bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatorenal Syndrome and Novel Advances in its Management
Authors: Fabrizi Fabrizio , Aghemo Alessio , Messa Piergiorgio
Published: April 2017

Hepatorenal syndrome is a complication of end stage liver disease. It is a unique form of functional renal failure related to kidney vasoconstriction in the absence of underlying kidney pathology. Hepatorenal syndrome is classified into 2 types: type-1 HRS shows a rapid and progressive decline in renal function with a very poor prognosis (median survival of about 2 weeks); type-2 HRS has a more stable kidney failure, with a median survival of 6 months; its main clinical manifestation is refractory ascites. The most appropriate therapy for HRS is liver transplantation but only a minority of HRS patients undergo the procedure due to the high mortality; survival among liver transplant recipients is lower in HRS than among their counterparts without HRS. A large body of evidence, based on observational studies and randomized controlled trials, has been accumulated in the last decade showing that terlipressin represents a milestone in the management of HRS. According to our meta-analysis of randomized trials comparing terlipressin vs. placebo (five trials, n=243 patients), the pooled rate of patients who reversed HRS by terlipressin was 8.09 (95% CI, 3.52; 18.59) (P<0.001). Among vasoconstrictors, terlipressin (a V1 vasopressin agonist) is the most widely used; however, noradrenaline is another good choice. Vasoconstrictor drugs alone or with albumin reduce mortality compared with no intervention or albumin (RR of mortality, 0.82; 95% Confidence Intervals, 0.70; 0.96) (P<0.01). Two series of patients with HRS recurrence after the first treatment have recently shown that long-term therapy with terlipressin and albumin is beneficial as a bridge to liver transplant. Nevertheless, recovery of renal function can be achieved in less than 50% of patients with HRS after terlipressin use and the recovery of renal function may also be partial in patients who are defined full responders. Renal replacement therapy should not be considered a first-line therapy for HRS Clinical trials are under way in order to assess efficacy and safety of novel therapeutic agents for the treatment of type-1 and type-2 HRS.
The Immunology of Delirium
Authors: Cerejeira Joaquim , Lagarto Luísa , Mukaetova-Ladinska Elizabeta B.
Published: April 2017

Delirium is an acute neuropsychiatric syndrome characterized by acute-onset global cognitive deficits, perceptual and behavioural disturbances affecting mainly elderly subjects with underlying medical or surgical conditions. The pathophysiology of delirium is complex and inflammation is a relevant precipitant factor of this syndrome, although it remains unclear how acute systemic inflammation induces the clinical picture of delirium. The central nervous system is able to detect peripheral infection or tissue destruction through circulating immune mediators and neural ascending signs. Activated microglia is responsible for an acute neuroinflammatory reaction underlying the symptoms of sickness. In healthy conditions descending pathways from the paraventricular nucleus, locus coeruleus and dorsal motor nucleus organize a centralized response to influence the immune response at the periphery and restore homeostasis. In the context of ageing and chronic neurodegeneration, adaptive changes to acute insults are characterized by exaggerated production of pro-inflammatory cytokines by primed microglia coupled with dysfunction of brain-to-immune pathways. In animal models, these changes underlie a more severe manifestation of sickness behaviour with working memory deficits suggesting that inattention, a core feature of delirium, can be a clinical correlate of an increased neuroinflammatory reaction. In patients with delirium, higher levels of pro-inflammatory cytokines and cortisol were identified in plasma and cerebrospinal fluid. However, to date it has not been clarified how peripheral inflammatory or endocrine biomarkers can reflect the likelihood or severity of delirium symptoms. In the future, a better understanding of the interaction between the brain and peripheral organs and the exact mechanism by which systemic inflammation can lead to delirium, will allow the development of new therapeutic agents.
Chronic Low-Grade Inflammation in Metabolic Disorders: Relevance for Behavioral Symptoms
Authors: Lasselin Julie , Capuron Lucile
Published: April 2017

The ability of cytokines to influence cerebral functions and to induce the development of behavioral alterations is well established in conditions of acute or chronic high-grade activation of the innate immune system. Recent evidence suggests that the release of these immune mediators during chronic low-grade endogenous inflammatory processes may also contribute to the development of behavioral alterations. Metabolic disorders, including obesity, type 2 diabetes and the metabolic syndrome, represent examples of those conditions which are both characterized by a chronic low-grade inflammatory state and an increased prevalence of behavioral disorders. In metabolic disorders, the increased production of acute-phase proteins and cytokines (e.g. C-reactive protein, interleukin-6 and tumor necrosis factor-α), but at relatively low levels, may promote and contribute to the development of behavioral symptoms, including depressive symptoms, cognitive impairment, fatigue, sleep problems and pain. This hypothesis is supported by a growing literature referring both to experimental and clinical findings that will be reviewed here.
First-Episode Psychosis: An Inflammatory State?
Authors: Zajkowska Zuzanna , Mondelli Valeria
Published: April 2017

In the last decade an increasing body of research has focussed on the potential role of inflammation in the onset of psychiatric disorders. Although the association between inflammation and depression appears now widely acknowledged, mixed findings have been reported in psychosis leaving the pathophysiological role of inflammation in psychosis still unclear. This paper aims to review studies focussing on inflammation in first-episode psychosis, in order to avoid the possible confounding effects of the long duration of illness and chronic treatment with psychotropic medications. Increased levels of IL-6, TNF-α and IL-1β are the most consistent findings from the studies conducted in first-episode psychosis patients. Mixed findings on other cytokines could be partly due to the different methodologies of the studies reviewed. The findings on the association between inflammatory markers and clinical symptoms and physical health, as well as on the effect of antipsychotic medications on inflammation at the onset of psychosis are also reviewed and discussed. The increased inflammation at onset of psychosis as well as in other psychiatric conditions, such as depression, suggests the presence of biological abnormalities which play a pathophysiological role across different diagnostic categories. Future research should test if increased inflammation could be used for the development of biomarkers, as well as as a potential therapeutic target for different subsamples of patients independently of their diagnostic category.
TAS-106: Preclinical, Clinical and Beyond
Authors: Abdelrahim Maen , Matsuda Akira , Naing Aung
Published: April 2017

5-Fluorouracil, other fluorinated pyrimidines and their derivatives are frequently used in chemotherapy to treat different types of cancer. These agents are classified as metabolic antagonists that target the DNA synthesis phase of the cell cycle. Therefore, these agents are more effective in rapidly growing tumors than in more indolent cancers. In order to develop new drugs that interfere with both DNA and RNA synthesis, the metabolism of pyrimidines was investigated, and new compounds were developed by the molecular design method, which analyzes the biochemical properties of the compounds. The nucleoside 3′-C-ethynylcytidine (TAS-106) was designed to inhibit RNA synthesis by blocking RNA polymerases I, II, and III, which occur throughout the cell cycle except for the M phase. This review article discusses the antitumor activity of TAS-106 as a single agent or in combination therapy with the focus on preclinical and clinical findings.
Evaluation of Weight Loss and Adipocytokine Levels after Two Hypocaloric Diets with Different Macronutrient Distribution in Obese Subjects with the rs6923761 Gene Variant of Glucagon-Like Peptide 1 Receptor
Authors: de Luis Daniel Antonio , Aller Rocío , Izaola Olatz , de la Fuente Beatriz , Primo David , Conde Rosa , Sagrado Manuel González
Published: April 2017

Background: The role of glucagon-like peptide-1 receptor (GLP-1R) variants on body weight response after dietary intervention has not been evaluated so far. Objective: Our aim was to evaluate weight loss and adipocytokine levels after two hypocaloric diets with different macronutrient distribution in obese subjects with rs6923761. Design: A sample of 280 obese subjects was randomized to two hypocaloric diets. Results: 124 patients (44.3%) had the genotype GG (wild-type) and 156 (55.7%) had another genotype (mutant), i.e. GA (n = 132, 47.1%) or AA (n = 24, 8.6%). With the type I diet (low in carbohydrates) in the wild-type and mutant groups, BMI, weight, fat mass, waist circumference, insulin levels, insulin resistance and triglycerides decreased. Anthropometric parameters were higher in non-A-allele carriers than A-allele carriers. With the type II diet (low in fats) in all genotypes, BMI, weight, fat mass, waist circumference, insulin levels, total cholesterol and LDL cholesterol decreased. Conclusion: Our data showed better anthropometric parameters in obese subjects with the mutant allele (A) of the rs6923761 GLP-1R polymorphism. A lack of association of this polymorphism with weight loss or biochemical parameters after two different hypocaloric diets was observed.
Lipopolysaccharide-Binding Protein as Marker of Fetal Inflammatory Response Syndrome after Preterm Premature Rupture of Membranes
Authors: Pavcnik-Arnol Maja , Lucovnik Miha , Kornhauser-Cerar Lilijana , Premru-Srsen Tanja , Hojker Sergej , Derganc Metka
Published: April 2017

Background: Intra-amniotic inflammation with preterm premature rupture of membranes (PPROM) is a risk factor for fetal inflammatory response syndrome (FIRS) and adverse neonatal outcome. Objectives: To evaluate the diagnostic accuracy of lipopolysaccharide-binding protein (LBP) for detecting FIRS in preterm neonates born after PPROM. Methods: This was a prospective study in the level III neonatal intensive care unit (42 neonates; 23 + 6 to 31 + 6 weeks' gestation) of mothers with PPROM. Umbilical cord blood concentrations of LBP, C-reactive protein (CRP), interleukin (IL)-6 and white blood cell count with differential were measured at delivery and 24 h after birth. Neonates were classified into FIRS (n = 22) and no FIRS (n = 20) groups according to clinical criteria and IL-6 level (≥17.5 pg/ml). Histological examination of the placenta and umbilical cord was performed. Neurological examination at 12 months' corrected age was performed. Results: Umbilical cord blood concentration of LBP was significantly higher in the FIRS group than in the no FIRS group at delivery (median 21.6 mg/l vs. median 2.3 mg/l; p < 0.0001) and 24 h after birth (median 17.2 mg/l vs. median 20.0 mg/l; p < 0.001). The area under the ROC curve for FIRS at delivery was 0.98 (95% CI 0.88-1.0) for LBP, 0.92 (95% CI 0.80-0.99) for CRP and 0.82 (95% CI 0.64-0.94) for immature to total neutrophil ratio. Similar results were obtained if FIRS was defined by funisitis. Umbilical cord blood concentration of LBP at delivery was significantly higher in neonates with abnormal neurological exam at 12 months than in those with normal exam (median 19.5 mg/l vs. median 3.75 mg/l; p < 0.015). Conclusions: In preterm neonates born to asymptomatic women with PPROM, LBP in cord blood at delivery is an excellent diagnostic biomarker of FIRS/funisitis with prognostic potential.
Cholesterol: The Good, the Bad, and the Ugly - Therapeutic Targets for the Treatment of Dyslipidemia
Authors: Elshourbagy Nabil A. , Meyers Harold V. , Abdel-Meguid Sherin S.
Published: April 2017

Maintaining cholesterol and triglyceride (TG) levels within healthy limits is critical for decreasing the risk of heart disease. Dyslipidemia refers to the abnormal levels of lipids in the blood, including low high-density lipoprotein cholesterol (HDL-C), also known as good cholesterol, high low-density lipoprotein cholesterol (LDL-C), also known as bad cholesterol, and/or high TG levels that contribute to the development and progression of atherosclerosis. In this article we reviewed some of the current therapeutic targets for the treatment of dyslipidemia, with a primary focus on endothelial lipase and lecithin cholesterol acyl transferase for raising HDL-C, and the proprotein convertase subtilisin-like kexin type 9 (PCSK9), microsomal triglyceride transfer protein, and the messenger RNA of apolipoprotein B for lowering LDL-C. In addition, we reviewed the role of apolipoprotein AI (apoAI) in raising HDL-C, where we discuss three apoAI-based drugs under development. These are its mutated dimer (apoAI-Milano), a complex with phospholipids, and a mimetic peptide. Atherosclerosis, mainly because of dyslipidemia, is a leading cause of cardiovascular disease. Regarding the title of this article, the ‘good' refers to HDL-C, the ‘bad' refers to LDL-C, and the ‘ugly' refers to atherosclerosis.
Orbital Cellulitis Presenting as a First Sign of Incomplete Kawasaki Disease
Authors: Çerman Eren , Eraslan Muhsin , Turhan Semra Akkaya , Usta Sinem Altınyuva , Akalın Figen
Published: April 2017

A 6-year-old boy was referred to our hospital with orbital cellulitis. He had a history of 7 days of fever despite antibiotherapy. At first, he only had pharyngitis and conjunctivitis, but then an orbital mass evolved which restricted the movement of his right eye and there was also periorbital inflammation resembling orbital cellulitis. Examination at presentation revealed conjunctivitis with secretion, periocular inflammation and edema, right-preauricular lymphadenopathy and restriction of upgaze in the right eye. Laboratory findings included a white blood cell count of 19,000 cells per mm3, with 81.5% neutrophils, 15.0% lymphocytes, 1.2% monocytes and 0.4% basophils. The erythrocyte sedimentation rate was 52 mm/h and the C-reactive protein level was 46.3 mg/dl. Magnetic resonance imaging confirmed orbital cellulitis and pansinusitis. Vancomycin (60 mg/kg/day) and meropenem (100 mg/kg/day) were administered, but desquamation on his fingertips and a rash appeared on the tenth day. A pediatric consultation resulted in a diagnosis of incomplete Kawasaki disease (KD). After administration of aspirin, the orbital inflammation regressed in 3 days. No coronary artery lesions were detected on the first echocardiography, but these did appear 6 weeks later. This confirmed the KD diagnosis.
Timely Diagnosis of Malalignment of the Distal Extremities Is Crucial in Morbidly Obese Juveniles
Authors: Landauer Franz , Huber Gerda , Paulmichl Katharina , O'Malley Grace , Mangge Harald , Weghuber Daniel
Published: April 2017

Background/Aims: To determine i) whether obesity in childhood can be related to malalignment of the distal extremities, ii) the proportion of genu valgum malalignment and abduction setting, and iii) the respective deviation dominance in children who are morbidly obese. Methods: 31 morbidly obese Caucasian children (16 males) recruited for the STYJOBS Study (ClinicalTrials.gov Identifier NCT00482924) with a mean age of 13.9 ± 0.5 years, a mean height of 162.3 ± 2.7 cm, a mean weight of 90.62 ± 5.0 kg, and a mean BMI of 33.8 ± 1.2 kg/m2 were clinically examined using the Mikulicz line in order to assess load distribution on the knee joint. 21 participants received a whole-leg X-ray because of a clinically estimated malalignment. Results: 8/31 participants examined were diagnosed with genu valgum, 1/31 with genu varum, and 22/31 did not have any malalignment of the femur or tibia. The majority of genu valgum presentation was due to femoral deviation. Of those without malalignment, 4/22 participants had an abduction setting, while 2/22 showed an adduction of the leg. Conclusion: Genu valgum as a predominant malalignment of the distal extremities is frequent in youth with morbid obesity. Timely guided correction of angular deformity of the knee seems pivotal in order to avoid osteotomy or osteoarthritis later in life.
Idiopathic Granulomatous Lobular Mastitis - Report of 43 Cases from Iran; Introducing a Preliminary Clinical Practice Guideline
Authors: Omranipour Ramesh , Mohammadi S-Farzad , Samimi Parisa
Published: April 2017

Background: We aimed to report a large series of idiopathic granulomatous lobular mastitis (IGLM) from Iran and sketch preliminary clinical practice guidelines (CPG) for approaching an inflammatory breast mass. Patients and Methods: In a retrospective records review, 43 consecutive IGLM cases were studied. Data on baseline, clinical, imaging, and pathologic characteristics were collected. Results: The mean age of the women was 33.5 years. All but 1 were married and had given birth. 16% had a cancer-like presentation. Inflammatory signs, architectural distortion, and a nodular pattern were the most common findings clinically, mammographically and ultrasonographically, respectively. 29.5% of the pathological reports indicated necrosis which was more common in younger subjects (p = 0.016); microabscesses were associated with a shorter lactation course (p = 0.006). Corticosteroids had been used as the initial treatment modality in 51%, immunosuppressive agents had not been administered, and a 16% relapse rate was recorded. We recognized the need for a multidisciplinary approach covering radiology, oncology, and surgery to best handle diagnostic and therapeutic issues and manage relevant infections as well as the major differential diagnosis, i.e. malignancy. Conclusion: We hypothesized that a shorter lactation period may cause more milk stasis and extravasation and be contributory to IGLM. CPGs are needed to incorporate the needed multidisciplinary approach and to standardize IGLM care. We present one such guideline.
The Association between Blood-Cerebrospinal Fluid Barrier Dysfunction and the Therapeutic Effect in Tuberculous Meningitis Patients
Authors: Tang Jiangtao , An Yunfei , Liao Yun , Li Yi , Li Lixin , Wang Lanlan
Published: April 2017

Objective: To explore the correlation of blood-cerebrospinal fluid (CSF) barrier (BCB) dysfunction with the therapeutic effect of antitubercular agents and their resistance, hoping to provide theoretical evidence for improvement of the therapeutic effect. Methods: Albumin in CSF and serum was assayed by IMMAGE. The CSF/serum albumin ratio (QALB) was used to evaluate the permeability of the BCB. Real-time fluorescence quantitative PCR was used to detect the amount of Mycobacterium tuberculosis DNA, and an MTBDRplus reagent kit was used to determine the type of drug resistance of the M. tuberculosis.Results: The correlation analysis showed that significant correlation existed between the grade of severity of tuberculous meningitis and the QALB, and the grade of severity and the total leukocyte count in the CSF, for which the correlation coefficients were 0.366 (p < 0.05) and 0.365 (p < 0.05), respectively. The QALB in the group of patients who recovered was significantly higher than that in those patients who experienced disease progression (p = 0.019). Conclusions: Our study showed that the permeability of the BCB correlated with the cure rate in tuberculous meningitis. Specifically, in the treatment of tuberculous meningitis, it is of key importance to utilize the benefit of the permeability of the BCB to achieve a better outcome.
Coming of Age in the Geospatial Revolution: The Geographic Self Re-Defined
Authors: Downs Roger M.
Published: April 2017

Intellectually, emotionally, and practically, our relationship to the geographic world has been changed by the geospatial revolution. Through technologies for data acquisition, analysis, and representation, we have access to real-time data about the locations and properties of people and places. Our sense of the world - what we know about it, how we see ourselves in relation to it, and how we behave spatially - is being irrevocably transformed. The impacts are experienced differentially as a function of birth year. Cohorts born in the last two decades are growing up immersed in geospatial information. The experiences of these cohorts, Generation M, are qualitatively different from those of preceding cohorts. From a life-span developmental perspective, what does it mean to grow up in a world in which we can always know our location and in which others can also know that location?
Reuse of Internal Pulse Generator in Cases of Infection after Deep Brain Stimulation Surgery
Authors: Gocmen Selcuk , Celiker Ozkan , Topcu Abdullah , Panteli Aikaterini , Acar Goksemin , Acar Feridun
Published: April 2017

Background: Hardware-related infection after deep brain stimulation (DBS) is one of the most serious complications and may need additional interventions. Objectives: To reuse the internal pulse generator (IPG) after DBS infection and to reduce the economic costs. Methods: A database of 102 patients who underwent DBS surgery was used in the study. The incidence, clinical characteristics and management of infections while reusing the IPG after DBS-related infection were analyzed and reported. Results: The overall infection rate was 5.9% (6 of 102 patients). Management consisted of total hardware removal followed by intravenous antibiotics. The IPG was at first kept in a solution, then rinsed with water and dried following sterilization with ethylene oxide gas at 38°C for 18 h. When the treatment of the infection was finished, we reused the IPG and reimplanted the DBS. No hardware-related infection or other complications were observed after reimplantation. Conclusions: Management of hardware-related infections can be challenging. The medical and economic costs associated with these infections are enormous. The IPG can often be saved in infected patients. Thus, a significant cost burden is eliminated. Properly executed, reuse of IPG should markedly reduce the costs of these devices.
Human Herpesvirus 6 Encephalitis Simulating Brain Metastases in a Patient with Advanced Small-Cell Lung Cancer
Authors: Mordenti Patrizia , Zaffignani Elena , Immovilli Paolo , Nobili Elisabetta , Cavanna Luigi
Published: April 2017

Background: The brain is a frequent site of metastases in small-cell lung cancer. Symptoms of cerebral involvement are headache, disorientation, nausea/vomiting and seizures. Case: A man with small-cell lung cancer developed a human herpesvirus 6 (HHV-6) meningoencephalitis with neurological symptoms that simulated brain involvement from the lung cancer. HHV-6 is a T cell lymphotropic virus which may be pathogenic in the immunocompromised host. HHV-6 remains latent after the first infection, and when the immune system is compromised it can reactivate. The treatment of HHV-6 infection is highly specific and the drugs recommended are the two antivirals, ganciclovir or foscarnet. Conclusion: In cancer patients neurologic symptoms are usually due to brain metastases. This case shows that in a cancer patient any aspecific neurologic symptom should be carefully evaluated in order to exclude a non-oncologic cause. This statement is particularly true if the therapies for the oncological and neurological diseases are effective.
Comparison of Myocardial Perfusion during Hemodialysis and Hemodiafiltration
Authors: De Andrade Roger , Kotze Tessa , Lesosky Maia , Swanepoel Charles
Published: April 2017

Background: We compared myocardial perfusion in patients first on conventional hemodialysis (HD) and then on hemodiafiltration (HDF). Methods: Myocardial perfusion scintigraphy was performed in 25 patients pre- and post-HD. Patients were then converted to HDF for 3 months prior to repeating the scintigraphy. 99mTc-methoxyisobutylisonitrile was administered intravenously pre-dialysis and then within the last hour of dialysis. Up to 90 min after injection, tomographic images were obtained. Clinical and laboratory data were collected pre- and post-dialysis. Results: Five patients did not complete the study. Patients entering the study were on average 41.7 years old and on HD for 4 years (median). The mean standard Kt/V for the two procedures was not statistically different (1.55 for HD and 1.48 for HDF). The mean substitution volume for HDF was 18.48 liters. There were no significant differences in changes in blood pressures between HD and HDF (p = 0.22). There were no significant differences in myocardial perfusion defects in patients on HD compared with those on HDF. During dialysis in both studies, the data showed a general trend to worsening of perfusion defects. Conclusions: There was no advantage of HDF over HD with no statistical difference in perfusion defects between HD and HDF. There was a trend to worsening of perfusion defects during dialysis in the majority on HD and HDF. Midweek dialysis perfusion scores appeared to be consistently lower than early-week dialysis, but this was not statistically significant. The pathogenesis of the defects may lie at a microcirculatory level.
Impact of Identifying Factors Which Trigger Bothersome Tinnitus on the Treatment Outcome in Tinnitus Retraining Therapy
Authors: Molini Egisto , Faralli Mario , Calzolaro Lucia , Ricci Giampietro
Published: April 2017

The aim of this work was to ascertain any differences in the effectiveness of rehabilitation therapy in relation to the presence or absence of a known negative reinforcement responsible for the tinnitus-related pathology. Between 1 January 2001 and 31 December 2008, we recruited 294 subjects suffering from incapacitating tinnitus and/or hyperacusis. The patients underwent tinnitus retraining therapy (TRT) according to the methods described by Jastreboff and Hazell [Tinnitus Retraining Therapy: Implementing the Neurophysiological Model. Cambridge, Cambridge University Press, 2004, pp 121-133]. We clinically assessed the presence or absence of known phenomena of associative learning, regarding the presence of adverse events temporally correlated with tinnitus and the treatment outcome. The separate analysis of the 2 subgroups shows a statistically significant difference in the improvement rate between the group with a known triggering factor and the group without a triggering factor, with a preponderance of the former with a 91% improvement rate versus approximately 56% for the latter. In our study, the inability to identify factors triggering bothersome tinnitus negatively affected the treatment outcome in TRT.
High Prevalence of Cross-Resistance to Aminoglycosides in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates
Authors: Tsukamoto Naoyuki , Ohkoshi Yasuo , Okubo Torahiko , Sato Toyotaka , Kuwahara Osamu , Fujii Nobuhiro , Tamura Yutaka , Yokota Shin-ichi
Published: April 2017

Background: Multidrug-resistant Escherichia coli, especially a lineage of O25b:H4-ST131, has increased and spread worldwide. The surveillance of cross-resistance of E. coli is necessary. Methods: Cross-resistance to fluoroquinolones (FQs) and aminoglycosides (AGs) was examined in E. coli isolated in Hokkaido Prefecture, Japan, between 2008 and 2009. Results: Gentamicin (GEN) resistance was more common in FQ-resistant isolates (30/112 strains; 26.8%) than in FQ-susceptible isolates (2/100 strains; 2%). The frequency of GEN resistance was similar in two groups of FQ-resistant strains, O25b:H4-ST131 genotype (22/87 strains; 25.3%) and a group of other FQ-resistant genotypes (8/25 strains; 32.0%). The main AG resistance gene was aac(3)-II (87.5% of GEN-resistant strains). The only amikacin-resistant strain which was FQ resistant carried the aac(6')-Ib-cr gene. CTX-M type extended-spectrum β-lactamase (ESBL) genes were also found in FQ-resistant strains at a high frequency. However, the number of strains with both ESBL and AG-modifying enzyme genes was relatively low (8 strains). Conclusion: All FQ-resistant strains, not only O25b:H4-ST131, appeared to preferentially acquire ESBL genes and/or genes encoding AG-modifying enzymes; however, the acquisitions of these genes seemed to occur independently.
Egr-1 Mediates Chronic Hypoxia-Induced Renal Interstitial Fibrosis via the PKC/ERK Pathway
Authors: Sun Shiren , Ning Xiaoxuan , Zhai Ying , Du Rui , Lu Yuanyuan , He Lijie , Li Rong , Wu Weini , Sun Wenjuan , Wang Hanmin
Published: April 2017

Background: Chronic hypoxia-induced epithelial-to-mesenchymal transition (EMT) is a crucial process in renal fibrogenesis. Egr-1, as a transcription factor, has been proven to be important in promoting EMT. However, whether it functions in hypoxia-induced renal tubular EMT has not been fully elucidated. Methods: Egr-1 were detected at mRNA and protein levels by qPCR and Western blot analysis respectively after renal epithelial cells were subjected to hypoxia treatment. Meanwhile, EMT phenotype was also observed through identification of relevant EMT-specific markers. siRNA was used to knock down Egr-1 expression and subsequent changes were observed. Specific PKC and MAPK/ERK inhibitors were employed to determine the molecular signaling pathway involved in Egr-1-mediated EMT phenotype. In vivo assays using rat remnant kidney model were used to validate the in vitro results. Furthermore, Egr-1 expression was examined in the samples of CKD patients with the clinical relevance revealed. Results: Hypoxia treatment enhanced the mRNA and protein levels of Egr-1 in HK-2 cells, which was accompanied by a reduced expression of the epithelial marker E-cadherin and an enhanced expression of the mesenchymal marker Fsp-1. Downregulation of Egr-1 with siRNA reversed hypoxia-induced EMT. Using the specific inhibitors to protein kinase C (calphostin C) or MAPK/ERK (PD98059), we identified that hypoxia induced Egr-1 expression through the PKC/ERK pathway. In addition, the upregulation of Egr-1 raised endogenous Snail levels, and the downregulation of Snail inhibited Egr-1-mediated EMT in HK-2 cells. Through in vivo assays using rat remnant kidney and CKD patients' kidney tissues, we found that Egr-1 and Snail were overexpressed in tubular epithelial cells with EMT. Conclusion: Egr-1 may be an important regulator of the development of renal tubular EMT induced by hypoxia through the PKC/ERK pathway and the activation of Snail. Targeting Egr-1 expression or activity might be a novel therapeutic strategy to control renal fibrosis.
Lymphocyte Levels of Redox-Sensitive Transcription Factors and Antioxidative Enzymes as Indicators of Pro-Oxidative State in Depressive Patients
Authors: Lukic Iva , Mitic Milos , Djordjevic Jelena , Tatalovic Nikola , Bozovic Natalija , Soldatovic Ivan , Mihaljevic Marina , Pavlovic Zorana , Radojcic Marija B. , Maric Nadja P. , Adzic Miroslav
Published: April 2017

Background: Oxidative stress is reliably observed in major depressive disorder (MDD). However, molecular data on the principal cellular redox-sensitive transcriptional factors and the levels of their downstream-regulated antioxidant enzymes in MDD are scarce. Methods: In the peripheral blood mononuclear cells (PBMC) of subjects with a current episode of MDD (n = 30) and healthy controls (n = 35), we investigated alterations in the levels of redox-sensing nuclear factor (erythroid-derived 2)-like 2 (Nrf2) protein, its inhibitor Keap1, and nuclear factor-κB (NF-κB), along with their cognate downstream effectors, the antioxidant enzymes (AOEs): manganese and copper zinc superoxide dismutase (MnSOD and CuZnSOD, respectively), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GLR). Results: MDD subjects exhibited higher levels of Nrf2 and its regulator Keap1, as well as NF-κB in the cytoplasm of PBMC compared to controls. This state was further reflected by increased levels of MnSOD, CuZnSOD and CAT proteins and by the lack of correlation between MnSOD and CAT, which could indicate impaired oxidative detoxification capacity in MDD patients. Moreover, increased levels of MnSOD, CuZnSOD and CAT in MDD patients positively correlated with levels of Nrf2, while increased levels of SODs were also positively related to NF-κB. There were no differences regarding the levels of GPx and GLR proteins, but the ratio of GLR/GPx was reduced, suggesting diminished capacity of GPx in antioxidative defence in PBMC of MDD subjects. Conclusion: These data provide evidence that MDD is characterized by up-regulation of redox-sensitive transcriptional factors (Nrf2 and NF-κB) and AOEs (MnSOD, CuZnSOD and CAT), indicating pro-oxidative state in the PBMC of MDD patients.
Accuracy of Scheimpflug Holladay Equivalent Keratometry Readings after Corneal Refractive Surgery in the Absence of Clinical History
Authors: Bialer Omer Y. , Kaiserman Igor , Bahar Irit
Published: April 2017

Background and Objective: To identify the most accurate combination of Pentacam's equivalent keratometry readings (EKR) and intraocular lens power formula when the clinical history is unavailable. Patients and Methods: A total of 18 patients underwent cataract surgery after refractive surgery. The Pentacam 4.5- and 3.0-mm EKR were combined with the SRK II, SRK/T, Hoffer-Q, and Holladay I and II formulas. Results: The smallest deviation from the predicted value was achieved by combining the 4.5 EKR with the Holladay II formula (mean arithmetic deviation, -0.2 ± 0.4 dpt). Conclusion: The 4.5-mm EKR + Holladay II formula can accurately calculate intraocular lens power in patients with previous refractive surgery.
Role of Riboflavin- and UV Light-Treated Plasma in Prevention of Transfusion-Related Acute Lung Injury
Authors: Jimenez-Marco Teresa , Ruiz-Alderton Daniel , Bautista-Gili Antonia M. , Girona-Llobera Enrique
Published: April 2017

Introduction: Risk reduction strategies for transfusion-related acute lung injury (TRALI) include the preferential use of male donors to provide fresh frozen plasma (FFP). Implementing this measure based on FFP quarantine program is a very complex process. To improve FFP inventory management and the availability of FFP from male donors, the Mirasol Pathogen Reduction Technology® (PRT) system for FFP using riboflavin and UV light was adopted in our region in 2012. Methods: The percentage of male/female FFP units issued and TRALI cases in patients receiving FFP in the period before implementing riboflavin and UV light (2010-2011) was compared with the period post implementation of riboflavin and UV light (2012-2013). Results: In 2010 and 2011, there was one FFP transfusion-related TRALI case reported per year, when the proportion of male/female FFP distributed to the hospitals was 60/40. During 2012 and 2013, there have been no FFP transfusion-related TRALI cases, when the proportion of male/female FFP distributed to the hospitals was around 97/3. Mirasol PRT allows quick availability (24 h from collection) compared to quarantined FFP (≥3 months from collection). Conclusion: Thanks to its readiness, simplicity and feasibility, riboflavin- and UV light-treated FFP implementation can facilitate the preferential use of FFP from male donors as a TRALI prevention strategy.
Dermoscopy Findings of Hidroacanthoma Simplex
Authors: Sato Yota , Fujimura Taku , Tamabuchi Erika , Haga Takahiro , Aiba Setsuya
Published: April 2017

Hidroacanthoma simplex (HAS), also known as intraepidermal eccrine poroma, is a rare eccrine adnexal tumor that tends to be misdiagnosed as other types of benign skin tumor, including clonal seborrheic keratosis. Notably, HAS is sometimes misdiagnosed and treated by cryosurgery as seborrheic keratosis, which could trigger the later development of porocarcinoma. Therefore, accurate diagnosis of HAS is indispensable for dermatologists to avoid the development of malignant tumors by an unsuitable treatment. In this report, we present the characteristic dermoscopy findings of HAS. Indeed, the dermoscopy findings might be related to the melanin-rich necrotic cells in the epidermis, which are quite different from dermoscopy findings of clonal seborrheic keratosis. As a previous report suggested, it is difficult for a dermatologist to differentiate HAS from clonal seborrheic keratosis by the naked eye. Our findings might be supportive for the early diagnosis of HAS.
Effectiveness of Text versus Pictorial Health Warning Labels and Predictors of Support for Plain Packaging of Tobacco Products within the European Union
Authors: Agaku Israel T. , Filippidis Filippos T. , Vardavas Constantine I.
Published: April 2017

Background: Tobacco product warning labels are a key health communication medium with plain packaging noted as the next step in the evolution of tobacco packaging. We assessed the self-reported impact of text versus pictorial health warnings and the determinants of support for plain packaging of tobacco products in the European Union (EU). Methods: The Special Eurobarometer 385 survey was analyzed for 26,566 adults from 27 EU countries in 2012. The self-reported impact of warning labels (text or pictorial) and determinants of EU-wide support for plain packaging were assessed using multivariate logistic regression. Results: Current smokers in countries where cigarette pictorial warnings were implemented had higher odds of reporting that health warning labels had any effect on their smoking behavior (making a quit attempt or reducing number of cigarettes smoked per day) compared to respondents in countries with text-only warning labels (adjusted odds ratio, aOR = 1.31; 95% confidence interval, 95% CI: 1.10-1.56). Population support for plain packaging of tobacco packs was higher in countries where cigarette pictorial warnings already existed (aOR = 1.17; 95% CI: 1.07-1.28). Conclusions: These findings indicate that the implementation of pictorial warnings at an EU level may have a positive behavioral impact among smokers and pave the way for population support for plain packaging in the EU.
Heparin Use in Hemodialysis Patients following Gastrointestinal Bleeding
Authors: Shen Jenny I. , Mitani Aya A. , Winkelmayer Wolfgang C.
Published: April 2017

Background: Heparin is commonly given during hemodialysis (HD). Patients undergoing HD have a high rate of gastrointestinal bleeding (GIB). It is unclear whether or when it is safe to give heparin after acute GIB. We describe the patterns and safety of heparin use with outpatient HD following an acute GIB. Methods: We identified patients aged ≥67 who, from 2004-2008, experienced GIB requiring hospitalization within 2 days of receiving maintenance HD with heparin. We used Cox regression to estimate the risk of recurrent GIB and death associated with receiving heparin the day they resumed outpatient HD post-GIB. Results: Of the 1,342 patients who had GIB, 1,158 (86%) received heparin at a median dose of 4,000 units with their first outpatient HD session after discharge from GIB. On average, their post-GIB doses were slightly lower than their pre-GIB doses (mean change: -214 ± 3,266 units, p < 0.02). However, only 27% of patients had a decrease in their dose, while 21% had their dose increased. We did not find an increased risk of death or recurrent GIB associated with using heparin post-GIB (HR; 95% confidence interval (CI), for death: 1.01; 0.69-1.48; for recurrent GIB: 0.78; 0.39-1.57). Conclusions: The vast majority of these high-risk patients received heparin on the very first day they resumed outpatient HD post-GIB, and the majority at unchanged doses to those received pre-GIB. Even if the practice was not associated with increased risks of death or re-bleeding, it highlights an area for possible system-based improvement to the care for patients on HD.
Sleep Duration and Chronic Kidney Disease: Analysis of the National Health Interview Survey
Authors: Salifu Idoko , Tedla Fasika , Pandey Abhishek , Ayoub Isabelle , Brown Clinton , McFarlane Samy I. , Jean-Louis Girardin
Published: April 2017

Background: Patients with chronic kidney disease (CKD) have a high prevalence of sleep disorders. The association between sleep duration and self-reported CKD was examined in a population of Americans who participated in a national survey over a 3-year period. Study Design: A cross-sectional study using survey data from the National Health Interview Survey (NHIS) from the year 2004-2006 was carried out. A retrospective examination of data from a community-based survey of 128,486 noninstitutionalized US civilian residents over the age of 18 years was conducted. Self-reported CKD was defined as having ‘weak or failing kidneys'. The sleep duration was defined by a self-reported estimate of habitual sleep duration. Results: The prevalence of participants self-reporting kidney disease was higher in those with short (≤6 h per night) and long (≥8 h per night) sleep durations when compared to those sleeping 7 h per night. Self-reported information about sleep, demographic information, and information on comorbidities were assessed using standardized validated questionnaires which reported no kidney disease. A multivariate logistic regression analysis showed increased odds of self-reported kidney disease in study participants with both short and long sleep durations compared to healthy sleepers (sleeping >7-8 h per night). Observational data do not permit examination of causality, although possible confounders in observations of interest can be adjusted. Conclusion: Among Americans surveyed in the NHIS (2004-2006), those with short or long sleep duration had higher odds of reporting that they had CKD. i 2014 S. Karger AG, Basel
Anti-Tumor Necrosis Factor Therapy Inhibits Lung Metastasis in an Osteosarcoma Cell Line
Authors: Kato Hiroaki , Wakabayashi Hiroki , Naito Yohei , Kato Sho , Nakagawa Taro , Matsumine Akihiko , Sudo Akihiro
Published: April 2017

Background: Osteosarcoma is the most common primary malignancy of bone, and patients often develop pulmonary metastases. In a previous study, tumor necrosis factor (TNF)-α treatment of human osteosarcoma cells increases their metastatic ability in an animal model. TNF-α can act as a tumor necrosis factor and also as a tumor-promoting factor. In the present study, the effect of a TNF-α inhibitor on osteosarcoma aggressiveness and pulmonary metastases was investigated in vitro and in vivo. Methods: The effect of infliximab, a TNF-α inhibitor, on a metastatic osteosarcoma 143B cell growth and motility was investigated in vitro. An orthotopic xenograft model of 143B cell growth and spontaneous metastasis in SCID mice was used to assess the in vivo effect of infliximab. Results: Infliximab greatly reduced cell motility and pulmonary metastases in 143B cells. The mechanism of pulmonary metastasis inhibition involved decreased expression of CXC chemokine receptor 4 (CXCR4), Rho (small GTPase protein), and its effector. Conclusions: These results suggest a novel role for TNF-α inhibition in the reduction or prevention of pulmonary metastases of osteosarcoma in this animal model. TNF-α inhibition may become a preventive therapeutic option for the pulmonary metastases of osteosarcoma. © 2014 S. Karger AG, Basel
Treatment of Hypertension: Favourable Effect of the Twice-Daily Compared to the Once-Daily (Evening) Administration of Perindopril and Losartan
Authors: Szauder Ipoly , Csajági Eszter , Major Zsuzsanna , Pavlik Gabor , Ujhelyi Gabriella
Published: April 2017

Background/Aims: Little is known about the effect of twice daily administration of same dose of ACE inhibitor and ARB on the diurnal/nocturnal blood pressure (BP) ratio. We aimed to assess the effect of two widely used long-acting drugs: perindopril and losartan in the treatment of hypertension comparing the once-daily (evening) vs. twice-daily (morning and evening) administration with the same daily doses. Methods: Untreated primary hypertensive patients without complaints (a total of 164: 65 men, 99 women, 55.7±13.7 years of age, 41-41 patients per treated groups) were selected with non-dipper phenomenon, estimated by diurnal index (DI) <10%. The effect of evening (8 mg perindopril or 100 mg losartan) vs morning and evening (4-4 mg perindopril or 50-50 mg losartan) administration was determined on a 14-day treatment by ABPM. Results: The mean BP, the percent time elevation index, and the hyperbaric impact decreased in both drug groups. Significant difference was observed in the DI in the case of twice-daily administration vs once-daily evening dosing. Conclusions: The twice-daily administration with the same daily dose of perindopril or losartan seems to be more effective compared to the once daily evening administration in eliminating the non-dipper phenomenon. According to some authors the non-dipping phenomenon increases cardiovascular risk, while others are of the opinion that the association of non-dipping with cardiovascular events does not necessarily mean that selective treatment of non-dipping improves cardiovascular outcomes.
Progress in New Diagnosis and Therapeutic Strategy for Gastrointestinal Malignancy: Focus on New Molecular-Targeted Treatments
Authors: Sugiyama Toshiro
Published: April 2017

The core symposiums of the Japanese Gastroenterological Association (JGA) annual scientific meetings focus on similar topics from year to year. The main topics of these symposiums for the last 3 years were centered on progress in new diagnostics and therapeutic strategies for gastrointestinal malignancy, with a special focus on new molecular-targeted treatments for gastrointestinal stromal tumors (GIST), neuroendocrine tumors (NET) and other gastrointestinal (GI) cancers, including malignant lymphoma, for which new molecular-targeted treatments are now being commonly used. The 8th annual meeting of the JGA was held in 2012 and 8 excellent papers were presented on progress in new diagnostics and therapy for GIST. The 9th annual meeting of the JGA was held in 2013 and 7 excellent papers were presented on new molecular-targeted treatments for colorectal carcinomas and GI lymphoma. At the 10th annual meeting of the JGA, which was held in 2014, novel concepts of and therapeutic strategies for GI cancers, NET and GIST were discussed. In 2010, the WHO proposed a new classification system in which NET was classified into three categories - NET-G1, NET-G2 and NEC - dependent on proliferative activity, and the term ‘carcinoid' was deleted. Regarding GIST, several management guidelines have already been published: by NCCN in 2004, by ESMO in 2005, and in Japan in 2006. The Japanese guidelines have recently been revised. In addition to the summaries of the annual meetings from 2012 to 2014, the major points of the recently revised Japanese guidelines for the diagnosis and management of GIST are described in this review.
Acupuncture Point Laterality: Evidence and Perspective
Authors: Wang Guangjun , Litscher Daniela , Tian Yuying , Gaischek Ingrid , Jia Shuyong , Wang Lu , Zhang Weibo , Litscher Gerhard
Published: April 2017

Background: In the Yellow Emperor Neijing, it is stated that ‘if someone has a disease related with the left side, the treatment point is on the right side, and vice versa' [Unschuld PU: Huang Di Nei Jing Su Wen, 2003], which emphasizes that specific lateral-side acupoint stimulation might lead to therapeutic advantages under specific conditions. Methods: We summarize the different effects resulting from namesake acupoint stimulation referred to as acupoint laterality. In this short review, the evidence of acupoint lateralization from Neiguan (PC6), Hegu (LI4), and Quchi (LI11) is discussed. Results and Conclusion: Investigations indicate that acupuncture at the contralateral side of PC6 has different effects on heart rate variability (HRV), which means that PC6 has laterality. However, such a difference in HRV could not be observed when the same stimulation was applied to both sides of LI4, although the difference in blood perfusion distribution was confirmed exactly. Considering the results from PC6, we hypothesize that acupoint laterality might be related to acupoint specificity. Although the evidence is not clear, our results indicate that in patients with hypertension, different-side LI11 stimulation can also produce different results, which might indicate that acupoint laterality is associated with the functional state of subjects. The perspective of acupoint lateralization is also preliminarily discussed in this review. i 2014 S. Karger AG, Basel