bluuebunny/crossref_metadata_2025 huggingface dataset:
Stress Determined through Heart Rate Variability Predicts Immune Function
Authors: Luo Hong , Wei Jing , Yasin Yousef , Wu Si Jia , Barszczyk Andrew , Feng Zhong-Ping , Lee Kang
Published: September 2019

Background: Stress is a prevalent health problem in modern society. If experienced for long periods of time it can lead to immune dysfunctions. Thus, public health management practices must include the assessment of stress. In health management settings, electrocardiography (ECG) is routinely used to assess cardiovascular health and make inferences about stress using information from heart rate variability (HRV). However, it is unclear whether stress assessment based on HRV can also be used to index immune function. Objectives: To compare stress that was determined by a measure of HRV (pNN50) from ECG with immune function indices (neutrophil, monocyte, and lymphocyte percentages) obtained from blood samples. Methods: A total of 184 healthy adults participated in the study, which took place in an examination room at the Health Management Center of The Affiliated Hospital of Hangzhou Normal University, China. Participants viewed a relaxing video while having a 2-min ECG recorded. They were then taken to have their blood drawn as part of their physical examination. Measures of stress (pNN50) were extracted from ECG, while measures of immune function (percentages of neutrophils, monocytes, and lymphocytes) were extracted from blood samples. Results: Stress correlated positively with neutrophil percentages (r = 0.21) and negatively with monocyte (r = –0.16) and lymphocyte percentages (r = –0.18). Conclusions: These findings show HRV analysis to be a potentially viable noninvasive and inexpensive method not only for indexing stress, but also predicting immune function, thus managing the health risks associated with stress.
Dual-Imaging Modality Approach to Evaluate Cerebral Hemodynamics in Growth-Restricted Fetuses: Oxygenation and Perfusion
Authors: Yadav Brijesh Kumar , Hernandez-Andrade Edgar , Krishnamurthy Uday , Buch Sagar , Jella Pavan , Trifan Anabela , Yeo Lami , Hassan Sonia S. , Haacke Ewart Mark , Romero Roberto , Neelavalli Jaladhar
Published: September 2019

Objective: To evaluate a dual-imaging modality approach to obtain a combined estimation of venous blood oxygenation (SνO2) using susceptibility-weighted magnetic resonance imaging (SWI-MRI), and blood perfusion using power Dopp­ler ultrasound (PDU) and fractional moving blood volume (FMBV) in the brain of normal growth and growth-restricted fetuses. Methods: Normal growth (n = 33) and growth-restricted fetuses (n = 10) from singleton pregnancies between 20 and 40 weeks of gestation were evaluated. MRI was performed and SνO2 was calculated using SWI-MRI data obtained in the straight section of the superior sagittal sinus. Blood perfusion was estimated using PDU and FMBV from the frontal lobe in a mid-sagittal plane of the fetal brain. The association between fetal brain SνO2 and FMBV, and the distribution of SνO2 and FMBV values across gestation were calculated for both groups. Results: In growth-restricted fetuses, the brain SνO2 values were similar, and the FMBV values were higher across gestation as compared to normal growth fetuses. There was a significantly positive association between SνO2 and FMBV values (slope = 0.38 ± 0.12; r = 0.7; p = 0.02) in growth-restricted fetuses. In normal growth fetuses, SνO2 showed a mild decreasing trend (slope = –0.7 ± 0.4; p = 0.1), whereas FMBV showed a mild increasing trend (slope = 0.2 ± 0.2; p = 0.2) with advancing gestation, and a mild but significant negative association (slope = –0.78 ± 0.3; r = –0.4; p = 0.04) between these two estimates. Conclusion: Combined MRI (SWI) and ultrasound (FMBV) techniques showed a significant association between cerebral blood oxygenation and blood perfusion in normal growth and growth-restricted fetuses. This dual-imaging approach could contribute to the early detection of fetal “brain sparing” and brain oxygen saturation changes in high-risk pregnancies.
Investing in Happiness: The Gerontological Perspective
Authors: Steptoe Andrew
Published: September 2019

Optimising happiness is a desirable societal aim in itself, but there are four more specific reasons why research on happiness is an important emerging theme in gerontology. First, happiness is not merely the mirror of depression, anxiety or distress, but has distinct relationships with a range of outcomes, so benefits from study in itself. Second, happiness appears to be a protective factor for morbidity and mortality; although studies are complex and take a long time to complete, there is accumulating evidence that greater happiness predicts survival among older people independently of covariates including health status and depression. Third, happiness has broad ramifications at older ages, being related to personal and social relationships, economic prosperity, biological risk factors, health behaviours, and time use as well as health. Fourth, happiness is malleable, and can potentially be modified in ways that will enhance the health and well-being of older people.
Association of Myoinositol Transporters with Schizophrenia and Bipolar Disorder: Evidence from Human and Animal Studies
Authors: Vawter Marquis P. , Hamzeh Abdul Rezzak , Muradyan Edgar , Civelli Olivier , Abbott Geoffrey W. , Alachkar Amal
Published: September 2019

Evidence from animal and human studies has linked myo-inositol (MI) with the pathophysiology and/or treatment of psychiatric disorders such as schizophrenia and bipolar disorder. However, there is still controversy surrounding the definitive role of MI in these disorders. Given that brain MI is differentially regulated by three transporters – SMIT1, SMIT2 and/or HMIT (encoded by the genes: SLC5A3, SLC5A11,and SLC2A13, respectively) – we used available datasets to describe the distribution in mouse and human brain of the different MI transporters and to examine changes in mRNA expression of these transporters in patients with schizophrenia and bipolar disorder. We found a differential distribution of the mRNA of each of the three MI transporters in both human and mouse brain regions. Interestingly, while individual neurons express SMIT1 and HMIT, non-neuronal cells express SMIT2, thus partially accounting for different uptake levels of MI and concordance to downstream second messenger signaling pathways. We also found that the expression of MI transporters is significantly changed in schizophrenia and bipolar disorder in a diagnostic-, brain region- and subtype-specific manner. We then examined the effects of germline deletion in mice of Slc5a3 on behavioral phenotypes related to schizophrenia and bipolar disorder. This gene deletion produces behavioral deficits that mirror some specific symptoms of schizophrenia and bipolar disorder. Finally, chronic administration of MI was able to reverse particular, but not all, behavioral deficits in Slc5a3 knockout mice; MI itself induced some behavioral deficits. Our data support a strong correlation between the expression of MI transporters and schizophrenia and bipolar disorder, and suggest that brain region-specific aberration of one or more of these transporters determines the partial behavioral phenotypes and/or symptomatic pattern of these disorders.
Psychometric Characteristics of Cognitive Reserve: How High Education Might Improve Certain Cognitive Abilities in Aging
Authors: Rodriguez Francisca S. , Zheng Ling , Chui Helena C. ,   Aging Brain: Vasculature, Ischemia, and Behavior Study
Published: September 2019

Background: The capacity to mitigate dementia symptomology despite the prevailing brain pathology has been attributed to cognitive reserve. Objectives: This study aimed to investigate how psychometric performance differs between individuals with a high school versus college education (surrogate measures for medium and high cognitive reserves) given the same level of brain pathology assessed using quantitative structural MRI. Methods: We used data from the Aging Brain: Vasculature, Ischemia, and Behavior Study (ABVIB). Cognition was assessed using a neuropsychological battery that included those contained in the National Alzheimer’s Coordinating Center (NACC) uniform data set. Participants with a medium and high cognitive reserve were matched by level of structural MRI changes, gender, and age. Results: Matched-pair regression analyses indicated that individuals with a higher education had a significantly better performance in recognition and verbal fluency animals, working memory, and processing speed in complex tasks. Moreover, they had a better performance in interference trails compared to individuals with a high school education (medium cognitive reserve). Conclusions: Our findings suggest that, given the same level of brain pathology, individuals with a higher education (cognitive reserve) benefit from a superior performance in semantic memory and executive functioning. Differences in these cognitive domains may be key pathways explaining how individuals with a high cognitive reserve are able to diminish dementia symptomatology despite physical changes in the brain.
Regression of Periocular Basal Cell Carcinoma: A Report of Four Cases with Clinicopathologic Correlation
Authors: Herwig-Carl Martina C. , Loeffler Karin U.
Published: September 2019

Objectives: To describe the spectrum of clinical and histopathological features of a case series of basal cell carcinoma (BCC) with spontaneous regression and to discuss this phenomenon. Method: Four cases of BCC with complete/substantial regression were retrospectively identified. Patients’ records were analyzed for demographic data, clinical appearance, and the postoperative course. Formalin-fixed, paraffin-embedded specimens were routinely processed and stained with hematoxylin and eosin and periodic acid Schiff. Results: Complete (n = 1) or partial (n = 3) regression of BCC was observed in 4 patients. Two lesions at the medial canthus were histologically diagnosed as nodular BCC with significant regression. One lesion at the lower eyelid exhibited a complete regression which did not require surgical intervention. The other lesion at the lower eyelid presenting with ulceration and madarosis was excised. Scar tissue without evidence for a neoplasm was present histologically. Subsequently, the patient developed a recurrence with a histologically proven micronodular BCC. Conclusions: BCC can show spontaneous substantial or complete regression. Histological tumor absence in lesions which are clinically suspicious for a neoplasm can be a hint for a regressive BCC. Recurrences may develop from remaining tumor islands warranting periodical clinical visits in cases of clinically as well as histologically suspected regressive BCC.
An Exploration of the Rapid Automatic Naming Test as Administered to Brazilian Children
Authors: Ferreira-Mattar Tais de Lima , Roama-Alves Rauni Jandé , Araceli Gomes Fernanda , Freire Thais , Ciasca Sylvia Maria , de Abreu Pinheiro Crenitte Patrícia
Published: September 2019

Objective: The purpose of this research was to conduct an exploratory study of the performance of Brazilian children on the Rapid Automatic Naming (RAN) test, examining schooling effects of schooling and associations with reading speed, comprehension, and reading level for each of the RAN subtests of colour, numbers, letters, and objects. Methods: Participants were 97 children, aged 7–11 years, enrolled in the first to fifth grade of elementary public education. Results: The findings indicated a school-year effect on RAN performance, with recurrent differences in grades 1–4 and no effect in RAN Numbers. Correlations ranged from moderate to high for reading level, speed, and comprehension. In addition, multiple linear regression analysis indicated that RAN Letters could significantly predict performance in the three reading abilities studied. Conclusion: Thus, the study provided initial evidence of RAN’s performance in testing Brazilian children’s phonological processing as a form of predictive monitoring of reading development in school-age children as it relates to scholastic progress and reading speed, comprehension, and level.
Managing the Unusual Causes of Fetal Anemia
Authors: Maisonneuve Emeline , Ben M’Barek Imane , Leblanc Thierry , Da Costa Lydie , Friszer Stéphanie , Pernot Françoise , Thomas Pauline , Castaigne Vanina , Toly N’Dour Cécile , Mailloux Agnès , Cortey Anne , Jouannic Jean-Marie
Published: September 2019

Background: Rare causes of fetal anemia requiring intrauterine transfusion (IUT) are challenging for fetal medicine specialists. Objectives: The aim of this study was to describe the perinatal patterns and prognosis in a consecutive series of fetuses transfused for fetal anemia of rare or unknown etiology, and to propose a protocol of investigation for fetal anemia of undetermined cause and for the management of subsequent pregnancies. Method: We conducted a retrospective descriptive study on fetuses transfused for severe anemia of rare or unknown etiology managed in our national referral center (Centre National de Référence d’Hémobiologie Périnatale) and born between 2010 and 2017. Results: During the study period, 584 IUT were performed in 253 fetuses. Among those IUT, 23 (3.9%) were performed for a rare or unknown cause of anemia in 13 fetuses (5.1% of transfused fetuses). The median gestational age at diagnosis was 26 weeks of gestation (WG; range 21–33). Hemoglobin levels ranged from 1.6 to 9.1 g/dL (0.18–0.83 multiples of median) before the first IUT. The fetuses received between 1 and 6 IUT (39% received at least 2 IUT). The definitive etiologies for central anemia were: congenital syphilis, neonatal poikilocytosis, type II congenital dyserythropoietic anemia (CDA), and neonatal hemochromatosis. There was 1 case with suspected type I CDA and 1 with suspected Diamond-Blackfan anemia. There was 1 case of peripheral anemia, secondary to cerebral hemorrhages of different ages, related to a variant of the COL4A1 gene. In 6 fetuses corresponding to 4 mothers, no precise diagnosis was found despite a complete workup. In our series, there were 8 live births, 4 terminations of pregnancy, and 1 intrauterine fetal death. Conclusions: Fetal anemia of rare or unknown diagnosis represents 5% of all transfused fetuses in our cohort. Fetal and neonatal anemias can be recurrent in further pregnancies, with variable expressivity.
The Cricothyroid versus Spray-As-You-Go Method for Topical Anesthesia during Flexible Bronchoscopy: The CRISP Randomized Clinical Trial
Authors: Madan Karan , Mittal Saurabh , Gupta Nishkarsh , Biswal Shiba Kalyan , Tiwari Pawan , Hadda Vijay , Mohan Anant , Guleria Randeep
Published: September 2019

Background: Comparative characteristics of the cricothyroid injection and spray-as-you-go methods for lidocaine administration during diagnostic flexible bronchoscopy are not clear. Objectives: Co-primary outcomes were comparison of cough count from bronchoscope introduction until reaching carina and operator-rated overall procedure satisfaction on a Visual Analogue Scale (VAS) between groups. Secondary outcomes were cumulative lidocaine dose, procedure duration, assistant-rated cough, willingness to return for repeat procedure, and procedural complications between groups. Methods: Consecutive subjects were randomized (1:1) to either the cricothyroid or the spray-as-you-go method for topical anesthesia to the vocal cords and trachea. All received nasal 2% lidocaine gel and pharyngeal 10% lidocaine spray. Results: A total of 500 subjects were randomized, and 495 subjects were analyzed (248 cricothyroid and 247 spray-as-you-go). Cough count until reaching carina (median [range]) was significantly lower (cricothyroid, 1 [0–10], and spray-as-you-go, 4 [0–30], p < 0.0001) and operator-rated overall procedure satisfaction, VAS (mean ± standard deviation) (cricothyroid, 7.86 ± 1.39 and spray-as-you-go, 6.86 ± 1.59, p < 0.0001) significantly greater in the cricothyroid group. Patient willingness to return for repeat procedure was greater (87.1 vs. 70.5%, p < 0.001)) and cumulative lidocaine dose significantly lower (305.08 ± 13.40 vs. 322.18 ± 10.67 mg, p < 0.001) in the cricothyroid group. Minor complications occurred in 6 patients in the cricothyroid group and 9 patients in the spray-as-you-go group. Conclusion: Cricothyroid lidocaine administration is associated with less cough and superior operator-rated procedure satisfaction during bronchoscopy at a lower cumulative lidocaine dose.
Synthesis and Evaluation of Pyridoxal Hydrazone and Acylhydrazone Compounds as Potential Angiogenesis Inhibitors
Authors: Chen Xuyang , Li Hui , Luo Hongjun , Lin Zhexuan , Luo Wenhong
Published: September 2019

Background/Aims: Hydrazone and acylhydrazone derivatives, which are produced from aldehyde reacting with hydrazine or acylhydrazine, have been reported to exhibit antitumor activities. However, the angionenic effects of this kind of derivatives haven’t been elucidated. Here, we synthesized 12 pyridoxal hydrazone and acylhydrazone compounds and investigated their antiangiogenic effects and the underlying mechanisms. Method: 3-(4,5-Dimethylthiazol-2-yl)-2, 5-dipheyltetrazolium bromide assay was used to screen the inhibitory effects of the synthesized compounds on endothelial cells (ECs) proliferation. The compound with best inhibitory effect was further evaluated with wound-healing assay and tube formation assay. Calcein-Am assay was carried out to determine the content of intracellular labile iron pool (LIP). Intracellular reduced glutathione (GSH) was determined by spectrophotometry. Flow cytometry was used to determine cell cycle and apoptosis. Results: Compound 10 (3-hydroxy-5-[hydroxymethyl]-2-methyl-pyridine-4-carbaldehyde-2-naphthalen-1-acetyl hydrazone) showed the best inhibitory effect on human umbilical vascular ECs proliferation, with IC50 value of 25.4 μmol/L. It not only inhibited wound-healing and tube formation of ECs, but also decreased the content of intracellular LIP and GSH. Furthermore, it arrested ECs cycle at S phase and induced cell apoptosis. Conclusions: Compound 10 exhibits antiangiogenic effects by reducing the content of intracellular LIP and GSH, and subsequently arresting cell cycle and inducing cell apoptosis.
Reproducibility of Microperimeter 3 (MP-3) Microperimetry in Open-Angle Glaucoma Patients
Authors: Leisser Christoph , Palkovits Stefan , Hirnschall Nino , Georgiev Stefan , Findl Oliver
Published: September 2019

Purpose: Primary open-angle glaucoma (POAG) is a chronic progressive optic neuropathy, leading to degeneration of retinal ganglion cells and characteristic morphological changes at the optic disc. In advanced stages of the disease, functional tests, such as standard automated perimetry (SAP), are the main diagnostic tools to detect progression. Compared to SAP, microperimetry offers fundus imaging with motion tracking to ensure precise stimulation of certain locations of the retina. Aim of the study was to assess reproducibility of microperimetry compared to SAP in patients with POAG. Methods: This prospective monocenter study included patients suffering from POAG with visual field defects in the central 20° zone. After inclusion into the study, 3 consecutive study visits were scheduled within 1 month, assessing microperimetry and SAP at each visit. Results: From 19 patients recruited, data from 18 patients could be analyzed. No significant difference between study visits could be detected in mean retinal sensitivity in microperimetry and SAP (microperimetry p = 0.401; SAP p = 0.644; Friedman’s 2-way analysis of variance). The intraclass-correlation coefficient was 0.981 (95% CI 0.978–0.984) for microperimetry and 0.948 (95% CI 0.941–0.955) for SAP. Absolute agreement between deep scotoma points was found in 81 test locations (79%) in microperimetry and in 35 test locations (20%) in SAP (p = 0.003, chi-square test). Conclusions: Microperimetry and conventional perimetry showed high reproducibility, with slightly better performance of microperimetry. However, the reduced angle of visual field in microperimetry limits its application to central glaucomatous field damage.
Intracranial Myxoid Mesenchymal Tumor with Rare EWSR1-CREM Translocation
Authors: White Michael D. , McDowell Michael M. , Pearce Thomas M. , Bukowinski Andrew J. , Greene Stephanie
Published: September 2019

Translocations between EWSR1 and members of the CREB family of transcription factors (CREB1, ATF1, and CREM) are rare genetic findings occurring in various sarcomas. Of these, the EWSR1-CREM translocation is the most rarely reported. We present the case of a 9-year-old boy who presented with a year of fatigue, weight loss, and abulia. A brain MRI revealed a frontal interhemispheric tumor arising from the falx. After resection, pathology demonstrated a myxoid mesenchymal tumor with an EWSR1-CREM translocation. A series of recent reports of similar tumors has generated ongoing debate in the literature over the classification of these tumors either as intracranial angiomatoid fibrous histiocytomas, which also harbor EWSR1-CREB family translocations, or as a novel diagnostic entity. The present case provides another example of the rare EWSR1-CREM fusion in an intracranial myxoid mesenchymal tumor that recurred in just 6 months despite gross total resection. The findings are discussed in the context of the existing literature and the ongoing effort to appropriately classify this type of tumor.
Wound Healing Effect of Lawsonia inermis
Authors: Rekik Dorsaf Moalla , Ben Khedir Sameh , Daoud Amal , Ksouda Moalla Kamilia , Rebai Tarak , Sahnoun Zouheir
Published: September 2019

Background: Lawsonia inermis-extracted oil is known for therapeutic properties, especially wound healing. This study assesses the potential of this oil for wound healing in a rat model. Methodology: To assess the potential of L. inermis-extracted oil for wound healing, phytochemical, antibacterial, and antioxidant analyses were conducted. Uniform wound excision was induced on the dorsum of randomly selected rats divided into 3 groups cleaned and treated with saline solution (control), Cicaflora (reference), and L. inermisoil. Biopsies performed after healing were histologically assessed. Conclusions: The quality and content of the fatty acids in the oil were determined. Results showed a high content of bioactive components inducing an efficient wound healing effect determined by an in vivo study. Histological and chromatic assessment findings revealed healing in the oil-treated group but not in the untreated group, a full reepithelialization with reappearance of skin appendages and well-organized collagen fibers without any inflammatory cells. This might be due to a synergistic effect of the phytoconstituents present in the oil.
Huge Gastrointestinal Stromal Tumor of the Jejunum Presenting as Bowel Obstruction: A Rare Presentation
Authors: Huda Tanweerul , Singh Mahendra Pratap
Published: September 2019

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract arising from interstitial Cajal cells. A 54-year-old male patient without any comorbidities presented to the emergency department with complaints of abdominal distension, inability to pass flatus, and no motion for the past 2 days. Abdominal X-ray showed multiple air-fluid levels suggesting bowel obstruction. The patient was managed conservatively at first. Later, ultrasonography and contrast-enhanced computed tomography (CECT) of the abdomen were done, which revealed a mass lesion arising from the jejunum suggestive of GIST. The patient was taken up for exploratory laparotomy, and a tumor was found in the proximal jejunum around 10 cm from the duodenojejunal junction and encompassing the hepatic flexure of the transverse colon, with the omentum found adhered to the anterior surface of the lesion and distended proximal bowel loops. There was no evidence of mesenteric lymphadenopathy. The mass was resected along with the jejunal loop and the hepatic flexure of the colon, followed by end-to-end jejunojejunal anastomosis and end-to-end colocolic anastomosis. The patient’s postoperative stay was uneventful. Imatinib therapy was started following histopathological confirmation and continued. The patient was followed up for 1 year postoperatively with CECT of the abdomen every 6 months, with no evidence of recurrence or any gastro­intestinal symptoms.
Intra- and Interobserver Reproducibility of Third Trimester Middle Cerebral Artery Pulsatility Index Measurement: A Prospective Cross-Sectional Study
Authors: Pasquini Lucia , Marchi Laura , Gaini Claudia , Franchi Chiara , Mecacci Federico , Bilardo Caterina Maddalena
Published: September 2019

Background: Middle cerebral artery (MCA) pulsatility index (PI) Doppler in the third trimester of pregnancy is increasingly used. Objectives: The aim of the study was to investigate intra- and interobserver reproducibility of MCA PI in the third trimester. Method: Singleton pregnancies between 30+0 and 40+0 weeks were recruited. MCA Doppler velocimetry measurements were performed prospectively, independently, and blindly. Intra- and interobserver reproducibility was assessed by concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC); Bland-Altman plots were built, and limits of agreement (LoA) were calculated. Results were interpreted according to the cutoff set by the True Reproducibility of Ultrasound Techniques Review. Results: We enrolled 101 patients. ICCs for intraobserver reproducibility were 0.84 and 0.78 for raw values and percentiles, respectively; CCCs were 0.72 and 0.64. For interobserver reproducibility ICCs were 0.84 and 0.78, CCCs 0.72 and 0.63. According to the chosen criteria, these values show a poor-moderate reproducibility of third trimester MCA PI. Cohen’s Kappa coefficients were 0.59 and 0.42, indicating a moderate agreement in discriminating normal and abnormal values. Conclusions: Intra- and interobserver reproducibility of third trimester MCA PI, as assessed by ICC, CCC, and LoA, is far from satisfactory. This should be taken into account before taking clinical decisions.
about:blank? Online Interventions for Postpartum Depression
Authors: Westerhoff Bettina , Trösken Anne , Renneberg Babette
Published: September 2019

Background: Despite the existence of effective interventions for postpartum depression, few women use them. Online interventions have the potential to overcome many barriers to treatment seeking. This systematic review describes the current state of research regarding online interventions for postpartum depression with special attention to the German-speaking area. Methods: We conducted a systematic Internet search to assess interventions found online. A systematic literature search identified publications on online interventions for women with postpartum depression, which targeted the reduction of symptoms of depression, the mother-child interaction, and/or other child-related variables. We extracted information on conceptual design, efficacy, and adherence to the interventions. Results: References to interventions on the Internet comprised mostly general advice about treatment options and some specific entries on face-to-face interventions. Online interventions were scarce. The systematic literature review yielded 14 articles on 6 mostly CBT-based interventions. While the programs were effective in reducing symptoms of depression, they had little impact on mother-child interaction. Other child-related variables were not included in the studies. There was no intervention from German-speaking countries. Discussion and Conclusions: The potential of online interventions for postpartum depression is hardly used. Guided CBT-based self-help interventions seem to be a promising treatment for postpartum depression, yet more research is needed.
Comparison of Danaparoid Sodium and Synthetic Protease Inhibitors for the Treatment of Disseminated Intravascular Coagulation Associated with Hematological Malignancies: A Retrospective Analysis
Authors: Minakata Daisuke , Fujiwara Shin-ichiro , Hayakawa Jin , Nakasone Hideki , Ikeda Takashi , Kawaguchi Shin-ichiro , Toda Yumiko , Ito Shoko , Ochi Shin-ichi , Nagayama Takashi , Mashima Kiyomi , Umino Kento , Nakano Hirofumi , Yamasaki Ryoko , Morita Kaoru , Kawasaki Yasufumi , Sugimoto Miyuki , Ishihara Yuko , Yamamoto Chihiro , Ashizawa Masahiro , Hatano Kaoru , Sato Kazuya , Oh Iekuni , Ohmine Ken , Muroi Kazuo , Ohmori Tsukasa , Kanda Yoshinobu
Published: September 2019

Background: Danaparoid sodium and synthetic protease inhibitors (SPIs) have been approved for the treatment of disseminated intravascular coagulation (DIC) in Japan. Objectives: To compare the clinical results of the treatment of DIC with danaparoid or SPIs. Methods: We retrospectively examined 188 patients with hematological malignancy-related DIC. Results: DIC resolution rate in the danaparoid group was higher than that in the SPIs group (61.5 vs. 42.6%; p = 0.031) on day 7. Multivariate analysis identified the response to chemotherapy as independent predictive factor for DIC resolution on day 7 (odds ratio, OR, 2.28; 95% confidence interval, CI, 1.21–4.31; p = 0.011). While there was no significant difference in the DIC resolution rate on day 14 (75.0 vs. 62.4%; p = 0.117), in a subgroup analysis of patients who did not show an improvement in the underlying disease, the danaparoid group showed a significantly better DIC resolution rate (OR 3.89; 95% CI 1.15–13.2; p = 0.030). There was no difference in the rate of cumulative mortality from bleeding within 28 days between the 2 groups (6.6 vs. 3.3%; p = 0.278). Conclusions: Danaparoid may be associated with more frequent resolution of DIC in patients with refractory underlying disease.
Risk Factors of Sexual Dysfunction in Patients with Hidradenitis Suppurativa: A Cross-Sectional Study
Authors: Cuenca-Barrales Carlos , Molina-Leyva Alejandro
Published: September 2019

Background: Hidradenitis suppurativa (HS) has a high impact on quality of life. However, sexual health has scarcely been investigated. Objective: To describe the frequency of sexual dysfunction (SD) in women and erectile dysfunction (ED) in men with HS and to explore potential risk factors. Patients and Methods:We conducted a cross-sectional study using a crowd-sourced online questionnaire spread by the Spanish hidradenitis suppurativa patients’ association (ASENDHI). Results: In total, 393 participants answered the questionnaire. SD was found in 51% (95% CI 45–57%) of women and ED in 60% (95% CI 49–70%) of men. Factors related to SD were education status, patient’s global assessment for disease activity, numeric rating scale for pain and unpleasant odour and the absence of a stable relationship. Factors related to ED were increasing age, the presence of active lesions in the genital area and the number of areas affected by active lesions. Conclusions: There is a high prevalence of SD and ED in HS patients. Being in a stable relationship has been a protective factor of SD in women. The results suggest that sexual impairment in HS patients is due, at least in part, to disease activity, symptoms and active lesions.
Reliability of Japan Narrow-Band Imaging Expert Team Classification for the Diagnosis of Colorectal Neoplasms: A Pilot Study
Authors: Sakamoto Taku , Takamaru Hiroyuki , Sekiguchi Masau , Yamada Masayoshi , Matsuda Takahisa , Saito Yutaka
Published: September 2019

Introduction: Magnifying narrow-band imaging (NBI) is a beneficial modality for the prediction of histology in colonoscopy. The Japan NBI Expert Team (JNET) classification has been established based on the results of online surveys of the diagnostic accuracy of histological features. However, the reliability of the JNET classification has not been examined. The aim of this study was to evaluate the degree of interobserver agreement for JNET classification among endoscopists when evaluating colonic lesions. Methods: We analyzed a total of 246 colonic lesions in this interpretation test. Each lesion image was subsequently reviewed by 3 experienced endoscopists and then classified based on 4 established JNET categories and indeterminate categories between fixed categories. The primary endpoint was the interobserver agreement rate for evaluation of endoscopic findings using the JNET classification. Results: The complete concordance (defined as 3 out of 3 observer agreement) rate was 73% (179/246), while the partial concordance (defined as 2 out of 3 observer agreement) rate was 26% (64/246). Therefore, concordance of at least 2 out of 3 was achieved in 99% of all the lesions and disagreement of the 3 endoscopists was found in only 1% (3/246). Fleiss’s kappa coefficient (κ) was 0.72 for all cases, which represents moderate interobserver agreement for observers. Discussion/Conclusion: Our study highlights the reliability of the JNET classification for colonic neoplastic lesions among experienced endoscopists and demonstrates acceptable interobserver agreement. Further studies validating the clinical applicability of JNET classification are required among endoscopists with a variety of expertise in several clinical settings.
Efficacy and Safety of Secukinumab in Patients with Plaque Psoriasis and Latent Tuberculosis
Authors: Ribero Simone , Licciardello Matteo , Quaglino Pietro , Dapavo Paolo
Published: September 2019

Upon the association of biologic treatments with reactivation of latent tuberculosis infection (LTBI), screening for Mycobacterium tuberculosisinfection and anti-tuberculosis chemoprophylaxis in positive patients are required prior to biologic drug administration. Nevertheless, the risk of infection relapses associated with biologic drugs seems to be different. No cases of reactivation of LTBI have been observed in secukinumab-treated subjects, in contrast with clinical reports on the risk associated with anti-tumor necrosis factor α-based therapy. Twelve patients with moderate to severe plaque psoriasis eligible for systemic treatment and found to have LTBI received secukinumab without previous chemoprophylaxis initiation because of clinical contraindication for 10 cases and refusal by 2 patients. None of them had tuberculosis reactivation.
Secukinumab for Psoriasis in Obese Patients: Minireview and Clinical Experience
Authors: Tiberio Rossana , Graziola Francesca , Miglino Benedetta , Veronese Federica , Annali Giordana , Savoia Paola
Published: September 2019

Psoriasis (PsO) has been associated with obesity, and its severity increases in obese subjects. The link between psoriatic condition and obesity is based on shared pathophysiological pathways where local and systemic inflammation promote each other; PsO is an inflammatory, immune-mediated disease, and the adipose tissue is the source of proinflammatory adipokines. Moreover, psoriatic arthritis (PsA) is an important comorbidity of PsO that reduces quality of life and makes difficult the patient’s management. Treatment of obese subjects with moderate to severe PsO, even more if PsA is present, is challenging because of reduced efficacy of several systemic drugs and increased risk of adverse events. Secukinumab, a monoclonal antibody that selectively binds to and neutralizes interleukin 17A, shows efficacy on PsO in all body weight groups, even in the highest, whose response has a slight downward trend. Clinical features of two obese subjects, affected by PsO and PsA, successfully treated with secukinumab, are described.
Optimizing Secukinumab Treatment in Psoriasis with Concomitant Methotrexate Administration: Minireview and A Case Report
Authors: Kostaki Dimitra , Aquila Emilia , Macaluso Laura , Mattozzi Carlo , Richetta Antonio Giovanni 
Published: September 2019

The introduction of biologic drugs for the treatment of moderate-to-severe psoriasis resulted in a significant improvement in patients’ health. Moreover, treatment regimens in psoriatic patients should be tailored to meet specific needs based on disease severity, impact on quality of life, response to previous therapies and presence of comorbidities. Combination therapy of biologic agents with conventional systemic drugs has been proposed to optimize psoriasis treatment outcomes in unresponsive or partial responsive severe psoriatic patients. We report the case of a patient with a long-standing recalcitrant plaque psoriasis and psoriatic arthritis who was administered secukinumab combined with methotrexate. The patient had previously been treated with several topical and systemic therapies associated with loss of efficacy or adverse event occurrence. Approximately 24 weeks after starting the combined regimen, significant clearance of psoriasis and reduction of arthritis ensued, with no drug side effects.
Hepatitis E-Induced Acute Myocarditis in an Elderly Woman
Authors: Sengupta Pratim , Biswas Sumanta , Roy Tapas
Published: September 2019

Hepatitis E is a common, mainly water-borne hepatotropic virus prevalent mainly in Southeast Asia, Africa, the Middle East, and Central America. In the eastern part of India epidemics of acute hepatitis E are well reported. Hepatitis E commonly presents as self-limiting acute viral hepatitis among young adults, except for some critical clinical complications during pregnancy. In epidemiological research, subclinical acute hepatitis E infection is also reported from different parts of the world, including developed nations such as the USA (predominantly in the population aged >60 years). Though primarily hepatotropic, in the literature there are reports of rare extrahepatic manifestation of acute hepatitis E. Here we present an elderly lady with acute hepatitis E who primarily presented with acute myocarditis.
Phenotypic and Genetic Characteristics of Five Korean Patients with Costello Syndrome
Authors: Choi Naye , Ko Jung Min , Shin Seung Han , Kim Ee Kyung , Kim Han Suk , Song Mi Kyoung , Choi Chang Won
Published: September 2019

Costello syndrome (CS) is a rare genetic disorder characterized by distinctive facial appearance, cardiopulmonary complications, severe growth retardation, skin and skeletal defects, developmental delay, and tumor predisposition. CS is caused by heterozygous de novo mutations in the proto-oncogene HRAS, which is a component of the RAS/mitogen-activated protein kinase pathway. Herein, we reviewed the phenotypic and genetic features of 5 Korean patients who were genetically diagnosed with CS. Atrial tachycardia and polyhydramnios, which are important prenatal features for CS, were observed in 4 and 5 patients, respectively. The distinctive coarse facial appearances of the patients and presence of deep palmoplantar creases supported the clinical diagnosis of CS, which was confirmed by HRAS sequence analysis. Extremely poor postnatal growth was observed in all 5 patients. Further, all patients exhibited cardiac abnormalities; left ventricular hypertrophy and hypertrophic cardiomyopathy were observed in 3 patients. All 5 patients suffered from airway problems; 3 of them required intubation right after birth, and 2 of them received tracheostomy. One patient with a p.Gly12Ser mutation was diagnosed with retroperitoneal rhabdomyosarcoma alveolar type at the age of 5 years. Consistent with previous reports, both patients with p.Gly12Cys mutations died within the first year of life due to cardiopulmonary failure. Our study summarizes the characteristics of these 5 Korean patients with CS and, along with previous studies, provides clues for genotype-phenotype correlation in patients with CS.
Apoptosis Induction by Pseudorabies Virus via Oxidative Stress and Subsequent DNA Damage Signaling
Authors: Lai I-Hsiang , Chang Ching-Dong , Shih Wen-Ling
Published: September 2019

Background: Pseudorabies virus (PRV) infection induces apoptosis in swine cells both in vitro and in vivo; however, the mechanism associated with host-cell signaling has not been studied. This study investigated the role of free radicals caused by cellular oxidative stress after viral infection and examined whether the DNA damage response plays an important role in PRV-induced apoptosis. Methods: Several apoptosis assays and western blotting confirmed PRV-induced apoptosis. PRV-mediated oxidative stress was evaluated by reactive oxygen species (ROS) assay. Results: Our results showed that PRV caused apoptosis in a porcine kidney cell line, PK15, and induced expressions of proapoptotic Bcl family proteins in a dose- and time-dependent manner. Expressions of specific DNA damage sensors and phosphorylation of histone H2AX were also significantly increased, which subsequently activated the expressions of checkpoint kinase 1/2 and proapoptotic p53. Caffeine, a known DNA damage inhibitor, was found to inhibit caspase-3 activation and protect cells from PRV-induced apoptosis. Additionally, the antioxidant N-acetyl-L-cysteine was shown to prevent the production of cellular ROS, protecting DNA from cleavage. Conclusions: Our results confirmed that oxidative stress and free radicals arising from PRV infection cause DNA damage, which consequently triggers apoptosis.
Nutritional Intervention in Chronic Liver Failure
Authors: Plauth Mathias
Published: September 2019

Patients suffering from chronic liver failure (CLF) frequently are malnourished and do not achieve an adequate intake of nutrients, in particular protein. Low protein intake and loss of muscle mass and function, termed sarcopenia, are indicators of a poor outcome. CLF patients, therefore, should be screened for risk of malnutrition using a validated tool, and if positive, full assessment of nutritional status is mandatory including search for sarcopenia. The main goal of nutritional intervention is to provide enough protein (1.2–1.5 g × kg–1 × day–1) and to ensure adequate energy intake (total energy 30 kcal × kg–1 × day–1; 1.3 × resting energy expenditure). Livers of CLF patients are deplete in glycogen and, therefore, prolonged periods of fasting (>12 h) must be avoided in order to prevent further breakdown of muscle protein for gluconeogenesis. Therefore, late evening snacks or even nocturnal oral nutritional supplements improve total body ­protein status and thus, are recommended. Nutrition intervention should be stepped up from nutrition counselling to oral nutritional supplements, to enteral tube feeding, or to parenteral nutrition as appropriate. As in other malnourished patients, the prevention of refeeding syndrome or vitamin/trace element deficiency should be taken care of.
Impact of Simulated Hyperventilation and Periodic Breathing on Sympatho-Vagal Balance and Hemodynamics in Patients with and without Heart Failure
Authors: Spiesshoefer Jens , Becker Sara , Tuleta Izabela , Mohr Michael , Diller Gerhard Paul , Emdin Michele , Florian Anca Rezeda , Yilmaz Ali , Boentert Matthias , Giannoni Alberto
Published: September 2019

Background: The effects of hyperventilation and hyperventilation in the context of periodic breathing (PB) on sympatho-vagal balance (SVB) and hemodynamics in conditions of decreased cardiac output and feedback resetting, such as heart failure (HF) or pulmonary arterial hypertension (PAH), are not completely understood. Objectives: To investigate the effects of voluntary hyperventilation and simulated PB on hemodynamics and SVB in healthy subjects, in patients with systolic HF and reduced or mid-range ejection fraction (HFrEF and HFmrEF) and in patients with PAH. Methods: Study participants (n = 20 per group) underwent non-invasive recording of diastolic blood pressure, heart rate variability (HRV), baroreceptor-reflex sensitivity (BRS), total peripheral resistance index (TPRI) and cardiac index (CI). All measurements were performed at baseline, during voluntary hyperventilation and during simulated PB with different length of the hyperventilation phase. Results: In healthy subjects, voluntary hyperventilation led to a 50% decrease in the mean BRS slope and a 29% increase in CI compared to baseline values (p < 0.01 and p < 0.05). Simulated PB did not alter TPRI or CI and showed heterogeneous effects on BRS, but analysis of dPBV revealed decreased sympathetic drive in healthy volunteers depending on PB cycle length (p < 0.05). In HF patients, hyperventilation did not affect BRS and TPRI but increased the CI by 10% (p < 0.05). In HF patients, simulated PB left all of these parameters unaffected. In PAH patients, voluntary hyperventilation led to a 15% decrease in the high-frequency component of HRV (p < 0.05) and a 5% increase in CI (p < 0.05). Simulated PB exerted neutral effects on both SVB and hemodynamic parameters. Conclusions: Voluntary hyperventilation was associated with sympathetic predominance and CI increase in healthy volunteers, but only with minor hemodynamic and SVB effects in patients with HF and PAH. Simulated PB had positive effects on SVB in healthy volunteers but neutral effects on SVB and hemodynamics in patients with HF or PAH.
β-Sitosterol Attenuates the Intracranial Aneurysm Growth by Suppressing TNF-α-Mediated Mechanism
Authors: Yang Qian , Yu Delin , Zhang Yi
Published: September 2019

Background: Onset of inflammation associated with increased extracellular matrix degradation of vascular walls in the neuronal area is the pathophysiology of cerebral aneurysms. It has been documented well that β-sitosterol has protective effects on various brain-related diseases independent of their lipid-lowering effects; the current work was framed to examine the effect of β-sitosterol on CA progression. Materials and Methods: To study whether β-sitosterol has a suppressive effect on the growth of CA, β-sitosterol administration started prior to aneurysm induction. CA was induced in Wistar male rats with or without oral administration of β-sitosterol. The expression of chemokines and inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin (IL)-8, IL-1β, IL-17, IL-6, matrix metalloproteinases (MMP)-2 and -9, was elucidated by ELISA and RT-PCR. Results: Rats treated with β-sitosterol exhibited a significant reduction in aneurysmal size compared with control rats. In addition, β-sitosterol administration reduced the expression of chemokines and inflammatory cytokines, while gelatin zymography data revealed declined activity of MMP-2 and -9 in aneurismal walls. Furthermore, the levels of cytokines were significantly reduced in β-sitosterol-administered rats compared to CA rats. Conclusions: Treatment with β-sitosterol suppresses the development of CA by inhibiting inflammatory reactions including TNF-α and thus β-sitosterol can be a suggestive candidate for the prevention of CA treatment and progression.
Factors Influencing the Onset of Neoadjuvant Therapy in Breast Cancer Patients
Authors: Müller Carolin , Juhasz-Böss Stephanie , Schmidt Gilda , Solomayer Erich-Franz , Juhasz-Böss Ingolf , Breitbach Georg-Peter
Published: September 2019

Background: Time to treatment onset (TTTO) is critical in breast cancer patients receiving neoadjuvant chemotherapy (NACT). We therefore investigated possible delaying factors of therapy onset. Methods: All patients were included who qualified for NACT in our hospital from 2015 to 2017. The time interval between core biopsy of tumor and date of therapy onset was defined as primary endpoint. Among other things, age, out- and in-patient presentation, and study or standard treatment were investigated as potentially delaying factors. Results: We analyzed 139 patients scheduled for NACT; 90 (64.7%) received standard NACT, and 49 (35.3%) were recruited for trials. The average age was 53 years (±13.2 years). A time interval of 30.7 days (±11.8 days) was seen between diagnosis and therapy onset. Patients had a mean of 5 (±1.9) pretherapeutic presentations, 4 (±1.8) on outpatient and 1 (±0.5) on inpatient basis, being of significant influence on TTTO. Conclusion: Any outpatient presentation extended the time interval by 2 days, inpatient presentation by 4 days. These presentations should be merged in order to minimize TTTO. Neither the site of pathology examinations, additional consultations (genetics, reproductive medicine), nor study participation delayed therapy onset.