Shoemaker M. Benjamin , Wells Quinn S. , Darbar Dawood , Shaffer Christian M. , Edwards Todd L. , Bastarache Lisa , McCarty Catherine A. , Thompson Will , Chute Christopher G. , Jarvik Gail P. , Crosslin David R. , Larson Eric B. , Kullo Iftikhar J. , Pacheco Jennifer A. , Peissig Peggy L. , Brilliant Murray H. , Linneman James G. , Witte John S. , Denny Josh C. , Roden Dan M.
Published: April 2017

Background—

One potential use for the PR interval is as a biomarker of disease risk. We hypothesized that quantifying the shared genetic architectures of the PR interval and a set of clinical phenotypes would identify genetic mechanisms contributing to PR variability and identify diseases associated with a genetic predictor of PR variability.

Methods and Results—

We used ECG measurements from the ARIC study (Atherosclerosis Risk in Communities; n=6731 subjects) and 63 genetically modulated diseases from the eMERGE network (Electronic Medical Records and Genomics; n=12 978). We measured pairwise genetic correlations (rG) between PR phenotypes (PR interval, PR segment, P-wave duration) and each of the 63 phenotypes. The PR segment was genetically correlated with atrial fibrillation (rG=−0.88;
P
=0.0009). An analysis of metabolic phenotypes in ARIC also showed that the P wave was genetically correlated with waist circumference (rG=0.47;
P
=0.02). A genetically predicted PR interval phenotype based on 645 714 single-nucleotide polymorphisms was associated with atrial fibrillation (odds ratio=0.89 per SD change; 95% confidence interval, 0.83–0.95;
P
=0.0006). The differing pattern of associations among the PR phenotypes is consistent with analyses that show that the genetic correlation between the P wave and PR segment was not significantly different from 0 (rG=−0.03 [0.16]).

Conclusions—

The genetic architecture of the PR interval comprises modulators of atrial fibrillation risk and obesity.
2-Methoxyestradiol Reduces Angiotensin II–Induced Hypertension and Renal Dysfunction in Ovariectomized Female and Intact Male Mice
Authors: Pingili Ajeeth K. , Davidge Karen N. , Thirunavukkarasu Shyamala , Khan Nayaab S. , Katsurada Akemi , Majid Dewan S.A. , Gonzalez Frank J. , Navar L. Gabriel , Malik Kafait U.
Published: April 2017

Cytochrome P450 1B1 protects against angiotensin II (Ang II)–induced hypertension and associated cardiovascular changes in female mice, most likely via production of 2-methoxyestradiol. This study was conducted to determine whether 2-methoxyestradiol ameliorates Ang II–induced hypertension, renal dysfunction, and end-organ damage in intact
Cyp1b1
−/−
, ovariectomized female, and
Cyp1b1
+/+
male mice. Ang II or vehicle was infused for 2 weeks and administered concurrently with 2-methoxyestradiol. Mice were placed in metabolic cages on day 12 of Ang II infusion for urine collection for 24 hours. 2-Methoxyestradiol reduced Ang II–induced increases in systolic blood pressure, water consumption, urine output, and proteinuria in intact female
Cyp1b1
−/−
and ovariectomized mice. 2-Methoxyestradiol also reduced Ang II–induced increase in blood pressure, water intake, urine output, and proteinuria in
Cyp1b1
+/+
male mice. Treatment with 2-methoxyestradiol attenuated Ang II–induced end-organ damage in intact
Cyp1b1
−/−
and ovariectomized
Cyp1b1
+/+
and
Cyp1b1
−/−
female mice and
Cyp1b1
+/+
male mice. 2-Methoxyestradiol mitigated Ang II–induced increase in urinary excretion of angiotensinogen in intact
Cyp1b1
−/−
and ovariectomized
Cyp1b1
+/+
and
Cyp1b1
−/−
female mice but not in
Cyp1b1
+/+
male mice. The G protein–coupled estrogen receptor 1 antagonist G-15 failed to alter Ang II–induced increases in blood pressure and renal function in
Cyp1b1
+/+
female mice. These data suggest that 2-methoxyestradiol reduces Ang II–induced hypertension and associated end-organ damage in intact
Cyp1b1
−/−
, ovariectomized
Cyp1b1
+/+
and
Cyp1b1
−/−
female mice, and
Cyp1b1
+/+
male mice independent of G protein–coupled estrogen receptor 1. Therefore, 2-methoxyestradiol could serve as a therapeutic agent for treating hypertension and associated pathogenesis in postmenopausal females, and in males.
Paradoxes of Plain Thinking
Authors: Melkonian Markar
Published: April 2017

Whatever common sense may be, it includes much else besides practically confirmed truisms. InCommon Sense: A Political History, Sophia Rosenfeld describes the backstories of modern common sense, locating its origins in debates among small groups of professors, publishers and pamphleteers in several cities on both sides of the Atlantic during the Age of Revolutions. From the eighteenth century on, champions and enemies of the rising ‘middling’ classes have brandished common sense as an ‘unspectacular instrument’ of non-coercive regulation, to promote or oppose the sovereignty of ‘the people’ by hitching their conflicting claims to an unassailable guarantor of truth. After taking a beating in the first decades of the twentieth century, common sense has been resuscitated and reconstituted, to sell all manner of goods and policies. As a description of the roles that common sense has played in the modern phenomenon of populism, Rosenfeld’s book casts doubt on Hannah Arendt’s claim that common sense is what true democracy creates. At the same time,Common Sense: A Political Historycorroborates and fills out Antonio Gramsci’s account of good sense and politics.