Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery.
The management of postoperative pain and recovery is still unsatisfactory in clinical practice. Opioids used for postoperative analgesia are frequently associated with adverse effects including nausea and constipation. These adverse effects prevent smooth postoperative recovery. On the other hand not all patients may be suited to, and take benefit from, epidural analgesia used to enhance postoperative recovery. The non-opioid lidocaine was investigated in several studies for its use in multi-modal management strategies to reduce postoperative pain and enhance recovery. The aim of this review was to assess the effects (benefits and risks) of perioperative intravenous lidocaine infusion compared to placebo/no treatment or compared to epidural analgesia on postoperative pain and recovery in adults undergoing various surgical procedures. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 5 2014), MEDLINE (January 1966 to May 2014), EMBASE (1980 to May 2014), CINAHL (1982 to May 2014), and reference lists of articles. We searched the trial registry database ClinicalTrials.gov, contacted researchers in the field, and handsearched journals and congress proceedings. We did not apply any language restrictions. We included randomized controlled trials comparing the effect of continuous perioperative intravenous lidocaine infusion either with placebo, or no treatment, or with epidural analgesia in adults undergoing elective or urgent surgery under general anaesthesia. The intravenous lidocaine infusion must have been started intraoperatively prior to incision and continued at least until the end of surgery. Trial quality was independently assessed by two authors according to the methodological procedures specified by the Cochrane Collaboration. Data were extracted by two independent authors. We collected trial data on postoperative pain, recovery of gastrointestinal function, length of hospital stay, postoperative nausea and vomiting (PONV), opioid consumption, patient satisfaction, surgical complication rates, and adverse effects of the intervention. We included 45 trials involving 2802 participants. Two trials compared intravenous lidocaine versus epidural analgesia. In all the remaining trials placebo or no treatment was used as a comparator. Trials involved participants undergoing open abdominal (12), laparoscopic abdominal (13), or various other surgical procedures (20).The risk of bias was low with respect to selection bias (random sequence generation), performance bias, attrition bias, and detection bias in more than 50% of the included studies. For allocation concealment and selective reporting the quality assessment yielded low risk of bias for only approximately 20% of the included studies.We found evidence of effect for intravenous lidocaine on the reduction of postoperative pain (visual analogue scale, 0 to 10 cm) compared to placebo or no treatment at 'early time points (one to four hours)' (mean difference (MD) -0.84 cm, 95% confidence interval (CI) -1.10 to -0.59; low-quality evidence) and at 'intermediate time points (24 hours)' (MD -0.34 cm, 95% CI -0.57 to -0.11; low-quality evidence) after surgery. However, no evidence of effect was found for lidocaine to reduce pain at 'late time points (48 hours)' (MD -0.22 cm, 95% CI -0.47 to 0.03; low-quality evidence). Pain reduction was most obvious at 'early time points' in participants undergoing laparoscopic abdominal surgery (MD -1.14, 95% CI -1.51 to -0.78; low-quality evidence) and open abdominal surgery (MD -0.72, 95% CI -0.96 to -0.47; moderate-quality evidence). No evidence of effect was found for lidocaine to reduce pain in participants undergoing all other surgeries (MD -0.30, 95% CI -0.89 to 0.28; low-quality evidence). Quality of evidence is limited due to inconsistency and indirectness (small trial sizes).Evidence of effect was found for lidocaine on gastrointestinal recovery regarding the reduction of the time to first flatus (MD -5.49 hours, 95% CI -7.97 to -3.00; low-quality evidence), time to first bowel movement (MD -6.12 hours, 95% CI -7.36 to -4.89; low-quality evidence), and the risk of paralytic ileus (risk ratio (RR) 0.38, 95% CI 0.15 to 0.99; low-quality evidence). However, no evidence of effect was found for lidocaine on shortening the time to first defaecation (MD -9.52 hours, 95% CI -23.24 to 4.19; very low-quality evidence).Furthermore, we found evidence of positive effects for lidocaine administration on secondary outcomes such as reduction of length of hospital stay, postoperative nausea, intraoperative and postoperative opioid requirements. There was limited data on the effect of IV lidocaine on adverse effects (e.g. death, arrhythmias, other heart rate disorders or signs of lidocaine toxicity) compared to placebo treatment as only a limited number of studies systematically analysed the occurrence of adverse effects of the lidocaine intervention.The comparison of intravenous lidocaine versus epidural analgesia revealed no evidence of effect for lidocaine on relevant outcomes. However, the results have to be considered with caution due to imprecision of the effect estimates. There is low to moderate evidence that this intervention, when compared to placebo, has an impact on pain scores, especially in the early postoperative phase, and on postoperative nausea. There is limited evidence that this has further impact on other relevant clinical outcomes, such as gastrointestinal recovery, length of hospital stay, and opioid requirements. So far there is a scarcity of studies that have systematically assessed the incidence of adverse effects; the optimal dose; timing (including the duration of the administration); and the effects when compared with epidural anaesthesia.


Activin-A and Bmp4 levels modulate cell type specification during CHIR-induced cardiomyogenesis.
The use of human pluripotent cell progeny for cardiac disease modeling, drug testing and therapeutics requires the ability to efficiently induce pluripotent cells into the cardiomyogenic lineage. Although direct activation of the Activin-A and/or Bmp pathways with growth factors yields context-dependent success, recent studies have shown that induction of Wnt signaling using low molecular weight molecules such as CHIR, which in turn induces the Activin-A and Bmp pathways, is widely effective. To further enhance the reproducibility of CHIR-induced cardiomyogenesis, and to ultimately promote myocyte maturation, we are using exogenous growth factors to optimize cardiomyogenic signaling downstream of CHIR induction. As indicated by RNA-seq, induction with CHIR during Day 1 (Days 0-1) was followed by immediate expression of Nodal ligands and receptors, followed later by Bmp ligands and receptors. Co-induction with CHIR and high levels of the Nodal mimetic Activin-A (50-100 ng/ml) during Day 0-1 efficiently induced definitive endoderm, whereas CHIR supplemented with Activin-A at low levels (10 ng/ml) consistently improved cardiomyogenic efficiency, even when CHIR alone was ineffective. Moreover, co-induction using CHIR and low levels of Activin-A apparently increased the rate of cardiomyogenesis, as indicated by the initial appearance of rhythmically beating cells by Day 6 instead of Day 8. By contrast, co-induction with CHIR plus low levels (3-10 ng/ml) of Bmp4 during Day 0-1 consistently and strongly inhibited cardiomyogenesis. These findings, which demonstrate that cardiomyogenic efficacy is improved by optimizing levels of CHIR-induced growth factors when applied in accord with their sequence of endogenous expression, are consistent with the idea that Nodal (Activin-A) levels toggle the entry of cells into the endodermal or mesodermal lineages, while Bmp levels regulate subsequent allocation into mesodermal cell types.


Defining nanotechnology.
A confusing array of terms has arisen with the rapid emergence of the subject of nanotechnology. In this article a recently derived framework for definitions of these terms is discussed.


Coagulation abnormalities in Dengue fever infection: A systematic review and meta-analysis.
Coagulation mechanisms are reported to be affected in dengue illness and evidenced by prolonged activated partial thromboplastin time (APTT) and prothrombin time (PT). The main aim of this systematic review and meta-analysis is to determine the magnitude of coagulation abnormalities among patients with dengue fever infection. This systematic review and meta-analysis were conducted per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The Joana Brigg's Institute (JBI) critical appraisal checklist was used for quality appraisal. STATA version 11 software was used for meta-analysis. The magnitude of coagulation abnormalities among dengue fever patients was determined by using a random-effects model. Subgroup and sensitivity analysis were performed to investigate the possible source of heterogeneity. Egger weighted regression tests were used to check the presence of publication bias among the included articles. Forty-two studies with a total of 12,221 dengue fever patients were eligible for meta-analysis in this study. Of which 22, 15, and 26 studies were used to determine the magnitude of prolonged APTT, PT, and thrombocytopenia, respectively. The magnitude of prolonged APTT and PT among patients with dengue fever infection were 42.91% (95% CI: 30.95, 54.87) I2 = 99.1% and 16.48% (95% CI: 10.95, 22.01) I2 = 97.0%, respectively. Besides, the magnitude of thrombocytopenia among dengue fever patients was 70.29% (95% CI: 62.69, 77.89) I2 = 99.3%. The magnitude of prolonged APTT in children and adults was 51.21% (95% CI: 24.54, 77.89) and 44.89% (95% CI: 28.32, 61.45), respectively. Similarly, the overall magnitude of prolonged PT in children and adults were 13.40% (95% CI: 6.09, 20.71) and 18.73% (95% CI: 7.49, 29.96), respectively. The result of this study showed that there is a high magnitude of prolonged APTT and PT in dengue fever patients. Therefore, screening and early correction of coagulation abnormalities may be helpful to reduce further complications in those patients.


Efficacy of preoperative Tranexamic Acid in patients undergoing intertrochanteric hip fracture surgery: A randomized placebo controlled trial.
To determine the efficacy of preoperative Tranexamic Acid (TXA) in reducing perioperative allogenic blood transfusion frequency in patients with intertrochanteric fractures treated with Dynamic Hip Screw (DHS). We conducted this placebo controlled double-blinded randomized trial in Orthopaedics & Traumatolgy Division Lady Reading Hospital, Peshawar from 1st January 2020 to 25th December 2022. All patients with intertrochanteric hip fractures fulfilling the inclusion criteria were treated with Dynamic Hip Screw (DHS) and were randomly divided into two equal groups. One group was administered single dose IV Tranexamic Acid (TXA) in a dose of 15mg/kg body weight in 100ml of saline while the other group (Placebo) was given 100 ml normal saline preoperatively. Post-operative Hemoglobin was measured on first, second and third day. The frequency of allogenic blood transfusions in the perioperative period was determined in both groups based upon the transfusion trigger (Hemoglobin 9g/dl). Categorical variables were compared with Chi-square test and mean with Independent sample t-test. P value of <0.05 was considered significant. The total number of patients in our trial were 200 which were equally but randomly allocated into TXA group and Placebo group each containing 100 patients. The mean age of the patients in TXA group was 48.16±1.75 years and the age of patients in the Placebo group was 48.35±1.60. The baseline demographic and clinical variables of both groups were identical (p< 0.05). The average preoperative hemoglobin was 11.5±4.2 g/dl in TXA group and 11.3±2.4g/dl in the Placebo group (p>0.05). The frequency of allogenic blood transfusion was significantly lower (p<0.05) in TXA group (13%, n=13) than in the Placebo group (41%, n=41). Tranexamic acid (TXA) significantly reduces the frequency of peri operative allogenic blood transfusion in patients undergoing Dynamic Hip Screw (DHS) for intertrochanteric fractures.


The development of expert face processing: are infants sensitive to normal differences in second-order relational information?
Sensitivity to second-order relational information (i.e., spatial relations among features such as the distance between eyes) is a vital part of achieving expertise with face processing. Prior research is unclear on whether infants are sensitive to second-order differences seen in typical human populations. In the current experiments, we examined whether infants are sensitive to changes in the space between the eyes and between the nose and the mouth that are within the normal range of variability in Caucasian female faces. In Experiment 1, 7-month-olds detected these changes in second-order relational information. Experiment 2 extended this finding to 5-month-olds and also found that infants detect second-order relations in upright faces but not in inverted faces, thereby exhibiting an inversion effect that has been considered to be a hallmark of second-order relational processing during adulthood. These results suggest that infants as young as 5 months are sensitive to second-order relational changes that are within the normal range of human variability. They also indicate that at least rudimentary aspects of face processing expertise are available early in life.


Questioning the Value of Brain Magnetic Resonance Imaging in the Evaluation of Children with Isolated Growth Hormone Deficiency.
Isolated growth hormone deficiency (IGHD) is a relatively common disorder. Current diagnostic protocol requires a brain magnetic resonance imaging (MRI) study of the hypothalamus and the hypophysis to determine the cause after establishment of the diagnosis. This study aimed to examine the yield of brain MRI in the evaluation of children with IGHD and to define clinical and laboratory parameters that justify its performance. A retrospective chart review of all children (<18 years) diagnosed with IGHD was conducted at 3 pediatric endocrinology units between 2008 and 2018. The study included 192 children (107 boys) with confirmed IGHD. The mean age ± standard deviation (SD) at diagnosis was 8.2 ± 3.7 years (median 8.5 years, range 0.8-15.9). The mean height SD score (SDS) at diagnosis was -2.25 ± 0.73. The mean height deficit SDS (defined as the difference between height SDS at diagnosis and mid-parental height SDS) was -1.7 ± 0.9. Fifteen children (7.8%) had pathological MRI findings. No space-occupying lesion was detected. Children with pathological MRIs had greater height deficit SDS and lower peak growth hormone levels on provocative tests compared to children with normal MRIs: -2.3 ± 1.2 vs. -1.6 ± 0.8 (p = 0.02) and 4.4 ± 1.9 vs. 5.7 ± 1.3 (p = 0.01), respectively. Our preliminary data indicate that most brain MRIs performed for routine evaluation of children with IGHD are not essential for determining cause. Further studies with larger cohorts are needed in order to validate this proposed revision of current protocols.


[A CxxC domain that binds to unmethylated CpG is required for KDM2A to control rDNA transcription].
Dysfunction of ribosome biogenesis is commonly found in cancers. Because the transcription of ribosomal RNA genes (rDNA) is a rate-limiting step in ribosome biogenesis and is elevated in many cancer cells, ribosomal RNA transcription can be a target for cancer therapy. In eukaryotes, ribosomal RNA is transcribed specifically in nucleoli by RNA polymerase I but not by RNA polymerase II. Therefore, ribosomal RNA transcription by RNA polymerase I would have a distinct nature compared to transcription by RNA polymerase II. Genomic DNA with proteins including histones constitutes chromatin. The structure of chromatin has plasticity and is regulated by chemical modifications of chromatin's components. We had reported that histone demethylase KDM2A reduced ribosomal RNA transcription in response to starvation. In this symposium, we reported our recent results showing the mechanism by which KDM2A was recruited to rDNA chromatin. We found that KDM2A bound to a rDNA promoter with unmethylated CpG dinucleotides via KDM2A CxxC-zinc finger motif. This binding was required for KDM2A to demethylate histone in the rDNA promoter and reduce rDNA transcription resulting from starvation. Further, this binding was detected before starvation, independent of the demethylase activity. We also found that the histone demethylation by KDM2A in response to starvation was detected only in the rDNA promoter, but not in a gene promoter transcribed by Pol II, the P2RX4 promoter. These results suggest that it is important to consider genome regions and cell conditions when developing epigenetic drugs.


Depth-encoded optical coherence elastography for simultaneous volumetric imaging of two tissue faces.
Depth-encoded optical coherence elastography (OCE) enables simultaneous acquisition of two three-dimensional (3D) elastograms from opposite sides of a sample. By the choice of suitable path-length differences in each of two interferometers, the detected carrier frequencies are separated, allowing depth-ranging from each interferometer to be performed simultaneously using a single spectrometer. We demonstrate depth-encoded OCE on a silicone phantom and a freshly excised sample of mouse liver. This technique minimizes the required spectral detection hardware and halves the total scan time. Depth-encoded OCE may expedite clinical translation in time-sensitive applications requiring rapid 3D imaging of multiple tissue surfaces, such as tumor margin assessment in breast-conserving surgery.


Rhodopsin kinase and recoverin modulate phosphodiesterase during mouse photoreceptor light adaptation.
Light stimulates rhodopsin in a retinal rod to activate the G protein transducin, which binds to phosphodiesterase (PDE), relieving PDE inhibition and decreasing guanosine 3',5'-cyclic monophosphate (cGMP) concentration. The decrease in cGMP closes outer segment channels, producing the rod electrical response. Prolonged exposure to light decreases sensitivity and accelerates response kinetics in a process known as light adaptation, mediated at least in part by a decrease in outer segment Ca(2+). Recent evidence indicates that one of the mechanisms of adaptation in mammalian rods is down-regulation of PDE. To investigate the effect of light and a possible role of rhodopsin kinase (G protein-coupled receptor kinase 1 [GRK1]) and the GRK1-regulating protein recoverin on PDE modulation, we used transgenic mice with decreased expression of GTPase-accelerating proteins (GAPs) and, consequently, a less rapid decay of the light response. This slowed decay made the effects of genetic manipulation of GRK1 and recoverin easier to observe and interpret. We monitored the decay of the light response and of light-activated PDE by measuring the exponential response decay time (τREC) and the limiting time constant (τD), the latter of which directly reflects light-activated PDE decay under the conditions of our experiments. We found that, in GAP-underexpressing rods, steady background light decreased both τREC and τD, and the decrease in τD was nearly linear with the decrease in amplitude of the outer segment current. Background light had little effect on τREC or τD if the gene for recoverin was deleted. Moreover, in GAP-underexpressing rods, increased GRK1 expression or deletion of recoverin produced large and highly significant accelerations of τREC and τD. The simplest explanation of our results is that Ca(2+)-dependent regulation of GRK1 by recoverin modulates the decay of light-activated PDE, and that this modulation is responsible for acceleration of response decay and the increase in temporal resolution of rods in background light.


Language and Literacy Together: Supporting Grammatical Development in Dual Language Learners With Risk for Language and Learning Difficulties.
Purpose Early Interventions in Reading (Vaughn et al., 2006), the only literacy intervention with demonstrated effectiveness for U.S. dual language learners, was enhanced to support the development of oral language (vocabulary, grammar, and narrative) and literacy, which we refer to as "Language and Literacy Together." The primary focus of this study is to understand the extent to which grammatical skills of bilinguals with risk for language and/or reading difficulties improve in the Language and Literacy Together intervention. Method Fifteen first-grade dual language learners with risk for language and/or reading difficulties participated in an enhanced version of Early Interventions in Reading in Spanish. Children completed pre- and postintervention evaluations in Spanish and English, including grammatical testing from the Bilingual English Spanish Oral Screener (Peña et al., 2008) and narrative evaluation Test of Narrative Language story prompts (Gillam & Pearson, 2004; Gillam et al., n.d.). Data from six comparison participants with typical language skills who completed pre- and posttesting demonstrate the stability of the measures. Results The intervention group made gains in English and Spanish as evidenced by significant increases in their cloze and sentence repetition accuracy on the Bilingual English Spanish Oral Screener Morphosyntax subtest. They increased productivity on their narratives in Spanish and English as indexed by mean length of utterance in words but did not make gains in their overall grammaticality. Conclusions Structured intervention that includes an emphasis on grammatical elements in the context of a broader intervention can lead to change in the production of morphosyntax evident in both elicited constructions and narrative productivity as measured by mean length of utterance in words. Additional work is needed to determine if and how cross-linguistic transfer might be achieved for these learners.


Persistent hiccups as a rare presenting symptom of pulmonary embolism.
Pulmonary embolism (PE) is a life-threatening condition that may present as dyspnea, chest pain, cough or hemoptysis, but often occurs without symptoms. It is not typically associated with hiccups. Hiccups are generally self-limiting benign contractions of the diaphragm that may be associated with medications or food but may also be symptomatic of serious disease when persistent. We report 3 cases of PE presenting as persistent hiccups.


Airborne Doppler lidar measurements.
This paper describes recent measurements using coherent Doppler lidars operating at a wavelength of 10.6 microm aboard the NASA Ames Convair 990. The purpose of the measurements was to obtain data on the atmospheric wind fields and the distribution of the backscatter coefficient at 10.6 microm. A description of the instruments is provided detailing the modifications incorporated following the 1981 test flights of the systems. The measurement program is outlined, and preliminary results are discussed.


Monitoring contact sensitization to p-phenylenediamine (PPD) by patch testing with PPD 0.3% in petrolatum.
Being a contact allergen of general relevance, p-phenylenediamine (PPD) is patch tested in the baseline series. However, PPD 1% in petrolatum may actively sensitize. Patch testing with PPD at 0.35% pet. proved to be safe, as far as active sensitization is concerned. To determine whether PPD 0.3% pet. reliably detects PPD sensitization. Patch testing with PPD 0.3% pet. and 1% pet. synchronously was performed in consecutive patients in a multicentre study within the Information Network of Departments of Dermatology. Altogether, 2042 patients were patch tested. PPD 1% pet. yielded 6.0% positive reactions (n = 123), and PPD 0.3% pet. yielded 4.7% (n = 95). The synchronous reproducibility of PPD reactions was similar as known from parallel patch tests with identical PPD concentrations. The diagnostic properties of PPD 0.3% pet. expressed as reaction index and positivity ratio were good. Of the 123 patients reacting to PPD 1% pet., 32 (26%) had no positive reaction to PPD 0.3% pet. In 22 of these 32 patients (69%), no clinical relevance could be found. As patch testing with PPD 0.3% pet. is reliable according to our results, we recommend replacing PPD 1% pet. in the baseline series with PPD 0.3% pet.


Coronary sinus adrenomedullin rises in response to myocardial injury.
Human adrenomedullin (ADM), a peptide comprising 52 amino acids, is a circulating hormone with vasodilator properties. We have evaluated its release by the heart following ischaemic myocardial damage, as indicated by elevated levels of the cardiospecific protein troponin-T (Tn-T) during cardiopulmonary bypass. ADM (pg/ml) and Tn-T (ng/ml) were measured in coronary sinus blood before and after aortic cross-clamp and in venous blood 6 h after surgery in 22 coronary-bypass patients. Based on the pre- and post-clamp Tn-T levels in the coronary sinus, the patients were divided into group I (no change; n=10) and group II (two times increase; n=12). Baseline ADM (362.7+/-106.2 and 303+/-58.7 pg/ml in groups I and II respectively; means+/-S.D.) and Tn-T (0.66+/-0.14 and 0.57+/-0.13 ng/ml respectively) levels were similar in both groups. In group I, the post-clamp ADM (317.6+/-80.8 pg/ml) and Tn-T (0.68+/-0.15 ng/ml) levels did not change significantly. In group II, the post-clamp ADM levels rose significantly above the baseline, mimicking the change in Tn-T (ADM, 541.4+/-89.4 pg/ml; Tn-T, 1.37+/-0.31 ng/ml; P=0.009). After 6 h, the systemic Tn-T levels were similar in both groups (2. 09+/-0.44 and 1.95+/-0.52 ng/ml in groups I and II respectively). We suggest that: (1) minor degrees of myocardial ischaemic damage result in release of ADM by the heart, and (2) ADM may play a protective role in the myocardium during an ischaemic insult. This suggests a possible therapeutic role for ADM in the management of intra-operative myocardial ischaemia.


Percutaneous Transvenous Transseptal Transcatheter Valve Implantation in Failed Bioprosthetic Mitral Valves, Ring Annuloplasty, and Severe Mitral Annular Calcification.
This study sought to examine the feasibility, safety, and intermediate-term outcomes in patients undergoing percutaneous transvenous transcatheter mitral valve implantation in failed bioprosthesis, ring annuloplasty, and calcific mitral stenosis. Surgical mitral valve replacement in patients with previous surgery or severe mitral annular calcification (MAC) is often associated with high or prohibitive risk. Percutaneous transfemoral antegrade transseptal implantation of Edwards SAPIEN prosthesis (Edwards Lifesciences, Irvine, California) was performed in 48 patients with degenerated mitral bioprosthesis (n = 33), previous ring annuloplasty (n = 9), and severe MAC (n = 6). The mean Society of Thoracic Surgeons risk score was 13.2 ± 7.4% with a mean age 76 ± 11 years. Acute procedural success was achieved in 42 of 48 patients (88%) in the overall group and 31 of 33 (94%) in the failed bioprosthetic mitral valve group and success rate of 11 of 15 (73%) in patients with failed annuloplasty rings and MAC. After successful procedure, no patients had > mild residual mitral prosthetic or periprosthetic regurgitation; mean transvalvular gradients were 6 ± 2.5 mm Hg. Thirty-day survival free of death and cardiovascular surgery was 85% in the overall group and 91% in the failed bioprosthetic mitral valve subgroup. Transfemoral percutaneous transvenous mitral valve implantation in high-risk patients with degenerated bioprosthesis is safe, effective, and associated with rapid improvement in hemodynamics, short length of stays, and improved functional status. Percutaneous mitral valve implantation in patients with failed annuloplasty rings and severe MAC is a promising therapy with significant short-term morbidity and mortality that requires further study.


Images of a spin-torque-driven magnetic nano-oscillator.
We present the first space- and time-resolved images of the spin-torque-induced steady-state oscillation of a magnetic vortex in a spin-valve nanostructure. We find that the vortex structure in a nanopillar is considerably more complicated than the 2D idealized structure often-assumed, which has important implications for the driving efficiency. The sense of the vortex gyration is uniquely determined by the vortex core polarity, confirming that the spin-torque acts as a source of negative damping even in such a strongly nonuniform magnetic system. The orbit radius is ∼10 nm, in agreement with micromagnetic simulations.


Idiomarina indica sp. nov., isolated from seawater.
Two Gram-negative, aerobic, rod-shaped bacteria, designated strains SW104(T) and X07, were isolated from a seawater sample collected from the Indian Ocean. The strains grew at a temperature range of 12-50 °C (optimum, 35-37 °C), and at pH 6.0-9.0 (optimum pH 7.0-7.5). The predominant cellular fatty acids of strain SW104(T) were iso-C15 : 0 (41.2 %), iso-C17 : 1ω9c (15.2 %) and iso-C17 : 0 (11.1 %). The major respiratory quinone was ubiquinone 8 (Q-8). The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The genomic DNA G+C contents of strains SW104(T) and X07 were 49.8 and 49.5 mol%, respectively. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the new isolates were related to members of the genus Idiomarina, showing the highest similarity with Idiomarina taiwanensis PIT1(T) and Idiomarina maritima 908087(T) (96.1 and 95.9 %, respectively). On the basis of phenotypic, genotypic and phylogenetic characteristics, it is proposed that strains SW104(T) and X07 should be described as representatives of a novel species of the genus Idiomarina, for which the name Idiomarina indica sp. nov. is proposed. The type strain is SW104(T) ( = CGMCC 1.10824(T) = JCM 18138(T)).


Paraffin oil as a "methane vector" for rapid and high cell density cultivation of Methylosinus trichosporium OB3b.
Slow growth and relatively low cell densities of methanotrophs have limited their uses in industrial applications. In this study, a novel method for rapid cultivation of Methylosinus trichosporium OB3b was studied by adding a water-immiscible organic solvent in the medium. Paraffin oil was the most effective at enhancing cell growth and final cell density. This is at least partially due to the increase of methane gas transfer between gas and medium phases since methane solubility is higher in paraffin than in water/nitrate minimal salt medium. During cultivation with paraffin oil at 5% (v/v) in the medium, M. trichosporium OB3b cells also showed higher concentrations of the intermediary metabolites, such as formic acid and pyruvic acid, and consumed more methane compared with the control. Paraffin as methane vector to improve methanotroph growth was further studied in a 5-L fermentor at three concentrations (i.e., 2.5%, 5%, and 10%). Cell density reached about 14 g dry weight per liter with 5% paraffin, around seven times higher than that of the control (without paraffin). Cells cultivated with paraffin tended to accumulate around the interface between oil droplets and the water phase and could exist in oil phase in the case of 10% (v/v) paraffin. These results indicated that paraffin could enhance methanotroph growth, which is potentially useful in cultivation of methanotrophs in large scale in industry.


Critical reappraisal of vitamin D deficiency.
The current surge of interest in vitamin D is fuelled not only by evidence that vitamin D supplementation decreases the risk of osteoporotic fractures but also by vast observational studies indicating a variety of beneficial extraskeletal effects (including decreases in the risks of cancer, inflammatory diseases, and even death). Serum 25-hydroxyvitamin D (25(OH)D) assay is now a highly reliable method for evaluating vitamin D stores in individual patients. Nevertheless, the normal or desirable 25(OH)D range for patients seen in everyday clinical practice needs to be more accurately defined. Maintaining serum 25(OH)D above 75 nmol/L is currently recommended to ensure optimal bone health, but higher levels may be required to obtain some of the extraskeletal benefits. Naturally occurring vitamin D is by far the most widely used form for correcting vitamin D deficiency, and the hydroxylated derivatives have only a few highly specific indications. However, controversy persists about the optimal modalities of natural vitamin D supplementation in terms of the type of vitamin (D2 or D3), schedule (once daily or at wider intervals), and route (oral or injectable). For chronic supplementation to protect against bone loss, a daily dosage of at least 800 IU seems required. Higher dosages (e.g., 100,000 to 200,000 IU every 2 months for 6 months) may be needed to correct established vitamin D deficiency; a repeat 25(OH)D assay after 4 to 6 months may help to assess the treatment response and to adjust the subsequent vitamin D dosage. The current emphasis is on the detection of vitamin D deficiency in the general population and in subgroups at risk for osteoporosis followed by an assessment of severity and the initiation of appropriate treatment. From a public health perspective, supplying at least 800 IU per day seems useful and safe.


Abnormal fertility, acrosome formation, IFT20 expression and localization in conditional Gmap210 knockout mice.
GMAP210 (TRIP11) is a cis-Golgi network-associated protein and a Golgi membrane receptor for IFT20, an intraflagellar transport component essential for male fertility and spermiogenesis in mice. To investigate the role of GMAP210 in male fertility and spermatogenesis, floxed Gmap210 mice were bred with Stra8-iCre mice so that the Gmap210 gene is disrupted in spermatocytes and spermatids in this study. The Gmap210flox/flox: Stra8-iCre mutant mice showed no gross abnormalities and survived to adulthood. In adult males, testis and body weights showed no difference between controls and mutant mice. Low-magnification histological examination of the testes revealed normal seminiferous tubule structure, but sperm counts and fertility were significantly reduced in mutant mice compared with controls. Higher resolution examination of the mutant seminiferous epithelium showed that nearly all sperm had more oblong, abnormally shaped heads, while the sperm tails appeared to have normal morphology. Electron microscopy also revealed abnormally shaped sperm heads but normal axoneme core structure; some sperm showed membrane defects in the midpiece. In mutant mice, expression levels of IFT20 and other selective acrosomal proteins were significantly reduced, and their localization was also affected. Peanut-lectin, an acrosome maker, was almost absent in the spermatids and epididymal sperm. Mitochondrion staining was highly concentrated in the heads of sperm, suggesting that the midpieces were coiling around or aggregating near the heads. Defects in acrosome biogenesis were further confirmed by electron microscopy. Collectively, our findings suggest that GMAP210 is essential for acrosome biogenesis, normal mitochondrial sheath formation, and male fertility, and it determines expression levels and acrosomal localization of IFT20 and other acrosomal proteins.


Lipidic cubic phase injector facilitates membrane protein serial femtosecond crystallography.
Lipidic cubic phase (LCP) crystallization has proven successful for high-resolution structure determination of challenging membrane proteins. Here we present a technique for extruding gel-like LCP with embedded membrane protein microcrystals, providing a continuously renewed source of material for serial femtosecond crystallography. Data collected from sub-10-μm-sized crystals produced with less than 0.5 mg of purified protein yield structural insights regarding cyclopamine binding to the Smoothened receptor.


Organic compounds in produced waters from shale gas wells.
A detailed analysis is reported of the organic composition of produced water samples from typical shale gas wells in the Marcellus (PA), Eagle Ford (TX), and Barnett (NM) formations. The quality of shale gas produced (and frac flowback) waters is a current environmental concern and disposal problem for producers. Re-use of produced water for hydraulic fracturing is being encouraged; however, knowledge of the organic impurities is important in determining the method of treatment. The metal content was determined by inductively coupled plasma optical emission spectrometry (ICP-OES). Mineral elements are expected depending on the reservoir geology and salts used in hydraulic fracturing; however, significant levels of other transition metals and heavier main group elements are observed. The presence of scaling elements (Ca and Ba) is related to the pH of the water rather than total dissolved solids (TDS). Using gas chromatography mass spectrometry (GC/MS) analysis of the chloroform extracts of the produced water samples, a plethora of organic compounds were identified. In each water sample, the majority of organics are saturated (aliphatic), and only a small fraction comes under aromatic, resin, and asphaltene categories. Unlike coalbed methane produced water it appears that shale oil/gas produced water does not contain significant quantities of polyaromatic hydrocarbons reducing the potential health hazard. Marcellus and Barnett produced waters contain predominantly C6-C16 hydrocarbons, while the Eagle Ford produced water shows the highest concentration in the C17-C30 range. The structures of the saturated hydrocarbons identified generally follows the trend of linear > branched > cyclic. Heterocyclic compounds are identified with the largest fraction being fatty alcohols, esters, and ethers. However, the presence of various fatty acid phthalate esters in the Barnett and Marcellus produced waters can be related to their use in drilling fluids and breaker additives rather than their presence in connate fluids. Halogen containing compounds are found in each of the water samples, and although the fluorocarbon compounds identified are used as tracers, the presence of chlorocarbons and organobromides formed as a consequence of using chlorine containing oxidants (to remove bacteria from source water), suggests that industry should concentrate on non-chemical treatments of frac and produced waters.


Tailoring the mechanical properties of polymer nanocomposites via interfacial engineering.
The improvement of mechanical properties of polymer nanocomposites (PNCs) has been studied for many years, with the main focus on the structure of the nanofillers. Much less effort has been devoted to unraveling the factors controlling the structure of the grafted chains. Herein, through coarse-grained molecular-dynamics simulations, we have successfully fabricated an ideal, mechanically-interlocked composite structure composed of end-functionalized chains grafted to the nanoparticle surface forming rings and making the matrix chains thread through these rings. Depending on the details of the grafting, the reinforcement effect can be remarkable, improving the tensile stress of the system significantly up to 700%. Meanwhile, anisotropy of the system's mechanical response is also observed. Furthermore, the influence of the grafted chain distribution on the mechanical properties of the system has been investigated as well. We observe that the mechanical properties of the system are closely related to the total number of the beads in the grafted chains or the synergistic effect between the length and density of the grafted chains leads to no significant difference in the performance of systems. At constant grafting density, the mechanical properties of the systems correlate negatively to the grafted chain length. In general, our study should help to design and fabricate high-performance PNCs with excellent mechanical properties.


Insulin therapy in people with type 2 diabetes: opportunities and challenges?
Given the continued interest in defining the optimal management of individuals with type 2 diabetes, the Editor of Diabetes Care convened a working party of diabetes specialists to examine this topic in the context of insulin therapy. This was prompted by recent new evidence on the use of insulin in such people. The group was aware of evidence that the benefits of insulin therapy are still usually offered late, and thus the aim of the discussion was how to define the optimal timing and basis for decisions regarding insulin and to apply these concepts in practice. It was noted that recent evidence had built upon that of the previous decades, together confirming the benefits and safety of insulin therapy, albeit with concerns about the potential for hypoglycemia and gain in body weight. Insulin offers a unique ability to control hyperglycemia, being used from the time of diagnosis in some circumstances, when metabolic control is disturbed by medical illness, procedures, or therapy, as well as in the longer term in ambulatory care. For those previously starting insulin, various other forms of therapy can be added later, which offer complementary effects appropriate to individual needs. Here we review current evidence and circumstances in which insulin can be used, consider individualized choices of alternatives and combination regimens, and offer some guidance on personalized targets and tactics for glycemic control in type 2 diabetes.


Is Thyroid Dysfunction Associated with Unruptured Intracranial Aneurysms? A Population-Based, Nested Case-Control Study from Korea.
Background: Few risk factors for the development of intracranial aneurysms (IAs) are known. We investigated the potential role of thyroid diseases in IA development using nationwide real-world data. Methods: A nested case-control study within the National Health Insurance Service-National Sample Cohort data from 2002 to 2019 was performed. A total of 5335 patients with unruptured IA were matched by age and sex with 80,025 controls at a ratio of 1:15. We estimated the odds ratios (ORs) and corresponding confidence intervals [CIs] between thyroid diseases and unruptured IA using a multivariable conditional logistic regression model. Results: Tobacco smoking, use of antihypertensive medication, and hypothyroidism were significantly associated with an elevated risk for unruptured IA in univariate analysis. In multivariable analysis, a history of hypothyroidism was associated with unruptured IA (adjusted OR: 1.46 [CI: 1.26-1.69]). Among patients with hypothyroidism, long-term use of thyroid hormone for >5 years was associated with a reduced risk for unruptured IA (adjusted OR: 0.69 [CI: 0.48-0.99]). A history of hyperthyroidism was associated with a reduced risk for unruptured IAs (adjusted OR: 0.71 [CI: 0.54-0.93]). In secondary analyses of the data according to sex, the respective observed associations between hypothyroidism and hyperthyroidism and the risk of IAs were found to be statistically significant in females but not in males. Conclusions: Hypothyroidism is associated with an increased risk of unruptured IAs, whereas hyperthyroidism is associated with a reduced risk. Overall, the findings suggest that thyroid hormones may play a protective role in the development of unruptured IAs. Further studies are needed to clarify potential direct causality and the biologic mechanisms relating thyroid dysfunction and unruptured IA.


MRSA: the leading pathogen of orthopedic infection in a tertiary care hospital, South India.
The rate of infection is high and heterogeneous in developing countries. This study aimed to find the rate and pattern of infection in a tertiary care hospital with a goal to improve the infection control practices. The study was conducted in the orthopedic units of a multispecialty teaching hospital. Medical records of major orthopedic surgery adult patients without immunosuppression state were included. The bacterial culture report of the wound swabs were noted over a period of one year. The bacterial culture testing was performed by a recommended method. Among 2,249 orthopedic surgery patients, 83.7% were males, 49.1% had open wounds during admission and 32.2% patients were infected. Majority (64.2%) of the injuries were in the lower limb with 19.4% patients having undergone multiple surgeries during hospitalization. A total of 946 pathogens were grown from 725 specimens. Staphylococcus aureus was the maximum (48.4%) followed by Pseudomonas aeruginosa (26.3%) and E coli (16.7%). Among them, 57.3% were Methicillin Resistant Staphylococcus aureus (MRSA) and was the leading pathogen causing infection among orthopedic patients. MRSA infection was high. Consequent to this, an interventional program entitled 'Extended Infection Control Measures' was designed to reduce the burden of infection.


Conical Modification of Forearm Free Flaps for Single-Stage Reconstruction After Total Orbital Exenteration.
Orbital exenteration is a significant reconstructive challenge for plastic surgeons. Options described for these defects range from healing by secondary intention to free tissue transfer. The authors present our preferred reconstruction of orbital defects with free forearm-based flaps, which provides quality soft tissue and orbital contouring in 1 stage to consistently allow placement of bone-anchored implants for eventual orbital prosthesis. This conical shape of the orbit is deconstructed into a "Pac-Man" type shaped flap that leaves adequate depth for a prosthesis. A retrospective chart review was performed of 2 separate patients receiving orbital exenteration reconstruction by the senior author (MFE). Two patients presented with adenoid cystic carcinoma of the orbit. Both patients underwent nonlid sparing orbital exenteration with adjuvant chemotherapy and radiation. Each patient subsequently developed delayed wound healing after prior local flap reconstruction. Vascularized radial forearm flaps in a Pac-Man shape were used in both patients. Both patients were discharged from the hospital on postoperative day 3. No partial or total flap loss was encountered. To date, each patient has undergone planning for osseointegrated implants. The authors present a simplified method of orbital reconstruction that provides high-quality vascularized tissue for resurfacing in 1 stage. This type of open-cavity flap reconstruction avoids the need for flap debulking procedures and facilitates 2-stage placement of osseointegrated implants.


Toxicity of Potential Fungal Defense Proteins towards the Fungivorous Nematodes Aphelenchus avenae and Bursaphelenchus okinawaensis.
Resistance of fungi to predation is thought to be mediated by toxic metabolites and proteins. Many of these fungal defense effectors are highly abundant in the fruiting body and not produced in the vegetative mycelium. The defense function of fruiting body-specific proteins, however, including cytoplasmically localized lectins and antinutritional proteins such as biotin-binding proteins, is mainly based on toxicity assays using bacteria as a heterologous expression system, with bacterivorous/omnivorous model organisms as predators. Here, we present an ecologically more relevant experimental setup to assess the toxicity of potential fungal defense proteins towards the fungivorous, stylet-feeding nematodes Aphelenchus avenae and Bursaphelenchus okinawaensis As a heterologous expression host, we exploited the filamentous fungus Ashbya gossypii Using this new system, we assessed the toxicity of six previously characterized, cytoplasmically localized, potential defense proteins from fruiting bodies of different fungal phyla against the two fungivorous nematodes. We found that all of the tested proteins were toxic against both nematodes, albeit to various degrees. The toxicity of these proteins against both fungivorous and bacterivorous nematodes suggests that their targets have been conserved between the different feeding groups of nematodes and that bacterivorous nematodes are valid model organisms to assess the nematotoxicity of potential fungal defense proteins.IMPORTANCE Our results support the hypothesis that cytoplasmic proteins abundant in fungal fruiting bodies are involved in fungal resistance against predation. The toxicity of these proteins toward stylet-feeding nematodes, which are also capable of feeding on plants, and the abundance of these proteins in edible mushrooms, may open possible avenues for biological crop protection against parasitic nematodes, e.g., by expression of these proteins in crops.


Service Value Activities by Nurse Practitioners in Ambulatory Specialty Care.
The increase in nurse practitioners (NPs) in ambulatory medical and surgical specialty settings has prompted inquiry into their role and contribution to patient care. We explored the role and contribution of NPs in ambulatory specialty care through their activities outside of direct care and billable visits (referred to as service value activities), and how NPs perceive these activities enhance quality and efficiency of care, for both patients and the health care institution. This qualitative thematic analysis examined interviews from 16 NPs at a large academic medical center about their role and contribution to patient care quality and departmental efficiency beyond billable visits. Five categories of NP contribution were identified: promoting patient care continuity, promoting departmental continuity, promoting institutional historical and insider knowledge, addressing time-sensitive issues, and participating in leadership and quality improvement activities. As the role of NPs in specialty care grows and health care systems emphasize quality of care, it is appropriate to explore the quality- and efficiency-enhancing activities NPs perform in specialty care beyond direct patient care.


[Ergonomic analysis of nursing activities in relation to the development of musculoskeletal disorders].
Musculoskeletal disorders are frequent among nurses. The literature so far focused mainly on back pain while paying little attention to disorders of the upper and lower limbs. Back pain is associated to patients' handling, but we know very little on the effect of awkward postures due to frequent bending and twisting and of work organisation which could also be involved in the genesis of these disorders. The pain localised to the musculoskeletal apparatus, including the presence of multiple complaints, was studied in a group of 70 nurses, with Estev and Vistat questionnaires, together with the possible association to work conditions. An ergonomic analysis of nursing activities (the postures and cognitive workload) was carried out to uncover associations to the risk of developing musculoskeletal disorders. Results show an involvement of all musculoskeletal sites and a high prevalence of multiple pain complaints (54% of the nurses). Ergonomic analysis highlighted the adoption of awkward postures for prolonged times. Moreover, nurses are frequently interrupted and their working pace is under continuous time pressure. Cognitive workload and work organisation should also be addressed, besides the postures, as factors which could compromise the health of nurses and influence the quality of care.


[Use of electroglottograph].
The most informative method of investigating the phonatoric function of the larynx is the one proposed by F. Fabre back in 1957. Utilization of a specially devised apparatus--electopharyngograph enables it to make a delicate differential diagnosis, to observe the patient dynamically during the treatment and to effect a comparative analysis of the vocal cords condition.


Ibuprofen prevents thrombin-induced lung vascular injury: mechanism of effect.
We compared pulmonary vascular responses with thrombin-induced pulmonary microembolism in awake sheep pretreated with ibuprofen or meclofenamate. Control sheep with lung lymph fistulas (n = 6) were challenged with 80 U/kg of alpha-thrombin, the native enzyme. Two groups of similarly prepared sheep received the cyclooxygenase inhibitors, ibuprofen (n = 4) or meclofenamate (n = 4), before the thrombin challenge. Thrombin-induced pulmonary microembolism in control sheep increased pulmonary lymph flow and lymph protein clearance (lymph flow X lymph-to-plasma protein concentration ratio). These lymph changes were associated with sustained increases in mean pulmonary arterial pressure (Ppa) and pulmonary vascular resistance (PVR) and a decrease in circulating neutrophil count. The steady-state pulmonary hemodynamic and lymph responses to thrombin persisted after cyclooxygenase inhibition with meclofenamate, although the increases in pulmonary lymph flow and lymph protein clearance were delayed. In contrast, ibuprofen reduced pulmonary lymph flow, lymph protein clearance, Ppa, and PVR responses. Neutrophil count in control and meclofenamate groups remained below base line after thrombin, whereas neutrophil count returned to base line in the ibuprofen group within 90 min after thrombin. Ibuprofen resulted in a greater decrease in vitro neutrophil adherence to pulmonary endothelium induced by serum generated by clotting whole blood with alpha-thrombin as compared with meclofenamate. Results indicate that ibuprofen attenuates the increases in Ppa and PVR and markedly attenuates the increase in pulmonary transvascular protein clearance after thrombin. The protective effect of ibuprofen may be due to reduction of neutrophil sequestration in lung.


YbdG in Escherichia coli is a threshold-setting mechanosensitive channel with MscM activity.
We describe a mechanosensitive (MS) channel that has mechanosensitive channel of miniconductance (MscM) activity, and displays unique properties with respect to gating. Mechanosensitive channels respond to membrane tension, are ubiquitous from bacteria to man, and exhibit a great diversity in structure and function. These channels protect Bacteria and Archaea against hypoosmotic shock and are critical determinants of shape in chloroplasts. Given the dominant roles played in bacteria by the mechanosensitive channel of small conductance (MscS) and the mechanosensitive channel of large conductance (MscL), the role of the multiple MS channel homologs observed in most organisms remains obscure. Here we demonstrate that a MscS homolog, YbdG, extends the range of hypoosmotic shock that Escherichia coli cells can survive, but its expression level is insufficient to protect against severe shocks. Overexpression of the YbdG protein provides complete protection. Transcription and translation of the ybdG gene are enhanced by osmotic stress consistent with a role for the protein in survival of hypoosmotic shock. Measurement of the conductance of the native channel by standard patch clamp methods was not possible. However, a fully functional YbdG mutant channel, V229A, exhibits a conductance in membrane patches consistent with MscM activity. We find that MscM activities arise from more than one gene product because ybdG deletion mutants still exhibit an occasional MscM-like conductance. We propose that ybdG encodes a low-abundance MscM-type MS channel, which in cells relieves low levels of membrane tension, obviating the need to activate the major MS channels, MscS and MscL.


Telomere shortening and telomerase reactivation in dysplastic nodules of human hepatocarcinogenesis.
The maintenance of telomere with telomerase reactivation, vital for carcinogenesis, was studied in human multistep hepatocarcinogenesis for the characterization of borderline lesions. The terminal restriction fragment length (TRFL) and telomerase activity (TA) were examined in 3 chronic hepatitis (CH), 10 cirrhosis, 7 large regenerative nodules (LRNs), 30 low grade dysplastic nodules (LGDNs), 6 high grade DNs (HGDNs), 3 DNs with hepatocellular carcinoma (HCC) foci, 11 HCCs, and 4 normal livers by Southern hybridization and TRAPeze Elisa telomerase detection. The TRFL and TA showed significant differences between the LGDNs and HGDNs. Most LGDNs had similar levels of TRFL and TA to those of the CH, cirrhosis and LRNs, however, 17% of LGDNs revealed shortening of telomeres up to the levels of HGDNs and 7% of LGDNs showed high levels of TA. The levels of TRFL and TA in HGDNs showed no significant differences from those of DNs with HCC foci and HCCs. The shortening of telomeres and reactivation of telomerase occur in the DNs during the early stages of hepatocarcinogenesis, with a significant change in the transition of LGDNs to HGDNs. The characteristics of HGDNs are considered to be closer to those of HCCs.


Insectivorous bats respond to vegetation complexity in urban green spaces.
Structural complexity is known to determine habitat quality for insectivorous bats, but how bats respond to habitat complexity in highly modified areas such as urban green spaces has been little explored. Furthermore, it is uncertain whether a recently developed measure of structural complexity is as effective as field-based surveys when applied to urban environments. We assessed whether image-derived structural complexity (MIG) was as/more effective than field-based descriptors in this environment and evaluated the response of insectivorous bats to structural complexity in urban green spaces. Bat activity and species richness were assessed with ultrasonic devices at 180 locations within green spaces in Vienna, Austria. Vegetation complexity was assessed using 17 field-based descriptors and by calculating the mean information gain (MIG) using digital images. Total bat activity and species richness decreased with increasing structural complexity of canopy cover, suggesting maneuverability and echolocation (sensorial) challenges for bat species using the canopy for flight and foraging. The negative response of functional groups to increased complexity was stronger for open-space foragers than for edge-space foragers. Nyctalus noctula, a species foraging in open space, showed a negative response to structural complexity, whereas Pipistrellus pygmaeus, an edge-space forager, was positively influenced by the number of trees. Our results show that MIG is a useful, time- and cost-effective tool to measure habitat complexity that complemented field-based descriptors. Response of insectivorous bats to structural complexity was group- and species-specific, which highlights the need for manifold management strategies (e.g., increasing or reinstating the extent of ground vegetation cover) to fulfill different species' requirements and to conserve insectivorous bats in urban green spaces.


Optimization and utilization of single chain metallocatanionic vesicles for antibacterial photodynamic therapy (aPDT) against E. coli.
Currently, bacterial infection due to multi-drug-resistant bacteria is one of the foremost problems in public health. Photodynamic therapy plays a significant role against bacterial infection, without causing any side effects. But the photosensitizers are associated with many drawbacks, which lessen their photodynamic efficiency. In this context, the current study describes the synthesis of new metallocatanionic vesicles and employs them in photodynamic therapy. These vesicles were synthesized by using a single-chain cationic metallosurfactant (CuCPC I) and sodium oleate (NaOl) as an anionic component. These vesicles were characterized from conductivity, dynamic light scattering, zeta potential, field emission scanning electron microscopy, and confocal microscopy measurements. Methylene blue (MB) was used as a photosensitizer and its singlet oxygen quantum yield in the presence of these vesicles was determined by irradiating with 650 nm wavelength laser light. These vesicles play a dual-functional role, one helping in delivering the photosensitizer and the second doubling their singlet oxygen production capability due to the presence of metal ions. Antibacterial photodynamic therapy (aPDT) was studied against E. coli bacteria (Gram-negative bacteria). These vesicles also inherit their antibacterial activity and MB-encapsulated metallocatanionic vesicles on irradiation have shown 100% killing efficiency. In summary, we offer metallocatanionic vesicles prepared via a facile approach, which encapsulate a photosensitizer and can be used to combat E. coli infection through photodynamic therapy. We envisage that these synthesized metallocatanionic vesicles will provide a new modification to the catanionic mixture family and could be used for various applications in the future.


Regional initiatives in support of surveillance in East Africa: The East Africa Integrated Disease Surveillance Network (EAIDSNet) Experience.
The East African Integrated Disease Surveillance Network (EAIDSNet) was formed in response to a growing frequency of cross-border malaria outbreaks in the 1990s and a growing recognition that fragmented disease interventions, coupled with weak laboratory capacity, were making it difficult to respond in a timely manner to the outbreaks of malaria and other infectious diseases. The East Africa Community (EAC) partner states, with financial support from the Rockefeller Foundation, established EAIDSNet in 2000 to develop and strengthen the communication channels necessary for integrated cross-border disease surveillance and control efforts. The objective of this paper is to review the regional EAIDSNet initiative and highlight achievements and challenges in its implementation. Major accomplishments of EAIDSNet include influencing the establishment of a Department of Health within the EAC Secretariat to support a regional health agenda; successfully completing a regional field simulation exercise in pandemic influenza preparedness; and piloting a web-based portal for linking animal and human health disease surveillance. The strategic direction of EAIDSNet was shaped, in part, by lessons learned following a visit to the more established Mekong Basin Disease Surveillance (MBDS) regional network. Looking to the future, EAIDSNet is collaborating with the East, Central and Southern Africa Health Community (ECSA-HC), EAC partner states, and the World Health Organization to implement the World Bank-funded East Africa Public Health Laboratory Networking Project (EAPHLNP). The network has also begun lobbying East African countries for funding to support EAIDSNet activities.


Semantic annotation of morphological descriptions: an overall strategy.
Large volumes of morphological descriptions of whole organisms have been created as print or electronic text in a human-readable format. Converting the descriptions into computer- readable formats gives a new life to the valuable knowledge on biodiversity. Research in this area started 20 years ago, yet not sufficient progress has been made to produce an automated system that requires only minimal human intervention but works on descriptions of various plant and animal groups. This paper attempts to examine the hindering factors by identifying the mismatches between existing research and the characteristics of morphological descriptions. This paper reviews the techniques that have been used for automated annotation, reports exploratory results on characteristics of morphological descriptions as a genre, and identifies challenges facing automated annotation systems. Based on these criteria, the paper proposes an overall strategy for converting descriptions of various taxon groups with the least human effort. A combined unsupervised and supervised machine learning strategy is needed to construct domain ontologies and lexicons and to ultimately achieve automated semantic annotation of morphological descriptions. Further, we suggest that each effort in creating a new description or annotating an individual description collection should be shared and contribute to the "biodiversity information commons" for the Semantic Web. This cannot be done without a sound strategy and a close partnership between and among information scientists and biologists.


Alterations in bacterial metabolites, cytokines, and mucosal integrity in the caecum of broilers caused by feed additives and host-related factors.
A total of 2,880 one-day-old male and female broiler chicks from two breeds, Ross308 and Cobb500 were randomly assigned to 72 pens. Broilers were offered three diets: a wheat-soybean diet without (CO), or with either a probiotic (probiotic; 2.4 x 109 CFU/kg diet of Bacillus subtilis DSM32324 and DSM32325 and B. amyloliquefaciens DSM25840) or a phytobiotic (phytobiotic; grape extract with 165 ppm procyanidin and 585 ppm polyphenol) product. The trial was conducted with a 3 × 2 × 2 factorial arrangement of diet, breed and sex in a completely randomized design and consisted of 6 replicate-pens per treatment (40 birds per pen). At day 7, 21, and 35, one chicken per pen was slaughtered for caecal sampling to quantify bacterial metabolites (digesta) as well as evaluate mRNA abundance and histomorphology (tissue). Data were subjected to ANOVA using GLM procedure to evaluate age, diet, breed and sex and their interactions. Spearman's correlation (r) was analyzed between metabolite concentration and mRNA abundance. Overall, the concentration of short chain fatty acids increased with age, while lactate decreased from day 7 to 21 (p < 0.05). The mRNA abundance of IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17α, IL-18, IFN-γ and TGF-β2 increased with age but IL-1β and TNF-α increased in abundance from day 7 to 21 and then decreased (p < 0.05). Abundance of MUC2 and CLDN5 increased after day 21 (p < 0.05). Caecal crypt depth increased with age (p < 0.05). Acidic goblet cell (GC) number peaked at day 21 (p < 0.05), while mixed GC number was not affected by age. A few impacts of breed, diet and interactions on the investigated variables showed no meaningful biological pattern. Propionate positively correlated with all cytokines investigated (r = 0.150-0.548), except TNF-α. Lactate negatively correlated with pro-inflammatory cytokines like IL-1β (r = -0.324). Aging affected caecal histomorphology, bacterial activity and genes responsible for barrier integrity and inflammatory response. This effect could be attributed to the interaction between gut microbiota and immune system as well as the direct effect of metabolites on gut histomorphology and cytokine mRNA abundance.


Hierarchy of evidence: differences in results between non-randomized studies and randomized trials in patients with femoral neck fractures.
There have been a number of non-randomized studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. However, there remains considerable debate about whether the results of non-randomized studies are consistent with the results of randomized, controlled trials. Given the economic burden of hip fractures, it remains essential to identify therapies to improve outcomes; however, whether data from non-randomized studies of an intervention should be used to guide patient care remains unclear. We aimed to determine whether the pooled results of mortality and revision surgery among non-randomized studies were similar to those of randomized trials in studies comparing arthroplasty with internal fixation in patients with femoral neck fractures. We conducted a Medline search from 1969 to June 2002, identifying both randomized and non-randomized studies comparing internal fixation with arthroplasty in patients with femoral neck fractures. Additional strategies to identify relevant articles included Cochrane database, SCISEARCH, textbooks, annual meeting programs, and content experts. We abstracted information on mortality and revision rates in each study and compared the pooled results between non-randomized and randomized studies. In addition, we explored potential reasons for dissimilar results between the two study designs. We identified 140 citations that addressed the general topic of comparison of arthroplasty and internal fixation for hip fracture. Of these, 27 studies met the eligibility criteria, 13 of which were non-randomized studies and 14 of which were randomized trials. Mortality data was available in all 13 non-randomized studies ( n=3108 patients) and in 12 randomized studies ( n=1767 patients). Non-randomized studies overestimated the risk of mortality by 40% when compared with the results of randomized trials (relative risk 1.44 vs 1.04, respectively). Information on revision risk was available in 9 non-randomized studies ( n=2764 patients) and all 14 randomized studies ( n=1901 patients). Both estimates from non-randomized and randomized studies revealed a significant reduction in the risk of revision surgery with arthroplasty compared with internal fixation (relative risk 0.38 vs 0.23, respectively). The reduction in the risk of revision surgery with arthroplasty compared with internal fixation was 62% for non-randomized studies and 77% for randomized trials. Thus, non-randomized studies underestimated the relative benefit of arthroplasty by 19.5%. Non-randomized studies with point estimates of relative risk similar to the pooled estimate for randomized trials all controlled for patient age, gender, and fracture displacement in their comparisons of mortality. We were unable to identify reasons for differences in the revision rate results between the study designs. Similar to other reports in medical subspecialties, non-randomized studies provided results dissimilar to randomized trials of arthroplasty vs internal fixation for mortality and revision rates in patients with femoral neck fractures. Investigators should be aware of these discrepancies when evaluating the merits of alternative surgical interventions, especially when both randomized trials and non-randomized comparative studies are available.


Slowdown in the Decline of Tuberculosis Rates in California, 2000-2016.
To determine the impact of the 2007-2009 economic crisis on tuberculosis (TB) trends among California residents. We analyzed available data from 4 different population-representative data sets. We used time charts, trend lines, and change-point detection tests during 2000 to 2016 to describe TB trends in California. We found statistically significant changes in California TB trends with the time of the onset of the economic downturn based on age-adjusted TB case rates and TB mortality rates, crude rate of TB hospitalizations, and self-reported TB. Change on TB incidence was especially apparent among racial/ethnic minority groups. To our knowledge, changes in TB trends in the United States matching in time with the 2007-2009 economic crisis have not been previously reported. This study identified a slowdown in the decline of TB rates by 2007 to 2009 and provides new knowledge on TB trends that can be used to achieve California's goal of eliminating TB by 2040 and in the prevention and control of TB in the United States.


Safety and feasibility of transjugular intrahepatic portosystemic shunt in elderly patients with liver cirrhosis and refractory ascites.
The management of patients with refractory ascites (RA) is challenging, particularly at higher age. Transjugular intrahepatic portosystemic shunt (TIPS) is an established treatment for RA, but safety data in elderly patients are rare. Our aim was to evaluate the safety and feasibility of TIPS in elderly patients with RA. Overall, 160 consecutive cirrhotic patients receiving a TIPS for RA at Hannover Medical School between 2012 and 2018 were considered for this retrospective analysis. Periinterventional complications such as acute-on-chronic liver failure (ACLF) as well as survival were compared between patients <65 and ≥65 years. Propensity score matching was conducted to match elderly TIPS patients and patients treated with paracentesis. A number of 53 out of the 160 patients were ≥65 years (33%). Periinterventional course in those ≥65 years appeared to be slightly more complicated than in <65 years as reflected by a significantly longer hospital stay (p = 0.030) and more ACLF-episodes (21% vs. 9%; p = 0.044). 28-day mortality was similar between both groups (p = 0.350), whereas survival of the younger patients was significantly higher at 90 days (p = 0.029) and numerically higher at 1 year (p = 0.171). In the multivariate analysis age ≥65 years remained an independent predictor for 90-day mortality (HR: 2.58; p = 0.028), while it was not associated with 28-day and 1-year survival. Importantly, after matching for potential confounders 1-year survival was similar in elderly patients if treated with TIPS or paracentesis (p = 0.419). TIPS placement in elderly patients with RA appears to be slightly more complicated compared to younger individuals, but overall feasible and at least not inferior to paracentesis.


Interval jejunoileal bypass reduces the morbidity and mortality of Roux-en-Y gastric bypass in the super-obese.
Among Roux-en-Y gastric bypass (RYGB) patients, large male patients carry the greatest risk for severe, life-threatening complications. The higher complication rate is partly related to large amounts of intra-abdominal fat that increases the technical difficulty of the RYGB. In order to minimize the risk for complications, we established a staged approach for weight loss surgery for high-risk, super-obese patients. Patients with intra-abdominal fat at exploration which precluded the performance of RYGB underwent jejunoileal bypass (JIB). Following an initial period of weight loss (6-24 months), they were converted to a RYGB during a second operation. Twenty-four patients underwent initial JIB that was associated with a major complication rate of 8.3 per cent (2/24) and no mortality. Eight patients lost 53.4 +/- 6.3 kg prior to their conversion to RYGB (mean, 14.1 months). There was one major complication (12%) and no deaths (0%). Following RYGB, an additional period of weight loss resulted in overall excess weight loss (EWL) totaling 62 per cent. A two-step procedure is a safe and effective approach for minimizing complications for high-risk patients undergoing RYGB. The initial JIB was associated with low morbidity and no mortality, and the follow-up RYGB procedure was a technically simple operation that could be performed with few complications.


[Medical treatment of ovarian malignant germ cell tumors in the adult].
Malignant ovarian germ cell tumors are infrequent neoplasms that usually affect young and otherwise healthy females. The outcome of patients has been significantly improved by the introduction of cisplatin-based chemotherapy. After conservative surgery which both establishes the diagnostic and initiates therapy, the postoperative management should be adapted to histological type as well as to tumor stage. In patients with nonseminomatous germ cell tumors, the standard treatment is a combination of bleomycin, etoposide and cisplatin (BEP protocol). The number of cycles to be given is 3 when surgery is optimal, and 4 in patients with residual or metastatic disease. In patients with pure dysgerminomas, 4 cycles of BEP are the optimal treatment for advanced stages. In early stages, the alternative to chemotherapy (3 cycles of BEP) is radiotherapy, typically given to the ipsilateral hemipelvis and para-aortic nodes. Results are satisfactory with a long-term survival rate ranging from 80 to 100%, and a minimal toxicity yielding a reasonable probability of having normal offspring.


Manipulating Crystallization of Organolead Mixed-Halide Thin Films in Antisolvent Baths for Wide-Bandgap Perovskite Solar Cells.
Wide-bandgap perovskite solar cells (PSCs) based on organolead (I, Br)-mixed halide perovskites (e.g., MAPbI2Br and MAPbIBr2 perovskite with bandgaps of 1.77 and 2.05 eV, respectively) are considered as promising low-cost alternatives for application in tandem or multijunction photovoltaics (PVs). Here, we demonstrate that manipulating the crystallization behavior of (I, Br)-mixed halide perovskites in antisolvent bath is critical for the formation of smooth, dense thin films of these perovskites. Since the growth of perovskite grains from a precursor solution tends to be more rapid with increasing Br content, further enhancement in the nucleation rate becomes necessary for the effective decoupling of the nucleation and the crystal-growth stages in Br-rich perovskites. This is enabled by introducing simple stirring during antisolvent-bathing, which induces enhanced advection transport of the extracted precursor-solvent into the bath environment. Consequently, wide-bandgap planar PSCs fabricated using these high quality mixed-halide perovskite thin films, Br-rich MAPbIBr2, in particular, show enhanced PV performance.


Inositol phosphate formation in fMet-Leu-Phe-stimulated human neutrophils does not require an increase in the cytosolic free Ca2+ concentration.
The accumulation of inositol phosphates in myo-[3H]inositol-labelled human neutrophils stimulated with the chemotactic peptide fMet-Leu-Phe was measured. The challenge with the chemotactic peptide caused the generation of inositol monophosphate (InsP), inositol bisphosphate (InsP2) and inositol trisphosphate (InsP3). The formation of the three inositol phosphates followed a differential time course: InsP3 accumulated very rapidly and transiently, whereas InsP increased steadily for more than 2 min. Inositol phosphate formation was only partially decreased by procedures which prevented the fMet-Leu-Phe-dependent increase of cytosolic free Ca2+ concentration.


Metalation of polyamine dendrimers with ethynylcobalticenium for the construction of mono- and heterobimetallic polycationic metallodendrimers.
The introduction of robust redox groups at the periphery of common amine-terminated dendrimers is of interest in the design of dendritic nanobatteries, sensors, and redox catalysts. Here we are applying the recently discovered uncatalyzed hydroamination of ethynylcobalticenium, a mild "green" reaction that quantitatively yields trans-enamines without the formation of any byproduct, to functionalize dendrimers that are terminated with primary or secondary amino groups. Poly(amido amine) (PAMAM) dendrimers terminated by primary amino groups and arene-centered dendrimers terminated by secondary amino groups yield dendrimers that contain up to 81 trans-enamine-cobalticenium termini using this reaction. The hydroamination reaction was also conducted with dendrimers that contained ferrocenylmethylamino groups, which yielded dendrimers that contained both ferrocenyl and cobalticenium termini. The size of the dendrimers was investigated using both dynamic light scattering and diffusion-ordered spectroscopy (DOSY) (1)H NMR spectroscopy, and the number of electrons involved in heterogeneous multielectron transfers at electrodes was searched by cyclic voltammetry. The latter works well up to the 27-branch dendrimer, whereas the 81-dendrimer yielded a result in an excess amount (110 electrons) owing to adsorption onto the cathode that becomes all the more significant as the metallodendrimer size increases.


Indirect effects drive coevolution in mutualistic networks.
Ecological interactions have been acknowledged to play a key role in shaping biodiversity. Yet a major challenge for evolutionary biology is to understand the role of ecological interactions in shaping trait evolution when progressing from pairs of interacting species to multispecies interaction networks. Here we introduce an approach that integrates coevolutionary dynamics and network structure. Our results show that non-interacting species can be as important as directly interacting species in shaping coevolution within mutualistic assemblages. The contribution of indirect effects differs among types of mutualism. Indirect effects are more likely to predominate in nested, species-rich networks formed by multiple-partner mutualisms, such as pollination or seed dispersal by animals, than in small and modular networks formed by intimate mutualisms, such as those between host plants and their protective ants. Coevolutionary pathways of indirect effects favour ongoing trait evolution by promoting slow but continuous reorganization of the adaptive landscape of mutualistic partners under changing environments. Our results show that coevolution can be a major process shaping species traits throughout ecological networks. These findings expand our understanding of how evolution driven by interactions occurs through the interplay of selection pressures moving along multiple direct and indirect pathways.


Psychological stress-induced, IDO1-dependent tryptophan catabolism: implications on immunosuppression in mice and humans.
It is increasingly recognized that psychological stress influences inflammatory responses and mood. Here, we investigated whether psychological stress (combined acoustic and restraint stress) activates the tryptophan (Trp) catabolizing enzyme indoleamine 2,3-dioxygenase 1(IDO1) and thereby alters the immune homeostasis and behavior in mice. We measured IDO1 mRNA expression and plasma levels of Trp catabolites after a single 2-h stress session and in repeatedly stressed (4.5-days stress, 2-h twice a day) naïve BALB/c mice. A role of cytokines in acute stress-induced IDO1 activation was studied after IFNgamma and TNFalpha blockade and in IDO1(-/-) mice. RU486 and 1-Methyl-L-tryptophan (1-MT) were used to study role of glucocorticoids and IDO1 on Trp depletion in altering the immune and behavioral response in repeatedly stressed animals. Clinical relevance was addressed by analyzing IDO1 activity in patients expecting abdominal surgery. Acute stress increased the IDO1 mRNA expression in brain, lung, spleen and Peyer's patches (max. 14.1+/-4.9-fold in brain 6-h after stress) and resulted in a transient depletion of Trp (-25.2+/-6.6%) and serotonin (-27.3+/-4.6%) from the plasma measured 6-h after stress while kynurenine levels increased 6-h later (11.2+/-9.3%). IDO1 mRNA up-regulation was blocked by anti-TNFalpha and anti-IFNgamma treatment. Continuous IDO1 blockade by 1-MT but not RU486 treatment normalized the anti-bacterial defense and attenuated increased IL-10 inducibility in splenocytes after repeated stress as it reduced the loss of body weight and behavioral alterations. Moreover, kynurenic acid which remained increased in 1-MT treated repeatedly stressed mice was identified to reduce the TNFalpha inducibility of splenocytes in vitro and in vivo. Thus, psychological stress stimulates cytokine-driven IDO1 activation and Trp depletion which seems to have a central role for developing stress-induced immunosuppression and behavioral alteration. Since patients showed Trp catabolism already prior to surgery, IDO is also a possible target enzyme for humans modulating immune homeostasis and mood.


Vascularization in tissue engineering.
Tissue engineering has been an active field of research for several decades now. However, the amount of clinical applications in the field of tissue engineering is still limited. One of the current limitations of tissue engineering is its inability to provide sufficient blood supply in the initial phase after implantation. Insufficient vascularization can lead to improper cell integration or cell death in tissue-engineered constructs. This review will discuss the advantages and limitations of recent strategies aimed at enhancing the vascularization of tissue-engineered constructs. We will illustrate that combining the efforts of different research lines might be necessary to obtain optimal results in the field.


Quantum Probability's Algebraic Origin.
Max Born's statistical interpretation made probabilities play a major role in quantum theory. Here we show that these quantum probabilities and the classical probabilities have very different origins. Although the latter always result from an assumed probability measure, the first include transition probabilities with a purely algebraic origin. Moreover, the general definition of transition probability introduced here comprises not only the well-known quantum mechanical transition probabilities between pure states or wave functions, but further physically meaningful and experimentally verifiable novel cases. A transition probability that differs from 0 and 1 manifests the typical quantum indeterminacy in a similar way as Heisenberg's and others' uncertainty relations and, furthermore, rules out deterministic states in the same way as the Bell-Kochen-Specker theorem. However, the transition probability defined here achieves a lot more beyond that: it demonstrates that the algebraic structure of the Hilbert space quantum logic dictates the precise values of certain probabilities and it provides an unexpected access to these quantum probabilities that does not rely on states or wave functions.


Directional heat dissipation across the interface in anatase-rutile nanocomposites.
Understanding the structures and properties of interfaces in (nano-)composites helps to reveal their important influence on reactivity and overall performance. TiO2 is a technologically important material, and anatase/rutile TiO2 composites have been shown to display enhanced photocatalytic performance over pure anatase or rutile TiO2. This has been attributed to a synergistic effect between the two phases, but the origin of this effect as well as the structure of the interface has not been established. Using Raman spectroscopy, here we provide evidence of distinct differences in the thermal properties of the anatase and rutile moieties in the composite, with anatase becoming effectively much warmer than the rutile phase under laser irradiation. With the help of first-principles calculations, we analyze the atomic structure and unique electronic properties of the composite and infer possible reasons for the directional heat dissipation across the interface.


Pavlovian conditioning of morphine hyperthermia: assessment of interstimulus interval and CS-US overlap.
The present study examined the effect of interstimulus interval on acquisition of conditioned thermal responses produced by trials in which a light/noise stimulus (CS) was repeatedly paired with infusion of morphine sulphate (US). Rats were implanted with a chronic intravenous catheter for drug delivery and a biotelemetry device for remote monitoring of core body temperature. In experiment 1, different groups received morphine either 0.5 (group P0.5) or 15 min (group P15) after onset of the 15-min CS. A third group was exposed to an identical number of CS and US presentations but in an explicitly unpaired manner (group UP). After repeated exposure to morphine, all groups showed a more rapid rise in body temperature in response to drug infusion. Test presentations of CS alone revealed conditioned hyperthermic responses to CS in groups P0.5 and P15. However, the response of the P15 group was smaller than that of the P0.5 group, suggesting weaker conditioning at the longer interstimulus interval. The contribution of CS-US overlap to the diminished associative strength observed in the P15 group was assessed in experiment 2. Groups P0.5/15 and P0.5/30 received infusions of morphine 0.5 min after onset of a 15- or 30-min CS, respectively. Group P15/30 received morphine 15 min after onset of a 30 min CS, whereas group UP/30 received explicitly unpaired presentations of the US and a 30-min CS. Enhancement of the hyperthermic effect of morphine was observed in all groups after ten conditioning trials. Test presentations of the CS without drug revealed that all paired groups had acquired conditioned hyperthermic responses. These results support the conclusion that drug-induced conditioning can occur at relatively long interstimulus intervals when there is sufficient temporal overlap between the CS and unconditioned response evoked by the drug US.


Planar polarity of multiciliated ependymal cells involves the anterior migration of basal bodies regulated by non-muscle myosin II.
Motile cilia generate constant fluid flow over epithelial tissue, and thereby influence diverse physiological processes. Such functions of ciliated cells depend on the planar polarity of the cilia and on their basal bodies being oriented in the downstream direction of fluid flow. Recently, another type of basal body planar polarity, characterized by the anterior localization of the basal bodies in individual cells, was reported in the multiciliated ependymal cells that line the surface of brain ventricles. However, little is known about the cellular and molecular mechanisms by which this polarity is established. Here, we report in mice that basal bodies move in the apical cell membrane during differentiation to accumulate in the anterior region of ependymal cells. The planar cell polarity signaling pathway influences basal body orientation, but not their anterior migration, in the neonatal brain. Moreover, we show by pharmacological and genetic studies that non-muscle myosin II is a key regulator of this distribution of basal bodies. This study demonstrates that the orientation and distribution of basal bodies occur by distinct mechanisms.


Spatial organization of visuomotor reflexes in Drosophila.
In most animals, the visual system plays a central role in locomotor guidance. Here, we examined the functional organization of visuomotor reflexes in the fruit fly, Drosophila, using an electronic flight simulator. Flies exhibit powerful avoidance responses to visual expansion centered laterally. The amplitude of these expansion responses is three times larger than those generated by image rotation. Avoidance of a laterally positioned focus of expansion emerges from an inversion of the optomotor response when motion is restricted to the rear visual hemisphere. Furthermore, motion restricted to rear quarter-fields elicits turning responses that are independent of the direction of image motion about the animal's yaw axis. The spatial heterogeneity of visuomotor responses explains a seemingly peculiar behavior in which flies robustly fixate the contracting pole of a translating flow field.


Transcriptional regulation of C/EBPdelta in G(0) growth-arrested mouse mammary epithelial cells.
Little is known about the control of cell cycle exit/G(0) entry, or the regulation of genes that are expressed during G(0). In this report we used primer extension analysis to demonstrate the high level of C/EBPdelta mRNA expression in G(0) growth-arrested HC11 mouse mammary epithelial cells and to identify the C/EBPdelta transcription start site. The C/EBPdelta gene transcription rate and promoter activity are both highly induced in G(0) growth-arrested HC11 cells. The C/EBPdelta gene promoter also exhibits G(0)-specific autoregulation. In contrast, the C/EBPdelta promoter activity decreases in G(0) growth-arrested NIH 3T3 cells. These data indicate that C/EBPdelta is among a relatively small number of genes actively transcribed during G(0) growth arrest. C/EBPdelta may regulate the expression of genes implicated in the initiation or maintenance of mammary epithelial cell G(0) growth arrest.


The influence of staff training and education on prosthetic and orthotic service quality: A scoping review.
Education and training in prosthetics and orthotics typically comply with International Society for Prosthetics and Orthotics standards based on three categories of prosthetic and orthotic professionals. This scoping study sought to describe the evidence base available to answer the question, How are prosthetic and orthotic services influenced by the training of staff providing them? Scoping review. A structured search of the peer-reviewed literature catalogued in major electronic databases yielded 3039 papers. Following review of title and abstract, 93 articles were considered relevant. Full-text review reduced this number to 25. Only two articles were identified as providing direct evidence of the effects of training and education on service provision. While both suggested that there was an impact, it is difficult to see how the more specific conclusions of either could be generalised. The other 23 articles provide a useful background to a range of issues including the specification of competencies that training programmes should deliver (3 articles), descriptions of a range of training programmes and the effects of training and education on student knowledge and skills. Although it is considered axiomatic, the service quality is dependent on practitioner education and training. There is insufficient evidence to establish whether levels of training and education in prosthetics and orthotics have an effect on the quality of prosthetic and orthotic services. Clinical relevance There is very little evidence about the effects of training and education of prosthetists and orthotists on service quality. While this is a somewhat negative finding, we feel that it is important to bring this to the attention of the prosthetics and orthotics community.


Multiple GAL pathway gene clusters evolved independently and by different mechanisms in fungi.
A notable characteristic of fungal genomes is that genes involved in successive steps of a metabolic pathway are often physically linked or clustered. To investigate how such clusters of functionally related genes are assembled and maintained, we examined the evolution of gene sequences and order in the galactose utilization (GAL) pathway in whole-genome data from 80 diverse fungi. We found that GAL gene clusters originated independently and by different mechanisms in three unrelated yeast lineages. Specifically, the GAL cluster found in Saccharomyces and Candida yeasts originated through the relocation of native unclustered genes, whereas the GAL cluster of Schizosaccharomyces yeasts was acquired through horizontal gene transfer from a Candida yeast. In contrast, the GAL cluster of Cryptococcus yeasts was assembled independently from the Saccharomyces/Candida and Schizosaccharomyces GAL clusters and coexists in the Cryptococcus genome with unclustered GAL paralogs. These independently evolved GAL clusters represent a striking example of analogy at the genomic level. We also found that species with GAL clusters exhibited significantly higher rates of GAL pathway loss than species with unclustered GAL genes. These results suggest that clustering of metabolic genes might facilitate fungal adaptation to changing environments both through the acquisition and loss of metabolic capacities.


Dynamic Changes in the Follicular Transcriptome and Promoter DNA Methylation Pattern of Steroidogenic Genes in Chicken Follicles throughout the Ovulation Cycle.
The molecular mechanisms associated with follicle maturation and ovulation are not well defined in avian species. In this study, we used RNA-seq to study the gene expression profiles of the chicken follicles from different developmental stages (pre-hierarchical, pre-ovulatory and post-ovulatory). Transcriptomic analysis revealed a total of 1,277 and 2,310 genes were differentially expressed when follicles progressed through the pre-hierarchical to hierarchical and pre-ovulatory to post-ovulatory transitions, respectively. The differentially expressed genes (DEG) were involved in signaling pathways such as adherens junction, apoptosis and steroid biosynthesis. We further investigated the transcriptional regulation of follicular steroidogenesis by examining the follicle-specific methylation profiles of Star (steroidogenic acute regulatory protein), Cyp11a1 (cytochrome P450, family 11, subfamily a, polypeptide 1) and Hsd3b (hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 1), genes encoding the key enzymes for progesterone synthesis. The varied patterns of DNA methylation in proximal promoters of Star and Cyp11a1but not Hsd3b in different follicles could play a major role in controlling gene expression as well as follicular steroidogenic activity. Finally, the promoter-reporter analysis suggests that TGF-β could be involved in the regulation of Hsd3b expression during ovulation. Together, current data not only provide novel insights into the molecular mechanisms of follicular physiology in chicken follicles, but also present the first evidence of epigenetic regulation of ovarian steroidogenesis in avian species.


Diabetes and work: The need of a close collaboration between diabetologist and occupational physician.
The Italian Society of Occupational Medicine (SIML), the Italian Diabetes Society (SID) and the Association of Diabetologists (AMD) joined a working group that produced a consensus paper aimed to assess the available evidence regarding the interplay between specific working conditions, including shift- and night-time work, working activities at high risk of accidents and work at heights, working tasks requiring high-energy expenditure, working activities at extreme temperatures and diabetes. Diabetes is a group of metabolic disorders caused by defects in insulin secretion and/or action affecting millions of people worldwide, many of whom are or wish to be active members of the workforce. Although diabetes, generally, does not prevent a person from properly performing his/her working tasks, disease complications can significantly compromise a person's ability to work. Therefore, it appears evident the need to understand the relationship between occupational risk factors and diabetes. The working group included in the document some practical recommendations useful to ensure diabetic workers the possibility to safely and effectively undertake their jobs and to adequately manage and treat their disease, also in the workplace. In this perspective concerted action of all the workplace preventive figures, occupational physicians and diabetologists should be strongly encouraged. Further studies are necessary to define workplace-based interventions, which should be minimally invasive towards the work organization, allowing diabetic workers to fully realize their work skills while improving their wellbeing at work.