Characteristics of circadian rhythm-related genes and establishment of a prognostic scoring system for lung adenocarcinoma with experimental verification: a bioinformatics analysis.
Non-small cell lung cancer (NSCLC) is one of the most common malignant tumors worldwide. Lung adenocarcinoma (LUAD), the main subtype of NSCLC, has a poor prognosis. In recent years, circadian rhythm (CR)-related genes (CRRGs) have demonstrated associations with tumor occurrence and development, but the relationship between CRRGs and LUAD is not clear. Because of the correlation between CRRGs and tumors, we have reason to believe that CRRGs will become an important prognostic indicator for LUAD and guide the treatment of LUAD prognosis. Based on data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we explored the biological function and immune cell infiltration of LUAD in different CR clusters and quantified CR genes using principal component analysis (PCA). Then, we built a CR scoring system (CRscore) to explore the relationship between CRRGs and LUAD prognosis. Patients were divided into three clusters (A, B, and C). Biological characteristics, such as survival, immune cell infiltration, and gene enrichment, were significantly different among the three clusters (P<0.001). We then established the usefulness of the CR score, which could probably predict the prognosis of LUAD. Specifically, patients with a high CR score had a better prognosis and were more sensitive to chemotherapy than those with a low CR score. It is possible to use CRRGs to assess the prognosis of patients with LUAD. Quantification of CR using the CRscore tool in patients with LUAD maybe help to guide personalized cancer immunotherapy strategies in the future. Thus, the CRscore may be a prognostic tool for LUAD.


Selective serotonin reuptake inhibitors and the risk of acute pancreatitis: a Swedish population-based case-control study.
Case reports have indicated an increased risk of acute pancreatitis during use of selective serotonin reuptake inhibitors (SSRIs), an association not found in a few epidemiological studies. We studied the use of SSRI in relation to risk of acute pancreatitis in a population-based case-control study of people aged 40 to 84 years between 2006 and 2008 in Sweden. The Patient Register was used to identify 6161 cases of first-episode acute pancreatitis. The Register of the Total Population was used to randomly select 61,637 control subjects from the general population using frequency-based density sampling, matched for age, sex, and calendar year. Use of SSRI was defined as "current," "recent," "past," or "former" if the drug had been dispensed 1 to 114 days, 115 to 180 days, 181 to 365 days, or 1 to 3.5 years before a given index date, respectively. Logistic regression with adjustment for potential confounding factors was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs). The OR for acute pancreatitis, adjusted for matching variables, was increased among present users of SSRI (OR, 1.5; 95% CI, 1.4-1.7). After adjusting for diseases or medications related to alcohol overconsumption, tobacco smoking, diabetes, ischemic heart disease, obesity, and severe pain together with educational level and marital status, the corresponding OR was 1.1 (95% CI, 1.0-1.3). After adjusting for the number of distinct medications, a proxy for comorbidity, the corresponding OR was 1.0 (95% CI, 0.9-1.1). The OR for antidepressant use other than SSRI showed a similar pattern. In conclusion, no increased risk of acute pancreatitis remained among users of SSRI after adjusting for confounding factors.


Changes in routine laboratory tests and survival in amyotrophic lateral sclerosis.
The aim of this study is to evaluate the association between changes in routinely prescribed laboratory tests and tracheostomy-free survival in amyotrophic lateral sclerosis (ALS). Two hundred seventy-five ALS patients were retrospectively studied. BMI, forced vital capacity, hemoglobin, hematocrit, lymphocytes, cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, proteins, albumin, creatine-phosphokinase, iron, ferritin, transferrin, glucose, urea, uric acid, and creatinine were measured every 6 months from baseline to 24 months, death or study end, together with the probability of death or tracheostomy. Missing data were handled using multiple imputation chained equations. Hemoglobin (OR = 1.71, 95%CI 1.24-2.36 for IQR increase), hematocrit (OR = 1.87, 95%CI 1.34-2.63 for IQR increase), urea (OR = 1.51, 95%CI 1.21-1.89 for IQR increase), and uric acid (OR = 1.98, 95%CI 1.23-3.20 for IQR increase) were directly associated, while triglycerides (OR = 0.69, 0.51 to 0.93 for IQR increase) were inversely associated with the odds of death or tracheostomy. In our cohort, an increase of hemoglobin, hematocrit, urea, and uric acid was directly associated, and an increase of triglycerides was inversely associated with the odds of death or tracheostomy. Should these findings be replicated in an external cohort, they might help to discriminate ALS progression and patients' decisions about procedures and end of life.


Physical properties, engine performance, and exhaust emissions of waste fish oil biodiesel/bioethanol/diesel fuel blends.
In the current study, the physicochemical, engine performance, and exhaust emission of different ternary fuel blends containing waste fish oil (WFO) biodiesel, bioethanol, and petro-diesel have been investigated. WFO Biodiesel was prepared from waste fish oil via transesterification method. Different physiochemical properties including the kinematic viscosity, density, flash point, pour point, cloud point, and heat value have been measured for different fuel blends and compared with the neat petro-diesel. The performance and exhaust emission of engine have been also studied using different fuel blends using a single-cylinder diesel engine in full load condition at 1800 rpm. It was found that the engine torque, engine power, and thermal efficiency of the ternary fuel blends was reduced by 2.45%, 9.25%, 2.35% averagely in comparison with the neat petro-diesel, respectively. The average break specific fuel consumption was also increased by 10.44% compared to the neat petro-diesel. The emission of carbon monoxide (CO), carbon dioxide (CO2), unburned hydrocarbons (UHC), and nitrogen oxides (NOx) was also measured. It was also found that the utilization of ternary fuel blends results in a considerable reduction in CO and UHC emission by 50.55% and 43.87% on average compared to the neat petro-diesel, respectively. The emission of NOx was also increased by 28.25% on average compared to the neat petro-diesel. It was also found that the NOx emission can be adjusted by tuning the WFO biodiesel and bioethanol contents of the ternary fuel blends.


Clinical neurophysiologic studies: which test is useful and when?
Neurophysiological studies test the integrity of nerve roots and nerves at different points from the spinal cord to the periphery. EMG is the most sensitive neurophysiological test for evaluating patients with radiculopathy, providing information on diagnosis, location, and prognosis. F-wave and H-reflex studies may be abnormal, but the information that they provide is nonspecific and usually redundant because the needle examination is abnormal anyway. Somatosensory evoked potentials are less sensitive and specific than EMG for diagnosing a radiculopathy, but uncommonly may be the only abnormality. Magnetic stimulation, paraspinal mapping, and cervical root stimulation are investigational techniques of uncertain utility.


Hydrogen Sulfide Improves the Cold Stress Resistance through the CsARF5-CsDREB3 Module in Cucumber.
As an important gas signaling molecule, hydrogen sulfide (H2S) plays a crucial role in regulating cold tolerance. H2S cooperates with phytohormones such as abscisic acid, ethylene, and salicylic acid to regulate the plant stress response. However, the synergistic regulation of H2S and auxin in the plant response to cold stress has not been reported. This study showed that sodium hydrosulfide (NaHS, an H2S donor) treatment enhanced the cold stress tolerance of cucumber seedlings and increased the level of auxin. CsARF5, a cucumber auxin response factor (ARF) gene, was isolated, and its role in regulating H2S-mediated cold stress tolerance was described. Transgenic cucumber leaves overexpressing CsARF5 were obtained. Physiological analysis indicated that overexpression of CsARF5 enhanced the cold stress tolerance of cucumber and the regulation of the cold stress response by CsARF5 depends on H2S. In addition, molecular assays showed that CsARF5 modulated cold stress response by directly activating the expression of the dehydration-responsive element-binding (DREB)/C-repeat binding factor (CBF) gene CsDREB3, which was identified as a positive regulator of cold stress. Taken together, the above results suggest that CsARF5 plays an important role in H2S-mediated cold stress in cucumber. These results shed light on the molecular mechanism by which H2S regulates cold stress response by mediating auxin signaling; this will provide insights for further studies on the molecular mechanism by which H2S regulates cold stress. The aim of this study was to explore the molecular mechanism of H2S regulating cold tolerance of cucumber seedlings and provide a theoretical basis for the further study of cucumber cultivation and environmental adaptability technology in winter.


Diagnosis of arteriosclerosis obliterans by impedance technique with special reference to relative blood flow of the lower extremity.
Simultaneous recordings of impedance cardiography of the chest and impedance plethysmography of the lower extremity were performed on 105 limbs with or without arteriosclerosis obliterans (ASO) documented by angiography. The ratios of blood flow to the lower extremity--leg stroke volume/cardiac stroke volume--(LSV/CSV) were 11.2 +/- 3.3% in normal male subjects, 11.1 +/- 5.5% in normal female subjects, and 3.1 +/- 1.2% in lower extremities with ASO, respectively. The normal value (range) for LSV/CSV calculated from the normal groups by the percentile method was between 4.9% and 17.8%, and the diagnostic accuracy of this value was 100% for sensitivity and 97.5% for specificity. LSV/CSV is a good index for the diagnosis of ASO and makes it possible to minimize error when expressed as an absolute value.


Validation and cross-cultural adaptation of the Multiple Sclerosis Intimacy and Sexuality Questionnaire-15 (MSISQ-15) into Spanish.
The Multiple Sclerosis Intimacy and Sexuality Questionnaire-15 (MSISQ-15) is a valid and reliable tool to assess the sexuality of people with multiple sclerosis. The objectives of this study were: 1) to cross-culturally adapt and examine the psychometric properties of the MSISQ-15 in the Spanish context and 2) to examine the association between sexual dysfunction and other related factors. We conducted a instrumental study. People diagnosed with multiple sclerosis and members of multiple sclerosis associations in Spain were included. The linguistic adaptation of the questionnaire was performed through a translation-back translation procedure. For the psychometric validation, the confirmatory factor analysis was used while the internal consistency was examined by the ordinal alpha test. The construct validity was examined by correlating the results with the Male Sexual Function (FSH), Female Sexual Function-2 (FSM-2), Dyadic Adjustment Scale-13 (EAD-13) and Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL) questionnaires. A total of 208 participants were included. Both the fit of the Spanish version of the MSISQ-15 to the original scale and the internal consistency were adequate (α = 0.89). The construct validity showed correlations with the FSH, FSM-2, and MusiQoL but not with the EAD-13. The Spanish version of the MSISQ-15 is a valid and reliable tool to assess the sexuality of people with multiple sclerosis in the Spanish context.


Cardiac neural crest.
Neural crest cells (NCCs) contribute to many organs and tissues during embryonic development. Amongst these, the cardiovascular system represents a fascinating example. In this review, recent advances in our understanding of the developmental biology and molecular genetics regulating cardiac NCC maturation will be summarized. While the existence of a significant neural crest (NC) contribution to the developing heart has been appreciated for more than 20 years, only in the last few years have molecular pathways regulating this process been elucidated and the significant contribution of these mechanisms to the etiology of congenital heart disease in man become apparent. Emerging data suggest that ongoing studies will reveal complex inductive interactions between cardiac NC and a series of other cell types contributing to the developing cardiovascular system.


The effect of age upon the entry of some amino acids into the brain, and their incorporation into cerebral protein.
The way in which the influx of amino acids into the brain changes as the age of rats increases from one to 25 weeks is reported. Most of the amino acids have a very high rate of influx during the first weeks of life, which falls progressively until an adult is reached by about 8 to 10 weeks of age. The high influx in early life is due to carrier-mediated transport systems which act more rapidly in the young than in the adult. These systems can be saturated by raised levels of amino acid in the blood, both in young and adult animals. The high influx in early life is necessary to provide abundant supplies of amino acids for cerebralprotein formation during the period of rapid brain growth. In adult life, influx declines to a level that is adequate to support the synthesis of cerebral protein, which is still being continuously broken down and renewed at a remarkably high rate.


Clinical pharmacology of cefadroxil in infants and children.
The pharmacokinetics of cefadroxil suspension were studied in 30 children, 13 months to 12 years of age (mean age, 5.7 years). Average peak concentrations in serum of 11 to 14 mug/ml and of 7 to 10 mug/ml after 15- and 10-mg/kg doses, respectively, were not substantially affected by the feeding status. The serum half-life values were 1.3 to 1.5 h. Cefadroxil was detected in saliva of all children 2 h after 15-mg/kg doses: the levels ranged from 0.17 to 2.6 mug/ml (mean, 0.46 mug/ml). The average concentrations in urine were 1,700 and 2,620 mug/ml at 0 to 2 and 2 to 4 h, respectively, after 15-mg/kg doses. In a randomized controlled study of 50 children with impetigo, cefadroxil was as effective as penicillin G in curing existing lesions and in preventing development of new lesions. Cefadroxil may be useful for therapy of mucocutaneous and urinary tract infections in infants and children.


Riboswitches, from cognition to transformation.
Riboswitches are functional RNA elements that regulate gene expression by directly detecting metabolites. Twenty years have passed since it was first discovered, researches on riboswitches are becoming increasingly standardized and refined, which could significantly promote people's cognition of RNA function as well. Here, we focus on some representative orphan riboswitches, enumerate the structural and functional transformation and artificial design of riboswitches including the coupling with ribozymes, hoping to attain a comprehensive understanding of riboswitch research.


Red blood cell transfusion in obstetrics and its implication for patient blood management: a retrospective analysis in Switzerland from 1998 to 2016.
Peripartum hemorrhage (PPH) remains one of the main causes of maternal mortality worldwide. Treatment includes administration of packed red blood cells (RBC) in severe cases and patient blood management (PBM) may reduce it significantly. In our study, we wanted to retrospectively assess red blood cell administration in PPH to evaluate the impact of PBM in Switzerland. Using data from the Swiss obstetric hospital registry (Arbeitsgemeinschaft Schweizer Frauenkliniken, ASF), we included patients with deliveries from 1998 to 2016. We examined available obstetric data as well as blood loss and RBC administration in the acute and subacute peripartal phase. We categorized data into two time intervals: 1998-2011 and 2012-2016, as new PPH guidelines in Switzerland were established in 2012. PPH incidence increased between 1998 and 2016 significantly. The number of vaginal instrumental deliveries and cesarean sections increased as well. Administration of three or more RBC units, as defined in the ASF registry, in the acute and subacute phase in Switzerland has decreased after 2012. Conversely, we saw an increase in the administration of one to two RBC units in the acute and subacute phase. Nevertheless, overall RBC administration has been decreasing from 1998 to 2016. The increase of patients obtaining one or two units of RBC for PPH suggests that there may be a potential for effective implication of PBM in obstetrics. Reduction of RBC transfusion in the context of PPH may not only decrease maternal morbidity, but decrease economic costs as well.


Lymphocyte defect in plasmacytoma-bearing mice.
Multiple myeloma is often associated with humoral immunodepression in both man and mouse. When mice bearing the humorally immunodepressive plasmacytomas TEPC-183 and SPQC-11 were injected with SRBC, the rise of serum haemolysins was significantly less than that of non-tumour-bearing mice. Mice with the plasmacytomas MPC-11 and MOPC-315 have an antibody response similar to normal mice when injected with SRBC. Following immunization, normal mice and those bearing MPC-11 showed a 2- to 3-fold increase in total spleen lymphocytes. Mice bearing TEPC-183 or SPQC-11, the plasmacytomas causing an impaired antibody response, has significant increase in spleen lymphocytes under the same conditions. Mice bearing MOPC-315 had a very high initial count of spleen lymphocytes, which did not further increase upon immune stimulation.Incubation of lymphocytes from plasmacytoma-bearing mice with PHA did not produce an increase in TdR incorporation and in some cases even caused a decrease in TdR incorporation.Lymphocytes from mice bearing TEPC-183, SPQC-11, and MOPC-315 incorporated less TdR in response to LPS than did normal mice. On the other hand, mice bearing MPC-11 incorporated about as much TdR as did normal mice following LPS stimulation. Thus, the defect in the ability to respond to LPS in vitro correlated with the lack of an increase of spleen lymphocytes in mice bearing these tumours following antigenic stimulation in vivo.No immunodepressive properties of serum from mice with plasmacytoma could be detected.


Well-defined Graphene Oxide as a Potential Component in Lung Cancer Therapy.
Graphene oxide (GO) has unique physical and chemical properties that can be used in anticancer therapy - especially as a drug carrier. Graphene oxide, due to the presence of several hybrid layers of carbon atoms (sp2), has a large surface for highly efficient drug loading. In addition, GO with a large number of carboxyl, hydroxyl and epoxy groups on its surface, can charge various drug molecules through covalent bonds, hydrophobic interactions, hydrogen bonds and electrostatic interactions. The aim of our work was to evaluate the possibility of future use of graphene oxide as an anticancer drug carrier. In this paper, we present GO synthesis and characterization, as well as a study of its biological properties. The cytotoxic effect of well-defined graphene oxide was tested on both carcinoma and non-malignant cells isolated from the same organ, which is not often presented in the literature. The performed research confirmed that GO in high concentrations (> 300 µgmL-1) selectively decreased the viability of cancer cell line. Additionally, we showed that the GO flakes have a high affinity to cancer cell nucleus which influences their metabolism (inhibition of cancer cell proliferation). Moreover, we have proved that GO in high concentrations can cause cell membrane damage and generate reactive oxygen species on a low level mainly in cancer cells. The proposed GO could be useful in anticancer therapy. A high concentration of GO selectively causes the death of tumor cells, whereas GO with low concentration could be a potential material for anticancer drug loading.


Pichia pastoris mutants as host strains for efficient secretion of recombinant branched chain aminotransferase (BCAT).
Branched chain aminotransferase (BCAT) is one of the enzymatic tools of choice for the production of chiral amines or amino acids; especially, non-natural amino acids are of interest as building blocks for the pharmaceutical industry. The expression and subsequent secretion of BCAT counteracts limited cell permeability of target substrates and facilitates downstream processing. Since Pichia pastoris secretes a negligible amount of native proteins and was previously shown to efficiently secrete recombinant proteins, it was chosen as the expression host. We examined different promoters and glycosylation states and also engineered the host strain by disrupting genes encoding proteins related to cell wall assembly (Scw10, Cwp1) and glycosylation (Och1). Finally, we were able not only to increase the extracellular BCAT production, but also to achieve a more homogenous product in terms of glycosylation and identified a deletion strain, which counteracts typical cell clustering in the Δoch1 strain.


Skin closure with 2-octyl cyanoacrylate and polyester mesh after primary total knee arthroplasty offers superior cosmetic outcomes and patient satisfaction compared to staples: a prospective trial.
The goals of this study were to compare patient satisfaction and wound-related complications in patients receiving 2-octyl cyanoacrylate (glue) and polyester mesh for skin closure after primary total knee arthroplasty (TKA) versus staples. A total of 60 knees in 54 patients undergoing TKA were enrolled in a prospective trial and randomized to receive either skin closure with glue and polyester mesh (n = 30) or a control group closed with staples (n = 30). Hollander wound cosmesis score (measured on a scale of 0-5, with 0 being the best) and visual analog scale (VAS) scores (range 0-100 mm) for patient satisfaction with wound cosmesis, as well as wound-related readmission, reoperation, and complications, including superficial surgical site infection, wound dehiscence, wound hematoma, stitch abscess, and wound discharge, were assessed at 6 weeks and 90 days after TKA. Baseline characteristics were not statistically significantly different between the groups (p > 0.05). At 6 weeks and 90 days, the Hollander wound cosmesis score was significantly lower (p < 0.01) in the glue and polyester mesh groups. Similarly, at 6 weeks and 90 days, the VAS for patient satisfaction with wound cosmesis was significantly higher (p < 0.01) in the glue and polyester mesh groups. The rate of superficial surgical site infection was 1/30 (3%) in glue and polyester mesh groups versus zero in the control group (p = 1.00). The rate of wound dehiscence was 1/30 (3%) in glue and polyester mesh groups versus zero in the control group (p = 1.00). These results suggest that glue and polyester mesh closure may offer superior cosmetic outcomes to staples for skin closure in TKA.


Ventilation in the patient with unilateral lung disease.
Severe ULD presents a challenge in ventilator management because of the marked asymmetry in the mechanics of the two lungs. The asymmetry may result from significant decreases or increases in the compliance of the involved lung. Traditional ventilator support may fail to produce adequate gas exchange in these situations and has the potential to cause further deterioration. Fortunately, conventional techniques can be safely and effectively applied in the majority of cases without having to resort to less familiar and potentially hazardous forms of support. In those circumstances when conventional ventilation is unsuccessful in restoring adequate gas exchange, lateral positioning and ILV have proved effective at improving and maintaining gas exchange. Controlled trials to guide clinical decision making are lacking. In patients who have processes associated with decreased compliance in the involved lung, lateral positioning may be a simple method of improving gas exchange but is associated with many practical limitations. ILV in these patients is frequently successful when differential PEEP is applied with the higher pressure to the involved lung. In patients in whom the pathology results in distribution of ventilation favoring the involved lung, particularly BPF, ILV can be used to supply adequate support while minimizing flow through the fistula and allowing it to close. The application of these techniques should be undertaken with an understanding of the pathophysiology of the underlying process; the reported experience with these techniques, including indications and successfully applied methods; and the potential problems encountered with their use. Fortunately, these modalities are infrequently required, but they provide a critical means of support when conventional techniques fail.


Gastrocolonic Response.
The gastrocolonic response (GCR), is a physiologic increase in motor activity of the colon, which usually occurs within minutes following meal ingestion. Over the years several triggers that provoke GCR were recognized including gastric dilation, caloric intake, and fat component of the meal. The response is mediated by the vagal nerve and neurohumoral mechanisms, and it can be modified by several pharmacological factors. Assessment of GCR is part of high-resolution colonic manometry studies, performed in patients with suspected colonic dysmotility. This review highlights the physiologic basis of GCR as well as its clinical and diagnostic features and implementation in variable pathological conditions and clinical practice. GCR has a role in patients with constipation, diabetes, dumping syndrome, bowel hyper and hypomotility and irritable bowel syndrome. Novel sensory triggers for GCR were recently recognized. GCR is a physiological response which is evaluated during colonic manometry studies. Abnormal GCR is a marker of an underlying pathology, which can provide a potential target for treatment.


Differential expression of DNA topoisomerase I gene between CPT-11 acquired- and native-resistant human pancreatic tumor cell lines: detected by RNA/PCR-based quantitation assay.
RNA/PCR quantitation method was developed to determine DNA Topoisomerase I(Topo I)-specific mRNA in order to study its gene expression in CPT-11 sensitive, acquired- or native-resistant human pancreatic tumor cell lines. The results were supported by Northern blotting and Western blotting analyses. Acquired-resistant cells have shown decreased levels of Topo I mRNA, compared with their parental cells. On the contrary, in the wild type cells no correlation was shown between sensitivity and gene expression. On the other, specific Topo I activity of the native resistant cell lines was fairly lower than that of sensitive cell lines, suggesting that immunoreactive Topo I protein contains low levels of active form enzyme which could be targets of CPT-11 in these native-resistant ones. Finally, the different mechanisms might be operative between acquired- and native-resistant tumor cells.


Epistemic Authority in Nursing Practice vs. Doctors' Orders.
The practice policy of doctors' orders is still deeply embedded in 21st century professional nurse practice, despite its profound incongruence with nursing's perspective, standards of practice, and advanced knowledge. The author in this article elaborates on the doctors' orders policy in relation to nursing's disciplinary perspective and epistemic authority in professional practice.


Eukaryotic initiation factor 4A stimulates translation in microinjected Xenopus oocytes.
The injection of heterologous mRNA into fully grown Xenopus oocytes results not only in the synthesis of the heterologous protein but also in a reciprocal decrease in the synthesis of endogenous proteins. This indicates that injected and endogenous mRNAs compete for some component which is rate-limiting for translation in oocytes. We have attempted to identify this rate-limiting translational component. We find that heterologous and homologous polysomes compete with endogenous mRNAs as effectively as naked mRNA, indicating that polysomes do not contain detectable levels of the rate-limiting factor. In addition, we have used micrococcal nuclease digestion and a mRNA-specific oligonucleotide to destroy the mRNA component of polysomes. The remaining polysome factors, when injected into oocytes, failed to stimulate translation. When several eukaryotic translation initiation factors were injected into oocytes, initiation factor 4A consistently increased general oocyte protein synthesis by about twofold. It is possible that the availability of eIF-4A in oocytes is a key factor in limiting the overall rate of protein synthesis.


The inclusion of nuclear area improves the Paris system for reporting urinary cytology.
The Paris System for Reporting Urinary Cytology (TPS) is a well-known urinary diagnostic model; however, occasional false-positives are a problem. To address this issue, we developed an improved algorithm (IA), based on additional cytological features, for TPS diagnosis. Cytological features were evaluated in 29 hard-to-classify cases, including 22 malignant cases and seven benign cases, using image analysis. The optimal IA was determined using the area under the receiver operating characteristic curve as an index. Re-evaluation was performed by applying measured values to the TPS and IA algorithms. Using TPS, 12 of the 22 malignant cases were reassigned to a more appropriate category, and the remaining 10 malignant cases remained hard-to-classify. Two of the seven benign cases were classified as suspicious for high-grade urothelial carcinoma, and the remaining five benign cases remained in the original category. The IA, which included nuclear area as a parameter, showed the same diagnostic sensitivity as TPS, and three of the seven benign cases were reassessed as negative. Thus, the positive and negative predictive values of the IA were higher than those of TPS (84.6% and 100% vs 75.9% and 0%). The newly developed IA is a practical algorithm with which to address the limitations of TPS and thus may contribute to improved diagnostic accuracy.


Can short-term memory be trained?
Is the capacity of short-term memory fixed, or does it improve with practice? It is already known that training on complex working memory tasks is more likely to transfer to untrained tasks with similar properties, but this approach has not been extended to the more basic short-term memory system responsible for verbal serial recall. Here we investigated this with adaptive training algorithms widely applied in working memory training. Serial recall of visually presented digits was found to improve over the course of 20 training sessions, but this improvement did not extend to recall of either spoken digits or visually presented letters. In contrast, training on a nonserial visual short-term memory color change detection task did transfer to a line orientation change detection task. We suggest that training only generates substantial transfer when the unfamiliar demands of the training activities require the development of novel routines that can then be applied to untrained versions of the same paradigm (Gathercole, Dunning, Holmes, & Norris, 2019). In contrast, serial recall of digits is fully supported by the existing verbal short-term memory system and does not require the development of new routines.


Cis effect of lacZ sequences in transgenic mice.
Transgenic mice carrying the 3-hydroxy-3-methylglutarylCoA reductase (HMG) promoter driving the Escherichia coli beta-galactosidase (lacZ) gene did not display the expected ubiquitous and constitutive expression in HMG-lacZ transgenic mice. The same promoter is however able to drive ubiquitous expression of the chloramphenicol acetyltransferase (cat) gene. Two lines of double HMG-lacZ and HMG-cat transgenic mice were obtained in which the two constructs were integrated at the same genomic sites. These mice expressed both reporter genes, but exclusively in the testes. These results suggest that the lacZ sequence might interfere negatively with the expression of the adjacent HMG-cat transgene.


The association between nocturnal trapezius muscle activity and shoulder and neck pain.
The study investigated the possible association between nocturnal trapezius muscle activity and shoulder and neck pain. Sixty female subjects participated in the study, 33 were classified as pain-afflicted on the basis of shoulder and neck pain reports for the previous 6 months. Electromyographic (EMG) activity was monitored bilaterally from the trapezius in all recordings. EMG recording of the deltoid, biceps, and hand flexors was included for 26 subjects (17 with pain) to provide a comparative basis for evaluation of the trapezius recordings. There was considerable variation in the amount of muscle activity between subjects; however, some subjects presented a continuous, low-level activity pattern throughout the presumed sleep period. Subjects classified as pain-afflicted had significantly higher activity level and longer duration of trapezius EMG activity than the pain-free subjects. The deltoid had significantly more activity than the trapezius, while the biceps and the hand flexors presented similar activity level and duration as the trapezius. Nocturnal trapezius activity was not associated with pain exacerbation the same night. We suggest nocturnal trapezius muscle activity is a pointer to physiological mechanisms that contribute to some forms of shoulder and neck pain, such as trapezius myalgia, but nocturnal muscle activity may not be casually implicated in the pain-induction process.


Recent advances in laser therapy for the treatment of cutaneous vascular disorders.
The use of lasers for the treatment of cutaneous vascular disorders has expanded rapidly since its inception in the early 1960s. The flashlamp-pumped pulsed tunable dye laser (PDL), which is the best laser system for the treatment of port-wine stains (PWS), is based on the premise of selective photothermolysis. Recent literature demonstrates enhanced selective photothermolysis by modifying the PDL to include a longer pulse width, a longer wavelength and higher energy fluences through the use of dynamic cooling. Multiple pulse laser irradiation, a new innovative method, shows promising preliminary results in eradicating hypertrophic PWS. In the treatment of capillary haemangiomas, previous uncontrolled studies suggest benefit with early PDL therapy but a recent randomised controlled trial does not support this claim. Mixed haemangiomas respond poorly to PDL treatment, uncomplicated tumours are best left to involute spontaneously whilst life/organ-threatening lesions require early active intervention. The efficacy of lasers in the treatment of telangiectatic leg veins (TLV) remains controversial. The literature revealed many conflicting claims. Larger and properly controlled studies are necessary to better define the role of lasers in the treatment of TLV.


Magnetic graphitic carbon nitride: its application in the C-H activation of amines.
Magnetic graphitic carbon nitride, Fe@g-C3N4, has been synthesized by adorning a graphitic carbon nitride (g-C3N4) support with iron oxide via non-covalent interaction. The magnetically recyclable catalyst showed excellent reactivity for the expeditious C-H activation and cyanation of amines.


Tumor necrosis factor alpha mediates the lethal hepatotoxic effects of poly(I:C) in D-galactosamine-sensitized mice.
Conserved molecular patterns of microbial pathogens, such as lipopolysaccharide (LPS) and cytosine-phosphate-guanine (CpG) DNA motifs are important signals for receptor-mediated activation of innate immune cells. It has been shown that the liver-specific transcription-blocking d-galactosamine (D-GalN) severely sensitizes to the lethal effects of LPS and CpG DNA. Lethality of LPS or CpG DNA in GalN-treated mice is entirely due to TNF-alpha, which leads to liver cell apoptosis and acute liver failure. We report that also polyinosinic-polycytidylic acid [poly(I:C)], a TLR-3 agonist, induces systemic TNF in mice. The increases of hepatic enzymes and induction of death induced by LPS, CpG DNA, and poly(I:C) in D-GalN sensitized mice are completely blocked by neutralizing anti-TNF-alpha antibodies and absent in TNF receptor p55-knockout mice. Our results provide direct evidence that poly(I:C) induces TNF-alpha in d-GalN sensitized mice, which leads to severe, acute, and TNF-dependent lethal hepatitis.


Substitutes for glutamine in proliferation of rat intestinal epithelial cells.
Glutamine (Gln) is important for intestinal epithelial proliferation. The purpose of this study was to determine whether glutamate (Glu), a mixture of nucleotide monophosphates, arginine, or glucosamine could support proliferation of rat intestinal crypt cells (IEC-6) in the absence of Gln. Glu with added ammonia acetate, glucosamine, arginine, and nucleotide monophosphates were tested at concentrations that were isonitrogenous with respect to Gln. To determine whether de novo synthesis of Gln was affected by these nutrients, a duplicate set of treatment groups was also tested with 1.0 mM/L of methionine sulfoximine, an inhibitor of Gln synthetase. Gln + methionine sulfoximine-treated cells showed suboptimal proliferation below 0.6 mM/L but normal proliferation between 0.6 and 4.0 mM/L of Gln. In the absence of exogenous Gln, isonitrogenous concentrations of Glu, glucosamine, arginine, or nucleotide monophosphates yielded similar proliferation as Gln. Cells treated with Glu, glucosamine, arginine, or nucleotide monophosphate mixture showed a decrease in proliferation compared with cells treated with Gln across all treatment doses (P < 0.03). The importance of these results is that, in the presence of active Gln synthetase, these nutrients can maintain intestinal epithelial proliferation similar to that observed with Gln.


Total and regional body composition are related with aerobic fitness performance in elite futsal players.
Body composition (i.e., fat and lean mass profile) has been related to aerobic performance, an essential capacity for futsal athletes. The present study aimed to verify the relationship between total and regional body composition (percentage of fat and lean mass) with aerobic performance in elite futsal players. Male professional futsal athletes (n = 44) from two Brazilian National Futsal League teams and athletes representing the National team participated in this study. Body composition was evaluated using DXA (Dual-Energy X-ray Absorptiometry) and aerobic fitness by ergospirometry. There was a negative (p < 0.05) correlation between maximum oxygen uptake and maximal velocity reached with total body (r = -0.53; r = -0.58), trunk (r = -0.52; r = -0.56) and lower-limb (r = -0.46; r = -0.55) fat mass percentage. Lower-limb lean mass percentage had a positive (p < 0.05) correlation with maximum oxygen uptake (r = 0.46) and maximal velocity (r = 0.55). In conclusion, total and regional body composition present a relationship with aerobic performance in professional futsal players.


Modelling Alzheimer-specific abnormal Tau phosphorylation independently of GSK3beta and PKA kinase activities.
In Alzheimer's disease, neurofibrillary degeneration results from the aggregation of abnormally phosphorylated Tau proteins into paired helical filaments. These Tau variants displayed specific epitopes that are immunoreactive with anti-phospho-Tau antibodies such as AT100. As shown in in vitro experiments, glycogen synthase kinase 3 beta (GSK3beta) and protein kinase A (PKA) may be key kinases in these phosphorylation events. In the present study, Tau was microinjected into Xenopus oocytes. Surprisingly, in this system, AT100 was generated without any GSK3beta and PKA contribution during the progesterone or insulin-induced maturation process. Our results demonstrate that a non-modified physiological process in a cell model can generate the most specific Alzheimer epitope of Tau pathology.


X-ray crystallographic analysis of 3-(2'-phenyl-2,4'-bithiazole-4-carboxamido) propyldimethylsulphonium iodide, an analogue of the DNA-binding portion of bleomycin A2.
The crystal and molecular structure of the title compound, an analogue of the DNA binding region of bleomycin A2, has been determined by X-ray crystallography. All the three independent molecules in an asymmetric unit are approximately planar with fully extended side chains. A computer graphics model-building study has shown that the phenyl group and the second thiazole ring can be intercalated between the base pairs of the double-stranded deoxydinucleoside phosphate d(CpG), and also that the sulphonium cation can interact with a backbone phosphate group. This model is in accord with NMR spectral data.


Insecticide use and risk of non-Hodgkin lymphoma subtypes: A subset meta-analysis of the North American Pooled Project.
Insecticide use has been linked to increased risk of non-Hodgkin lymphoma (NHL), however, findings of epidemiologic studies have been inconsistent, particularly for NHL subtypes. We analyzed 1690 NHL cases and 5131 controls in the North American Pooled Project (NAPP) to investigate self-reported insecticide use and risk of NHL overall and by subtypes: follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and small lymphocytic lymphoma (SLL). Odds ratios (OR) and 95% confidence intervals for each insecticide were estimated using logistic regression. Subtype-specific associations were evaluated using ASSET (Association analysis for SubSETs). Increased risks of multiple NHL subtypes were observed for lindane (OR = 1.60, 1.20-2.10: FL, DLCBL, SLL), chlordane (OR = 1.59, 1.17-2.16: FL, SLL) and DDT (OR = 1.36, 1.06-1.73: DLBCL, SLL). Positive trends were observed, within the subsets with identified associations, for increasing categories of exposure duration for lindane (Ptrend = 1.7 × 10-4 ), chlordane (Ptrend = 1.0 × 10-3 ) and DDT (Ptrend = 4.2 × 10-3 ), however, the exposure-response relationship was nonlinear. Ever use of pyrethrum was associated with an increased risk of FL (OR = 3.65, 1.45-9.15), and the relationship with duration of use appeared monotonic (OR for >10 years: OR = 5.38, 1.75-16.53; Ptrend = 3.6 × 10-3 ). Our analysis identified several novel associations between insecticide use and specific NHL subtypes, suggesting possible etiologic heterogeneity in the context of pesticide exposure.


Crystal structures of Leptospira interrogans FAD-containing ferredoxin-NADP+ reductase and its complex with NADP+.
Ferredoxin-NADP(H) reductases (FNRs) are flavoenzymes that catalyze the electron transfer between NADP(H) and the proteins ferredoxin or flavodoxin. A number of structural features distinguish plant and bacterial FNRs, one of which is the mode of the cofactor FAD binding. Leptospira interrogans is a spirochaete parasitic bacterium capable of infecting humans and mammals in general. Leptospira interrogans FNR (LepFNR) displays low sequence identity with plant (34% with Zea mays) and bacterial (31% with Escherichia coli) FNRs. However, LepFNR contains all consensus sequences that define the plastidic class FNRs. The crystal structures of the FAD-containing LepFNR and the complex of the enzyme with NADP+, were solved and compared to known FNRs. The comparison reveals significant structural similarities of the enzyme with the plastidic type FNRs and differences with the bacterial enzymes. Our small angle X-ray scattering experiments show that LepFNR is a monomeric enzyme. Moreover, our biochemical data demonstrate that the LepFNR has an enzymatic activity similar to those reported for the plastidic enzymes and that is significantly different from bacterial flavoenzymes, which display lower turnover rates. LepFNR is the first plastidic type FNR found in bacteria and, despite of its low sequence similarity with plastidic FNRs still displays high catalytic turnover rates. The typical structural and biochemical characteristics of plant FNRs unveiled for LepFNR support a notion of a putative lateral gene transfer which presumably offers Leptospira interrogans evolutionary advantages. The wealth of structural information about LepFNR provides a molecular basis for advanced drugs developments against leptospirosis.


Glaucoma treatment adherence at a United Kingdom general practice.
PurposeTo estimate patient adherence with glaucoma therapy and identify factors associated with adherence using computerised patient prescribing records.MethodsIdentification of patients diagnosed with glaucoma, ocular hypertension or suspect glaucoma and/or prescribed topical glaucoma medications registered at a United Kingdom general practice with 13 422 patients. Adherence was defined as the average difference in the actual number of prescriptions collected annually compared to twelve prescriptions required annually (one bottle per month) over the duration of treatment.ResultsOverall, 278 patients were identified of which 139 (50%) were male. The average age was 72 years (range: 22-100). A total of 206 patients (74%) were prescribed glaucoma treatment. Adherence varied significantly between age groups with younger patients demonstrating poorest adherence (P=0.0347). There was no statistical difference when comparing medication class, diagnosis, co-morbidities, or the number of drops being taken.ConclusionsGlaucoma treatment adherence improves with increasing age. Older patients require more prescriptions and may be experiencing drop wastage. Younger patients should be targeted with educational interventions to improve their understanding of glaucoma, and older patients for drop technique review. General practices are well placed to provide such interventions.


Association between telomere length and diabetes mellitus: A meta-analysis.
Objective We investigated the relationship between diabetes and telomere length by meta-analysis. Methods We searched five popular databases for articles published between 1990 and 2015 using "diabetes" and "telomere" as search terms. Data were processed with RevMan5, and random- or fixed-effects meta-analysis was applied. The effects of geographical region, diabetes type, body mass index (BMI), age and sex were examined. Funnel plots were applied to evaluate publication bias. Results Seventeen articles were obtained from 571 references. We identified a significant association between telomere length and diabetes mellitus (standardized mean difference [SMD]: -3.41; 95% confidence interval [CI]: -4.01, -2.80; heterogeneity, I2 = 99%) by comparing 5575 patients with diabetes and 6349 healthy individuals. The pooled SMD by geographic region indicated a significant association between shortened telomere length and diabetes mellitus (SMD: -3.41; 95% CI: -4.01, -2.80; heterogeneity, I2 = 99%). In addition, telomere length was significantly associated with age (SMD: -3.41; 95% CI: -4.01, -2.80), diabetes type (SMD: -3.41; 95% CI: -4.01, -2.80), BMI (SMD: -1.61; 95% CI: -1.98, -1.23) and sex (SMD: -4.94; 95% CI: -9.47, -0.40). Conclusions The study demonstrated a close relationship between diabetes mellitus and telomere length, which was influenced by region, age, diabetes type, BMI and sex.


Measurement of activated clotting time in children--comparison of the Celite i-STAT ACT with the Medtronic ACT II.
To evaluate a recently introduced blood-saving method for the measurement of activated clotting time (ACT), the Celite i-STAT ACT, by comparing the values obtained with those from the widely used Medtronic ACT II device. In a prospective clinical study, we compared ACT values from the i-STAT device with the Medtronic ACT II device in 60 paediatric, interventional, cardiac catheterization procedures necessitating prophylactic heparinization. Blood samples were pair-analyzed using two i-STAT analyzers and one Medtronic ACT II device with double-tube-cartridges before and after heparinization. Data were compared using Bland-Altman bias analysis, Student's t-test and simple regression analysis. Bias and precision between the Medtronic ACT II and the i-STAT ACT values was -5.4 +/- 26.3. The i-STAT and Medtronic ACT II values were similar before heparinization (P = 0.22), but i-STAT ACT values became significantly longer than Medtronic ACT II values after heparinization (P = 0.021). The increase of ACT after heparinization was greater (median 86.3; range 40-187 s) in the i-STAT analyzer than in the Medtronic ACT II analyzer (median 73.0; range 19-235.5 s). Increase in ACT values was inversely affected by intraoperative haemoglobin concentration in the Medtronic ACT II analyzer (P = 0.001) but not in the i-STAT analyzer. Activated clotting times obtained from the Celite i-STAT ACT and the Medtronic ACT II demonstrated poor agreement. The technical principles are quite different and the two methods showed diverse susceptibility to intraoperative haemoglobin concentration. Users have to be aware of technique-specific ACT target ranges and their confounders, which need to be provided by the manufacturers.


Bioinspired "cage traps" for closed-loop lead management of perovskite solar cells under real-world contamination assessment.
Despite the remarkable progress made in perovskite solar cells, great concerns regarding potential Pb contamination risk and environmental vulnerability risks associated with perovskite solar cells pose a significant obstacle to their real-world commercialization. In this study, we took inspiration from the ensnaring prey behavior of spiders and chemical components in spider web to strategically implant a multifunctional mesoporous amino-grafted-carbon net into perovskite solar cells, creating a biomimetic cage traps that could effectively mitigate Pb leakage and shield the external invasion under extreme weather conditions. The synergistic Pb capturing mechanism in terms of chemical chelation and physical adsorption is in-depth explored. Additionally, the Pb contamination assessment of end-of-life perovskite solar cells in the real-world ecosystem, including Yellow River water and soil, is proposed. The sustainable closed-loop Pb management process is also successfully established involving four critical steps: Pb precipitation, Pb adsorption, Pb desorption, and Pb recycling. Our findings provide inspiring insights for promoting green and sustainable industrialization of perovskite solar cells.


Zinc neurotoxicity to hippocampal neurons in vitro induces ubiquitin conjugation that requires p38 activation.
There is increasing evidence showing that zinc plays a key role in inducing neuronal death during central nervous system injury. However, the underlying mechanisms are poorly understood. Here we assessed the effect of zinc on ubiquitin conjugation and subsequent neurodegeneration using cultured hippocampal cells. We report that cultured neurons are vulnerable to increased level of extracellular Zn²⁺. Zn²⁺-induced poly-ubiquitination in cultured neurons is in a concentration- and time-dependent manner. Furthermore our data demonstrated that Zn²⁺-induced ubiquitination requires p38 activation. These findings indicate that excessive zinc could impair the protein degradation pathway and may be a crucial factor mediating neuronal death following traumatic brain injury.


Tri-iodothyronine inhibition of thyrotrophin-releasing hormone-induced growth hormone release from the chicken adenohypophysis in vitro.
Tri-iodothyronine (T3) had no effect on the basal level of GH release from chicken hemipituitary glands perifused in vitro. The GH response to TRH was, however, markedly suppressed following exposure to T3. Suppression of TRH-stimulated GH secretion was observed after a 2-h preincubation with T3, and was induced, in a dose-related way, by 0.01-10 mumol T3/l. Exposure to T3 also reduced the effectiveness of TRh, at concentrations of 0.001-10 micrograms/ml, to stimulate GH release. These results demonstrate that, in addition to a hypothalamic site of action, T3 is likely to suppress GH secretion in vivo by direct effects on pituitary GH release.


Risk stratification for prediction of locoregional recurrence in patients with pathologic T1-2N0 breast cancer after mastectomy.
Previous studies have revealed that nearly 15-20% of selected high-risk T1-2N0 breast cancers developed LRR after mastectomy. This study is aim to indentify the risk factors of locoregional recurrence (LRR) in patients with pathologic T1-2N0 breast cancer after mastectomy in a real-world and distinguish individuals who warrant postmastectomy radiotherapy (PMRT). Female patients treated from 1999 to 2014 in National Cancer Center of China were retrospectively reviewed. A competing risk model was developed to estimate the cumulative incidence of LRR with death treated as a competing event. A total of 4841 patients were eligible. All underwent mastectomy plus axillary nodes dissection or sentinel node biopsy without PMRT. With a median follow-up of 56.4 months (range, 1-222 months), the 5-year LRR rate was 3.9%.Besides treatment era, age ≤ 40 years old (p < 0.001, hazard ratio [HR] = 2.262), tumor located in inner quadrant (p < 0.001, HR = 2.236), T2 stage (p = 0.020, HR = 1.419), and negative expressions of estrogen receptor (ER) and progesterone receptor (PR) (p = 0.032, HR = 1.485), were patients-related independent risk factors for LRR. The 5-year LRR rates were 1.7, 3.5, and 15.0% for patients with zero, 1-2, and 3-4 risk factors (p < 0.001). Risk Stratification based on age, T stage, ER/PR status and tumor location can stratify patients with pT1-2 N0 breast cancer into subgroups with different risk of LRR. PMRT might be suggested for patients with 3-4 risk factors.


Subcellular localization of ubiquitin and ubiquitinated proteins in Arabidopsis thaliana.
Ubiquitin is a highly conserved, 76-amino acid, eukaryotic protein. Its widely accepted role as a proteolytic cofactor depends on its unique ability to covalently ligate to other cellular proteins. While there is good evidence for the existence of such ubiquitinated proteins in the cytosolic and nuclear compartments, relatively little is known about the presence of free ubiquitin and ubiquitinated proteins in other subcellular compartments. This is especially true of higher plants, which have not previously been the subject of extensive biochemical subcellular localizations of ubiquitinated proteins. We extracted cell wall proteins and purified nuclei, vacuoles, chloroplasts, and microsomes from chlorophyllous tissues of Arabidopsis. Immunoblot analyses were used to compare the profiles of ubiquitinated proteins from purified subcellular fractions to those from unfractionated extracts. Purified nuclei contained, in addition to a complex mixture of high molecular mass ubiquitinated proteins, a strongly immunoreactive 28-kDa protein. In the apoplastic extract, we did not detect any ubiquitinated proteins enriched above the background level of those due to cytosolic contamination. Vacuoles appeared to contribute significantly to the ubiquitinated proteins present in the whole protoplast extract. At least three high molecular mass ubiquitinated proteins were unique to the vacuolar extract. Chloroplast stromal proteins did not react specifically with anti-ubiquitin antibodies. When microsomal ubiquitinated proteins were compared to those found in a whole protoplast extract, a distinct pattern was evident. Microsomal ubiquitinated proteins were not visible in the 10,000 x g supernatant used to prepare the 100,000 x g pellet, indicating that they were probably low abundance proteins in the protoplast extract.


Isolation by distance in the spore-forming soil bacterium Myxococcus xanthus.
Genetic differentiation between spatially separated populations within a species is commonly observed in plants and animals, but its existence in microbes has long been a contentious issue. Traditionally, many microbial ecologists have reasoned that microbes are not limited by dispersal as a result of their immense numbers and microscopic size. In this view, the absence of barriers to gene flow between populations would prevent differentiation of populations by genetic drift and hinder local adaptation. Myxococcus xanthus is a globally distributed, spore-forming bacterium that offers a robust test for genetic differentiation among populations because sporulation is expected to enhance dispersal. Using multi-locus sequence data, we show here that both diversity and the degree of differentiation between populations increase as a function of distance in M. xanthus. Populations are consistently differentiated at scales exceeding 10(2)-10(3) km, and isolation by distance, the divergence of populations by genetic drift due to limited dispersal, is responsible. Our results provide new insights into how genetic diversity within species of free-living microbes is distributed from centimeter to global scales.


Interoccurrence time statistics in fully-developed turbulence.
Emergent extreme events are a key characteristic of complex dynamical systems. The main tool for detailed and deep understanding of their stochastic dynamics is the statistics of time intervals of extreme events. Analyzing extensive experimental data, we demonstrate that for the velocity time series of fully-developed turbulent flows, generated by (i) a regular grid; (ii) a cylinder; (iii) a free jet of helium, and (iv) a free jet of air with the Taylor Reynolds numbers Reλ from 166 to 893, the interoccurrence time distributions P(τ) above a positive threshold Q in the inertial range is described by a universal q- exponential function, P(τ) = β(2 - q)[1 - β(1 - q)τ](1/(1-q)), which may be due to the superstatistical nature of the occurrence of extreme events. Our analysis provides a universal description of extreme events in turbulent flows.


Self-assembly of short peptides to form hydrogels: design of building blocks, physical properties and technological applications.
Hydrogels are unique supramolecular solid-like assemblies composed mainly of water molecules that are held by molecular networks. Physical hydrogels that are formed by a set of non-covalent interactions to establish a well-ordered scaffold devoid of any chemical cross-linking are especially intriguing for various biotechnological and medical applications. Peptides are particularly interesting building blocks of physical gels because of the role of polypeptides as structural elements in biological systems, the extensive ability for their chemical and biological decoration and functionalization, and the facile synthesis of natural and modified peptides. This review describes the assembly and properties of physical hydrogels that have been formed by the self-association of very simple peptide building blocks. Natural short peptides, as short as dipeptides, can form ordered gel assemblies. Moreover, in the case of N-terminal protection, even a protected amino acid can serve as an efficient hydrogelator. Further elucidation of hydrogelators' assembly, as well as the characterization of their physical properties, can guide the rational design of building blocks for a desired application. The possible mechanism of self-assembly is discussed in line with the chemical nature of the short peptides. Different methods have been used to induce hydrogel assembly, which may significantly affect the mechanical characteristics of the resulting gels. Here, special emphasis is given to methods that allow either spatial control of hydrogel formation or modulation of physical properties of the gel. Finally, the parameters that influence hydrogelation are described, and insights for their design are provided.


Triamcinolone acetonide with vitrectomy for treatment of macular edema associated with branch retinal vein occlusion.
To review the efficacy of a combination of triamcinolone acetonide (TA) injection and pars plana vitrectomy (PPV) for the treatment of macular edema associated with branch retinal vein occlusion (BRVO). Seventeen eyes with macular edema associated with BRVO underwent PPV with an intraoperative injection of TA (10 mg) into the vitreous cavity. Residual or recurrent macular edema was treated with postoperative sub-Tenon capsule injections of TA (20 mg). With PPV and an intraoperative injection of TA, 82% of eyes showed rapid reduction of macular edema; foveal thickness decreased from 507 +/- 115 microm preoperatively to 261 +/- 123 microm 2 months after surgery (P = 0.0041). However, 59% of eyes showed recurrence of macular edema during the follow-up period. Twelve eyes with residual or recurrent macular edema received sub-Tenon capsule injections of TA; of these eyes, 9 showed substantial reduction of macular edema. Foveal thickness decreased from 381 +/- 102 microm to 256 +/- 56 microm (P = 0.0076) 2 weeks after postoperative injections of TA. At the final visit, visual acuity (logMAR) improved from 0.74 +/- 0.40 preoperatively to 0.40 +/- 0.34 (P = 0.010). An intraoperative injection of TA in combination with PPV has the potential to facilitate the absorption of macular edema associated with BRVO. In addition, residual or recurrent macular edema can be treated with additional sub-Tenon capsule injections of TA.


Enhancing the anti-angiogenic action of histone deacetylase inhibitors.
Histone deacetylase inhibitors (HDACIs) have many effects on cancer cells, such as growth inhibition, induction of cell death, differentiation, and anti-angiogenesis, all with a wide therapeutic index. However, clinical trials demonstrate that HDACIs are more likely to be effective when used in combination with other anticancer agents. Moreover, the molecular basis for the anti-cancer action of HDACIs is still unknown. In this study, we compared different combinations of HDACIs and anti-cancer agents with anti-angiogenic effects, and analysed their mechanism of action. Trichostatin A (TSA) and alpha-interferon (IFNalpha) were the most effective combination across a range of different cancer cell lines, while normal non-malignant cells did not respond in the same manner to the combination therapy. There was a close correlation between absence of basal p21WAF1 expression and response to TSA and IFNalpha treatment. Moreover, inhibition of p21WAF1 expression in a p21WAF1-expressing breast cancer cell line by a specific siRNA increased the cytotoxic effects of TSA and IFNalpha. In vitro assays of endothelial cell function showed that TSA and IFNalpha decreased endothelial cell migration, invasion, and capillary tubule formation, without affecting endothelial cell viability. TSA and IFNalpha co-operatively inhibited gene expression of some pro-angiogenic factors: vascular endothelial growth factor, hypoxia-inducible factor 1alpha and matrix metalloproteinase 9, in neuroblastoma cells under hypoxic conditions. Combination TSA and IFNalpha therapy markedly reduced tumour angiogenesis in neuroblastoma-bearing transgenic mice. Our results indicate that combination TSA and IFNalpha therapy has potent co-operative cytotoxic and anti-angiogenic activity. High basal p21WAF1 expression appears to be acting as a resistance factor to the combination therapy.


ACOG educational bulletin. Psychosocial risk factors: perinatal screening and intervention. Number 255, November 1999. American College of Obstetricians and Gynecologists.
Addressing the broad range of psychosocial issues with which pregnant women are confronted is an essential step toward improving women s health and birth outcomes. This may be difficult to do completely in a private physician s office setting, therefore, an effective system of referrals is helpful. To increase the likelihood of successful interventions, psychosocial screening should be performed on a regular basis and documented in the patient s prenatal record.


Soluble Urokinase Plasminogen Activator Receptor (suPAR) and All-Cause and Cardiovascular Mortality in Diverse Hemodialysis Patients.
The soluble receptor of urokinase plasminogen activator (suPAR) is an innate immunity/inflammation biomarker predicting cardiovascular (CV) and non-CV events in various conditions, including type 2 diabetic patients on dialysis. However, the relationship between suPAR and clinical outcomes in the hemodialysis population at large has not been tested. We measured plasma suPAR levels (R&D enzyme-linked immunosorbent assay [ELISA]) in 1038 hemodialysis patients with a follow-up of 2.9 years (interquartile range = 1.7-4.2) who were enrolled in the PROGREDIRE study, a cohort study involving 35 dialysis units in 2 regions in Southern Italy. suPAR was strongly (P < 0.001) and independently related to female gender (β = -0.160), age (β = 0.216), dialysis vintage (β = 0.264), CV comorbidities (β = 0.105), alkaline phosphatase (β = 0.136), albumin (β = -0.147), and body mass index (BMI; β = 0.174) (all P < 0.006). In fully adjusted analyses, suPAR tertiles predicted the risk of all-cause mortality (third tertile vs. first tertile hazard ratio (HR) = 1.91, 95% confidence interval (CI) = 1.47 - 2.48, P < 0.001), CV mortality (HR = 1.47, 95% CI = 1.03-2.09, P = 0.03), and non-CV mortality (HR = 1.94, 95% CI = 1.28-2.93, P = 0.002); these relationships were not modified by diabetes or other risk factors. suPAR added only modest prognostic risk discrimination and reclassification power for these outcomes to parsimonious models based on simple clinical variables. In conclusion, suPAR robustly predicted all-cause and both CV and non-CV mortality in a large unselected hemodialysis population. Intervention studies are needed to definitively test the hypothesis that suPAR is causally implicated in clinical outcomes in this population.


Medial Collateral Ligament Pie-Crusting for Isolated Medial Meniscal Root Repair Is Associated With Improved Clinical Outcomes with Minimum 2-Year Follow-Up.
The purpose of this study was to determine clinical and radiographic outcomes of medial collateral ligament (MCL) pie-crusting during isolated medial meniscal root repair. A retrospective review was conducted between August 2013 and December 2019 in patients undergoing isolated medial meniscal root repair. Outcomes, including International Knee Documentation Committee (IKDC) score, Lysholm score, re-tears, MCL laxity, and conversion to total knee arthroplasty (TKA), were compared between pie crust (PC) and non-pie crust (NPC) cohorts. Other assessments included subjective instability or stiffness, infection, and intra-operative chondromalacia. Additionally, radiographic outcomes were compared to determine progression of medial compartment arthrosis. Final analysis included 97 knees, 45 in the PC, and 52 in the NPC group. IKDC and Lysholm scores were similar between both groups preoperatively and 3 months postoperatively. However, at the 6,12, and 24-month follow up, the PC group had a significantly higher measured IKDC and Lysholm scores than the NPC group. PASS percentages for the IKDC score were significantly higher in the PC group at 6 months, 1 year, and 2 years (96.2%; P = .02) follow-up compared to the NPC group. MCID percentages for the IKDC score were also significantly higher at the 1- and 2-year (100%; P = .05) follow-up in the PC group compared to the NPC group. There was also a significantly higher rate of recurrent medial meniscal root tears in the NPC group (4 [8.9%]) compared to the PC group (0 [P = .03]). No MCL laxity was observed at 6 months follow-up. MCL pie-crusting during isolated medial meniscal root repair can be used as an alternative surgical technique, as it leads to improved clinical and patient outcomes compared to patients who do not undergo MCL pie-crusting in the short term. Additionally, those that underwent MCL pie-crusting had a lower incidence of recurrent tears, and no patients experienced MCL laxity at 6 months. Level III, retrospective cohort/comparative study.


Planned Aerobic Exercise Increases Energy Intake at the Preceding Meal.
Effects of exercise on subsequent energy intake are well documented, but whether preexercise energy intake is affected by future planned exercise is unknown. This study investigated the effect of planned late-afternoon exercise on appetite and energy intake before (breakfast and lunch) and after (evening meal/snacks) exercise. Twenty healthy, active participants (10 male; age, 23 ± 5 yr; body mass index 23.7 ± 3.2 kg·m; V˙O2peak, 44.1 ± 5.4 mL·kg··min) completed randomized, counterbalanced exercise (EX) and resting (REST) trials. After trial notification, participants were provided ad libitum breakfast (0800 h) and lunch (1200 h) in the laboratory, before completing 1-h exercise (30-min cycling, 30-min running) at 75%-80% maximal HR (EX, 2661 ± 783 kJ) or 1-h supine rest (REST, 310 ± 58 kJ) 3 h after lunch. Participants were provided a food pack (pasta meal/snacks) for consumption after exercise (outside laboratory). Appetite was measured regularly, and meal and 24-h energy intake were quantified. Ad libitum energy intake was greater during EX at lunch (EX, 3450 ± 1049 kJ; REST, 3103 ± 927 kJ; P = 0.004), but similar between trials at breakfast (EX, 2656 ± 1291 kJ; REST, 2484 ± 1156 kJ; P = 0.648) and dinner (EX, 6249 ± 2216 kJ; REST, 6240 ± 2585 kJ; P = 0.784). Total 24-h energy intake was similar between trials (P = 0.388), meaning that relative energy intake (24-h energy intake minus EX/REST energy expenditure) was reduced during EX (EX, 9694 ± 3313 kJ; REST, 11,517 ± 4023 kJ; P = 0.004). Energy intake seems to be increased in anticipation of, rather than in response to, aerobic exercise, but the increase was insufficient to compensate for energy expended during exercise, meaning that aerobic exercise reduced energy balance relative to rest.


Neural is Fundamental: Neural Stemness as the Ground State of Cell Tumorigenicity and Differentiation Potential.
Tumorigenic cells are similar to neural stem cells or embryonic neural cells in regulatory networks, tumorigenicity and pluripotent differentiation potential. By integrating the evidence from developmental biology, tumor biology and evolution, I will make a detailed discussion on the observations and propose that neural stemness underlies two coupled cell properties, tumorigenicity and pluripotent differentiation potential. Neural stemness property of tumorigenic cells can hopefully integrate different observations/concepts underlying tumorigenesis. Neural stem cells and tumorigenic cells share regulatory networks; both exhibit neural stemness, tumorigenicity and pluripotent differentiation potential; both depend on expression or activation of ancestral genes; both rely primarily on aerobic glycolytic metabolism; both can differentiate into various cells/tissues that are derived from three germ layers, leading to tumor formation resembling severely disorganized or more degenerated process of embryonic tissue differentiation; both are enriched in long genes with more splice variants that provide more plastic scaffolds for cell differentiation, etc. Neural regulatory networks, which include higher levels of basic machineries of cell physiological functions and developmental programs, work concertedly to define a basic state with fast cell cycle and proliferation. This is predestined by the evolutionary advantage of neural state, the ground or initial state for multicellularity with adaptation to an ancient environment. Tumorigenesis might represent a process of restoration of neural ground state, thereby restoring a state with fast proliferation and pluripotent differentiation potential in somatic cells. Tumorigenesis and pluripotent differentiation potential might be better understood from understanding neural stemness, and cancer therapy should benefit more from targeting neural stemness.


Increased intramuscular adipose tissue of the quadriceps is more strongly related to declines in ADL than is loss of muscle mass in older inpatients.
Recent studies have shown that increased intramuscular adipose tissue of the quadriceps in older people is more strongly related to decreased muscle strength, sit-up and sit-down ability, and gait ability than is loss of muscle mass. However, whether increased intramuscular adipose tissue of the quadriceps is more strongly related to declines in activities of daily living (ADL) than is loss of muscle mass in older inpatients remains unclear. This study was performed to examine the relationships of intramuscular adipose tissue and muscle mass of the quadriceps with ADL in older inpatients. This cross-sectional study included 371 inpatients aged ≥65 years. The primary outcomes were ADL and intramuscular adipose tissue of the quadriceps. ADL were assessed using the motor-Functional Independence Measure (FIM). Ultrasound images were acquired using B-mode ultrasound imaging. Intramuscular adipose tissue and muscle mass of the quadriceps were assessed based on echo intensity and muscle thickness, respectively. A stepwise multiple regression analysis was performed to identify factors independently associated with the motor-FIM score. The independent variables were the echo intensity and muscle thickness of the quadriceps, age, sex, length of hospital stay, Food Intake Level Scale (FILS), Geriatric Nutritional Risk Index (GNRI) score, C-reactive protein (CRP) concentration, updated Charlson comorbidity index (UCCI), number of medications, and subcutaneous fat thickness of the thigh. Quadriceps echo intensity (β = - 0.17), FILS (β = 0.38), GNRI score (β = 0.24), UCCI (β = - 0.16), subcutaneous fat thickness of the thigh (β = - 0.11), and length of hospital stay (β = 0.09) were independently and significantly associated with the motor-FIM score. Quadriceps thickness (β = 0.10), age (β = - 0.07), sex (β = - 0.04), CRP concentration (β = - 0.04), and number of medications (β = 0.03) were not associated with the motor-FIM score. Increased intramuscular adipose tissue of the quadriceps is more strongly related to declines in ADL than is loss of muscle mass. Randomized controlled trials are needed to determine whether decreasing intramuscular adipose tissue of the quadriceps in older inpatients leads to improvement of ADL.


Langerhans' cell histiocytosis and juvenile xanthogranuloma of the orbit. Clinicopathologic, CT, and MR imaging features.
The clinical, radiologic, and histopathologic features of two main disorders of the orbit are discussed. Group I, Langerhans cell histiocytosis (histiocytosis X, Class I), is caused by proliferation of X histiocytic Langerhans' cells. Group II is juvenile xanthogranuloma, and Class II is related to the proliferation of non-X histiocytic (monocyte-macrophage) cells. The two diseases are of unknown cause and differ in their clinical, radiologic, and histopathologic features.


Scalp reconstruction with free flaps using the external carotid artery and internal jugular vein as the recipient vessels without the need for interpositional vein grafts or arterio-venous loops.
The technique of lengthening of the pedicles of the rectus abdominus and latissimus dorsi free flaps are described in five patients. Lengthening of these pedicles allowed scalp reconstruction using the external carotid artery and internal jugular vein as the recipient vessels without the need for interpositional vein grafts or arterio-venous loops. Post-operative recovery was uneventful in all cases.


Robotic ultrasound imaging: State-of-the-art and future perspectives.
Ultrasound (US) is one of the most widely used modalities for clinical intervention and diagnosis due to the merits of providing non-invasive, radiation-free, and real-time images. However, free-hand US examinations are highly operator-dependent. Robotic US System (RUSS) aims at overcoming this shortcoming by offering reproducibility, while also aiming at improving dexterity, and intelligent anatomy and disease-aware imaging. In addition to enhancing diagnostic outcomes, RUSS also holds the potential to provide medical interventions for populations suffering from the shortage of experienced sonographers. In this paper, we categorize RUSS as teleoperated or autonomous. Regarding teleoperated RUSS, we summarize their technical developments, and clinical evaluations, respectively. This survey then focuses on the review of recent work on autonomous robotic US imaging. We demonstrate that machine learning and artificial intelligence present the key techniques, which enable intelligent patient and process-specific, motion and deformation-aware robotic image acquisition. We also show that the research on artificial intelligence for autonomous RUSS has directed the research community toward understanding and modeling expert sonographers' semantic reasoning and action. Here, we call this process, the recovery of the "language of sonography". This side result of research on autonomous robotic US acquisitions could be considered as valuable and essential as the progress made in the robotic US examination itself. This article will provide both engineers and clinicians with a comprehensive understanding of RUSS by surveying underlying techniques. Additionally, we present the challenges that the scientific community needs to face in the coming years in order to achieve its ultimate goal of developing intelligent robotic sonographer colleagues. These colleagues are expected to be capable of collaborating with human sonographers in dynamic environments to enhance both diagnostic and intraoperative imaging.


Development of automated marine floating plastic detection system using Sentinel-2 imagery and machine learning models.
The increasing level of marine plastic pollution poses severe threats to the marine ecosystem and biodiversity. Open remote sensing data and advanced machine learning (ML) algorithms could be a cost-effective solution for identifying large plastic patches across the scale. The potential application of such resources in detecting and discriminating marine floating plastics (MFP) are not fully explored. Therefore, the present study attempted to explore the full functionality of open Sentinel satellite data and ML models for detecting and classifying the MFP in Mytilene (Greece), Limassol (Cyprus), Skala Loutron, Greece, Calabria (Italy), and Beirut (Lebanon). Two ML models, i.e. Support Vector Machine (SVM) and Random Forest (RF), were utilized to perform the classification analysis. In-situ plastic location data was collected from the control experiments conducted in Mytilene, Greece (in 2018 and 2019), Skala Loutron, Greece (2021), and Limassol, Cyprus (2018), and the same was considered for training the models. The accuracy and performances of the trained models were further tested on unseen new data collected from Calabria, Italy and Beirut, Lebanon. Both remote sensing bands and spectral indices were used for developing the ML models. A spectral signature profile for marine plastic was created for discriminating the floating plastic from other marine debris. A newly developed index, kernel Normalized Difference Vegetation Index (kNDVI), was incorporated into the modelling to examine its contribution to model performances. Both SVM and RF were performed well in five models and test case combinations. Among the two ML models, the highest performance was measured for the RF. The inclusion of kNDVI was found effective and increased the model performances, reflected by high balanced accuracy measured for model 2 (~89% to ~100% for SVM and ~92% to ~98% for RF). An automated floating plastic detection system was developed and tested in Calabria and Beirut using the best-performed model. The trained model had detected the floating plastic for both sites with ~80%-90%% accuracy. Among the six predictors, the Floating Debris Index (FDI) was the most important variable for detecting marine floating plastic. These findings collectively suggest that high-resolution remote sensing imagery and the automated ML models can be an effective alternative for the cost-effective detection of MFP. Future research will be directed toward collecting quality training data to develop robust automated models and prepare a spectral library for different plastic objects for discriminating plastic from other marine floating debris and advancing the marine plastic pollution research by taking full advantage of open-source data and technologies.


Purinergic modulation of the evoked release of [3H]acetylcholine from the hippocampus and cerebral cortex of the rat: role of the ectonucleotidases.
Modulation by exogenous and endogenous adenine nucleotides and adenosine of [3H]acetylcholine release evoked by veratridine (10 microM) was compared in synaptosomal fractions from the hippocampus and the cerebral cortex of the rat. In both brain areas, exogenously added ATP or adenosine (10-100 microM) inhibited the evoked tritium release. In the hippocampus, ATP gamma S, an ATP analogue more resistant to catabolism than ATP, was virtually devoid of effect on tritium release, and the effect of ATP was prevented by the ecto-5'-nucleotidase inhibitor alpha,beta-methylene ADP (100 microM), by adenosine deaminase (2 U/ml) and by the A1 adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 20 nM). In contrast, in the cerebral cortex, the effect of ATP on tritium release was not prevented by either alpha,beta-methylene ADP (100 microM) or adenosine deaminase (2 U/ml), and several ATP analogues (30 microM) inhibited release. The order of intensity of the inhibitory effects of the ATP analogues was: ATP gamma S > ATP > beta,gamma-imido ATP > beta,gamma-methylene ATP >> 2-methyl-S-ATP, alpha,beta-methylene ATP. The effect of ATP gamma S in the cerebral cortex was prevented by DPCPX (20 nM) and was not affected by the P2 purinoceptor antagonist suramin (100 microM). In the hippocampus, alpha,beta-methylene ADP (100 microM) increased the evoked release of tritium, and adenosine deaminase (2 U/ml) produced an even greater increase; when adenosine deaminase was added in the presence of alpha,beta-methylene ADP, adenosine deaminase still increased the evoked release of tritium. In the cerebral cortex, DPCPX (20 nM) and adenosine deaminase (2 U/ml) increased the evoked tritium release by a similar magnitude, but the effect of adenosine deaminase was smaller than in the hippocampus. It is concluded that in the cerebral cortex ATP as such presynaptically inhibits acetylcholine release, whereas in the hippocampus the role of adenine nucleotides is as a source of endogenous extracellular adenosine that tonically inhibits acetylcholine release. The results also show that besides formation of adenosine from adenine nucleotides, released adenosine as such contributes in nearly equal amounts to the pool of endogenous adenosine that presynaptically inhibits acetylcholine release in the hippocampus.


Clinical features of Mycoplasma pneumoniae infections in the 2010 epidemic season: report of two cases with unusual presentations.
Mycoplasma pneumoniae (Mp) is one of the main pathogens causing community-acquired pneumonia, particularly in young individuals. Host immune response appears to play an important role in prolonged symptoms, as well as in the recent increasing prevalence of drug-resistant Mp isolated from patients. Case 1 had a prolonged clinical course caused by drug-resistant Mp and received steroid therapy despite Mp susceptibility to some antimicrobial agents. Serum cytokine profiles revealed elevation of interleukin-6/-10 and interferon-γ in acute phase. Case 2 had mycoplasmal myocarditis without any respiratory symptoms, which resolved spontaneously without the administration of any antimicrobial agent. These observations suggest that host immune response probably contributes to the etiology of Mp-associated complications.


The effect of a lipid suspension on amitriptyline disposition.
A 5-h infusion of a lipid suspension or saline was given on separate occasions to four healthy volunteers taking amitriptyline. Mean plasma levels of amitriptyline plus nortriptyline were 14% higher at the end of the lipid infusion but the difference was not statistically significant. Infusion of a lipid suspension is unlikely to materially affect the severity of amitriptyline intoxication.


Substituent effects on the UV spectra of extended benzylidene anilines p-X-PhCH=NPhCH=CHPh-p-Y.
Benzylidene anilines with p-substituted styryl groups substituted on the aniline ring, p-X-PhCH=NPhCH=CHPh-p-Y (X=NMe2, OMe, Me, H, Cl, F, CN, or NO2; Y=NMe2, OMe, Me, H, Cl, or CN) have been studied photochemically in ethanol. The substituent effects in the title compounds are more similar to p-X-PhCH=NPh-p-Y than p-X-PhCH=CHPh-p-Y. The introduction of styryl group to XBAY leads to a more planar geometry and a red shift of the maximum absorption wavelength. This can be described as a "styryl conjugation effect". Furthermore, a quantitative model has been established to correlate the UV maximum absorption wavenumbers of the title compounds and substituent parameters. The results help understand the substituent effects of conjugated compounds consisting of both benzylidene aniline and stilbene moieties.


Profiling safety of intravitreal injections for retinoblastoma using an anti-reflux procedure and sterilisation of the needle track.
The preservation of globe integrity has always been a major concern during the treatment of retinoblastoma for fear of extraocular or metastatic spread. Intravitreal chemotherapy has been attempted as a desperate salvage therapy only for eyes with refractory retinoblastoma. Published data on the safety and efficacy of this route are, however, limited. A modified technique of intravitreal injection in eyes with retinoblastoma is described. All children with retinoblastoma who received one or more intravitreal injections using this technique were retrospectively reviewed concerning ocular complications of the injection procedure as well as clinical or histopathological evidence of tumour spread. 30 eyes of 30 children with retinoblastoma received a total of 135 intravitreal injections, with a median follw-up duration of 13.5 months. No extraocular spread was seen on clinical follow-up in any patients and there was no tumour contamination of the retrieved entry sites histopathologically analysed among the five enucleated eyes. No significant ocular side effects were observed except transient localised vitreous haemorrhage (3/135). This technique is potentially safe and effective at a low cost and may play a promising role, especially in the treatment of recurrent and/or resistant vitreous disease in retinoblastoma, as an alternative to enucleation and/or external beam radiotherapy. However, this treatment should not replace the primary standard of care of retinoblastoma and should not be considered in group E eyes. Its application should be approved by an ophthalmological-oncological team and it should be performed by an experienced eye surgeon in a tertiary referral centre after careful selection of a tumour-free injection site.


Diagnostic accuracy of narrow-band imaging for the differentiation of neoplastic from non-neoplastic colorectal polyps: a meta-analysis.
Narrow-band imaging (NBI) is a novel imaging technology that makes the superficial vasculature of gastrointestinal mucosa visible. However, the real accuracy for the differentiation of neoplastic from non-neoplastic polyps by NBI for the colorectum is still unknown. A meta-analysis was carried out of studies which assessed the precision of NBI in the diagnosis of colorectal neoplastic polyps. Searches included PubMed and Embase and two reviewers independently assessed their quality with a modified version of the quadas and stard tools. The study pooled estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and area under the curve (AUC). There were 11 relevant original papers which fulfilled the inclusion criteria. The pooled sensitivity and specificity were 0.92 (95% CI 0.90-0.93) and 0.83 (95% CI 0.81-0.86) respectively. The AUC for NBI was 0.95 [SE 0.01; DOR 53.72 (95% CI 35.66-80.92)]. The sensitivity and specificity were 0.92 (95% CI 0.90-0.94) and 0.81 (95% CI 0.78-0.84) with magnification, and 0.91 (95% CI 0.88-0.93) and 0.86 (95% CI 0.82-0.89) without magnification. For the mucosal pattern sensitivity and specificity were 0.90 (95% CI 0.85-0.940) and 0.88 (95% CI 0.82-0.93), and for vascular pattern intensity they were 0.92 (95% CI 0.90-0.94) and 0.88 (95% CI 0.83-0.91). Narrow-band imaging, with or without magnification, has a high diagnostic precision for colorectal neoplastic polyps using either vascular pattern intensity or mucosal pattern assessment as the measure.


[The course of illness and problems of schizophrenic women and men from the relatives' perspective].
Members of HPE, an Austrian self-help organization for the relatives of mentally ill people, were questioned about their opinion with regard to the situation of families with a mentally ill member. A questionnaire was sent to the addresses of members of this self-help organisation. 182 respondents reported to care for 132 male and 50 female sufferers diagnosed as having a psychosis from the schizophrenic spectrum replied. Relatives, who care for male sufferers reported greater distress than those caring for females. Depression and exhaustion are reported significantly more frequently in caregivers of males. Other burdens, for example financial burdens, to assist the sufferer in the household, renunciation of holidays, and the problem of neglect also have a tendency to be more common among those caring for men. These gender differences cannot be accounted for by differences in the course of illness. Our study showed no evidence of gender differences in this regard. Contrary to our expectations women in our study are less compliant with medication and psychosocial treatment. Despite a better compliance with treatment strategies among men, relatives of males generally experience a greater burden. Our results indicate a greater need for the development of independence strategies for male sufferers and a requirement that professionals support sufferers and carers in this direction.


Hyperthyroid chorea in an elderly woman associated with sole elevation of T3.
A 72-year-old woman presented with chorea, mild tachycardia, and elevation of T3RIA. T4 was not elevated until the third determination. Chorea resolved with treatment of hyperthyroidism. This case represents the first case of T3 hyperthyroid chorea and the oldest patient with hyperthyroid chorea described in the literature. It demonstrates yet another subtle way in which thyroid disease can present in the elderly.


Mechanisms of Interferon-alpha induced apoptosis in malignant cells.
Interferon alpha (IFNalpha) has been used in the treatment of several types of cancer for almost 30 years, yet the mechanism(s) responsible for its anti-tumoral action remains unknown. A variety of cellular responses, including inhibition of cell growth and induction of apoptosis are induced by IFNs, and apoptotic induction by this cytokine has been proposed to be of importance for both its anti-tumoral in addition to its anti-viral responses. The aim of the present study was to delineate the pathways activated during IFNalpha-induced apoptosis in malignant cell lines. We found that apoptosis induced by IFNalpha was associated with activation of caspases-1, -2, -3, -8 and -9 and that this activation was a critical event. Caspase-3 activation was dependent on activity of caspases-8 and -9, moreover, activation of caspase-8 seems to be the upstream event in IFNalpha-induced caspase cascade. We also found loss of mitochondrial membrane potential as well as release of cytochrome c post IFN-treatment, clearly implicating the involvement of mitochondria in IFN-mediated apoptosis. Furthermore, IFNalpha-induced apoptosis was found to be independent on interactions between the Fas-receptor and its ligand. These studies form the basis for further investigations aiming to improve IFN therapy and the development of future strategies to overcome the IFN resistance observed in some malignancies.


Exploring the anti-virulence potential of plants used in traditional Mayan medicine to treat bacterial infections.
While the antimicrobial activity of a number of plants used in traditional Mayan medicine against infectious diseases has been documented, their potential to inhibit quorum sensing (QS) as means of discovering novel anti-virulence agents remains unexplored. To evaluate the anti-virulence potential of plants used in traditional Mayan medicine by determining their inhibition of QS- regulated virulence factors in Pseudomonas aeruginosa. A group of plants used in traditional Mayan medicine against infectious diseases was selected, and their methanolic extracts were evaluated at 10 mg/mL for their antibacterial and anti-virulence activity using the reference strain P. aeruginosa PA14WT. The broth microdilution method was used to determine antibacterial activity (MIC), while anti-virulence activity was evaluated by measuring the anti-biofilm effect and the inhibition of pyocyanin and protease activities. The most bioactive extract was fractionated using a liquid-liquid partition procedure and the semipurified fractions were evaluated at 5 mg/mL for antibacterial and anti-virulence activity. Seventeen Mayan medicinal plants traditionally used to treat infection-associated diseases were selected. None of the extracts exhibited antibacterial activity, whereas anti-virulence activity was detected in extracts of Bonellia flammea, Bursera simaruba, Capraria biflora, Ceiba aesculifolia, Cissampelos pareira and Colubrina yucatanensis. The most active extracts (74% and 69% inhibition) against biofilm formation were from C. aesculifolia (bark) and C. yucatanensis (root), respectively. Alternatively, the extracts of B. flammea (root), B. simaruba (bark), C. pareira (root), and C. biflora (root), reduced pyocyanin and protease production (50-84% and 30-58%, respectively). Fractionation of the bioactive root extract of C. yucatanensis allowed the identification of two semipurified fractions with anti-virulence activity. The anti-virulence activity detected in the crude extracts of B. flammea, B. simaruba, C. biflora, C. aesculifolia, C. pareira, and C. yucatanensis, confirms the efficacy and traditional use of these medicinal plants against infectious diseases. The activity of the extract and semipurified fractions of C. yucatanensis indicates the presence of hydrophilic metabolites capable of interfering with QS in P. aeruginosa. This study represents the first report of Mayan medicinal plants with anti-QS properties and suggests they represent an important source of novel anti-virulence agents.


Nonimmune "Fulminant" type 1 diabetes presenting with diabetic ketoacidosis during pregnancy.
Ketoacidosis in pregnant women with previously undiagnosed diabetes is rare. Although insulin-dependent diabetes has recently been classified as either autoimmune (type 1A) or nonimmune (type 1B; "chronic" and "fulminant" subtypes), the clinical characteristics of diabetes in such settings are not fully understood. We report two pregnant patients with previously undiagnosed diabetes. They presented with severe diabetic ketoacidosis characterized by an abrupt onset, normal, or slightly elevated level of glycosylated hemoglobin, absence of diabetes-related autoimmune antibodies, and features typical of the "fulminant" subtype of nonimmune diabetes. The fetuses died in utero, and the mothers became insulin dependent. The "fulminant" subtype of diabetes may be associated with fetal death.


Synthesis of ITP and ATP and regeneration of 2,3-DPG in human erythrocytes incubated with adenosine, pyruvate and inorganic phosphate.
In the stored, 2,3-DPG depleted human erythrocytes incubated for four hours in a medium containing adenosine (10 mM), pyruvate (10 mM), and inorganic phosphate (50 mM) the regeneration of 2,3-DPG reached the value of five times higher than the physiological concentration and the ATP synthesis exceeded four times the physiological level. It has been also found that these erythrocytes are able to synthesize hypoxanthine nucleotides, namely IMP to 58 and ITP to 61 mumoles per 100 ml of erythrocytes.


Silver and copper as pollution tracers in Neogene to Holocene estuarine sediments from southwestern Spain.
Estuaries are very sensitive ecosystems to human activities and the natural evolution of their drainage basins located upstream. Pollution derived from human activities, such as historical mining or recent industrial wastes, can significantly affect their environmental quality. This paper analyzes the silver and copper contents of four cores extracted in two estuaries of SW Spain. Its chronology and vertical evolution allow to differentiate the effects of several pollution episodes (natural, Roman, 19th-20th centuries) on its different sedimentary environments in the last 6 million years. Possible future applications are included in the fields of environmental management or even education.


Inhibitory effects on esterase enzymes buche and ache in rainbow trout (Oncorhyncus mykiss) produced by the slow release insecticide chitosan diethyl phosphate.
The study on the toxicity of chitosan diethyl phosphate (ChDP), a controlled release insecticide, on the activities of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) in rainbow trout exposed to this pesticide was carried out. It was found that ChDP reduced BuChE activity in O. mykiss by a factor of eight at 6 days, with high fluctuation to the end of the exposition time at 12 days. The in vitro analysis of brain AChE treated with ChDP and Phenamiphos showed that it was competitively inhibited by both organophosphates. The values obtained for Km and Vmax for the AChE-ChDP (Km: 21.23 microM; Vmax: 43.10 micromol/min/g) and AChE-Phenamiphos (Km: 38.62 microM; Vmax: 38.91 micromol/min/g) systems were relatively low compared to values of the AChE (control) system (Km: 62.99 microM; Vmax: 63.29 micromol/min/g). Results reported in this study confirmed that chitosan diethyl phosphate performs similarly to organophosphate pesticides, producing inhibition in cholinesterases in rainbow trout.


[Robotics].
Content of this paper is the current state of the art of robots in surgery and the ongoing work on the field of surgical robotics at the Clinic for Maxillofacial Surgery at the Charité. Robots in surgery allows the surgeon to transform the accuracy of the imaging systems directly during the intervention and to plan an intervention beforehand. In this paper firstly the state of the art is described. Subsequently the scientific work at the clinic is described in detail. The paper closes with a outlook for future applications of robotics systems in maxillofacial surgery.