Lack of association of genetic variants in the LRP8 gene with familial and sporadic myocardial infarction.
Coronary artery disease (CAD) and myocardial infarction (MI) have a genetic basis, but the precise genetic underpinning remains controversial. Recently, an association of the LRP8 R952Q polymorphism (rs5174) with familial premature CAD/MI was reported. We analysed rs5174 (or the perfect proxy rs5177) in 1,210 patients with familial MI and 1,015 controls from the German MI Family study, in 1,926 familial CAD (1,377 with MI) patients and 2,938 controls from the Wellcome Trust Case Control Consortium (WTCCC) MI/CAD cohort, in 346 CAD patients and 351 controls from the AtheroGene study and in 295 men with incident CAD and 301 controls from the Prospective Epidemiological Study of MI study and found no evidence for association in any of the populations studied. In the WTCCC and the German MI Family studies, additional single-nucleotide polymorphisms in the LRP8 gene were analysed and displayed no evidence for association either.


Revising the simple measures of assortativity in complex networks.
We find that traditional statistics for measuring degree mixing are strongly affected by superrich nodes. To counteract and measure the effect of superrich nodes, we propose a paradigm to quantify the mixing pattern of a real network in which different mixing patterns may appear among low-degree nodes and among high-degree nodes. This paradigm and the simple revised measure uncover the true complex degree mixing patterns of complex networks with superrich nodes. The alternate method indicates that some networks show a false disassortative mixing induced by superrich nodes and have no tendency to be genuinely disassortative. Our results also show that the previously observed fragility of scale-free networks is actually greatly exacerbated by the presence of even a very small number of superrich nodes.


Evaluation of a computerized polysomnographic system.
Computerized polysomnographic systems have came into common use in sleep laboratories around the world. Despite potential advantages over standard paper polysomnography, these computerized systems have been minimally evaluated as to accuracy, analysis time, or cost effectiveness when compared to paper. We evaluated the Healthdyne ALICE 3 system for comparability to paper polysomnography in sleep quantification and technician analysis time. Fifty patients were recorded simultaneously both on paper and on the ALICE 3 system and analyzed blindly with summary data from these records being quantified and compared. Five additional patients were studied for epoch-by-epoch analysis. Score-rescore assessments were accomplished for both groups. The results indicate that when allowed to autoscore, this computerized system produced substantial errors in sleep staging (REM sleep time 56.4 + 4.9 minutes vs 73.2 + 8.4 minutes for paper versus computer). This was the case for respiratory (AHI of 26.5 + 4.3 vs 15.3 + 2.6 for paper vs computer) and arousal assessment as well. However, with editing, similar results to those obtained with paper were achieved (REM sleep time -56.4 + 4.9 vs 59.0 + 4.6; AHI -26.5 + 4.3 vs 26.1 + 4.7 for paper and computer respectively), with differences rarely exceeding score-rescore discrepancies. Analysis time was substantially reduced by use of the computer (172.6 + 9.9 vs 79.7 + 4.8 minutes for paper vs computer). Epoch-by-epoch analysis revealed a trend to score toward wakefulness or lighter sleep on computer compared to paper although the differences were small. Respiratory, arousal and PLM scoring were quite similar. In conclusion, this study suggests that the ALICE 3 system with editing can produce results similar to those obtained with paper.


Urothelial neoplasms in patients 20 years or younger: a clinicopathological analysis using the world health organization 2004 bladder consensus classification.
Urothelial neoplasms in patients younger than 20 years are rare, with conflicting data regarding clinical outcomes. We identified 23 patients 4 to 20 years old with urothelial neoplasms, reclassified the microscopic diagnoses using the 2004 WHO/International Society of Urologic Pathology grading classification and collected data on presentation, risk factors and outcomes. Pathological grading revealed 2 urothelial papillomas, 10 papillary urothelial neoplasms of low malignant potential (PUNLMPs), and 8 low grade and 3 high grade papillary urothelial cancers, all without invasion. Mean patient age was 13.2 years (range 4 to 20), 19 patients were male and 19 presented with gross hematuria. All lesions were solitary and measured 0.1 to 6 cm. One patient had a history of smoking and 1 had parents who smoked. Three patients (13%) had recurrences classified as either urothelial papilloma (1) or PUNLMP (2). All patients were alive with no evidence of disease after a mean followup of 4.5 years (range 6 months to 13 years). Urothelial neoplasms in individuals younger than 20 years more commonly occur in males and are predominantly low grade with a favorable clinical outcome. Before the current classification system the 10 patients with a diagnosis of PUNLMP would have been classified as having papillary carcinoma. Thus, the diagnostic category of PUNLMP allowed 43.5% of patients in this series to avoid being labeled with "cancer" at a young age.


Interleukin-1 receptor-associated kinase-4 (IRAK4) promotes inflammatory osteolysis by activating osteoclasts and inhibiting formation of foreign body giant cells.
Formation of foreign body giant cells (FBGCs) occurs following implantation of medical devices such as artificial joints and is implicated in implant failure associated with inflammation or microbial infection. Two major macrophage subpopulations, M1 and M2, play different roles in inflammation and wound healing, respectively. Therefore, M1/M2 polarization is crucial for the development of various inflammation-related diseases. Here, we show that FBGCs do not resorb bone but rather express M2 macrophage-like wound healing and inflammation-terminating molecules in vitro. We also found that FBGC formation was significantly inhibited by inflammatory cytokines or infection mimetics in vitro. Interleukin-1 receptor-associated kinase-4 (IRAK4) deficiency did not alter osteoclast formation in vitro, and IRAK4-deficient mice showed normal bone mineral density in vivo. However, IRAK4-deficient mice were protected from excessive osteoclastogenesis induced by IL-1β in vitro or by LPS, an infection mimetic of Gram-negative bacteria, in vivo. Furthermore, IRAK4 deficiency restored FBGC formation and expression of M2 macrophage markers inhibited by inflammatory cytokines in vitro or by LPS in vivo. Our results demonstrate that osteoclasts and FBGCs are reciprocally regulated and identify IRAK4 as a potential therapeutic target to inhibit stimulated osteoclastogenesis and rescue inhibited FBGC formation under inflammatory and infectious conditions without altering physiological bone resorption.


Computer-based classification of chromoendoscopy images using homogeneous texture descriptors.
Computer-aided analysis of clinical pathologies is a challenging task in the field of medical imaging. Specifically, the detection of abnormal regions in the frames collected during an endoscopic session is difficult. The variations in the conditions of image acquisition, such as field of view or illumination modification, make it more demanding. Therefore, the design of a computer-assisted diagnostic system for the recognition of gastric abnormalities requires features that are robust to scale, rotation, and illumination variations of the images. Therefore, this study focuses on designing a set of texture descriptors based on the Gabor wavelets that will cope with certain image dynamics. The proposed features are extracted from the images and utilized for the classification of the chromoendoscopy (CH) frames into normal and abnormal categories. Moreover, to attain a higher accuracy, an optimized subset of descriptors is selected through the genetic algorithm. The results obtained using the proposed features are compared with other existing texture descriptors (e.g., local binary pattern and homogeneous texture descriptors). Furthermore, the selected features are used to train the support vector machine (SVM), naive Bayes (NB) algorithm, k-nearest neighbor algorithm, linear discriminant analysis, and ensemble tree classifier. The performance of these state-of-the-art classifiers for different texture descriptors is compared based on the accuracy, sensitivity, specificity, and area under the curve (AUC) derived by using the CH images. The classification results reveal that the SVM classifier achieves 90.0% average accuracy and 0.93 AUC when it is employed with an optimized set of features obtained by using a genetic algorithm.


Acupuncture and Traditional Chinese Herbal Medicine Integrated With Conventional Rehabilitation for Post-stroke Functional Recovery: A Retrospective Cohort Study.
Stroke leads to tremendous impacts on patients and the healthcare system. It is crucial to explore the potential management of rehabilitation. Acupuncture and traditional Chinese herbal medicine (TCHM) integrated with conventional rehabilitation benefit post-stroke functional recovery. We retrospectively reviewed the medical records of all patients included in the Integrated Traditional Chinese-Western Medicine care program for stroke (ITCWM-stroke care program) in 2019 in Taipei Tzu Chi Hospital to investigate the effects of acupuncture and TCHM integrated with conventional rehabilitation on National Institutes of Health Stroke Scale (NIHSS) and Barthel Index (BI) scores before and after the program. A total of 255 stroke inpatients were retrieved and divided into acupuncture and acupuncture + TCHM group by hemorrhagic and ischemic stroke types, respectively. All the patients were recruited in the program at the early subacute phase after stroke onset. Of the hemorrhagic and ischemic stroke subjects, the NIHSS and BI total scores were significantly improved in the acupuncture and acupuncture + TCHM groups. The subgroup analysis results showed that in subjects with a baseline BI score ≤ 40, the acupuncture + TCHM group significantly improved BI total score better than the acupuncture group in both hemorrhagic (p < 0.05) and ischemic (p < 0.05) stroke subjects. Acupuncture and TCHM integrated with conventional rehabilitation significantly improve stroke patients' functional recovery at the early subacute phase. Acupuncture + TCHM contributes to better activities of daily living (ADL) improvements in stroke patients with a baseline BI score ≤ 40. We suggest integrating acupuncture and TCHM into the post-stroke rehabilitation strategy, especially for stroke patients with poor ADL function.


N-acetylcysteine inhibits lipid accumulation in mouse embryonic adipocytes.
Oxidative stress plays critical roles in the pathogenesis of diabetes, hypertension, and atherosclerosis; some authors reported that fat accumulation correlates to systemic oxidative stress in human and mice, but cellular redox environment effect on lipid accumulation is still unclear. In our laboratory we used mouse embryonic fibroblasts (undifferentiated cells: CC), which are capable of differentiating into mature adipocytes (differentiated cells: DC) and accumulate lipids, as obesity model. Here we analyzed the role of the well-known antioxidant and glutathione precursor N-acetylcysteine (NAC) in cellular MAPK modulation and lipid accumulation. We evaluated the effect of NAC on the adipogenic differentiation pathway using different doses: 0.01, 0.1, 1 and 5mM; no toxic doses in these cells. A dose of 5mM NAC [DCN-5] provoked a significant decrease in triglyceride accumulation (72±10 [DCN-5] vs 169±15 [DC], p<0.01), as well in Oil Red O stained neutral lipid content (120±2 [DCN-5] vs 139±12 [DC], p<0.01). Molecular mechanisms responsible for adipogenic differentiation involve increase of the expression of phosphoERK½ and phosphoJNK, 5mM NAC treatment inhibited both pERK½ and pJNK protein levels. We also evaluated the mitotic clonal expansion (MCE) which takes place during adipogenesis and observed an increase in DC at a rate of 1.5 cells number compared to CC at day 2, whereas the highest doses of NAC significantly inhibited MCE. Our results suggest that NAC inhibits lipid accumulation and the MAPK phosphorylation in mouse embryonic fibroblasts during adipogenic differentiation and further contribute to probe the importance of cellular redox environment in adipogenesis.


Childhood blindness in India.
To date there are no published studies on blindness in children or on its incidence. Recently information on the causes of blindness in children identified by community based rehabilitation programmes in two states of India has provided very useful population based data. Prevalence and magnitude of blindness in children in India, avoidable causes and control of blindness in children at the primary, secondary and tertiary levels of health care are discussed in this article along with probable areas of research.


[Anaerobic bacteria isolated from appendices and appendicitis cases].
Anaerobic bacteria were isolated from 17 of 40 normal appendices and appendicitis cases in Ankara. In both cases gram positive, nonsporulating, and gram negative organisms were isolated. Gram positive cocci were only isolated from appendicitis cases. The bacteria isolated from appendicitis are usually like the anaerobic bacteria of the colon flora. All anaerobic bacteria in appendix flora can cause appendicitis in suitable conditions.


The Influence of COVID-19 Pandemic on the Health Seeking Behaviors of Adults Living With Chronic Conditions: A View Through the Health Belief Model.
The COVID-19 pandemic resulted in disruption in every facet of life including health service delivery. This has threatened the attainment of global targets to improve health and wellbeing of all persons. In particular, for persons living with chronic diseases, who require consistent monitoring by health professionals and medication to enhance their health, understanding how the pandemic has disruption their access to health care delivery is critical for interventions aimed at improving health service delivery for all as well as preparedness for future pandemic. This study applied the constructs of the Health Belief Model, to explore the influences of the COVID-19 pandemic on the health seeking behaviors of persons living with chronic diseases. The design was exploratory descriptive. Semi-structured interviews were conducted to collect data among persons living with chronic diseases in the Cape Coast Metropolis of Ghana. Thematic analysis, both inductive and deductive, was conducted to unearth the findings. Awareness of increased susceptibility and risk of a more severe episode if they contracted COVID-19 as a result of the existing chronic diseases was identified. Lack of access to health professionals during the peak of the pandemic as well as the fear of contracting the virus while accessing their regular chronic disease clinic was the main barriers identified. Information in the media served as cues to action for adopting preventive health strategies. Behavior modifications; dietary and lifestyle, self-medication and adoption of COVID-19 related precautions were practiced. Susceptibility to contracting COVID-19 contributed to missed adherence to treatment appointment. The health belief model was a useful framework in exploring the health seeking behavior of the adults living with chronic conditions during the COVID-19 in this study setting. Intensifying targeted education for persons living with chronic diseases will contribute to the adoption of positive health seeking behaviors during future pandemic.


Sonography in primary hyperparathyroidism: review with emphasis on scanning technique.
To review the sonographic features and focused sonographic scanning techniques that may assist in the preoperative localization of parathyroid adenomas in patients with primary hyperparathyroidism. The sonographic findings were reviewed in 54 of 58 consecutive patients with pathologically proven parathyroid adenomas. A systematic scanning approach including real-time gray scale, color and power Doppler, and graded compression gray scale imaging was used in all patients. Fifty-four (93%) of 58 proven adenomas were correctly identified by sonography. Gray scale imaging alone was sufficient for identifying 26 (100%) of 26 large (> or =1-cm) and 3 (11%) of 25 small (<1-cm) parathyroid adenomas. However, for 25 (89%) of 28 small adenomas, a combination of color and power Doppler and graded compression real-time gray scale imaging was required for sonographic localization and identification. Knowledge of typical locations and characteristic imaging features, as well as a systematic scanning approach, can result in accurate preoperative sonographic localization of parathyroid adenomas.


A systematic literature review on the role of glial cells in the pathomechanisms of migraine.
The pathomechanisms underlying migraine are intricate and remain largely unclear. Initially regarded as a neuronal disorder, migraine research primarily concentrated on understanding the pathophysiological changes within neurons. However, recent advances have revealed the significant involvement of neuroinflammation and the neuro-glio-vascular interplay in migraine pathogenesis. A systematic search was conducted in PubMed, Scopus, and Web of Science databases from their inception until November 2022. The retrieved results underwent a screening process based on title and abstract, and the full texts of the remaining papers were thoroughly assessed for eligibility. Only studies that met the predetermined inclusion criteria were included in the review. Fifty-nine studies, consisting of 6 human studies and 53 animal studies, met the inclusion criteria. Among the 6 human studies, 2 focused on genetic analyses, while the remaining studies employed functional imaging, serum analyses and clinical trials. Regarding the 53 animal studies investigating glial cells in migraine, 19 of them explored the role of satellite glial cells and/or Schwann cells in the trigeminal ganglion and/or trigeminal nerve. Additionally, 17 studies highlighted the significance of microglia and/or astrocytes in the trigeminal nucleus caudalis, particularly in relation to central sensitization during migraine chronification. Furthermore, 17 studies examined the involvement of astrocytes and/or microglia in the cortex. Glial cells, including astrocytes, microglia, satellite glial cells and Schwann cells in the central and peripheral nervous system, participate both in the development as well as chronic progression of migraine in disease-associated regions such as the trigeminovascular system, trigeminal nucleus caudalis and cortex, among other brain regions.


Manipulation of pro-inflammatory cytokine production by the bacterial cell-penetrating effector protein YopM is independent of its interaction with host cell kinases RSK1 and PRK2.
The effector protein Yersinia outer protein M (YopM) of Yersinia enterocolitica has previously been identified and characterized as the first bacterial cell-penetrating protein (CPP). We found that recombinant YopM (rYopM) enters different eukaryotic cell types and downregulates the expression of several pro-inflammatory cytokines (e.g., tumor necrosis factor-α [TNF-α]) after autonomous translocation. After infection with Y. enterocolitica or transfection of host cells, YopM interacts with isoforms of the two kinases ribosomal S6 protein kinase (RSK) and protein kinase C-related kinase (PRK). This interaction caused sustained RSK activation due to interference with dephosphorylation. Here we demonstrate by co-immunoprecipitation that rYopM interacts with RSK and PRK following cell-penetration. We show that autonomously translocated rYopM forms a trimeric complex with different RSK and PRK isoforms. Furthermore, we constructed a series of truncated versions of rYopM to map the domain required for the formation of the complex. The C-terminus of rYopM was identified to be essential for the interaction with RSK1, whereas any deletion in rYopM's leucin-rich repeat domains abrogated PRK2 binding. Moreover, we found that the interaction of cell-penetrating rYopM with RSK led to enhanced autophosphorylation of this kinase at serine 380. Finally, we investigated whether downstream signaling of the trimeric rYopM-RSK/PRK complex modulates the expression of pro-inflammatory TNF-α. Here, we could exclude that interaction with RSK1 and PRK2 is essential for the anti-inflammatory effects of rYopM.


Stent Graft Implantation and Superselective Embolization with Liquid Embolic Agent, Onyx for Iatrogenic Common Iliac Artery Pseudoaneurysm and Persistant Endoleak.
A 68-year-old male patient with a history of femoro-femoral bypass following unsuccessful intervention for chronic total iliac occlusion was found to have a saccular pseudoaneurysm of the right common iliac artery (CIA) due to interventional device-related injuries associated with the past endovascular intervention. An iatrogenic pseudoaneurysm in the CIA is generally asymptomatic, but it has a high risk of rupture, regardless of its size or symptoms. Endovascular therapy may be the best treatment option; however, ineffective sealing with a stent graft may lead to a type I endoleak. Under such conditions, use of the liquid embolic agent, Onyx, as a bailout solution for the type 1 endoleak is promising.


Left atrial isomerism in the adolescence: report of two cases.
Atrial isomerism is very rare in adolescence. Two cases of left atrial isomerism are reported here in 2 females, aged 21 and 19 years. They had presented with cyanosis and dyspnea since childhood. High kilovoltage filter films showed a bilateral morphologically left bronchus. Cardiac catheterization in Case 1 revealed normal pulmonary artery pressure, severe subvalvular pulmonic stenosis, a double outlet right ventricle, a significant oxygen step-up at the atrial level and moderate systemic oxygen desaturation; while Case 2 disclosed pulmonary hypertension and mild systemic oxygen desaturation. Both cases had the following anatomical features: ipsilateral connection of pulmonary veins to the bilateral morphological left atrium; interrupted inferior vena cave with azygos or hemiazygos continuation; total anomalous hepatic venous return to the right-sided atrium; complete atrioventricular canal. The diagnoses were confirmed in both cases at surgical correction.


Congenital cytomegalovirus infection with osteolytic lesions: use of DNA hybridization in diagnosis.
A case of congenital cytomegalovirus (CMV) infection with long-bone lesions is presented. The bone lesions consisted of broad regions of generalized osteopenia with irregular fragmentation and spiculization at the zone of provisional calcification. Diagnosis of CMV infection was made by DNA spot hybridization of the urine sediment to DNA from the Towne strain of CMV, demonstrating the usefulness of DNA hybridization for identification of CMV in clinical specimens. Bone lesions associated with congenital CMV infection are useful early clues to diagnosis but can be indistinguishable from those of congenital rubella syndrome.


Waiting for the changes after the adoption of steatotic liver disease.
Steatotic liver disease was suggested as an overarching term encompassing various etiologies of hepatic steatosis. Experts from multinational liver societies went through the Delphi process, including four rounds of surveys, and consented to adopt a new nomenclature and definition instead of the conventional nonalcoholic fatty liver disease (NAFLD). This was to improve the understanding of the patients and primary care physicians, with an explanation of the pathophysiology in the name of the disease. Also, it could minimize the stigmatization of patients by using the histological neutral term "steatosis" instead of "fatty". Herein, we will discuss the changes and continuity between the two nomenclatures, metabolic dysfunction-associated steatotic liver disease (MASLD) and NAFLD, as well as the challenges to MASLD which need to be addressed in future.


A Web-Based Instrument for Infantile Atopic Dermatitis Identification (Electronic Version of the Modified Child Eczema Questionnaire): Development and Implementation.
Atopic dermatitis (AD) is a chronic inflammatory cutaneous disease that affects 30.48% of young children; thus, there is a need for epidemiological studies in community settings. Web-based questionnaires (WBQs) are more convenient, time-saving, and efficient than traditional surveys, but the reliability of identifying AD through WBQs and whether AD can be identified without the attendance of doctors, especially in community or similar settings, remains unknown. This study aimed to develop and validate a web-based instrument for infantile AD identification (electronic version of the modified Child Eczema Questionnaire [eCEQ]) and to clarify the possibility of conducting WBQs to identify infantile AD without the attendance of doctors in a community-representative population. This study was divided into 2 phases. Phase 1 investigated 205 children younger than 2 years to develop and validate the eCEQ by comparison with the diagnoses of dermatologists. Phase 2 recruited 1375 children younger than 2 years to implement the eCEQ and verify the obtained prevalence by comparison with the previously published prevalence. In phase 1, a total of 195 questionnaires were analyzed from children with a median age of 8.8 (IQR 4.5-15.0) months. The identification values of the eCEQ according to the appropriate rules were acceptable (logic rule: sensitivity 89.2%, specificity 91.5%, positive predictive value 97.1%, and negative predictive value 72.9%; statistic rule: sensitivity 90.5%, specificity 89.4%, positive predictive value 96.4%, and negative predictive value 75%). In phase 2, a total of 837 questionnaires were analyzed from children with a median age of 8.4 (IQR 5.2-14.6) months. The prevalence of infantile AD obtained by the eCEQ (logic rule) was 31.9% (267/837), which was close to the published prevalence (30.48%). Based on the results of phase 2, only 20.2% (54/267) of the participants identified by the eCEQ had previously received a diagnosis from doctors. Additionally, among the participants who were not diagnosed by doctors but were identified by the eCEQ, only 6.1% (13/213) were actually aware of the possible presence of AD. Infantile AD can be identified without the attendance of doctors by using the eCEQ, which can be easily applied to community-based epidemiological studies and provide acceptable identification reliability. In addition, the eCEQ can also be applied to the field of public health to improve the health awareness of the general population.


The emperor's new clothes: hypersensitivity of the new cardiac isoenzymes.
Right ventricular (RV) myocardial infarction (MI) and pulmonary embolism (PE) are commonly recognized as two of the most challenging and vexing entities in clinical practice. When either is considered in a differential diagnosis, they warrant close consideration because of the life-threatening nature of these conditions. Their signs and symptoms overlap and, on rare occasions, they both can be simultaneously present in a single patient. Cardiac troponins are considered reliable markers of myocardial injury and are critical to the diagnosis of acute coronary syndromes. However, they can also be elevated in cases of PE. We herewith present a case of a woman who initially presented with syncope and then subsequently dyspnea. She manifested elevated cardiac isoenzymes, right-sided electrocardiogram abnormalities, and RV hypokinesis on echocardiography. She was initially diagnosed with RV infarct and managed with an interventional cardiology approach. However, her symptom of dyspnea persisted and the patient was eventually diagnosed with PE. Clinicians should entertain the diagnosis of PE in patients with elevated troponin I and evidence of right-sided cardiac compromise.


Does genomic selection have a future in plant breeding?
Plant breeding largely depends on phenotypic selection in plots and only for some, often disease-resistance-related traits, uses genetic markers. The more recently developed concept of genomic selection, using a black box approach with no need of prior knowledge about the effect or function of individual markers, has also been proposed as a great opportunity for plant breeding. Several empirical and theoretical studies have focused on the possibility to implement this as a novel molecular method across various species. Although we do not question the potential of genomic selection in general, in this Opinion, we emphasize that genomic selection approaches from dairy cattle breeding cannot be easily applied to complex plant breeding.


Association Between Procalcitonin and Antibiotics in Children With Community-Acquired Pneumonia.
To determine whether empirical antibiotic initiation and selection for children with pneumonia was associated with procalcitonin (PCT) levels when results were blinded to clinicians. We enrolled children <18 years with radiographically confirmed pneumonia at 2 children's hospitals from 2014 to 2019. Blood for PCT was collected at enrollment (blinded to clinicians). We modeled associations between PCT and (1) antibiotic initiation and (2) antibiotic selection (narrow versus broad-spectrum) using multivariable logistic regression models. To quantify potential stewardship opportunities, we calculated proportions of noncritically ill children receiving antibiotics who also had a low likelihood of bacterial etiology (PCT <0.25 ng/mL) and those receiving broad-spectrum therapy, regardless of PCT level. We enrolled 488 children (median PCT, 0.37 ng/mL; interquartile range [IQR], 0.11-2.38); 85 (17%) received no antibiotics (median PCT, 0.32; IQR, 0.09-1.33). Among the 403 children receiving antibiotics, 95 (24%) received narrow-spectrum therapy (median PCT, 0.24; IQR, 0.08-2.52) and 308 (76%) received broad-spectrum (median PCT, 0.46; IQR, 0.12-2.83). In adjusted analyses, PCT values were not associated with antibiotic initiation (odds ratio [OR], 1.02, 95% confidence interval [CI], 0.97%-1.06%) or empirical antibiotic selection (OR 1.07; 95% CI, 0.97%-1.17%). Of those with noncritical illness, 246 (69%) were identified as potential targets for antibiotic stewardship interventions. Neither antibiotic initiation nor empirical antibiotic selection were associated with PCT values. Whereas other factors may inform antibiotic treatment decisions, the observed discordance between objective likelihood of bacterial etiology and antibiotic use suggests important opportunities for stewardship.


Draft Genome Sequences of Two Psychrotolerant Strains, Colwellia polaris MCCC 1C00015T and Colwellia chukchiensis CGMCC 1.9127T.
Colwellia polaris MCCC 1C00015T and Colwellia chukchiensis CGMCC 1.9127T are psychrotolerant bacteria isolated from the Canadian Basin and Chukchi Sea, respectively. Here, we report the draft genome sequences of C. polaris MCCC 1C00015T and C. chukchiensis CGMCC 1.9127T, which will help reveal how they adapt to cold environments.


Gas-Phase Hydrogen/Deuterium Exchange for Distinguishing Isomeric Carbohydrate Ions.
The structural diversity of carbohydrates presents a major challenge for glycobiology and the analysis of glycoconjugates. Mass spectrometry has become a primary tool for glycan analysis thanks to its speed and sensitivity, but the information content regarding the glycan structure of protonated glycoconjugates is hindered by the inability to differentiate linkage and stereoisomers. Here, we examine a variety of protonated carbohydrate structures by gas-phase hydrogen/deuterium exchange (HDX) to discover that the exchange rates are distinct for isomeric carbohydrates with even subtle structural differences. By incorporating an internal exchange standard, HDX could effectively distinguish all linkage and stereoisomers that were examined and presents a mass spectrometry-based approach for glycan structural analysis with immense potential.


Focal point analysis of the singlet-triplet energy gap of octacene and larger acenes.
A benchmark theoretical study of the electronic ground state and of the vertical and adiabatic singlet-triplet (ST) excitation energies of n-acenes (C(4n+2)H(2n+4)) ranging from octacene (n = 8) to undecacene (n = 11) is presented. The T1 diagnostics of coupled cluster theory and further energy-based criteria demonstrate that all investigated systems exhibit predominantly a (1)A(g) singlet closed-shell electronic ground state. Singlet-triplet (S(0)-T(1)) energy gaps can therefore be very accurately determined by applying the principle of a focal point analysis (FPA) onto the results of a series of single-point and symmetry-restricted calculations employing correlation consistent cc-pVXZ basis sets (X = D, T, Q, 5) and single-reference methods [HF, MP2, MP3, MP4SDQ, CCSD, and CCSD(T)] of improving quality. According to our best estimates, which amount to a dual extrapolation of energy differences to the level of coupled cluster theory including single, double, and perturbative estimates of connected triple excitations [CCSD(T)] in the limit of an asymptotically complete basis set (cc-pV∞Z), the S(0)-T(1) vertical (adiabatic) excitation energies of these compounds amount to 13.40 (8.21), 10.72 (6.05), 8.05 (3.67), and 7.10 (2.58) kcal/mol, respectively. In line with the absence of Peierls distortions (bond length alternations), extrapolations of results obtained at this level for benzene (n = 1) and all studied n-acenes so far (n = 2-11) indicate a vanishing S(0)-T(1) energy gap, in the limit of an infinitely large polyacene, within an uncertainty of 1.5 kcal/mol (0.06 eV). Lacking experimental values for the S(0)-T(1) energy gaps of n-acenes larger than hexacene, comparison is made with recent optical and electrochemical determinations of the HOMO-LUMO band gap. Further issues such as scalar relativistic, core correlation, and diagonal Born-Oppenheimer corrections (DBOCs) are tentatively examined.


Frequency and management outcome of pneumothorax patients.
Primary spontaneous pneumothorax is a common clinical problem and its incidence is thought to be increasing. This study was conducted to see the frequency, aetiology, presentation and management outcomes of pneumothorax in patients presenting at Pulmonology unit, Ayub Teaching Hospital, Abbottabad, Pakistan. Pneumothorax patients reporting at the Pulmonology unit of Ayub Teaching Hospital, Abbottabad from 2002 to December 2008 were included in the study. Patients of all ages were included. They were admitted and followed up to the full recovery. A total of 195 pneumothorax patients reported during this period. Majority of the patients were diagnosed to have pneumothorax due to pulmonary tuberculosis making about 36.92% of the total cases. Second most common cause was primary spontaneous pneumothorax (21.53%). COPD were also sizeable at 8.71%. Other causes included Bacterial infections, Asthma, iatrogenic, interstitial lung disease, bronchiectasis and Trauma. It was concluded from this study that pulmonary tuberculosis is the commonest cause of pneumothorax in our setup.


Multilevel models for estimating incremental net benefits in multinational studies.
Multilevel models (MLMs) have been recommended for estimating incremental net benefits (INBs) in multicentre cost-effectiveness analysis (CEA). However, these models have assumed that the INBs are exchangeable and that there is a common variance across all centres. This paper examines the plausibility of these assumptions by comparing various MLMs for estimating the mean INB in a multinational CEA. The results showed that the MLMs that assumed the INBs were exchangeable and had a common variance led to incorrect inferences. The MLMs that included covariates to allow for systematic differences across the centres, and estimated different variances in each centre, made more plausible assumptions, fitted the data better and led to more appropriate inferences. We conclude that the validity of assumptions underlying MLMs used in CEA need to be critically evaluated before reliable conclusions can be drawn.


MicroRNA Regulation of the Small Rho GTPase Regulators-Complexities and Opportunities in Targeting Cancer Metastasis.
The small Rho GTPases regulate important cellular processes that affect cancer metastasis, such as cell survival and proliferation, actin dynamics, adhesion, migration, invasion and transcriptional activation. The Rho GTPases function as molecular switches cycling between an active GTP-bound and inactive guanosine diphosphate (GDP)-bound conformation. It is known that Rho GTPase activities are mainly regulated by guanine nucleotide exchange factors (RhoGEFs), GTPase-activating proteins (RhoGAPs), GDP dissociation inhibitors (RhoGDIs) and guanine nucleotide exchange modifiers (GEMs). These Rho GTPase regulators are often dysregulated in cancer; however, the underlying mechanisms are not well understood. MicroRNAs (miRNAs), a large family of small non-coding RNAs that negatively regulate protein-coding gene expression, have been shown to play important roles in cancer metastasis. Recent studies showed that miRNAs are capable of directly targeting RhoGAPs, RhoGEFs, and RhoGDIs, and regulate the activities of Rho GTPases. This not only provides new evidence for the critical role of miRNA dysregulation in cancer metastasis, it also reveals novel mechanisms for Rho GTPase regulation. This review summarizes recent exciting findings showing that miRNAs play important roles in regulating Rho GTPase regulators (RhoGEFs, RhoGAPs, RhoGDIs), thus affecting Rho GTPase activities and cancer metastasis. The potential opportunities and challenges for targeting miRNAs and Rho GTPase regulators in treating cancer metastasis are also discussed. A comprehensive list of the currently validated miRNA-targeting of small Rho GTPase regulators is presented as a reference resource.


Pinhole Zone Plate Lens for Ultrasound Focusing.
The focusing capabilities of a pinhole zone plate lens are presented and compared with those of a conventional Fresnel zone plate lens. The focusing properties are examined both experimentally and numerically. The results confirm that a pinhole zone plate lens can be an alternative to a Fresnel lens. A smooth filtering effect is created in pinhole zone plate lenses, giving rise to a reduction of the side lobes around the principal focus associated with the conventional Fresnel zone plate lens. The manufacturing technique of the pinhole zone plate lens allows the designing and constructing of lenses for different focal lengths quickly and economically and without the need to drill new plates.


Informed refusal: the patient's influence on long-term treatment.
Outpatient studies in private practices revealed that psychiatric treatments often do not meet therapeutic standards. One possible explanation for this is that the autonomous patient substantially participates in therapeutic decision-making. Basic preconditions for the therapeutic decision-making are the patient's right of self-determination, the doctor's duty to inform, and a risk-benefit assessment on the part of patient and doctor. However, ethical and possibly also legal problems may result if the physician has to be responsible for a treatment decision which was influenced by the autonomous patient, but which is less effective and less safe than the treatment he recommends to the patient. Two outpatient examples will be given where doctor and patient come to different risk-benefit assessments. Emerging ethical problems will be discussed.


Urinary excretion of phthalate metabolites in school children of China: implication for cumulative risk assessment of phthalate exposure.
We analyzed 13 metabolites of 9 phthalates in urine of 782 Chinese school children aged 8–11 years and estimated the daily intake for phthalates based on urinary metabolite levels. The daily intakes were compared with acceptable intake levels to calculate the hazard quotient (HQ) for single phthalate. Finally, the cumulative risk for each child was assessed by means of a hazard index (HI) which is the sum of HQs. Overall, 11 metabolites were found in at least 85% of the urine samples with the highest median concentration of 47.1 ng/mL (93.4 μg/g creatinine) for mono-n-butyl phthalate (MnBP). Monooctyl phthalate (MOP) and monoisononyl phthalate (MiNP) were not detectable. The cumulative risk assessment covering di(2-ethylhexyl) phthalate (DEHP), di-n-butyl phthalate (DnBP), di-isobutyl phthalate (DiBP), and butyl-benzyl phthalate (BBzP) demonstrated that 19.8% (volume model-based) and 40.3% (creatinine model-based) of the children exceeded 1 for the HI based on tolerable daily intake (TDI) values (considered as potential adverse antiandrogenic effect). Furthermore, at least 36% of the children from the manufacturing-intensive region had a HI higher than 1. The results indicate that Chinese children are widely exposed to phthalates and those from manufacturing-intensive regions are probably at a high risk of cumulative phthalate exposure.


Decellularization-Based Modification Strategy for Bioactive Xenografts Promoting Tendon Repair.
Xenografts have emerged as a promising option for severe tendon defects treatment. However, despite undergoing decellularization, concerns still remain regarding the immunogenicity of xenografts. Because certain components within the extracellular matrix also possess immunogenicity. In this study, a novel strategy of post-decellularization modification aimed at preserving the endogenous capacity of cells on collagen synthesis to mask antigenic epitopes in extracellular matrix is proposed. To implement this strategy, a human-derived rosiglitazone-loaded decellularized extracellular matrix (R-dECM) is developed. R-dECM can release rosiglitazone for over 7 days in vitro. By suppressing M1 macrophage polarization, R-dECM protects the migration and collagen synthesis abilities of tendon-derived stem cells (TDSCs), while also stabilizing the phenotype of M2 macrophages in vitro. RNA sequencing reveals R-dECM can mitigate the detrimental crosstalk between TDSCs and inflammatory cells. When applied to a rat patellar tendon defect model, R-dECM effectively inhibits early inflammation, preventing chronic inflammation. Its duration of function far exceeds the release time of rosiglitazone, implying the establishment of immune evasion, confirming the effectiveness of the proposed strategy. And R-dECM demonstrates superior tendon repair outcomes compared to dECM. Thus, this study provides a novel bioactive scaffold with the potential to enhance the long-term clinical outcomes of xenogeneic tendon grafts.


[Analysis of traditional cardiovascular risk factors in patients with systemic lupus erythematosus].
To evaluation the prevalence of hypertension, diabetes, dyslipidemia in systemic lupus erythematosus (SLE) patients, and investigate the factors that affecting lipid levels in SLE patients. A total of 540 adult SLE patients hospitalized in Peking Union Medical College Hospital from March 2010 to March 2013 were retrospectively included (SLE group), and 1 080 gender and age matched (1: 2) healthy controls were selected from our medical examination center (control group). The prevalence rate of hypertension, diabetes, dyslipidemia and the levels of serum lipid were compared between the two groups, the factors affecting lipid levels in SLE patients were also analyzed. The percentage of hypertension, diabetes, dyslipidemia, elevated total cholesterol (TC), elevated triglyceride (TG), decreased high density lipoprotein cholesterol (HDL-C) and elevated low density lipoprotein cholesterol (LDL-C) in SLE patients were significantly higher than those in healthy controls (all P < 0.01) . Compared with the control group, SLE patients had significantly higher TC, TG, LDL-C levels and significantly lower HDL-C levels (all P < 0.01) . Multifactor regression analysis showed that TC and LDL-C levels were positively correlated with lupus nephritis (β = 0.695,0.437), corticosteroids therapy (β = 1.195, 0.715), complement C4 levels (β = 4.817, 3.382) and 24 hours urine protein content (β = 0.112, 0.078) (all P < 0.01) , but negatively correlated with serum albumin (Alb) (β = -0.107, -0.077) and high sensitive C reactive protein (hsCRP) levels (β = -0.021, -0.014) (all P < 0.01). TG levels were positively correlated with lupus nephritis (β = 0.359) and 24 hours urine protein content (β = 0.045) (both P < 0.05), negatively correlated with male gender (β = -0.605), age (β = -0.014) and Alb levels (β = -0.053) (P < 0.01 or 0.05). HDL-C levels were positively correlated with age (β = 0.007), lupus nephritis (β = 0.188), corticosteroids therapy (β = 0.342), consecutive 30 days cumulative corticosteroids dose before serum lipid were measured (β<0.001), and complement C3 levels(β = 0.351) (all P < 0.01) , negatively correlated with hsCRP levels (β = -0.005, P < 0.01). Serum lipid levels did not correlate with disease duration, disease activity, corticosteroids therapy time, corticosteroids daily dose before serum lipid measurement, serum creatinine levels and erythrocyte sedimentation rate (ESR) (all P > 0.05). The prevalence rate of hypertension, diabetes and dyslipidemia in SLE hospitalized patients are significantly higher compared to normal controls and lipid levels of SLE patients are related to various SLE disease factors.


Restoration of the type and palate of Ankarapithecus meteai: taxonomic and phylogenetic implications.
A small number of large hominoid specimens are known from the late Miocene of Turkey. (This paper focuses on the two specimens known until 1996. New fossils described by Alpagut et al. ([1996] Nature 382:349-351) are briefly discussed in this paper as well.) Among these, a fragmentary mandible is the type specimen of Ankarapithecus meteai. Another specimen, a partial face, is from the same taxon. Based on the morphology of this face, Ankarapithecus meteai was synonymized with Sivapithecus (Andrews and Tekkaya [1980], Paleontology 23:85-95). The facial specimen was recently restored by the authors, exposing much anatomy that had previously been obscured. The new anatomical details reveal many important differences from Sivapithecus and justify a revision of the nomen Ankarapithecus. Ankarapithecus was a large hominid (great apes and humans) in the clade that also includes Sivapithecus and Pongo. Sivapithecus and Pongo share derived characters not found in Ankarapithecus, which is thus the sister clade to the Sivapithecus-Pongo clade. While the results of this analysis support the sister relationship of Sivapithecus and Pongo, there is some uncertainty regarding paleobiogeographic and taxonomic relationships to the large hominids from the Siwaliks. An Ankarapithecus-like taxon may have been ancestral to Sivapithecus, or an early Siwalik (Chinji formation) taxon, which predates both Sivapithecus sensu stricto and Ankarapithecus, may be ancestral to both.


Eating disorders among college women: prevention, education, and treatment responses.
Eating-related problems, particularly among college women, represent a significant health concern on university campuses. Body image dissatisfaction, weight preoccupation, and unhealthy weight management are prevalent among even normal-weight students, but discussions of broad college health interventions in this area have been limited. Two conceptual tools that are useful in developing a comprehensive health center response to eating disorders in the college setting are described. The diagnosis of Eating Disorders Not Otherwise Specified is suggested as a framework for defining target populations and eating problems requiring intervention, and a picture of the prototypical eating problem candidate is developed. A multiple-level model of intervention that includes preventive, intermediate, and remedial responses to varied forms of eating-related concerns is described. The intervention model is illustrated with examples, and limitations of the method are discussed.


[A case of parathyroid carcinoma].
A case of parathyroid carcinoma in a 49-year-old female is described. She is found to have renal stones and high serum calcium levels. On physical examination a fixed walnut-sized mass was detected on her right neck. Laboratory studies disclosed a serum calcium level of 12.7 mg/dl, serum phosphorus level of 2.5 mg/dl, serum Ca++ level of 3.12 mEq/l, and positive Gold-Smith test. Computer-assisted tomography scan and ultrasonogram showed a mass in the posterior region of the right lobe of her thyroid. The tumor was resected and histopathological examination showed parathyroid carcinoma. The patient had no evidence of recurrence 2 years following surgery. Our report is the 70th case among Japanese literature.


Discontinued dermatological drugs in 2014.
Dermatology is a relatively small field concerned with conditions of the hair, skin, nails and their related diseases; yet there is considerable active research and development within the field. Pharmaceutical companies seek more effective treatments through various therapeutic classes and delivery routes. However, 28 drugs have been discontinued for the treatment of dermatologic diseases in 2014. Herein, the authors summarize the details about each discontinued drug in 2014. The dermatological conditions covered are: psoriasis, eczema, leg ulcers, wounds, allergies, acne, scleroderma, lupus erythematosus, urticaria, mastocytosis, epidermolysis bullosa, onychomycosis and one other unspecified disease. The authors also provide suggestions for improving and accelerating the future of dermatological drug development. It is clear that improved metrics, especially for early assessment, emphasizing clinical relevance, are necessary to increase success rate. Transparency and clear communication within the field is necessary to reduce and salvage the waste that accumulates from these costly studies. Focused attention on how preclinical and early clinical studies failed to indicate subsequent toxicity profiles in patients would accelerate drug development. Distinguishing between disappointing study results and business/financial factors is important when analyzing discontinuations. A reformed approach toward study design would aid both. Ultimately, relevance and practicality for the patient must be kept in mind at all times.


[Clinicopathologic analysis of Langerhans cell histiocytosis in adults].
To explore the clinical features, pathomorphology, immunohistochemical characteristics and prognosis of Langerhans cell histiocytosis (LCH) in adults. Twenty-three cases of adult LCH were retrieved from Ningbo Diagnostic Pathology Center during the period from January 2005 to December 2011. And their clinical presentation, pathomorphology and immunohistochemical characteristics were analyzed. The mean age of patients was 37.2 years (range: 20 - 58). The male-to-female ratio was 1.6:1. Of 23 LCH patients, 26 lesions were found including 14 bone tissue lesions (53.8%), followed by 4 lymph node lesions and 4 skin lesions (both 15.4%), as well as 1 soft tissue, liver, parotid and buccal lesion respectively (all 3.8%). Clinically, uni-system and unifocal disease was predominant (19 cases, 82.6%), followed by uni-system and multifocal disease (1 case, 4.3%), multi-system disease (3 cases, 13.0%). Histologically, all cases of LCH revealed diffused distribution of Langerhans cells, accompanied by a variable number of eosinophils, lymphocytes, neutrophils and multinucleated giant cells. Immunohistochemically, the expression of CD1a, Langerin, S-100 protein and CD68 was 100% (23/23), 100% (20/20), 95.6% (22/23) and 90.5% (19/21) respectively. All lesions were treated by surgical therapy. Sixteen patients were available for follow-up examination and 14 patients survived. The 3 and 5-year cumulative survival rates were 92.9% and 79.6% respectively. LCH of adults occurs predominantly in bone and presents mainly as uni-system or unifocal defects. Surgical excision is generally effective and the prognosis is fair.


Conflict resolution in healthcare management.
Conflict causes decided tension in the workplace and often produces poor professional outcomes. A manager dealing with conflict can experience a crisis of confidence and often ends up second-guessing himself or herself, regardless of how a situation has been handled. In some organizations, conflict is not viewed positively or as an opportunity for improvement. In these organizations, most individuals will see conflict as being unproductive, unpleasant, and a waste of time and energy. Yet, conflict provides employees with critical feedback on how things are going. When viewed in a positive context, even personality conflicts may provide information to the healthcare manager about what is not working in the organization. If conflict is not directed and controlled, it can have damaging effects in the workplace, stifling the growth of departments and deflating employee morale. Our job as healthcare managers is to deal with conflict so that it does not decrease productivity or detract from the provision of patient-centered care. There are 4 general sources for interpersonal conflict: personal differences, informational deficiency, role incompatibility, and environmental stress. There are 5 common responses used in dealing with conflict: forcing, accommodating, avoiding, compromising, and collaborating. Healthcare managers should become comfortable with using all of these approaches.


Dietary guidelines in type 2 diabetes: the Nordic diet or the ketogenic diet?
To highlight recent developments in research regarding nutrition therapies for type 2 diabetes mellitus (T2DM) with a focus on the different approaches of the Nordic diet and the ketogenic diet. Recent short-term studies have revealed that similar beneficial outcomes are seen after different dietary treatments for T2DM, with different approaches resulting in comparable weight loss and impacts on metabolic factors. More individualized approaches in nutrition therapy should be considered for T2DM patients and clinical guidelines should reflect this. More studies, especially long-term studies, are urgently needed on the impacts of the diets on different health parameters. Such studies should be prioritized because of the high and increasing prevalence of T2DM and because dietary changes may have greater benefits than previously thought. Furthermore, studies that focus on patient compliance to different types of diets, and personal and environmental factors that may affect compliance, are needed.


[The use of cerepro (choline alfoscerate) in the treatment of outpatients with chronic progressive cerebrovascular disease].
The main aim of the study was the evaluation of the efficacy and drug safety of cerepro (choline alfoscerate) used for treating outpatients with cerebrovascular disease. Ninety patients with cerebrovascular disease, who had motor, coordination, emotional and cognitive disturbances were enrolled in the study. Sixty patients of the group 1 had stroke, 30 patients (group 2) had chronic ischemic brain disease. All patients received basic therapy (antihypertensive, antiaggregant or anticoagulant, cholesterol-lowering drugs). Cerepro was administrated in combined therapy according to the scheme: 1000 mg cerepro (in 200 ml of the 0.9% NaCl solution) once a day intravenously in drops during 10 days; then 1200 mg daily per os during 6 weeks. We assessed the dynamic of neurological symptoms and restoration of lost functions (MMSE, Feeling-activity-mood test, HDRS, GCI). The results indicate the efficacy of cerepro in outpatients with chronic cerebrovascular disease and stroke. It was demonstrated that cerepro led to improvement of coordination neurological symptoms, cognitive and emotional functions, activity and mood in patients of both groups. Clinical effect was higher in patients after stroke. Cerepro was well tolerated.


Diagnosis of diabetic kidney disease: state of the art and future perspective.
Approximately 20% to 40% of patients with type 1 or type 2 diabetes mellitus develop diabetic kidney disease. This is a clinical syndrome characterized by persistent albuminuria (> 300 mg/24 h, or > 300 mg/g creatinine), a relentless decline in glomerular filtration rate (GFR), raised arterial blood pressure, and enhanced cardiovascular morbidity and mortality. There is a characteristic histopathology. In classical diabetic nephropathy, the first clinical sign is moderately increased urine albumin excretion (microalbuminuria: 30-300 mg/24 h, or 30-300 mg/g creatinine; albuminuria grade A2). Untreated microalbuminuria will gradually worsen, reaching clinical proteinuria or severely increased albuminuria (albuminuria grade A3) over 5 to 15 years. The GFR then begins to decline, and without treatment, end-stage renal failure is likely to result in 5 to 7 years. Although albuminuria is the first sign of diabetic nephropathy, the first symptom is usually peripheral edema, which occurs at a very late stage. Regular, systematic screening for diabetic kidney disease is needed in order to identify patients at risk of or with presymptomatic diabetic kidney disease. Annual monitoring of urinary albumin-to-creatinine ratio, estimated GFR, and blood pressure is recommended. Several new biomarkers or profiles of biomarkers have been investigated to improve prognostic and diagnostic precision, but none have yet been implemented in routine clinical care. In the future such techniques may pave the way for personalized treatment.


Phenolic compounds and antioxidant activities of tea-type infusions processed from sea buckthorn (Hippophaë rhamnoides) leaves.
Sea buckthorn (Hippophaë rhamnoides, SB) leaves contain wide-ranging bioactive compounds. Processing of the leaves into beverages/food presents great potential for supporting human health. The research aimed to investigate the impact of different processing methods on phenolic compounds and antioxidant activities of tea-type infusions prepared from SB leaves. Leaves of two SB cultivars, 'Terhi' and 'Tytti', were processed with different methods commonly used for tea processing. Phenolic compounds in the infusions were analyzed with High-Performance Liquid Chromatography-Diode-Array Detection and High-Performance Liquid Chromatography Electrospray Ionization-Tandem Mass Spectrometry. Isorhamnetin-3-O-glucoside-7-O-rhamnoside, isorhamnetin-3-O-rutinoside and kaempferol-3-O-hexoside-7-O-rhamnoside were the three major flavonol glycosides, stachyurin and casuarinin were the most abundant ellagitannins. The infusions of 'Tytti' contained more total phenolics than those of 'Terhi' (p < 0.05). High temperature processing resulted in higher content of total phenolics and ellagitannins in the infusions compared with low temperatures (p < 0.05). Thermal processing decreased the antioxidant activities of the infusions.


Murine models of Sjögren's syndrome. Immunohistologic analysis of different strains.
Lacrimal gland inflammation develops in several strains of autoimmune mice, including MRL/Mp-lpr/lpr (MRL/lpr), MRL/Mp-+/+ (MRL/+), and NZBxNZW F1 hybrids (NZB/W). These mice all develop an autoimmune disease characterized by glomerulonephritis and autoantibody formation, but each strain has unique clinical features and immunologic abnormalities. Previous studies have suggested that the intrinsic immunologic defect in MRL/lpr mice may be at the level of T cells, while in NZB/W mice it appears to be B cell-mediated. Immunohistologic analysis of the lacrimal gland lesions was performed on all three strains. Although T cells predominated (MRL/lpr 85%, MLR/+ 78%, and NZB/W 57%), differences in the immunohistologic profiles did exist. NZB/W mice had a significantly higher percentage of B cells (33% vs. 10% for MRL/lpr and 13% for MRL/+) and a correspondingly lower percentage of T cells. MRL/lpr mice differed from MRL/+ mice in that they exhibited a significantly higher percentage of helper T cells (63% vs. 49%) and a lower percentage of suppressor/cytotoxic T cells (14% vs. 30%). Class II antigen expression could be detected on the mononuclear cells at inflammatory sites within the lacrimal glands of all three strains, suggesting T cell activation and an active autoimmune immunologic event occurring in the lacrimal gland.


Host niche may determine disease-driven extinction risk.
The fungal pathogen Batrachochytrium dendrobatidis (Bd) drives declines and extinctions in amphibian communities. However, not all regions and species are equally affected. Here, we show that association with amphibian aquatic habitat types (bromeliad phytotelmata versus stream) across Central America results in the odds of being threatened by Bd being five times higher in stream microhabitats. This differential threat of Bd was supported in our study by a significantly lower prevalence of Bd in bromeliad-associated amphibian species compared to riparian species in Honduran cloud forests. Evidence that the bromeliad environment is less favorable for Bd transmission is exemplified by significantly less suitable physicochemical conditions and higher abundance of Bd-ingesting micro-eukaryotes present in bromeliad water. These factors may inhibit aquatic Bd zoospore survival and the development of an environmental reservoir of the pathogen. Bromeliad phytotelmata thus may act as environmental refuges from Bd, which contribute to protecting associated amphibian communities against chytridiomycosis-driven amphibian declines that threaten the nearby riparian communities.


Expression of resolvin D1 biosynthetic pathways in salivary epithelium.
Resolvins are potent anti-inflammatory mediators derived from ω-3 fatty acids. Results from our previous studies indicated that resolvin D1 (RvD1) blocks pro-inflammatory responses in salivary glands. Furthermore, RvD1 enhances salivary epithelial integrity, demonstrating its potential use for the restoration of salivary gland function in Sjögren's syndrome (SS). We investigated whether the RvD1 biosynthetic machinery (e.g., cytosolic phospholipase A2, calcium-independent phospholipase A2, 12/15 and 5-lipoxygenase) is expressed in mouse submandibular glands (mSMG), using qPCR and Western blot analyses. Additionally, we determined the localization of RvD1 biosynthetic machinery in mSMG and human minor salivary glands (hMSG), with and without SS, using confocal microscopy. Finally, we measured RvD1 levels in cell supernatants from mSMG cell cultures and freshly isolated mSMG cells, with and without SS, using ELISA. Our results indicate that: (1) RvD1 machinery is expressed in mouse and human salivary glands; (2) polar distribution of RvD1 biosynthetic machinery is lost in hMSG with SS; (3) RvD1 levels in mSMG cell culture supernatants increased with time; and (4) RvD1 levels in mSMG cell supernatants, with and without SS, were similar. These studies demonstrate that the RvD1 biosynthesis machinery is expressed and functional in salivary glands with and without SS.


Microcephaly Outcomes among Zika Virus-Infected Pregnant Women in Honduras.
The impact of Zika virus (ZIKV) infection on pregnancies shows regional variation emphasizing the importance of studies in different geographical areas. We conducted a prospective study in Tegucigalpa, Honduras, recruiting 668 pregnant women between July 20, 2016, and December 31, 2016. We performed Trioplex real-time reverse transcriptase-PCR (rRT-PCR) in 357 serum samples taken at the first prenatal visit. The presence of ZIKV was confirmed in seven pregnancies (7/357, 2.0%). Nine babies (1.6%) had microcephaly (head circumference more than two SDs below the mean), including two (0.3%) with severe microcephaly (head circumference [HC] more than three SDs below the mean). The mothers of both babies with severe microcephaly had evidence of ZIKV infection. A positive ZIKV Trioplex rRT-PCR was associated with a 33.3% (95% CI: 4.3-77.7%) risk of HC more than three SDs below the mean.


A Domain-General Developmental "Do-GooD" Network Model of Prosocial Cognition in Adolescence: A Systematic Review.
Adolescence is a period of substantial neural and social development, and prosocial decisions are beneficial to personal well-being, the well-being of others, and the functioning of society. Advances in network neuroscience call for a systematic synthesis and reappraisal of prosocial neural correlates during adolescent development. In this systematic review, we aim to outline the progress made in this field, identify the similarities between study results, and propose a model for prosocial cognition in adolescents to young adults. A total of 25 articles were included in this review. After reviewing and synthesizing the literature, we propose a DOmain-General Developmental "Do-GooD" network model of prosocial cognition that aligns with the reviewed literature, accounts for development, and combines elements of the value-based decision-making model with distinct value contributions from the default mode network, salience network, and control network. We offer predictions to test the "Do-GooD" model and propose new future directions for studying prosocial behavior and its development during adolescence, which in turn may lead to improving education and the development of better health interventions for adolescents.


Endogenous histamine in immune inflammation in 6-day-old air pouch of facsimile synovium.
Immune inflammation was induced by injecting bovine serum albumin (BSA) into 6-day-old air pouches of mice presensitized with 2 weekly injections of an emulsion containing BSA and complete Freund's adjuvant. Control mice were also similarly pretreated with the same emulsion without BSA. The results show that the numbers of exudate leucocytes in the air pouches of both test and control groups increased and peaked at 4 h and then declined after the antigen challenge. However, the values of exudate leucocytes in the test animals at 4- and 24-hour intervals were significantly lower than those of the control. On the other hand, exudate histamine of the test group peaked at 1 h, and this was significantly higher than that of the control. Injection of exogenous histamine or histaminase with the challenging antigen increased the number of exudate leucocytes in both test and control animals. The findings thus suggest that endogenous histamine released in immune inflammation most probably plays the same role as in non-immune inflammation by enhancing the vascular permeability at the inflammatory site in the early phase of the inflammatory reaction.


Law and older people--the rise and fall of Israel's Senior Citizens' Act.
Within the broad and complex framework of those Israeli laws that relate to the social welfare of the older population, this article uses a case study approach to focus on Israel's Senior Citizens' Act of 1989. During its hitherto brief life, this law has undergone numerous transformations, additions, and deletions as well as successes and failures. At the time of its enactment, many hoped that this law would considerably bolster the rights of older people. Echoing legal and political theories of the 1980s, it seemed to reflect the fact that politicians were sensitive to the potential power of the pensioner vote, while echoing the approach to social engineering that advocated the use of the law both as a means for social change and a symbol of power. As of today, however, this article argues that the law has failed to realize what were declared to be its objectives. Instead of promoting social change and providing older people with political power, the Senior Citizens' Act has become an empty symbol that hides the fact that the older generation in Israel still lacks the real political power it needs in order to use the law to improve society's treatment of older people.


Immunocytochemical and molecular data guide peptide identification by mass spectrometry: orcokinin and orcomyotropin-related peptides in the stomatogastric nervous system of several crustacean species.
In order to identify new orcokinin and orcomyotropin-related peptides in crustaceans, molecular and immunocytochemical data were combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). In the crayfish Procambarus clarkii, four orcokinins and an orcomyotropin-related peptide are present on the precursor. Because these peptides are highly conserved, we assumed that other species have an identical number of peptides. To identify the peptides, immunocytochemistry was used to localize the regions of the stomatogastric nervous system in which orcokinins are predominantly present. One of the regions predominantly containing orcokinins was a previously undescribed olive-shaped neuropil region within the commissural ganglia of the lobsters Homarus americanus and Homarus gammarus. MALDI-TOF MS on these regions identified peptide masses that always occur together with the known orcokinins. Seven peptide ions occurred together in the peptide massspectra of the lobsters. Mass spectrometric fragmentation by MALDI-MS post-source decay (PSD) and electrospray ionization quadrupole time-of-flight mass spectrometry (ESI Q-TOF MS) collision-induced dissociation (CID) were used in the identification of six of these masses, either as orcokinins or as orcomyotropin-related peptides and revealed three hitherto unknown peptide variants, two of which are [His13]-orcokinin ([M+H]+ = 1540.8 Da) and an orcomyotropin-related peptide FDAFTTGFGHN ([M+H]+ = 1213.5 Da). The mass of the third previously unknown orcokinin variant corresponded to that of an identified orcokinin, but PSD fragmentation did not support the suggested amino acid sequence. CID analysis allowed partial de novo sequencing of this peptide. In the crab Cancer pagurus, five orcokinins and an orcomyotropin-related peptide were unambigously identified, including the previously unknown peptide variant [Ser9-Val13]-orcokinin ([M+H]+ = 1532.8 Da).


Twist-angle-controlled neutral exciton annihilation in WS2 homostructures.
Exciton-exciton annihilation (EEA), as typical nonradiative recombination, plays an unpopular role in semiconductors. The nonradiative process significantly reduces the quantum yield of photoluminescence, which substantially inhibits the maximum efficiency of optoelectronic devices. Recently, laser irradiation, introducing defects and applying strain have become effective means to restrain EEA in two-dimensional (2D) transition metal dichalcogenides (TMDCs). However, these methods destroy the atomic structure of 2D materials and limit their practical applications. Fortunately, twisted structures are expected to validly suppress EEA through excellent interface quality. Here, we develop a non-destructive way to control EEA in WS2 homostructures by changing the interlayer twist angle, and systematically study the effect of interlayer twist angle on EEA, using fluorescence lifetime imaging measurement (FLIM) technology. Due to the large moiré potential at a small interlayer twist angle, the diffusion of excitons is hindered, and the EEA rate decreases from 1.01 × 10-1 cm2 s-1 in a 9° twisted WS2 homostructure to 4.26 × 10-2 cm2 s-1 in a 1° twisted WS2 homostructure. The results reveal the important role of the interlayer twist angle and EEA interaction in high photoluminescence quantum yield optoelectronic devices based on TMDC homostructures.


Squamous cell carcinoma on the palate in a patient with systemic lupus erythematosus: case report and review of literature.
Squamous cell carcinoma is a rare consequence of lupus erythematosus and it is generally associated with skin lesions rather than with oral mucosa. This paper reports a patient diagnosed with systemic lupus erythematosus who developed a squamous cell carcinoma on the palate as an outcome of a persistent ulcer, a frequent lesion in patients with this disease and, in fact, clinical criterion for its diagnosis. A 38-year-old female patient diagnosed with systemic lupus erythematosus 12 years previously, who attended the dental school for routine dental control. The patient was being treated with prednisone 10 mg per day and cyclophosphamide 750 mg per month until 10 months prior to her diagnostic biopsy. She had, however, been previously treated with chloroquine. Oral lesions started 6 months before consultation as symptomatic multiple ulcers on the palate. After topical treatment with steroids for 1 month, the lesions regressed except for the central lesion, from which an incisional biopsy was taken and a well differentiated squamous cell carcinoma was diagnosed. The oncological phase consisted of partial palatectomy. To date, 3 years after surgery, the patient is free from malignant lesions. Lupus erythematosus is considered a potentially malignant disorder, although the cause for neoplasic transformation in these patients is still not clear, but cyclophosphamide consumption may be implicated; the case emphasizes the importance of periodical oral evaluation of such patients. Repeated biopsies should be performed if there is failure to respond to conventional therapy.


Therapeutic application of cardiac stem cells and other cell types.
Various researches on regenerative medicine were carried out experimentally, and selected modalities have been introduced to the clinical arena. Meanwhile, the presence of resident stem cells in the heart and their role in physiological cell turnover were demonstrated. So far skeletal myoblasts, bone marrow-derived cells, mesenchymal stromal cells, and resident cardiac cells have been applied for therapeutic myocardial regeneration. Among them, autologous transplantation of c-kit-positive cardiac stem cells in congestive heart failure patients resulted in an outstanding outcome, with long-lasting beneficial effects without major adverse events. By reviewing these clinical trials, an endeavor was made to seek for an ideal cellular therapy for cardiovascular diseases.


Neuronal correlates of risk-seeking attitudes to anticipated losses in binge drinkers.
Abnormal decision making under risk is associated with a number of psychiatric disorders. Here, we focus on binge drinkers (BD), characterized by repeated episodes of heavy alcohol intoxication. Previous studies suggest a decreased sensitivity to aversive conditioning in BD. Here, we asked whether BD might be characterized by enhanced risk seeking related to decreased sensitivity to the anticipation of negative outcomes. Using an anticipatory risk-taking task (40 BD and 70 healthy volunteers) and an adapted version of this task for functional magnetic resonance imaging (21 BD and 21 healthy volunteers), we assessed sensitivity to reward and loss across risk probabilities. In the behavioral task, BD showed a higher number of risky choices in high-risk losses. In the neuroimaging task, the high-risk attitude in the loss condition was associated with greater activity in dorsolateral prefrontal, lateral orbitofrontal, and superior parietal cortices in BD. Explicit exposure of BD to the probability and magnitude of loss, via introduction of feedback, resulted in a subsequent decrease in risky choices. This change in risk attitude in BD was associated with greater activity in inferior frontal gyrus, which also correlated with the percentage of decrease in risky choices after feedback presentation, suggesting a possible role for cognitive control toward risk-seeking attitudes. Our findings suggest that a decrease in sensitivity to the anticipation of high-risk negative outcomes might underlie BD behavior. Presentation of explicit feedback of probability and loss in BD can potentially modify risk-taking attitudes, which have important public health implications and suggest possible therapeutic targets.


[Clinical comparative analysis of comprehensive laparoscopic and laparotomic staging of early-stage epithelial ovarian cancer].
Objective: To investigate the value of laparoscopy in comprehensive early ovarian cancer staging by comparing the feasibility and safety of laparoscopy and laparotomy in surgical staging of early-stage epithelial ovarian cancer (EOC). Methods: A total of 102 patients with EOC who underwent comprehensive laparoscopic (LPS group, n=71) or laparotomic (LPT group, n=31) staging at Southwest Hospital from November 2007 to November 2014 were retrospectively analyzed. The perioperative parameters, postoperative complication rate and the long-term curative effect were compared between the two groups. Results: (1) LPS group had less intra-operative blood loss [(288±239) vs (631±463) ml], lower rate of blood transfusion (14% vs 58%) , larger number of pelvic dissected lymph nodes (18.1±5.6 vs 15.5±4.6), lower vasual analogue scalescore (VAS) pain score (2.1±1.6 vs 3.0±1.1), shorter gastrointestinal recovery time [(2.6±0.8) vs (3.5±0.9) days] and shorter hospital stay [(9.9±2.9) vs (11.3±5.0) days] when compared with LPT group (all P<0.01). No significant difference were found in operation time, number of para-aortic lymph nodes, rate of postoperative upstaging and adjuvant chemotherapy between the two groups (all P>0.05). (2) No significant difference was found in postoperative rate of complications [11%(8/71) vs 19% (6/31), χ(2)=1.192, P=0.275]. (3) No significant difference was found in recurrence rate [17%(11/66) vs 14%(4/29), χ(2)=0.125, P=0.724] and 5-year overall survival (86.7% vs 86.8%, P=0.874) . Conclusion: Compared with LPT group, there are no significance differences in recurrence rate and mortality between two groups, laparoscopic staging, which could be recommended as a choice of surgical treatment of early ovarian cancer, shows more favorable operative outcomes including minimally invasive, less intra-operative blood loss, less postoperative pain and quicker recovery.


Update on Substance Use in Adolescence.
With alarming frequency, an individual's first substance use occurs in childhood or adolescence. However, the use of many types of substances among individuals younger than 18 has been gradually declining over the past 6 years, and our understanding of risk factors for youth substance use has improved. Risk factors identified as possibly contributing to a young individual's first encounter with cigarettes or alcohol include parents' own substance use or mental health problems. Mental disorders of children have been implicated in substance use as well. Screening and interventions are available to reduce the frequency and intensity of adolescent substance use and are suggested in the current article. Nurses are in a position to identify adolescents who are at risk for substance use disorders and link the family system to effective intervention. [Journal of Psychosocial Nursing and Mental Health Services, 54(8), 24-27.].


Late atrioventricular groove disruption presenting 7 years after mitral valve replacement: a case report.
Left ventricular rupture is the most feared complication in mitral valve surgery. Despite its low incidence, mortality rates can reach up to 75%. It usually presents on the operating room with a dissecting haematoma followed by massive bleeding after discontinuing cardiopulmomary bypass. However, cardiac rupture may be contained by adherent pericardium or scar tissue leading to chronic formation of a pseudoaneurysm (PSA). A 44-year-old man came to our institution with acute heart failure triggered by community-acquired pneumonia. He underwent mitral valve replacement with a mechanical prosthesis 7 years before and reported suffering from chronic worsening dyspnoea for 18 months. He underwent chest computed tomography scan and cardiac magnetic resonance imaging (CMRI), which showed two extensive left ventricular (LV) multilobulated PSAs. An operative approach was chosen and a tear was found on the posterior atrioventricular groove (AVG), communicating left ventricle with the PSA, which was closed with bovine pericardium patch. After weaning from cardiopulmonary bypass, he presented a diffuse life-threatening bleeding. The surgeons packed his chest with compresses before closing the sternum and he was operatively revised after 48 h. Post-operative CMRI showed that one of the PSAs remained connected with the LV. Despite of all, 1 year after hospital discharge, he remains asymptomatic without signs of heart failure. This case illustrates PSAs' potential to grow for a long period before causing symptoms, the complexity and risks of chronic AVG disruption surgery and the importance of careful annular manipulation and debridement as preventive measures in mitral valve surgery.


Understanding, Modulating, and Leveraging Transannular M → Z Interactions.
Density functional theory calculations have been performed on metallatranes featuring a group 13 elements at the bridgehead position to understand the factors that influence the nature of the M···Z (M = Fe, Co, Ni; Z = Al, Ga, In) interaction present in these complexes and the resultant reactivity at the metal center. The strength of the M···Z interaction increases with the increase in the size and polarizability of the bridgehead group 13 elements. The calculated reaction free energies (ΔG° values) for binding of different Lewis bases to the metallatranes are found to be significantly more exergonic for the larger In(III) ions. Quantum theory of atoms in molecules calculations reveal the covalent nature of the M···Z interactions, while the EDA-NOCV analysis indicates the strong binding ability of these metallatranes not only to different σ-donor and π-acceptor ligands but also to relatively inert species, such as N2.


Identification of the Fc-alpha/mu receptor in Xenopus provides insight into the emergence of the poly-Ig receptor (pIgR) and mucosal Ig transport.
The polyimmunoglobulin receptor (pIgR) transcytoses J chain-containing antibodies through mucosal epithelia. In mammals, two cis-duplicates of PIGR, FCMR, and FCAMR, flank the PIGR gene. A PIGR duplication is first found in amphibians, previously annotated as PIGR2 (herein xlFCAMR), and is expressed by APCs. We demonstrate that xlFcamR is the equivalent of mammalian FcamR. It has been assumed that pIgR is the oldest member of this family, yet our data could not distinguish whether PIGR or FCAMR emerged first; however, FCMR was the last family member to emerge. Interestingly, bony fish "pIgR" is not an orthologue of tetrapod pIgR, and possibly acquired its function via convergent evolution. PIGR/FCAMR/FCMR are members of a larger superfamily, including TREM, CD300, and NKp44, which we name the "double-disulfide Ig superfamily" (ddIgSF). Domains related to each ddIgSF family were identified in cartilaginous fish (sharks, chimeras) and encoded in a single gene cluster syntenic to the human pIgR locus. Thus, the ddIgSF families date back to the earliest antibody-based adaptive immunity, but apparently not before. Finally, our data strongly suggest that the J chain arose in evolution only for Ig multimerization. This study provides a framework for further studies of pIgR and the ddIgSF in vertebrates.


Dependent rubor as a predictor of limb risk in patients with claudication.
We followed up 133 patients with claudication to determine the prognostic value of dependent rubor. Life tables analysis was used, with a threatened limb as the endpoint. A threatened limb was defined as the development of ischemic rest pain, skin ulceration, or gangrene. At four years, the rubor group had a limb-threat incidence of 25%, compared with only 9% in the nonrubor group. While not indicative of imminent limb loss, the presence of dependent rubor defines patients whose limb risk is greater than in those with claudication alone.


Doctors' views on diabetes.
Children with diabetes may be managed by either paediatricians or adult physicians with a particular interest in diabetes. This study compares the views of these two groups of doctors on juvenile onset diabetes. A questionnaire was given to all doctors attending two conferences, one primarily for paediatricians and one primarily for adult physicians with a particular interest in diabetes. Adult physicians estimated morbidity and mortality from juvenile onset diabetes to be significantly higher after 30 years than did paediatricians. The two groups of doctors also differed in the target blood glucose concentrations they considered optimal for diabetic children--more paediatricians opted for higher values than did adult physicians. The findings of this study support the view that paediatricians and adult physicians view juvenile onset diabetes differently. The origin of these differences is uncertain but may relate to the contrasting clinical experiences of the two groups of specialists.


Diagnoses of traumatic brain injury not clearly associated with deployment, active component, U.S. Armed Forces, 2001-2016.
From 2001 through 2016, a total of 276,858 active component service members received first-time diagnoses of traumatic brain injury (TBI). Person-time and incident cases of TBI were assigned to one of three groups. Group 1 included only service members' person-time before their first-ever deployments. Group 2 included service members' person-time during their overseas deployments and the 30 days after their return from deployment. Group 3 included only service members' person-time more than 30 days after return from deployment. The crude overall incidence rate of TBI among deployed service members (1,690.5 cases per 100,000 person-years [p-yrs]) was 1.5 times that of service members in group 1 (1,141.3 cases per 100,000 p-yrs), and 1.2 times that of service members in group 3 (1,451.2 cases per 100,000 p-yrs). The portion of the surveillance period during which the annual incidence rates of TBI in groups 3 and 2 exceeded the rates in group 1 likely represents, at least in part, the increased risk of service in an active combat zone. For group 2, this period extended from 2007 through 2013. For group 3, this period lasted from 2007 through 2016. Examination of the TBI case-defining encounters with recorded injury causes yielded leading causes similar to those of TBIs in same-aged civilians (land transport and slips, trips, and falls). Factors that may explain why the TBI incidence rates among the previously deployed were higher than those of the never-deployed group are discussed.


Endotoxin-induced inflammation disturbs melatonin secretion in ewe.
The study examined the effect of intravenous administration of bacterial endotoxin-lipopolysaccharide (LPS) -on the nocturnal secretion of melatonin and on the expression of enzymes of the melatonin biosynthetic pathway in the pineal gland of ewes, taking into account two different photoperiodic conditions: short-night (SN; n = 12) and long-night (LN; n = 12). In both experiments, animals (n = 12) were randomly divided into two groups: control (n = 6) and LPS-treated (n = 6) one. Two hours after sunset, animals received an injection of LPS or saline. Blood samples were collected starting one hour after sunset and continuing for 3 hours after the treatment. The ewes were euthanized 3 hours after LPS/saline treatment. The concentration of hormones in plasma was assayed by radioimmunoassay. In the pineal gland, the content of serotonin and its metabolite was determined by HPLC; whereas the expression of examined genes and protein was assayed using real-time polymerase chain reaction and Western Blot, respectively. Endotoxin administration lowered (p<0.05) levels of circulating melatonin in animals from LN photoperiod only during the first hour after treatment, while in ewes from SN photoperiod only in the third hour after the injection. Inflammation more substantially suppressed biosynthesis of melatonin in ewes from SN photoperiod, which were also characterised by lower (p<0.05) cortisol concentrations after LPS treatment compared with animals from LN photoperiod. In the pineal gland of ewes subjected to SN photoperiod, LPS reduced (p<0.05) serotonin content and the expression of melatonin biosynthetic pathway enzymes, such as tryptophan hydroxylase and arylalkylamine-N-acetyltransferase. Pineal activity may be disturbed by circulating LPS and proinflammatory cytokines because the expression of mRNAs encoding their corresponding receptors was determined in this gland. The present study showed that peripheral inflammation reduces the secretion of melatonin, but this effect may be influenced by the photoperiod.


Serum and diet long-chain omega-3 fatty acid nutritional status in Chinese elite athletes.
Omega-3 polyunsaturated fatty acids (omega-3 PUFAs) are essential for improving the health and performance of athletes. The present study aimed to evaluate the nutritional status of omega-3 PUFAs in Chinese elite athletes by both dietary intake analysis and serum biomarker detection. A cross-sectional analysis of data from 54 elite athletes (24 men and 30 women) from Shanghai professional sports teams was conducted. A food frequency questionnaire (FFQ) was employed to analyze dietary intake, and gas chromatography-mass spectrometry (GC-MS/MS) was conducted to measure serum biomarkers of PUFAs. Correlation analysis was performed to investigate the relationships of PUFA biomarkers with diet, inflammation and oxidative stress. The results showed that the median intake of EPA + DHA among athletes was 132 mg/d, which is lower than the minimum value recommended by dietary guidelines (250 mg/d). The average serum EPA + DHA was 4.0 ± 1.1%, and the ratio of omega-6/omega-3 was 7.7 ± 1.7. Most (96.3%) of the athletes were below the targeted value of serum EPA + DHA, which is associated with a reduction in cardiovascular risk. Correlation analysis showed that the serum EPA + DHA was positively correlated with the long-term dietary intake of EPA + DHA and negatively correlated with inflammatory markers. In conclusion, the serum circulating EPA + DHA and omega-6/omega-3 ratio are effective biomarkers reflecting the nutritional status of PUFAs in athletes. Omega-3 PUFAs have a potential effect on inhibiting inflammatory markers. Hence, it is necessary for Chinese athletes to improve their suboptimal nutritional status of PUFAs through dietary intervention.


Utility of routine ultrasound after laparoscopic cholecystectomy to detect early postoperative complication.
In up to 3% of laparoscopic cholecystectomies, procedure-related complications occur. Routine postoperative ultrasound is one means of screening for these complications. The aim of this study was to determine the utility of this practice after laparoscopic cholecystectomy. A series of consecutive patients (n = 1,044) undergoing laparoscopic cholecystectomy from January 2007 to January 2011 was analysed. Primary endpoint was the detection of procedure-related complications by routine ultrasound. Routine ultrasound within the first 48 h after laparoscopic cholecystectomy was performed in 967 of 1,044 patients. Overall, 25 (2.4%) of the 1,044 patients suffered from procedure-related complications, but only in 2 patients was the complication detected by routine ultrasound. Findings were false-positive in 103 patients. This corresponds to a sensitivity of 8% and a specificity of 89%. Hospital stay was prolonged in the false-positive group. Routine postoperative ultrasound has a low sensitivity for the detection of complications after laparoscopic cholecystectomy. In almost all cases, the diagnosis is initiated by clinical findings. Therefore, routine ultrasound is of limited value in screening for postoperative complications after cholecystectomy.


Biosorption of silver cations onto Lactococcus lactis and Lactobacillus casei isolated from dairy products.
The current work deals with the phenomenon of silver cations uptake by two kinds of bacteria isolated from dairy products. The mechanism of sorption of silver cations by Lactococcus lactis and Lactobacillus casei bacteria was investigated. Inductively coupled plasma-mass spectrometry (ICP-MS) was used for determination of silver concentration sorbed by bacteria. Analysis of charge distribution was conducted by diffraction light scattering method. Changes in the ultrastructure of Lactococcus lactis and Lactobacillus casei cells after treatment with silver cations were investigated using transmission electron microscopy observation. Molecular spectroscopy methods, namely Fourier transform-infrared spectroscopy (FT-IR) and matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) were employed for description of the sorption mechanism. Moreover, an analysis of volatile organic compounds (VOCs) extracted from bacterial cells was performed.


Fully automated dose prediction using generative adversarial networks in prostate cancer patients.
Although dose prediction for intensity modulated radiation therapy (IMRT) has been accomplished by a deep learning approach, delineation of some structures is needed for the prediction. We sought to develop a fully automated dose-generation framework for IMRT of prostate cancer by entering the patient CT datasets without the contour information into a generative adversarial network (GAN) and to compare its prediction performance to a conventional prediction model trained from patient contours. We propose a synthetic approach to translate patient CT datasets into a dose distribution for IMRT. The framework requires only paired-images, i.e., patient CT images and corresponding RT-doses. The model was trained from 81 IMRT plans of prostate cancer patients, and then produced the dose distribution for 9 test cases. To compare its prediction performance to that of another trained model, we created a model trained from structure images. Dosimetric parameters for the planning target volume (PTV) and organs at risk (OARs) were calculated from the generated and original dose distributions, and mean differences of dosimetric parameters were compared between the CT-based model and the structure-based model. The mean differences of all dosimetric parameters except for D98% and D95% for PTV were within approximately 2% and 3% of the prescription dose for OARs in the CT-based model, while the differences in the structure-based model were within approximately 1% for PTV and approximately 2% for OARs, with a mean prediction time of 5 seconds per patient. Accurate and rapid dose prediction was achieved by the learning of patient CT datasets by a GAN-based framework. The CT-based dose prediction could reduce the time required for both the iterative optimization process and the structure contouring, allowing physicians and dosimetrists to focus their expertise on more challenging cases.


Adherence to the Mediterranean Diet and Its Association With Sleep Quality and Chronotype Among Youth: A Cross-Sectional Study.
Evidence indicates that many university students have poor adherence to a healthy diet accompanied by unhealthy lifestyle behaviors. Chrono-nutrition is an emerging field of research that examines the pattern of optimum daily activity in relation to the human's dietary patterns, and their reflections of variable health indicators such as sleep quality. However, there is a scarcity of research that examines the relationship between adherence to the healthy eating pattern, like the Mediterranean diet (MD), with sleep quality and chronotype among university students. A cross-sectional study was conducted, and convenience sampling was used. Participants were assessed for adherence to the MD using the Mediterranean Diet Quality Index (KIDMED), for sleep quality using the Pittsburgh Sleep Quality Index (PSQI), and for chronotype using the Morningness-Eveningness questionnaire (MEQ). The study included 503 university students, most of them (81.5%) were females. Only 15.1 and 16.9% reported morningness chronotype and good sleep quality, respectively. About half of the students showed medium and high adherence to the KIMED. In-depth analysis revealed that students with good adherence to the MD were more likely to have a good sleep quality (OR = 0.35; 95%CI: 0.21-0.59; P < 0.001) even after adjustment for age and sex (OR = 0.36; 95%CI: 0.21-0.62; P < 0.001). The regression analysis also showed that those with good adherence to the MD had a significant association with better subjective sleep quality, less sleep latency, sleep disturbance, and daytime dysfunction even after adjustment for age and sex. Those with morningness chronotype had about a six-fold higher chance to have good adherence to the MD (OR = 5.67; 95%CI: 2.86-11.26; P < 0.001, respectively). Good adherence to the healthy diet presented in the MD among university students is associated with morningness chronotype and with improved overall sleep quality and sleep components. Long-term, controlled intervention research works are warranted for more elaboration on the impact of chronotype and dietary habits on sleep quality and other important aspects such as mental health and academic achievement.


Is cannabis use a contributory cause of psychosis?
To assess whether cannabis use in adolescence and young adulthood is a contributory cause of schizophreniform psychosis in that it may precipitate psychosis in vulnerable individuals. We reviewed longitudinal studies of adolescents and young adults that examined the relations between self-reported cannabis use and the risk of diagnosis with a psychosis or of reporting psychotic symptoms. We also reviewed studies that controlled for potential confounders, such as other forms of drug use and personal characteristics that predict an increased risk of psychosis. We assessed evidence for the biological plausibility of a contributory causal relation. Evidence from 6 longitudinal studies in 5 countries shows that regular cannabis use predicts an increased risk of a schizophrenia diagnosis or of reporting symptoms of psychosis. These relations persisted after controlling for confounding variables, such as personal characteristics and other drug use. The relation did not seem to be a result of cannabis use to self-medicate symptoms of psychosis. A contributory causal relation is biologically plausible because psychotic disorders involve disturbances in the dopamine neurotransmitter systems with which the cannabinoid system interacts, as demonstrated by animal studies and one human provocation study. It is most plausible that cannabis use precipitates schizophrenia in individuals who are vulnerable because of a personal or family history of schizophrenia.