Definition of an N-terminal actin-binding domain and a C-terminal Ca2+ regulatory domain in human brevin.
Brevin is a Ca2+-modulated actin-associated protein that will sever F-actin and cap barbed filament ends. Limited proteolysis with chymotrypsin or subtilisin cleaves the molecule approximately in half. Cleavage is approximately 10-fold more rapid in Ca2+ than in EGTA. The two fragments are readily separated from each other and from undigested brevin by high pressure liquid chromatography on a DEAE resin. A 40,000-mol-wt fragment from the N-terminal is not retained by DEAE, while a 45,000-mol-wt C-terminal fragment binds more tightly than brevin. The N-terminal fragment retains approximately 10% of the nucleation activity, caps barbed ends, and retains 50% of the total severing activity defined by dilution induced depolymerization of pyrenyl actin, but, in contrast to brevin, none of these functions are affected by Ca2+. Fluorescent actin binding studies and gel-filtration demonstrate that the 40,000-mol-wt fragment binds two actin monomers. The 45,000-mol-wt C-terminal fragment has no severing, nucleating, or capping activity. Cross-reaction with two monoclonal antibodies against two specific Ca2+-induced conformations of human platelet gelsolin suggest that both Ca2+ binding sites are located on the carboxyl half of the brevin molecule. One epitope, defined as the rapidly exchanging Ca2+ binding site in the gelsolin-actin complex, is lost when a 20,000-mol-wt fragment is cleaved from the carboxyl terminal. The second epitope, related to the poorly exchanging Ca2+ binding site in the complex, is nearer the middle of the brevin molecule.


Ophthalmic patients on antithrombotic drugs: a review and guide to perioperative management.
The changing profile of patients undergoing ophthalmic surgery, with an increase in prevalence of antiplatelet and anticoagulant drug use, predisposes to bleeding complications. This mandates an awareness of these agents, allowing optimal patient management. We review traditional and newer agents in the context of cataract, vitreoretinal, glaucoma and oculoplastic surgery. Recommendations are given for continuation, cessation and re-commencement of these agents in order to minimise the risk of bleeding and thrombotic/thromboembolic complications.


Involvement of the larynx motor area in singing-voice perception: a TMS study(†).
Recent evidence has reported that the motor system has a role in speech or emotional vocalization discrimination. In the present study we investigated the involvement of the larynx motor representation in singing perception. Twenty-one non-musicians listened to short tones sung by a human voice or played by a machine and performed a categorization task. Thereafter continuous theta-burst transcranial magnetic stimulation was applied over the right larynx premotor area or on the vertex and the test administered again. Overall, reaction times (RTs) were shorter after stimulation over both sites. Nonetheless and most importantly, RTs became longer for sung than for "machine" sounds after stimulation on the larynx area. This effect suggests that the right premotor region is functionally involved in singing perception and that sound humanness modulates motor resonance.


PAM binding ensures orientational integration during Cas4-Cas1-Cas2-mediated CRISPR adaptation.
Adaptation in CRISPR-Cas systems immunizes bacteria and archaea against mobile genetic elements. In many DNA-targeting systems, the Cas4-Cas1-Cas2 complex is required for selection and processing of DNA segments containing PAM sequences prior to integration of these "prespacer" substrates as spacers in the CRISPR array. We determined cryo-EM structures of the Cas4-Cas1-Cas2 adaptation complex from the type I-C system that encodes standalone Cas1 and Cas4 proteins. The structures reveal how Cas4 specifically reads out bases within the PAM sequence and how interactions with both Cas1 and Cas2 activate Cas4 endonuclease activity. The Cas4-PAM interaction ensures tight binding between the adaptation complex and the prespacer, significantly enhancing integration of the non-PAM end into the CRISPR array and ensuring correct spacer orientation. Corroborated with our biochemical results, Cas4-Cas1-Cas2 structures with substrates representing various stages of CRISPR adaptation reveal a temporally resolved mechanism for maturation and integration of functional spacers into the CRISPR array.


Physical modeling of animal cell damage by hydrodynamic forces in suspension cultures.
Physical damage of animal cells in suspension culture, due to stirring and sparging, is coupled with complex metabolic responses. Nylon microcapsules, therefore, were used as a physical model to study the mechanisms of damage in a stirred bioreactor and in a bubble column. Microcapsule breaskage folowed first-order kinetices in all experiments Entrainment of bubbles into the liquid phase in the stirred bioreactor gave more microcapsule breakage. In the bubble column, the bubble bursting zone at gas-liquid interface was primarily responsible for microcapsule breakage. The forces on the microcapsules were equivalent to an external pressure of approximately 4 x 10(4) N. m(-2), based on the critical microcapsule diameter for survival of 190 microm. A stable foam layer, however, was found to be effective in protecting microcapsules from damage. The microcapsule transport to the gas-liquid interface and entrainment into the foam phase was consistent with flotation by air bubbles. This result implies that additives and operation of bioreactors should be selected to minimize flotation of cells.


[Rainfall and acute febrile syndrome in a dengue-endemic area].
Describing patterns of acute febrile syndrome (AFS) consultation related to dengue and evaluating association with rainfall. 318 undifferentiated AFS patients were detected in two clinics during a 7-month period (March to September) and then included in systematic clinical follow-up. 31 % of them (81/281) were IgM positive for dengue. Rainfall (litres/square meter-day) during the previous weeks was evaluated as a variable for predicting consultation patterns. June, July and September were the months in which the greatest number of AFS cases occurred. Cases of dengue were only significantly more frequent during July. When evaluating the previous weeks' rainfall patterns, consultation for AFS was seen to be associated with the average rainfall registered 5 weeks beforehand and such association was independent of the institution and/or month (incidence rate ratio IRR=1,04; 1-1.08 95 %CI, p=0.045). On the other hand, 5 consecutive weeks' average rainfall was an independent predictor of consultation for dengue 4 weeks later on (RTI=1 ,6 ; 1,15-2,22 95 %CI, p=0.006). A linear relationship was thus proposed (regarding these sentinel clinics) between consultation for dengue and rainfall: lt/mt-day (5 weeks' average rainfall) X 0 ,72 (0,60-0,84 95 %CI, p<0.001) = cases for each 100 000 habitants per week (4 weeks later). Studying rainfall could predict the pattern of consultation for dengue in endemic regions.


Apparent diffusion coefficient value for a B-cell central nervous system lymphoma in a cat.
This report involves a 10-year-old male mixed-breed cat with a B-cell central nervous system (CNS) lymphoma. The cat presented with ataxia progressing to left hemiparesis. While haematological findings were normal, serum biochemistry showed a high creatine phosphokinase concentration. MRI revealed a homogeneously enhancing well-demarcated extra-axial lesion involving the region of the left lateral aperture with oedema in left flocculus and left medulla oblongata. On diffusion-weighted imaging, the lesion margins showed marked hyperintensity relative to the right cerebellar hemisphere. On an apparent diffusion coefficient map, the lesion appeared hypointense, with an apparent diffusion coefficient value of 0.57 ± 0.01 × 10-3 mm2/s. Cerebrospinal fluid (CSF) analysis and cytology, and genetic analysis of CSF lymphoblasts confirmed a diagnosis of B-cell lymphoma. The owner opted for palliative treatment with prednisolone (1 mg/kg q12h); however, the cat died of dyspnoea 10 days after presentation. CNS lymphomas, which are the second most common intracranial tumours in cats, are highly infiltrative lesions and radical surgical excision is not recommended. Therefore, accurate diagnosis is crucial. However, contrast-enhanced MRI cannot always differentiate these lesions from other conditions, including other CNS tumours and strokes. To the best of our knowledge, this is the first report to document the diffusion-weighted imaging features and apparent diffusion coefficient value for a feline CNS lymphoma. These findings are expected to improve the diagnostic accuracy of these lesions in cats.


New species and new geographical record of Ochrotrichia Mosely 1934 Trichoptera: Hydroptilidae) from Rio de Janeiro state, Brazil.
Ochrotrichia, with about 160 extant species in the New World, is the most diverse genus assigned to the Ochrotrichiinae. Despite its diversity, only eight species were previously recorded from Brazil, only one from Rio de Janeiro state. In this paper, we describe three new species from Parque Nacional da Tijuca, an Atlantic Forest area at Rio de Janeiro. Ochrotrichia nematomorpha sp. nov. is placed within the O. xena Group, having a plate-like tergum X, with an unusual phallus which is slender and pointed apically. Ochrotrichia sagitta sp. nov. and O. taunay sp. nov. belong to the O. aldama Group, each having a divided tergum X, but being distinguished from the others in this group by the arrowhead-like apex of left lateral process of tergum X (O. sagitta) and the presence of two dorsal spine-like projections on tergum X (O. taunay). Furthermore, O. caatinga Souza, Santos Takiya, 2014 is reported for the first time from Rio de Janeiro state.


Chromatin structure is required to block transcription of the methylated herpes simplex virus thymidine kinase gene.
Inhibition of herpes simplex virus (HSV) thymidine kinase (TK) gene transcription (pHSV-106, pML-BPV-TK4) by DNA methylation is an indirect effect, which occurs with a latency period of approximately equal to 8 hr after microinjection of the DNA into TK- rat 2 and mouse LTK- cells. We have strong evidence that chromatin formation is critical for the transition of the injected DNA from methylation insensitivity to methylation sensitivity. Chromatin was reconstituted in vitro by using methylated and mock-methylated HSV TK DNA and purified chicken histone octamers. After microinjection, the methylated chromatin was always biologically inactive, as tested by autoradiography of the cells after incubation with [3H]thymidine and by RNA dot blot analysis. However, in transformed cell lines, reactivation of the methylated chromatin occurred after treatment with 5-azacytidine. Furthermore, integration of the TK chromatin into the host genome is not required to block expression of the methylated TK gene. Mouse cells that contained the pML-BPV-TK4 chromatin permanently in an episomal state also did not support TK gene expression as long as the TK DNA remained methylated.


Study of transitions between wetting states on microcavity arrays by optical transmission microscopy.
In this article, we present a simple and fast optical method based on transmission microscopy to study the stochastic wetting transitions on micro- and nanostructured polymer surfaces immersed in water. We analyze the influence of immersion time and the liquid pressure on the degree of water intrusion in individual microcavities on these surfaces as well as the lifespan of their superhydrophobicity. We show that transitions among the three wetting states (Cassie, Cassie-impregnating, and Wenzel) occur with a certain pressure threshold (300 mbar for a microcavity diameter of 7.5 μm). Below this threshold, the transitions between the Cassie and the Cassie-impregnating states are reversible, whereas above this threshold, irreversible transitions to the Wenzel state start to occur. The transitions between the different wetting states can be explained by taking into account both the Young-Laplace equation for the water menisci in the cavities and the diffusion of dissolved gas molecules in the water. In addition, the wetting transitions had a stochastic nature, which resulted from the short diffusion distance for dissolved gas molecules in the water between neighboring cavities. Furthermore, we compared the contact angle properties of two polymeric materials (COC and PP) with moderate hydrophobicity. We attributed the difference in the water repellency of the two materials to a difference in the wetting of their nanostructures. Our experimental observations thus indicate that both the diffusion of gas molecules in water and the wetting properties of nanostructures are important for understanding the sustainability of superhydrophobicity of surfaces under water and for improving the structural design of superhydrophobic surfaces.


Endplate topography of denervated and disused rat neuromuscular junctions: comparison by scanning and light microscopy.
The effect of denervation and tetrodotoxin-induced muscle disuse on endplate structure was investigated in rat hind-limb muscles. The endplate was visualized by light microscopic cholinesterase staining and by scanning electron microscopy. Denervation resulted in a reduction in histochemically determined endplate dimensions proportionate to the decrease in muscle fiber circumference. Scanning electron microscopy, on the other hand, revealed a flattening or more often collapse of primary grooves with a reduction in the width of the endplate but no longitudinal shrinkage. Primary groove area per se was not measurable due to the loss of primary groove structural integrity. Thus, the apparent histochemical diminution of endplate length after denervation was artefactual, probably due to loss of cholinesterase activity and impeded access of substrate. In disuse, cholinesterase staining revealed a similar reduction in endplate girth with fiber atrophy but with a corresponding increase in endplate length. Scanning electron microscopy of disused muscle fibers confirmed these histochemical findings and the overall preservation of primary groove area. Disuse also resulted in an increase in the number of intrasynaptic primary groove branches as visualized by scanning electron microscopy. Finally, a specialized endplate "raised area", prominent in soleus muscle, was greatly reduced after disuse but much less so after denervation. Thus, after denervation, primary groove structural integrity is lost and the shape of the endplate passively follows that dictated by circumferential loss of surface membrane. In disused muscle, presence of an intact axon preserves the structure and area but not the orientation of the primary grooves which are distorted by fiber atrophy. Disuse also strongly affects other endplate surface structures visualized by scanning electron microscopy.


Current trends in bilateral internal thoracic artery use for coronary revascularization: Extending benefit to high-risk patients.
We sought to identify the trends in bilateral internal thoracic artery use and determine the degree to which the survival advantage of bilateral internal thoracic artery revascularization persists among perceived "high-risk" patients, compared with the use of left internal thoracic artery alone. A retrospective review was conducted of patients who underwent isolated coronary artery bypass grafting for multivessel coronary artery disease at the Mayo Clinic between January 2000 and December 2015. Propensity score matching was performed between patients with bilateral internal thoracic artery and left internal thoracic artery alone grafts (1011 matched pairs). Effect of bilateral internal thoracic artery use on survival in "high-risk" patients (ejection fraction <40%, body mass index ≥30, age ≥70 years, diabetes, chronic lung disease, cerebrovascular accident) was evaluated. A total of 6468 isolated coronary artery bypass grafts were performed (5431 using left internal thoracic artery alone, 1037 using bilateral internal thoracic artery). There was an increasing trend in bilateral internal thoracic artery use (P value for linear trend = .005), with the percentage of coronary artery bypass grafting cases with bilateral internal thoracic artery doubling over the last 4 years (13% in 2012 to 27% in 2015). Propensity-matched comparisons showed a survival advantage for bilateral internal thoracic artery (hazard ratio, 0.81; 95% confidence interval, 0.66-0.99; P = .043). Risk of deep sternal wound infection, although higher in the bilateral internal thoracic artery group, was not significant (1.2% vs 0.5%; P = .088). None of the "high-risk" subsets of patients showed an adverse effect of bilateral internal thoracic artery on survival. Bilateral internal thoracic artery use in coronary artery bypass grafting is increasing over time. There is a consistent survival benefit with bilateral internal thoracic artery use, extending to patients with higher-risk comorbidities, suggesting the need for further expansion in use of this technique.


Up-regulated microRNA-299 corrected with poor prognosis of glioblastoma multiforme patients by targeting ELL2.
An increasing understanding of the genes and molecular pathways of glioblastoma multiforme (GBM) can provide us a useful insight for the development of more effective targeted therapeutic. To investigate the expression and clinical significance of miR-299 and its target genes in GBM, the expression levels of miR-299 and its target gene in human normal brain tissues and GBM were analyzed in silico using genes microarray and hierarchical clustering analysis followed by validation with quantitative RT-PCR. Our results show that miR-299 is up-regulated in GBM patients. Moreover, patients with low miR-299 expression had longer overall survival (OS) compared with those with high miR-299 expression. RNA polymerase II elongation factor, ELL2, was identified as a miR-299 direct target. High expression of ELL2 together with miR-299 down-regulation correlated with a shorter median OS. Our results provide the first evidence that ELL2 is a direct target of miR-299 and increased ELL2 expression and down-regulation of miR-299 are associated with GBM progression and poor prognosis in patients, suggesting that ELL2 and miR-299 might have potential prognostic value and be used as tumor biomarkers for the diagnosis of patients with GBM.


Injuries and behavior of raccoons (Procyon lotor) captured in the Soft Catch and the EGG traps in simulated natural environments.
The behavior and injuries of raccoons held for 12 and 24 hr in the Soft Catch and the EGG traps were studied in simulated natural environments. Nine raccoons held for 12 hr in the Soft Catch received minor injuries. However, one of nine raccoons held for 24 hr in this trap mutilated itself. The EGG trap caused only minor injuries to nine raccoons held for 12 hr, and nine others held for 24 hr. Thus the EGG trap can be expected, at a 95% level of confidence, to hold > or = 70% of the raccoons on traplines for 24 hr without serious injury. Raccoons captured in the Soft Catch fought their surroundings more than the trap. Those captured in the EGG trap fought the trap more than their surroundings. During the 24-hr capture study, escape behavior was more intense during the first 12 hr of capture, during both day and night.


Light absorption by aerosol particles: First International Workshop.
The First International Workshop on light absorption by aerosol particles is introduced, and its goal-to separate the two sources of variability in light absorption measurements by establishing instrumentation errors-is reviewed.


Technological characteristics and clinical indications of piezoelectric bone surgery.
Piezoelectric bone surgery, also simply known as piezosurgery, is a new technique for osteotomy and osteoplasty utilizing an innovative ultrasonic surgical apparatus. This technique was created and developed in response to the need to reach major levels of precision and safety in bone surgery, as compared to that available by the usual manual and motorized instruments. The instrument which offers these results, known as the Mectron Piezosurgery Device, is characterized by piezoelectric ultrasonic vibrations of a frequency of 29 kHz and a range between 60/200 Hz. Due to their characteristics, the microvibrations allow a selective cut of only mineralized structures without damaging soft tissues, which remain undamaged even in case of accidental contact. The micrometric vibration ensures precise cutting action and at the same time maintains a blood-free site because of the physical phenomenon of cavitation. The micrometric vibration makes the instrument manageable and permits major interoperative control with a consequent increase in safety especially in anatomically difficult areas. The absence of macrovibrations makes the instrument more manageable and allows greater interoperative control with a significant increase in the cutting safety in the more difficult anatomical cutting zones. Given its innovative nature, piezosurgery distinguishes itself as being different from the conventional techniques utilised in bone surgery. Consequently, it requires different surgical skill. To master the right surgical skill it is essential to demonstrate an adequate learning curve.


Latissimus dorsi breast reconstruction: how much nerve resection is necessary to prevent postoperative muscle twitching?
The latissimus dorsi muscle flap represents a valuable option in breast reconstruction but can result in postoperative twitching and retraction, discomfort, arm movement limitations, and breast deformation. These complications can be avoided by denervation of the thoracodorsal nerve; however, the optimal method of nerve management is unknown. This study presents the authors' experience with the outcomes of latissimus dorsi flaps for breast reconstruction in the light of thoracodorsal nerve management strategies. The authors retrospectively collected data from 74 patients who underwent partial or total breast reconstruction with a latissimus dorsi flap alone or with an implant between January of 1999 and October of 2011. Follow-up data were collected at 12 and 24 months postoperatively. In 56 patients (75.7 percent), the latissimus dorsi muscle was denervated at the time of surgery, whereas the thoracodorsal nerve remained intact in 18 patients (24.3 percent). No partial or total flap loss was observed. At 12 and 24 months' follow-up, all patients with an intact thoracodorsal nerve showed twitching of the muscle, and 50 percent and 67.9 percent, respectively, of the denervated patients showed twitching (p < 0.001). No patient had twitching if more than 4 cm of nerve was excised at 12 or 24 months postoperatively, and the length of nerve resection was predictive of the presence of twitching. Denervation of the latissimus dorsi is a safe and reliable procedure that should be performed at the time of breast reconstruction and should include more than 4 cm to achieve a nontwitching breast with a stable volume and shape.


Escherichia coli ribosomal protein L4 stimulates transcription termination at a specific site in the leader of the S10 operon independent of L4-mediated inhibition of translation.
Transcription of the 11-gene S10 operon of Escherichia coli is inhibited by excess ribosomal protein L4, the product of the third gene of the operon. Previous studies suggested that L4 regulates transcription by modulating the level of readthrough at an attenuator in the S10 leader. To understand better the molecular details of the transcriptional regulation, we have determined the site of L4-induced termination of transcription using a method that allows us to map the 5' and 3' ends of newly synthesized RNA. Our results indicate that L4 stimulates termination about 140 bases from the transcription start site. Thus, the termination point is more than 30 bases upstream from the most proximal structural gene of the S10 operon, and coincides with a string of U residues on the descending side of a terminator-like hairpin structure. Since L4 is also known to inhibit translation of the S10 operon, we have analyzed the role of translation control in the protein's regulation of transcription by deleting sequences downstream from the termination site, including bases involved in translation initiation of the proximal structural gene. We find that the first 150 bases of the S10 leader contain the information sufficient for L4-mediated attenuation control and, therefore, that L4 regulates transcription by a mechanisms that is independent of the protein's inhibition of translation.


Overexpression of TACC3 in Breast Cancer Associates With Poor Prognosis.
Increasing evidences suggest that transforming acidic coiled-coil protein 3 (TACC3) is associated with various types of human cancer. However, the expression of TACC3 in breast cancer tissues remains largely unknown. To identify whether TACC3 can serve as a biomarker for the diagnosis and prognosis of breast cancer, quantitative polymerase chain reaction, western blotting, and immunohistochemistry staining were utilized to detect the expression of TACC3. The mRNA and protein levels of TACC3 in breast cancer samples were novelty higher compared with nontumorous breast tissues. Immunohistochemistry results revealed TACC3 expression was significantly correlated to lymphoid nodal metastasis (P=0.035) and HER-2 status (P=0.021). The patients with high expression of TACC3 had a significantly poor prognosis compared with patients with low expression (P=0.017), especially in the patients with pathological tumor size 2-4 status (P=0.028). Furthermore, multivariate analysis indicated that TACC3 expression was an independent prognostic factor for breast cancer patients (P=0.029). This study, first, suggested TACC3 might be an important molecular marker for diagnosis and prognosis of breast cancer.


Marked improvement of cytotoxic effects induced by docetaxel on highly metastatic and androgen-independent prostate cancer cells by downregulating macrophage inhibitory cytokine-1.
Overexpression of macrophage inhibitory cytokine-1 (MIC-1) frequently occurs during the progression of prostate cancer (PC) to androgen-independent (AI) and metastatic disease states and is associated with a poor outcome of patients. The gain- and loss-of-function analyses of MIC-1 were performed to establish its implications for aggressive and chemoresistant phenotypes of metastatic and AI PC cells and the benefit of its downregulation for reversing docetaxel resistance. The results have indicated that an enhanced level of secreted MIC-1 protein in PC3 cells is associated with their acquisition of epithelial-mesenchymal transition features and higher invasive capacity and docetaxel resistance. Importantly, the downregulation of MIC-1 in LNCaP-LN3 and PC3M-LN4 cells significantly decreased their invasive capacity and promoted the antiproliferative, anti-invasive and mitochrondrial- and caspase-dependent apoptotic effects induced by docetaxel. The downregulation of MIC-1 in PC3M-LN4 cells was also effective in promoting the cytotoxic effects induced by docetaxel on the side population (SP) endowed with stem cell-like properties and the non-SP cell fraction from PC3M-LN4 cells. These data suggest that the downregulation of MIC-1 may constitute a potential therapeutic strategy for improving the efficacy of current docetaxel-based chemotherapies, eradicating the total mass of PC cells and thereby preventing disease relapse and the death of PC patients.


Parenchymal interdependence and airway response to methacholine in excised dog lobes.
The objective of this investigation was to determine the minimum transpulmonary pressure (PL) at which the forces of interdependence between the airways and the lung parenchyma can prevent airway closure in response to maximal stimulation of the airways in excised canine lobes. We first present an analysis of the relationship between PL and the transmural pressure (Ptm) that airway smooth muscle must generate to close the airways. This analysis predicts that airway closure can occur at PL less than or equal to 10 cmH2O with maximal airway stimulation. We tested this prediction in eight excised canine lobes by nebulizing 50% methacholine into the airways while the lobe was held at constant PL values ranging from 25 to 5 cmH2O. Airway closure was assessed by comparing changes in alveolar pressure (measured by an alveolar capsule technique) and pressure at the airway opening during low-amplitude oscillations in lobar volume. Airway closure occurred in two of the eight lobes at PL = 10 cmH2O; in an additional five it occurred at PL = 7.5 cmH2O. We conclude that the forces of parenchymal interdependence per se are not sufficient to prevent airway closure at PL less than or equal to 7.5 cmH2O in excised canine lobes.


QTL and association analysis for skin and fibre pigmentation in sheep provides evidence of a major causative mutation and epistatic effects.
The pursuits of white features and white fleeces free of pigmented fibre have been important selection objectives for many sheep breeds. The cause and inheritance of non-white colour patterns in sheep has been studied since the early 19th century. Discovery of genetic causes, especially those which predispose pigmentation in white sheep, may lead to more accurate selection tools for improved apparel wool. This article describes an extended QTL study for 13 skin and fibre pigmentation traits in sheep. A total of 19 highly significant, 10 significant and seven suggestive QTL were identified in a QTL mapping experiment using an Awassi × Merino × Merino backcross sheep population. All QTL on chromosome 2 exceeded a LOD score of greater than 4 (range 4.4-30.1), giving very strong support for a major gene for pigmentation on this chromosome. Evidence of epistatic interactions was found for QTL for four traits on chromosomes 2 and 19. The ovine TYRP1 gene on OAR 2 was sequenced as a strong positional candidate gene. A highly significant association (P < 0.01) of grandparental haplotypes across nine segregating SNP/microsatellite markers including one non-synonymous SNP with pigmentation traits could be shown. Up to 47% of the observed variation in pigmentation was accounted for by models using TYRP1 haplotypes and 83% for models with interactions between two QTL probabilities, offering scope for marker-assisted selection for these traits.


Octenidine hydrochloride for the care of central venous catheter insertion sites in severely immunocompromised patients.
To determine the efficacy and tolerability of octenidine hydrochloride, a non-alcoholic skin antiseptic, for the care of central venous catheter (CVC) insertion sites. Prospective, observational study. Bone marrow transplantation unit of a university hospital. All consecutive patients with a nontunneled CVC were enrolled prospectively after informed consent. Octenidine hydrochloride (0.1%) was applied for disinfection at the CVC insertion site during dressing changes. The following cultures were performed weekly as well as at the occurrence of any systemic inflammatory response syndrome criteria: cultures of the skin surrounding the CVC entry site, cultures of the three-way hub connected to the CVC, blood cultures, and cultures of the CVC tip on removal. Enhanced microbiological methods (skin swabs of a 24-cm2 standardized area, roll plate, and sonication of catheter tips) were applied. One hundred thirty-five CVCs were inserted in 62 patients during the study period and remained for a mean period of 19.1 days, corresponding to 2,462 catheter-days. Bacterial density at the insertion site declined substantially over time, and most cultures became negative 2 weeks after insertion. Only 6 patients had a documented catheter-related bloodstream infection. The incidence density was 2.39 catheter infections per 1,000 catheter-days. No side effects were noted with application of the antiseptic. Disinfection with a skin antiseptic that contains octenidine hydrochloride is highly active and well tolerated. It leads to a decrease in skin colonization over time and may be a new option for CVC care.


Do additional full-length radiographs of the humerus and forearm improve the decision making in children with supracondylar humerus fractures?
We sought to determine the diagnostic utility of additional full-length radiographs of the forearm and humerus for pediatric supracondylar humerus fractures. A pediatric orthopedic surgeon and a senior orthopedic resident individually reviewed the initial humerus, forearm, and elbow radiographs of 55 children with a supracondylar humerus fracture and recommended definitive treatment (operative vs. nonoperative) on the basis of the modified Gartland classification. Interobserver agreements for classification and the recommended treatment were highest for the elbow radiographs (weighted κ=0.92). All disagreements in the recommended treatment were in fractures classified as Gartland type I versus II fractures. Although two children (4%) had an ipsilateral distal forearm fracture, selective versus routine use of additional full-length radiographs in children with a supracondylar humerus fracture needs to be evaluated further.


Poliovirus infections in four unvaccinated children--Minnesota, August-October 2005.
On September 29, 2005, the Minnesota Department of Health (MDH) identified poliovirus type 1 in an unvaccinated, immunocompromised infant girl aged 7 months (the index patient) in an Amish community whose members predominantly were unvaccinated for polio. The patient has no paralysis; the source of the patient's infection is unknown. Subsequently, poliovirus infections in three other children within the index patient's community have been documented. This report summarizes the ongoing investigation, provides information regarding poliovirus exposure risks and prevention measures in the United States, and offers recommendations to state health departments and clinicians.


Androgen receptor expression predicts different clinical outcomes for breast cancer patients stratified by hormone receptor status.
In this study we sought to correlate androgen receptor (AR) expression with tumor progression and disease-free survival (DFS) in breast cancer patients. We investigated AR expression in 450 breast cancer patients. We found that breast cancers expressing the estrogen receptor (ER) are more likely to co-express AR compared to ER-negative cancers (56.0% versus 28.1%, P < 0.001). In addition, we found that AR expression is correlated with increased DFS in patients with luminal breast cancer (P < 0.001), and decreased DFS in TNBC (triple negative breast cancer, P = 0.014). In addition, patients with HR+ tumors (Hormone receptor positive tumors) expressing low levels of AR have the lowest DFS among all receptor combinations. We also propose a novel prognostic model using AR receptor status, BRCA1, and present data showing that our model is more predictive of disease free survival compared to the traditional TMN staging system.


Why do poor adults rate their oral health poorly?
The reasons why socioeconomic circumstances are associated with oral health are not well understood. This study investigated whether psychosocial factors might play an explanatory role. Cross-sectional survey data were used from the 1999 National Dental Telephone Interview Survey together with information from an accompanying questionnaire sent to adult interviewees. Household income and self-rated oral health were assessed with single items and life dissatisfaction, personal constraint and perceived stress were evaluated with standard psychometric scales. Bivariate associations were tested using chi-square and ANOVA and odds ratios estimated for low self-rated oral health using logistic regression. Response to the questionnaire was 64.6 per cent and analysis was limited to dentate adults (n = 3678). Low household income was positively associated with low self-rated oral health. Higher dissatisfaction with life, personal constraint and perceived stress scores were associated with low income and with low self-rated oral health. After adjusting for gender, age, income and missing teeth, adults with high personal constraint scores had greater odds of low self-rated oral health (OR 1.26; 1.10-1.43) as had adults with higher perceived stress scores (OR 1.69; 1.34-2.13). Psychosocial factors are important in understanding pathways between socioeconomic position and oral health status.


Real-Time Hybrid Multi-Sensor Fusion Framework for Perception in Autonomous Vehicles.
There are many sensor fusion frameworks proposed in the literature using different sensors and fusion methods combinations and configurations. More focus has been on improving the accuracy performance; however, the implementation feasibility of these frameworks in an autonomous vehicle is less explored. Some fusion architectures can perform very well in lab conditions using powerful computational resources; however, in real-world applications, they cannot be implemented in an embedded edge computer due to their high cost and computational need. We propose a new hybrid multi-sensor fusion pipeline configuration that performs environment perception for autonomous vehicles such as road segmentation, obstacle detection, and tracking. This fusion framework uses a proposed encoder-decoder based Fully Convolutional Neural Network (FCNx) and a traditional Extended Kalman Filter (EKF) nonlinear state estimator method. It also uses a configuration of camera, LiDAR, and radar sensors that are best suited for each fusion method. The goal of this hybrid framework is to provide a cost-effective, lightweight, modular, and robust (in case of a sensor failure) fusion system solution. It uses FCNx algorithm that improve road detection accuracy compared to benchmark models while maintaining real-time efficiency that can be used in an autonomous vehicle embedded computer. Tested on over 3K road scenes, our fusion algorithm shows better performance in various environment scenarios compared to baseline benchmark networks. Moreover, the algorithm is implemented in a vehicle and tested using actual sensor data collected from a vehicle, performing real-time environment perception.


Structure-function analysis of human triacylglycerol hydrolase by site-directed mutagenesis: identification of the catalytic triad and a glycosylation site.
Triacylglycerol hydrolase is a microsomal enzyme that hydrolyzes stored cytoplasmic triacylglycerol in the liver and participates in the lipolysis/re-esterification cycle during the assembly of very-low-density lipoproteins. The structure-activity relationship of the enzyme was investigated by site-directed mutagenesis and heterologous expression. Expression of human TGH in Escherichia coli yields a protein without enzymatic activity, which suggests that posttranslational processing is necessary for the catalytic activity. Expression in baculovirus-infected Sf-9 cells resulted in correct processing of the N-terminal signal sequence and yielded a catalytically active enzyme. A putative catalytic triad consisting of a nucleophilic serine (S221), glutamic acid (E354), and histidine (H468) was identified. Site-directed mutagenesis of the residues (S221A, E354A, and H468A) yielded a catalytically inactive enzyme. CD spectra of purified mutant proteins were very similar to that of the wild-type enzyme, which suggests that the mutations did not affect folding. Human TGH was glycosylated in the insect cells. Mutagenesis of the putative N-glycosylation site (N79A) yielded an active nonglycosylated enzyme. Deletion of the putative C-terminal endoplasmic reticulum retrieval signal (HIEL) did not result in secretion of the mutant protein. A model of human TGH structure suggested a lipase alpha/beta hydrolase fold with a buried active site and two disulfide bridges (C87-C116 and C274-C285).


A two-hour procedure for determining the susceptibility of enterococci and staphylococci to antibiotics by a colourimetric method.
Rapid determination of the antibiotic susceptibility test in bacteria remains a challenge for Clinical Microbiology laboratories. An improvement in the colorimetric antimicrobial susceptibility testing performed with resazurin in enterococci and staphylococci has been carried out. The design of method was performed using two collection strains, which have a known susceptibility. This procedure was then validated against standard commercial methods on 15 strains of staphylococci and 15 strains of enterococci from patients. The essential agreement between the colorimetric method and commercial methods (E-test, MicroScan and VITEK2) was 100%. Resazurin allows us to obtain a reliable antibiotic susceptibility test in staphylococci and enterococci in less than two hours.


An opportunity to increase human papillomavirus vaccination rates: Change the guidelines.
Given the low rates of Human Papillomavirus (HPV) vaccination initiation and timely series completion in 11- and 12-year old children, we sought to assess potential opportunities for initiating routine vaccination at a younger age. A cross-sectional study of Latino parents of HPV vaccine-eligible 9- or 10-year-old children in New York City assessed whether there were opportunities to discuss the HPV vaccine during their most recent primary care provider (PCP) visit. Parents were approached between November, 2016 and January, 2018. Of 86 parents who participated, 97% reported having visited the child's PCP in the previous year for an annual checkup and 85% reported that they had neither discussed the HPV vaccine nor received a recommendation for the vaccine during that visit. In a population of Latino parents, predominantly Mexican immigrants with less than a high school education and limited English proficiency, most 9- to 10-year-old children followed the recommendation for an annual PCP visit. Lowering the recommended age for routine vaccination with the HPV vaccine to 9 - 10 years of age should be considered as an important strategy to increase HPV vaccination rates in this and other populations.


Steering nitrogen fertilisation by means of portable chlorophyll meter reduces nitrogen input and improves quality of fertigated cantaloupe (Cucumis melo L. var. cantalupensis Naud.).
Farming is considered one of the main causes of land degradation and underground water pollution. The increased availability of agricultural inputs has led to a dramatic rise in yields, which has resulted in soil fertility spoilage and overuse of fertilisers. Therefore horticultural practice improvement must consider appropriate nitrogen (N) management. This paper reports results on the application of an optical diagnostic system (N-tester) to guide N fertilisation in muskmelon (Cucumis melo L.) over a 3 year trial. Results on fresh and postharvest quality are also presented. Fertilisation events mirrored increases in N-tester values during the season, and a significant linear relationship (R(2) = 0.628) was observed between N-tester readings and leaf chlorophyll content. The N-tester-guided fertilisation treatments were characterised by yields comparable to the control, but with significantly lower applications of N (down to 17-66% of the N distributed in the control). Moreover, the N-tester treatments yielded fruits with higher sugar content. This was also true after storage, when N-tester fruits also showed reduced weight loss associated with lower transpiration and ethylene emission rates. Through the use of 'spy plots' kept at optimal nutritional status and the adoption of a threshold for N application throughout the growing cycle of muskmelon, the N supply was significantly reduced. Therefore a correct application of N-tester allowed the plant N requirement to be reduced and the fruit sugar content and storability to be increased without adversely affecting the yield.


Locomotor Behavior of Chickens Anticipating Incline Walking.
Keel bone damage (KBD) is prevalent in hens raised for egg production, and ramps between different tiers in aviaries have potential to reduce the frequency of falls resulting in KBD. Effective use of ramps requires modulation of locomotion in anticipation of the incline. Inadequate adaptive locomotion may be one explanation why domestic layer hens (Gallus gallus domesticus) exhibit high rates of KBD. To improve understanding of the capacity of hens to modulate their locomotion in anticipation of climbing, we measured the effects of incline angle upon the mechanics of the preparatory step before ascending a ramp. Because the energetic challenge of climbing increases with slope, we predicted that as angle of incline increased, birds during foot contact with the ground before starting to climb would increase their peak force and duration of contact and reduce variation in center of pressure (COP) under their foot. We tested 20 female domestic chickens on ramp inclines at slopes of +0°, +40°, and +70° when birds were 17, 21, 26, 31, and 36 weeks of age. There were significantly higher vertical peak ground reaction forces in preparation at the steepest slope, and ground contact time increased significantly with each increase in ramp angle. Effects upon variation in COP were not apparent; likewise, effects of limb length, age, body mass were not significant. Our results reveal that domestic chickens are capable of modulating their locomotion in response to incline angle.


Immunocytochemical Characterization of Disseminated Tumour Cells from Bone Marrow of Breast Cancer Patients.
The occurrence of disseminated tumour cells in bone marrow of patients with breast cancer is linked to a worse prognosis. We present a method for DTC detection from bone marrow samples based on immunocytochemistry, using breast cancer-associated glycosylation molecules as markers for detection and characterization. A double immunofluorescence staining of a pan-cytokeratin (CK) marker and either Tn or O-Acetyl-GD3 was carried out in artificial and patient bone marrow samples. The sample in which most cells stained positive for CK/Tn and CK/O-AC-GD3, was obtained from a patient who certainly had remote metastases. All other bone marrow samples showed heterogenous staining, so no correlation to tumour characteristics could be revealed. A certain characterization of tumour cells can be achieved by a double staining of bone marrow samples with CK and a glycosylation marker. For future studies, analysis should be extended to a larger patient collective and further examination of more glycosylation markers should be carried out.


A stochastic analysis of autoregulation of gene expression.
This paper analyzes, in the context of a prokaryotic cell, the stochastic variability of the number of proteins when there is a control of gene expression by an autoregulation scheme. The goal of this work is to estimate the efficiency of the regulation to limit the fluctuations of the number of copies of a given protein. The autoregulation considered in this paper relies mainly on a negative feedback: the proteins are repressors of their own gene expression. The efficiency of a production process without feedback control is compared to a production process with an autoregulation of the gene expression assuming that both of them produce the same average number of proteins. The main characteristic used for the comparison is the standard deviation of the number of proteins at equilibrium. With a Markovian representation and a simple model of repression, we prove that, under a scaling regime, the repression mechanism follows a Hill repression scheme with an hyperbolic control. An explicit asymptotic expression of the variance of the number of proteins under this regulation mechanism is obtained. Simulations are used to study other aspects of autoregulation such as the rate of convergence to equilibrium of the production process and the case where the control of the production process of proteins is achieved via the inhibition of mRNAs.


CARE OF A PATIENT'S VASCULAR ACCESS FOR HAEMODIALYSIS: A NARRATIVE LITERATURE REVIEW.
Patients requiring haemodialysis have diverse clinical needs impacting on the longevity of their vascular access and their quality of life. A clinical practice scenario is presented that raises the potential of unsafe cannulation of a patient's vascular access as a result of minimal patient empowerment. Vascular access care is the responsibility of everyone, including the patient and carer. The aim of this narrative literature review (1997-2014) is to explore the current understanding of what factors influence the care of vascular access for haemodialysis. A narrative literature review allows the synthesis of the known literature pertinent to the research question into a succinct model or unique order to enable new understandings to emerge. The bio-ecological model was used to guide the thematic analysis of the literature. The narrative literature review revealed five themes related to care of vascular access: patient experience; relationships-empowerment and shared decision making; environment of healthcare; time; and quality of life as the outcome of care. The management of vascular access is complicated. Current available literature predominantly concentrates on bio-medical aspects of vascular access care. Contextualised vascular access care in the complex ecology of the patient and carer's lives has the potential to enhance nursing practice and patient outcomes.


Tetracycline-inducible viral interleukin-10 intraocular gene transfer, using adeno-associated virus in experimental autoimmune uveoretinitis.
Members of the adeno-associated virus (AAV) family are good candidates for the treatment of ocular diseases because of their relative lack of pathogenicity. We studied the effect of intraocular injection of AAV2-viral IL-10 (vIL-10) on retinal S-antigen-induced experimental autoimmune uveoretinitis (EAU) in Lewis rats. We demonstrated that AAV2/2-GFP injected into the vitreous body transduced the iris and ciliary body, or anterior uvea, and the retina. We showed that intravitreal injection of the AAV2/2-tetON-vIL-10 construct achieved detectable levels of vIL-10 mRNA and protein within the eye and was effective in protecting the rat retina against destruction. This protection was dependent on the level of vIL-10 present in the aqueous humor/ vitreous body. Intravitreal injection of the same construct encased within an AAV5 shell, AAV2/5-tetONvIL- 10, did not confer any degree of protection. It appeared that the AAV2/5 vectors did not transduce the anterior uvea, the site at which inflammatory cells first localize in EAU, nor the ganglion cell layer; induced low expression of vIL-10 mRNA; and did not achieve detectable levels of transgene expression in the aqueous humor/vitreous body. Local treatment with AAV2/2-tetON-vIL-10 did not dampen the systemic immune response, as determined by S-antigen-specific lymphocyte proliferation. Our results show that local intravitreal injection of AAV2/2 is an effective means by which to deliver immunoregulatory molecules into the eye during uveitis, a chronic human ocular disease.


Genome-Wide Introgression and Quantitative Trait Locus Mapping Reveals the Potential of Asian Cotton (Gossypium arboreum) in Improving Upland Cotton (Gossypium hirsutum).
Gossypium arboreum (2n=2x=26, A2), the putative progenitor of the At-subgenome of Gossypium hirsutum (2n=4x=52, AD), is a repository of genes of interesting that have been eliminated during evolution/domestication of G. hirsutum. However, its valuable genes remain untapped so far due to species isolation. Here, using a synthetic amphiploid (AADDA2A2) previously reported, we developed a set of 289 G. arboreum chromosome segment introgression lines (ILs) in G. hirsutum by expanding the backcrossing population and through precise marker-assisted selection (MAS) although complex chromosomal structural variations existed between parents which severely hindered introgression. Our results showed the total coverage length of introgressed segments was 1,116.29 Mb, representing 78.48% of the At-subgenome in the G. hirsutum background, with an average segment-length of 8.69 Mb. A total of 81 co- quantitative trait loci (QTLs) for yield and fiber quality were identified by both the RSTEP-ADD-based QTL mapping and the genome-wide association study (GWAS) analysis, with 1.01-24.78% of the phenotypic variance explained. Most QTLs for boll traits showed negative additive effects, but G. arboreum still has the potential to improve boll-number traits in G. hirsutum. Most QTLs for fiber quality showed negative additive effects, implying these QTLs were domesticated in G. hirsutum compared with G. arboreum and, a small quantity of fiber quality QTLs showing positive additive effects, conversely; however, indicates that G. arboreum has the underlying genes of enhancing fiber quality of G. hirsutum. This study provides new insights into the breeding genetic potential of G. arboreum, lays the foundation for further mining favorable genes of interest, and provides guidance for inter-ploidy gene transference from relatives into cultivated crops.


Magneto-optical diffractive deep neural network.
We propose a magneto-optical diffractive deep neural network (MO-D2NN). We simulated several MO-D2NNs, each of which consists of five hidden layers made of a magnetic material that contains 100 × 100 magnetic domains with a domain width of 1 µm and an interlayer distance of 0.7 mm. The networks demonstrate a classification accuracy of > 90% for the MNIST dataset when light intensity is used as the classification measure. Moreover, an accuracy of > 80% is obtained even for a small Faraday rotation angle of π/100 rad when the angle of polarization is used as the classification measure. The MO-D2NN allows the hidden layers to be rewritten, which is not possible with previous implementations of D2NNs.


Effects of transjugular intrahepatic portosystemic shunt using the Viatorr stent on hepatic reserve function in patients with cirrhosis.
As transjugular intrahepatic portosystemic shunt (TIPS) creation alters the hemodynamic status of the portal system, whether reduced portal blood supply affects the synthetic reserve function of the liver has been the focus of clinical attention. Since the Viatorr stent entered the Chinese market in 2015, it has not yet been widely used in clinical practice. Further, unlike other countries, the main cause of liver cirrhosis in China is viral hepatitis. Therefore, use of the Viatorr stent to establish a TIPS channel in patients with liver cirrhosis with differing etiologies is of great clinical interest. To investigate factors affecting changes in liver reserve function after TIPS Viatorr stent implantation. Clinical data from 200 patients with cirrhotic portal hypertension who received TIPS treatment from March 2016 to March 2020 were analyzed retrospectively. The patients were divided into three groups (A-C), according to their disease etiology, with post-hepatitis, autoimmune, and alcoholic cirrhosis, respectively. Preoperative and postoperative liver and renal function and coagulation data, Child-Pugh grade, and model for end-stage liver disease (MELD) scores were collected. Statistical analyses were performed using the t-test or chi-square test. The incidence and of hepatic encephalopathy and patient survival were calculated using Kaplan-Meier method. The surgical success rate was 100%, with mean portal pressure gradient (mmHg) decreasing from 25.5 ± 5.22 to 10.04 ± 2.76 (t = 45.80; P < 0.001). After 24 mo, the cumulative incidence of hepatic encephalopathy in group A was significantly lower than that in group B/C, while the cumulative survival rate was significantly higher in group A than in group B/C (P < 0.05 for both). The Child-Pugh score for group A was 6.96 ± 1.21, which was significantly better than those of groups B (7.42 ± 0.99; t = -2.44; P = 0.016) and C (7.52 ± 1.12; t = -2.67; P = 0.009). Further, the MELD score for group A (9.62 ± 2.19) was significantly better than those for groups B (10.64 ± 1.90; t = -2.92; P = 0.004) and C (10.82 ± 2.01; t = -3.29; P = 0.001). Insertion of 8 mm internal diameter Viatorr stent has no significant effects on liver reserve function. Changes of liver reserve function in the medium and long term may be related to the etiology and treatment of portal hypertension.


Leak after vertical banded gastroplasty.
We have reported the case of a morbidly obese patient who became gravely ill during the first day after vertical banded gastroplasty. The diagnosis of a leak from the stomach was established by a Gastrografin swallow, and ten additional operations were done before the patient was discharged on the 135th postoperative day.


[The effect of the binding of the antigenic determinant of tetrodotoxin-sensitive protein on the phytohemagglutinin-induced proliferative response of the mononuclear cells in mouse spleen].
Mammalian brain-derived "tetrodotoxin-sensitive protein" has been shown to share an epitope with as yet unidentified structure of the human and rodent lymphocyte surface. Previously obtained observations that a monoclonal antibody to this epitope induces a proliferative response of murine splenic mononuclear cells are confirmed. However, this antibody fails to modify the phytohemagglutinin-induced response. Moreover, lectin with submitogenic concentration inhibited the antibody-induced response provided that monocytes were present in the culture. The antibody-induced proliferation appeared to be less monocyte-dependent than the lectin-induced one. Taken together, these findings argue against hypothesis that a lymphocyte structure with epitope of the "tetrodotoxin-sensitive protein" is associated with either T cell receptor for antigen or interleukin-2 receptor.


Strategies for reducing per-sample costs in target capture sequencing for phylogenomics and population genomics in plants.
The reduced cost of high-throughput sequencing and the development of gene sets with wide phylogenetic applicability has led to the rise of sequence capture methods as a plausible platform for both phylogenomics and population genomics in plants. An important consideration in large targeted sequencing projects is the per-sample cost, which can be inflated when using off-the-shelf kits or reagents not purchased in bulk. Here, we discuss methods to reduce per-sample costs in high-throughput targeted sequencing projects. We review the minimal equipment and consumable requirements for targeted sequencing while comparing several alternatives to reduce bulk costs in DNA extraction, library preparation, target enrichment, and sequencing. We consider how each of the workflow alterations may be affected by DNA quality (e.g., fresh vs. herbarium tissue), genome size, and the phylogenetic scale of the project. We provide a cost calculator for researchers considering targeted sequencing to use when designing projects, and identify challenges for future development of low-cost sequencing in non-model plant systems.


Development and research of a coaxial microwave plasma thruster.
An overview of the research on a coaxial microwave plasma thruster at Northwestern Polytechnic University is presented. Emphasis is put on the development and research on key components of the thruster system, a microthrust balance, plasma plume diagnostics, and a numerical simulation of the plasma flow field inside the thruster cavity. The developed thruster cavity is chosen from a coaxial resonant cavity with concentrated capacitance, which can operate well in atmosphere and vacuum conditions. The development of a microwave source shows that a magnetron powered by a switch power supply has advantages in the power level and efficiency, but a solid state microwave source synthesized from the arsenide field effect transistor is superior in weight and volume. Through elimination of the effect of large gravity and resistance force induced by a gas pipe line and a microwave transmitting line on the microthrust, 15 mN and 340 s in the performance of the microwave plasma thruster at 70 W and with helium gas are measured. Diagnosing experiment shows that the plasma plume density is in the range of (1-7.2)x10(16)m(3). Numerical simulation of the plasma flow field inside the coaxial thruster cavity shows that there is a good match between the microwave power and gas flow rate.


H3N2 influenza A virus gradually adapts to human-type receptor binding and entry specificity after the start of the 1968 pandemic.
To become established upon zoonotic transfer, influenza A viruses (IAV) need to switch binding from "avian-type" α2-3-linked sialic acid receptors (2-3Sia) to "human-type" Siaα2-6-linked sialic acid receptors (2-6Sia). For the 1968 H3N2 pandemic virus, this was accomplished by two canonical amino acid substitutions in its hemagglutinin (HA) although a full specificity shift had not occurred. The receptor repertoire on epithelial cells is highly diverse and simultaneous interaction of a virus particle with a range of low- to very low-affinity receptors results in tight heteromultivalent binding. How this range of affinities determines binding selectivity and virus motility remains largely unknown as the analysis of low-affinity monovalent HA-receptor interactions is technically challenging. Here, a biolayer interferometry assay enabled a comprehensive analysis of receptor-binding kinetics evolution upon host-switching. Virus-binding kinetics of H3N2 virus isolates slowly evolved from 1968 to 1979 from mixed 2-3/2-6Sia specificity to high 2-6Sia specificity, surprisingly followed by a decline in selectivity after 1992. By using genetically tuned HEK293 cells, presenting either a simplified 2-3Sia- or 2-6Sia-specific receptor repertoire, receptor-specific binding was shown to correlate strongly with receptor-specific entry. In conclusion, the slow and continuous evolution of entry and receptor-binding specificity of seasonal H3N2 viruses contrasts with the paradigm that human IAVs need to rapidly acquire and maintain a high specificity for 2-6Sia. Analysis of the kinetic parameters of receptor binding provides a basis for understanding virus-binding specificity, motility, and HA/neuraminidase balance at the molecular level.


Oral disodium cromoglycate in mastocytosis.
Oral disodium cromoglycate was found useful for the treatment of gastrointestinal manifestations of mastocytosis in 2 patients with systemic disease. The urinary excretion of histamine in these 2 patients decreased following treatment. Oral disodium cromoglycate had no effect on cutaneous symptoms, either in these 2 patients nor in 2 other patients with urticaria pigmentosa without signs of systemic mastocytosis. In the latter 2 patients the urinary excretion of histamine was unaffected. Treatment was given for 4 to 6 weeks and the dose of disodium cromoglycate was 100 mg four times daily in the 3 adult patients and 100 mg three times daily in the fourth patient, an 8-year-old boy.


Contrasting bee pollination in two co-occurring distylic species of Cordia (Cordiaceae, Boraginales) in the Brazilian semi-arid Caatinga: generalist in C. globosa vs. specialist in C. leucocephala.
In this study we compare the reproductive biology of Cordia globosa and C. leucocephala (Cordiaceae, Boraginales; formerly referred to Boraginaceae) to understand the functioning of the floral morphs and the relations with their effective pollinators. The species are synchronopatric, distylic, and self-incompatible. Though they share melittophilous traits, the main visitor and pollinator of C. globosa was the generalist and exotic bee Apis mellifera, while the only one of C. leucocephala was the oligoletic bee Ceblurgus longipalpis. These two latter species are restricted to the Caatinga of NE Brazil, contrasting with the wide distribution of Cordia globosa. While the fruit-set for C. globosa was high, independently if the pollen donor/stigma receptor was a pin (long-styled) or thrum (short-styled) individual, in C. leucocephala the fruit-set was low and occurred only when a thrum individual was the pollen donor. This raises the possibility of this species moving towards dioecy. The high natural fruit-set of C. globosa confirms the generalist bee as its effective pollinator. The low fruit-set after manual crosses in C. leucocephala may be due to low pollen viability. Additionally, the low natural fruit-set (two times lower than after crosses) may be related with the foraging behavior of the specialist pollinator.


Flos Abelmoschus manihot extract attenuates DSS-induced colitis by regulating gut microbiota and Th17/Treg balance.
Flos Abelmoschus manihot is widely used as traditional drug in China. Abelmoschus manihot (AM) extracted from Flos Abelmoschus manihot that has been applied for treating chronic inflammatory diseases. Here we showed that AM significantly alleviated DSS-induced colitis in mice. AM modified gut microbiota composition, increased microbial diversity, and in particularly, elevated the abundance of short chain fatty acids (SCFAs)-producing gut microbiota in colitic mice. Consequently, levels of SCFAs especially butyrate and acetate were increased upon AM treatment, which, primarily through peroxisome proliferator-activated receptor gamma (PPARγ) pathway, led to the enhanced Treg generation and the suppressed Th17 development. Together, we herein provide the first evidences to support that AM, a natural plant-derived complex, can potentially reset gut microbiome and metabolism, resume immune and tissue homeostasis, and hence prevent colitis, which may provide a new perspective on IBD pathogenesis and suggest a novel microbiota-targeting therapy for inflammatory gut diseases.


Cutaneous collagenous vasculopathy: description of two new cases in elderly women and review of the literature.
Cutaneous collagenous vasculopathy (CCV) is an idiopathic microangiopathy with characteristic histological findings. It was described in 2000, and 9 cases have since been described. Two women of 83 and 74 years consulted for long-standing telangiectasias. In case 1, they affected the limbs and trunk and in case 2 were located on the legs. Biopsies of these lesions showed dilated vascular structures whose walls were thickened due to deposition of eosinophilic hyaline material. The affected vessels were located in the superficial dermis in case 1, and in case 2 the reticular dermis was also affected. CCV is a microangiopathy of unknown etiology. Clinically it is indistinguishable from generalized essential telangiectasia and differs in its histology. CCV may be underdiagnosed, and some nonbiopsied cases of generalized essential telangiectasia may really be CCV. We contribute 2 new cases of this entity to help establish its clinical and epidemiological characteristics and make its etiology better known.


A identification method for critical causes of lifting injuries based on topological potential.
In view of the deficiency that the traditional importance ranking method cannot be used to objectively and comprehensively evaluate the importance of the causes of hoisting injuries, an importance ranking method based on topological potential is proposed by using complex network theory and field theory in physics. First, the causes of 385 reported lifting injuries are divided into 36 independent causes at four levels through a systematic analysis approach, and the relationships among these causes are obtained through the Delphi method. Then, the accident causes are treated as nodes, and the relationships among the causes are used as edges to establish a network model of the causes of lifting accidents. The out-degree and in-degree topological potential of each node are calculated, and an importance ranking of lifting injuries causes is obtained. Finally, based on 11 evaluation indexes commonly used to assess node importance (node degree, betweenness centrality, etc.), the ability of the method proposed in this paper to effectively identify the key nodes in the cause network of lifting accidents is verified, and the conclusions can guide the safe implementation of lifting operations.


[A good clinical guideline is an orientational tool, not a checklist].
Lege artis procedures, medical standards as well as guideline contents ought to be defined by health care professionals themselves. Therefore the medical profession carries a great responsibility to both continuously optimise diagnostic and therapeutic methods as well as their results and adapt them to medical progress. Standards and guidelines cannot replace a doctor's responsibility towards his patients. They can help doctors to find the right answer but they are not check-off lists. The practical application of an evidence-based guideline must result from a doctor's identification of a certain patient problem. This stage of identification is predominated by the individual doctor's internal evidence which reflects his medical knowledge, practical experience and the information arising from the individual relation between patient and doctor.


QUANTITATIVE GENETICS, DEVELOPMENT, AND PHYSIOLOGICAL ADAPTATION IN HOST STRAINS OF FALL ARMYWORM.
Two genetically differentiated host strains of fall armyworm were reared on their own and each other's host plants, rice and corn, to determine whether they were physiologically adapted to their natural hosts and whether they exhibited genetically based differences in development. Larval host had a greater impact on development in the rice strain than in the corn strain, indicating that physiology could have facilitated specialization in one strain but not the other. Consequently, behavioral mechanisms are also likely to be important in the maintenance of host specificity. Comparisons between strains indicated significant differences in one trait, the rate at which larvae gained weight. Because this character had consistently high heritabilities, genetic differentiation in development is indicated. An analysis of genotype-by-environment interactions within each strain detected significant interactions for three of five traits, suggesting that genotypic performance on one host was not indicative of performance on the other. Each strain thus exhibited genetic variation that would facilitate host-associated divergence and adaptation if coupled with a mechanism that reduced gene flow between hosts. Finally, significant genetic correlations between several characters were detected when strains were reared on their natural hosts but not when they were reared on nonnatural hosts. Apparently, feeding on novel hosts caused developmental uncoupling of characters. Release from genetic constraints could provide a mechanism for physiological adjustments to newly occupied habitats.


Acute humoral rejection of an ABO-unmatched liver allograft in a pediatric recipient.
Acute humorally mediated rejection of organ allografts has long been recognized in kidney transplantation as the syndrome of hyperacute rejection. This reaction precludes renal transplantation across the major blood-group system and in many other instances in which preformed antibodies are present in the host. There is increasing evidence of the importance of humoral rejection in graft survival following liver transplantation. Although the antibodies responsible for this process have seldom been definitively identified, it is clear that the antibodies of the major blood-group system are of particular importance. Humoral rejection of a transplanted liver has not been well documented previously in a pediatric recipient. We present a case illustrating acute hepatic graft failure resulting from circulating anti-B IgM isohemagglutinins following an ABO-unmatched liver transplantation.


[Fluorescent carbon dots and the application in biomedicine].
As a new type of carbon nanomaterials, fluorescent carbon dots (fluorescent CDs) have many advantages when compared with the traditional fluorescent probes. They are photoluminescence stable and resistance to photo bleaching. Moreover, they are excellent in biocompatibility, low-toxic and easy to modify. All these above make them a promising optical image material as a probe in optical image. This article reviews structure, the common carbon sources, the preparation methods, and the light-emitting principles of the carbon dots. We also introduce the research progress of fluorescent carbon dots in biomedicine, and the problems need to be resolved in the study of fluorescent CDs.


Nasal decongestant effect of propylhexedrine.
Propylhexedrine was evaluated for its objective and subjective effectiveness and duration of action as an inhaled topical nasal decongestant. It was studied with and without aromatic oils in subjects with nasal congestion due to acute upper respiratory infection (URI) or to allergic rhinitis. A logarithmic transformation of nasal airway resistance (Rn) was performed to allow the application of standard statistical test to Rn changes. Subjective rating scales for congestion and symptoms were analyzed by nonparametric statistical procedures. Rn was statistically decreased from control values for 120 minutes after propylhexedrine vapors. Responses were the same for subjects with URI and allergic rhinitis, and no effect of the aromatic oils could be demonstrated. A comparison of the relationship between objective and subjective assessments of congestion demonstrated that the subjective rating scale had reduced sensitivity and poor reliability when compared with the objective measurement of Rn.


Gemcitabine in non-small cell lung cancer.
Gemcitabine is considered to be one of the most active drugs in the treatment of non-small cell lung cancer (NSCLC). When used as a single agent, gemcitabine yielded response rates consistently > 20%, with a uniformly good tolerance profile. Preclinical data indicated synergism between gemcitabine and platinum compounds, such as cisplatin or carboplatin. The gemcitabine-cisplatin combination is considered one of the reference regimens for advanced NSCLC and the recommended schedule is gemcitabine 1000 - 1250 mg/m(2) on days 1 - 8 and cisplatin 70 - 80 mg/m(2) on days 1 or 2. In order to avoid many of the non-haematological toxicities associated with cisplatin, several trials evaluated the gemcitabine-carboplatin combination. Previous trials using the 28-day schedule showed unacceptable haematological toxicity. Recent studies demonstrated the activity and feasibility of gemcitabine-carboplatin combination using a 21-day schedule, with carboplatin administered on day 1 and gemcitabine on days 1 and 8. Gemcitabine can be combined with one of the other new agents, such as the taxanes or vinorelbine, to create novel non-platinum-doublets. Although encouraging, the available data are still conflicting and non-platinum-based combinations are not indicated outside clinical trials. Three-drug combinations increased toxicity and failed to demonstrate any advantage over standard doublets in advanced NSCLC. Gemcitabine is active and well tolerated in elderly patients and represents a reasonable therapeutic option. Although no Phase III trials have been conducted to compare gemcitabine to the best supportive care or docetaxel in pretreated NSCLC, gemcitabine alone or in combination with vinorelbine or one of the taxanes can be considered a valid option for second-line treatment in patients who had a previous response or who achieved stable disease with a platinum-containing regimen. Gemcitabine is considered the most radiopotentiating agent available amongst the newer agents we have in terms of activity and toxicity, but the routine use of gemcitabine in combination with radical thoracic radiotherapy, although promising, is not yet recommended. Further testing of gemcitabine-based combinations with concurrent radiation is underway.


Case report: A case of injury to the infrapatellar branch of the saphenous nerve caused by medial approach in knee arthroscopy.
We present the case of a 72-year-old man who was referred to our department for treatment of pain on the anteromedial infrapatellar side of the right knee with sensory disturbance that began 2 years earlier. The patient previously underwent right knee arthroscopy at another hospital for a meniscus injury 2 years earlier, which relieved his knee pain, but pain and discomfort near the incision of the medial portal persisted. Given this situation, various physical treatments, such as ice compress, were administered postoperatively. However, the symptom was only partially relieved before discharge. Subsequently, the patient visited two other hospitals and began taking oral pregabalin and duloxetine for treatment of the pain based on a diagnosis of right common peroneal nerve injury. The pain in the same dermatomal distribution was slightly relieved, but a withdrawal reaction was observed. However, the results of an ultrasound at our hospital indicated that the right medial quadriceps femoris tendon showed a hypoechoic area suggesting inflammatory changes. Physical examination of the right knee detected atrophy of the quadriceps femoris muscle, decreased muscle strength (M4), obvious tenderness in the medial side, radiating pain along the anterior tibia, and sensory disturbance (S3+); the results of a drawer test, McMurray test, pivot shift test, and lateral stress test were negative. Based on the aforementioned evidence, a diagnosis was made of injury to the infrapatellar branch of the saphenous nerve, after which neurolysis of the nerve in question was carried out. An enlarged incision was made along the original medial approach. Scar hyperplasia was observed after careful separation of the subcutaneous tissue. During neurolysis, branches were found wrapped in the scar; their continuity and integrity were confirmed after relief. The released nerve was placed in a physiological position. The patient's pain was clearly relieved, and numbness disappeared on the first postoperative day. At 1-month follow-up, all symptoms were found to have resolved.


High loading and low maintenance doses of a gonadotropin-releasing hormone antagonist effectively suppress serum luteinizing hormone, follicle-stimulating hormone, and testosterone in normal men.
The GnRH antagonist cetrorelix effectively suppresses serum LH, FSH, and testosterone (T) in normal men without major side-effects. However, as with other available GnRH antagonists, relatively high doses of 10 mg/day were required for sustained reduction of T levels during 1-week administration in normal men. Therefore, we investigated whether a suppression of LH, FSH, and T achieved by initial high dose cetrorelix can be maintained by continued low dose injections. Sixteen young male volunteers were randomly assigned to four study groups (n = 4/group). Twelve men were injected s.c. with 10 mg cetrorelix at 0800 h for 5 days, followed by injections of 2 mg/day (group I), 2 x 1 mg/day (group II), and 1 mg/day (group III) up to the end of the 3-week injection period. For the control, group IV was given daily placebo injections for 3 weeks. Morning and evening blood samples were obtained daily for 4 weeks and then at increasing time intervals up to week 13. Initial injections of 10 mg/day cetrorelix suppressed LH, FSH, and T effectively. This initial reduction of serum levels was maintained during the following low dose maintenance injections in all groups. In comparison to the initial suppression, significantly lower levels of LH, FSH, and T near the assay detection limits were measured during study weeks 2 and 3. The results show that compared to previous long term studies, much lower daily doses of the GnRH antagonist are sufficient for effective suppression of LH, FSH, and T after initial high loading dose injections. In addition to competitive receptor blockage, other mechanisms of GnRH antagonist action, such as receptor down-regulation, appear to be involved during long term administration in men.


Novel screening systems for HIV-1 fusion mediated by two extra-virion heptad repeats of gp41.
Entry of human immunodeficiency virus type 1 (HIV-1) into target cells is mediated by its envelope protein gp41 through membrane fusion. Interaction of two extra-virion heptad repeats (HRs) in the gp41 plays a pivotal role in the fusion, and its inhibitor, enfuvirtide (T-20), blocks HIV-1 entry. To identify agents that block HIV-1 fusion, two screening methods based on detection and quantification by the enzyme-linked immunosorbent assay (ELISA) principle have been established. One method uses an alkaline phosphatase (ALP)-conjugated antibody (Ab-ELISA) and the other uses an ALP-fused HR (F-ELISA) to detect and quantify the interaction of the two HRs. The F-ELISA was more simple and rapid, since no ALP-conjugated antibody reaction was required. Both ELISAs detected all the fusion inhibitors tested except for T-20. Interaction of the two HRs was observed in both ELISAs, even in the presence of 10% dimethyl sulfoxide. Ab-ELISA performed best in a pH ranging from 6 to 8, while F-ELISA performed best at a pH ranging from 7 to 8. These results indicate that both established ELISAs are suitable for the identification of HIV-1 fusion inhibitors.


Mutational state of von Hippel-Lindau and adenomatous polyposis coli genes in renal tumors.
Genetic alterations of the von Hippel-Lindau (VHL) tumor suppressor gene and the adenomatous polyposis coli (APC) gene in renal tumors were examined by PCR-SSCP analysis and direct sequencing. Tissues from 58 primary sporadic human renal cell tumors (49 clear-cell carcinomas, 6 non-clear-cell carcinomas and 3 oncocytomas) from Japanese patients were used in this study. Somatic VHL mutations were detected in 26 (53%) of the clear-cell carcinomas, although no mutations in this gene were observed in any non-clear-cell carcinomas or oncocytomas. The frequency of mutations did not correlate with histological grade, clinical stage or any of several other clinical factors examined. No differences in the frequency of VHL mutations or in the exons where mutations occurred within the gene were evident when we compared our results with those reported for American patients. However, frameshifts were more common in our Japanese panel of tumors than in American cases, where single-point mutations appear to be more frequent. No APC gene mutation was detected in any of our samples. These results indicate that VHL gene mutations are related to the carcinogenesis of the clear-cell type of primary renal cell carcinomas, whereas alteration of the APC gene is not involved in the pathogenesis of this cancer.


Anti-cholinesterase activity of lycopodium alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis.
A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. Among them, lycosquarosine A (1) is the new metabolite of the natural source. Lycosquarosine A completely inhibited AChE activity in a dose dependent manner with an IC50 value of 54.3 μg/mL, while acetylaposerratinine (2) showed stronger inhibitory activity than 1 with an IC50 value of 15.2 µg/mL. This result indicates that these alkaloids may be a potent source of AChE inhibitors.


Design, manufacture, and analysis of customized phantoms for enhanced quality control in small animal MRI systems.
Magnetic resonance imaging (MRI) is widely used in human brain research to evaluate the effects of healthy aging and development, as well as neurological disorders. Although standardized methods for quality assurance of human MRI instruments have been established, such approaches have typically not been translated to small animal imaging. We present a method for the generation and analysis of customized phantoms for small animal MRI systems that allows rapid and accurate system stability monitoring. Computer-aided design software was used to produce a customized phantom using a rapid prototyping printer. Automated registration algorithms were used on three-dimensional images of the phantom to allow system stability to be easily monitored over time. The design of the custom phantom allowed reliable placement relative to the imaging coil. Automated registration showed superior ability to detect gradient changes reflected in the images than with manual measurements. Registering images acquired over time allowed monitoring of gradient drifts of less than one percent. A low cost, MRI compatible phantom was successfully designed using computer-aided design software and a three-dimensional printer. Registering phantom images acquired over time allows monitoring of gradient stability of the MRI system.


Gold Nanoparticle-Based Photoluminescent Nanoswitch Controlled by Host-Guest Recognition and Enzymatic Hydrolysis for Arginase Activity Assay.
The development of simple yet powerful methods for monitoring enzyme activity is of great significance. Herein, a facile, convenient, cost-effective, and continuous fluorescent method for the detection of arginase and its inhibitor has been reported based on a host-guest interaction-controlled and enzymatic hydrolysis-controlled luminescent nanoswitch. The fluorescence intensity of 6-aza-2-thiothymine-stabilized gold nanoparticle (ATT-AuNP) is enhanced by l-arginine, owing to the formation of a supramolecular host-guest assembly between the guanidine group of l-arginine and ATT molecules capped on the AuNP surface. However, hydrolysis of l-arginine, catalyzed by arginase, leads to a decrease in the fluorescence intensity of l-arginine/ATT-AuNPs hybrids. Upon incorporation of the arginase inhibitor l-norvaline, the fluorescence of the ATT-AuNP-based detecting system is restored. The linear range of arginase activity determination is from 0.0625 to 1.15 U/mL and the limit of detection is 0.056 U/mL. The half-maximal inhibition value IC50 of l-norvaline is determined to be 5.6 mM. The practicability of this luminescent nanoswitch is validated by assaying the arginase activity in rat liver and monitoring the response of rat liver arginase to pharmacological agent. Compared to the existing fluorescent method of arginase activity assay, the approach demonstrated here does not involve any complicated technical manipulation, thereby greatly simplifying the detection steps. We propose that this AuNP-based luminescent nanoswitch would find wide applications in the field of life sciences and medicine.


An approach to estimate the activation energies of fragmentation occurring in quadrupole collision cell of the mass spectrometer.
The classical semi-quantitative Rice-Ramsperger-Kassel (RRK) theory was used for the calculation of the internal energy dependent reaction rate coefficient of the collision-induced dissociation (CID) reaction in tandem mass spectrometry (MS/MS). The survival yield (SY) was determined by the reaction rate equation for the unimolecular dissociation of the precursor ion. The parameters of the rate equation and the RRK model were approximated based on the instrumental conditions. We used the RRK equation for the description of the basic behavior of the fragmentation reactions and for the estimation of the internal energy of the precursor ion. The critical energies for fragmentation (Eo ) of various molecules were estimated and compared with those reported in the literature. The model was extended by taking into account the initial internal energy distribution of the ions created in the ion source. It must be emphasized that our approach provides only a crude estimate for Eo .


Histopathological concordance between prostate biopsies and radical prostatectomy specimens-implications of transrectal and transperineal biopsy approaches.
This study aimed to evaluate the histopathological concordance rates between prostate biopsies and radical prostatectomy specimens according to the applied biopsy approach (transrectal or transperineal). We studied patients who had been newly diagnosed with clinically significant prostate cancer and who underwent a radical prostatectomy between 2018 and 2022. Patients were included if they underwent a prebiopsy magnetic resonance imaging and if they had not been previously treated for prostate cancer. Histopathological grading on prostate biopsies was compared with that on radical prostatectomy specimens. Univariable and multivariable logistic regression analyses were performed to assess the effect of the applied biopsy approach on histopathological concordance. Additional analyses were performed to assess the effect of the applied biopsy approach on American Urological Association risk group migration, defined as any change in risk group after radical prostatectomy. In total, 1058 men were studied, of whom 49.3% (522/1058) and 50.7% (536/1058) underwent transrectal and transperineal prostate biopsies, respectively. Histopathological disconcordance was observed in 37.8% (400/1058) of men while American Urological Association risk group migration was observed in 30.2% (320/1058) of men. A transperineal biopsy approach was found to be independently associated with higher histopathological concordance rates (OR 1.33 [95% CI 1.01-1.75], p = 0.04) and less American Urological Association risk group migration (OR 0.70 [95% CI 0.52-0.93], p = 0.01). The use of a transperineal biopsy approach improved histopathological concordance rates compared to the use of a transrectal biopsy approach. A transperineal biopsy approach may provide more accurate risk stratification for clinical decision-making. Despite recent improvements, histopathologic concordance remains suboptimal and should be considered before initiating management.


[Evolution of Root Nodule Bacteria: Reconstruction of the Speciation Processes Resulting from Genomic Rearrangements in a Symbiotic System].
The processes of speciation and macroevolution of root nodule bacteria (rhizobia), based on deep rearrangements of their genomes and occurring in the N₂-fixing symbiotic system, are reconstructed. At the first stage of rhizobial evolution, transformation of free-living diazotrophs (related to Rhodopseudomonas) to symbiotic N₂-fixers (Bradyrhizobium) occurred due to the acquisition of the fix gene system, which is responsible for providing nitrogenase with electrons and reducing equivalents, as well as for oxygen-dependent regulation of nitrogenase synthesis in planta, and then of the nod genes responsible for the synthesis of the lipo- chito-oligosaccharide Nod factors, which induce root nodule development. The subsequent rearrangements of bacterial genomes included: (1) increased volume of hereditary information supported by species, genera (pan-genome), and individual strains; (2) transition from the unitary genome to a multicomponent one; and (3) enhanced levels of bacterial genetic plasticity and horizontal gene transfer, resulting in formation of new genera, of which Mesorhizobium, Rhizobium, and Sinorhizobium are the largest, and of over 100 species. Rhizobial evolution caused by development and diversification of the Nod factor synthesizing systems may result in both increased host specificity range (transition of Bradyrhizobium from autotrophic to symbiotrophic carbon metabolism in interaction with a broad spectrum of legumes) and to its contraction (transition of Rhizobium and Sinorhizobium to "altruistic" interaction with legumes of the galegoid clade). Reconstruction of the evolutionary pathway from symbiotic N₂-fixers to their free-living ancestors makes it possible to initiate the studies based on up-to-date genome screening technologies and aimed at the issues of genetic integration of organisms into supracpecies complexes, ratios of the macro- and microevolutionary mechanisms, and developmetn of cooperative adaptations based on altruistic relationship between the symbiotic partners.


What is a normal lactate level during cardiopulmonary bypass?
Blood lactate levels during cardiopulmonary bypass are often used to verify adequacy of perfusion. The present investigation aimed to propose a threshold for hyperlactatemia. Blood lactate levels in 5 121 cardiac surgical patients were retrospectively analysed by a review of database records. Hyperlactatemia was defined as a value equal to the 90th percentile of the identified lactate distribution at weaning from cardiopulmonary bypass. Patient demographics, background and outcome statistics were performed stratified on presence of hyperlactatemia. The threshold for hyperlactatemia was found to equal 2 mmol/l. Significant predictors of hyperlactatemia based on logistic regression modelling were age, complex surgery, duration of cardiopulmonary bypass, blood transfusion, acid base level, emergency operations, diabetes, vasoactive intervention, venous-blood-return to the heart-lung machine and renal function. Patients with hyperlactatemia required longer intensive care and postoperative ventilatory support. Complications were more frequent, especially: renal dysfunction, infections, respiratory and circulatory disorders. Hospital mortality was 13.3% compared to an overall level at 2.2%. The threshold for hyperlactatemia during cardiopulmonary bypass attained 2 mmol/l and predicted increased morbidity and mortality.


[Palliative therapy in cancer--Significance and practice].
Most of advanced cancer-patients will have suffered symptoms from the local spread or dissemination of the malignancy for a variable time, but possibly for months or years. During recent years, advances in diagnosis and therapy have allowed earlier and most effective intervention, which has served to increase longevity and enhance the quality of life. However, the overall mortality from malignant disease has hardly changed in the last 40 years. There is usually a progression from unsuccessful attempt at cure to symptom palliation and, ultimately, terminal care. There will be some patients in whom appropriate palliation is compatible with cure and others who are terminal, but are amenable to palliation of certain symptoms. Therefore, the objection of palliative therapy in these individuals is to maximise their quality of life. Many differing tumors may produce a given symptom. So palliative therapy can be defined most simply as the alleviation of symptoms. Palliative therapy is most certainly not only the treatment of recurrent, but also of asymptomatic disease. The significance and practice of palliative therapy for advanced cancer will be reported.


Loss of m1acp3Ψ Ribosomal RNA Modification Is a Major Feature of Cancer.
The ribosome is an RNA-protein complex that is essential for translation in all domains of life. The structural and catalytic core of the ribosome is its ribosomal RNA (rRNA). While mutations in ribosomal protein (RP) genes are known drivers of oncogenesis, oncogenic rRNA variants have remained elusive. We identify a cancer-specific single-nucleotide variation in 18S rRNA at nucleotide 1248.U in up to 45.9% of patients with colorectal carcinoma (CRC) and present across >22 cancer types. This is the site of a unique hyper-modified base, 1-methyl-3-α-amino-α-carboxyl-propyl pseudouridine (m1acp3Ψ), a >1-billion-years-conserved RNA modification at the peptidyl decoding site of the ribosome. A subset of CRC tumors we call hypo-m1acp3Ψ shows sub-stoichiometric m1acp3Ψ modification, unlike normal control tissues. An m1acp3Ψ knockout model and hypo-m1acp3Ψ patient tumors share a translational signature characterized by highly abundant ribosomal proteins. Thus, m1acp3Ψ-deficient rRNA forms an uncharacterized class of "onco-ribosome" which may serve as a chemotherapeutic target for treating cancer patients.


Spontaneous reversion of FTA-ABS test reactions.
In a series of 56 clinically healthy persons with no history of syphilis and negative VDRL tests but reactive fluorescent treponemal antibody absorption (FTA-ABS) tests, 20 spontaneously developed nonreactive FTA-ABS tests in a period of eight months or less. All but one of these had been of 2+ or less fluorescence. In such a situation, the serologic tests for syphilis (VDRL and FTA-ABS tests) should be repeated at intervals for up to a year before coming to a decision regarding the diagnosis of syphilis. Laboratories could facilitate that decision by reporting degrees of fluorescence of the FTA-ABS test.


Self-control protects Tibetan adolescent orphans from mental problems: A mediating role of self-esteem.
Orphans are usually adopted by eligible families or raised by the government and organizations mutually. Although their basic needs are taken care of, the absence of parents in life makes orphans face higher risks of mental health problems, such as anxiety and depression, leading to lower levels of self-esteem and happiness. Previous studies have shown that self-control may have an effect on improving self-esteem; thus, it could become a way to protect mental health. Building on the structural equation model, the current study tested the possible effects of self-control on levels of self-esteem and mental problems among Tibetan orphans. Participants were 143 adolescents from age 16 to 22 years (Mage = 18.77, 54.8% female) from an institutionalized orphanage in Tibet and they completed questionnaires measuring self-esteem, self-control, and clinical symptoms (Symptom Checklist-90-Revised). Self-control was negatively associated with psychological illness through improved self-esteem. The present study suggested that self-control was a protective factor for the mental health of adolescent orphans through influencing the levels of self-esteem. Limitations and future directions were discussed.


Superselective targeting using multivalent polymers.
Despite their importance for material and life sciences, multivalent interactions between polymers and surfaces remain poorly understood. Combining recent achievements of synthetic chemistry and surface characterization, we have developed a well-defined and highly specific model system based on host/guest interactions. We use this model to study the binding of hyaluronic acid functionalized with host molecules to tunable surfaces displaying different densities of guest molecules. Remarkably, we find that the surface density of bound polymer increases faster than linearly with the surface density of binding sites. Based on predictions from a simple analytical model, we propose that this superselective behavior arises from a combination of enthalpic and entropic effects upon binding of nanoobjects to surfaces, accentuated by the ability of polymer chains to interpenetrate.