bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Striatal and Pallidal Regions in the Subpallium of Anamniotes
Authors: González Agustín , Morona Ruth , Moreno Nerea , Bandín Sandra , López Jesús M.
Published: April 2017

The telencephalic basal ganglia (BG) of amniotes consist of two subdivisions, striatum and pallidum, which share many features, including development, cell types, neurotransmitter organization and hodology. In particular, these two subdivisions during development are defined on the basis of discrete gene expression patterns (genoarchitecture or genoarchitectonics). The characterization of the BG in the subpallium of representatives of the different classes of anamniote vertebrates was first approached in studies dealing with their localization, hodology and main neurochemical characteristics. Thus, it was proposed that an impressive degree of conservation exists across species. New insights can be gained by the comparative analysis of the expression of conserved transcription factors that distinctly define the striatal and pallidal components of the BG in all vertebrates. In addition, the expression of other genes that characterize neighboring regions of the BG is also useful to define the boundaries of each subdivision. Following this approach, we have analyzed the BG in the brain of juvenile representatives of amphibians, lungfishes, holosteans, Polypteriformes and Chondrichthyes. In addition, we briefly review previous data in teleosts and agnathans. The markers used include islet 1 and Dlx as striatal markers, whereas Nkx2.1 is essential for the identification of the pallidum. In turn, Pax6 and in particular Tbr1 are expressed in the pallium. These markers have been systematically analyzed in combination with neuronal markers of specific subpallial territories and cell populations, such as tyrosine hydroxylase, γ-aminobutyric acid, nitric oxide synthase, substance P and enkephalin. The results highlight that many genes share common distribution patterns and are arranged in conserved combinations whose identification has served to define homologies between components of the BG in distant species.
Immunoreactivity Distribution of Vasotocin and Vasoactive Intestinal Peptide in Brain Nuclei of Two Songbird Species with Different Breeding Systems
Authors: Montagnese Catherine M. , Székely Tamás , Gray David , Balázsa Tamás , Zachar Gergely
Published: April 2017

Vasopressin influences social behaviour in mammals, in particular social recognition and bonding. However, much less is known about its avian analogue, vasotocin, although vasotocin appears to modulate singing behaviour and agonistic interactions together with vasoactive intestinal peptide (VIP) in some songbirds. The objectives of our study were to compare the expression of vasotocin and VIP in brain nuclei hypothetised to be part of the social behavioural network, i.e. septal areas, bed nucleus of the stria terminalis and medial preoptic nucleus (POM), in two songbird species in the wild: the blue tit (Cyanistes caeruleus) and European penduline tit (Remiz pendulinus). These two closely related passerine birds differ in their pair bonding and mating systems: blue tits are socially monogamous with extensive pair bond lasting for several months, whereas in the European penduline tit, pair bond is short and it dissolves during or after laying of the eggs. The two species did not differ in the distribution of vasotocin in the observed brain regions; however, VIP was more abundant in all three regions of penduline tits than in blue tits. We found a sex difference in favour of males in the distribution of vasotocin- and VIP-immunoreactive neurones, fibres and terminals in all three regions in penduline tits. In blue tits, such gender differences were only observed in the POM. The limited differences between the two species suggest that the levels of vasotocin and VIP in the socially relevant brain regions are likely influenced by many other social or environmental factors than just by differences in the duration of pair bonding.
Effect of Laser Wavelength on Delivering Appropriate Laser Burns through the Opaque Lens Using a Pattern Scan Laser
Authors: Hirano Takao , Iesato Yasuhiro , Imai Akira , Toriyama Yuichi , Kikushima Wataru , Murata Toshinori
Published: April 2017

Background/Aims: We evaluated the effects of pattern scan laser (PSL) wavelength in delivering appropriate laser burns to the retina of eyes with an opaque lens. Methods: Sixteen shots of 2 × 2 square grids (64 laser spots) were delivered using green (532-nm), yellow (577-nm) and red (647-nm) lasers to the retinas of mice with mild cataract induced by chloral hydrate (400 mg/kg). Three eyes with clear lenses served as controls. One week after laser coagulation, the ratio of appropriate burns, defined as coagulation restricted to the outer half of the retina without retinal or choroidal hemorrhage, was investigated histologically. Results: With the green laser, we confirmed only 3.0 ± 2.0 appropriate burns in eyes with an opaque lens, in contrast to 13.7 ± 4.0 effective burns in eyes with a clear lens. On the other hand, the yellow and red lasers produced 18 ± 5.2 and 13 ± 1.5 appropriate burns, respectively, in eyes with an opaque lens. Conclusion: Although all three PSL wavelengths successfully delivered appropriate burns restricted to the outer half of the retina in eyes with an opaque lens, the longer-wavelength yellow and red lasers were significantly more effective than the green laser. PSL may be a treatment option to accompany anti-vascular endothelial growth factor drug therapy.
Molecular Studies of the Structural Ecology of Natural Occlusal Caries
Authors: Dige Irene , Grønkjær Lene , Nyvad Bente
Published: April 2017

Microbiological studies of occlusal dental biofilms have hitherto been hampered by inaccessibility to the sampling site and demolition of the original biofilm architecture. This study shows for the first time the spatial distribution of bacterial taxa in vivo at various stages of occlusal caries, applying a molecular methodology involving preparation of embedded hard dental tissue slices for fluorescence in situ hybridization (FISH) and confocal microscopy. Eleven freshly extracted teeth were classified according to their occlusal caries status. The teeth were fixed, embedded, sectioned and decalcified before FISH was performed using oligonucleotide probes for selected abundant species/genera associated with occlusal caries including Streptococcus, Actinomyces, Veillonella, Fusobacterium, Lactobacillus and Bifidobacterium. The sites showed distinct differences in the bacterial composition between different ecological niches in occlusal caries. Biofilm observed along the entrance of fissures showed an inner layer of microorganisms organized in palisades often identified as Actinomyces, covered by a more loosely structured bacterial layer consisting of diverse genera, similar to supragingival biofilm. Biofilm within the fissure proper seemed less metabolically active, as judged by low fluorescence signal intensity and presence of material of non-bacterial origin. Bacterial invasion (often Lactobacillus and Bifidobacterium spp.) into the dentinal tubules was seen only at advanced stages of caries with manifest cavity formation. It is concluded that the molecular methodology represents a valuable supplement to previous methods for the study of microbial ecology in caries by allowing analysis of the structural composition of the undisturbed biofilm in caries lesions in vivo.
Lung Ultrasound Accuracy in Respiratory Distress Syndrome and Transient Tachypnea of the Newborn
Authors: Vergine Michela , Copetti Roberto , Brusa Giacomo , Cattarossi Luigi
Published: April 2017

Background: Lung ultrasound (LUS) is a promising technique for the diagnosis of neonatal respiratory diseases. Preliminary data has shown a good sensitivity and specificity of LUS in the diagnosis of respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN). Objective: The aim of this study was to calculate the sensitivity, specificity, and negative (NPV) and positive predictive value (PPV) of LUS for RDS and TTN, using an external reader blinded to the clinical condition. Design and Methods: Neonates with respiratory distress had a LUS within 1 h of admission. Images were uploaded and sent to the external reader, who made the ultrasound diagnosis according to the appearance of the images. The final clinical diagnosis was made according to all the available data, except LUS data. Sensitivity, specificity, PPV, and NPV were calculated considering the final clinical diagnosis as the gold standard. Results: Fifty-nine neonates were studied (mean gestational age: 33 ± 4 weeks, mean birth weight: 2,145 ± 757 g). Twenty-three infants had a final diagnosis of RDS and 30 of TTN. LUS showed a sensitivity of 95.6% and specificity of 94.4%, with a PPV of 91.6% and a NPV of 97.1% for RDS, and a sensitivity of 93.3% and specificity of 96.5% with a PPV of 96.5% and a NPV of 93.4% for TTN. Conclusions: LUS showed high sensitivity and specificity in diagnosing RDS and TTN.
Growth in Preterm Infants until 36 Weeks' Postmenstrual Age Is Close to Target Recommendations
Authors: Sáenz de Pipaón Miguel , Martínez-Biarge Miriam , Dorronsoro Izaskun , Salas Sofía , Madero Rosario , Martos Gabriel Ángel , Argente Jesús , Quero José
Published: April 2017

Objective: To establish the determinants of weight, length and head circumference changes during their initial hospitalization in very-low-birth-weight preterm infants. Subjects/Methods: A prospective cohort study was performed. Weight z-score and percentage of target dietary intakes (TDIs) were prospectively determined daily during the first 5 weeks of life in a group of preterm infants (n = 111, birth weight <1,500 g, gestational age <34 weeks). Weight, length and head circumference at 36 weeks' postmenstrual age (PMA) were recorded. A mixed effects regression model was used to evaluate changes in weight z-score during the first 5 weeks of life. Simple Pearson correlations and stepwise logistic regression were used to determine the relationship between fetal growth, illness severity, nutritional intake and growth at 36 weeks' PMA. Results: Weight z-score decreased significantly in all infants during the first 5 weeks of life from -0.92 ± 0.66 at birth to -1.89 ± 0.65 at 5 weeks. The variation of weight z-score during the first 5 weeks of life was influenced by weight z-score at birth, energy and protein intakes and gestational age. Mean energy and protein intakes were 95.5 and 86.4% of TDIs. Weight z-score fell to -2.05 ± 0.64 at 36 weeks' PMA. Birth weight z-score was significantly correlated with weight z-score at 36 weeks (R2 = 0.71; p < 0.001). Severity of illness influenced the weight z-score at 36 weeks. Conclusion: Despite achieving a protein and energy intake close to the described target intake, the rate of growth in our infants was lower than indicated by the intrauterine growth curve. Lower gestational age, lower birth weight and severe illness had a negative effect on growth.
Main Congenital Cerebral Anomalies: How Prenatal Imaging Aids Counseling
Authors: Garel Catherine , Moutard Marie-Laure
Published: April 2017

The purpose of this article is to discuss some common cerebral lesions that may be detected during prenatal screening: corpus callosum dysgenesis, absent septum pellucidum, localized parenchymal ischemic-hemorrhagic lesions, megacisterna magna, Blake's pouch cyst, posterior fossa arachnoid cyst and Dandy-Walker malformation. For each cerebral defect, the main imaging findings are reminded, certain differential diagnoses are discussed and prenatal diagnostic accuracy is analyzed with emphasis on uncertainties encountered during analysis of ultrasound or magnetic resonance images. Detecting cerebral lesions in fetuses requires rapid counseling by neuropediatricians. Keeping in mind that the prenatal diagnostic accuracy is not 100%, the neuropediatricians have to answer the parents' questions regarding the outcome of the unborn child as well as the risk of recurrence for future pregnancies. This article is based on the authors' large experience in both prenatal imaging and neurocounseling. The frequently asked questions are set up. Answers are provided, underscoring the importance of an appropriate description of the cerebral defect, and therefore the pivotal role of prenatal imaging. However, prenatal neurocounseling remains challenging and the parents must be aware of uncertainties regarding both diagnostic accuracy and prognostic evaluation.
Second-Line Chemotherapy in Recurrent Clear Cell Ovarian Cancer: Results from the Multicenter Italian Trials in Ovarian Cancer (MITO-9)
Authors: Esposito Francesca , Cecere Sabrina Chiara , Magazzino Francescapaola , Katsaros Dionyssios , Ottaiano Alessandro , Gadducci Angiolo , Pisano Carmela , Scalone Simona , Rabaiotti Emanuela , Salutari Vanda , Cormio Gennaro , Canuto Emilie Marion , Greggi Stefano , Savarese Antonella , Marinaccio Marco , Scollo Paolo , Santeufemia Davide Adriano , Sacco Cosimo , Facchini Gaetano , Pignata Sandro
Published: April 2017

Background and Aims: Ovarian clear cell carcinoma (CCC) has a poorer prognosis than other subtypes of ovarian cancer. In this study, we evaluated the responsiveness to second-line chemotherapy in recurrent ovarian CCC. Methods: The MITO-9 project investigated a cohort of patients observed between 1991 and 2007 in 20 centers. We identified 72 out of 240 patients with recurrent disease (28% stage I-II and 72% stage III-IV at diagnosis). Results: In 56% of patients, the clear cell histology was pure. Twenty-five patients were platinum-resistant, 18 were platinum-sensitive with a platinum-free interval (PFI) of 6-12 months, and 29 had a PFI >12 months. Upon recurrence, 47% of patients were treated with platinum chemotherapy according to the PFI. The overall response rate (RR) to platinum was 80%, with 55, 100, and 80% RR in patients with PFI of 6-12, >12, and >24 months. The RR to nonplatinum agents in resistant patients was 33%. Among the nonplatinum agents used in primary and secondary resistant cases, gemcitabine, administered in 12 cases, had a higher activity (RR = 66%) compared to topotecan or liposomal doxorubicin (n = 31; RR = 33 and 10%, respectively). Conclusions: This study showed that the treatment of recurrent ovarian CCC should be based on the PFI as in the other subtypes. Data in platinum-resistant patients suggest gemcitabine as the drug with the highest activity. We recommend that gemcitabine be studied prospectively in a phase 2 trial.
Confounding Factors in Diagnostics of MGMT Promoter Methylation Status in Glioblastomas in Stereotactic Biopsies
Authors: Weise Lutz M. , Harter Patrick N. , Eibach Sebastian , Braczynski Anne K. , Dunst Maika , Rieger Johannes , Bähr Oliver , Hattingen Elke , Steinbach Joachim P. , Plate Karl H. , Seifert Volker , Mittelbronn Michel
Published: April 2017

Background: In nonresectable glioblastoma (GBM), stereotactic biopsies are performed to retrieve tissue for diagnostic purposes. The analysis of O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation adds prognostic and predictive information. Objectives: The aim of the study was to detect confounding factors that limit the number of conclusive MGMT promoter methylation results. Methods: We analyzed 71 consecutive GBM patients undergoing stereotactic biopsy on whom MGMT analysis was performed by methylation-specific polymerase chain reaction. Specimens were correlated to imaging by coregistration and prospective documentation of biopsy localization. Our findings were validated in an additional 62 GBM stereotactic biopsies. Results: Our results demonstrate that the best MGMT promoter methylation results were obtained from samples (n = 71) taken in a tangential manner from tumor areas showing contrast enhancement in magnetic resonance imaging. In the additional validation series of 62 stereotactically biopsied GBM, we were able to increase the rate of conclusive MGMT promoter methylation results from 76.1 to 85.48% by strictly planning the route of biopsy in a tangential manner if possible. Conclusions: These results underline that within the contrast-enhanced tumor part, choosing the trajectory in a tangential manner increases the diagnostic yield for conclusive MGMT promoter methylation analyses in stereotactic biopsies as a basis for patient stratification and individualized therapy.
Titer and Product Affect the Distribution of Gene Expression after Intraputaminal Convection-Enhanced Delivery
Authors: Emborg Marina E. , Hurley Samuel A. , Joers Valerie , Tromp Do P.M. , Swanson Christine R. , Ohshima-Hosoyama Sachiko , Bondarenko Viktorya , Cummisford Kyle , Sonnemans Marc , Hermening Stephan , Blits Bas , Alexander Andrew L.
Published: April 2017

Background: The efficacy and safety of intracerebral gene therapy for brain disorders like Parkinson's disease depends on the appropriate distribution of gene expression. Objectives: To assess whether the distribution of gene expression is affected by vector titer and protein type. Methods: Four adult macaque monkeys seronegative for adeno-associated virus 5 (AAV5) received a 30-µl inoculation of a high- or a low-titer suspension of AAV5 encoding glial cell line-derived neurotrophic factor (GDNF) or green fluorescent protein (GFP) in the right and left ventral postcommissural putamen. The inoculations were conducted using convection-enhanced delivery and intraoperative MRI (IMRI). Results: IMRI confirmed targeting and infusion cloud irradiation from the catheter tip into the surrounding area. A postmortem analysis 6 weeks after surgery revealed GFP and GDNF expression ipsilateral to the injection site that had a titer-dependent distribution. GFP and GDNF expression was also observed in fibers in the substantia nigra (SN) pars reticulata (pr), demonstrating anterograde transport. Few GFP-positive neurons were present in the SN pars compacta (pc), possibly by direct retrograde transport of the vector. GDNF was present in many neurons of the SNpc and SNpr. Conclusions: After controlling for target and infusate volume, the intracerebral distribution of the gene product was affected by the vector titer and product biology.
Selective Antegrade Cerebral Perfusion Attenuating the TLR4/NF-κB Pathway during Deep Hypothermia Circulatory Arrest in a Pig Model
Authors: Tang Zhi-Xian , Chen Guang-Xian , Liang Meng-Ya , Rong Jian , Yao Jian-ping , Yang Xiao , Wu Zhong-Kai
Published: April 2017

Objectives: The alteration of the Toll-like receptor/nuclear factor-kappa B (TLR4/NF-κB) signaling pathway during deep hypothermia circulatory arrest (DHCA) has not yet been defined. The aim of this study was to explore the expression of the TLR4/NF-κB pathway cytokine in cerebral injury resulting from DHCA as well as the effect of selective antegrade cerebral perfusion (SACP) on TLR4/NF-κB pathway expression. Methods: Twelve pigs were randomly assigned to DHCA alone (n = 6) or DHCA with SACP (n = 6) at 18°C for 80 min. Serum interleukin (IL)-6 was assayed by ELISA. Apoptosis and NF-κB proteins were detected by fluorescence TUNEL and Western blot, respectively. The level of TLR4 mRNA and protein were determined through qRT-PCR and Western blot. Results: The serum IL-6 level of the SACP group was significantly lower than that of the DHCA group at the end of circulation arrest and experimentation. Apoptotic index and NF-κB protein were apparently lower in SACP animals (p < 0.05). Compared to the DHCA group, the levels of TLR4 protein and mRNA in the SACP group were lower with significance (p < 0.05). Conclusions: The TLR4/NF-κB signaling pathway plays a critical role in the pathogenesis of DHCA cerebral injury. Attenuation of the TLR4/NF-κB inflammatory cytokines probably contributes to the neuroprotective effect of SACP. The TLR4/NF-κB inflammatory signaling pathway may be a novel therapeutic target for developing a new strategy for neuroprotection in DHCA.
Allergy to Formaldehyde: Basophil Histamine-Release Test Is Useful for Diagnosis
Authors: Tanaka Yusuke , Nakase Yuko , Yamaguchi Masao , Sugimoto Naoya , Ohara Kenshin , Nagase Hiroyuki , Ohta Ken
Published: April 2017

We describe a case of formaldehyde-induced urticaria with a positive test result for serum IgE antibody against this substance. Formaldehyde's slow protein-binding property may explain why basophil histamine-release tests using fresh formaldehyde solutions are not diagnostic, whereas the tests are useful if formaldehyde that had been stored with albumin is used.
Maternal Nicotine Exposure Exacerbates Neonatal Hyperoxia-Induced Lung Fibrosis in Rats
Authors: Huang Liang-Ti , Chou Hsiu-Chu , Lin Chun-Mao , Yeh Tsu-Fu , Chen Chung-Ming
Published: April 2017

Background: Maternal nicotine exposure increases lung collagen in fetal and newborn animals. Connective tissue growth factor (CTGF) plays a role in hyperoxia-induced pulmonary fibrosis. Objective: To determine whether pre- and postnatal nicotine exposure can augment CTGF expression and postnatal hyperoxia-induced lung fibrosis. Methods: Nicotine was administered to pregnant Sprague-Dawley rats at a dose of 6 mg/kg/day from gestational days 7-21 (prenatal nicotine-treated group) and gestational day 7 to postnatal day 14 (pre- and postnatal nicotine-treated group). A control group of pregnant dams was injected with an equal volume of saline. Within 12 h of birth, rats were exposed to room air or 1 week of >95% O2 and an additional 2 weeks of 60% O2 (3 weeks of hyperoxia). Lungs were taken for total collagen, CTGF expression and histological analyses. Results: In each maternal treatment group, the rats reared in hyperoxia had a higher total collagen compared with rats reared in room air on postnatal days 7 and 21. Collagen content was significantly higher in rats born to pre- and postnatal nicotine-treated dams than rats born to saline-treated and prenatal nicotine-treated dams on postnatal days 7 and 21. Pre- and postnatal nicotine exposure and neonatal hyperoxia exposure increased CTGF expression on postnatal days 7 and 21. Conclusions: CTGF may be involved in the pathogenesis of lung fibrosis induced by maternal nicotine and neonatal hyperoxia, and maternal nicotine exposure exacerbates neonatal hyperoxia-induced lung fibrosis. These results are relevant to neonates who require supplemental oxygen and are exposed to the breast milk of smoking mothers during infancy.
Hepatic Arterial Infusion of Gemcitabine plus Oxaliplatin as Second-Line Treatment for Locally Advanced Intrahepatic Cholangiocarcinoma: Preliminary Experience
Authors: Ghiringhelli François , Lorgis Veronique , Vincent Julie , Ladoire Sylvain , Guiu Boris
Published: April 2017

Background: The aim of this study was to evaluate the efficacy and tolerability of hepatic arterial infusion (HAI) of gemcitabine plus oxaliplatin as second-line treatment for unresectable locally advanced intrahepatic cholangiocarcinoma. Patients and Methods: We retrospectively analyzed the outcome of 12 consecutive patients with unresectable locally advanced intrahepatic cholangiocarcinoma treated with HAI of gemcitabine (1,000 mg/m2 over 30 min) followed by oxaliplatin (100 mg/m2 over 2 h), which was repeated every 2 weeks. Results: All patients presented with disease limited to the liver and all had failed at least one line of chemotherapy with gemcitabine and oxaliplatin. The best tumor responses using RECIST criteria were partial responses in 8 patients and stable disease in 3 patients for at least 3 months; in 1 patient, disease progressed, resulting in a disease control rate of 91% (95% CI 45-100%). The median overall survival and time to progression were 9.1 months (95% CI 4.9-8.1) and 20.3 months (95% CI 13.2-49.7), respectively. Partial responses enabled R0 liver surgery in 2 patients and stereotactic radiation therapy in 3 patients. Grade 3/4 toxicities included neutropenia in 2 patients, thrombocytopenia in 2 patients, and oxaliplatin allergy in 2 patients. Conclusions: HAI combining gemcitabine and oxaliplatin showed promising efficacy and safety as second-line treatment for locally advanced intrahepatic cholangiocarcinoma.
Carpal Tunnel Surgery as Proxy for Dialysis-Related Amyloidosis: Results from the Japanese Society for Dialysis Therapy
Authors: Hoshino Junichi , Yamagata Kunihiro , Nishi Shinichi , Nakai Shigeru , Masakane Ikuto , Iseki Kunitoshi , Tsubakihara Yoshiharu
Published: April 2017

Background/Aims: This study aims to identify current risk factors for developing dialysis-related amyloidosis using carpal tunnel syndrome (CTS) as proxy for general amyloidosis. Methods: The cohort consisted of 166,237 patients on dialysis (mean age 66.1 ± 12.4 years; mean dialysis vintage 7.2 ± 6.4 years) who could be followed for a year between 2010 and 2011. Of these, 2,157 (1.30%) needed first-time CTS surgery during the study period. Odds ratios (ORs) for CTS were calculated at a 95% confidence interval (95% CI) after adjusting for age, gender, primary kidney disease, history of smoking, history of hypertension vintage, dialysis modality, use of high-flux membrane, body mass index, serum albumin, Kt/V, normalized protein catabolic rate, C-reactive protein, pretreatment β2-microglobulin (β2MG), and β2MG clearance. Results: Adjusted ORs of first-time CTS for vintages 10-15, 15-20, 20-25 (referent), 25-30, and >30 years were, respectively, 0.18 (0.12-0.26), 0.43 (0.31-0.62), 1.00, 2.37 (1.64-3.40), and 3.87 (2.52-5.93). Adjusted ORs for ages 40-50, 50-60 (referent), 60-70, 70-80, and >80 were 0.53 (0.30-0.94), 1.00, 1.89 (1.41-2.52), 1.52 (1.08-2.14), and 1.04 (0.60-1.80). Female gender, low serum albumin, and diabetic nephropathy were also associated with CTS. Pretreatment serum β2MG and β2MG clearance <80% were not significant, although β2MG clearance >80% was negatively associated with CTS [OR 0.34 (0.13-0.90)]. Conclusion: ORs of first-time CTS almost doubled with every 5-year increase in dialysis vintage. ORs of CTS were highest for patients aged 60-70. Other factors associated with CTS were gender, serum albumin, and diabetic nephropathy. β2MG clearance >80% may decrease the incidence of CTS.
Targeting Neurogenesis: A Promising Therapeutic Strategy for Post-Stroke Treatment with Chinese Herbal Medicine
Authors: Shen Jiangang , Chen Xingmiao , Chen Xi , Deng Ruixia
Published: April 2017

Recent progress suggests that neural stem/progenitor cells can potentially develop into new functional neurons in adult brain, offering hope for regeneration therapies for stroke treatment. Targeting adult neurogenesis becomes a novel and promising therapeutic strategy for brain repair and recovery of neurological functions. Traditional Chinese Medicine (TCM) has a long history with accumulated experiences and case reports using herbal formulas to treat stroke disability. The combination of Chinese herbal medicine and stem cell biology approaches provides great potential for post-stroke rehabilitations. In the last decade, large efforts have been made to investigate the molecular targets for the regulation of adult neurogenesis and to explore the active compounds and molecular targets of herbal medicine for regeneration therapy. Herein, we reviewed the current progress concerning the molecular targets and cellular signaling pathways involved in adult neurogenesis after cerebral ischemia. We then briefly introduced Chinese medical theory and herbs for stroke treatment in TCM. Finally, we reviewed the current knowledge about the effects of Chinese herbal formulas, active fractions and active compounds on promoting adult neurogenesis as well as their molecular targets. Although the precise mechanisms and molecular targets of herbal medicine for neurogenesis are still unclear, current progress at least provides a cue for exploring the therapeutic principles of Chinese herbal medicine and developing new drugs for brain repair after stroke.
Interdialytic Weight Gain and Cardiovascular Outcome in Incident Hemodialysis Patients
Authors: Lee Mi Jung , Doh Fa Mee , Kim Chan Ho , Koo Hyang Mo , Oh Hyung Jung , Park Jung Tak , Han Seung Hyeok , Yoo Tae-Hyun , Kim Yong-Lim , Kim Yon Su , Yang Chul Woo , Kim Nam-Ho , Kang Shin-Wook
Published: April 2017

Background: Interdialytic weight gain (IDWG) has been regarded as a surrogate of volume overload, but also as a marker of a better nutritional status in end-stage renal disease (ESRD) patients on hemodialysis (HD). This paradoxical meaning of IDWG requires further investigation, particularly in adverse cardiovascular outcomes. Methods: A prospective cohort of 1,013 incident HD patients from 36 HD centers of the Clinical Research Center for ESRD in Korea was included. Patients were categorized into five groups according to the IDWG%, a ratio of absolute IDWG to dry weight: <1.0, ≥4.0, and every 1.0 increment in between. Primary outcome was major adverse cardiac and cerebrovascular events (MACCE). Results: During a mean follow-up of 18.7 months, primary outcome was observed in 104 patients (10.3%). In multivariate analysis, compared to patients with IDWG% of 1.0-1.9 (reference group), the hazard ratios (HRs) for primary outcome in the IDWG% <1.0, 2.0-2.9, 3.0-3.9, and ≥4.0 groups were 1.10 [95% confidence interval (CI) 0.55-2.20, p = 0.80], 1.15 (95% CI 0.59-2.27, p = 0.68), 1.80 (95% CI 0.95-3.41, p = 0.07), and 1.93 (95% CI 1.02-3.64, p = 0.04), respectively. Furthermore, even when residual renal function and 24-hour urine volume were adjusted, IDWG% ≥4.0 remained as a significant predictor of primary outcome (HR 2.03, 95% CI 1.02-4.02, p = 0.04). Conclusion: Increased IDWG% is a significant independent predictor of MACCE in incident HD patients. It could be helpful to prevent excessive IDWG for improving clinical outcomes in incident HD patients.
Neoadjuvant, Anthracycline-Free Chemotherapy with Carboplatin and Docetaxel in Triple-Negative, Early-Stage Breast Cancer: A Multicentric Analysis of Feasibility and Rates of Pathologic Complete Response
Authors: Kern Peter , Kalisch Anne , Kolberg Hans-Christian , Kimmig Rainer , Otterbach Friederich , von Minckwitz Gunter , Sikov William M. , Pott Dirk , Kurbacher Christian
Published: April 2017

Background: Triple-negative breast cancer (TNBC) attracts a disproportionate share of intensive research because of its poor prognosis. Standard anthracycline- and taxane-based regimens still yield an unsatisfactorily low rate of pathologic complete response (pCR). The pCR rate is a recognized surrogate marker for good long-term survival. Methods: A multicentric, retrospective study was conducted including all patients not willing to undergo or not suitable for an anthracycline-based regimen. Six cycles of docetaxel 75 mg/m2 and carboplatin AUC 6 q3w were administered. The primary endpoint was pCR (ypT0/ypTis + ypN0) and near-pCR (≤5 mm residual disease). The secondary endpoint was feasibility (CTCAE version 4.03 criteria) and adherence to treatment. Results: Six cycles of carboplatin AUC 6 and docetaxel 75 mg/m2 resulted in a high pCR rate of 50% and a combined pCR/near-pCR rate of 70%. Grade 3 and 4 toxicities were rare events and 28 of 30 (93%) patients completed all 6 cycles. No toxicity-related treatment discontinuation and no febrile neutropenia were registered. Conclusion: This chemotherapy regimen provides a highly effective and feasible strategy for patients not willing to receive or not suitable for an anthracycline-based treatment (cardiac ejection fraction <65% or age >65 years). Combinations of platinum compounds with taxanes and anthracyclines may be also desirable in TNBC.
Snoring Amplifies the Risk of Heart Failure and Mortality in Dialysis Patients
Authors: Torino Claudia , Mattace-Raso Francesco , van Saase Jan L.C.M. , D'Arrigo Graziella , Tripepi Rocco , Tripepi Giovanni Luigi , Postorino Maurizio , Mallamaci Francesca , Zoccali Carmine ,   on behalf of the PROGREDIRE Working Group
Published: April 2017

Background: Snoring, an indicator of sleep-disordered breathing (SDB), associates with all-cause and cardiovascular (CV) mortality in high-risk conditions such as chronic heart failure (HF). Because SDB and HF are exceedingly frequent in end-stage kidney disease (ESKD), we hypothesized that SDB as detected by snoring may impact upon the relationship between chronic HF and all-cause and CV mortality in these patients. Methods: We tested this hypothesis in a cohort of 827 ESKD patients, followed up for 2.3 years. Results: In this population, snoring was a strong modifier of the risk of chronic HF for all-cause and CV death. In fully adjusted Cox models, the hazard ratio (HR) associated to chronic HF for the study outcomes was highest in heavy snorers [all-cause death: HR 2.6 (95% CI 1.6-4.3, p < 0.001); CV death: HR 4.0 (95% CI 2.1-7.6, p < 0.001)], intermediate in moderate snorers [all-cause death: HR 1.6 (95% CI 1.1-2.2, p = 0.01); CV death: HR 1.8 (95% CI 1.2-2.8, p = 0.01)], and lowest and not significant in non-snorers [all-cause death: HR 0.9 (95% CI 0.6-1.6, p = NS); CV death: HR 0.8 (95% CI 0.4-1.6, p = NS)]. Conclusions: Snoring is a strong and independent effect modifier of the relationship between chronic HF and all-cause and CV mortality in ESKD. Since SDB and snoring are in part attributable to reversible pharyngeal oedema, intensified surveillance and treatment of chronic HF snorers on dialysis may translate into better clinical outcomes in this very high-risk population, an issue which remains to be tested in specifically designed clinical trials.
Neural Predictors of Successful Brief Psychodynamic Psychotherapy for Persistent Depression
Authors: Roffman Joshua L. , Witte Janet M. , Tanner Alexandra S. , Ghaznavi Sharmin , Abernethy Robert S. , Crain Laura D. , Giulino Patricia U. , Lable Ira , Levy Raymond A. , Dougherty Darin D. , Evans Karleyton C. , Fava Maurizio
Published: April 2017

Background: Psychodynamic psychotherapy has been used to treat depression for more than a century. However, not all patients respond equally well, and there are few reliable predictors of treatment outcome. Methods: We used resting 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) scans immediately before and after a structured, open trial of brief psychodynamic psychotherapy (n = 16) in conjunction with therapy process ratings and clinical outcome measures to identify neural correlates of treatment response. Results: Pretreatment glucose metabolism within the right posterior insula correlated with depression severity. Reductions in depression scores correlated with a pre- to posttreatment reduction in right insular metabolism, which in turn correlated with higher objective measures of patient insight obtained from videotaped therapy sessions. Pretreatment metabolism in the right precuneus was significantly higher in patients who completed treatment and correlated with psychological mindedness. Conclusions: Resting brain metabolism predicted both clinical course and relevant psychotherapeutic process during short-term psychodynamic psychotherapy for depression.
Effects of Uric Acid on Hearts of Rats with Chronic Kidney Disease
Authors: Bao Xiaorong , Wang Yu , Wei Cuifang , Zhang Qing
Published: April 2017

Aims: To study the effects of uric acid on cardiac lesions and its possible mechanism by establishing an early-stage CKD animal model with hyperuricemia. Allopurinol was used to see whether it could reduce cardiac lesions. Methods: The experimental rats were randomly divided into 4 groups (n = 15): Group A (sham-operative group), Group B (CKD group), Group C (CKD with hyperuricemia group), Group D (CKD with hyperuricemia + allopurinol group). After 16 weeks, the rats were sacrificed and blood samples were collected for detection of Scr, SUA, hs-CRP and IL-6. Kidney and heart tissues were pathologically examined. The collagen I of heart tissues was examined by immunohistochemistrical methods. Results: Obvious pathological changes could be observed in Group C. However, compared to Group C, the pathological changes in Group D were lighter. The proportion of collagen I positive area (PCIPA) in Group C was significantly higher than that in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with PCIPA in myocardium. IL-6 and hs-CRP levels in Group C were significantly higher than in Group A, B and D. Univariate analysis showed that the SUA level had a significant positive correlation with IL-6 and hs-CRP, and PCIPA in myocardium had a significant positive correlation with hs-CRP and IL-6 levels. Conclusions: There were obvious cardiac lesions in early-stage CKD rats with hyperuricemia, and the severity of cardiac lesions was positively related to the level of SUA. Micro-inflammation might be one mechanism causing cardiac lesions. Allopurinol could alleviate cardiac lesions in early-stage CKD rats by lowering the SUA level, which, in turn, could reduce the severity of micro-inflammation.
Iron Status and Inflammation in Early Stages of Chronic Kidney Disease
Authors: Łukaszyk Ewelina , Łukaszyk Mateusz , Koc-Żórawska Ewa , Tobolczyk Jolanta , Bodzenta-Łukaszyk Anna , Małyszko Jolanta
Published: April 2017

Background/Aims: One of the most common causes of anemia of chronic disease (ACD) is chronic kidney disease. The main pathomechanism responsible for ACD is subclinical inflammation. The key element involved in iron metabolism is hepcidin, however, studies on new indices of iron status are in progress.The aim of the study was to assess the iron status in patients in early stages of chronic kidney disease, iron correlation with inflammation parameters and novel biomarkers of iron metabolism. Methods: The study included 69 patients. Standard laboratory measurements were used to measure the iron status, complete blood count, fibrinogen, prothrombin index, C-reactive protein concentration (CRP), creatinine, urea, uric acid. Commercially available kits were used to measure high-sensitivity CRP, interleukin 6 (IL-6), hepcidin-25, hemojuvelin, soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15) and zonulin. Results: Absolute iron deficiency was present in 17% of the patients, functional iron deficiency was present in 12% of the patients. Functional iron deficiency was associated with significantly higher serum levels of fibrinogen, ferritin, transferrin saturation, total iron binding capacity, hepcidin and older age relative to patients with absolute iron deficiency. In comparison with patients without iron deficiency, patients with functional iron deficiency were older, with lower prothrombin index, higher fibrinogen, CRP, hsCRP, sTfR, GDF-15, urea and lower eGFR. Hepcidin was predicted by markers of inflammation:ferritin, fibrinogen and IL-6. Conclusion: Inflammation is correlated with iron status. Novel biomarkers of iron metabolism might be useful to distinguish iron deficiency anemia connected with inflammation and absolute iron deficiency.
Administration of Cyclosporine A in Pregnant Rats - the Effect on Blood Pressure and on the Glomerular Number in Their Offspring
Authors: Slabiak-Blaz Natalia , Adamczak Marcin , Gut Nadezda , Grajoszek Aniela , Nyengaard Jens R. , Ritz Eberhard , Wiecek Andrzej
Published: April 2017

Background/Aims: Cyclosporine A (CsA) is a commonly used immunosuppressive agent. In some patients treatment with CsA has to be continued during pregnancy. The aim of the study was to assess in an experimental model whether the exposure to CsA during fetal life influences the number and volume of glomeruli, kidney function and blood pressure in the offspring. Methods: Eight pregnant female Sprague-Dawley rats were allocated to 2 treatment regimens: with CsA or solvent. Blood pressure was measured in the offspring at 7 and 11 weeks of age and albuminuria was determined at 11 weeks of age. In the kidney the number and mean volume of glomeruli was assessed using stereological methods. Results: In the offspring of pregnant rats treated with CsA the number of glomeruli was significantly lower and the mean volume of glomeruli was higher when compared to the offspring of pregnant rats receiving solvent. Systolic and diastolic blood pressures as well as albuminuria were significantly higher in the offspring of mothers treated with CsA during gestation compared to the offspring from the control group. Conclusions: Exposure of rats to CsA during fetal life impairs kidney development, thus potentially predisposing to chronic kidney disease and hypertension in the adult life.
The Therapeutic Potential of Carbon Monoxide for Inflammatory Bowel Disease
Authors: Takagi Tomohisa , Uchiyama Kazuhiko , Naito Yuji
Published: April 2017

Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn's disease, are chronic, relapsing and remitting inflammatory disorders of the intestinal tract. Because the precise pathogenesis of IBD remains unclear, it is important to investigate the pathogenesis of IBD and to evaluate new anti-inflammatory strategies. Recent accumulating evidence has suggested that carbon monoxide (CO) may act as an endogenous defensive gaseous molecule to reduce inflammation and tissue injury in various organ injury models, including intestinal inflammation. Furthermore, exogenous CO administration at low concentrations is protective against intestinal inflammation. These data suggest that CO may be a novel therapeutic molecule in patients with IBD. In this review, we present what is currently known regarding the therapeutic potential of CO in intestinal inflammation.
Calycosin and Genistein Induce Apoptosis by Inactivation of HOTAIR/p-Akt Signaling Pathway in Human Breast Cancer MCF-7 Cells
Authors: Chen Jian , Lin Changrong , Yong Wang , Ye Yu , Huang Zhaoquan
Published: April 2017

Background: Calycosin and genistein are the two main components of isoflavones. Previously, we reported that these compounds display antitumor activities in the breast cancer cell lines MCF-7 and T47D. In the present study, we investigated the mechanism of action of calycosin and genistein, and their respective efficacies as potential therapies for the treatment of breast carcinoma in the clinic. Methods: MCF-7 cells were treated with calycosin or genistein. Cell proliferation and apoptosis were measured using CCK8 assay and Hoechst 33258. The expression level of phosphorylated Akt protein was determined by western blotting. Expression level of HOTAIR was quantified by real-time PCR. Results: Both calycosin and genistein inhibited proliferation and induced apoptosis in MCF-7 breast cancer cells, especially after treatment with calycosin. Treatment of MCF-7 cells with calycosin or genistein resulted in decreased phosphorylation of Akt, and decreased expression of its downstream target, HOTAIR. Conclusion: Calycosin is more effective in inhibiting breast cancer growth in comparison with genistein, through its regulation of Akt signaling pathways and HOTAIR expression.
Idiopathic Calcium Nephrolithiasis: A Review of Pathogenic Mechanisms in the Light of Genetic Studies
Authors: Arcidiacono Teresa , Mingione Alessandra , Macrina Lorenza , Pivari Francesca , Soldati Laura , Vezzoli Giuseppe
Published: April 2017

Background: Calcium nephrolithiasis is a multifactorial disease with a polygenic milieu. Association studies identified genetic polymorphisms potentially implicated in the pathogenesis of calcium nephrolithiasis. The present article reviews the mechanisms of calcium stone formation and the potential contribution of gene polymorphisms to lithogenic mechanisms. Summary: Endoscopy observations suggested that precipitation of calcium-oxalate on the Randall's plaque at the papilla surface may cause idiopathic calcium-oxalate stones. The Randall's plaque is a hydroxyapatite deposit in the interstitium of the kidney medulla, which resembles a soft tissue calcification. Conversely, calcium-phosphate stones may develop from crystalline deposits located at the tip of the Bellini duct. Polymorphisms of eleven genes have been associated with stones in genome-wide association studies and replicated candidate-gene association studies: VDR, SLC34A1, SLC34A4, CLDN14, and CaSR genes coding for proteins regulating tubular phosphate and calcium reabsorption; CaSR, MGP, OPN, PLAU, and UMOD genes coding for proteins preventing calcium salt precipitation; AQP1 gene coding for a water channel in the proximal tubule. The renal activity of the last gene, DGKH, is unknown. Polymorphisms in these genes may predispose to calcium-oxalate and -phosphate stones by increasing the risk of calcium-phosphate precipitation in the tubular fluid. Key Messages: Genetic findings suggest that tubular fluid supersaturation with respect to calcium and phosphate predisposes to calcium-oxalate stones by triggering cellular mechanisms that lead to the Randall's plaque formation. © 2014 S. Karger AG, Basel
The Protective Effect of Erythropoietin on the Retina
Authors: Luo Wentao , Hu Liumei , Wang Fang
Published: April 2017

Erythropoietin (Epo) was once considered to be a regulator of erythropoiesis by controlling the apoptosis, proliferation and differentiation of erythroid precursor cells over an extended period of time. However, the expression of Epo and Epo receptor (Epo-R) occurs in the brain and retina in addition to the kidney. These expression behaviors lead to physiological effects in addition to hematocrit elevation. In this review we discuss the protective effect of Epo on retinal cells.
Hypodysfibrinogenemia with a Heterozygous Mutation of γCys326Ser by the Novel Transversion of TGT to TCT in a Patient with Pulmonary Thromboembolism and Right Ventricular Thrombus
Authors: Ushijima Akiko , Komai Taichi , Masukawa Atsuko , Oikawa Keiko , Morita Norishige , Asai Satomi , Mukai Saki , Okumura Nobuo , Kobayashi Yoshinori , Miyachi Hayato
Published: April 2017

We encountered a 45-year-old Japanese man who suffered from pulmonary thromboembolism and huge right ventricular thrombus after inferior vena cava (IVC) filter implantation without apparent thrombus in either the deep veins or inside the IVC filter. The biochemical data showed a discrepancy in the level of fibrinogen between the immunological and thrombin time methods, suggesting hypodysfibrinogenemia. The sequencing of the fibrinogen γ-chain gene (FGG) revealed a novel heterozygous missense mutation in exon 8 - a TGT to TCT transversion in codon 326 - resulting in an amino acid substitution of serine for cysteine (γCys326Ser). The characterization of the protein did not show known mechanisms for thrombosis in dysfibrinogenemia, such as dimer or albumin-binding complex formation. In summary, the current case with a life-threatening thrombotic event was found to have a novel heterozygous missense mutation resulting in γCys326Ser, which was suggested as a predisposing factor of the thrombosis. Known mechanisms responsible for thrombosis in the current case were not demonstrated, suggesting other mechanisms including superimposing inherited and/or acquired risk factors. When a patient presents with unusual thrombosis such as breakthrough pulmonary embolism and huge thrombus in the right ventricle, as in the current case, the laboratory process for heritable thrombophilia should be considered.