Relationship between leptin and C-reactive protein in young Finnish adults.
Leptin and C-reactive protein (CRP) concentrations are increased in inflammation, and both have been linked to increased risk for cardiovascular diseases. The objective of the study was to explore in a population-based sample whether the relation between leptin and CRP is independent of obesity level and whether genetic causes of CRP elevation contribute to leptin levels. This was a population-based study including 1862 young adults (971 women; 891 men) aged 24-39 yr. The study was conducted at five centers in Finland. Associations between leptin and CRP adjusted for obesity indices, risk factors, genetic variables, and lifestyle variables were measured. Women had 3.0-fold higher median concentrations of leptin (12.5 vs. 4.1 ng/ml) and 1.3-fold higher median concentrations of CRP (0.75 vs. 0.56 mg/liter) than men (P < 0.0001 in both comparisons). In univariate analyses, CRP and leptin were significantly intercorrelated (r = 0.47, P < 0.0001 for women; r = 0.46, P < 0.0001 for men). In multiple regression analysis including age, body mass index, waist circumference, insulin, lipids, systolic and diastolic blood pressures, smoking status, and use of oral contraceptives in women, leptin was the main determinant of CRP in men (P < 0.0001) and the second most important determinant in women (P < 0.0001). A Mendelian randomization test based on genetic variants in the CRP gene (five single nucleotide polymorphisms) provided no support for CRP as a causal agent for leptin. Leptin, obesity, and oral contraceptive use in women were the main factors related to CRP. The relation between leptin and CRP was independent of obesity and cardiovascular risk factors.


Effect of mild essential hypertension on control of forearm blood flow during exercise in the heat.
Six essential hypertensive (resting mean arterial pressure, MAP greater than 110 mmHg) and eight normotensive (resting MAP less than 95 mmHg) men, aged 30-58 yr, were tested during 1 h of dynamic leg exercise in the heat. Environmental conditions were fixed at 38 degrees C dry-bulb temperature and 28 degrees C wet-bulb temperature; exercise intensity was preset to approximate 40% of each subject's maximal aerobic capacity (actual range 38-43%). Forearm blood flow (FBF) was measured by impedance plethysmography. The intergroup difference in arterial pressure was maintained but not increased or decreased during exercise in the heat. FBF increased in both groups, but the increase was significantly less for the hypertensive subjects. FBF showed a significant linear correlation (different from 0) with core temperature in seven of eight control subjects but in none of the hypertensive subjects. The magnitude of FBF increase was inversely proportional to resting MAP (r = -0.89). It was concluded that essential hypertensive subjects respond to exercise in the heat with a diminished FBF response related to an alteration in control relative to central (core temperature) influences. This may be due to an imbalance between thermal and nonthermal (baroreflex) mechanisms controlling cutaneous blood flow.


Trends of maternal waterpipe, cigarettes, and dual tobacco smoking in Jordan. A decade of lost opportunities.
Maternal tobacco use is a global public health problem. In the literature, the focus was mainly on cigarette smoking, minimally on waterpipe use, and totally ignored dual use among pregnant women. We estimated the prevalence of current maternal tobacco use by tobacco product (cigarette, waterpipe, and dual use) over a period of ten years (2007 to 2017), and examined the socio-demographic patterning of maternal tobacco use. A secondary analysis of Jordan DHS four data waves was conducted for women who reported to be pregnant at the time of the survey. Current cigarette and waterpipe tobacco use were investigated. Prevalence estimates for cigarette-only, waterpipe-only, and dual use, as well as for cigarette, regardless of waterpipe, and waterpipe, regardless of cigarette, were reported. The effect of independent variables on cigarette smoking, waterpipe use, and dual use was assessed. Logistic regression models assessed the adjusted effects of socio-demographic variables on cigarette smoking, waterpipe use, and on dual use. For each outcome variable, a time-adjusted and a time-unadjusted logistic models were conducted. Over the last decade, the prevalence estimates of current cigarette-only smoking slightly decreased. The prevalence estimates of current waterpipe-only use exceeded those for cigarette-only after 2007 and showed a steady overall increase. Current dual use showed a continuous rise especially after 2009. Gradual increase in cigarette smoking (4.1%, in 2007, and 5.7% in 2017) and in waterpipe use (2.5% to 6.4%) were detected. Education showed an inverse relationship with cigarette and waterpipe smoking. Household wealth demonstrated a positive association with cigarette and waterpipe smoking. Tobacco use epidemic is expanding its roots among pregnant women in Jordan through not only waterpipe use but also dual cigarette-waterpipe smoking. Maternal and child services should consider tobacco counseling and cessation.


Influence of different stimuli on electromyographic variables of the biceps brachii.
The objective of this study was to assess the influence of different stimuli on the muscular response of 30 young sedentary male and female subjects. A conditioning module with A/D 16/32 signals of 12 bits (LYNX), with band-pass filter of 10-500 Hz and sampling frequency of 1000 Hz was used. A bipolar active surface electrode (LYNX), a load cell (MM-100 KRATOS) and a pressure cuff were also used. The volunteers were submitted to four conditions: Without stimulus (WS), auditive stimulus (AS), visual stimulus (VS), and auditive + visual stimuli (AVS). Matlab 6.5.1 software was used to process the signals for analyzing RMS and median frequency (MF), as well as muscular force (F) and cuff pressure (P). Statistical analysis consisted of the Wilcoxon and Mann-Whitney test with a critical level of 5%. As to RMS, females presented a significant increase in all types of stimuli compared to WS. As to MF there was no significant difference between the different groups for either sex. P in both sexes presented a significant increase when submitted to VS and AVS. F was higher for AVS in males and for any of the stimuli in females when compared to WS. In all the variables analyzed, males presented significantly higher values than females for all types of stimuli.


Identification of antibiotic mycelia residue in protein rich feed using on near-infrared microscopy imaging.
Antibiotic mycelial residues (AMRs) added to animal feeds easily lead to drug resistance that affects human health and environment. However, there is a lack of effective detection methods, especially a fast and convenient detection technology, to distinguish AMRs from other components in animal feeds. To develop effective detection methods, two types of global Mahalanobis distance (GH) algorithms based on near-infrared microscopy (NIRM) imaging are proposed. The aim of this study is to investigate the feasibility of using NIRM imaging to identify AMRs in soybean meals. We prepared 15 mixed samples containing 5% AMRs using three types of soybean meals and four types of AMRs. The GH algorithm was used to identify non-soybean meals among the mixed samples. The hierarchical cluster analysis was employed to verify the recognition accuracy. The results indicate that use of the GH algorithm could identify soybean meals with AMR at a level as low as 5%.


Learning graph in graph convolutional neural networks for robust seizure prediction.
Brain-computer interface (BCI) has demonstrated its effectiveness in epilepsy treatment and control. In a BCI-aided epilepsy treatment system, therapic electrical stimulus is delivered in response to the prediction of upcoming seizure onsets, therefore timely and accurate seizure prediction algorithm plays an important role. However, unlike typical signatures such as slow or sharp waves in ictal periods, the signal patterns in preictal periods are usually subtle, and highly individual-dependent. How to extract effective and robust preictal features is still a challenging problem. Most recently, graph convolutional neural network (GCNN) has demonstrated the strength in the electroencephalogram (EEG) and intracranial electroencephalogram (iEEG) signal modeling, due to its advantages in describing complex relationships among different EEG/iEEG regions. However, current GCNN models are not suitable for seizure prediction. The effectiveness of GCNNs highly relies on prior graphs that describe the underlying relationships in EEG regions. However, due to the complex mechanism of seizure evolution, the underlying relationship in the preictal period can be diverse in different patients, making it almost impossible to build a proper prior graph in general. To deal with this problem, we propose a novel approach to automatically learn a patient-specific graph in a data-driven way, which is called the joint graph structure and representation learning network (JGRN). JGRN constructs a global-local graph convolutional neural network which jointly learns the graph structures and connection weights in a task-related learning process in iEEG signals, thus the learned graph and feature representations can be optimized toward the objective of seizure prediction. Experimental results show that our JGRN outperforms CNN and GCNN models remarkably, and the improvement is more obvious when preictal features are subtle. The proposed approach promises to achieve robust seizure prediction performance and to have the potential to be extended to general problems in brain-computer interfaces.


Treatment of severe Clonorchiasis sinensis by endoscopic nasobiliary drainage and oral praziquantel.
To assess the therapeutic value of endoscopic nasobiliary drainage (ENBD) and oral praziquantel for severe Clonorchiasis sinensis infection. Of the 84 Clonorchiasis sinensis-infected patients enrolled, 58 were treated with ENBD (as observing group, ENBD group), 26 received operations (control group, operation group). Both of the two groups were comparable in terms of patient's age, body mass index. Before and one week after treatment, the average diameters of common bile ducts were measured by ultrasound, and serum bilirubin, ALP, gamma-GT and ALT were detected by biochemical methods. After ENBD or operation, the patients took praziquantel for two days. Compared with the patients in operation group, ENBD patients in ENBD group had higher recovery rates of abdominal pain and fever as well as jaundice, quicker remission, smaller trauma, fewer complications and lower cost. ENBD combined with oral praziquantel is an effective and safe method for the treatment of severe Clonorchiasis sinensis.


Decoupling Lineage-Associated Genes in Acute Myeloid Leukemia Reveals Inflammatory and Metabolic Signatures Associated With Outcomes.
Acute myeloid leukemia (AML) is a heterogeneous disease with variable responses to therapy. Cytogenetic and genomic features are used to classify AML patients into prognostic and treatment groups. However, these molecular characteristics harbor significant patient-to-patient variability and do not fully account for AML heterogeneity. RNA-based classifications have also been applied in AML as an alternative approach, but transcriptomic grouping is strongly associated with AML morphologic lineages. We used a training cohort of newly diagnosed AML patients and conducted unsupervised RNA-based classification after excluding lineage-associated genes. We identified three AML patient groups that have distinct biological pathways associated with outcomes. Enrichment of inflammatory pathways and downregulation of HOX pathways were associated with improved outcomes, and this was validated in 2 independent cohorts. We also identified a group of AML patients who harbored high metabolic and mTOR pathway activity, and this was associated with worse clinical outcomes. Using a comprehensive reverse phase protein array, we identified higher mTOR protein expression in the highly metabolic group. We also identified a positive correlation between degree of resistance to venetoclax and mTOR activation in myeloid and lymphoid cell lines. Our approach of integrating RNA, protein, and genomic data uncovered lineage-independent AML patient groups that share biologic mechanisms and can inform outcomes independent of commonly used clinical and demographic variables; these groups could be used to guide therapeutic strategies.


Effects of seasonal temperature regimes on embryo growth and endogenous hormones of Taxus chinensis var. mairei seeds.
Seed dormancy is a mechanism that prevents seeds from germinating at times of the year when conditions are unfavorable, that is, when the chance of seed survival is low. Determining the seasonal dynamics of seed dormancy is important for exploring how plant regeneration is adapted to the environment. We studied the seed dormancy status of Taxus chinensis var. mairei, an endangered species in China, under simulated seasonal temperature regimes. The embryo length, embryo-to-seed (E : S) ratio, and percentage of seeds with a split seed coat increased when seeds were stratified at spring and autumn temperature regimes. The abscisic acid (ABA) content decreased during stratification at simulated seasonal temperatures, but no obvious pattern in the content of gibberellic acid (GA) and indole acetic acid (IAA) was observed. The GA-ABA and IAA-ABA ratios increased during stratification. These results suggest that T. chinensis var. mairei seeds have morphophysiological dormancy, and that the seasonal dynamics of seed dormancy break are controlled by endogenous hormones and their balances, which was confirmed by the results of a field experiment. Our study provides useful information for understanding the natural population regeneration and propagation of this threatened species.


Economic costs of hemophilia and the impact of prophylactic treatment on patient management.
Hemophilia is a rare congenital bleeding disorder characterized by spontaneous and potentially life-threatening bleeding episodes. In addition to its clinical burden on the patient, the condition also places a significant economic burden on healthcare payers, patients/caregivers, and society. Hemophilia is associated with staggering direct costs from hospitalizations, outpatient visits, and drug treatments, as well as high indirect costs from diminished work productivity and absenteeism from work and school. Additionally, hemophilia incurs tremendous intangible costs, including reduced quality of life, pain and suffering, and the emotional and physical toll on the patient and caregivers. The evolution of treatment patterns in hemophilia has transformed the once-fatal disease into a chronic but potentially well-managed condition through the use of prophylaxis treatment. However, other complications, such as development of inhibitory antibodies, have added to the complexity of managing the disease and its costs. To ensure optimal treatment outcomes and disease management, there is a critical need to understand the utilization of healthcare resources in the treatment of hemophilia and to educate patients on the importance of treatment adherence and compliance to reduce long-term effects on musculoskeletal health.


Primary adenocarcinoma of distal ileum used as outlet from a right colonic urinary reservoir.
A case of primary adenocarcinoma of distal ileum used as intussuscepted nipple valve and outlet from a right colonic reservoir is reported. The tumour was diagnosed 5.5 years after the patient was operated on with cystectomy and right colonic reservoir for a moderately differentiated, muscle-invasive transitional carcinoma of the bladder.


Catalytic Partial Oxidation of Cyclohexane by Bimetallic Ag/Pd Nanoparticles on Magnesium Oxide.
The liquid-phase oxidation of cyclohexane to cyclohexanol and cyclohexanone was investigated by synthesizing and testing an array of heterogeneous catalysts comprising: monometallic Ag/MgO, monometallic Pd/MgO and a set of bimetallic AgPd/MgO catalysts. Interestingly, Ag/MgO was capable of a conversion comparable to current industrial routes of approximately 5 %, and with a high selectivity (up to 60 %) to cyclohexanol, thus making Ag/MgO an attractive system for the synthesis of intermediates for the manufacture of nylon fibres. Furthermore, following the doping of Ag nanoparticles with Pd, the conversion increased up to 10 % whilst simultaneously preserving a high selectivity to the alcohol. Scanning transmission electron microscopy and energy dispersive spectroscopy of the catalysts showed a systematic particle-size-composition variation with the smaller Ag-Pd nanoparticles being statistically richer in Pd. Analysis of the reaction mixture by electron paramagnetic resonance (EPR) spectroscopy coupled with the spin-trapping technique showed the presence of large amounts of alkoxy radicals, thus providing insights for a possible reaction mechanism.


Cognitive eating restraint scores are associated with body fatness but not with other measures of dieting in women.
Nearly 50% of women report dieting to lose weight, but the ability of cognitive eating restraint (CER) scores to separate women based on indicators of restricted intake has not been adequately demonstrated. We examined the ability of the CER subscale of the eating inventory to distinguish differences in resting energy expenditure (REE), body composition, cortisol, dietary intake, and physical activity, in a group of women. Subjects (20.4+/-2.3 years) were divided into high (score>9; n=31) and low (score< or =9; n=34) CER groups based on questionnaire responses. Indirect calorimetry was used to measure REE and dual-energy X-ray absorptiometry to measure body composition. Salivary and 24-hour urinary cortisol were measured by bioassays. Food frequency questionnaires and 4-day food records, physical activity recalls, and anthropometric measures were completed. Women in the high CER group possessed more fat mass (p<0.05) and higher body fat percent (p<0.05) and consumed more servings of fruits and vegetables per day (p<0.05) compared to women in the low CER group. Differences in other indicators were not observed between CER groups. Our findings suggest that cognitive restraint and body fatness may not be independent of one another.


Multiple systems for recognition of apoptotic lymphocytes by macrophages.
In vivo, apoptotic lymphocytes are recognized and phagocytosed by macrophages well before the final stages of DNA degradation and cell lysis. The recognition process is apparently triggered by the exposure of phosphatidylserine (PS) on the cell surface, an event which precedes cell lysis by several hours. However, multiple receptors appear to respond to this event. We demonstrate here that both activated and unactivated macrophages recognize PS, but with different receptor systems. Phagocytosis of apoptotic lymphocytes by activated (but not by unactivated) macrophages is inhibited by pure PS vesicles as well as by N-acetylglucosamine, implicating involvement of a lectin-like receptor in this case. Conversely, uptake of apoptotic lymphocytes by unactivated (but not by activated) macrophages is inhibited by PS on the surface of erythrocytes as well as by the tetrapeptide RGDS and cationic amino acids and sugars, implicating involvement of the vitronectin receptor in this case. Recognition by both classes of macrophages is blocked by the monocyte-specific monoclonal antibody 61D3. The signal recognized by activated macrophages appears to develop on the lymphocyte prior to assembly of the signal recognized by unactivated macrophages. Collectively, these results suggest that PS exposure on the surface of apoptotic lymphocytes generates a complex and evolving signal recognized by different receptor complexes on activated and unactivated macrophages.


Insertion of perilipin 3 into a glycero(phospho)lipid monolayer depends on lipid headgroup and acyl chain species.
Lipid droplets (LDs) are organelles that contribute to various cellular functions that are vital for life. Aside from acting as a neutral lipid storage depot, they are also involved in building new membranes, synthesis of steroid hormones, and cell signaling. Many aspects of LD structure and function are not yet well-understood. Here we investigate the interaction of perilipin 3, a member of the perilipin family of LD binding proteins, and three N-terminal truncation mutants with lipid monolayers. The interaction is studied as a function of surface pressure for a series of systematically chosen lipids. We find that the C terminus of perilipin 3 has different insertion behavior from that of the longer truncation mutants and the full-length protein. Inclusion of N-terminal sequences with the C terminus decreases the ability of the protein construct to insert in lipid monolayers. Coupling of anionic lipids to negative spontaneous curvature facilitates protein interaction and insertion. The C terminus shows strong preference for lipids with more saturated fatty acids. This work sheds light on the LD binding properties and function of the different domains of perilipin 3.


Differential transient and long-term expression of DNA sequences introduced into T-lymphocyte lines.
We have used a protoplast fusion protocol to introduce the genes encoding neomycin phosphotransferase (neo) and chloramphenicol acetyltransferase (CAT) into murine and human T-lymphocyte lines. Plasmid constructs containing the neo gene under the control of the promoters from the Rous sarcoma virus long terminal repeat (RSV LTR), the SV40 early region, or the herpes simplex virus thymidine kinase gene (HSV TK) can stably transform each of three T-cell lines to G-418 resistance. The characteristic frequencies for different cell lines can differ by at least two orders of magnitude, although initial DNA uptake and transient expression are similar. In the two murine cell lines, low numbers of gene copies are retained in long-term transformants. Prior to integration, transient expression assays for cat or neo gene products reveal that the differences in intrinsic promoter strength of different constructs are further influenced by the coding sequences being transcribed. Thus, while transient expression of the neo protein is similar from both the Rous LTR and the SV40 early promoter, the Rous LTR directs synthesis of CAT protein at levels two orders of magnitude higher than those from the SV40 early promoter.


Sub-wavelength grating-assisted polarization splitter-rotators for silicon-on-insulator platforms.
We propose and demonstrate broadband, entirely mode-evolution-based, polarization splitter-rotators (PSR) using sub-wavelength grating (SWG) assisted adiabatic waveguides for two SOI platforms. Our PSRs are more compact than previously demonstrated entirely mode-evolution-based designs. The devices were fabricated using two fabrication processes and, in both cases, the measured spectra show close matches to the simulation results. One of the processes uses standard optical lithography and, hence, this is the first time that an SWG-based PSR has been experimentally implemented using such a process. Finally, measurements for arbitrary input polarizations on an active, automated polarization receiver, that uses one of our PSRs, are also presented.


[Effect of 1-(chloromethyl)silatrane on biochemical indices in the tissue of experimental gastric ulcer].
It has been demonstrated in rats with experimental gastric ulcer that 1-(chloromethyl) silatrane intensifies the development of granulation-fibrous tissue and favours optimization of the ratio of collagens and glycosaminoglycans, the main connective tissue biopolymers. Furthermore, 1-(chloromethyl) silatrane produces a more pronounced effect on hexosamine-containing glycoproteins in the ulcer tissue as compared with methyluracil and oxyferriscorbon. At the same time, judging by the time course of sialoproteins, the antiulcerous drugs, methyluracil and oxyferriscorbon, are much more effective antiinflammatory agents than 1-(chloromethyl)silatrane.


Brainstem primitive neuroectodermal tumors (bstPNET): results of treatment with intensive induction chemotherapy followed by consolidative chemotherapy with autologous hematopoietic cell rescue.
We have evaluated the response rate and survival utilizing intensified chemotherapy followed by myeloablative chemotherapy with autologous hematopoietic cell rescue (AuHCR) and adjuvant radiation therapy in six young children with newly diagnosed brainstem primitive neuroectodermal tumors (bstPNET). Following maximum surgical resection of the tumor, patients received high dose induction chemotherapy including vincristine, cisplatin, cyclophosphamide, and etoposide. Eligible patients received a single cycle of myeloablative chemotherapy followed by AuHCR. Two patients survive at least 32 months with stable disease. This approach provides an alternative for young patients with bstPNET who in prior reports have had a uniformly fatal prognosis.


Metformin Modulates Cyclin D1 and P53 Expression to Inhibit Cell Proliferation and to Induce Apoptosis in Cervical Cancer Cell Lines.
Background: Cervical cancer is one of the most prevalent gynecological cancers worldwide and contributes in high mortality of Indonesian women. The efficacy of chemotherapy as a standart therapy for cervical cancer decreases because it frequenly rises adverse effects. Recent studies have found that metformin has a potential anticancer effect mostly through reduction of cyclin expression and activation of Activated Adenosine Monophosphate Kinase (AMPK). This study aimed to investigate the effect of metfomin on expression of cyclin D1 and p53 and apoptosis in HeLa cancer cell line. Methods: HeLa cells were treated with various doses of metformin and doxorubicin as a positive control. Cytotoxic effect of metformin was determined using the MTT assay. Immunocytochemistry was used to assess cyclin D1 and p53 expression and apoptosis levels of treated HeLa cells were analyzed using flowcytometry. Data of cyclin D1 expression was statistically analyzed using the Kruskal-Wallis test followed by the Tamhane test, whilst ANOVA and Tukey post Hoc tests were used to analyze data of p53 and apoptosis level. The significant value was p< 0.05. Results: Metformin was able to inhibit proliferation of HeLa cells with IC50 60 mM. HeLa cells treated with 60 and 120 mM metformin had lower cyclin D1 expression than HeLa cells treated without metformin and reached a significant difference (p= 0.001). Moreover, 30 mM or higher doses of metformin increase significantly p53 expression (p< 0.001). Induction of apoptosis was observed in HeLa cells treated with all doses of metformin and reached statistically difference (p= 0.04 and p < 0.001). Conclusion: Metformin can modulate cyclin D1 and p53 expression in HeLa cancer cell line, leading to inhibition of cell proliferation and induction of apoptosis. Other cyclin family members, CDK inhibitors and AMPK signaling should be further investigated in order to know mechanism of metformin action.


Distribution and light microscopic features of granule cells in the cochlear nuclei of cat, rat, and mouse.
In the present study the cytology and the topography of the cochlear granule cell domain (a comprehensive term introduced here for all granule cell-containing regions of the cochlear nuclear complex) have been studied light microscopically in Nissl, Bielschowsky, and Golgi-Del Rio-Hortega material of cats, rats, and mice; in Golig rapid material of 0-14-day-old kittens; and in sections of 6-week-old kittens following HRP injections in the superficial dorsal cochlear nucleus (DCN). The domain has been parcellated in seven subdivisions which, in spite of some species' differences, are easily identifiable in all of the included animals. The cochlear granule cells are considered as a particular class of neuron, which is slightly different from, but nevertheless principally similar to the cerebellar granule cells in both shape and mode of neuronal connections. The digitiform terminals of the cochlear granule cells differentiate after the first two weeks of extrauterine life. In several respects these cells show larger variation among species than do the cerebellar granules, the similarity between the two classes of granule cells being most conspicuous in the rodent. The silver, Golgi rapid, and HRP material suggest that all, or at least the majority, of the granule cell axons project to the molecular layer of the DCN, forming parallel fibers similar to those of the cerebellar cortex. Also, the cochlear parallel fibers traverse the spiny apical dendrites of principal neurons (the pyramidal cells) and the smoother dendrites of molecular layer stellate cells.


Is preoperative distinction between complicated and uncomplicated acute appendicitis feasible without imaging?
One of the main aims of appendicitis research is the differential diagnostics between complicated and uncomplicated acute appendicitis that enable provision of the optimal treatment for each patient. Data in the present study were collected prospectively in our randomized antibiotic treatment for uncomplicated acute appendicitis trial (APPAC) comparing surgery and antibiotic treatment for uncomplicated acute appendicitis (NCT01022567). We evaluated 705 patients who had acute appendicitis on computed tomography. Patients with uncomplicated acute appendicitis (n = 368) were compared with all complicated acute appendicitis patients (n = 337), and subgroup analyses were performed between uncomplicated acute appendicitis and an appendicolith appendicitis (CA1; n = 256) and uncomplicated acute appendicitis and perforation and/or abscess (CA2; n = 78). Age, sex, body temperature (°C), duration of symptoms, white blood cell count (E9/L), and C-reactive protein (mg/L) were recorded on admission. Receiver operating characteristic curves were calculated for white blood cell count, C-reactive protein, and temperature. CA2 patients had significantly greater C-reactive protein levels (mean 122 and 47, respectively, P < .001) and longer duration of symptoms than uncomplicated acute appendicitis patients; 81% of CA2 patients and 38% of uncomplicated acute appendicitis patients had symptoms >24 hours before admission (P < .001). In receiver operating characteristic analysis, C-reactive protein and temperature had clinically significant results only in comparison with uncomplicated acute appendicitis and CA2 (area under the curve >0.7), but no optimum cutoff points could be identified. In clinical decision making, neither clinical findings nor laboratory markers are reliable enough to estimate the severity of the acute appendicitis accurately or to determine the presence of an appendicolith. The current results emphasize the role of computed tomography in the differential diagnosis of complicated and uncomplicated acute appendicitis.


[Toxoplasmosis in Niger. A serological analysis of 400 subjects].
A toxoplasmosis serological study using an indirect immunofluorescence method was made in 400 subjects in the Republic of Niger because the epidemiologic findings of this disease were very poor. Serum antitoxoplasmic antibodies were present in 18.2%. In sahelian areas prevalence of such toxoplasmic antibodies is low in the majority of studies. Analysis of seropositivity and age pointed out a late seroconversion.


Adenosine kinase inhibitors. 3. Synthesis, SAR, and antiinflammatory activity of a series of l-lyxofuranosyl nucleosides.
Chronic inflammatory diseases, such as arthritis and rheumatoid arthritis, remain major health problems worldwide. We previously demonstrated that adenosine kinase inhibitors (AKIs) exhibit antiinflammatory effects by inhibiting TNF-alpha production, neutrophil accumulation, and edema formation. Although adenosine receptor agonists produce similar effects, AKIs showed the antiinflammatory activity without the cardiovascular side effects that prevented the development of adenosine receptor specific agonists. However, previously described potent AKIs, such as 5-iodotubercidin, are nucleosides which have the potential to undergo in vivo 5'-O-phosphorylation and therefore produce cytotoxicity. In an effort to eliminate toxicities produced by phosphorylated nucleosides, l-lyxofuranosyl analogues of tubercidin were tested as potential AKIs since the opposite stereochemical orientation of the CH(2)OH was expected to eliminate intracellular phosphorylation. Described herein are the discovery of a new series of AKIs based on alpha-l-lyxofuranosyl nucleosides, their SAR, as well as the antiinflammatory activity of the lead compound GP790 (IC(50) = 0.47 nM, 47% inhibition of paw swelling at 10 mg/kg in rat carrageenan paw edema model). In addition, a study showing that in the skin lesion model the antiinflammatory activity is reversed by an A2 selective adenosine receptor antagonist 3,7-dimethyl-1-propargyl xanthine [correction of propylxanthine] (DMPX) is also described.


Atherectomy in Peripheral Artery Disease: A Review.
Peripheral arterial disease (PAD) is a clinical manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. The physiological force and shear stress from angioplasty and stenting have made PAD treatment challenging. Atherectomy devices have continued to emerge as a major therapy in the management of peripheral vascular disease. This article presents a review of the current literature for the atherectomy devices used in PAD.


[Detection of SARS-coronavirus in both human and animals by RT-PCR].
To find the most suitable RT-PCR detection method for SARS-Coronavirus (SARS-CoV) detection in both human and animals, and to study the source of SARS virus by investigating the condition of virus carried by wild, domestic animals and animals sold in market. 350 throat washes of confirmed, suspected and observed SARS cases were tested by TaqMan and molecular beacon fluorescence RT-PCR methods. 386 animals with 442 nasal-throat swabs, fecal swabs of animals and cell cultured were detected by TaqMan method and conventional RT-PCR method. 10 positive were detected from 41 SARS clinical confirmed cases (24.39%). The results of TaqMan and molecular beacon are basically coincident with the coincident rate of 88.89%. 18 cell cultures with CPE were detected and find 16 positive, among which, 14 were civet cats (87.5%). The detecting results of animal samples from Dongmen Market (Shenzhen) and other markets and farms in peripheral areas show that: the total positive rate of 4 kinds of wild animal (civet cat, raccoon dog, hog-badge and Chinese ferret-badge) is 39.02% , which has an significant difference (P < 0.01) compared with the positive rate of other animals as 0. The positive rate of PCR for nasal and fecal swabs from 109 major wild animals is 44.04%, but the positive rate of 145 wild live-animals is 0. TaqMan and molecular beacon PCR methods both can be used in SARS detection.The results could support the hypothesis that animals (especially civet cat) could carry SARS virus.


Permissiveness toward tobacco sponsorship undermines tobacco control support in Africa.
School personnel, who are respected members of the community, may exert significant influence on policy adoption. This study assessed the impact of school personnel's permissiveness toward tobacco industry sponsorship activities on their support for complete bans on tobacco advertisements, comprehensive smoke-free laws and increased tobacco prices. Representative data were obtained from the Global School Personnel Survey for 29 African countries (n = 17 929). Adjusted prevalence ratios (aPR) were calculated using multi-variable Poisson regression models to assess the impact of permissiveness toward tobacco sponsorship activities on support for tobacco control policies (p < 0.05). The median of prevalence of support for different tobacco control policies among all countries was as follows: complete ban on tobacco advertisements (84.9%); comprehensive smoke-free laws (92.4%) and tobacco price increases (80.8%). School personnel who believed that the tobacco industry should be allowed to sponsor school events were significantly less likely to support complete bans on tobacco advertisements [aPR = 0.89; 95% confidence interval (CI) 0.84-0.95] and comprehensive smoke-free laws (aPR = 0.95; 95% CI 0.92-0.98). In contrast, support for complete tobacco advertisement bans was more likely among those who believed that the tobacco industry encourages youths to smoke (aPR = 1.27; 95% CI 1.17-1.37), and among those who taught about health sometimes (aPR = 1.06; 95% CI 1.01-1.11) or a lot (aPR = 1.05; 95% CI 1.01-1.10) compared with those who did not teach about health at all. These findings underscore the need to educate school personnel on tobacco industry's strategies to undermine tobacco control policies. This may help to build school personnel support for laws intended to reduce youth susceptibility, experimentation and established use of tobacco products.


Comparative Proteomic Analysis of Cotton Fiber Development and Protein Extraction Method Comparison in Late Stage Fibers.
The distinct stages of cotton fiber development and maturation serve as a single-celled model for studying the molecular mechanisms of plant cell elongation, cell wall development and cellulose biosynthesis. However, this model system of plant cell development is compromised for proteomic studies due to a lack of an efficient protein extraction method during the later stages of fiber development, because of a recalcitrant cell wall and the presence of abundant phenolic compounds. Here, we compared the quality and quantities of proteins extracted from 25 dpa (days post anthesis) fiber with multiple protein extraction methods and present a comprehensive quantitative proteomic study of fiber development from 10 dpa to 25 dpa. Comparative analysis using a label-free quantification method revealed 287 differentially-expressed proteins in the 10 dpa to 25 dpa fiber developmental period. Proteins involved in cell wall metabolism and regulation, cytoskeleton development and carbohydrate metabolism among other functional categories in four fiber developmental stages were identified. Our studies provide protocols for protein extraction from maturing fiber tissues for mass spectrometry analysis and expand knowledge of the proteomic profile of cotton fiber development.


Magnetic resonance demonstration of normal CSF flow.
The magnetic resonance (MR) imaging appearance and incidence of flowing cerebrospinal fluid (CSF) in the brain were investigated. The MR scans of 46 randomly selected patients with normal examinations were retrospectively reviewed. All patients were studied using both T2-weighted and T1-weighted spin-echo pulse sequences. Thirty-one patients (67%) had decreased intensity in the aqueduct of Sylvius on the T2-weighted images when compared with the intensity of CSF in the lateral ventricles. This was termed the CSF flow-void sign. The feature was present in the caudal fourth ventricle in 15 patients (32%) and in the third ventricle in two patients (4%) on T2-weighted scans. It was seen in only 13% of patients on T1-weighted scans. It is believed the CSF flow-void sign represents pulsatile CSF flow. Its recognition is important because it explains the inhomogeneity in the appearance of the CSF, which could be confused with pathologic processes. It may be valuable in the routine evaluation of MR examinations if it does reflect CSF circulatory dynamics.


Some critical developments in acquiring native language sound organization during the first year.
Although infants are born with rather sophisticated capacities for discriminating and categorizing speech sounds, they still must learn about the sound organization of their native language. Before 6 months, infants show relatively little sensitivity to native language versus non-native language sound organization. Shortly thereafter, infants recognize which sounds and sound sequences and rhythmic patterns are likely to appear in native language words. Knowledge of these features plays a critical role in how and when infants segment words from fluent speech. Word segmentation abilities develop rapidly between 7.5 and 10.5 months. Initially, English-learners segment words using stress cues. Soon after, they learn to use other potential cues to word boundaries. As their lexicons develop during the second year, they begin to use information about known words in segmenting and learning new words.


Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2).
Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in 'lockdown', social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.


Tools and techniques to identify, study, and control Candida auris.
Candida auris, is an emerging fungal pathogen that can cause life-threatening infections in humans. Unlike many other Candida species that colonize the intestine, C. auris most efficiently colonizes the skin. Such colonization contaminates the patient's environment and can result in rapid nosocomial transmission. In addition, this transmission can lead to outbreaks of systemic infections that have mortality rates between 40% and 60%. C. auris isolates resistant to all known classes of antifungals have been identified and as such, understanding the underlying biochemical mechanisms of how skin colonization initiates and progresses is critical to developing better therapeutic options. With this review, we briefly summarize what is known about horizontal transmission and current tools used to identify, understand, and control C. auris infections.


Bees without Flowers: Before Peak Bloom, Diverse Native Bees Find Insect-Produced Honeydew Sugars.
Bee foragers respond to complex visual, olfactory, and extrasensory cues to optimize searches for floral rewards. Their abilities to detect and distinguish floral colors, shapes, volatiles, and ultraviolet signals and even gauge nectar availability from changes in floral humidity or electric fields are well studied. Bee foraging behaviors in the absence of floral cues, however, are rarely considered. We observed 42 species of wild bees visiting inconspicuous, nonflowering shrubs during early spring in a protected Mediterranean habitat. We determined experimentally that these bees were accessing sugary honeydew secretions from scale insects without the aid of standard cues. While honeydew use is known among some social Hymenoptera, its use across a diverse community of solitary bees is a novel observation. The widespread ability of native bees to locate and use unadvertised, nonfloral sugars suggests unappreciated sensory mechanisms and/or the existence of an interspecific foraging network among solitary bees that may influence how native bees cope with scarcity of floral resources and increasing environmental change.


[Intra-orbital explosion of a rocket].
Orbito-palpebral ballistic wounds are relatively common, most often due to firearms, and raise the problem of their surgical management. Excision of the intra-orbital foreign bodies remains difficult, above all when there is impaction of the anterior portion. The authors report a model case of orbital trauma by rocket splinter, excision of which was possible via the entry orifice.


A novel PKHD1 splicing variant identified in a fetus with autosomal recessive polycystic kidney disease.
Objective: Variants of the polycystic kidney and hepatic disease 1 (PKHD1) gene are associated with autosomal recessive polycystic kidney disease (ARPKD). This study aimed to identify the genetic causes in a Chinese pedigree with ARPKD and design a minigene construct of the PKHD1 gene to investigate the impact of its variants on splicing. Methods: Umbilical cord samples from the proband and peripheral blood samples from his parents were collected, and genomic DNA was extracted for whole-exome sequencing (WES). Bioinformatic analysis was used to identify potential genetic causes, and Sanger sequencing confirmed the existence of variants within the pedigree. A minigene assay was performed to validate the effects of an intronic variant on mRNA splicing. Results: Two variants, c.9455del (p.N3152Tfs*10) and c.2408-13C>G, were identified in the PKHD1 gene (NM_138694.4) by WES; the latter has not been previously reported. In silico analysis predicted that this intronic variant is potentially pathogenic. Bioinformatic splice prediction tools revealed that the variant is likely to strongly impact splice site function. An in vitro minigene assay revealed that c.2408-13C>G can cause aberrant splicing, resulting in the retention of 12 bp of intron 23. Conclusion: A novel pathogenic variant of PKHD1, c.2408-13C>G, was found in a fetus with ARPKD, which enriches the variant spectrum of the PKHD1 gene and provides a basis for genetic counseling and the diagnosis of ARPKD. Minigenes are optimal to determine whether intron variants can cause aberrant splicing.


Effectiveness Evaluation of Real-Time Scalp Signal Separating Algorithm on Near-Infrared Spectroscopy Neurofeedback.
Near-infrared spectroscopy (NIRS), one of the candidates to be used in a neurofeedback system or brain-computer interface (BCI), measures the brain activity by monitoring the changes in cerebral hemoglobin concentration. However, hemodynamic changes in the scalp may affect the NIRS signals. In order to remove the superficial signals when NIRS is used in a neurofeedback system or BCI, real-time processing is necessary. Real-time scalp signal separating (RT-SSS) algorithm, which is capable of separating the scalp-blood signals from NIRS signals obtained in real-time, may thus be applied. To demonstrate its effectiveness, two separate neurofeedback experiments were conducted. In the first experiment, the feedback signal was the raw NIRS signal recorded while in the second experiment, deep signal extracted using RT-SSS algorithm was used as the feedback signal. In both experiments, participants were instructed to control the feedback signal to follow a predefined track. Accuracy scores were calculated based on the differences between the trace controlled by feedback signal and the targeted track. Overall, the second experiment yielded better performance in terms of accuracy scores. These findings proved that RT-SSS algorithm is beneficial for neurofeedback.


Modification of dopamine release by nociceptin in conscious rat striatum.
Nociceptin (NOC), an endogenous ligand for the orphan receptor ORL1, has recently been recognized as a neuropeptide. We used brain microdialysis and on-line high performance liquid chromatography to examine the effect of NOC on the basal outflow of dopamine (DA) and its metabolite in the freely moving rat striatum in vivo. The percent change of DA release induced by NOC at concentrations of 10-6 and 10-5 M were 383% and 398%, respectively. This effect of NOC was attenuated by naloxone, suggesting that NOC activates classic (micro, delta, kappa) receptors in a very little way. These data indicates that NOC may act as a neuropeptide which enhances DA release from the striatum of rat brain via an opioid receptor.


Comparison of one-stage and two-stage upper arm brachiobasilic arteriovenous fistula in the Vascular Quality Initiative.
An upper arm brachiobasilic arteriovenous fistula (BBAVF) is a reliable autogenous hemodialysis access created with a one-stage or two-stage technique. Although both techniques are variably used, the optimal approach is uncertain. In this study, we compared the outcomes of one-stage and two-stage BBAVF procedures. We identified 2648 patients who had received BBAVFs within the Vascular Quality Initiative data set (2010-2016) and compared those created using the one-stage and two-stage technique. The primary outcome measures were primary and secondary patency rates at 12 months. Other outcomes assessed were wound infection, steal, and swelling at 3 months. The log-rank test was used to evaluate patency by Kaplan-Meier analysis. Cox proportional hazards models were used to examine the adjusted association between surgical technique and outcomes. There were 1234 (47%) one-stage and 1414 (53%) two-stage BBAVFs in the study cohort, including 1848 (70%) patients who were on dialysis at the time of surgery and 1795 (68%) patients with a history of previous access. Patients who underwent a one-stage BBAVF were more likely to be male (54% vs 45%; P < .001), to be white (60% vs 41%; P < .001), and to have a history of coronary artery disease (22% vs 17%; P = .001). Patients undergoing one-stage BBAVFs have larger vein diameters (4.1 vs 3.4 mm; P < .001) and have the procedure in an inpatient setting (21% vs 13%; P < .001) compared with patients undergoing a two-stage procedure. The 12-month primary patency rate was higher for the one-stage BBAVF (49.1% vs 40.4%; P = .005), although the secondary patency rate was comparable (80.0% vs 77.9%; P = .54). Postoperative bleeding (4% vs 1.5%; P < .001), wound infection (1.01% vs 0.4%; P = .047), and arm swelling (2.1 % vs 0.8%; P = .006) were higher for one-stage BBAVFs. In multivariable analysis, although loss of primary patency at 12 months (adjusted hazard ratio [aHR], 1.12; 95% confidence interval [CI], 0.97-1.30; P = .12) and 3-month wound infection (aHR, 0.42; 95% CI, 0.14-1.25, P = .12) were similar between the two approaches, the risk of 3-month arm swelling was significantly lower for two-stage BBAVFs (aHR, 0.35; 95% CI, 0.16-0.77; P = .009). Whereas surgeons were more likely to perform a two-stage BBAVF in patients with a history of previously failed access and smaller basilic vein, our data show no difference in primary or secondary patency of one-stage and two-stage BBAVFs at 12 months.


The effect of trifluoperazine on maturation of Xenopus laevis oocytes.
Full grown Xenopus oocytes were incubated with trifluoperazine (TFP) or injected with TFP. Incubation of oocytes in TFP resulted in normal-appearing meiotic maturation, as judged by the presence of the white spot and the absence of the germinal vesicle. Cortical granule breakdown in TFP-incubated oocytes was not normal. Abnormal cortical granule breakdown was also observed when progesterone-maturated oocytes were activated in the presence of TFP. Oocytes microinjected with TFP and incubated with progesterone appeared to mature in a normal manner, as judged by the absence of the germinal vesicle; these underwent cortical granule breakdown following activation, but frequently lacked the white spot. Oocytes microinjected with TFP did not mature in the absence of progesterone. We conclude that incubation, although not microinjection, of oocytes with TFP induces essentially normal resumption of meiotic maturation.


Analysis of flavonoids and other phenolic compounds using high-performance liquid chromatography with coulometric array detection: relationship to antioxidant activity.
High-performance liquid chromatography coupled with a coulometric array detector was used to characterize the electrochemical behavior of 17 flavonoids and three cinnamic acid derivatives. The antioxidant activity of these phenolic compounds was evaluated by the ferric reducing activity power (FRAP), the oxygen radical absorbance capacity (ORAC), and the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical assays. All flavonoids, except kaempferol-3-rutinoside, malvidin-3-glucoside, and peonidin-3-glucoside, had two oxidation potentials (100-300 and 700-800 mV). Quercetin and myricetin had an additional oxidation wave at 400 mV. The electrochemical responses at a relatively low oxidation potential (300 mV) and the cumulative responses at medium oxidation potentials (400 and 500 mV) had the highest correlations with antioxidant activities. The highest correlations between electrochemical characteristics and antioxidant activities were found between electrochemical responses and antioxidant activities obtained in the FRAP assay and in the DPPH assay after short reaction periods. Lower correlations were revealed between electrochemical responses and antioxidant activities obtained in the ORAC assay.


Surgical strategy for congenital blepharophimosis syndrome.
So far, most of the surgical techniques for congenital blepharophimosis syndrome are two-stage procedures. In this study, we investigated a modified one-stage procedure to reduce the suffering of patients. From 2003 to 2005, we adopted an one-stage technique combining blepharoptosis correction with medial canthoplasty in 16 patients with congenital blepharophimosis syndrome (10 male, 6 female; aged from 6 to 21). All the patients had bilateral severe blepharoptosis, epicanthus inversus, and flat dorsum nasi. The movement of the upper lid was 0 to 3 mm, vertical length of the eye fissure 2 to 4 mm, horizontal length 13 to 22 mm, and the distance between the eyes was 35 to 39 mm. The patients were followed up for one half to 2 years after the operation. In all the patients, after the operation, the horizontal length of the eyelid > 25 mm, the vertical length > 6 mm. and the distance between the eyes < 35 mm. The appearance of their double eyelids was satisfying. The modified one-stage technique combining blepharoptosis correction with medial canthoplasty can achieve favorable outcomes for patients with congenital blepharophimosis syndrome.


[Radical cystectomy with sparing partial prostate for invasive bladder cancer].
Classical radical cystectomy for invasive bladder cancer removes the urinary bladder and prostate completely and was associated with high incidence of post-operative impotence and urinary incontinence. It is uncertain whether prostate excision has any effects on the prognosis of patients undergone cystectomy if the prostate is not involved by the tumor. Sparing the prostate in radical cystectomy might improve potency and urinary control. This paper was to report our experience of sparing partial prostate in radical cystectomy for ten male patients. Transurethral resection of the prostate and radical cystectomy with sparing partial prostatic capsula were carried out in 10 male patients with invasive bladder transitional cell carcinoma. Intestinal neobladder, anastomosed with the residual capsula, were used for reconstruction of the lower urinary tract. Clinical outcome of these patients including tumor control,urinary continence, and sexual status was evaluated. Mean follow-up was 9 months (range 3-12 months). Postoperative pathological stage was T2N0M0 in all patients. Nine patients survived free of disease. One patient who had recurrence of poorly differentiated transitional cell carcinoma developed metastasis in bone and lymph nodes two months after cystectomy. All patients voided smoothly. Nine patients were continent day and night. One patient had mild incontinence. Of 8 patients with previously sexual function, 6 maintained potency. Satisfactory urinary control and sexual potency could be achieved in radical cystectomy with sparing partial prostate. Further study is needed about the long-term effects of sparing prostate in cystectomy on tumor control.


Age determination and longevity in amphibians.
Methods of age determination of amphibians by counting annual layers in the bone tissue and data on longevity of amphibians (both anurans and urodeles) in nature are presented. Age compositions of amphibian populations are discussed and their variations analysed.


[Synthetic ultrasound blocks and contact gels in sonography: hygienically satisfactory?].
Different sponge-like plastic blocks and several samples of two coupling gels used during small-parts real-time sonography were investigated microbiologically. Whereas the coupling gels showed no contamination a great deal of different bacteria could be found on the plastic blocks. These findings lead to a restricted use of those devices especially when investigating immunocompromised patients. Sufficient procedures of decontamination do not exist. Because of the relative high purchase cost the one-way use of plastic blocks is uneconomical.


Outcomes of Catheter-Based Pulmonary Artery Embolectomy in Patients With Sub-Massive to Massive Pulmonary Embolism.
Background Pulmonary embolism (PE) is the third leading cause of cardiovascular death after myocardial infarction and stroke. The ideal therapeutic approach for these patients remains undetermined. We report our single-center outcome data for using a catheter-based pulmonary artery thrombectomy using the FlowTriever (Inari Medical, Irvine, CA) device as management for patients with submassive PE. Methods We retrospectively collected data from a single center of patients who underwent thrombectomy using INARI FlowTriever device. The data on baseline characteristics, procedural and clinical outcomes was collected and analysed Results A total of 38 patients with PE treated endovascularly with the FlowTriever device were identified: 33 with submassive PE and five with massive PE. The mean age was 65.9 years (95% CI 61.9 - 69.8), and most patients were male (73.7%). All patients had right heart strain as the main indication for thrombectomy. Four patients (10.53%) required pressor support before the procedure. In 31 patients, pre- and post-thrombectomy average mean pulmonary artery pressure (mPAP) was improved significantly by 22% (p < 0.01). Two patients had significant adverse events at 48 hours (5.26%). One patient experienced procedure-related access site hematoma and life-threatening bleeding, while another developed intraprocedural-related massive hemoptysis and cardiopulmonary arrest. Overall post-procedural length of stay was 7.7 ± 5.6 days; 52.63% of patients (n = 20) required intensive care. Three patients (7.89%) required pressor support before the procedure, and 78.9% of patients (n = 30 of 38) survived hospital discharge. Thirty patients who survived were discharged with oral anticoagulation. There were no device-related complications. Conclusion Randomized trials of interventional devices for submassive PE are warranted to either support or alert the medical community of the safety and efficacy of their use for patients with submassive and massive PE. In time, pulmonary embolism response team (PERT) may generate outcome data that better inform treatment decisions.


A new method for establishing operative channels in unilateral biportal endoscopic surgery: Technical notes and preliminary results.
The unilateral biportal endoscopic (UBE) technique has been widely used in spine surgery. At present, a traditional rigid working channel is available for the UBE system. A metal semicircular canal is located in the working channel. However, due to the metal material of the working channel, arthroscopy and instruments are constrained from moving in UBE surgery. Additionally, an assistant is needed during the procedure to hold the traditional working channel. For simplicity of operation and convenient movement of the arthroscopy and instrument, we describe a new method for establishing operative channels in UBE surgery. We retrospectively reviewed 50 patients who underwent unilateral biportal endoscopic discectomy (UBED) from February 2020 to August 2020 via our new method. The Oswestry Disability Index (ODI) and visual analogue scale (VAS) score were measured preoperatively and 1 month, 3 months, 6 months and 12 months postoperatively. Statistical comparisons were made using analysis of covariance and paired t tests. The VAS scores for back pain at the five time points were 5.20 ± 2.57, 1.96 ± 0.95, 1.50 ± 0.84, 1.64 ± 1.08 and 1.18 ± 0.39. The leg pain VAS scores were 7.02 ± 2.25, 2.02 ± 1.27, 1.48 ± 0.89, 1.32 ± 0.79 and 0.88 ± 0.52. The ODI values were 51.08 ± 19.97, 19.62 ± 15.51, 8.26 ± 7.40, and 7.54 ± 6.42 to 3.24 ± 1.10. The postoperative ODIs and VAS scores of low back pain and leg pain were significantly lower than those before surgery, and differences were statistically significant (all p< 0.05). The pressure of the closed outflow was significantly higher than that of the open outflow (37.35 ± 13.11 mm Hg vs. 24.55 ± 12.64 mm Hg p= 0.003). After we tightened the infusion strap to open the outflow, the pressure decreased significantly (26.4 ± 14.08 mm Hg vs. 37.35 ± 13.11 mm Hg p= 0.015). There were 2 cases of complications, including 1 case of postoperative recurrence and 1 case of dural tears. This study demonstrates the technical feasibility, safety, and efficacy of modified channel establishment in UBE surgery.


Mitomycin-C plus a 3-day continuous intravenous infusion of 5-fluorouracil: an inactive salvage regimen for platinum-resistant ovarian carcinoma.
In a Phase II trial, patients with refractory ovarian cancer were given 10 mg/m2 mitomycin-C i.v. every 8 weeks and 1000 mg/m2/day 5-fluorouracil for 3 consecutive days by continuous intravenous infusion repeated every 4 weeks. Sixteen heavily pretreated patients with platinum-resistant disease were treated and no major responses were observed. Only 2 patients required subsequent dose reduction for myelotoxicity. No sign of gastrointestinal toxicity was seen. This regimen is inactive as salvage treatment for refractory ovarian cancer.


Platelet activation and aggregation by the opportunistic pathogen Cutibacterium (Propionibacterium) acnes.
Cutibacterium (Propionibacterium) acnes, considered a part of the skin microbiota, is one of the most commonly isolated anaerobic bacteria from medical implants in contact with plasma. However, the precise interaction of C. acnes with blood cells and plasma proteins has not been fully elucidated. Herein, we have investigated the molecular interaction of C. acnes with platelets and plasma proteins. We report that the ability of C. acnes to aggregate platelets is dependent on phylotype, with a significantly lower ability amongst type IB isolates, and the interaction of specific donor-dependent plasma proteins (or concentrations thereof) with C. acnes. Pretreatment of C. acnes with plasma reduces the lag time before aggregation demonstrating that pre-deposition of plasma proteins on C. acnes is an important step in platelet aggregation. Using mass spectrometry we identified several plasma proteins deposited on C. acnes, including IgG, fibrinogen and complement factors. Inhibition of IgG, fibrinogen or complement decreased C. acnes-mediated platelet aggregation, demonstrating the importance of these plasma proteins for aggregation. The interaction of C. acnes and platelets was visualized using fluorescence microscopy, verifying the presence of IgG and fibrinogen as components of the aggregates, and co-localization of C. acnes and platelets in the aggregates. Here, we have demonstrated the ability of C. acnes to activate and aggregate platelets in a bacterium and donor-specific fashion, as well as added mechanistic insights into this interaction.


Image Retrieval Method for Multiscale Objects from Optical Colonoscopy Images.
Optical colonoscopy is the most common approach to diagnosing bowel diseases through direct colon and rectum inspections. Periodic optical colonoscopy examinations are particularly important for detecting cancers at early stages while still treatable. However, diagnostic accuracy is highly dependent on both the experience and knowledge of the medical doctor. Moreover, it is extremely difficult, even for specialist doctors, to detect the early stages of cancer when obscured by inflammations of the colonic mucosa due to intractable inflammatory bowel diseases, such as ulcerative colitis. Thus, to assist the UC diagnosis, it is necessary to develop a new technology that can retrieve similar cases of diagnostic target image from cases in the past that stored the diagnosed images with various symptoms of colonic mucosa. In order to assist diagnoses with optical colonoscopy, this paper proposes a retrieval method for colonoscopy images that can cope with multiscale objects. The proposed method can retrieve similar colonoscopy images despite varying visible sizes of the target objects. Through three experiments conducted with real clinical colonoscopy images, we demonstrate that the method is able to retrieve objects of any visible size and any location at a high level of accuracy.


Patellar position in weight-bearing radiographs compared with non-weight-bearing: significance for the detection of osteoarthritis.
Background Diagnosis and treatment of patellofemoral disorders including osteoarthritis are currently often based on imaging and clinical assessment with patients in the supine position. Purpose To evaluate differences in patellar position in the trochlear groove and to assess the detection of medial and lateral patellofemoral (PF) osteoarthritis (OA) on axial radiographs in supine and standing positions, respectively. Material and Methods Thirty-five women and 23 men (mean age, 56 years; age range, 18-87 years) referred for routine radiographic examinations of the knees were included. Axial radiographs of the PF joint in both supine non-weight-bearing and standing weight-bearing position in 30° knee flexion were obtained of 111 knees. Measurements performed on the radiographs: patellar tilt, patellar displacement, joint space width, and grade of OA according to Ahlbäck. Results From supine to standing position the patella moved medially and medial joint space width and lateral patellar tilt angle decreased ( P < 0.0001 for the three measured parameters). In the standing position, medial PF OA was observed in 19 knees compared to three knees in the supine position. Fourteen knees had lateral PF OA with almost unchanged grade of OA irrespective of position. Conclusion In weight-bearing positions, the patella is positioned medially in the trochlear groove compared to supine non-weight-bearing positions. Therefore, this study suggests that the common occurrence of medial PF OA can generally not be detected on axial radiographs in supine non-weight-bearing positions and confirms the importance of imaging the PF joint in standing weight-bearing positions.


Early laparoscopic cholecystectomy in a district general hospital: is it safe and feasible?
Early laparoscopic cholecystectomy (ELC) is becoming the accepted treatment for the management of acute gallstone disease in specialist centres. It has also been achieved safely in the district general hospital (DGH) setting. We audited the management of acute gallstone disease in our DGH and set about to see if we could implement ELC safely and effectively. A retrospective audit of 2 years of practice was performed using our hospital-computerised systems. Following this, departmental education regarding the benefits of early cholecystectomy was widely disseminated. Management guidelines were altered to promote and consider ELC for all suitable patients. A prospective audit of practice was then performed for 6 months. The first cycle revealed that only 10.42% of emergency patients admitted with gallstone-related disease had ELC. In the second cycle, 63 patients were admitted with acute gallstone disease. Three died from acute pancreatitis. Twenty-one (58%) of the 36, who were deemed suitable, had ELC. Fifteen (42%) had planned delayed laparoscopic cholecystectomy (DLC), with six (40%) being readmitted whilst waiting for their elective surgery (all undergoing ELC during their readmission). Conversion rates were similar between all groups. One of the patients having DLC had a bile leak, which settled following Endoscopic Retrograde Cholangiopancreatography and stent. We were able to increase ELC rates following the implementation of necessary changes. There did not appear to be any difference in conversion or morbidity rates between ELC and DLC. We conclude ELC is safe and feasible in the DGH setting.


Comparison of the oral and rectal mucosal and colonic serosal microcirculations of healthy, anesthetized horses.
The objectives of the study were to: i) determine baseline microvascular perfusion indices (MPI) and assess their repeatability in healthy horses under general anesthesia, and ii) compare the MPIs of 3 microvascular beds (oral mucosa, colonic serosa, and rectal mucosa). Healthy adult horses were anesthetized and sidestream dark field microscopy was used to collect video loops of the oral mucosa, rectal mucosa, and colonic serosa under normotensive conditions without cardiovascular support drugs; videos were later analyzed to produce MPIs. Baseline MPI values were determined for each site, which included the total vessel density (TVD), perfused vessel density (PVD), portion perfused vessels (PPV), and microcirculatory flow index (MFI). Differences in MPIs between microvascular beds were not statistically significant. Repeatability of the measurements varied for each MPI. In particular, the site of sampling had a profound effect on the repeatability of the PPV measurements and should be considered in future studies.


A systematic review of the effect of therapeutic drug monitoring on patient health outcomes during treatment with penicillins.
Dosing regimens guided by therapeutic drug monitoring (TDM) may be able to improve penicillin exposure in patients, which could result in improved patient health outcomes. This systematic review aims to describe the impact penicillin TDM has on health outcomes, including antimicrobial resistance (AMR). Studies measuring penicillins in patient samples that adjusted regimens according to the result, and reported health outcomes were selected. Study bias was assessed according to study type. Included study characteristics were tabulated and described by narrative synthesis. Three randomized controlled trials (RCTs), 16 cohort studies, and 9 case studies were included. No RCTs showed statistically significant improvements in health outcomes. Five cohort studies showed improvement in at least one health outcome associated with target attainment. However, there was a high risk of bias in all studies for health outcomes. One study assessed the impact of penicillin TDM on AMR and found that improved target attainment was associated with suppression of resistance. No studies found a detrimental effect of penicillin TDM. There is little evidence to suggest that TDM improves health outcomes, however neither health outcomes nor impact on AMR were adequately addressed. Variations in TDM implementation meant that a meta-analysis was not suitable. Penicillin TDM needs standardization, however there is currently no clear evidence of optimal conditions. Suitably powered studies are required to resolve the ambiguity surrounding the impact of TDM on clinical outcomes, including AMR. Further, standardized protocols and concentration targets need to be identified for TDM to be implemented successfully.


[Posttraumatic stress disorder and bipolar mood disorder].
Bipolar disorder (BD) is not only an endogenous condition. Severe negative life events have been shown to influence the development of the first episode and lifetime course of BD. Posttraumatic stress disorder (PTSD) is a severe and incapacitating mental condition that affect a significant proportion of the general population at some time in their lives. The concomitant presence of BD and PTSD has been shown to be more frequent than previously suggested and psychotic patients with trauma histories have a tendency to present more severe symptoms and are more proned to present substance use disorders. Trauma-related intrusive memories and nightmares of PTSD have been associated with mood changes. Also, kindling and behavioral sensitization have been proposed to explain the etiology and course of both disorders. Pharmacological approaches for this comorbidity are still based on empirical or not controlled approaches. In this article, we critically review the current literature regarding this co morbid condition, and highlight some aspects related to epidemiology, etiology, course and pharmacological treatment of both disorders. Overall, our review emphasizes the importance of systematically evaluate trauma histories in patients with BD.


Diversity of expressed V and J regions of immunoglobulin light chains in Xenopus laevis.
In Xenopus laevis, two immunoglobulin light chain isotypes, designated L1 or rho and L2 or sigma, have been identified. The genomic organization of the L1 locus has been described previously: a constant (C) gene segment is preceded by a joining (J) gene segment; in addition, there are many cross-hybridizing variable (V) gene segments. To evaluate the extent of sequence diversity of L1 V regions, we screened three cDNA libraries, constructed from mitogen-stimulated Xenopus splenocytes, with probes for the C or the J gene segment. Eighteen cDNA clones that contain complete or truncated V regions were chosen for sequence analysis. The C regions of all clones are identical or nearly identical to the genomic C gene segment; the V regions are greater than 80% identical in nucleotide sequence and are presumably derived from a single family of V gene segments. Although framework regions are nearly identical, complementarity-determining regions are quite diverse. The expressed J segments fall into distinct groups, suggesting the presence of more than one germ-line J segment. Therefore, a genomic library was screened with a J region probe. A clone overlapping with the previously identified J-C clone, and containing four additional J gene segments, was isolated. All five J gene segments are very similar and three are identical in nucleotide sequence. Each of the three distinct germ-line J sequences is represented in the set of cDNA clones, suggesting that combinatorial diversification occurs; imprecision of V-J joining also appears to contribute to variability. Overall, these results suggest that the immunoglobulin repertoire in this species is not significantly restricted by a limitation in the diversity of light chain V regions.


Human progesterone receptor transformation and nuclear down-regulation are independent of phosphorylation.
We have studied the phosphorylation of progesterone receptors (PR) in T47Dco human breast cancer cells using a monoclonal antibody directed against human PR called AB-52. This antibody recognizes both the A- (Mr approximately 94,000) and B- (Mr approximately 120,000) hormone binding proteins of PR, and was used to immunoprecipitate phosphorylated receptors isolated from cells incubated in vivo with [32P]orthophosphate. The specific activity, or phosphorylation levels, relative to protein levels was quantified by combined immunoblotting and autoradiography followed by densitometry. We find that immunopurified untransformed hormone-free receptors, which have a characteristic triplet B, singlet A structure, are phosphoproteins with similar levels of phosphate incorporation in all protein bands. If PR are first transformed to the nuclear binding form by treatment of cells with progesterone, and then labeled with [32P]orthophosphate, the receptor proteins are additionally phosphorylated. These chromatin-bound hormone occupied receptors incorporate five to 10 times more labeled phosphate per total receptor protein than do PR from untreated cells during the same [32P]incubation time. The second round of phosphorylation may also account for mobility shifts of transformed A- and B-receptors observed in sodium dodecyl sulfate-polyacrylamide gels. Both untransformed and transformed species of A- and B-receptors are phosphorylated only on serine residues, and neither the extent of phosphorylation, nor the phosphoamino acids, are affected by treatment of the cells with epidermal growth factor or insulin. We previously reported that after hormone binding and transformation of receptors to the tight chromatin binding state, PR undergo processing, or nuclear down-regulation. AB-52 was used to compare PR protein and phosphorylation levels when cells were treated for 0.5-48 h with progesterone or the synthetic progestin R5020. Both agonists lead to hyperphosphorylation of nuclear PR before phosphorylation levels decrease, in parallel with the drop in protein levels as receptors down-regulate. Treatment of cells with RU 486, an antiprogestin, leads to PR transformation as determined by immunoblotting, but subsequent down-regulation does not occur. After transformation, chromatin-bound RU 486-occupied receptors become intensely phosphorylated however, with specific activities 15 times greater than those of untransformed PR. Since these receptors are phosphorylated but not processed, the hormone-induced nuclear phosphorylation of PR is unlikely to be a signal for receptor processing.(ABSTRACT TRUNCATED AT 400 WORDS)


Development and implementation of a computer-generated reminder system for diabetes preventive care.
Diabetes mellitus is a chronic condition with several late complications that can be delayed or avoided through proper preventive health care. Although practice guidelines have been established to improve the preventive care in diabetics, dissemination of these guidelines among physicians and educational programs have been only moderately successful in changing physicians' practice patterns. Previous efforts, however, did not utilize computer-generated reminders. We developed a system of computer-generated reminders for diabetic preventive care. We completed an implementation of the system in the outpatient clinics of internal medicine residents at our institution. This paper describes the development and implementation of this system. Our results showed that the system flagged an average of 13 items that deviated from diabetes guideline compliance, out of a possible 21 items per patient. The residents completed encounter forms used by the system for 37% of patients seen during a six month period. Physician users exhibited positive attitudes toward the use of guidelines which they judged improved quality at no additional cost of care. However, the complexity and length of the guideline encounter forms and the additional time demands proved to be significant obstacles to current routine use. Our experience will help to improve the system so that it is more usable and acceptable to physicians, especially in the future as health care increasingly makes use of electronic medical record systems.


Wavelength-dependent fibre-optic transillumination of small approximal caries lesions: the use of a dye, and a comparison to bitewing radiography.
The mere detection of caries lesions is insufficient for optimal treatment decision-making. Hence, the aim of this study was to investigate whether quantitative information about approximal lesion depth can be obtained from a technique based on the wavelength dependency of light propagation and additional use of a dye. Another aim was to compare the diagnostic performance of the optical technique and bitewing radiography. Measurements were performed on 33 extracted premolar teeth. Twelve proximal surfaces had white-spot, and 17 had discoloured small lesions. Four surfaces were sound. The teeth were transilluminated with a single glass fibre at the approximal surface before and after dye application. The occlusal surface was imaged with a CCD camera. Light in the blue and red part of the electromagnetic spectrum was selected using Schott glass filters. Average decadic optical thickness differences, delta bl-rd tau eff, were estimated and plotted as a function of normalised lesion depth, dhist, established from histological validation by two observers. The Spearman rank correlation was rs (delta bl-rd tau eff, dhist) = 0.87 (95% confidence interval, CI: 0.74-0.94). A marked increase in average decadic optical thickness in the blue part of the electromagnetic spectrum, delta dye tau eff, was observed for those lesion that, upon direct visual inspection of the approximal surface, clearly showed dye uptake. Bitewing radiographic depth ratings of two observers were plotted as a function of dhist. The correlations were rs (dRA,1, dhist) = 0.62 (95% CI: 0.34-0.80), rs (dRA,2, dhist) = 0.75 (95% CI: 0.54-0.87), and between the observers rs (dRA,1, dRA,2) = 0.44 (95% CI: 0.10-0.69). The p values of rs (delta bl-rd tau eff, dhist) -rs (dRA1,1, dhist) and rs (delta bl-rd tau eff, dhist) -rs (dRA,2, dhist) were p1 = 0.01 and p2 = 0.08, respectively. It was concluded that quantitative information about lesion depth can be obtained optically. The dye penetrates into only a limited number of caries lesions, in which cases dye uptake is detectable in transillumination geometry. Under laboratory circumstances the optical technique performs as well as bitewing radiography in the diagnosis of small approximal caries lesions.


New Insights into Protein Kinase B/Akt Signaling: Role of Localized Akt Activation and Compartment-Specific Target Proteins for the Cellular Radiation Response.
Genetic alterations driving aberrant activation of the survival kinase Protein Kinase B (Akt) are observed with high frequency during malignant transformation and cancer progression. Oncogenic gene mutations coding for the upstream regulators or Akt, e.g., growth factor receptors, RAS and phosphatidylinositol-3-kinase (PI3K), or for one of the three Akt isoforms as well as loss of the tumor suppressor Phosphatase and Tensin Homolog on Chromosome Ten (PTEN) lead to constitutive activation of Akt. By activating Akt, these genetic alterations not only promote growth, proliferation and malignant behavior of cancer cells by phosphorylation of various downstream signaling molecules and signaling nodes but can also contribute to chemo- and radioresistance in many types of tumors. Here we review current knowledge on the mechanisms dictating Akt's activation and target selection including the involvement of miRNAs and with focus on compartmentalization of the signaling network. Moreover, we discuss recent advances in the cross-talk with DNA damage response highlighting nuclear Akt target proteins with potential involvement in the regulation of DNA double strand break repair.


Abrupt and gradual transitions between low and hyperexcited firing frequencies in neuronal models with fast synaptic excitation: a comparative study.
Hyperexcitability of neuronal networks is one of the hallmarks of epileptic brain seizure generation, and results from a net imbalance between excitation and inhibition that promotes excessive abnormal firing frequencies. The transition between low and high firing frequencies as the levels of recurrent AMPA excitation change can occur either gradually or abruptly. We used modeling, numerical simulations, and dynamical systems tools to investigate the biophysical and dynamic mechanisms that underlie these two identified modes of transition in recurrently connected neurons via AMPA excitation. We compare our results and demonstrate that these two modes of transition are qualitatively different and can be linked to different intrinsic properties of the participating neurons.


Differential effects of exogenous and endogenous estrogen on anxiety as measured by elevated T-maze in relation to the serotonergic system.
The effects of estrogen on anxiety-like behaviors have been widely studied but the mechanisms responsible are still inconclusive. The purpose of the current study was to compare the effects of transient high levels of endogenous estrogen and chronic exogenous estrogen treatment on the anxiety-like behaviors using the elevated T-maze (ETM) test. In addition, serotonin (5-HT) and its metabolite (5-HIAA), serotonin reuptake transporter (SERT) and tryptophan hydroxylase enzyme (TPH) were measured at the end of the study and correlated to the task performances. Female sham-operated rats in proestrous phase (Sham-Pro) and ovariectomized rats treated with or without 17beta-estradiol (10 microg/kg, s.c.; Ovx+E(2) or Ovx) for 4 weeks were used. In the ETM test, the Ovx+E(2) group had reduced inhibitory avoidance responses compared to others, suggesting that exogenous E(2) replacement is anxiolytic, while escape latency was prolonged in the Sham-Pro group suggesting endogenous E(2) is panicolytic. Further, the serotonin turnover rate (5-HIAA/5-HT ratio) in the hippocampus and nucleus accumbens was highest in the Ovx+E(2) group. While the TPH protein in the midbrain of Ovx rats was significantly higher than others, the SERT levels were not significantly different among groups in all measured brain areas. In conclusion, Ovx rats with chronic estrogen administration and Sham-Pro rats with naturally high levels of estrogen, demonstrated anxiolytic behavior by exhibiting different forms of anxiety that related to the changes in the function of serotonergic system.


Free Functioning Gracilis Muscle Transfer With and Without Simultaneous Intercostal Nerve Transfer to Musculocutaneous Nerve for Restoration of Elbow Flexion After Traumatic Adult Brachial Pan-Plexus Injury.
After complete 5-level root avulsion brachial plexus injury, the free-functioning muscle transfer (FFMT) and the intercostal nerve (ICN) to musculocutaneous nerve (MCN) transfer are 2 potential reconstructive options for restoration of elbow flexion. The aim of this study was to determine if the combination of the gracilis FFMT and the ICN to MCN transfer provides stronger elbow flexion compared with the gracilis FFMT alone. Sixty-five patients who underwent the gracilis FFMT only (32 patients) or the gracilis FFMT in addition to the ICN to MCN transfer (33 patients) for elbow flexion after a pan-plexus injury were included. The 2 groups were compared with respect to postoperative elbow flexion strength according to the modified British Medical Research Council grading system as well as preoperative and postoperative Disability of the Arm, Shoulder, and Hand scores. Two subgroup analyses were performed for the British Medical Research Council elbow flexion strength grade: FFMT neurotization (spinal accessory nerve vs ICN) and the attachment of the distal gracilis tendon (biceps tendon vs flexor digitorum profundus/flexor pollicis longus tendon). The proportion of patients reaching the M3/M4 elbow flexion muscle grade were similar in both groups (FFMT vs FFMT + ICN to MCN transfer). Statistically significant improvement in postoperative Disability of the Arm, Shoulder, and Hand score was found in the FFMT + ICN to MCN transfer group but not in the FFMT group. There was a significant difference between gracilis to biceps (M3/M4 = 52.6%) and gracilis to FDP/flexor pollicis longus (M3/M4 = 85.2%) tendon attachment. The use of the ICN to MCN transfer associated with the FFMT does not improve the elbow flexion modified British Medical Research Council grade, although better postoperative Disability of the Arm, Shoulder, and Hand scores were found in this group. The more distal attachment of the gracilis FFMT tendon may play an important role in elbow flexion strength. Therapeutic IV.


Homeostasis of extracellular matrix by TGF-beta and lefty.
Both normal and neoplastic tissues have a stroma comprised of fibroblasts which deposit an extracellular matrix (ECM) enriched in collagen. In most normal tissues, the synthesis and breakdown of the ECM is maintained at a low level. However, in normal adult tissues such as endometrium, and in rapidly growing embryonic and neoplastic tissues, there is a significant increase in the synthesis and/or breakdown of ECM. The homeostasis of the ECM is maintained by a molecular repertoire which appears to consist of TGF-beta and lefty. TGF-beta acts as a pro-fibrogenic cytokine by increasing the synthesis of collagen and decreasing the degradation of ECM. Physiologic levels of TGF-beta maintains tissue homeostasis and aberrant over-expression of TGF-beta leads to tissue fibrosis. TGF-beta acts through a core Smad signaling pathway which is initiated by the binding of homo-dimeric TGF-beta protein to two type I and II receptors. The constitutively active receptor type II leads to phosphorylation of receptor type I which, in turn, causes the R-Smads to get phosphorylated. The downstream gene transcriptional activity of this event includes significant increase in connective tissue growth factor (CTGF) and collagen mRNA synthesis which leads to deposition of collagen in tissues. Lefty inhibits Smad2 phosphorylation initiated by TGF-beta or its receptor and prevents CTGF promoter activity driven by TGF-beta. Moreover, lefty inhibits CTGF and collagen mRNA synthesis and increases collagenolysis and elastolysis and as a result of these actions, lefty significantly reduces the amount of collagen deposited in tissues. Thus, TGF-beta and lefty might coordinately participate in the homeostasis of ECM in tissues.


Nanotubes fabricated from Ni-naphthalocyanine by a template method.
Novel naphthalocyanine (Nc) nanotubes with special wall structures were fabricated by a template method using Nc molecules as building blocks. Thermal stabilization of the ordered columnar structures of the tetrakis(tert-butyl)naphthalocyanine (Ni-BNc) molecules, induced from the pi-pi interactions in the nanoscale channels of an alumina template, resulted in Nc nanotubes with walls consisting of well-ordered Nc molecular disks. Further thermal treatment of Ni-BNc at 600 degrees C produced carbonized Nc nanotubes containing ordered columnar, graphitic wall structures with the graphene disks arranged perpendicular to the tube axis. These nanotubes may be useful for extending the application of Nc molecules for nanodevice fabrication.


Facilitators and barriers influencing the readiness to receive dental implants in a geriatric institutionalised population-A randomized non-invasive interventional study.
Although elderly people have many serious dental issues and are in need of prosthesis, few opt for dental implants. The aim of this study was to investigate barriers that prevent elderly people from receiving dental implants. Specifically, we examined (i) whether the message was delivered before or after the interview had an impact, and (ii) whether it did matter who delivered the message. Sixty-six residents from seven residential homes in the Canton of Grisons, Switzerland were included. The sample was randomized to a treatment group that received comprehensive education about dental implants before the interview and a control group that received education after completing the questionnaire. The sample consisted of 54 women (81.8%) and 12 males (18.2%) with an average age of 86.2 years. Education before the interview did not show any impact on the attitude towards dental implants. Main reasons for a negative attitude towards implants were old age and high costs. Participants who received information about implants from their relatives and their own dentist and not from the study dentist were significantly more willing to receive implants. Providing an adequate education about benefits and risks of receiving dental implants does not change the attitude towards dental implants. The source of information/messenger does influence attitudes towards implants. If the person delivering the education and information is a relative or a known medical person, the person's attitude is more likely to change as compared to people receiving the information from an unrelated person.


Intracellular calcium leak lowers glucose storage in human muscle, promoting hyperglycemia and diabetes.
Most glucose is processed in muscle, for energy or glycogen stores. Malignant Hyperthermia Susceptibility (MHS) exemplifies muscle conditions that increase [Ca2+]cytosol. 42% of MHS patients have hyperglycemia. We show that phosphorylated glycogen phosphorylase (GPa), glycogen synthase (GSa) - respectively activated and inactivated by phosphorylation - and their Ca2+-dependent kinase (PhK), are elevated in microsomal extracts from MHS patients' muscle. Glycogen and glucose transporter GLUT4 are decreased. [Ca2+]cytosol, increased to MHS levels, promoted GP phosphorylation. Imaging at ~100 nm resolution located GPa at sarcoplasmic reticulum (SR) junctional cisternae, and apo-GP at Z disk. MHS muscle therefore has a wide-ranging alteration in glucose metabolism: high [Ca2+]cytosol activates PhK, which inhibits GS, activates GP and moves it toward the SR, favoring glycogenolysis. The alterations probably cause these patients' hyperglycemia. For basic studies, MHS emerges as a variable stressor, which forces glucose pathways from the normal to the diseased range, thereby exposing novel metabolic links.


Virus enhances IgE- and non-IgE-dependent histamine release induced by bacteria and other stimulators.
Histamine release from human basophil leukocytes was triggered by Staph. aureus, Salmonella enteritidis, non-haemolytic streptococci, or E. coli. Influenza A virus was found to enhance the mediator release and the effect was caused by synergism, since the virus did not induce release of histamine per se. This potentiating effect of the virus was seen both when the bacteria-induced histamine release was IgE-dependent (i.e. patient sensitized to the bacterium) and when the bacterium caused mediator release by a non-immunological mechanism independent of IgE (putative sugar-lectin mediated). Histamine release induced by anti-IgE and calcium ionophore or agarose-beads was also enhanced in the presence of the virus. These findings indicate that influenza A virus potentiates both IgE- and non-IgE-mediated histamine release induced by bacteria and other stimulators.


Rhegmatogenous retinal detachment in phakic eyes after posterior chamber phakic intraocular lens implantation for severe myopia.
To report the clinical presentation, surgical management, and outcomes of rhegmatogenous retinal detachment (RRD) in patients with severe myopia corrected by posterior chamber phakic (PCP) intraocular lens (IOL) implantation. Retrospective, noncomparative, interventional case series. Sixteen eyes of 15 patients in whom retinal detachment developed after PCP IOL implantation. The 16 eyes with retinal detachment after PCP IOL implantation underwent scleral buckling and pars plana vitrectomy. Uncorrected visual acuity, refraction, best spectacle-corrected visual acuity (BSCVA), time between refractive procedure and RRD, vitreoretinal findings, and anatomic reattachment rate. The incidence of RRD after PCP IOL implantation was 2.07%. Mean patient age was 32.9 years (range, 23-46). Nine patients underwent bilateral PCP IOL implantation (60%). Primary RRD developed in 16 eyes of 15 patients. Prophylactic laser photocoagulation was performed in 3 eyes of 3 patients (18.75%). Mean preoperative spherical equivalent (SE) was -17.3+/-2.47 diopters (D) (range, -13.75 D to -22 D). Rhegmatogenous retinal detachment occurred from 1 to 70 months after PCP IOL implantation (mean, 29.12 months). Each of 11 RRDs (68.75%) had 1 causative break. Fourteen breaks (60.86%) were horseshoe tears and 9 (39.14%) were atrophic holes. Scleral buckling was performed in 10 eyes (62.5%). Pars plana vitrectomy alone was performed in 5 cases (31.25%) with posterior breaks. Initial reattachment rate was 90.9%. Final retinal reattachment was 100%. Mean postoperative BSCVA was 20/28 (decimal fraction, 0.72+/-0.25). Mean follow-up after retinal detachment surgery was 35.25+/-17.29 months (range, 12-67 months). Rhegmatogenous retinal detachment after PCP IOL implantation is rare. Case-control studies are warranted to determine whether this surgical procedure increases the risk of retinal detachment in these patients. The characteristics of RRD do not differ from the natural history of retinal detachment. Surgical management of RRD was successful in restoring vision in our patients. This article contains additional online-only material available at .