Diverse Pharmacological Potential of different Substituted Pyrazole Derivatives.
The chemistry of heterocyclic compounds has been a topic of research interest. Some five-membered heterocyclic compounds have been the subject of extensive research due to their different types of pharmacological effects. The five-membered nitrogen-containing heterocyclic compounds pyrazole, pyrazoline, and pyrazolone derivatives have a lot of interest in the fields of medical and agricultural chemistry due to their diverse spectrum of therapeutic activities. Various substituted pyrazole, pyrazoline, and pyrazolone compounds exhibited diverse pharmacological effects like Anti-microbial, anti-inflammatory, anti-tubercular, anti-fungal, anti-malarial, anti-di-abetic, diuretic, anti-depressant, anticonvulsant, antioxidant, anti-leishmanial, antidiabetic, and antiviral, etc. In recent decades, the synthesis of numerous pyrazole, pyrazoline, and pyrazolone derivatives by different synthetic methods as well as research into their chemical and biological behavior have become more important. This review focuses on synthetic methods of the pyrazole, pyrazoline, and pyrazolone derivatives, which have significant biological properties and a variety of applications.


Enhancement of vascular endothelial growth factor's angiogenic capacity by the therapeutic modulation of notch signalling improves tram flap survival in rats submitted to nicotine.
Smoke of cigarettes, and specifically nicotine, has been shown to diminish pedicled transverse rectus abdominis musculocutaneous (TRAM) flap survival. Considering that Notch signalling through its ligand Delta-like 4 (Dll4) functions as anti-angiogenic factor by inhibiting the pro-angiogenic effects of vascular endothelial growth factor (VEGF), it is hypothesised that inhibition of the Notch would promote angiogenesis and increase TRAM flap survival in rats submitted to nicotine. Twenty rats were treated with nicotine for 28 days preoperatively. Thereafter, a pedicled TRAM flap was created in all animals. The Notch inhibitor N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine-t-butyl-ester was administered in animals of the treatment group. Animals in the control group were given the same amount of solvent. Five days after the surgery, viable flap areas were determined. Skin samples were evaluated for VEGF and Dll4 mRNA levels. Immunohistochemical analysis was used for the assessment of endothelial Dll4 expression. Vascular density was determined histologically. Plasma levels of VEGF and Dll4 were measured. A significant improvement in TRAM flap surviving area was observed in the treatment group (53.50 ± 14.25%) compared with the controls (32.20 ± 9.15%). Immunohistochemical analysis revealed a significant increase in the number of Dll4 stained vessels in animals of the treatment group (9.2 ± 1.6) in comparison with the controls (5.7 ± 1.9). VEGF mRNA levels (0.22 ± 0.08) in the treatment group were significantly lower than those in the control group (0.36 ± 0.09). Notch inhibition significantly improved TRAM flap survival in animals exposed to nicotine by promoting VEGF-induced angiogenesis.


TNF-alpha single nucleotide polymorphisms in atopic dermatitis.
Tumor necrosis factor-alpha (TNF-α) could be considered as potential biomarkers in atopic dermatitis (AD), while its level could be influenced by cytokine single gene polymorphisms (SNP). This study was performed in 89 pediatric patients with AD and 137 controls to assess polymorphisms of the TNF-α gene at positions -308 and -238, using the polymerase chain reaction and the sequence-specific primers method. The highest positive allelic association that made the patients susceptible to AD was seen for TNF-α -238/G (p<0.001) and TNF-α -308/G (p = 0.003). The GG genotypes at TNF-α -238 and TNF-α -308, were both significantly higher in the patients with AD, compared to the controls (p<0.01). The GG haplotype at TNF-α (-308,-238) was seen in 92.7% of the patients, which was significantly higher than the controls (p<0.001), while a negative haplotypic association with AD was seen for TNF-α (-308, -238) AG and GA (p<0.01). This study showed that the AG genotype of TNF-α -308, associated with a high production of cytokines, was significantly decreased in patients with AD, while the low-producing GG genotype, which could lead to low production of TNF-α, was over-expressed in the atopic patients.


Dynamics, multistability, and crisis analysis of a sine-circle nontwist map.
We propose a one-dimensional dynamical system, the sine-circle nontwist map, that can be considered a local approximation of the standard nontwist map and an extension of the paradigmatic sine-circle map. The map depends on three parameters, exhibiting a simple mathematical form but with a rich dynamical behavior. We identify periodic, quasiperiodic, and chaotic solutions for different parameter sets with the Lyapunov exponent and Slater's theorem. From the bifurcation analysis, we determine two bifurcation lines, those that depend on just two of the control parameters, for which the bifurcation that occurs is of the saddle-node type. In order to investigate multistability, we analyze the bifurcation diagrams in the two directions of parameter variation and we observe some regions of hysteresis, representing the coexistence of different attractors. We also analyze different multistable scenarios, as single attractor, coexistence of periodic attractors, coexistence of chaotic and periodic attractors, chaotic behavior, and coexistence of different chaotic bands, by the Lyapunov exponent and the analysis of the domain occupied by the solutions. From the parameter spaces constructed, we observe the prevalence of single attractor and only chaotic behavior scenarios. The multistable scenario is, mostly, formed by different periodic attractors. Lastly, we analyze the crisis in chaotic attractors and we identify the interior and the boundary crisis. From our results, the boundary crisis plays a key role for the extinction of multistability.


Improved detection of rough defects for ultrasonic nondestructive evaluation inspections based on finite element modeling of elastic wave scattering.
Defects which possess rough surfaces greatly affect ultrasonic wave scattering behavior, usually reducing the magnitude of reflected signals. Understanding and accurately predicting the influence of roughness on signal amplitudes is crucial, especially in nondestructive evaluation (NDE) for the inspection of safety-critical components. An extension of Kirchhoff theory has formed the basis for many practical applications; however, it is widely recognized that these predictions are pessimistic because of analytical approximations. A numerical full-field modeling approach does not fall victim to such limitations. Here, a finite element (FE) modeling approach is used to develop a realistic methodology for the prediction of expected backscattering from rough defects. The ultrasonic backscatter from multiple rough surfaces defined by the same statistical class is calculated for normal and oblique incidence. Results from FE models are compared with Kirchhoff theory predictions and experimental measurements to establish confidence in the new approach. At lower levels of roughness, excellent agreement is observed between Kirchhoff theory, FE, and experimental data, whereas at higher values, the pessimism of Kirchhoff theory is confirmed. An important distinction is made between the total, coherent, and diffuse signals and it is observed, significantly, that the total signal amplitude is representative of the information obtained during an inspection. This analysis provides a robust basis for a less sensitive, yet safe, threshold for inspection of rough defects.


An uncommon multicentered ZnI-ZnI bond-based MOF for CO2 fixation with aziridines/epoxides.
A novel cluster-based MOF with uncommon multicentered ZnI-ZnI bonds {[K1.2Na2.8ZnI8(HL)12]·4H2O}n (HL = tetrazole monoanion) (1) was synthesized, which showed higher stability than the reported ZnI-ZnI bonded compounds. Moreover, 1 can effectively and circularly catalyze the cyclization of CO2 and aziridines or epoxides with five substituent groups. Importantly, this is the first time that the catalytic properties of MOFs with multicentered metal-metal bonded clusters as the catalyst have been studied.


Rad52 multimerization is important for its nuclear localization in Saccharomyces cerevisiae.
Rad52 is essential for all homologous recombination and DNA double strand break repair events in Saccharomyces cerevisiae. This protein is multifunctional and contains several domains that allow it to interact with DNA as well as with different repair proteins. However, it has been unclear how Rad52 enters the nucleus. In the present study, we have used a combination of mutagenesis and sequence analysis to show that Rad52 from S. cerevisiae contains a single functional pat7 type NLS essential for its nuclear localization. The region containing the NLS seems only to be involved in nuclear transport as it plays no role in repair of MMS-induced DNA damage. The NLS in Rad52 is weak, as monomeric protein species that harbor this NLS are mainly located in the cytosol. In contrast, multimeric protein complexes wherein each subunit contains a single NLS(Rad52) sort efficiently to the nucleus. Based on the results we propose a model where the additive effect of multiple NLS(Rad52) sequences in a Rad52 ring-structure ensures efficient nuclear localization of Rad52.


Pharmacokinetics and pharmacodynamics of rocuronium bromide in adult patients.
In seven patients (M/F: 4:3) rocuronium 0.6 mg kg-1 was given after the induction of anaesthesia with propofol, and during maintenance with N2O/O2, halothane 0.5% and alfentanil 60-90 micrograms kg-1 h-1. Intubation conditions were scored at 60 s and lag time, onset time, maximal block achieved, recovery to 25% of T1, and Recovery Index, were measured using a Relaxograph. Blood samples were taken over a 300 min period and analysed for rocuronium. Intubating conditions at 60 s were excellent in all patients. Mean clearance was 5.2 ml kg-1 min-1, the terminal half-life was 69 min and distribution volume at steady state was 0.22 litre kg-1. Cumulative urinary excretion was around 18% within 24 h.


Patient safety through patient education in a charity medical program.
As perioperative registered nurses, we tend to think of patient safety as protection from injury immediately prior to, during, and immediately after surgical procedures. However, patient safety extends beyond discharge and is a measurement of how effective patient teaching is in attaining desired outcomes. This article describes the Fresh Start program, the patient population we serve, and our planning cycle. It also describes the use of the "Perioperative Patient-Focused Model" to deliver care and the relationship between patient education and safety. A description of challenges encountered in the clinical setting examines their role as critical factors in the education and safety of patients, and identifies possible ways to address them.


Hemodynamic signal changes during saliva and water swallowing: a near-infrared spectroscopy study.
Here, we compared the hemodynamic response observed during swallowing of water or saliva using near-infrared spectroscopy (NIRS). Sixteen healthy adults swallowed water or saliva in a randomized order. Relative concentration changes in oxygenated and deoxygenated hemoglobin during swallowing were assessed. Both swallowing tasks led to the strongest NIRS signal change over the bilateral inferior frontal gyrus. Water swallowing led to a stronger activation over the right hemisphere while the activation focus for saliva swallowing was stronger left lateralized. The NIRS time course also differed between both swallowing tasks especially at the beginning of the tasks, which might be a sign of differences in task effort. Our results show that NIRS is a sensitive measure to reveal differences in the topographical distribution and time course of the hemodynamic response between distinct swallowing tasks and might be therefore an adequate diagnostic and therapy tool for swallowing difficulties.


Cloning of the Syrian hamster p53 gene: structural and functional characterization of the upstream promoter region.
We isolated the p53 gene from Syrian hamster embryo cells by cosmid cloning procedures. The organization of the hamster p53 gene was similar to that of other mammalian p53 genes; it had 11 exons, a noncoding exon 1, and a long intron 1 (about 6.5 kb). The upstream p53 promoter was isolated, and the nucleotide sequence of a region encompassing 694 bp upstream from the exon/intron 1 boundary plus the first 6 nt of intron 1 was determined. This genomic region was highly homologous to those of mice and humans but contained a repetitive element not present in either species. Sequence comparisons with the murine and human promoters revealed the presence of similar transcription-factor binding motifs mapping within a 431-bp SacI-PstI fragment. Transient transfection assays of primary Syrian hamster embryo cells and neoplastic cell lines with recombinant constructs in which the SacI-PstI fragment was placed upstream of a bacterial chloramphenicol acetyltransferase (CAT) gene revealed the efficient expression of CAT activity. Primer extension analyses identified several putative transcription initiation sites within the p53 upstream promoter, the strongest of which was located 315 bp upstream from the exon/intron 1 junction and about 30 bp upstream from the region encompassing the regulatory motifs.


Drawing a distinction between familiar and unfamiliar voice processing: A review of neuropsychological, clinical and empirical findings.
Thirty years on from their initial observation that familiar voice recognition is not the same as unfamiliar voice discrimination (van Lancker and Kreiman, 1987), the current paper reviews available evidence in support of a distinction between familiar and unfamiliar voice processing. Here, an extensive review of the literature is provided, drawing on evidence from four domains of interest: the neuropsychological study of healthy individuals, neuropsychological investigation of brain-damaged individuals, the exploration of voice recognition deficits in less commonly studied clinical conditions, and finally empirical data from healthy individuals. All evidence is assessed in terms of its contribution to the question of interest - is familiar voice processing distinct from unfamiliar voice processing. In this regard, the evidence provides compelling support for van Lancker and Kreiman's early observation. Two considerations result: First, the limits of research based on one or other type of voice stimulus are more clearly appreciated. Second, given the demonstration of a distinction between unfamiliar and familiar voice processing, a new wave of research is encouraged which examines the transition involved as a voice is learned.


Retinal Dialysis and Associated Rhegmatogenous Retinal Detachment in Patients with Neurofibromatosis Type 1: A Case Series.
While ophthalmic manifestations of neurofibromatosis type 1 (NF1), including iris Lisch nodules and optic gliomas have been well described, retinal involvement in these patients has yet to be established. Characterizing the relationship between NF1 and the retina is necessary to optimize outcomes for these patients. Independent chart review of NF1 patients was conducted. Chart review yielded four patients, with a history of NF1, with subsequent retinal dialysis and rhegmatogenous retinal detachment. These four patients presented to our institution with a rhegmatogenous retinal detachment secondary to a retinal dialysis with no history of trauma. These patients also demonstrated hyperreflective choroidal abnormalities on near-infrared reflectance (NIR) imaging and optical coherence tomography (OCT). Seeing that patients diagnosed with NF1 are susceptible to various ocular manifestations and pathologies, routine ophthalmic examinations are essential in maintaining their ocular health and minimizing morbidity.


Assessment of left ventricular end-systolic elastance from aortic pressure-left ventricular volume relations.
The left ventricular (LV) end-systolic pressure-volume relation (ESPVR) is a load-insensitive method for evaluating LV contractility, which needs invasive measurement. Some noninvasive methods substitute peak aortic pressure (Ps) for end-systolic LV pressure by assuming there is no difference between these pressures. However, this assumption has not been directly validated. With conductance catheter and dual micromanometers, ESPVRs and the slope (EesLv) were constructed from simultaneous LV pressures (LVP) and volumes, aortic pressures (AOP) and LV volumes (Ees(AO)), and Ps and LV end-ejection volumes (VEE) (Ees(PP-EEV)) during preload reduction in 50 subjects. The ratio of steady-state P(s) over V(EE) (P(S)/V(EE)) was also checked. AOP and LVP displayed differences of 11 +/- 6 and -30 +/- 12 mm Hg at the onset and end-ejection, respectively, and -2 +/- 4 mm Hg at end-systole. Ees(AO) and Ees(LV) were nearly identical: Ees(AO) = 0.97 x Ees(LV) + 0.05, r2 = 0.99. Ees(PP-EEV) correlated with EesLV (EesPP-EEV = 0.57 x EesLV + 0.61, r2 = 0.46) but with much more scatter. Ps/V(EE) correlated worst with Ees(LV). Central AOP can be substituted for LVP to derive EesLV. Other estimation methods yield weaker and poor correlations to directly measured Ees.


Selection at work in self-incompatible Arabidopsis lyrata: mating patterns in a natural population.
Identification and characterization of the self-incompatibility genes in Brassicaceae species now allow typing of self-incompatibility haplotypes in natural populations. In this study we sampled and mapped all 88 individuals in a small population of Arabidopsis lyrata from Iceland. The self-incompatibility haplotypes at the SRK gene were typed for all the plants and some of their progeny and used to investigate the realized mating patterns in the population. The observed frequencies of haplotypes were found to change considerably from the parent generation to the offspring generation around their deterministic equilibria as determined from the known dominance relations among haplotypes. We provide direct evidence that the incompatibility system discriminates against matings among adjacent individuals. Multiple paternity is very common, causing mate availability among progeny of a single mother to be much larger than expected for single paternity.


Update on Clostridium difficile-induced colitis, Part 1.
Recent findings on the epidemiology, pathogenesis, clinical manifestations, diagnosis, and treatment of Clostridium difficile-induced colitis (CDIC) are discussed. CDIC is a gastrointestinal disorder that results from colonization by and overgrowth of C. difficile. Among patients in the community who are treated with an oral antimicrobial, only 1 to 3 individuals per 100,000 develop CDIC, compared with as many as 1 per 100 hospitalized patients treated with an antimicrobial. The requirements for CDIC are (1) a readily available source of C. difficile; (2) exposure to drugs, most commonly certain antimicrobials, that disrupt the normal colonic microflora; (3) production of the requisite cytotoxins by the C. difficile strain colonizing the colon; and (4) the presence of individual risk factors, including advanced age, severe underlying illness, and a prolonged hospital stay. Among the varied clinical manifestations of CDIC, diarrhea is predominant and is often the sole symptom. In more severe cases, fever and leukocytosis are also present. The formation of pseudomembranous plaques is pathognomonic but relatively infrequent. Presumptive diagnosis is usually based on a positive cytotoxin assay result in the symptomatic patient. Patients who respond to discontinuation of the inciting drug or drugs should not be treated indiscriminately with antimicrobials. Asymptomatic carriers should not be treated, and a period of watchful waiting may be advisable in mild cases. When treatment is necessary, oral metronidazole is the agent of choice in all but the most severe cases. Whether oral metronidazole is therapeutically equivalent to oral vancomycin in severe CDIC is controversial. Regardless of the antimicrobial used, some patients suffer a recurrence of CDIC and a few have several relapses. There have been no comparative studies of treatment for relapsing CDIC. Of the investigational treatments, the tiacumicin macrolides and the yeast Saccharomyces boulardii appear most promising. Diagnostic assays based on the polymerase chain reaction should allow more timely intervention. Health care professionals who improve their understanding of CDIC will be better able to recognize the disorder, select the best treatment, and perhaps reduce the frequency of CDIC in hospitalized patients by working to alter patterns of antimicrobial use.


Physiotherapy interventions may relieve pain in individuals with central neuropathic pain: a systematic review and meta-analysis of randomised controlled trials.
To evaluate the effectiveness of any form of physiotherapy intervention for the management of central neuropathic pain (cNeP) due to any underlying cause. Multiple databases were searched from inception until August 2021. Randomised controlled trials evaluating physiotherapy interventions compared to a control condition on pain among people with cNeP were included. Methodological quality and the quality of evidence were assessed using the Physiotherapy Evidence Database Scale and the Grading of Recommendations, Assessment, Development, and Evaluation tool, respectively. The searches yielded 2661 studies, of which 23 randomised controlled trials met the inclusion criteria and were included in the meta-analyses. Meta-analyses of trials examining non-invasive neurostimulation revealed significant reductions in pain severity due to spinal cord injury (SCI; standardised mean difference (SMD): -0.59 (95% confidence interval [CI]: -1.07, -0.11), p = 0.02) and phantom limb pain (weighted mean difference (WMD): -1.57 (95% CI: -2.85, -0.29), p = 0.02). The pooled analyses of trials utilising acupuncture, transcutaneous electrical nerve stimulation (TENS), and mirror therapy showed significant reductions in pain severity among individuals with stroke (WMD: -1.46 (95% CI: -1.97, -0.94), p < 0.001), multiple sclerosis (SMD: -0.32 (95% CI: -0.57, -0.06), p = 0.01), and phantom limb pain (SMD: -0.74 (95% CI: -1.36, -0.11), p = 0.02), respectively. Exercise was also found to significantly reduce pain among people with multiple sclerosis (SMD: -1.58 (95% CI: -2.85, -0.30), p = 0.02). Evidence supports the use of non-invasive neurostimulation for the treatment of pain secondary to SCI and phantom limb pain. Beneficial pain management outcomes were also identified for acupuncture in stroke, TENS in multiple sclerosis, and mirror therapy in phantom limb pain.


Serum CA125: a tumor marker for monitoring response to treatment and follow-up in patients with non-Hodgkin's lymphoma.
Serum CA125 is an important prognostic factor in patients with non-Hodgkin's lymphoma (NHL). Elevation of CA125 level correlates with advanced disease, poor response to treatment, and poor survival rates. The aim of the current study is to evaluate CA125 levels in patients with NHL and to investigate the correlations between high CA125 level and other presenting features. Thirty-eight patients (14 with low-grade and 24 with aggressive histologically proven NHL) were studied prospectively. Serum CA125 assessment was done at diagnosis, during treatment, and at follow-up. The associations between CA125 levels and other presenting features were examined. CA125 levels were elevated in 43% of patients with low-grade NHL and in 46% of patients with aggressive NHL (i.e., 45% of all patients). A higher CA125 level was associated with advanced disease, bone marrow involvement, extranodal involvement, poor performance status, the presence of B symptoms, and high serum lactate dehydrogenase level. Complete responses occurred in 86% of patients with normal CA125 levels and in 59% of patients with elevated CA125 levels. In both low-grade and aggressive NHL, the estimated 5-year overall survival rate was higher in patients with normal CA125 levels than in patients with elevated CA125 levels (88% versus 50% and 70% versus 27%, respectively). High serum CA125 is an important prognostic factor in NHL and correlates with more advanced disease, low response rates, and worse survival. CA125 measurements may be used for staging, monitoring response to treatment, and follow-up of patients with NHL.


Conservative management of massive hematoperitoneum caused by ovulation in a patient with severe form of von Willebrand disease--a case report.
Von Willebrand disease (VWD) is the most common inherited bleeding condition that involves extended or excessive bleeding, caused by the deficiency or defect of von Willebrand factor (VWF). Hematoperitoneum as a complication of gynecologic diseases represents acute condition which is usually caused by the hemorrhagic corpus luteum or a rupture of either ectopic pregnancy or a hemorrhagic ovarian cyst. The authors present a unique case of conservatively managed massive hematoperitoneum caused by ovulation in a patient with severe form of von Willebrand disease who had right adnexectomy due to hemorrhagic corpus luteum four months prior. This conservative management by blood product and factor concentrate support could be a method of choice in selected hemodynamically stable patients. Furthermore, recurrent bleeding episodes following ovulation could be prevented by suppression of ovulation using oral contraceptive pills.


Mid-trimester preterm premature rupture of membranes (PPROM): etiology, diagnosis, classification, international recommendations of treatment options and outcome.
Mid-trimester preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 28 weeks of gestation, complicates approximately 0.4%-0.7% of all pregnancies. This condition is associated with a very high neonatal mortality rate as well as an increased risk of long- and short-term severe neonatal morbidity. The causes of the mid-trimester PPROM are multifactorial. Altered membrane morphology including marked swelling and disruption of the collagen network which is seen with PPROM can be triggered by bacterial products or/and pro-inflammatory cytokines. Activation of matrix metalloproteinases (MMP) have been implicated in the mechanism of PPROM. The propagation of bacteria is an important contributing factor not only in PPROM, but also in adverse neonatal and maternal outcomes after PPROM. Inflammatory mediators likely play a causative role in both disruption of fetal membrane integrity and activation of uterine contraction. The "classic PPROM" with oligo/an-hydramnion is associated with a short latency period and worse neonatal outcome compared to similar gestational aged neonates delivered without antecedent PPROM. The "high PPROM" syndrome is defined as a defect of the chorio-amniotic membranes, which is not located over the internal cervical os. It may be associated with either a normal or reduced amount of amniotic fluid. It may explain why sensitive biochemical tests such as the Amniosure (PAMG-1) or IGFBP-1/alpha fetoprotein test can have a positive result without other signs of overt ROM such as fluid leakage with Valsalva. The membrane defect following fetoscopy also fulfils the criteria for "high PPROM" syndrome. In some cases, the rupture of only one membrane - either the chorionic or amniotic membrane, resulting in "pre-PPROM" could precede "classic PPROM" or "high PPROM". The diagnosis of PPROM is classically established by identification of nitrazine positive, fern positive watery leakage from the cervical canal observed during in specula investigation. Other more recent diagnostic tests include the vaginal swab assay for placental alpha macroglobulin-1 test or AFP and IGFBP1. In some rare cases amniocentesis and infusion of indigo carmine has been used to confirm the diagnosis of PPROM. The management of the PPROM requires balancing the potential neonatal benefits from prolongation of the pregnancy with the risk of intra-amniotic infection and its consequences for the mother and infant. Close monitoring for signs of chorioamnionitis (e.g. body temperature, CTG, CRP, leucocytes, IL-6, procalcitonine, amniotic fluid examinations) is necessary to minimize the risk of neonatal and maternal complications. In addition to delayed delivery, broad spectrum antibiotics of penicillin or cephalosporin group and/or macrolide and corticosteroids have been show to improve neonatal outcome [reducing risk of chorioamnionitis (average risk ratio (RR)=0.66), neonatal infections (RR=0.67) and abnormal ultrasound scan of neonatal brain (RR=0.67)]. The positive effect of continuous amnioinfusion through the subcutaneously implanted perinatal port system with amniotic fluid like hypo-osmotic solution in "classic PPROM" less than 28/0 weeks' gestation shows promise but must be proved in future prospective randomized studies. Systemic antibiotics administration in "pre-PPROM" without infection and hospitalization are also of questionable benefit and needs to be further evaluated in well-designed randomized prospective studies to evaluate if it is associated with any neonatal benefit as well as the relationship to possible adverse effect of antibiotics on to fetal development and neurological outcome.


Psychological Stress and Functional Endometrial Disorders: Update of Mechanism Insights.
The human endometrium plays a vital role in providing the site for embryo implantation and maintaining the normal development and survival of the embryo. Recent studies have shown that stress is a common factor for the development of unexplained reproductive disorders. The nonreceptive endometrium and disturbed early maternal-fetal interaction might lead to infertility including the repeated embryo implantation failure and recurrent spontaneous abortion, or late pregnancy complications, thereby affecting the quality of life as well as the psychological status of the affected individuals. Additionally, psychological stress might also adversely affect female reproductive health. In recent years, several basic and clinical studies have tried to investigate the harm caused by psychological stress to reproductive health, however, the mechanism is still unclear. Here, we review the relationship between psychological stress and endometrial dysfunction, and its consequent effects on female infertility to provide new insights for clinical therapeutic interventions in the future.


'Routine is a blind alley' (C. G. Jung): on the similarities between artistic-creative and psychoanalytic work.
The transformation processes in artistic-creative work and those of the analytic process can be considered to be comparable. To illustrate the relatedness of the two, the author describes three self-states that characterized the artist Alberto Giacometti's creative process. With reference to Jungian concepts, the author subsequently illustrates how these states of mind can be found in the analyst during the analytic encounter. By comparing both processes, he explores the temptations and denials that accompany the analyst's struggle for an analytic attitude.


Application of tea polyphenols in combination with 6-gingerol on shrimp paste of during storage: biogenic amines formation and quality determination.
Tea polyphenols (TP) have shown antioxidant activity and antimicrobial properties in the food industry. Assessment of anti-oxidation potential of 6-gingerol (GR) has also been verified. As little is known about the use of tea polyphenols either individually or in combination with 6-gingerol in shrimp paste, we aimed to investigate the effect of tea polyphenols combined with 6-gingerol on the biogenic amines inhibition and quality of shrimp paste stored at 25°C for 160 days. The shrimp paste samples were assigned into four groups: (1) control; (2) tea polyphenols treatment (0.3%); (3) 6-gingerol treatment (0.3%); (4) tea polyphenols (0.15%) + 6-gingerol (0.15%). Samples with no addition were used as control. The results indicate that treatment with tea polyphenols + 6-gingerol (TPGR) maintained paste appearance, inhibited oxidation of protein and lipids, and reduced microorganism counts compared to control treatment. The efficiency was superior to that of tea polyphenols or 6-gingerol treatment. Furthermore, shrimp paste treated with TPGR also exhibited significantly higher inhibition of biogenic amines. Total amino acids determination proved the efficacy of TPGR by maintaining the more amino acids of shrimp paste during ambient temperature storage. Our study suggests that TPGR might be a promising candidate for fermented foods due to its synergistic effect to maintain products quality and extending their shelf-life.


High frequency of sex chromosomal disomy in spermatozoa of Lebanese infertile men.
In Lebanon, assisted reproductive techniques (ART) are widely used to overcome infertility, but the genetic risk associated with these techniques is still ignored. In this study, in order to estimate the transmission risk of paternal chromosomal anomalies to ART offspring, the meiotic segregation of chromosomes X, Y, 18, and 21 was analyzed by fluorescent in situ hybridization on the spermatozoa of 19 Lebanese infertile men. Our results show significantly higher frequencies of sex chromosome disomies in the group of patients with oligozoospermia compared with a control group of fertile males. Interestingly, the sex chromosome aneuploidy rates were highly variable between oligozoospermic patients, and ranged between 0.9% and 12.87%. No significant increase in aneuploidy rates was found for the group of nonoligozoospermic patients with asthenozoospermia and/or teratozoospermia. In addition, the disomy rate for chromosome 21 was analyzed in 8 patients, in whom higher disomy rates were shown as compared with the controls. Altogether, the results suggest that Lebanese oligozoospermic men undergoing ART may have an increased risk of transmitting sex chromosome anomalies to their offspring, as well as, in some cases, trisomy 21. Based on this work, genetic counseling programs for Lebanese infertile couples undergoing ART procedures should be developed, in order to improve the investigation and selection of Lebanese infertile couple candidates for ART procedures and optimize the choice of ART techniques.


Childhood and adolescent depression. II: Research in clinical populations.
The tremendous increase in interest in childhood and adolescent depression that has occurred since the early 1970s has resulted in a large and contradictory literature. Development of the concept of childhood depression, and the many clinical studies of depression and its concomitants, both psychosocial and biological, are critically reviewed. A number of methodological and theoretical problems are discussed.


[Equipment for electro-convulsive therapy].
ECT (electro-convulsive therapy) has been used for the treatment of depressive patients. First it was applied in patients only with sedatives without muscle relaxants, but now we employ muscle relaxants to avoid convulsion and its complications. It is called modified ECT (mECT). General anesthesia using muscle relaxant for ECT is now increasingly employed in Japan. Furthermore, there are some reports that ECT is effective not only in depressive patients but in chronic pain patients. This is why anesthesiologists are especially interested in ECT. In this chapter, clinical application, equipment and complications of ECT are discussed.


Potential of land use activities to offset road traffic greenhouse gas emissions in Central Spain.
The transport sector is one of the main sources of greenhouse gases, adding in Spain near a quarter of the total national emissions, the majority in road transport. Therefore, road contribution to climate change should be mitigated to achieve the proposed goals in the fight against climate change. Policies and strategies suggest several preventive mitigation options, but have paid little attention to compensatory mitigation. We have conducted a theoretical case study in a Spanish province, Segovia, estimating the carbon dioxide emissions in the road network between 2015 and 2050, and analysing different compensation possibilities through conservation agriculture, agroforestry, afforestation and hedgerow plantation. We have calculated carbon sequestration in the reference period and costs per tonne for each option, estimating the budget range of offsetting road carbon emission, and funding possibilities, especially through fuel taxes. The paper demonstrates that offsetting carbon emissions produced by roads in this area is technically possible and highly desirable, unifying carbon sequestration, biodiversity improvement and rural development. The main challenge is funding, which depends largely on the political will and the awareness of the citizens.


Dynamically Expressed miR-BART16 Functions as a Suppressor of CAND1 in Infectious Mononucleosis Caused by Epstein-Barr Virus in Children.
MiR-BART16 is a newly discovered Epstein-Barr Virus-encoded microRNA (miRNA). We aimed to explore the role of EBV-miR-BART16 in infectious mononucleosis (IM). Peripheral blood lymphocyte subsets were analyzed in 30 IM and 10 healthy children by flow cytometry. MiR-BART16 and its targets were measured by real-time PCR, western blot, ELISA, and dual-luciferase assay. Serum miR-BART16 expression was significantly higher in the IM children than that in the healthy children, and was positively correlated with EBV copy number. Receiver operating characteristic analysis revealed serum miR-BART16 could differentiate IM and healthy individuals (P=0.0041). CAND1 was targeted and downregulated by miR-BART16 in an EBV infection-dependent way. These results highlight that EBV-miR-BART16 plays an important role in regulating the expression of CAND1 to affect pediatric IM.


Two Triacylglycerol Pathway Genes, CTDNEP1 and LPIN1, are Down-Regulated by hsa-miR-122-5p in Hepatocytes.
Expression of miR-122 is highly specific to hepatocytes of the liver. This miRNA is involved in lipid hemostasis of the tissue; however, there is no comprehensive understanding of its function in lipid hemostasis. Since hepatocytes are responsible for part of Triacylglycerol (TAG) synthesis in the body, we hypothesized that miR-122, as the most abundant miRNA in the tissue, might regulate TAG metabolism by targeting key enzymes that are involved in its production pathway. A systematic computational analysis of putative targets of miR-122 identified CTDNEP1 and LPIN1 genes in the TAG pathway. We used dual-luciferase reporter assay, quantitative RT-PCR as well as western blot to confirm the repressive effect of miR-122 on CTDNEP1 and LPIN1 in TAG pathway. Real time PCR on liver needle biopsies with hepatosteatosis showed that miR-122 is up-regulated in hepatosteatosis. Surprisingly, the protein and RNA level of identified targets of miR-122 are also up-regulated in clinical samples, probably as a disproportionate feedback response to the high level of miR-122. Our findings suggest that up-regulation of miR-122 can trigger the compensatory response of LPIN1 and CTDNEP1 in hepatosteatosis.


Injury Patterns in Posterolateral Corner Knee Injury.
Posterolateral corner (PLC) knee injuries associated with different injury mechanisms are not well known. This study sought to assess the patterns of associated injuries in the setting of PLC injury. The hypothesis was that there are recognizable injury patterns in PLC injuries that may correlate with injury mechanism. Cross-sectional study; Level of evidence, 3. Patients who sustained a multiligament knee injury were retrospectively reviewed. Patients who sustained an acute grade 3 PLC injury and underwent surgery were enrolled in this study. A description of the PLC injury (location of the injury of the fibular collateral ligament [FCL], popliteus tendon, and/or popliteofibular ligament) and reported concomitant injuries (biceps femoris tendon or meniscal tears, cartilage pathology and/or peroneal nerve palsy, or bone bruises) were collected and classified based on intraoperative and magnetic resonance imaging (MRI) findings. Of 135 patients reviewed, 83 did not have PLC involvement and 13 were excluded due to insufficient MRI scans available. Thus, 39 patients were included in this study. For both the anterior cruciate ligament (ACL)-PLC and ACL-posterior cruciate ligament-PLC injury patterns, the most frequent injury pattern entailed a bone bruise of the anteromedial (AM) femur and tibia, an FCL tear from the fibular head, the popliteus tendon avulsed off the femur, a biceps femoris tendon torn off the fibular head, and a common peroneal nerve palsy. Conversely, when no bone bruise occurred on the AM femur and tibia, the FCL was injured on the femoral side and the popliteus tendon, biceps femoris, and peroneal nerve were not injured. AM bone bruise was associated with a peroneal nerve injury in almost half of the patients, and peroneal nerve injury was not seen if there was no AM bone bruise.


Congenital brain dysplasias of different genesis can differently affect susceptibility to pilocarpine- or kainic acid-induced seizures in the rat.
Interruption of neurogenesis and/or neuronal migration produces brain dysplasia modifying susceptibility to epileptic seizures in adulthood. The course of neurogenesis has a strictly defined time-table. Consequently, the developmental stage at which the interruption occurs determines what functional subsystem potentially involved in epileptogenesis will suffer from irreversible neuronal deficit. The present study attempts to verify a hypothesis that brain dysplasias of different genesis should also lead to different susceptibility to seizures evoked by receptor agonists of different functional specificity, like kainic acid or pilocarpine, a cholinergic or glutaminergic agonist, respectively. Pregnant Wistar rats were exposed to gamma-rays on gestation days 13, 15, 17 or 19 (E13, E15, E17 or E19). Sixty-day-old offsprings of the females were injected with kainic acid or pilocarpine to evoke status epilepticus. During a 6-h period following the injection, motor manifestations of seizure activity were recorded. Generally, the intensity of pilocarpine-induced symptoms was relatively low in rats irradiated on E13 or E15 but high in rats irradiated on E17 or E19. In rats treated with kainic acid, the trend was opposite, viz. the later the prenatal irradiation was performed, the less intense epileptic symptoms were induced in adulthood. The data provide evidence that dysplasias acquired during prenatal development may significantly amplify or reduce the brain susceptibility to seizures. However, this relation depends not only on the developmental stage at which the dysplasias were produced but also on the functional specificity of epileptogenic stimuli used in the experimental model of epilepsy.


Effect of inhaled carbon dioxide on laryngeal abduction.
Hypercapnia produces a profound effect on respiratory drive and upper airway function to maintain airway patency. Previous work has evaluated the effects of hypercapnia on the sole arytenoid abductor, the posterior cricoarytenoid (PCA), using indirect measures of function, such as electromyography and direct nerve recording. Here we describe a novel method to evaluate PCA function in anesthetized animals and use this method to determine the effects of hypercapnia on PCA function. Eight dogs were anesthetized, and a laryngeal mask airway was used, in combination with high-speed videoendoscopy, to evaluate laryngeal function. A stepwise increase in inspired partial pressure of CO2 produced marked arytenoid abduction above 70-mmHg end-tidal CO2 (ETCO2 ) (P < 0.001). Glottic length increased above 80-mmHg ETCO2 (P < 0.02), and this lead to underrepresentation of changes in glottic area, if standard measures of glottic area (normalized glottic gap area) were used. Use of a known scale to determine absolute glottic area demonstrated no plateau with increasing ETCO2 up to 120 mmHg. Ventilatory parameters also continued to increase with no evidence of a maximal response. In a second anesthetic episode, repeated bursts of transient hypercapnia for 60 s with an ETCO2 of 90 mmHg produced a 43-55% increase in glottic area (P < 0.001) at or shortly after the end of the hypercapnic burst. A laryngeal mask airway can be used in combination with videoendoscopy to precisely determine changes in laryngeal dimensions with high temporal resolution. Absolute glottic area more precisely represents PCA function than normalized glottic gap area at moderate levels of hypercapnia.


Amazing stability of phosphate-quaternary amine interactions.
We have previously used MALDI mass spectrometry to highlight ammonium- or guanidinium-aromatic interactions via cation-pi bonding and ammonium- or guanidinium-phosphate interactions through salt bridge formation. In the present work, the gas-phase stability and dissociation pathways of the interaction between phosphorylated peptides and compounds containing quaternary amines are demonstrated using electrospray ionization mass spectrometry. The presence of one quaternary amine in a compound is enough to form a noncovalent complex with a phosphorylated residue. However, if two quaternary amines are present in one molecule, the electrostatic interactions of the quaternary amines with the phosphate results in a "covalent-like" stability, and these bonds can withstand fragmentation by collision-induced dissociation at energies similar to those that fragment covalent bonds. Such interactions are important in accounting for physiological, pathophysiological, and pharmacological effects of many therapeutic compounds and small molecules containing quaternary amines or phosphates.


[Repair of an electrode breakage in a permanent pacemaker by internal bypassing].
A possible complication of the definitive pacemaker therapy is the fracture on the electrode which usually needs new electrode replacement. A new method is discussed as the electrical fault caused by fracture is resolved by internally bypassing the broken part of the electrode with a guide-wire. This method is more simple and economical and quicker than the electrode replacement and provides more safety for the patients. This method is therefore recommended to be spread.


Is (99m)Tc-labelled pamidronate a better agent than (99m)Tc-medronate for bone imaging?
To evaluate the potential of (99m)Tc-pamidronate ((99m)Tc-APD) against (99m)Tc-medronate ((99m)Tc-MDP) as a new bone-seeking agent using intact bone and fractured femur in a rat model. (99m)Tc-APD was prepared by the stannous reduction method. Scintigraphic images were obtained at 2 h and 24 h after intravenous injection of (99m)Tc-APD or (99m)Tc-MDP in rats, then they were culled to estimate activities in various organs. Bone uptake (as percent injected dose/gram weight) was estimated in an intact femur and in 1 week post-fracture model. The urinary excretion dose (as percent injected dose) was also estimated. The bone uptake of (99m)Tc-APD was significantly higher (P<0.05) than (99m)Tc-MDP at 2 h and 24 h post-injection studies. (99m)Tc-APD uptake was further increased (P<0.05) in the fracture model than the intact femur. (99m)Tc-APD uptake in the soft tissues including liver and the kidneys was lower than (99m)Tc-MDP. Renal excretion was faster and the ratios of bone to blood and bone to soft tissues were higher with APD than MDP. APD dose was selected at 1% of MDP, to obviate therapeutic effect, as the former compound is 100 times more potent than MDP. Our results suggest that (99m)Tc-APD uptake by intact bone and fractured bone was significantly higher than (99m)Tc-MDP. The renal clearance of (99m)Tc-APD was faster and soft tissue uptake was lower than (99m)Tc-MDP. These results suggest that APD has the potential to become an excellent bone-imaging agent.


Flow-Mediated Dilation, a Marker of Endothelial Cell Dysfunction, in Patients with Pulmonary Hypertension.
Flow-mediated dilation (FMD) is considered a marker of endothelial cell dysfunction (ECD) and has been mostly evaluated in coronary artery disease. The role of ECD in the pathogenesis of pulmonary hypertension (PH) is not well-known. This study sought to evaluate the relationship between FMD and PH. In this cross-sectional study, the FMD of the brachial artery was measured in 40 confirmed PH patients. Meanwhile, echocardiographic findings, the 6-minute walk test (6MWT), and serum pro-brain natriuretic peptide (pro-BNP) level were evaluated. Overall, 20 patients accomplished all evaluations, and their data were analyzed using SPSS software (version 23). There was an inverse relationship between pro-BNP and 6MWT (r<0, P<0.05). A significant direct relationship was observed between left ventricular ejection fraction and FMD (P=0.031). Right ventricular (RV) dilation was significantly correlated with pro-BNP (P=0.046). There was a significant direct correlation between RV function and FMD and a significant inverse relationship between pro-BNP and FMD (P=0.05). The independent t-test showed no relationship between FMD and syncope (P=0.75). Endothelial cell function, which can be evaluated by FMD, was involved in patients with PH. The FMD and 6MWT were helpful as objective prognostic markers in PH. Furthermore, pro-BNP was a noninvasive indicator in the diagnosis of RV systolic dysfunction.


The sequence of the tms transcript 2 locus of the A. tumefaciens plasmid pTiA6 and characterization of the mutation in pTiA66 that is responsible for auxin attenuation.
The incorporation of Ti plasmid sequences, the T-DNA, into the genomes of dicotyledenous plants causes the formation of tumors. Here we report the nucleotide sequence of one of the T-DNA "oncogenes", the transcript 2 gene of pTiA6 and we further characterize the 2.7 Kb element that has spontaneously inserted into this gene in plasmid pTiA66. The results indicate that the transcript 2 portion of the T-DNA has an open reading frame that could encode a polypeptide of 49.8 Kd. The open reading frame is surrounded by sequences that typically have roles in eucaryotic gene expression. Nucleotide sequence and Southern blot analysis also indicates that the 2.7 Kb insert in the transcript 2 gene of pTiA66 is located within the coding sequence of the gene and suggests that the element is an insertion sequence. We designate this element, IS66.


Breast Cancer Treatment: A Review.
Breast cancer will be diagnosed in 12% of women in the United States over the course of their lifetimes and more than 250 000 new cases of breast cancer were diagnosed in the United States in 2017. This review focuses on current approaches and evolving strategies for local and systemic therapy of breast cancer. Breast cancer is categorized into 3 major subtypes based on the presence or absence of molecular markers for estrogen or progesterone receptors and human epidermal growth factor 2 (ERBB2; formerly HER2): hormone receptor positive/ERBB2 negative (70% of patients), ERBB2 positive (15%-20%), and triple-negative (tumors lacking all 3 standard molecular markers; 15%). More than 90% of breast cancers are not metastatic at the time of diagnosis. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Triple-negative breast cancer is more likely to recur than the other 2 subtypes, with 85% 5-year breast cancer-specific survival for stage I triple-negative tumors vs 94% to 99% for hormone receptor positive and ERBB2 positive. Systemic therapy for nonmetastatic breast cancer is determined by subtype: patients with hormone receptor-positive tumors receive endocrine therapy, and a minority receive chemotherapy as well; patients with ERBB2-positive tumors receive ERBB2-targeted antibody or small-molecule inhibitor therapy combined with chemotherapy; and patients with triple-negative tumors receive chemotherapy alone. Local therapy for all patients with nonmetastatic breast cancer consists of surgical resection, with consideration of postoperative radiation if lumpectomy is performed. Increasingly, some systemic therapy is delivered before surgery. Tailoring postoperative treatment based on preoperative treatment response is under investigation. Metastatic breast cancer is treated according to subtype, with goals of prolonging life and palliating symptoms. Median overall survival for metastatic triple-negative breast cancer is approximately 1 year vs approximately 5 years for the other 2 subtypes. Breast cancer consists of 3 major tumor subtypes categorized according to estrogen or progesterone receptor expression and ERBB2 gene amplification. The 3 subtypes have distinct risk profiles and treatment strategies. Optimal therapy for each patient depends on tumor subtype, anatomic cancer stage, and patient preferences.


Epidemiology of the viral hepatitis-HIV syndemic in San Francisco: a collaborative surveillance approach.
To describe the epidemiology of people coinfected with hepatitis B virus (HBV) or hepatitis C virus (HCV) and HIV in San Francisco, the San Francisco Department of Public Health's Communicable Disease Control and Prevention Section and the HIV Epidemiology Section collaborated to link their registries. In San Francisco, hepatitis reporting is primarily through passive laboratory-based surveillance, and HIV/AIDS reporting is primarily through laboratory-initiated active surveillance. We conducted the registry linkage in 2010 using a sequential algorithm. The registry match included 31,997 HBV-infected people who were reported starting in 1984; 10,121 HCV-infected people who were reported starting in 2001; and 34,551 HIV/AIDS cases reported beginning in 1981. Of the HBV and HCV cases, 6.3% and 12.6% were coinfected with HIV, respectively. The majority of cases were white males; however, black people were disproportionately affected. For more than 90% of the HBV/HIV cases, male-to-male sexual contact (men who have sex with men [MSM]) was the risk factor for HIV infection. Injection drug use was the most frequent risk factor for HIV infection among the HCV/HIV cases; however, 35.6% of the HCV/HIV coinfected males were MSM but not injection drug users. By linking the two registries, we found new ways to foster collaborative work and expand our programmatic flexibility. This analysis identified particular populations at risk for coinfection, which can be used by viral hepatitis and HIV screening, prevention, and treatment programs to integrate, enhance, target, and prioritize prevention services and clinical care within the community to maximize health outcomes.


Real-Time Control of a Multi-Degree-of-Freedom Mirror Myoelectric Interface During Functional Task Training.
Motor learning mediated by motor training has in the past been explored for rehabilitation. Myoelectric interfaces together with exoskeletons allow patients to receive real-time feedback about their muscle activity. However, the number of degrees of freedom that can be simultaneously controlled is limited, which hinders the training of functional tasks and the effectiveness of the rehabilitation therapy. The objective of this study was to develop a myoelectric interface that would allow multi-degree-of-freedom control of an exoskeleton involving arm, wrist and hand joints, with an eye toward rehabilitation. We tested the effectiveness of a myoelectric decoder trained with data from one upper limb and mirrored to control a multi-degree-of-freedom exoskeleton with the opposite upper limb (i.e., mirror myoelectric interface) in 10 healthy participants. We demonstrated successful simultaneous control of multiple upper-limb joints by all participants. We showed evidence that subjects learned the mirror myoelectric model within the span of a five-session experiment, as reflected by a significant decrease in the time to execute trials and in the number of failed trials. These results are the necessary precursor to evaluating if a decoder trained with EMG from the healthy limb could foster learning of natural EMG patterns and lead to motor rehabilitation in stroke patients.


Outstanding Phenotypic Differences in the Profile of Amyloid-β between Tg2576 and APPswe/PS1dE9 Transgenic Mouse Models of Alzheimer's Disease.
APPswe/PS1dE9 and Tg2576 are very common transgenic mouse models of Alzheimer's disease (AD), used in many laboratories as tools to research the mechanistic process leading to the disease. In order to augment our knowledge about the amyloid-β (Aβ) isoforms present in both transgenic mouse models, we have developed two chromatographic methods, one acidic and the other basic, for the characterization of the Aβ species produced in the brains of the two transgenic mouse models. After immunoprecipitation and micro-liquid chromatography-electrospray ionization mass spectrometry/mass spectrometry, 10 species of Aβ, surprisingly all of human origin, were detected in the brain of Tg2576 mouse, whereas 39 species, of both murine and human origin, were detected in the brain of the APP/PS1 mouse. To the best of our knowledge, this is the first study showing the identification of such a high number of Aβ species in the brain of the APP/PS1 transgenic mouse, whereas, in contrast, a much lower number of Aβ species were identified in the Tg2576 mouse. Therefore, this study brings to light a relevant phenotypic difference between these two popular mice models of AD.


Metalloporphyrin-based porous polymers prepared via click chemistry for size-selective adsorption of protein.
Zinc porphyrin-based porous polymers (PPs-Zn) with different pore sizes were prepared by controlling the reaction condition of click chemistry, and the protein adsorption in PPs-Zn and the catalytic activity of immobilized enzyme were investigated. PPs-Zn-1 with 18 nm and PPS-Zn-2 with 90 nm of pore size were characterized by FTIR, NMR and nitrogen absorption experiments. The amount of adsorbed protein in PPs-Zn-1 was more than that in PPs-Zn-2 for small size proteins, such as lysozyme, lipase and bovine serum albumin (BSA). And for large size proteins including myosin and human fibrinogen (HFg), the amount of adsorbed protein in PPs-Zn-1 was less than that in PPs-Zn-2. The result indicates that the protein adsorption is size-selective in PPs-Zn. Both the protein size and the pore size have a significant effect on the amount of adsorbed protein in the PPs-Zn. Lipase and lysozyme immobilized in PPs-Zn exhibited excellent reuse stability.


Pathogen and drought stress affect cell wall and phytohormone signaling to shape host responses in a sorghum COMT bmr12 mutant.
As effects of global climate change intensify, the interaction of biotic and abiotic stresses increasingly threatens current agricultural practices. The secondary cell wall is a vanguard of resistance to these stresses. Fusarium thapsinum (Fusarium stalk rot) and Macrophomina phaseolina (charcoal rot) cause internal damage to the stalks of the drought tolerant C4 grass, sorghum (Sorghum bicolor (L.) Moench), resulting in reduced transpiration, reduced photosynthesis, and increased lodging, severely reducing yields. Drought can magnify these losses. Two null alleles in monolignol biosynthesis of sorghum (brown midrib 6-ref, bmr6-ref; cinnamyl alcohol dehydrogenase, CAD; and bmr12-ref; caffeic acid O-methyltransferase, COMT) were used to investigate the interaction of water limitation with F. thapsinum or M. phaseolina infection. The bmr12 plants inoculated with either of these pathogens had increased levels of salicylic acid (SA) and jasmonic acid (JA) across both watering conditions and significantly reduced lesion sizes under water limitation compared to adequate watering, which suggested that drought may prime induction of pathogen resistance. RNA-Seq analysis revealed coexpressed genes associated with pathogen infection. The defense response included phytohormone signal transduction pathways, primary and secondary cell wall biosynthetic genes, and genes encoding components of the spliceosome and proteasome. Alterations in the composition of the secondary cell wall affect immunity by influencing phenolic composition and phytohormone signaling, leading to the action of defense pathways. Some of these pathways appear to be activated or enhanced by drought. Secondary metabolite biosynthesis and modification in SA and JA signal transduction may be involved in priming a stronger defense response in water-limited bmr12 plants.


The role of scanning electron microscopy in ophthalmic science.
The eyeglobe is one of the classical domains of Scanning Electron Microscopy (SEM) in biology as it exposes several inner and outer surfaces. Both corneal and conjunctival epithelia towards the tear film as well as the corneal endothelial cells facing the anterior chamber may be accurately evaluated. The architecture of the angle and particularly the morphology of the Schlemm's canal inner wall are clarified by SEM more than by TEM serial reconstruction. The surfaces of the iris and ciliary body, the zonula and the choroidal vessel arrangement are described in great detail. Three distinct types of membrane anchoring devices are demonstrated among the lens fibers. SEM impressively describes the retina, but it has not yet added any new information as to previous observations in a more conventional way. SEM plays a fundamental role in teaching ocular anatomy and physiology as it makes more comprehensive the interrelationships among different structures. In addition, it represents a proper structural approach of the clinician who is familiar with the three-dimensional observations obtained by means of biomicroscopy, ophthalmoscopy and fluorescein angiography. Therefore, SEM application should be further spread and possibly joined to immunocytochemistry, in order to obtain a more dynamic and functional analysis of the eye.


A selective journal.
The stringent selection criteria applied at EMBO Reports result in the publication of around 16% of submitted papers. What do we select for and why is this a service to the scientific community? A counterpoint to EMBO Reports (2023) e58127.


One-component plasma of point charges and of charged rods.
An approximate theory is developed to describe the properties of mobile particles with extended charge distributions in the presence of a neutralizing fixed background charge. Long-wavelength fluctuations of the electric potential are handled within a variational perturbation approximation, and the short-wavelength fluctuations are handled within a cumulant (fugacity) expansion. The distinct treatment of these two contributions to the free energy enables the theory to provide quantitative predictions for the properties of these systems from the weak- to the strong-coupling regimes. With this theory, we study three different variations in the classical one-component plasma model: a plasma of point charges, a plasma of particles consisting of 8 linearly bonded point charges (8-mer), and a plasma of line charges. The theory was found to agree well with the available computer simulation data for the electrostatic interaction energy of these systems for all values of the plasma coupling parameter examined ( Gamma=0 to 400). In addition, we find that both the 8-mer rod and the line charge systems form a strongly ordered nematic phase, which is entirely driven by electrostatic interactions. The nematic phase only exists within a finite range of lengths of the charged particles. If the particles are too short or too long, the nematic phase does not appear. Finally, we find that the nematic phase is stable over a broader range of conditions for the line charge system than for the 8-mer rod system; consequently, the phase behavior of the one-component plasma is sensitive to the manner in which the charge is distributed on the particles.


Secondary chondrosarcoma in cartilage bone tumors: report of 32 patients.
Secondary malignancies arising from benign bone tumors are rare. Their recognition and diagnosis are difficult, and their slow growth and late recurrence require long-term follow-up. In this study, malignant transformation rates of various histological types of benign cartilage-forming bone tumors in large series were evaluated. Between 1986 and 2004, a retrospective analysis of 627 cartilage-forming benign bone tumors revealed that 32 patients had malignant transformation. Of the 32 patients, 14 had solitary osteochondromas, 10 had multiple osteochondromas, 6 had a solitary enchondroma, 1 had Ollier's disease, and 1 had Maffucci's syndrome. The patient with Ollier's disease had two chondrosarcomas, and one patient with multiple osteochondroma had three chondrosarcomas. The cases were included in the study only when complete clinical documentation, radiological records, and histological analyses were available. The rate of malignant transformation for cartilage-originating tumors was 5.1% (solitary osteochondromas 4.2%, multiple osteochondromas 9.2%, solitary enchondromas 4.2%). The average time between the initial diagnosis and malignant transformation was 9.8 years. The most common site of involvement was the proximal portion of the femur. The tumors generally were well differentiated. The mean follow-up period was 57.3 months. Five patients (15.6%) died of tumor recurrence or metastasis at an average of 20.6 months. One patient is alive with tumor at 104 months. Cartilage-forming benign bone tumors are rather prone to undergo malignant transformation. Although malignant transformation of a benign bone tumor is a rarely encountered situation, orthopedic surgeons should be cautious while following patients with a benign bone neoplasm. Early recognition and appropriate surgical treatment are required to achieve successful outcomes. The rate of local recurrence in secondary chondrosarcomas depends not only on adequate surgical treatment but also on the localization and histological grade.


Vaginal Ewing Sarcoma: An Uncommon Clinical Entity in Pediatric Patients.
Ewing sarcoma, including classical Ewing sarcoma of the bone and primitive neuroectodermal tumors arising in bone or extraosseous primary sites, is a highly aggressive childhood neoplasm. We present two cases of Ewing sarcoma arising from the vagina in young girls. Previously reported cases in literature focused on their pathologic rather than radiographic features. We describe the spectrum of multimodality imaging appearances of Ewing sarcoma at this unusual primary site. Awareness of vaginal Ewing tumors may facilitate prompt diagnosis and lead to a different surgical approach than the more commonly encountered vaginal rhabdomyosarcoma.


Host inflammatory response to polypropylene implants: insights from a quantitative immunohistochemical and birefringence analysis in a rat subcutaneous model.
To describe acute and sub acute aspects of histological and immunohistochemical response to PP implant in a rat subcutaneous model based on objective methods. Thirty rats had a PP mesh subcutaneously implanted and the same dissection on the other side of abdomen but without mesh (sham). The animals were euthanized after 4 and 30 days. Six slides were prepared using the tissue removed: one stained with hematoxylin-eosin (inflammation assessment); one unstained (birefringence evaluation) and four slides for immunohistochemical processing: IL-1 and TNF-α (pro-inflammatory cytokines), MMP-2 (collagen metabolism) and CD-31 (angiogenesis). The area of inflammation, the birefringence index, the area of immunoreactivity and the number of vessels were objectively measured. A larger area of inflammatory reaction was observed in PP compared to sham on the 4th and on the 30th day (p=0.0002). After 4 days, PP presented higher TNF (p=0.0001) immunoreactivity than sham and no differences were observed in MMP-2 (p=0.06) and IL-1 (p=0.08). After 30 days, a reduction of IL-1 (p=0.010) and TNF (p=0.016) for PP and of IL-1 (p=0.010) for sham were observed. Moreover, area of MMP-2 immunoreactivity decreased over time for PP group (p=0.018). Birefringence index and vessel counting showed no differences between PP and sham (p=0.27 and p=0.58, respectively). The implantation of monofilament and macroporous polypropylene in the subcutaneous of rats resulted in increased inflammatory activity and higher TNF production in the early post implant phase. After 30 days, PP has similar cytokines immunoreactivity, vessel density and extracellular matrix organization.


Silver(I)-Catalyzed C4-H Amination of 1-Naphthylamine Derivatives with Azodicarboxylates.
A simple and efficient protocol for silver(I)-catalyzed picolinamide directed C4-H amination of 1-naphthylamine derivatives with readily available azodicarboxylates has been developed, demonstrating a new approach to 1,4-naphthalenediamine derivatives in high yields. Note that this reaction system could proceed under external-oxidant- and additive-free conditions (only requires 5 mol % of AgOAc as the catalyst in acetone).


Consensus protein design.
A popular and successful strategy in semi-rational design of protein stability is the use of evolutionary information encapsulated in homologous protein sequences. Consensus design is based on the hypothesis that at a given position, the respective consensus amino acid contributes more than average to the stability of the protein than non-conserved amino acids. Here, we review the consensus design approach, its theoretical underpinnings, successes, limitations and challenges, as well as providing a detailed guide to its application in protein engineering.


Killing by cytotoxic T cells and natural killer cells: multiple granule serine proteases as initiators of DNA fragmentation.
The vectorial secretion of the contents of highly specialized cytoplasmic granules is of pivotal importance to the killing by cytotoxic T cells and natural killer cells. The purification and biochemical characterization of some of the granule constituents, in particular the pore-forming protein perforin, had engendered the notion that the killing of cellular targets was largely an osmotic phenomenon analogous to the insult delivered by complement attack. However, the apparent absence of membrane perforation in various examples of lymphocyte-mediated killing, and the observation that perforin alone could not account for apoptosis associated with programmed cell death, suggested that perforin activity represented, at best, only a part of the whole mechanism. More recently, the characterization of a large family of granule serine proteases (granzymes) has provided evidence that these molecules may collaborate in the killing process by inducing a 'suicide' pathway in target cells, resulting in DNA fragmentation. However, the serine proteases are inactive alone, their natural substrates have not been defined and they require access into the target cell cytoplasm via perforin-induced pores to exert their deleterious effects. Thus, we propose that the cytotoxic granule-mediated mechanism comprises at least two interdependent arms, perforin and serine proteases, that together are capable of inflicting cell death by osmotic shock and/or nuclear collapse.


Trace element levels in the liver of rats with acute and chronic fascioliasis and after treatment with zinc-copper hydroxochloride mixed crystals.
Quantities of trace elements including copper, zinc, cobalt, manganese and iron were investigated in the liver tissue of rats at the acute or chronic stages of fascioliasis following treatment with zinc-copper hydroxochloride mixed crystals. Oral dosing (with food) of zinc-copper mixed crystals to healthy rats increased zinc and copper levels in the liver and decreased the iron content compared with controls. Manganese and cobalt levels did not change significantly. Significant reductions in all trace elements except manganese occurred in the liver of rats with acute or chronic fascioliasis. Manganese levels were slightly increased in rats at the acute stage and slightly decreased in rats at the chronic stage of fascioliasis. The application of mixed zinc-copper crystals at the acute or chronic stages of fascioliasis lead to a restoration of zinc and copper levels and a slight reduction in the iron levels in liver tissue of rats. The beneficial effects of applied salts were more apparent in rats chronically infected with Fasciola hepatica.


Effect of the Camelid's Seminal Plasma Ovulation-Inducing Factor/β-NGF: A Kisspeptin Target Hypothesis.
Female mammals are classified into spontaneous and induced ovulators based on the mechanism eliciting ovulation. Ovulation in spontaneous species (e.g., human, sheep, cattle, horse, pigs, and most rodents) occurs at regular intervals and depends upon the circulating estradiol. However, in induced ovulators (e.g., rabbits, ferrets, cats, and camelids), ovulation is associated with coitus. In the later, various factors have been proposed to trigger ovulation, including auditory, visual, olfactory, and mechanic stimuli. However, other studies have identified a biochemical component in the semen of induced ovulators responsible for the induction of ovulation and named accordingly ovulation-inducing factor (OIF). In camelids, intramuscular or intrauterine administration of seminal plasma (SP) was shown to induce the preovulatory luteinizing hormone (LH) surge followed by ovulation and subsequent formation of corpus luteum. Recently, this OIF has been identified from SP as a neurotrophin, the β subunit of nerve growth factor (β-NGF). β-NGF is well known as promoting neuron survival and growth, but in this case, it appears to induce ovulation through an endocrine mode of action. Indeed, β-NGF may be absorbed through the endometrium to be conveyed, via the blood stream, to the central structures regulating the LH preovulatory surge. In this review, we provide a summary of the most relevant results obtained in the field, and we propose a working hypothesis for the central action of β-NGF based on our recent demonstration of the presence of neurons expressing kisspeptin, a potent stimulator of GnRH/LH, in the camel hypothalamus.


The molecular characteristics, diagnosis, and treatment of macrolide-resistant Mycoplasma pneumoniae in children.
The purpose of this study is to review the molecular characteristics, the diagnosis, and treatment of the widespread infection of macrolide-resistant Mycoplasma pneumoniae (M. pneumoniae; MRMP) in children, thus providing a better knowledge of this infection and presenting the associated problems. Single point mutations in the V region of the 23S rRNA gene of M. pneumoniae genome are associated with macrolide resistance. P1-1, MLVA4-5-7-2, and ST3 are usually the predominated genetic types in the M. pneumoniae epidemics. The short-term two times serological IgM (or together with IgG) test in the acute stage can be used for confirmation. Combined serological testing and PCR might be a more prudent method to reduce macrolide consumption and antibiotic selective pressure in a clinical setting. Molecular methods for the detection of single-nucleotide mutations in the V region of the 23S rRNA gene can be used for the diagnosis of MRMP. The routine use of macrolide for the treatment of macrolide-sensitive Mycoplasma pneumoniae (MSMP) infections can get good effect, but the effects are limited for severe MRMP infections. Additional corticosteroids may be required for the treatment of severe MRMP infections in children in China during the era of MRMP.


Theoretical CD spectrum calculations of the crown-ether aralkyl-ammonium salt complex.
Rotatory strengths of the alpha-(1-naphtyl)-ethylammonium perchlorate (NEA)-phenazino-18-crown-6 ether molecular complex is determined theoretically by the coupled oscillator model and using ab initio random phase approximation (RPA) to describe local excitations on the chromophores. The computational results are compared to the experimental circular dichroism (CD) spectrum published previously. The good qualitative agreement between calculated and measured optical rotatory strengths allows one to assign the CD bands of the complex in a unique manner.


Treatment of blast injuries of the extremity.
Blast trauma is a complex event. Pathophysiologically, blast injuries are identified as primary (caused solely by the direct effect of blast overpressure on the tissue), secondary (caused by flying objects or fragments), tertiary (caused by bodily displacement), or quaternary (indirectly caused by the explosion). The range of primary blast injuries includes fractures, amputations, crush injury, burns, cuts, lacerations, acute occlusion of an artery, air embolism-induced injury, compartment syndrome, and others. Secondary injuries are the most common extremity blast injuries. Like primary injuries, they may necessitate limb amputation, be life-threatening, and produce severe contamination. Tertiary blast injuries of the extremity may result in traumatic amputations, fractures, and severe soft-tissue injuries. Quaternary injuries most often are burns. Following treatment and stabilization of immediate life-threatening conditions, all patients are given antibiotic and tetanus prophylaxis. Débridement and wound excision are started as early as possible, with repeat débridement performed as necessary; fasciotomies also are performed to prevent compartment syndrome. Well-vascularized muscular free flaps provide soft-tissue coverage for blast-injured extremities. The closed-open technique of flap closure allows reexamination of the wound, further irrigation, débridement, and later bone and soft-tissue reconstruction.


[Determination of levofloxacin in plasma and cerebrospinal fluid with HPLC and its pharmacokinetics in patients undergoing neurosurgical operations].
A RP-HPLC method was developed to determine the concentrations of levofloxacin in plasma and cerebrospinal fluid and its pharmacokinetics were studied in patients undergoing neurosurgical operations. C18H37 column was eluted with the mobile phase consisting of 10 mmol.L-1 KH2PO4-10 mmol.L-1(C4H9)4Br-CH3CN(45:45:10, pH 3.0) and the utraviolet absorbance was monitored at 295 nm. Ciprofloxacin was used as internal standard. The mean recoveries were 74.76% in plasma and 82.43% in cerebrospinal fluid, with the lowest detectable limits of 10 micrograms.L-1 and 6 micrograms.L-1, respectively. The RSD for the intra-day and inter-day were all less than 5%. A single oral administration of 300 mg levofloxacin tablet was given to 10 patients undergoing neurosurgical operations. The pharmacokinetic parameters in blood and in cerebrospinal fluid could be described by one compartment open model. The pharmacokinetic parameters were: blood Ke 0.12 +/- 0.04 h-1, T1/2 6.05 +/- 1.68 h, Tmax 1.05 +/- 0.29 h, Cmax 3.67 +/- 0.42 mg.L-1, AUC 33.43 +/- 7.32 mg.h.L-1, CLs 9.46 +/- 2.53 L.h-1, Vd 77.49 +/- 7.39 L; cerebrospinal fluid Ke 0.11 +/- 0.04 h-1, T1/2 6.95 +/- 1.88 h, Tmax 3.56 +/- 1.24 h, Cmax 1.68 +/- 0.25 mg.L-1, AUC 23.70 +/- 5.62 mg.h.L-1, CLs 13.70 +/- 5.11 L.h-1, Vd 126.61 +/- 13.20 L.


Effect of protein S-glutathionylation on Ca2+ homeostasis in cultured aortic endothelial cells.
Diamide is a membrane-permeable, thiol-oxidizing agent that rapidly and reversibly oxidizes glutathione to GSSG and promotes formation of protein-glutathione mixed disulfides. In the present study, the acute effect of diamide on free cytosolic Ca2+ concentration ([Ca2+]i) was examined in fura-2-loaded bovine aortic endothelial cells. At low concentrations (50, 100 μM), diamide reversibly increased spontaneous, asynchronous Ca2+ oscillations, whereas, at higher concentrations (250, 500 μM), diamide caused an immediate synchronized Ca2+ oscillation in essentially all cells of the monolayer, followed by a time-dependent rise in basal [Ca2+]i. The effects of diamide on [Ca2+]i dynamics were independent of extracellular Ca2+. Inhibition of phospholipase C by U-73122 prevented the observed changes in [Ca2+]i. Additionally, the diamide-induced oscillations, but not the rise in basal [Ca2+]i, were blocked by inhibition of the inositol-1,4,5-trisphosphate (IP3) receptor (IP3R) by 2-aminoethyl diphenyl borate. However, diamide failed to alter the plasmalemmal distribution of a green fluorescent protein-tagged phosphatidylinositol-4,5-bisphosphate binding protein, demonstrating that diamide does not activate phospholipase C. Inhibition of glutathione reductase by N,N'-bis(2-chloroethyl)-N-nitrosourea or depletion of glutathione by l-buthionine-sulfoximine enhanced the effects of diamide, which, under these conditions, could only be reversed by addition of dithiothreitol to the wash buffer. Biochemical assays showed that both the IP3R and the plasmalemmal Ca2+-ATPase pump could be reversibly glutathionylated in response to diamide. These results demonstrate that diamide promotes Ca2+ release from IP3-sensitive internal Ca2+ stores and elevates basal [Ca2+]i in the absence of extracellular Ca2+, effects that may be related to a diamide-induced glutathionylation of the IP3R and the plasmalemmal Ca2+-ATPase Ca2+ pump, respectively.


Management of sight-threatening optic nerve sheath meningioma with fractionated stereotactic radiotherapy.
Previous management of optic nerve sheath meningioma included conservative observation, surgery, radiosurgery and conventional radiotherapy. All carried significant risk, either of visual loss or damage to adjacent structures. Fractionated stereotactic radiotherapy appears to have few side-effects and may preserve or improve vision. To date only three groups have published their experience with this modality. A retrospective review of patients with optic nerve sheath meningioma treated with stereotactic radiotherapy in an academic complex was conducted. Patients with greater than 18 months follow up and no previous related surgery were eligible for inclusion. Patients received an average of 43.5 Gy to the tumour in 26 fractions. Case records from the treating institutions as well as those of the referring ophthalmologist were analysed. The limited literature on the subject was reviewed in order to draw conclusions relevant to contemporary patient management. Four patients had undergone follow up for over 18 months. Prior to treatment all had exhibited progressive loss of visual function. In all cases visual function remained stable or improved at the last assessment. Side-effects included radiologically detected cerebral changes in one patient and transient hair loss in one patient. This treatment modality represents a promising refinement of previous treatment options. It may be offered to patients who demonstrate progressive loss of visual function caused by optic nerve sheath meningioma. It offers significant advantages over other currently available therapeutic options but its use should be tempered by the knowledge that long-term side-effects are yet to be determined.


Subcutaneous cerebrospinal fluid reservoirs in patients with acute leukaemia.
Subcutaneous cerebrospinal fluid (Ommaya) reservoirs were inserted in 23 patients wich acute leukaemia and 2 patients with malignant lymphoma. In 9 leukaemia patients reservoirs were used for the prophylaxis of central nervous system leukaemia: only 1 patient developed meningeal leukaemia but less invasive therapy has now been shown to achieve effective prophylaxis and prophylactic use of Ommaya reservoirs has been discontinued. In 16 patients, reservoirs were inserted as aids to the treatment of meningeal leukaemia or lymphoma. Intracranial disease was successfully controlled and recurrences were prevented but patients eventually died from relapse of their systemic disease. The principal complications of the subcutaneous reservoirs were obstruction, misplacement, and one case of infection. Leucoencephalopathy in several patients was attributable to irradiation and cytotoxic drugs and not to the reservoirs. Problems due to misplacement of the reservoir occurred in 3 out of 13 reservoirs inserted by the occipital route and in only 1 of 12 reservoirs inserted by a frontal approach. With adequate supervision, the reservoirs are valuable aids to intrathecal therapy in patients with established meningeal leukaemia or lymphoma.


PIASgamma is required for faithful chromosome segregation in human cells.
The precision of the metaphase-anaphase transition ensures stable genetic inheritance. The spindle checkpoint blocks anaphase onset until the last chromosome biorients at metaphase plate, then the bonds between sister chromatids are removed and disjoined chromatids segregate to the spindle poles. But, how sister separation is triggered is not fully understood. We identify PIASgamma as a human E3 sumo ligase required for timely and efficient sister chromatid separation. In cells lacking PIASgamma, normal metaphase plates form, but the spindle checkpoint is activated, leading to a prolonged metaphase block. Sister chromatids remain cohered even if cohesin is removed by depletion of hSgo1, because DNA catenations persist at centromeres. PIASgamma-depleted cells cannot properly localize Topoisomerase II at centromeres or in the cores of mitotic chromosomes, providing a functional link between PIASgamma and Topoisomerase II. PIASgamma directs Topoisomerase II to specific chromosome regions that require efficient removal of DNA catenations prior to anaphase. The lack of this activity activates the spindle checkpoint, protecting cells from non-disjunction. Because DNA catenations persist without PIASgamma in the absence of cohesin, removal of catenations and cohesin rings must be regulated in parallel.


The PROCESS experiment: an astrochemistry laboratory for solid and gaseous organic samples in low-earth orbit.
The PROCESS (PRebiotic Organic ChEmistry on the Space Station) experiment was part of the EXPOSE-E payload outside the European Columbus module of the International Space Station from February 2008 to August 2009. During this interval, organic samples were exposed to space conditions to simulate their evolution in various astrophysical environments. The samples used represent organic species related to the evolution of organic matter on the small bodies of the Solar System (carbonaceous asteroids and comets), the photolysis of methane in the atmosphere of Titan, and the search for organic matter at the surface of Mars. This paper describes the hardware developed for this experiment as well as the results for the glycine solid-phase samples and the gas-phase samples that were used with regard to the atmosphere of Titan. Lessons learned from this experiment are also presented for future low-Earth orbit astrochemistry investigations.


The 12-hour weekend plan--does the nursing staff really like it?
After nursing administrators at one Boston hospital implemented a new system for weekend coverage, they surveyed the staff's response to the trial plan. Here the author explains their system, what they learned when they measured its effects, and how they used staff responses to improve it. They proceed to examine the new system's effects on recruitment and absenteeism. The experiences shared here should assist other nursing administrators who are looking at new scheduling approaches and their viability in resolving staffing problems.


Biomimetic synthesis: discovery of xanthanolide dimers.
Starting from xanthatin, the biomimetic synthesis of 4β,5β-epoxyxanthatin-1α,4α-endoperoxide, a novel monomeric xanthanolide, has been achieved. Moreover, four unprecedented xanthanolide dimers were synthesized by three different dimerizations of xanthatin, either in a head-to-head or head-to-tail fashion. Notably, these dimeric compounds were firstly identified as artifacts in the laboratory, and two of them, mogolides A and B, proved to be natural products present in the Xanthium mogolium Kitag plant.


War-related trauma and symptoms of posttraumatic stress disorder among adult Kosovar refugees.
Since 1999, almost 16,000 Kosovar refugees have entered the United States. Few studies have investigated trauma and symptoms of posttraumatic stress disorder (PTSD) in this population. We conducted a caseworker-assisted survey of 129 Kosovar refugees (aged 18 to 79 years, 55% male). Of these individuals, 78 (60.5%) showed the likely presence of PTSD. The mean number of war-related traumatic events reported was 15 (SD = 4.5). Higher PTSD scores were associated with more traumatic events and female gender.


Patients who have undergone rotator cuff repair experience around 75% functional recovery at 6 months after surgery.
The purposes of this study were to (1) evaluate changes in recovery patterns [i.e., clinical outcomes, range of motion (ROM)] in the first 12 months following surgery, (2) identify potential prognostic factors of early clinical outcomes after rotator cuff repair (RCR). The study cohort included 344 consecutive patients treated with RCR. Data were collected prospectively and included pre- and perioperative variables. Univariate and multivariate linear regression analyses for various parameters including demographics, pre- and perioperative variables were used to predict shoulder function at 12-month follow-up, as measured by clinical outcomes and ROM. Significant improvement in all clinical scores and ROM were noted during serial follow-ups after RCR (all p < 0.001). Multivariate analysis revealed that female sex, older age, more anchors, diabetes mellitus, and preoperative stiffness were independently associated with worse shoulder function 3 months after RCR. Including the 3 months factors, heavy labor, use of the suture-bridge technique, and large tears were also independently associated with worse outcomes 6 months after surgery. Heavy labor, suture-bridge technique, diabetes mellitus, and preoperative stiffness were associated with significantly worse functional outcomes at 12 months after surgery (all p < 0.05). Functional recovery based on clinical outcomes (i.e., UCLA, ASES scores) showed approximately 60% of ultimate recovery at 3 months and approximately 75% recovery at 6 months after RCR. Female sex, diabetes mellitus, preoperative stiffness, a larger number of anchors, suture bridge technique, heavy labor, old age and, larger tears were prognostic factors of poor clinical results or ROM in the short-term follow-up intervals. Knowledge of these prognostic factors may lead to improved insight for physicians to predict the pattern of the recovery and patient expectations accordingly. III, A cohort study.


The role of liaison psychiatry in an AIDS unit.
The experience of a liaison psychiatry team working in the setting of an AIDS unit is described. Several clinical themes are identified which highlight crucial issues with regard to both diagnosis and management. These issues are illustrated by case histories. Discussion draws attention to the value of using a biopsychosocial model in order to understand aetiology and to formulate appropriate management. Issues related to staff involvement provide a further theme for discussion.


SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection.
The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients. In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis.


[Endocardial fibroelastosis (E.F.) and its differential diagnosis].
The endocardial fibroelastosis (EFE) is the most frequent cardiomyopathy. This disease is characterised by endocardial hyperplasia due to proliferation of elastic and collagenous fibres. There are primary and secondary forms. Within the primary form, the infantile form is the most frequent and of greatest importance to the pediatrician. This form is more a syndrom than a distinct disease. It is a reaction of the endocard due to several noxes. Lately a possible viral etiology is being discussed e.g. Parotitis, Coxsackie or other viruses. Clinical criteria for diagnosis are: cardiomegaly, left ventricular hypertrophy seen in 97% in the ECG, the absence of a murmur (or a soft apical mumur) absence of cyanosis and absence of systemic disease. Differential diagnosis is mainly between fibroplastic parietal endocarditis (FPE), cardiovascular collagenosis (CC) and endomyocard fibrosis (EMF). In FPE thrombosis is frequent and typically there is eosinophilia. CC is found in South Africa and is characterised by edema and fibrinoid necrosis. MEF is present mainly in Uganda, Nigeria and South India, characterised by endocardial fibrosis, valve involvement and eosinophilia. The obstructive hypertrophic cardiomyopathy is characterised by a pronounced cardiomegaly, insufficient weight gain as well as dyspnea and cyanosis. Catheterization shows a gradient across one or both of the outflow tracts due to hypertrophic subaortic or subpulmonic stenosis. Therapy of EFE consists in treating the cardiac decompensation and according to the severity of the disease, in steroids.


[Hemangiopericytoma of the lumbar spine].
Hemangiocytoma are rare malignant vascular tumor. Vertebral location is uncommun. They occur preferentially at the lumbo-sacrul spine with paravertebral extension. The features include spinal pains, para vertebral tumefaction and paresthesia. The CT and MRI scans can help to diagnosis which is histological. The treatment is surgical combined or no with radiotherapy. The pronostic is marqued by the recidive risk and metastases. We report a new case of vertebral hemangiopericytoma of the thoraco-lumbar spine with litteratur review.


Amino acid selective unlabeling for sequence specific resonance assignments in proteins.
Sequence specific resonance assignment constitutes an important step towards high-resolution structure determination of proteins by NMR and is aided by selective identification and assignment of amino acid types. The traditional approach to selective labeling yields only the chemical shifts of the particular amino acid being selected and does not help in establishing a link between adjacent residues along the polypeptide chain, which is important for sequential assignments. An alternative approach is the method of amino acid selective 'unlabeling' or reverse labeling, which involves selective unlabeling of specific amino acid types against a uniformly (13)C/(15)N labeled background. Based on this method, we present a novel approach for sequential assignments in proteins. The method involves a new NMR experiment named, {(12)CO( i )-(15)N( i+1)}-filtered HSQC, which aids in linking the (1)H(N)/(15)N resonances of the selectively unlabeled residue, i, and its C-terminal neighbor, i + 1, in HN-detected double and triple resonance spectra. This leads to the assignment of a tri-peptide segment from the knowledge of the amino acid types of residues: i - 1, i and i + 1, thereby speeding up the sequential assignment process. The method has the advantage of being relatively inexpensive, applicable to (2)H labeled protein and can be coupled with cell-free synthesis and/or automated assignment approaches. A detailed survey involving unlabeling of different amino acid types individually or in pairs reveals that the proposed approach is also robust to misincorporation of (14)N at undesired sites. Taken together, this study represents the first application of selective unlabeling for sequence specific resonance assignments and opens up new avenues to using this methodology in protein structural studies.


Effects of noise-cancelling headphones on music experience during aerobic exercise.
Exercise psychology researchers have repeatedly demonstrated the positive effects of music on exercise performance and affective responses. However, the impact of ambient noise (i.e., any environmental and/or bodily sound interference) on psychological responses to music during aerobic exercise has not been thoroughly examined. To test the effects of ambient noise, participants were randomly assigned to either a control group or one of two experimental groups (music with or without noise-cancelling features). Participants completed the Balke and Ware Treadmill Exercise Test until voluntary exhaustion. Measures of attentional focus and perceived exertion were taken every minute during the test. A significant main effect of group on attentional focus was observed, indicating that participants in the control group experienced more associative thoughts when compared to the experimental groups (ηp2 = .15). No significant differences were observed across conditions for any other dependent variable. Accordingly, it appears reasonable to postulate that the attentional shifts caused by interoceptive sensory cues may have a more pronounced influence on movement execution than the presence/absence of ambient noise and/or music.