Caspase-mediated cleavage of miRNA processing proteins Drosha, DGCR8, Dicer, and TRBP2 in heat-shocked cells and its inhibition by HSP70 overexpression.
Cells respond to stress through adaptive mechanisms that limit cellular damage and prevent cell death. MicroRNAs act as regulators of stress responses and stress can impact the functioning of miRNA biogenesis pathways. We were interested in the effect that severe proteotoxic stress capable of inducing apoptosis may have on miRNA biogenesis and the impact of the molecular chaperone protein HSP70 under these conditions. We found that the miRNA processing enzymes Drosha and Dicer and their accessory proteins DGCR8 and TRBP2 are cleaved by caspases in apoptotic cells. Overexpression of HSP70 prevented caspase activation and the degradation of these processing proteins. Caspase cleavage of TRBP2 was mapped to amino acid 234 which separates the two dsRNA-binding domains from the C-terminal Dicer interacting domain. Overexpression of TRBP2 was found to increase miRNA maturation, while expression of either of the fragments generated by caspase cleavage impaired maturation. These results indicate that inactivation of miRNA biogenesis is a critical feature of apoptosis and that cleavage of TRBP2, rather than simply a loss of function, serves to create positive acting inhibitors of pre-miRNA maturation.


RNA polymerisation capacity and permeability to ribonucleoside triphosphates of nuclei from livers of whole-body X-irradiated rats.
For 4--18 h following whole-body X-irradiation of rats, liver nuclei showed a progressive increase in the permeability to ribonucleoside triphosphates (as assessed in vitro using tritiated uridine triphosphate (UTP) and in the capacity to polymerise RNA in vitro (Mg++-containing and Mn++/(NH4)2SO4-containing assay systems).


Programming nonreciprocity and harmonic beam steering via a digitally space-time-coded metamaterial antenna.
Recent advancement in digital coding metasurfaces incorporating spatial and temporal modulation has enabled simultaneous control of electromagnetic (EM) waves in both space and frequency domains by manipulating incident EM waves in a transmissive or reflective fashion, resulting in time-reversal asymmetry. Here we show in theory and experiment that a digitally space-time-coded metamaterial (MTM) antenna with spatiotemporal modulation at its unit cell level can be regarded as a radiating counterpart of such digital metasurface, which will enable nonreciprocal EM wave transmission and reception via surface-to-leaky-wave transformation and harmonic frequency generation. Operating in the fast wave (radiation) region, the space-time-coded MTM antenna is tailored in a way such that the propagation constant of each programmable unit cell embedded with varactor diodes can toggle between positive and negative phases, which is done through providing digital sequences by using a field-programmable gate array (FPGA). Owing to the time-varying coding sequence, harmonic frequencies are generated with different main beam directions. Furthermore, the space time modulation of the digitally coded MTM antenna allows for nonreciprocal transmission and reception of EM waves by breaking the time-reversal symmetry, which may enable many applications, such as simultaneous transmitting and receiving, unidirectional transmission, radar sensing, and multiple-input and multiple-output (MIMO) beamformer.


Endogenous Opiates and Behavior: 2018.
This paper is the forty-first consecutive installment of the annual anthological review of research concerning the endogenous opioid system, summarizing articles published during 2018 that studied the behavioral effects of molecular, pharmacological and genetic manipulation of opioid peptides and receptors as well as effects of opioid/opiate agonists and antagonists. The review is subdivided into the following specific topics: molecular-biochemical effects and neurochemical localization studies of endogenous opioids and their receptors (2), the roles of these opioid peptides and receptors in pain and analgesia in animals (3) and humans (4), opioid-sensitive and opioid-insensitive effects of nonopioid analgesics (5), opioid peptide and receptor involvement in tolerance and dependence (6), stress and social status (7), learning and memory (8), eating and drinking (9), drug abuse and alcohol (10), sexual activity and hormones, pregnancy, development and endocrinology (11), mental illness and mood (12), seizures and neurologic disorders (13), electrical-related activity and neurophysiology (14), general activity and locomotion (15), gastrointestinal, renal and hepatic functions (16), cardiovascular responses (17), respiration and thermoregulation (18), and immunological responses (19).


Protective Effects of Icariin on Traumatic Brain Injury.
Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Icariin (ICA) is a flavonoid derived from the genus Epimedium, a traditional Chinese herb and a potential therapeutic drug for TBI. This study aims to explore the protective effect of ICA on TBI and its mechanism. Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received ICA (15 mg/kg, 30 mg/kg, and 60 mg/kg), while the sham group was gavaged with equal volumes of saline. The beam-balance testing and prehensile traction test were used for neurological scoring. Pathological changes were observed by H & E staining. The protein expression levels of inflammatory factors were measured by Western blot analysis. It was found that ICA significantly improved the neuroethology function and alleviated the pathological injury in TBI rats. The protein expression levels of inflammatory factors COX-2, IL-1β, and TNF-α and its regulatory proteins p-NF-κB-p65, p-ERK1/2, p-JNK, and p-p38 were increased in the cerebral cortex injured by TBI. The protein expression levels of inflammatory cytokines were markedly decreased in the cerebral cortex of TBI rats when administrated with ICA. The present study demonstrates that ICA may be a promising therapeutic strategy for reducing inflammation in TBI.


Five-year prospective outcome of psychopathology in the adolescent offspring of bipolar parents.
For nearly 5 years a prospective high risk cohort study was carried out in the Netherlands among adolescent offspring of parents with bipolar disorder (BD). The purpose of this study was to determine the prevalence of psychopathology, specifically mood disorders, in adolescents and young adults with a bipolar parent. At first and second measurement 140 and 132 children of bipolar parents, respectively, were psychiatrically evaluated with a semi-structured psychiatric interview (K-SADS-PL). At follow up (third measurement), nearly 5 years later, lifetime DSM IV diagnoses were obtained from the SCID interview for 129 subjects (aged 16--26 years). Compared with the first measurement, the lifetime prevalence of BD increased from 3 to 10% at follow up. In addition, the lifetime prevalence of overall mood disorders increased to 40% and of overall psychopathology to 59%. All subjects except for one with BD, debuted with a unipolar mood disorder with a mean of 4.9 (SD 3.4) years prior to the first (hypo)manic episode. At follow up, we noticed an increase in BD onset, while a further increase could be expected. In addition, we found that a unipolar depression in bipolar offspring is a risk factor for, and at the same time the first sign of, the development of BD.


Is repeated pulmonary metastasectomy justified?
Recurrence after pulmonary metastasectomy (PM) is frequent, but it is unclear to whom repeated pulmonary metastasectomy (RPM) offers highest benefits. Retrospective analysis of oncological and post-operative outcomes of consecutive patients who underwent PM from 2003 to 2018. Overall survival (OS) and disease-free interval (DFI) were calculated. Cox regression was used to identify variables influencing OS and DFI. In total, 264 patients (female/male: 114/150; median age: 62 years) underwent PM for colorectal cancer (32%), sarcoma (19%), melanoma (16%) and other primary tumors (33%). Pulmonary metastasectomy was approached by video-assisted thoracic surgery (VATS) in 73% and pulmonary resection was realized by non-anatomical resection in 76% of cases. The overall median follow-up time was 33 months (IQR 16-56 months) and overall 5-year survival rate was 62%. Local or distant recurrences were observed in 172 patients (65%) and RPM could be performed in 66 patients (25%) for a total of 116 procedures. RPM was realized by VATS in 49% and pulmonary resection by wedge in 77% of cases. In RPM patients, the 5-year survival rate after first PM was 79%. Post-operative cardio-pulmonary complication rate (13% vs. 12%; p = 0.8) and median length of stay (4 vs. 5 days; p = 0.2) were not statistically different between first PM and RPM. Colorectal cancer (HR 0.56), metachronous metastasis (HR 0.48) and RPM (HR 0.5) were associated with better survival. In conclusion, our results suggest that RPM offers favorable survival rates without increasing post-operative morbidity.


p75 and TrkC neurotrophin receptors demonstrate a different immunoreactivity profile in comparison to TrkA and TrkB receptors in human normal pituitary gland and adenomas.
Recent knowledge indicates that neurotrophins play a significant role in neuroendocrine systems through their specific receptors TrkA, TrkB, TrkC and low-affinity p75(NTR) receptor. TrkA and TrkB receptors have been previously detected in numerous endocrine cells in human anterior pituitary and adenomas. In the present study, the localization of p75(NTR) and TrkC along with TrkA and TrkB receptors was investigated. Semi-serial paraffin-embedded sections of 5 human normal pituitaries and 30 adenomas were immunostained using specific antibodies. Expression of p75(NTR) receptor was demonstrated in the intricate capillary and reticulin network in the anterior pituitary and in the pericapillary tissue and pituicytes in the posterior lobe. p75(NTR) immunoreactivity was absent from all adenomas. In normal anterior pituitary, a few scattered cells showed weak TrkC immunoreactivity in contrast to a high percentage of endocrine cells distributed throughout the pars distalis and pars intermedia which exhibited strong TrkA and/or intermediate TrkB immunoreactivity. Double immunohistochemistry demonstrated TrkA immunoreactivity in more than 80% of lactotropes and 70% of corticotropes and to a lesser extent in other cell types. Furthermore, in the majority of adenomas, independently of type, sex and age, a high percentage of TrkA- and/or TrkB-positive cells was detected. Interestingly, TrkC expression appeared to be increased in some adenomas compared to normal pituitary. Endothelial cells and perivascular connective tissue were always TrkB-immunostained. The above findings support a potential role of all neurotrophins, through their different receptors, in pituitary functions.


Pharmaceutical care- urgency: Proposing a practical clinical framework for pharmacy students.
Prioritizing a drug therapy problem (DTP) during an experiential placement is challenging for some pharmacy students, suggesting a gap in pre-placement preparedness and the need to modify existing resources. A modified DTP prioritizing framework is proposed to enhance clinical reasoning and increase students' confidence in performing this important step in the pharmaceutical care process. Students' baseline DTP prioritizing capability was assessed in an informal focus group consisting of pharmacy students and experienced hospital pharmacy preceptors. Participants ranked the urgency for addressing 47 common medical conditions and selected a time frame to resolve the DTP. Participants also provided feedback on a proposed DTP prioritizing framework. A modified, student-focused DTP prioritizing framework, incorporating elements of curricular knowledge, principal elements of urgency, and time frame for taking action to resolve the identified DTP is described. Students' DTP urgency rankings were heterogeneous and showed greater deviation from the anticipated ranking (R = 0.61) compared to the pharmacist cohort (R = 0.807), reinforcing our view of the need for a modified DTP prioritizing framework for students. In qualitative terms, students felt the framework's focus on curricular knowledge would contribute to the development of expertise. Preceptors felt the framework reflected their usual practice and would help guide discussions with students. The modified DTP prioritizing framework, described in this article, may be utilized both to enhance student success and preceptor development in the experiential setting.


Vigabatrin in complex partial seizures: a long-term study.
The efficacy and safety of oral vigabatrin (VGB) as add-on therapy in the long-term treatment of poorly controlled epilepsy were evaluated in 19 patients with complex partial seizures, either with or without secondary generalization. The study was run with a single-blind, placebo-controlled, crossover design, and included 2 months of placebo and 13-15 months of treatment with VGB, at doses ranging from 1 to 4 g/day. Of the 14 patients who completed the trial, 2 were seizure free, in 5 seizure frequency dropped by more than 75% and in another 5 by more than 50% with respect to baseline. The decrease in seizure frequency in the group as a whole was significant at all observation points of the trial. Three patients were not entered into the long-term phase due to lack of improvement (an increase in seizure frequency was observed in one of them), and 2 were excluded later because improvement disappeared leading to unauthorized changes in comedication. Side effects were mild and never caused discontinuation of treatment. In conclusion, VGB showed a remarkable efficacy and safety in the long-term treatment of complex partial seizures.


Assessment of cancer pain in a patient with communication difficulties: a case report.
The number of patients who have difficulty with mutual understanding has been increasing recently due to an aging society. This emerging issue needs to be addressed. We report an instructive case of a patient who had communication difficulties due to dementia and sequelae of alcoholic encephalopathy. A 66-year-old man of Mongolian race presented with coronary arteriosclerosis, spinal canal stenosis, transverse colon cancer, and alcoholic encephalopathy. We had been requested to remove wires that had been used for the closure of his chest in a coronary artery bypass grafting procedure. However, on admission, a tortured expression and abdominal distention were observed, along with emaciation. We diagnosed terminal stage cancer, and palliative care was offered. An abdominal computed tomographic scan revealed rectal cancer with stenosis and invasion to the adjacent tissues. A metallic stent was inserted, leading to reduction of the abdominal distention and an improvement of tachycardia. However, the patient's tortured expression was not completely relieved; therefore, an assessment of cancer pain was considered. The Abbey Pain Scale was applied. On the basis of the patient's score, analgesics and an opioid, among other medications, were administered. These led to relief of the patient's tortured expression and reduced his Abbey Pain Scale score. Following this, the patient's vital signs continued to be stable, and he was transferred to the referral institution. Management of cancer pain in elderly patients with mutual understanding difficulties must be performed carefully. In the case of our patient, staff at the referral institution informed us of the patient's latent torture, and we applied the Abbey Pain Scale. There was some confusion and uncertainty regarding clinical management throughout the patient's care; however, his condition eventually stabilized. We believe the application of the Abbey Pain Scale assists in the relief of cancer pain. However, accumulation of further cases and experiences to verify this assessment is required.


Surgical Society Podcasts: A Novel Way to Engage and Educate the Community.
Podcasts are increasingly being utilized in the surgical field as an asynchronous educational resource. This article discusses podcasts devoted to the field of surgery and their growing contribution to surgical education. We provide examples of current podcasts and their varied structures, including those that distribute clinical and educational content, discuss recent literature and advancements, interview leaders in the field, and/or showcase unique perspectives on topics such as career development, diversity, and wellness. Podcasts generated from surgical societies stand on unique ground to educate and engage the surgical community.


Atherosclerotic aortic lesions increase the risk of cerebral embolism during carotid stenting in patients with complex aortic arch anatomy.
Carotid artery stenting (CAS) leads to frequent embolic brain lesions; their source has not been clearly identified yet. In order to investigate this phenomenon, we have evaluated embolic brain lesions (BL) after CAS and correlated them with aortic arch (AA) characteristics. The AAs of 59 patients undergoing CAS under distal protection were evaluated by angiography and transesophageal echocardiography (TEE). AAs were stratified according to morphology (type I and II "simple" vs type III and bovine "difficult"), atherosclerotic arch lesions (complicated: >5 mm or with mobile debris vs uncomplicated: <5 mm), and tortuosity index (TI; sum of all angles diverging from ideal carotid axis, <150 vs >150). Diffusion weighted imaging (DWI) was performed before and within 24 hours from CAS. New BL were considered ipsilateral (IL) if ipsilateral to the site of CAS and non-ipsilateral (CL) if contralateral to it or bilateral. Normality distribution was by Shapiro-Wilk test (variables reported as medians +/- interquartile range) and statistical significance (P < .05) by Wilcoxon and Fisher's exact test. Difficult arches were present in 17 patients (28.8%), complicated aortic plaque in 21 (35.5%), and TI > 150 in 34 (57.6%). New BL appeared in 34 or 57.6% patients (6 or 18% IL and 28 or 82% CL). The mean number of BL was 5.7 (range, 0 to 20), 4.7 IL, and 5.7 CL, with a median volume of 560.95 +/- 1677.7 mm(3). Type of arch and TI were not correlated with mean number of BL. Mean volume of BL were greater in patients with difficult AA, complicated plaques, and TI > 150 (258 (572) mm(3) vs 15.6 (353) mm(3), P = .2; and 86 (828) mm(3) vs 85.9 (352) mm(3), P = .4 172 (766) mm(3) vs 0 (228) mm(3), P = .06, respectively). In patients with all three AA characteristics, mean number and volume of BL was significantly greater compared with other patients. Specifically, this increase was due mainly to CL (IL 0 (117) mm(3) vs 0 (172) mm(3), P = .9; CL 564 (687) mm(3) vs 0 (133) mm(3), P = .001). None of the technical details considered was correlated with either IL or CL. BL are frequent after protected CAS and are correlated with AA characteristics, thus underlining the role of catheterization maneuvers in determining embolic events. TEE may be useful in patient's selection for CAS.


Overfed Ossabaw swine with early stage metabolic syndrome have normal coronary collateral development in response to chronic ischemia.
Ossabaw miniswine have been naturally selected to efficiently store large amounts of lipids offering them a survival advantage. Our goal was to evaluate the myocardial response to chronic ischemia of the Ossabaw consuming a hypercaloric, high-fat/cholesterol diet with and without metformin supplementation. At 6 weeks of age animals were fed either a regular diet (OC, n = 9), a hypercaloric high-fat/cholesterol diet (OHC, n = 9), or a hypercaloric high-fat/cholesterol diet supplemented with metformin (OHCM, n = 8). At 9 weeks, all animals underwent ameroid constrictor placement to the left circumflex coronary artery to simulate chronic ischemia. Seven weeks after ameroid placement, all animals underwent hemodynamic and functional measurements followed by cardiac harvest. Both OHC and OHCM animals developed significantly greater weight gain, total cholesterol, and LDL:HDL ratio compared to OC controls. Metformin administration reversed diet-induced hypertension and glucose intolerance. There were no differences in global and regional contractility, myocardial perfusion, capillary and arteriolar density, or total protein oxidation between groups. Myocardial protein expression of VEGF, PPAR-α, γ, and δ was significantly increased in the OHC and OHCM groups. Microvessel reactivity was improved in the OHC and OHCM groups compared to controls, and correlated with increased p-eNOS expression. Overfed Ossabaw miniswine develop several components of metabolic syndrome. However, impairments of myocardial function, neovascularization and perfusion were not present, and microvessel reactivity was paradoxically improved in hypercholesterolemic animals. The observed cardioprotection despite metabolic derangements may be due to lipid-dependant upregulation of the PPAR pathway which is anti-inflammatory and governs myocardial fatty acid metabolism.


Development of airborne oil thickness measurements.
A laboratory sensor has now been developed to measure the absolute thickness of oil on water slicks. This prototype oil slick thickness measurement system is known as the laser-ultrasonic remote sensing of oil thickness (LURSOT) sensor. This laser opto-acoustic sensor is the initial step in the ultimate goal of providing an airborne sensor with the ability to remotely measure oil-on-water slick thickness. The LURSOT sensor employs three lasers to produce and measure the time-of-flight of ultrasonic waves in oil and hence provide a direct measurement of oil slick thickness. The successful application of this technology to the measurement of oil slick thickness will benefit the scientific community as a whole by providing information about the dynamics of oil slick spreading and the spill responder by providing a measurement of the effectiveness of spill countermeasures such as dispersant application and in situ burning. This paper will provide a review of early developments and discuss the current state-of-the-art in the field of oil slick thickness measurement.


Incidences, causes and risk factors of unplanned reoperation within 30 days of craniovertebral junction surgery: a single-center experience.
To investigate the incidences, causes, and risk factors for unplanned reoperation within 30 days of craniovertebral junction (CVJ) surgery. From January 2002 to December 2018, a retrospective analysis of patients who underwent CVJ surgery at our institution was conducted. The demographics, history of the disease, medical diagnosis, approach and type of operation, surgery duration, blood loss, and complications were recorded. Patients were divided into the no-reoperation group and the unplanned reoperations group. Comparison between two groups in noted parameters was analyzed to identify the prevalence and risk factors of unplanned revision and a binary logistic regression was performed to confirm the risk factors. Of 2149 patients included, 34(1.58%) required unplanned reoperation after the initial surgery. The causes for unplanned reoperation contained wound infection, neurologic deficit, improper screw placement, internal fixation loosens, dysphagia, cerebrospinal fluid leakage, and posterior fossa epidural hematomas. No statistical difference was found in demographics between two groups (P > 0.05). The incidence of reoperation of OCF was significantly higher than that of posterior C1-2 fusion (P = 0.002). In terms of diagnosis, the reoperation rate of CVJ tumor patients was significantly higher than that of malformation patients, degenerative disease patients, trauma patients, and other patients (P = 0.043). The binary logistic regression confirmed that different disease, fusion segment (posterior) and surgery time were independent risk factors. The unplanned reoperation rate of CVJ surgery was 1.58% and the major causes were implant-related failures and wound infection. Patients with posterior occipitocervical fusion or diagnosed with CVJ tumors had an increased risk of unplanned reoperation.


Intratympanic Gene Delivery of Antimicrobial Molecules in Otitis Media.
Otitis media (OM) in children is clinically important because of its detrimental effects on the development of language and motor coordination and is the most common reason for prescription of antibiotics. A recent bacteriological change in OM pathogens such as emergence of antibiotic resistance and vaccination-mediated pathogenic shift urges us to develop a new non-antibiotic strategy. The middle ear epithelium abundantly secretes a variety of antimicrobial molecules suppressing the viability of the common OM pathogens. Recently, we have demonstrated that the adenoviral vector is able to deliver the β-defensin 2 gene to the middle ear epithelial cells in vitro and in vivo, and adenovirus-mediated overexpression of β-defensin 2 is protective for experimental OM. There are many hurdles limiting successful clinical application of gene delivery to the respiratory epithelium of the tubotympanum; however, intratympanic gene therapy with β-defensin 2 is a promising alternative or adjuvant strategy for the management of OM.


[Early treatment and nursing role in the case of a haemorrhagic stroke].
Paediatric stroke constitute a medical and/or surgical emergency. The speed and timeliness of the treatment have a significant impact on the prognosis. The nursing role, from carrying out continuous observation to specific procedures, is essential in the assessment, the care pathway and the short-, medium- and long-term outcome for the child.


Glucagon.
Despite its infrequent usage, glucagon is an important drug in the ED. It has both well established and less well established indications. This article reviews its role for the practising emergency physician.


Habitat potential modelling and mapping of Teucrium polium using machine learning techniques.
Determining suitable habitats is important for the successful management and conservation of plant and wildlife species. Teucrium polium L. is a wild plant species found in Iran. It is widely used to treat numerous health problems. The range of this plant is shrinking due to habitat destruction and overexploitation. Therefore, habitat suitability (HS) modeling is critical for conservation. HS modeling can also identify the key characteristics of habitats that support this species. This study models the habitats of T. polium using five data mining models: random forest (RF), flexible discriminant analysis (FDA), multivariate adaptive regression splines (MARS), support vector machine (SVM), and generalized linear model (GLM). A total of 119 T. poliumlocations were identified and mapped. According to the RF model, the most important factors describing T. polium habitat were elevation, soil texture, and mean annual rainfall. HS maps (HSMs) were prepared, and habitat suitability was classified as low, medium, high, or very high. The percentages of the study area assigned high or very high suitability ratings by each of the models were 44.62% for FDA, 43.75% for GLM, 43.12% for SVM, 38.91% for RF, 28.72% for MARS, and 39.16% for their ensemble. Although the six models were reasonably accurate, the ensemble model had the highest AUC value, demonstrating a strong predictive performance. The rank order of the other models in this regard is RF, MARS, SVM, FDA, and GLM. HSMs can provide useful output to support the sustainable management of rangelands, reclamation, and land protection.


A discriminative shape-texture convolutional neural network for early diagnosis of knee osteoarthritis from X-ray images.
Knee Osteoarthritis (OA) is one of the most common causes of physical disability worldwide associated with a significant personal and socioeconomic burden. Deep Learning approaches based on Convolutional Neural Networks (CNNs) achieved remarkable improvements in knee OA detection. Despite this success, the problem of early knee OA diagnosis from plain radiographs remains a challenging task. This is due to the high similarity between the X-ray images of OA and non-OA subjects and the disappearance of texture information regarding bone microarchitecture changes in the top layers during the learning process of the CNN models. To address these issues, we propose a Discriminative Shape-Texture Convolutional Neural Network (DST-CNN), which automatically diagnoses early knee OA from X-ray images. The proposed model incorporates a discriminative loss to improve class separability and deal with high inter-class similarities. In addition, a new Gram Matrix Descriptor (GMD) block is embedded in the CNN architecture to compute texture features from several intermediate layers and combine them with the shape features in the top layers. We show that merging texture features with deep ones leads to better prediction of the early stages of OA. Comprehensive experimental results on two large public databases, Osteoarthritis Initiative (OAI) and Multicenter Osteoarthritis Study (MOST) demonstrate the potential of the proposed network. Ablation studies and visualizations are provided for a detailed understanding of our proposed approach.


CdS nanocrystallites sensitized ZnO nanosheets for visible light induced sonophotocatalytic/photocatalytic degradation of tetracycline: From experimental results to a generalized model based on machine learning methods.
CdS/ZnO nanosheets heterostructures ((x)CdS/ZNs) with different mole ratios of Cd/Zn ((x) = 0.2, 0.4, and 0.6) were synthesized by the impregnation-calcination method. PXRD patterns showed that the (100) diffraction of ZNs was the most significant in the (x)CdS/ZNs heterostructures, and it confirmed that CdS nanoparticles (in cubic phase) occupied the (101) and (002) crystal facets of ZNs with hexagonal wurtzite crystal phase. UV-Vis DRS results indicated that CdS nanoparticles decreased the band gap energy of ZNs (2.80-2.11 eV) and extended the photoactivity of ZNs to the visible light region. The vibrations of ZNs were not observed clearly in the Raman spectra of (x)CdS/ZNs due to the extensive coverage of CdS nanoparticles shielding the deeper-laying ZNs from Raman response. The photocurrent of (0.4) CdS/ZNs photoelectrode reached 33 μA, about 82 times higher than that for ZNs (0.4 μA, 0.1 V vs Ag/AgCl). The formation of an n-n junction at the (0.4) CdS/ZNs reduced the recombination of electron-hole pairs and increased the degradation performance of the as-prepared (0.4) CdS/ZNs heterostructure. The highest percentage removal of tetracycline (TC) in the sonophotocatalytic/photocatalytic processes was obtained by (0.4) CdS/ZNs under visible light. The quenching tests showed that O2•-, h+, and OH• were the main active species in the degradation process. The degradation percentage decreased negligibly in the sonophotocatalytic (84%-79%) compared to the photocatalytic (90%-72%) process after four re-using runs due to the presence of ultrasonic waves. For the estimation of degradation behavior, two machine learning methods were applied. The comparison between the ANN and GBRT models evidenced that both models had high prediction accuracy and could be used for predicting and fitting the experimental data of the %removal of TC. The excellent sonophotocatalytic/photocatalytic performance and stability of the fabricated (x)CdS/ZNs catalysts made them promising candidates for wastewater purification.


Experiences and Perspectives on Stressors and Organizational Strategies to Bolster Resiliency During the COVID-19 Pandemic: A Qualitative Study of Health Care Workers at a Tertiary Medical Center.
This qualitative study included a sample of health care workers (HCWs) at a tertiary care center providing direct care to patients with COVID-19 to explore experiences and perceptions regarding care delivery during the COVID-19 pandemic as well as factors that helped HCWs cope with the challenges of the pandemic. Methods: Grounded theory methodology was used to conduct virtual focus groups with a semistructured interview guide May to June 2020. Results: We identified major themes related to (1) HCWs' emotions during the pandemic, (2) the perceived triggers of these feelings, (3) organizational factors that made HCWs feel more supported and appreciated, and (4) personal factors that helped HCWs cope with the pandemic. Conclusion: Results highlighted the stress and challenges associated with exposure to SARS-CoV-2. The findings can help inform interventions to support HCWs during pandemics and other crises.


Comparison of Maddrey Discriminant Function, Child-Pugh Score and Glasgow Alcoholic Hepatitis Score in predicting 28-day mortality on admission in patients with acute hepatitis.
Acute hepatitis (AH) in patients with chronic alcoholic liver disease is associated with high mortality. It is therefore vital to identify patients at greatest risk of mortality who may benefit from aggressive intervention. The scoring systems used to assess the severity of AH [Maddrey Discriminant Function (mDF), Child-Pugh Score (CPS) and Glasgow Alcoholic Hepatitis Score (GAHS)] have shown to be useful in determining severity and predicting mortality in these patients. The aim of this study was to compare three scoring systems in predicting 28-day mortality in AH on admission. Case notes of 82 patients with AH were reviewed on admission; mDF, CPS, GAHS were calculated and their outcome recorded on day 28. Thirty-six patients (44%) died within 28 days of admission. There was no difference in the age of patients who survived (51.2 ± 11 years) and those who died (52.6 ± 10 years). However, mDF, CPS and GAHS were significantly higher in dead patients (68.7 ± 56.4, 11.8 ± 1.3, 8.6 ± 1.6, respectively) compared to those who survived (36.2 ± 25.9, 10 ± 1.6, 7.6 ± 1.5, respectively) (p < 0.01). Similarly, prothrombin time (PT) was significantly higher in patients who died (23 ± 2 s) compared to those who survived (17.6 ± 0.7 s) (p = 0.007). There was no difference among three scoring systems in predicting 28-day mortality at the time of admission in patients with AH. In addition, increased PT, gastro-intestinal bleeding and advanced encephalopathy at presentation were associated with high mortality. Furthermore, rise in creatinine from admission increased risk of mortality.


Functional groups characteristics of EPS in biofilm growing on different carriers.
This study investigated extracellular polymeric substances (EPSs), including soluble EPS, loosely bound EPS and tightly bound EPS (TB-EPS), in biofilms growing on different carriers from a CANON system to elucidate their different compositions and characteristics. The zeta potentials of all EPS fractions of the two samples were decreased systematically. The soft combination packing (SCP) was more hydrophilic than activated carbon fiber (ACF), and it obtained a significantly higher biomass. However, Raman spectroscopy and Fourier transform infrared spectroscopy revealed the same EPS fraction had similar functional groups between two carriers. Especially for the TB-EPS, total amount and the contents of proteins and polysaccharides in the SCP sample were much higher than those in the ACF sample. Moreover, the TB-EPS fraction of the SCP sample had better bioflocculation activity compared with that of the ACF sample. Therefore the result demonstrated that the characteristics of EPS varied from carrier to carrier.


Incremental value of magnification and indocyanine green for parathyroid preservation in thyroid surgery.
To assess the promise of surgical magnification and of intraoperative indocyanine green (ICG) assisted near-infrared fluorescence (NIRF) in improving parathyroid identification and viability assessment during thyroidectomy. Prospective comparative study. Parathyroid gland identification sequentially assessed by naked eye, surgical microscopy, and by NIRF imaging following ICG administration (5 mgIV). Parathyroid perfusion/vitality reassessed end-surgery by ICG-NIRF. An expected total of 104 parathyroid glands were assessed in 35 patients (17 total-thyroidectomy, 18 hemi-thyroidectomy). 54/104 (51.9%) were identified by naked eye, and sequentially greater numbers identified by microscope magnification (n = 61; 58.7%; p = 0.33), and by ICG-NIRF (n = 72; 69.2%; p = 0.01). ICG-NIRF detected additional parathyroid glands in 16/35 patients (45.7%). Confident identification of at least one parathyroid remained unachieved in 5/35 by naked eye, in 4/35 by microscopic magnification, and in no patient by ICG-NIRF. ICG-NIRF indicated end-of-surgery devascularization in 12/72 glands and informed decisions regarding gland implantation. Significantly greater parathyroid glands are identified and preserved with surgical magnification and with ICG-NIRF. Both techniques merit routine adoption for thyroidectomy.


Evidence for the involvement of platelet glycoproteins other than GP Ib in heparin-associated thrombocytopenia and thrombosis.
Heparin-associated thrombocytopenia and thrombosis (HATT) is a potentially fatal complication of heparin therapy which is characterized by a progressive fall in the platelet count associated with arterial or venous thrombosis. The etiology is consistent with the development an antibody which, in the presence of heparin, induces intravascular platelet aggregation. Biochemical analysis has demonstrated that the platelet membrane glycoprotein (GP) Ib binds heparin. Recent studies have shown that polyclonal antisera or monoclonal antibodies to GP Ib can inhibit platelet aggregation induced by HATT plasma in the presence of heparin implicating GP Ib as the site of heparin-antibody interaction. The Bernard-Soulier syndrome (BSS) is an inherited bleeding disorder in which the platelets fail to adhere to exposed subendothelium due to a deficiency of GP Ib. We have used the platelets from a patient with documented BSS to further investigate the role of GP Ib in the heparin- dependent platelet aggregation induced by the plasma of three patients with HATT. We have shown that platelet aggregation by HATT plasma in the presence of heparin occurred as readily with BSS platelets as with normal donor platelets. These results indicate that glycoprotein Ib cannot be the only site of platelet-heparin-antibody interactions.


Cognitive function assessment and comparison on lateral ventricular tumors resection by the frontal transcortical approach and anterior transcallosal approach respectively in children.
Currently, there are few studies on cognitive impairment caused by neurosurgery, and there have been no studies on cognitive impairment after resection of lateral ventricular tumors in children. Previously, our research team has reported that the frontal transcortical approach can impair cognitive function. In this study, we explored which functions would be damaged by the transcallosal approach and compared the cognitive function changes caused by the two surgical approaches, so as to provide a theoretical basis for the selection of pre-operative surgical approaches. The authors prospectively collected pediatric patients with lateral ventricular tumors who had undergone surgical resection through the frontal transcortical approach and anterior transcallosal approach in Beijing Tiantan Hospital from November 2012 to May 2017. The inclusion criteria according to the Children Wechsler Scale requirements and clinical performance were formulated. Wechsler Intelligence Scale for Children®-fourth edition: Chinese version (WISC-IV) was adopted for general intelligence and cognitive function assessment in the study. In addition, the resting-state functional magnetic resonance imaging (resting-state fMRI) and diffusion tensor imaging (DTI) were carried out to measure the level of co-activation and to explore the functional connectivity between the brain regions at the pre-operative period and 6-month follow-up in post-operation. A total of 30 patients were enrolled. Gross total resection was achieved in all patients, and no severe post-operative complications were observed. The frontal transcortical approach was applied in 19 patients, and the transcallosal approach was conducted for 11 patients. Compared with the pre-operative indices of WISC-IV, patients generally had a lower level of indices of the WISC-IV in post-operation. In patients accepting lateral ventricular tumors resection through the anterior transcallosal approach, the total IQ was declined to M = 84.82, SD = 8.072 from M = 93.27, SD = 6.635 within the 6-month convalescence. The data of working memory (t = - 2.990, p = 0.002) and total IQ (t = - 2.205, p = 0.028) pre- and post-operative showed statistical significance. But in the comparison of two surgical approaches, it was found that IQ had no statistical difference in WISC-IV tasks data. Previous studies suggest that the frontal transcortical approach impair perceptual reasoning, processing speed, and IQ, while this study indicates that the anterior transcallosal approach impairs patients' working memory and IQ. Both approaches make equal damage to IQ. Through comparing the two surgical approaches, it can be known that the anterior transcallosal approach cannot replace the frontal transcortical approach. The protection of cognitive function should be considered as one of the bases for neurosurgeons to select the operative approach before the operation. However, in an actual situation, the specific approach should be carefully selected by comprehensive consideration.


Adsorption of urease on PE-MCM-41 and its catalytic effect on hydrolysis of urea.
Pore-expanded MCM-41 (PE-MCM-41) silica exhibits a unique combination of high specific surface area (ca. 1000 m(2)/g), pore size (up to 25 nm) and pore volume (up to 3.5 cm(3)/g). As such, this material is highly suitable for the adsorption of large biomolecules. The current study focused primarily on the application of PE-MCM-41 material as suitable host for urease (nickel-based large metalloenzyme) in controlled hydrolysis of urea. Urease adsorbed on PE-MCM-41, regular MCM-41 and silica gel (SGA) were used as catalysts for urea hydrolysis reaction. Adsorption studies of urease on these materials from aqueous solution at pH 7.2 revealed that the adsorption capacity of PE-MCM-41 (102 mg/g) is significantly higher than that of MCM-41 (56 mg/g) and SGA (21 mg/g). The equilibrium adsorption data were well fitted using the Langmuir-Freundlich model. Furthermore, the kinetic study revealed that the uptake of urease follow the pseudo-first order kinetics. The in vitro urea hydrolysis reaction on pristine urease and different urease-loaded catalysts showed that the rate of hydrolysis reaction is significantly slower on U/PE-MCM-41 compared to that of bulk urease and urease on MCM-41 and SGA. This technique could be an alternative means to the use of urease inhibitors to control the ammonia release from urea fertilizer.


Surgically induced astigmatism with superior and temporal incisions in cases of with-the-rule preoperative astigmatism.
To evaluate surgically induced astigmatism (SIA), postoperative astigmatism, and uncorrected visual acuity (UCVA) after cataract surgery with superior corneal, superior scleral, and temporal corneal 4.0 mm sutureless incisions in cases of preoperative with-the-rule (WTR) astigmatism. Hopital des Quinze-Vingts, Paris, France. This prospective evaluation included patients having phacoemulsification with foldable lens implantation through a 4.0 mm incision. Patients with preoperative WTR astigmatism were randomly assigned to 1 of 3 incisions: superior corneal (Group 1), superior scleral (Group 2), or temporal corneal (Group 3). All patients had autokeratometry preoperatively and postoperatively (1 day, 1 week, 1 month, 1 year). Surgically induced astigmatism using the vector method, postoperative astigmatism, and UCVA (patients whose spherical equivalent was with +/- 1 diopter) were evaluated. Ninety patients were included in the study; there were 30 in each incision group. One year postoperatively, Group 1 had 1.52 diopters (D) of SIA and 1.36 D of postoperative astigmatism; 53.5% of patients had a UCVA of 20/32 or better, Group 2 had 0.69 D of SIA (P < .05) and 0.67 D of postoperative astigmatism (P < .05); 82.7% of patients had a UCVA of 20/32 or better (P < .05). Group 3 had 0.69 D (P > .05), 0.98 D (P < .05), and 79.3% (P > .05), respectively. In this study, the superior corneal incision produced significant SIA, leading to high postoperative astigmatism and poor UCVA. The scleral and temporal incisions produced minimal SIA and good UCVA.


Sequential changes in plasma selenium concentration after cadaveric renal transplantation.
Previous investigations have shown that plasma selenium concentrations are significantly lower in patients with established chronic graft nephropathy (CGN) than in healthy transplant controls. The aims of this study were to determine when in the transplant process low selenium concentrations become apparent and to explore the relationship between selenium levels and risk factors for CGN. Plasma selenium concentrations were measured in 40 patients (20 receiving cyclosporin, 20 receiving tacrolimus) undergoing transplantation. Samples were obtained immediately before transplantation and at 3, 6 and 12 months after transplantation. A low plasma selenium concentration was found in 30 patients at the time of transplantation but this had normalized in the majority of patients by 3 months. Plasma selenium concentrations at 3, 6 and 12 months were significantly higher than baseline values for both treatment arms, but were significantly lower at 3 months in patients who experienced either clinical acute rejection (CAR) or cytomegalovirus (CMV) infection during the preceding months. Low plasma selenium concentrations are common at the time of transplantation but appear to normalize thereafter. The identification of low selenium levels in patients who experience CAR or CMV (two important risk factors for clinically apparent CGN) suggests that the relationship between selenium and CGN warrants further investigation.


Endotoxin stimulates glycogenolysis in the liver by means of intercellular communication.
Escherichia coli endotoxin (lipopolysaccharide) was shown to increase glycogenolysis in the perfused liver 2-3-fold. In isolated parenchymal liver cells, however, endotoxin did not influence glycogenolysis, whereas stimulation by endotoxin of glycogenolysis in the perfused liver could be blocked by aspirin. This suggests that the effect of endotoxin on liver glycogenolysis is mediated by eicosanoids. The amount of prostaglandin D2 (which is the major prostanoid formed by Kupffer cells) in the liver perfusates was increased 5-fold upon endotoxin addition, with a time course which preceded the increase in glucose output. It is concluded that endotoxin stimulates glycogenolysis in the liver by stimulating prostaglandin D2 release from Kupffer cells, with a subsequent activation of glycogenolysis in parenchymal liver cells. This mechanism of intercellular communication may be designed to provide the carbohydrate source of energy necessary for the effective destruction of invaded microorganisms, by phagocytic cells, including the Kupffer cells.


Constant-Load Exercise Versus High-Intensity Interval Training on Aerobic Fitness in Moderate-to-Severe Asthma: A Randomized Controlled Trial.
The effects of high-intensity interval training (HIIT) on dyspnea and aerobic fitness in adults with asthma are poorly understood. To compare constant-load exercise (CLE) versus HIIT for improvements in dyspnea symptoms and clinical control in adults with moderate-to-severe asthma. Participants were randomized into 2 groups: CLE (n = 27; started with 70% of maximal watts [Wmax] obtained during cardiopulmonary exercise testing [CPET]) and HIIT (n = 28; started with 80% and increased until 140% Wmax). Exercise training lasted 12 weeks (twice/week, 40 minutes/session on a cycle ergometer), and the intensity was based on CPET. Clinical asthma control (Asthma Control Questionnaire), aerobic fitness (the peak of oxygen uptake), health-related quality of life (Asthma Quality of Life Questionnaire), physical activity levels (PAL; accelerometer), symptoms of anxiety and depression (Hospital Anxiety and Depression Scale questionnaire), and dyspnea were evaluated before and after the intervention. Systemic and airway inflammation were also assessed. Two-way analysis of variance and χ2 tests were used for comparisons. Sixteen participants dropped out during the interventions and returned for the final evaluations. The CLE and HIIT groups showed similar improvements in aerobic fitness. The HIIT group had lower dyspnea and fatigue perception scores and higher PAL than the CLE group (P < .05) and clinical improvements in the psychosocial distress. In addition, only the HIIT group achieved a minimal clinically important difference in asthma symptoms. There was no change in the systemic and airway inflammation (P > .05). Both interventions promoted similar improvements in aerobic fitness; however, HIIT induced a greater reduction in dyspnea and fatigue perception. Similar responses were observed for other variables.


Placental location and risk of retained placenta in women with a previous cesarean section: A population-based cohort study.
Some studies have shown that women with a previous cesarean section, compared with women with a previous vaginal delivery, have an increased risk of retained placenta during a subsequent vaginal delivery. It is unknown whether this is mediated by anterior placental location, when the placenta might cover the uterine scar. The aim of this study was to evaluate whether the increased risk of retained placenta in women with a previous cesarean section is mediated by anterior placental location. This is a population-based cohort study, with data from the regional population-based Stockholm-Gotland Obstetric Cohort, Sweden, from 2008 to 2014. The overall study population included 49 598 women with a vaginal second delivery, where adequate information about placental location from the second-trimester ultrasound scan was available. For the main analysis, including the 3921 women with a previous cesarean section, we calculated the relative risk of retained placenta in women with an anterior placental location, using women with non-anterior placental locations as reference. Relative risks were calculated as odds ratios (OR) with 95% CI. In a second model, adjustments were made for maternal age, height, country of birth, smoking in early pregnancy, infant sex, and in vitro fertilization. In the overall study population, the rate of retained placenta at the second delivery was 2.0%. The proportion of women with a retained placenta was higher among women with a previous cesarean compared with those with a previous vaginal delivery (3.4% vs 1.9%; P < .0001). In the main analysis, including women with a previous cesarean section, the risk for retained placenta was not increased with anterior compared with non-anterior placental location (OR 0.84, 95% CI 0.60-1.20). Adjustments did not affect the estimates in a significant way. The increased risk of retained placenta in women with a previous cesarean section is not mediated by anterior placental location.


Impact of mobile phone intervention on intermittent preventive treatment of malaria during pregnancy in Burkina Faso : A pragmatic randomized trial.
Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine for pregnant women (IPTp-SP) coverage remains far below the desirable goal of at least three doses before delivery. This study evaluates an innovative intervention using mobile phones as a means of increasing coverage for the third dose of IPTp-SP. This study in Burkina Faso was designed as an open-label, pragmatic, two-arm, randomised trial. Pregnant women who attended antenatal clinic (ANC) visits were included at their first ANC visit and followed until delivery. The intervention was built around the use of mobile phones as means ensuring direct tracking of pregnant women. Two hundred and forty-eight (248) pregnant women were included in the study. The proportion of women who received at least three doses of IPTp-SP was 54.6 %. In the intervention group, 54.1 % of women received at least three doses of IPTp-SP versus 55.1 % in the control group, a non-significant difference (adjusted odds ratio "aOR", 0.86 ; 95 % confidence interval "95 % CI", 0.49-1.51). Women in the intervention group were more likely to carry out their ANC visits in a timely manner than those in the control group (aOR, 3.21 ; 95 % CI, 1.91-5.39). While mobile phone intervention did not increase the proportion of women receiving three doses of IPTp-SP, it did help to increase the proportion of timely ANC visits. PACTR202106905150440.


Waist-to-Height Ratio Is a Better Predictor of Hyperuricemia than Body Mass Index and Waist Circumference in Chinese.
Our study aimed to compare the predictive value of waist-to-height ratio (WHtR) for hyperuricemia with body mass index (BMI) and waist circumference (WC). This is a cross-sectional study of 9,206 South China residents (male/female: 4,433/4,773) aged 18-89 years recruited during years 2009-2010 and 2014-2015. Anthropometric measurements, serum uric acid, blood pressure, and plasma glucose, lipid, lipoprotein, and transferase levels were measured. Receiver operating characteristic (ROC) curve and logistic regression analyses were applied to evaluate the predictive values of anthropometric indices for hyperuricemia. The prevalence of hyperuricemia increased significantly with higher quartiles of WHtR in both genders. The best cutoff points of WHtR to predict hyperuricemia are 0.52 for men and 0.49 for women and differed between different BMI and WC stratums. Although there was no significant difference between the area under the ROC curves, subjects in the top quartile of WHtR were at a highest risk of hyperuricemia (p for linear trend <0.001) and the adjusted ORs of WHtR (2.24-2.77 in men and 2.66-4.95 in women) were higher than those of BMI or WC in the multivariable regression model. WHtR was an independent and better predictor of hyperuricemia compared with BMI and WC.


Synthesis and evaluation of changes induced by solvent and substituent in electronic absorption spectra of some azo disperse dyes.
Five azo disperse dyes were prepared by diazotizing 4'-aminoacetophenone and p-anisidine and coupling with varies N-alkylated aromatic amines. Characterization of the dyes was carried out by using UV-vis, FTIR and 1H NMR spectroscopic techniques. The electronic absorption spectra of dyes are determined at room temperature in fifteen solvents with different polarities. The solvent dependent maximum absorption band shifts, were investigated using dielectric constant (ɛ), refractive index (n) and Kamlet-Taft polarity parameters (hydrogen bond donating ability (α), hydrogen bond accepting ability (β) and dipolarity/polarizability polarity scale (π*)). Acceptable agreement was found between the maximum absorption band of dyes and solvent polarity parameters especially with π*. The effect of substituents of coupler and/or diazo component on the color of dyes was investigated. The effects of acid and base on the visible absorption maxima of the dyes are also reported.


Atrial flutter in myotonic dystrophy type 1: Patient characteristics and clinical outcome.
The prevalence and the incidence of atrial flutter in patients with myotonic dystrophy type 1 (DM1) and the most appropriate strategies for its management are unknown. We retrospectively included in the DM1 Heart Registry 929 adult patients with DM1 admitted to our Institutions between January 2000 and September 2013. We selected patients presenting with atrial flutter and analysed data relative to the occurrence of arterial thromboembolism, severe bradyarrhythmias and atrial flutter recurrences. Atrial flutter was present in 79 of the 929 patients included in our Registry, representing a 8.5% prevalence. Patients with atrial flutter were older, had a higher muscular disability rating scale score and had higher prevalence of other cardiac manifestations of DM1. Sixty patients presented with a first episode of atrial flutter, representing a 4.6% incidence. Severe bradyarrhythmias requiring permanent pacing were present in 4 patients (6.7%). Over a 53 ± 28 months mean follow-up duration, 2 patients (3.3%) had ischaemic stroke and 12 (20%) had atrial flutter recurrences. Patients who underwent radiofrequency ablation were more frequently free of atrial flutter recurrence than other patients (95 vs. 61%; HR = 0.17; P = 0.04). Atrial flutter is a common manifestation of DM1, potentially complicated by arterial thromboembolism or severe bradyarrhythmias. Radiofrequency catheter ablation is associated with a lower risk for recurrences.


Conformational analysis of ulvans from Ulva fasciata and their anticoagulant polycarboxylic derivatives.
This study investigates conformational aspects of ulvans (F2) and their polycarboxyl derivatives obtained through periodate-chlorite oxidation (C3) followed by DEAE-Sephacel fractioning (C3b and C3c). Size exclusion chromatography coupled with laser light scattering and viscometric detection, in addition to circular dichroism (CD) and molecular modeling analyses, suggested that F2 had a compact sphere conformation with a helical motif as secondary structure. In contrast, all the polycarboxyl ulvans showed a random coil conformation, although C3c (NaSO3- 21.0%; COO- 1.81 mmol·g-1; Mw 18 kg·mol-1) had a more rigid and constrained backbone than C3 (NaSO3- 21.0%; COO- 1.81 mmol·g-1; Mw 49 kg·mol-1), largely due to its higher sulfate and carboxyl content. Despite the higher ionic character of C3c, its anticoagulant activity (ACA), determined by activated partial thromboplastin time (APTT) assay, was not improved compared to that of C3. Moreover, C3b (NaSO3- 14.1%; COO- 1.23 mmol·g-1; Mw 8.1 kg·mol-1) had higher activity than F2 (NaSO3- 20.6.%; COO- 0.36 mmol·g-1; Mw 123 kg·mol-1), even with its lower sulfate content and molar mass. These results suggest that the ACA of polycarboxyl ulvans relies on carboxyl and sulfate content and may depend, in addition, on a proper flexible conformation.


Suprascapular nerve palsy secondary to spinoglenoid cysts: results of arthroscopic treatment.
The purpose of this study was to investigate the results of arthroscopic treatment in 14 patients with suprascapular nerve palsy secondary to spinoglenoid ganglion cysts. Fourteen patients underwent arthroscopic decompression of ganglion cysts associated with suprascapular neuropathy. The most common presenting symptoms were pain and weakness, which lasted an average of 7.5 months. Ten of 14 patients were noted on examination to have atrophy, and all 14 patients had weakness of the infraspinatus. Magnetic resonance imaging (MRI) showed spinoglenoid ganglion cysts in all 14 patients; average cyst size was 3 cm. MRI revealed labral pathology in 12 of 14 cases; labral pathology was identified intraoperatively in all 14 patients. Postoperatively, the average Simple Shoulder Test (SST) score was 11.5 (12 maximum), which was improved from an estimated preoperative score of 4.3. Improvement in external rotation strength was seen in 100% of patients who were examined postoperatively. No patients were taking pain medicine at latest follow-up. No complications were reported, and there were no clinical or symptomatic recurrences at an average follow-up of 51 months. Arthroscopic treatment of patients with spinoglenoid ganglion cysts is safe and effective, resulting in good clinical outcomes. In our study of 14 patients, no recurrences were seen at an average of 51 months of follow-up. Level of Evidence: Level IV, therapeutic case series. Level IV, therapeutic case series.


Inflammatory cytokine responses to synthetic extracellular matrix injection to the vocal fold lamina propria.
We determined cytokine profiles for tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, IL-1alpha, and IL-1beta after injection of a synthetic extracellular matrix into the vocal fold lamina propria. Transcript expression of inflammatory cytokines was measured with real-time polymerase chain reaction on postoperative days 1, 3, 5, 10, and 21 in 25 rabbits that underwent bilateral vocal fold biopsy with Extracel-LG (Carbylan-GSX 5%) immediately injected into the wound in the left vocal fold and saline solution injected into the wound in the right vocal fold. Two unwounded normal rabbit larynges were also harvested for controls. Significantly elevated levels of TNF-alpha, IL-1beta, and IL-6 were measured on day 3 in a comparison between Extracel-LG-injected vocal folds and saline solution-injected control vocal folds and between Extracel-LG-injected vocal folds and normal vocal folds. All cytokine levels returned to baseline by day 21. A mild short-term inflammatory response was measured early after injection of a synthetic extracellular matrix into the vocal fold lamina propria.


A survey of potential huperzine A natural resources in China: the Huperziaceae.
The Huperziaceae is comprised of two genera, Huperzia and Phlegmariurus. Because of the content of Lycopodium alkaloids like huperzine A, which are used to treat a number of human ailments, plants of the Huperziaceae are experiencing a rapid decline in China, mostly due to over-harvesting. Because of this trend, we engaged from 1995 to 2001 in an investigation of the natural resources of the Huperziaceae in China. The main objectives of this study were: to catalog Huperziaceae plant resources including the occurrence, general distribution, and abundance of the various Huperziaceae species in China; and to determine traditional use and pharmaceutical values of each species. Twenty-nine species, 2 varieties, and 2 forma of Huperzia and 19 species of Phlegmariurus were identified through field investigation, collection, visits with local traditional doctors, and review of specimens in herbaria and of the literature. Ethnobotanical studies of these plants revealed that 33 of these species are used by the local communities for medicinal purposes. One species, Huperzia serrata, is one of the most popular. As a result, it is observing the greatest decline, mandating a change in collection practice and general attitude towards these plants. Introduction of conservation plans and training of the local communities regarding appropriate collection practices of these plants and their marketing in China are required to reverse the trend of decline among these species. In addition, development of cultivation or other propagation practices, such as in vitro propagation, would have the added benefits of socio-economic uplift of the local communities and sustainability of this important source of huperzine A.


Adenomatous hyperplasia in the vicinity of small hepatocellular carcinoma.
The nodular lesions seen in the noncancerous areas of the 80 consecutively resected small hepatocellular carcinoma associated with cirrhosis were pathomorphologically studied. A total of 51 nodular lesions were found, and they were classified into the following four groups: large regenerative nodule (30 nodules), adenomatous hyperplasia (12 nodules), atypical adenomatous hyperplasia (4 nodules) and adenomatous hyperplasia containing cancerous foci (5 nodules). Grossly, all large regenerative nodules were well demarcated, but some of the adenomatous hyperplasia group were vaguely nodular. Atypical adenomatous hyperplasia and adenomatous hyperplasia containing cancerous foci accounted for 43% of the adenomatous hyperplasia group found in the vicinity of the 16 resected hepatocellular carcinoma (20%) out of 80 cases. The mean size (+/- S.D.) of the adenomatous hyperplasias containing cancerous foci, 15.8 +/- 2.2 mm, was significantly larger than 10.1 +/- 2.6 mm of the adenomatous hyperplasias p less than 0.01). All adenomatous hyperplasias containing cancerous foci and 75% of the atypical adenomatous hyperplasias demonstrated a marked fatty change, but none of the large regenerative nodules were accompanied by any fatty changes. This study demonstrated the morphological transition from adenomatous hyperplasia to hepatocellular carcinoma that was suggestive of multistep hepatocarcinogenesis. As a result, it is predicted that approximately 20% of all hepatocellular carcinomas may have the potential for being of multicentric origin and that approximately 40% of adenomatous hyperplasias may undergo malignant transformation, but it is difficult to estimate the exact number of incidences. The presence of varying degrees of fatty change may be one of the significant morphological markers for a malignant transformation from adenomatous hyperplasia to hepatocellular carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of enzymes homologous to isocitrate dehydrogenase that are involved in coenzyme B and leucine biosynthesis in methanoarchaea.
Two putative Methanococcus jannaschii isocitrate dehydrogenase genes, MJ1596 and MJ0720, were cloned and overexpressed in Escherichia coli, and their gene products were tested for the ability to catalyze the NAD- and NADP-dependent oxidative decarboxylation of DL-threo-3-isopropylmalic acid, threo-isocitrate, erythro-isocitrate, and homologs of threo-isocitrate. Neither enzyme was found to use any of the isomers of isocitrate as a substrate. The protein product of the MJ1596 gene, designated AksF, catalyzed the NAD-dependent decarboxylation of intermediates in the biosynthesis of 7-mercaptoheptanoic acid, a moiety of methanoarchaeal coenzyme B (7-mercaptoheptanylthreonine phosphate). These intermediates included (-)-threo-isohomocitrate [(-)-threo-1-hydroxy-1,2, 4-butanetricarboxylic acid], (-)-threo-iso(homo)(2)citrate [(-)-threo-1-hydroxy-1,2,5-pentanetricarboxylic acid], and (-)-threo-iso(homo)(3)citrate [(-)-threo-1-hydroxy-1,2, 6-hexanetricarboxylic acid]. The protein product of MJ0720 was found to be alpha-isopropylmalate dehydrogenase (LeuB) and was found to catalyze the NAD-dependent decarboxylation of one isomer of DL-threo-isopropylmalate to 2-ketoisocaproate; thus, it is involved in the biosynthesis of leucine. The AksF enzyme proved to be thermostable, losing only 10% of its enzymatic activity after heating at 100 degrees C for 10 min, whereas the LeuB enzyme lost 50% of its enzymatic activity after heating at 80 degrees C for 10 min.


Development of preoperative planning software for transforaminal endoscopic surgery and the guidance for clinical applications.
Preoperative planning is of great importance for transforaminal endoscopic techniques applied in percutaneous endoscopic lumbar discectomy. In this study, a modular preoperative planning software for transforaminal endoscopic surgery was developed and demonstrated. The path searching method is based on collision detection, and the oriented bounding box was constructed for the anatomical models. Then, image reformatting algorithms were developed for multiplanar reconstruction which provides detailed anatomical information surrounding the virtual planned path. Finally, multithread technique was implemented to realize the steady-state condition of the software. A preoperative planning software for transforaminal endoscopic surgery (TE-Guider) was developed; seven cases of patients with symptomatic lumbar disc herniations were planned preoperatively using TE-Guider. The distances to the midlines and the direction of the optimal paths were exported, and each result was in line with the empirical value. TE-Guider provides an efficient and cost-effective way to search the ideal path and entry point for the puncture. However, more clinical cases will be conducted to demonstrate its feasibility and reliability.


Time-courses of the appearance/disappearance of nuclear androgen + receptor complexes in the brain and adenohypophysis following testosterone administration/withdrawal to castrated male rats: relationships with gonadotropin secretion.
We characterized the temporal dynamics of brain and pituitary cell nuclear androgen receptor binding and serum androgen and gonadotropin levels associated with the implantation and removal of testosterone (T)-filled Silastic capsules into performed s.c. flank pouches of castrated, awake male rats. These capsules produced serum T levels in the physiologic range. The number of cell nuclear androgen + receptor complexes, as measured in an exchange assay using [3H]R1881, increased 15-fold at 0.5 h after capsule insertion in the HPAS (combined hypothalamus, preoptic area, amygdala and septum) and anterior pituitary gland, but then showed a second progressive rise within the next 8 h. This pattern suggests that T exerts an initial action in the tissues to alter the affinity and/or number of available androgen receptors. There was a lag time of 2-4 h to the first indication of negative feedback suppression of LH secretion. Serum LH levels declined only slightly at 4 h after capsule insertion but continued to fall thereafter, reaching undetectable values by 24 h. In contrast, serum FSH levels declined only slightly after 24 h of T exposure. After removal of the T capsules, serum T levels declined to castrate values within 2 h at which time the level of androgen + receptor complexes had fallen to 60% in the brain and pituitary. Serum LH and FSH concentrations were unchanged at 2 h after capsule removal, but rose significantly within the next 2 h. The data indicate that the occupation of androgen receptors rapidly changes in response to variations in circulating T in a fashion that implicates their involvement in the expression of this steroid's negative feedback actions on gonadotropin secretion.


Digital pattern recognition-based image analysis quantifies immune infiltrates in distinct tissue regions of colorectal cancer and identifies a metastatic phenotype.
Several studies in colorectal cancer (CRC) indicate a relationship between tumour immune infiltrates and clinical outcome. We tested the utility of a digital pattern recognition-based image analysis (DPRIA) system to segregate tissue regions and facilitate automated quantification of immune infiltrates in CRC. Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed immunohistochemically. Genie pattern recognition software was used to segregate distinct tissue regions in combination with image analysis algorithms to quantify immune cells. Immune infiltrates were observed predominately at the invasive margin. Quantitative image analysis revealed a significant increase in the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31 (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared with tumour cell mass. A direct comparison between non-metastatic primary CRC (MET-) and primary CRC that resulted in metastasis (MET+) showed an immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of CD8 (P<0.05) cells in the stroma of MET+ compared with MET- samples. By combining immunohistochemistry with DPRIA, we demonstrate a potential metastatic phenotype in CRC. Our study accelerates wider acceptance and use of automated systems as an adjunct to traditional histopathological techniques.


Low-level laser reduces the production of TNF-α, IFN-γ, and IL-10 induced by OVA.
Delayed, or type IV, hypersensitivity reactions are a useful model to study the effects of new substances on the immune system. In this study, the experimental model of the delayed type hypersensitivity (DTH) reaction to ovalbumin (OVA) was used to evaluate the immunomodulating effects of low-level laser therapy (LLLT), which is used as an adjuvant therapy in medicine, dentistry, and physical therapy because of its potential anti-inflammatory and analgesic effects observed in several studies. The effects of LLLT (λ 780 nm, 0.06 W/cm(2) of radiation, and fluency of 3.8 J/cm(2)) in reaction to ovalbumin in Balb/C mice were examined after the induction phase of the hypersensitivity reaction. The animals treated with azathioprine (AZA), the animals that received a vehicle instead of ovalbumin, and those not immunized served as controls (n = 6 for each group). Footpad thickness measurements and hematoxylin-eosin histopathological exams were performed. Proliferation tests were also performed (spontaneous, in the presence of concanavalin A and ovalbumin) to determine the production in mononuclear cells cultures of tumor necrosis factor-alpha (TNF-α), INF-γ, and IL-10. In the group of animals irradiated with lasers and in the group treated with AZA, footpad thickness measurements were significantly reduced in comparison to the control group (p < 0.05). This reduction was accompanied by a very significant reduction in the density of the inflammatory infiltrate and by a significant reduction in the levels of TNF-α, INF-γ, and IL-10. LLLT radiation was shown to have an immunomodulating effect on DTH to OVA in Balb/C mice.


Risk of sexually transmitted infections among Mayan women in rural Guatemala whose partners are migrant workers.
HIV and sexually transmitted infection (STI) are of concern in Mayan districts of Guatemala in which labor migration is common. This study assessed whether the migration status of men is associated with reported STI symptoms among their female primary partners. In a multivariate analysis of survey data taken from a larger Mayan sexual health study, the odds of reporting STI symptoms were twofold higher among women who reported that their partner migrated (OR 2.08, 95 % CI, 1.16-3.71), compared to women whose partners did not. Women from the Mam and Kaqchikel ethnolinguistic groups reported higher rates of STI symptoms after adjustment for their partners' migration status.


Impact of retinal vein occlusion on cardiovascular events in elderly Japanese patients.
To assess the relationship between retinal vein occlusion (RVO) and the incidence of cardiovascular (CV) events.This was a single-institution, retrospective cohort study. We enrolled 57 patients diagnosed with RVO between January 2012 and December 2019, and 125 non-RVO patients who had undergone cataract surgery by a single surgeon between January and April 2012. We compared the relative risk and incidence rate ratio of CV events between the 2 groups. In addition, survival analysis was performed to calculate the hazard ratio (HR) using the Cox proportional hazards model. RVO, age, sex, blood pressure, body mass index, presence of diabetes, blood sample data, and smoking were considered confounders.The mean observation period (± standard deviation) for the RVO and non-RVO groups was 2.68 ± 2.04 and 2.81 ± 2.70 years, respectively. Seven CV events were observed in the RVO group and 2 in the non-RVO group. Relative risk and incidence rate ratio were 7.68 (95% confidence interval [CI]: 1.65-35.8) and 8.07 (95% CI: 1.54-79.6), respectively. Multivariate analysis revealed that the RVO group had a high HR for CV events (HR: 16.13 [95% CI: 2.29-113.74]) and older age (HR: 1.26 [95% CI: 1.06-1.49]).RVO can predict future CV events, especially in the elderly population. Fundus observations should be shared between ophthalmologists and internists to prevent future CV events.


Milk proteins and iron absorption: contrasting effects of different caseinophosphopeptides.
Clusters of phosphoserine residues in cow milk caseins bind iron (Fe) with high affinity. Casein inhibits Fe absorption in humans, but protein hydrolysis lessens this effect. Phosphopeptides from different caseins gave conflicting results on Fe absorption; release of phosphate residues by intestinal alkaline phosphatase could be a key point of that metabolism. The objectives of this study were to compare the absorption of Fe complexed to caseinophosphopeptides (CPP) of the main cow milk caseins beta-casein (beta-CPP) and alpha(s)-caseins (alpha(s1)-CPP) and to assess the role of alkaline phosphatase on this absorption. Two experimental models were used: an in vivo perfused rat intestinal loop and an in vitro Caco-2 cell culture model. In addition, we determined the effect of an intestinal phosphatase inhibitor on these various forms of Fe. Gluconate Fe was used as control. In both models, uptake and net absorption of Fe complexed to CPP from alpha(S1)-caseins were significantly lower than from Fe complexed to beta-CPP. Inhibition of the intestinal phosphatase significantly increased the uptake and the absorption of Fe complexed to beta-CPP without effect on the other forms of Fe. These results confirm the enhancing effect of beta-casein and its CPP on Fe absorption. The differences between CPP could be explained by their structural and/or conformational features: binding Fe to alpha(S1)-CPP could impair access to digestive enzymes, whereas beta-CPP-bound Fe is better absorbed than its free form. The differences in protein composition between cow and breast milk, which does not contain alpha-casein, could explain some of their differences in Fe bioavailability.


Iodine deficiency disorders in 15 districts of India.
A multicentre study to assess iodine deficiency disorders (goitre and deaf-mutism/cretinism) in 1, 45, 264 children (6 - <12 years old) from 15 districts of ten states was carried out during 1997-2000. Urinary iodine excretion was also determined in 27481 children, while iodine content was estimated in 5881 samples of edible salt. The sampling methodology followed was a "30 cluster survey". The overall prevalence of goitre was 4.78% (4.66% of grade I and 0.12% of grade II) amongst the children examined. The highest prevalence of 31.02% goitre was observed in Dehradun district, while the lowest prevalence of 0.02% goitre was recorded in Bishnupur and Badaun districts. The overall prevalence of cretinism among children examined from seven districts was 0.072% whereas that of deaf-mutism was 0.27% among children examined from 8 districts. Median urinary iodine values was marginally less than the WHO cut-off values only in children of the 3 out of the 15 districts surveyed. Iodine content was found to be adequate in 55.45% of the salt samples. The results suggested a significant decline in the prevalence of goitre in most parts of the country.


Redistributional consequences of early childhood intervention.
Recently, early investment in the human capital of children from socially disadvantaged environments has attracted a great deal of attention. Programs of such early intervention, aimed at children's health and well-being, are spreading considerably in the US and are currently being tested in several European countries. In a discrete version of the Mirrlees model with a parents' and a children's generation, we model the intra-generational and the inter-generational redistributional consequences of such intervention programs. It turns out that the parents' generation loses whenever such intervention programs are implemented. Furthermore, the rich part of the children's generation always benefits. Despite the expectation that early intervention puts the poor descendants in a better position, our analysis reveals that the poor among the children's generation may even be worse off, if the effect of early intervention on their productivity is not large enough.


Preliminary Results from a Pragmatic Clinical Trial of MyPEEPS Mobile to Improve HIV Prevention Behaviors in Young Men.
Our study team developed the MyPEEPS Mobile App for improving HIV prevention behaviors in diverse young men. We conducted a randomized controlled trial and evaluated the preliminary outcomes in the first half (N=350) of our intended study sample. Higher self-efficacy for HIV prevention behaviors (p=0.0042) and more recent HIV tests in the past 3 months (p=0.0156) were reported by the intervention group compared to control. Numbers of condomless anal sex acts were lower among the intervention group for both insertive anal sex acts (p=0.0283) and receptive anal sex acts (p=0.0001). Preliminary results indicate that some sexual risk behaviors were reduced among the intervention group in the preliminary analytic sample.


Micronutrient Deficiencies in Patients With Heart Failure: Relationships With Body Mass Index and Age.
It is conceivable that lean patients (body mass index 18.5-24.9 kg/m(2)) with heart failure (HF) have low body weight due to low food consumption and that this may contribute to micronutrient deficiencies and to their poorer prognosis compared with overweight/obese patients. We hypothesized that lean patients have a greater number of inadequate micronutrient intakes (<50% of recommendations) than overweight/obese patients and that this also depends on age. Lean (n = 15) and overweight/obese (n = 49) patients underwent 24-hour diet and physical activity recall interviews. Inadequate essential micronutrient intakes were ubiquitous (intakes of 13 ± 1 of 27 micronutrients were inadequate) and did not depend on race, status, or access to supermarkets. Younger (40-64 y) lean patients had inadequate intakes of 20 ± 2 micronutrients, which was more than the other weight/age subgroups (all P < .01). Physical activity levels did not differ across weight and age groups. Patients with HF may be at risk of malnutrition due to numerous inadequate micronutrient intakes; younger lean patients may have an especially high risk. Future studies are needed to confirm these preliminary findings and to investigate the possibility that incorporating a micronutrient-dense meal plan will improve patient outcomes.


A comparison of the effects of different stretching methods on flexibility, muscle activity, and pain threshold in ballet dancers; a preliminary randomized controlled trial.
The purpose of this study is to compare the effects of stretching methods on flexibility, muscle activation, and pressure pain threshold in ballet dancers, and to suggest an effective stretching method. Thirty-three ballet dancers were randomized to the static stretching group (n = 11), muscle energy technique stretching group (n = 11), and vibration-assisted stretching group (n = 11). The angle of hip joint extension in arabesque, activation of the rectus femoris in devéloppé, and pressure pain threshold on the rectus femoris in the sitting position were measured to compare the effects of the different stretching methods. Paired t-test was used to compare the pre and post-intervention findings within each group and one-way analysis of variance to compare the difference in the amount of changes among the groups. The hip joint extension angles increased in all stretching methods (p < 0.05); however, vibration-assisted stretching and muscle energy technique stretching were more effective than static stretching (p < 0.05). The activation of the rectus femoris decreased in all groups (p < 0.05); however the muscle energy technique stretching group and vibration-assisted stretching group showed a significant decrease in muscle activation compared with the static stretching group (p < 0.05). The pressure pain threshold significantly improved only in the static stretching group (p < 0.05); and vibration-assisted stretching group (p < 0.05). Compared with static stretching and muscle energy technique stretching, vibration-assisted stretching is a beneficial method for improving flexibility, muscle activation, and pressure pain threshold in ballet dancers.


Evidence for a novel FMRFamide-related heptapeptide in the pulmonate snail Siphonaria pectinata.
Extracts of whole false limpets (Siphonaria pectinata) were analysed to determine their complement of FMRFamide-related peptides. As in other pulmonates, FMRFamide itself was found to account for only a portion of the immunoreactivity; the largest immunoreactive peptide peak eluted during HPLC under acidic conditions at the same position as a peak also found in other pulmonates. This major peak was resolved into two components by HPLC at neutral pH, and one component was identified as the heptapeptide amide, GDPFLRFamide, previously described from Lymnaea. The amino acid composition of the second component indicates that it is also a heptapeptide, but that it has two Asx (aspartic acid or asparaginyl) residues instead of the one found in the previously identified pulmonate heptapeptides.


Accumulation of risk markers predicts the incidence of sudden death in patients with chronic heart failure.
Sudden death is common in chronic heart failure (CHF). Risk stratification is the first step for primary prevention. To evaluate the use of risk markers for estimating sudden death risk. We prospectively examined 680 stable patients with CHF. Risk markers were evaluated using the Cox's proportional hazard model in a stepwise manner. Ejection fraction <30%, left ventricular end-diastolic diameter >60 mm, brain natriuretic peptide >200 pg/ml, non-sustained ventricular tachycardia, and diabetes were significantly associated with increased risk of sudden death. When the number of risk markers were included as co-variables, only "number of risk markers >or=3'' entered the model (hazard ratio 8.95, 95% confidence interval 4.57-17.52), while the effects of individual markers did not enter the model. The annual mortality from sudden death was 11% in patients with 3 or more risk markers and 1.4% in patients with 2 or less. Rather than particular risk markers, the number of accumulated risk markers was a more powerful predictor for sudden death in patients with CHF. The number of risk markers could be useful for risk stratification of sudden death.


Macrocephaly-cutis marmorata telangiectatica congenita: A case report and review of salient features.
Macrocephaly-cutis marmorata telangiectatica congenita is a recently recognized syndrome described mainly in the genetics literature. However, children with macrocephaly-cutis marmorata telangiectatica congenita are likely to present first to a dermatologist, with generalized cutis marmorata telangiectatica congenita as the main feature. These children are at risk of neurologic abnormalities and life-threatening complications. Therefore it is important for dermatologists to recognize this syndrome to monitor these children for potential complications. We report the case of a 2-year-old boy with macrocephaly-cutis marmorata telangiectatica congenita in association with dysmorphic facies, seizures, and facial and limb asymmetry, and we review the salient features of this syndrome.


Age-related oxidative decline of mitochondrial functions in rat brain is prevented by long term oral antioxidant supplementation.
A combination of antioxidants (N-acetyl cysteine, α-lipoic acid, and α-tocopherol) was selected for long term oral supplementation study in rats for protective effects on age-related mitochondrial alterations in the brain. Four groups of rats were chosen: young control (6-7 months); aged rats (22-24 months); aged rats (22-24 months) on daily antioxidant supplementation from 18 month onwards and young rats (6-7 months) on daily antioxidant supplementation from 2 month onwards. The brain mitochondrial functional parameters, status of antioxidant enzymes and accumulation of oxidative damage markers were measured in the four groups of rats. A significant decrease in complex IV activity and a loss of transmembrane potential and phosphorylation capacity along with an increased accumulation of oxidative damage markers and compromised antioxidant enzyme status were noticed in aged rat brain mitochondria as compared to that in young controls, but in aged rats supplemented with oral antioxidants the mitochondrial alterations were largely prevented. Antioxidant supplementation in young rats had no effect on mitochondrial parameters investigated in this study. The results have implications in biochemical and functional deficits of brain during aging as well as in neurodegenerative disorders.


On the microphthalmous Lathrobium Gravenhorst species of Turkey III. Two new species from central northern Anatolia, and an updated key to Turkish species (Coleoptera: Staphylinidae: Paederinae).
In this study, Lathrobium tokatense sp. n. (Tokat province) and L. amasiacum sp. n. (Amasya province), two new microphthalmous species of the genus Lathrobium s. str. from central northern Anatolia, are described and compared to closely related species, L. brignolii Bordoni, L. distortum and L. deforme Assing. Some specimens of the new species were obtained using subterranean pitfall traps in the mesovoid shallow substratum (MSS). The new species are included in an identification key for all microphthalmous Lathrobium s. str. species in Turkey. A total of 10 nominal microphthalmous species are now known to occur in Turkey.


New concepts of personalized therapy in salivary gland carcinomas.
Salivary gland carcinomas are rare tumours and therapy strategies are less standardized than in lung, gastric or breast cancer. Therapy is based on surgery, but not all carcinomas are completely resectable, e.g. because carcinomas often show infiltration of nerves. For further therapy decision pathology is recommended, but evaluation of potential targets for personalized therapy is not part of the routine panel. Many salivary gland carcinomas can be resistant to radio- and/or chemotherapy, which limits therapeutic options. This review summarizes new concepts for personalized therapy in salivary gland carcinoma patients. Targeting growth receptors HER2, EGFR, AR and ER is possible but, in some studies, potential target molecules were not adequately tested before therapy. In addition, approximately 20-25% of carcinomas have RAS mutation (mainly H-RAS), which could explain resistance to therapy. Possible therapy options in the future could be immunomodulation (inhibition of PDL1/PD1 signalling), nanoparticles (gold nanoparticles conjugated to cetuximab can increase radiosensitivity) and drug delivery systems (trastuzumab emtansine/T-DM1).


Melatonin utility in neonates and children.
Melatonin (N-acetyl-5-methoxytryptamine) is an endogenously produced indoleamine secreted by the pineal gland and the secretion is suppressed by light. Melatonin is a highly effective antioxidant, free radical scavenger, and has anti-inflammatory effect. Plenty of evidence supports the utility of melatonin in adults for cancer, neurodegenerative disorders, and aging. In children and neonates, melatonin has been used widely, including for respiratory distress syndrome, bronchopulmonary dysplasia, periventricular leukomalacia (PVL), hypoxia-ischemia encephalopathy and sepsis. In addition, melatonin can be used in childhood sleep and seizure disorders, and in neonates and children receiving surgery. This review article discusses the utility of melatonin in neonates and children.


Toward isolating reward changes in diet-induced obesity: A demand analysis.
Although hormonal and metabolic factors are well known to influence obesity, recent evidence suggests that obesity may be influenced also by changes in reward sensitivity akin to that seen in other 'reward pathologies', like substance use disorders. The current study sought to isolate changes in reward that may occur after the onset of diet-induced obesity by characterizing the economic demand for caloric (sucrose) and non-caloric (saccharin) reinforcers in a preclinical model of diet-induced obesity (DIO). We utilized economic demand analysis to measure baseline demand intensity (Q0) and demand elasticity (α) for sucrose and saccharin reinforcers in rats. After baseline measures were collected, rats were assigned randomly to a high-fat (HF) diet or low-fat (LF) control diet. After 8-weeks of diet exposure, HF rats were divided into obesity-resistant (OR) or obesity-prone (OP) groups based on weight after the 8-week HF diet exposure. Post-DIO demand data for each reinforcer were reassessed. At baseline, rats had higher demand intensity and lower elasticity for sucrose compared to saccharin. After 8-weeks of the high-fat diet, OP rats had significantly greater weight gain and lower demand elasticity for sucrose and saccharin and higher demand intensity for saccharin. The changes in sucrose and saccharin elasticity suggest that DIO-induced changes in food-related behavior are associated with changes in reward processes. The changes in demand intensity for saccharin suggest that demand intensity, as a measure of 'set point', is not directly linked to metabolic processes. The current study shows that microeconomic theory and demand analysis is able to isolate independent aspects of diet-induced reward changes related to caloric and non-caloric reinforcers.


Postnatal B cell development: influence of trinitrobenzenesulfonic acid treatment during pregnancy.
Prenatal treatment with a reactive hapten may be well suited for analyzing the establishment of self tolerance because the hapten binds ubiquitously to proteins and cells and persists for a long period in the developing organism. Based on this consideration, pregnant BALB/c mice were treated with 2,4,6-trinitrobenzenesulfonic acid (TNBS), searching for differences in 2,4,6-trinitrophenyl (TNP) responsiveness in their offspring as compared to litters of untreated mice. The frequency of TNP-specific T-independent B cells of litters from TNBS-treated mothers was very low at birth and remained below 10% of controls until the age of 42 days. On the contrary, in 8-day-old prenatally TNBS-treated litters, the frequency of TNP-specific T-dependent B cells was higher than in controls. Expansion of TNP-specific B cells after antigenic stimulation of control mice started at the age of 3-4 weeks and expansion rates increased with age, while in prenatally TNBS-treated mice, significant expansion rates were seen at the age of 2 weeks only. Yet, after restimulation with TNP-lipopolysaccharide or with a TNP-anti-TNP conjugate, but not after restimulation with TNP-ovalbumin, similar numbers of plaque-forming cells (PFC) were observed with spleen cells of prenatally untreated and TNBS-treated mice, the latter revealing an exceptional predominance of IgG PFC. Thus, TNP-specific B cells were not deleted, but prenatal TNBS treatment resulted in an altered composition of TNP-specific B cell subpopulations, their regulation differing qualitatively from the one observed in prenatally untreated mice.


Klebsiella pneumoniae in a nephrological department.
The repeated isolation of Klebsiella pneumoniae biotypes 16 and 17 from haemodialysis fluid in concentrations exceeding 10(4) cfu/ml led to an investigation of strains isolated from routine specimens of nephrological patients to elucidate whether the dialysate strains could be a source of infection. A total of 118 patient-isolates were identified over a 4-year period. Biotypes 16 and 17 accounted for only nine patient-isolates. The distribution pattern of biotypes among haemodialysis patients and other nephrological patients during a 2-year period, when K. pneumoniae colonized the dialysate, and during a succeeding 2-year period, when it had been eradicated from the dialysate, indicated that there was no epidemiological connection. The patient-isolates comprised 21 different biotypes. Biotype 36 (indole-positive) remained the predominant strain throughout the whole period studied.


Heat stress and the photosynthetic electron transport chain of the lichen Parmelina tiliacea (Hoffm.) Ach. in the dry and the wet state: differences and similarities with the heat stress response of higher plants.
Thalli of the foliose lichen species Parmelina tiliacea were studied to determine responses of the photosynthetic apparatus to high temperatures in the dry and wet state. The speed with which dry thalli were activated by water following a 24 h exposure at different temperatures decreased as the temperature was increased. But even following a 24 h exposure to 50 °C the fluorescence induction kinetics OJIP reflecting the reduction kinetics of the photosynthetic electron transport chain had completely recovered within 128 min. Exposure of dry thalli to 50 °C for 24 h did not induce a K-peak in the fluorescence rise suggesting that the oxygen evolving complex had remained intact. This contrasted strongly with wet thalli were submergence for 40 s in water of 45 °C inactivated most of the photosystem II reaction centres. In wet thalli, following the destruction of the Mn-cluster, the donation rate to photosystem II by alternative donors (e.g. ascorbate) was lower than in higher plants. This is associated with the near absence of a secondary rise peak (~1 s) normally observed in higher plants. Analysing the 820 nm and prompt fluorescence transients suggested that the M-peak (occurs around 2-5 s) in heat-treated wet lichen thalli is related to cyclic electron transport around photosystem I. Normally, heat stress in lichen thalli leads to desiccation and as consequence lichens may lack the heat-stress-tolerance-increasing mechanisms observed in higher plants. Wet lichen thalli may, therefore, represent an attractive reference system for the evaluation of processes related with heat stress in higher plants.


Pharmacokinetics and the drug-target residence time concept.
The concept of drug-target residence time has been in focus in recent drug discovery literature. However, few studies consider the combined effect of pharmacokinetics (PK) and binding kinetics (BK) on the duration of effect of a drug. Using a simple model that takes both PK and BK into account, we found that prolongation of binding owing to a long drug-target residence time can only occur when the binding dissociation is slower than the PK elimination. Data for several drugs and/or drug candidates in the literature indicate that the opposite is observed, that is, they have a slower elimination compared with dissociation. These observations greatly reduce the usability of drug-target residence times for estimating the duration of effect of a drug in vivo.


Cilostazol enhances IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle via PKA-dependent pathway.
Interleukin-1beta (IL-1beta) stimulates nitric oxide (NO) production and induces apoptosis in several tissues. Cilostazol is a Type 3 phosphodiesterase inhibitor. We investigated whether cilostazol affects IL-1beta-induced NO production and apoptosis in rat vascular smooth muscle cells. Cilostazol (100 nM-10 microM) potentiated NO production triggered by IL-1beta. The mRNA and protein expression of inducible NO synthase was also upregulated by cilostazol. KT5720, an inhibitor of protein kinase A, and N(G)-monomethyl-L-arginine, an inhibitor of NO synthase, abrogated cilostazol-enhanced IL-1beta-stimulated NO production and apoptosis. These results shows that cilostazol potentiates IL-1beta-induced NO production via PKA-pathway and thereafter augments apoptosis via NO-dependent pathway.