TNFAIP6 promotes invasion and metastasis of gastric cancer and indicates poor prognosis of patients.
TNFα-stimulated gene-6 (TNFAIP6) plays an important role in the prognosis of many tumors. Our objective was to investigate the clinical and prognostic value of TNFAIP6 expression in gastric cancer (GC) patients. Here, we investigated the expression of TNFAIP6 in GC tissues using western blotting and immunohistochemistry and the association between TNFAIP6 expression and the prognosis and clinicopathological parameters of GC patients. Our results revealed that the expression of TNFAIP6 was higher in GC tissue than in normal gastric tissue, and the levels were positively correlated with the depth of tumor invasion (P = 0.010), tumors with lymph node metastasis (P = 0.000) and TNM stage (P = 0.003) of GC patients. Moreover, the results revealed that patients with high TNFAIP6 expression exhibited poorer overall survival than those with low TNFAIP6 expression (P = 0.037). Additionally, knockdown of TNFAIP6 inhibited the proliferation, invasion and metastasis of GC cells in vitro. High TNFAIP6 expression was associated with the depth of tumor invasion, lymph node metastasis, TNM stage and poor prognosis of GC patients, suggesting that TNFAIP6 may serve as a novel indicator of the prognosis and as a treatment target of GC.


Fine tuning of the redox function of Pseudomonas aeruginosa cytochrome c551 through structural properties of a polypeptide loop bearing an axial Met residue.
Pseudomonas aeruginosa cytochrome c(551) (PA) possesses a long polypeptide loop near its heme, and a unique hydrogen bond network among Ser52, axial Met61, and the heme 13-propionate side chain, i.e., Ser52 amide NH is hydrogen bonded to axial Met61 carbonyl CO, Met61 amide NH to Ser52 carbonyl CO, and Ser52 side chain OH to the heme 13-propionate side chain, contributes to stabilization of the structure of the loop [Y. Matsuura, T. Takano, R.E. Dickerson, J. Mol. Biol. 156 (1982) 389-409]. In this study, the structure and redox function of S52N and S52G mutants were characterized in order to elucidate the role of Ser52 in functional regulation of the protein. We found that the redox function of PA was hardly affected by an S52N mutation, but was slightly by an S52G one. The functional similarity between the wild-type protein and the S52N mutant demonstrated that Asn52 in the mutant plays a similar pivotal role in the formation of the unique hydrogen bond network that stabilizes the structure of the loop as Ser52 in the wild-type protein does. On the other hand, the functional alteration induced by the S52G mutation can be attributed to a structural change of the loop due to the lack of the hydrogen bond between the Gly52 and heme 13-propionate side chain in the mutant. Thus, this study demonstrated that the function of the protein can be tuned through the structural properties of the polypeptide loop near its heme.


Constitutive mTOR activation in TSC mutants sensitizes cells to energy starvation and genomic damage via p53.
Miscoordination of growth and proliferation with the cellular stress response can lead to tumorigenesis. Mammalian target of rapamycin (mTOR), a central cell growth controller, is highly activated in some malignant neoplasms, and its clinical implications are under extensive investigation. We show that constitutive mTOR activity amplifies p53 activation, in vitro and in vivo, by stimulating p53 translation. Thus, loss of TSC1 or TSC2, the negative regulators of mTOR, results in dramatic accumulation of p53 and apoptosis in response to stress conditions. In other words, the inactivation of mTOR prevents cell death by nutrient stress and genomic damage via p53. Consistently, we also show that p53 is elevated in TSC tumors, which rarely become malignant. The coordinated relationship between mTOR and p53 during cellular stress provides a possible explanation for the benign nature of hamartoma syndromes, including TSC. Clinically, this also suggests that the efficacy of mTOR inhibitors in anti-neoplastic therapy may also depend on p53 status, and mTOR inhibitors may antagonize the effects of genotoxic chemotherapeutics.


Effectiveness of eslicarbazepine acetate in dependency of baseline anticonvulsant therapy: Results from a German prospective multicenter clinical practice study.
Eslicarbazepine acetate (ESL) is a third-generation antiepileptic drug (AED) approved as monotherapy for partial-onset seizures in adults and as adjunctive therapy in patients aged above 6 years in the European Union (EU). The prospective observational Zebinix Effects in DEpendency of BAseline Conditions (ZEDEBAC) study aimed at investigating the effectiveness of ESL in clinical practice, with ESL being administered as monotherapy (mono group), as only add-on to a current monotherapy (1+ group), or as add-on to ≥2 baseline AEDs (≥2+ group). In total, 237 patients were included, 35 in the mono group, 114 in the 1+, and 88 in the ≥2+ group. Six-month retention rates were 93.9%, 78.0%, and 75.3% in the mono, 1+, and ≥2+ group. There were 90.5%, 77.6%, and 48.3% of patients in the mono, 1+, and ≥2+ groups who were responders (patients with a ≥50% reduction in seizure frequency at follow-up vs. baseline). Seizure freedom rates were 81.5%, 47.9%, and 23.4%, respectively. Adverse drug reactions (ADRs) occurred in 11.4% of patients of the mono, 19.3% of the 1+, and 28.4% of patients of the ≥2+ group. Hyponatremia was reported as ADR in 3.4% of all patients. Although baseline variables differed considerably, with most elderly patients with tumor-related and vascular etiologies in the mono group and most patients with refractory epilepsies with pronounced use of concomitant sodium channel blockers (SCBs) in the ≥2+ group, retention as a measure of real-life effectiveness turned out not to be substantially different and favorable in all groups.


Muon Tracing and Image Reconstruction Algorithms for Cosmic Ray Muon Computed Tomography.
Cosmic ray muon-computed tomography (μCT) is a new imaging modality with unique characteristics that could be particularly important for diverse applications including nuclear nonproliferation, spent nuclear fuel monitoring, cargo scanning, and volcano imaging. The strong scattering dependence of muons on atomic number Z in combination with high penetration range could offer a significant advantage over existing techniques when dense, shielded containers must be imaged. However, μCT reconstruction using conventional filtered back-projection is limited due to the overly simple assumptions that do not take into account the curved path caused by multiple Coulomb scattering prompting the need for more sophisticated approaches to be developed. In this paper, we argue that the use of improved muon tracing and scattering angle projection algorithms as well as an algebraic reconstruction technique should produce muon tomographic images with improved quality - or require fewer muons to produce the same image quality - compared to the case where conventional methods are used. We report on the development and assessment of three novel muon tracing methods and two scattering angle projection methods for μCT. Simulated dry storage casks with single and partial missing fuel assemblies were used as numerical examples to assess and compare the proposed methods. The reconstructed images showed an expected improvement in image quality when compared with conventional techniques, even without muon momentum information, which should lead to improved detection capability, even for partial defects.


Metformin is associated with reduced COVID-19 severity in patients with prediabetes.
Studies suggest that metformin is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemics. We assessed if metformin is associated with reduced incidence of severe COVID-19 for patients with prediabetes or polycystic ovary syndrome (PCOS), common diseases that increase the risk of severe COVID-19. This observational, retrospective study utilized EHR data from 52 hospitals for COVID-19 patients with PCOS or prediabetes treated with metformin or levothyroxine/ondansetron (controls). After balancing via inverse probability score weighting, associations with COVID-19 severity were assessed by logistic regression. In the prediabetes cohort, when compared to levothyroxine, metformin was associated with a significantly lower incidence of COVID-19 with "mild-ED" or worse (OR [95% CI]: 0.636, [0.455-0.888]) and "moderate" or worse severity (0.493 [0.339-0.718]). Compared to ondansetron, metformin was associated with lower incidence of "mild-ED" or worse severity (0.039 [0.026-0.057]), "moderate" or worse (0.045 [0.03-0.069]), "severe" or worse (0.183 [0.077-0.431]), and "mortality/hospice" (0.223 [0.071-0.694]). For PCOS, metformin showed no significant differences in severity compared to levothyroxine, but was associated with a significantly lower incidence of "mild-ED" or worse (0.101 [0.061-0.166]), and "moderate" or worse (0.094 [0.049-0.18]) COVID-19 outcome compared to ondansetron. Metformin use is associated with less severe COVID-19 in patients with prediabetes or PCOS.


Seasonal variations in [3H]citalopram platelet binding between healthy controls and violent offenders in Finland.
Monthly binding densities (B(max)) of [3H]citalopram to the platelet serotonin transporter (SERT) was measured longitudinally over 1 year in a control group of 18 healthy Finnish male volunteers. Single platelet samples were also analysed from 33 men who were incarcerated for violent crimes during the same calendar year. A statistically significant seasonal variation in SERT B(max) was observed in both data sets, and bi-monthly floating averages for SERT B(max) were calculated and then fit to an annual sinusoidal curve for both groups. The B(max) for platelet [3H]citalopram binding showed a statistically significant (p = 0.001) seasonal variance between a winter (January-February) maximum of 1590 fmol/mg protein and a summer (July-August) minimum of 1216 fmol/mg protein for the control group, with an R2 of 70% for the annual sinusoidal curve fit. A statistically significant (p = 0.007) seasonal variance was also observed between a winter (January-February) maximum of 1980 fmol/mg protein and an autumnal (August-September) minimum of 1234 fmol/mg protein for the violent offenders, again with an R2 of 70% for the annual sinusoidal curve fit. This observation lends additional support to the idea that violent human behavior and impulsivity may be directly linked to values of SERT B(max), which can be affected by various psychoactive drugs and also varies with the natural change of seasons.


Development of Novel DNA Cleavage Systems Based on Copper Complexes. Synthesis and Characterisation of Cu(II) Complexes of Hydroxyflavones.
Copper(II) complexes of several hydroxyflavones were prepared and characterised through their physico-chemical properties. The nuclease activity of three synthesised complexes is reported. These copper(II) complexes present more nuclease activity than the ligands and the copper(II) ion.


Imaging of urinary bladder injury: the role of CT cystography.
Although conventional radiographic cystography has been traditionally considered the reference standard in detecting bladder injuries, computed tomography (CT) cystography has become the initial imaging method of choice in the acute setting. CT cystography has been shown to provide comparable accuracy as conventional cystography, and can be easily performed in conjunction with trauma CT surveys in patients with suspected bladder injuries. Despite increasing enthusiasm toward CT cystography in dealing with patients with suspected bladder injuries, there is little information in this regard in the literature. This article aims to discuss the role of CT cystography in the evaluation of bladder injuries.


Diabetic macular oedema: pilot randomised trial of pars plana vitrectomy vs macular argon photocoagulation.
Focal macular photocoagulation for clinically significant macular oedema (CSME) is the proven method for treatment of this condition, but with little chance of visual improvement. Pars plana vitrectomy (PPV) may produce resolution of macular oedema and improvement in visual acuity. However, there have been no randomised trials to ascertain role of vitrectomy in the management of persistent CSME. Patients with persistent CSME despite previous macular photocoagulation and Snellen visual acuity 6/15 to 6/60 were recruited. Dilated fundoscopy, best-corrected visual acuity including Early Treatment Diabetic Retinopathy Study (ETDRS) vision, ocular coherence tomography and fundus fluorescein angiography (FFA) at baseline and up to 12 months post-treatment was performed. Exclusion criteria were signs of posterior vitreous detachment, macular traction or the taut posterior hyaloid face syndrome, or macular ischaemia on FFA. In all, 20 patients were randomised (10 in each arm) to either standard macular photocoagulation or PPV and removal of the posterior hyaloid face. Of the 20 patients recruited, seven patients completed the protocol in the vitrectomy and eight in the laser arms, respectively. There was little evidence of any difference in the foveal thickness at 12 months between the two treatment arms despite a gradual improvement. Only one patient, from the vitrectomy arm, suffered moderate visual loss (defined as loss of 15 ETDRS letters) (our primary outcome). In this pilot RCT, standard PPV provides little visual benefit compared to macular photocoagulation, but a larger definitive study is required to confirm this early appraisal.


Non-small-bowel lesions detected by capsule endoscopy in patients with obscure GI bleeding.
Approximately two thirds of patients undergoing capsule endoscopy for obscure GI bleeding will have an abnormality found in the small intestine. This report describes 9 patients (4 men, 5 women) of 140 with obscure bleeding in whom a source of their blood loss was found in the stomach or the colon at capsule endoscopy. A review was made of a prospective database of 140 consecutive patients undergoing capsule endoscopy for obscure GI bleeding at a single center. Patients with a definite or likely cause of bleeding within reach of conventional upper or lower GI endoscopy were identified. Three patients had gastric antral vascular ectasia and another an inflamed pyloric canal polyp. Two patients had actively bleeding cecal carcinoma, missed at previous colonoscopies. Two others had bleeding cecal angiodysplasia. The final patient had severe nonspecific cecal inflammation. The identification of these lesions was aided by the suspected blood indicator. All patients underwent endoscopic therapy or surgery for their non-small-bowel lesions. Like push enteroscopy, capsule endoscopy also can identify lesions within reach of conventional endoscopy and colonoscopy. These subsequently can be treated successfully. The reasons why these lesions have been missed are unclear.


Piloting a statewide emergency department take-home naloxone program: Improving the quality of care for patients at risk of opioid overdose.
Emergency department (ED) patients with nonfatal opioid overdose are at high risk for subsequent fatal overdose, yet ED programs aimed at reducing harm from opioid use remain underdeveloped. The objective was to pilot a statewide ED take-home naloxone program and improve the care of patients with opioid use disorder (OUD) and risky drug use through training and interprofessional network building. Nine hospital EDs with pharmacy, nurse, and physician champions were recruited, surveyed, and trained. Take-home naloxone rescue kits were developed, disseminated, and tracked. Two overdose prevention summits were convened prior to the COVID pandemic, and two X-waiver training courses aimed at emergency physicians and advanced practice providers were arranged, both in person and virtual. A total of 872 naloxone rescue kits were distributed to ED patients at risk of opioid overdose during the first phase of this project, and more than 140 providers were trained in the use of medications for OUD in acute care settings. A statewide ED take-home naloxone program was shown to be feasible across a range of different hospitals with varying maturity in preexisting OUD resources and capabilities. Future work will be aimed at both expanding and measuring the effectiveness of this work.


Two novel bacteriophages of thermophilic bacteria isolated from deep-sea hydrothermal fields.
Bacteriophages of thermophiles are of great interest due to their important roles in many biogeochemical and ecological processes. However, no virion has been isolated from deep-sea thermophilic bacteria to date. In this investigation, two lytic bacteriophages (termed Bacillus virus W1 and Geobacillus virus E1) of thermophilic bacteria were purified from deep-sea hydrothermal fields in the Pacific for the first time. Bacillus virus W1 (BVW1) obtained from Bacillus sp. w13, had a long tail (300nm in length and 15 nm in width) and a hexagonal head (70 nm in diameter). Another virus, Geobacillus virus E1 (GVE1) from Geobacillus sp. E26323, was a typical Siphoviridae phage with a hexagonal head (130 nm in diameter) and a tail (180 nm in length and 30 nm in width). The two phages contained double-stranded genomic DNAs. The genomic DNA sizes of BVW1 and GVE1 were estimated to be about 18 and 41 kb, respectively. Based on SDS-PAGE of purified virions, six major proteins were revealed for each of the two phages. The findings in our study will be very helpful to realize the effect of virus on thermophiles as well as the communities in deep-sea hydrothermal fields.


Design, synthesis and biological evaluation of thieno[3,2-d]pyrimidine derivatives containing aroyl hydrazone or aryl hydrazide moieties for PI3K and mTOR dual inhibition.
Recently, PI3K and mTOR have been regarded as promising targets for cancer treatment. Herein, we designed and synthesized four series of novel thieno[3,2-d]pyrimidine derivatives that containing aroyl hydrazone or aryl hydrazide moieties. These derivatives act as PI3K/mTOR dual inhibitors, suggesting that they can be used as cancer therapeutic agents. All compounds were tested for anti-proliferative activity against four cancer cell lines. The structure-activity relationship (SAR) studies were conducted by varying the moieties at the C-6 and C-2 positions of the thieno[3,2-d]pyrimidine core. It indicated that aryl hydrazide at C-6 position and 2-aminopyrimidine at C-2 position are optimal fragments. Compound 18b showed the most potent in vitro activity (PI3Kα IC50 = 0.46 nM, mTOR IC50 = 12 nM), as well as good inhibition against PC-3 (human prostate cancer), HCT-116 (human colorectal cancer), A549 (human lung adenocarcinoma) and MDA-MB-231 (human breast cancer) cell lines. Furthermore, Annexin-V and propidium iodide (PI) double staining confirmed that 18b induces apoptosis in cytotoxic HCT-116 cells. Moreover, the influence of 18b on cell cycle distribution was assessed on the HCT-116 cell line, and a cell cycle arrest was observed at the G1/S phases.


Reisolation and NMR characterization of the satratoxins G and H.
The exquisitely cytotoxic macrolides, satratoxins G and H, have been reisolated from a solvent extract of a rice culture inoculated with Stachybotrys chartarum to be used as high-purity reference compounds for analytical analyses. Extensive chromatographic separation realized the compounds that were fully recharacterized in two solvents by 1D- and 2D-NMR spectroscopy, revealing some discrepancies in the nuclear magnetic resonance (NMR) data as compared with the previously reported values found in the literature. Detailed spectra are provided in order to aid future identification and dereplication.


Hepatitis B prevention and treatment needs in women in Senegal (ANRS 12356 AmBASS survey).
Although mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is prevalent in West Africa, epidemiological data on HBV infection in women remain scarce. We studied i) hepatitis B surface antigen (HBsAg) prevalence and its correlates, ii) HBV screening history and serological status awareness, iii) MTCT risk and treatment needs in Senegalese women. A cross-sectional population-based serosurvey for HBsAg positivity was conducted in 2018-2019 in the rural area of Niakhar (Fatick region, Senegal). Participants were offered home-based HBV screening and answered face-to-face questionnaires. HBsAg-positive participants underwent clinical and biological assessments. Data were weighted and calibrated to be representative of the area's population. Logistic regression models helped identify factors associated with HBsAg-positivity in adult women (> 15 years old). HBsAg prevalence in adult women was 9.2% [95% confidence interval: 7.0-11.4]. Factors associated with HBsAg-positivity were being 15-49 years old (ref: ≥ 50), living in a household with > 2 other HBsAg-positive members, and knowing someone with liver disease. Only 1.6% of women had already been tested for HBV; no one who tested HBsAg positive was already aware of their serological status. In women 15-49 years old, 5% risked MTCT and none were eligible for long-term antiviral treatment. Adult women have a high HBsAg prevalence but a low MTCT risk. Low rates of HBV screening and serological status awareness argue for the adoption of systematic screening during pregnancy using free and rapid diagnostic tests. Additionally, screening household members of HBsAg-positive women may greatly improve the cascade of care in rural Senegal. ClinicalTrials.gov identifier (NCT number): NCT03215732.


Synthesis of 5H-pyrido[3,2-b]pyrrolizin-5-one tripentone analogs with antitumor activity.
Pyrrolizinones represent an interesting class of compounds with varied degrees of structural complexity and pharmacological activity. Among these, 9H-pyrido[2,3-b]pyrrolizin-9-one, tripentone analogs, recently reported by us, showed significant antiproliferative activity against human tumor cell lines, inducing apoptosis and not affecting viability of Caco-2 differentiated in normal intestinal-like cells. Considering their interesting biological activity, their 5H-pyrido[3,2-b]pyrrolizin-5-one analogs were efficiently synthesized in good to excellent yields (61-91%). All tripentone derivatives were tested to assess their cytotoxicity against two human tumor cell lines, HCT-116 (human colorectal carcinoma) and MCF-7 (human breast cancer). The most active derivatives, with IC50 ranging from 0.11 to 16.11 μM, did not affect viability of Caco-2 differentiated in normal intestinal-like cells, suggesting tumor cells as the main target of their cytotoxic action. The same compounds, further investigated, showed that they did not exert necrotic effects, while induced a clear shift of viable cells towards early apoptosis confining the cells in the mitotic phases.


Effect of oral motor facilitation technique on oral motor and feeding skills in children with cerebral palsy : a case study.
Deficiencies in oral motor function and feeding skills are common in children with cerebral palsy (CP). Oral motor therapy is a useful method to improve oral motor function and feeding skills. Oral motor facilitation technique (OMFT) is a newly designed comprehensive oral motor therapy, including postural control, sensory adaptation, breathing control, sensorimotor facilitation, and direct feeding. This study was performed to identify the effect of OMFT on oral motor function and feeding skills in children with CP. A total of 21 children with CP (3-10 years, GMFCS III-V) participated in 16 weeks (16 sessions) of OMFT. The effects on oral motor function and feeding skills were assessed using the Oral Motor Assessment Scale (OMAS) before the treatment, 8 and 16 weeks after OMFT. Data were analyzed using the Friedman test and post-hoc analysis. Significant improvement was found in oral motor function and feeding skills including mouth closure, lip closure on the utensil, lip closure during deglutition, control of the food during swallowing, mastication, straw suction, and control of liquid during deglutition after OMFT. Mouth closure was the most effective and mastication was the least effective item. Sixteen weeks is more effective than 8 weeks of OMFT. OMFT could be an effective and useful oral motor therapy protocol to improve oral motor function and feeding skills in children with CP.


A comparative study on the production of exopolysaccharides between two entomopathogenic fungi Cordyceps militaris and Cordyceps sinensis in submerged mycelial cultures.
The present study comparatively investigates the optimal culture conditions for the production of exopolysaccharides (EPS) and cordycepin during submerged mycelial culture of two entomopathogenic fungi Cordyceps militaris and Cordyceps sinensis. Fermentations were performed in flasks and in 5-l stirred-tank fermenters. In the case of C. militaris, the highest mycelial biomass (22.9 g l(-1)) and EPS production (5 g l(-1)) were achieved in a medium of 40 g l(-1) sucrose, 5 g l(-1) corn steep powder at 30 degrees C, and an initial pH 8.0. The optimum culture conditions for C. sinensis was shown to be (in g l(-1)) 20 sucrose, 25 corn steep powder, 0.78 CaCl2, 1.73 MgSO4.7H2O at 20 degrees C, and an initial pH 4.0, where the maximum mycelial biomass and EPS were 20.9 and 4.1 g l(-1) respectively. Cordycepin, another bioactive metabolite, was excreted at low levels during the early fermentation period (maximum 38.8 mg l(-1) in C. militaris; 18.2 mg l(-1) in C. sinensis). The two fungi showed different nutritional and environmental requirements in their submerged cultures. Overall, the concentrations of mycelial biomass, EPS and cordycepin achieved in submerged culture of C. militaris were higher than those of C. sinensis. C. militaris and C. sinensis are representative insect-born fungi which have been longstanding and widely used as traditional medicines in eastern Asia. Comparative studies between two fungi are currently not available and this is the first report on the optimum medium composition for submerged culture of C. sinensis.


Cadmium-tolerant endophytic Pseudomonas rhodesiae strains isolated from Typha latifolia modify the root architecture of Arabidopsis thaliana Col-0 in presence and absence of Cd.
In this work, we isolated four Cd-tolerant endophytic bacteria from Typha latifolia roots that grow at a Cd-contaminated site. Bacterial isolates GRC065, GRC066, GRC093, and GRC140 were identified as Pseudomonas rhodesiae. These bacterial isolates tolerate cadmium and have abilities for phosphate solubilization, siderophore production, indole acetic acid (IAA) synthesis, and ACC deaminase activity, suggesting that they are plant growth-promoting rhizobacteria. Bacterial inoculation in Arabidopsis thaliana seedlings showed that P. rhodesiae strains increase total fresh weight and number of lateral roots concerning non-inoculated plants. These results indicated that P. rhodesiae strains promote A. thaliana seedlings growth by modifying the root system. On the other hand, in A. thaliana seedlings exposed to 2.5 mg/l of Cd, P. rhodesiae strains increased the number and density of lateral roots concerning non-inoculated plants, indicating that they modify the root architecture of A. thaliana seedlings exposed to cadmium. The results showed that P. rhodesiae strains promote the development of lateral roots in A. thaliana seedlings cultivated in both conditions, with and without cadmium. These results suggest that P. rhodesiae strains could exert a similar role inside the roots of T. latifolia that grow in the Cd-contaminated environment.


Detection and classification of intracranial haemorrhage on CT images using a novel deep-learning algorithm.
A novel deep-learning algorithm for artificial neural networks (ANNs), completely different from the back-propagation method, was developed in a previous study. The purpose of this study was to assess the feasibility of using the algorithm for the detection of intracranial haemorrhage (ICH) and the classification of its subtypes, without employing the convolutional neural network (CNN). For the detection of ICH with the summation of all the computed tomography (CT) images for each case, the area under the ROC curve (AUC) was 0.859, and the sensitivity and the specificity were 78.0% and 80.0%, respectively. Regarding ICH localisation, CT images were divided into 10 subdivisions based on the intracranial height. With the subdivision of 41-50%, the best diagnostic performance for detecting ICH was obtained with AUC of 0.903, the sensitivity of 82.5%, and the specificity of 84.1%. For the classification of the ICH to subtypes, the accuracy rate for subarachnoid haemorrhage (SAH) was considerably excellent at 91.7%. This study revealed that our approach can greatly reduce the ICH diagnosis time in an actual emergency situation with a fairly good diagnostic performance.


Mapping the growth hormone--Stat5b--IGF-I transcriptional circuit.
Growth hormone (GH) and insulin-like growth factor-I (IGF-I) exert powerful influences on somatic growth, metabolism, and tissue repair, and have been implicated in aging and carcinogenesis. Since the formulation of the somatomedin hypothesis over 50 years ago, GH and IGF-I have been linked intimately to one another. Recent studies have established that GH potently stimulates IGF-I gene transcription, and through this mechanism controls production of IGF-I. A key mediator of the GH-IGF-I biosynthetic pathway is the latent transcription factor Stat5b. This review summarizes the potentially complex mechanistic relationship between GH action, Stat5b, and IGF-I gene activation, and suggests that Stat5b may have a broad role in mediating IGF-I gene regulation in response to diverse physiological inputs.


μ-Oxido-bis-[(5,10,15,20-tetra-phenyl-porphyrinato-κ4 N,N',N'',N''')manganese(III)].
In the crystal structure of the title oxido-bridged binuclear complex, [MnIII(TPP)]2O (TPP = tetra-phenyl-porphyrinate, C44H28N4) or [Mn2(C44H28N4)2O], the two penta-coordinate manganese(III) ions are bridged by a single oxido ligand, with an Mn-O distance of 1.7600 (3) Å and an Mn-O-Mn bridging angle of 176.1 (2)°. The bridging O2- ligand is located on a twofold rotation axis, resulting in point group 2 for the entire complex. The MnIII atom is displaced out of the 24-atom mean plane of the porphyrine entity by 0.52 Å. C-H⋯π and π-π inter-actions help to stabilize the mol-ecular packing within the crystal structure.


Design and synthesis of astatinated benzothiazole compounds for their potential use in Targeted Alpha Therapy (TAT) strategies to treat Alzheimer's disease-associated amyloid plaques.
Alzheimer's disease (AD) is a terminal neurodegenerative disease characterized by the buildup of amyloid fibrils, amorphous aggregates and tauopathies. Several treatment modalities, which rely on various biological processes to reduce disease burden, have been largely ineffective at treating Alzheimer's disease. Targeted alpha therapy (TAT) has demonstrated positive results in the treatment of cancer. Benzothiazole derivatives have been successfully shown to target these plaques and are used in several imaging applications. One such derivative, Flutemetamol (VizamylTM) is an FDA approved diagnostic tool for PET imaging of AD-associated plaques. We report the radiolabeling of benzothiazole derivatives with 211At, a 7.2 h alpha emitting radionuclide, using a copper catalyzed reaction with a boronic acid precursor molecule. Our final compound [211At]3'-At-PIB-OMe had a radiochemical yield of 55% and was found to be stable for at least 3 h in phosphate buffered saline.


Motor cortex stimulation activates the incertothalamic pathway in an animal model of spinal cord injury.
We have shown previously that electrical stimulation of the motor cortex reduces spontaneous painlike behaviors in animals with spinal cord injury (SCI). Because SCI pain behaviors are associated with abnormal inhibition in the inhibitory nucleus zona incerta (ZI) and because inactivation of the ZI blocks motor cortex stimulation (MCS) effects, we hypothesized that the antinociceptive effects of MCS are due to enhanced inhibitory inputs from ZI to the posterior thalamus (Po)-an area heavily implicated in nociceptive processing. To test this hypothesis, we used a rodent model of SCI pain and performed in vivo extracellular electrophysiological recordings in single well-isolated neurons in anesthetized rats. We recorded spontaneous activity in ZI and Po from 48 rats before, during, and after MCS (50 μA, 50 Hz; 300-ms pulses). We found that MCS enhanced spontaneous activity in 35% of ZI neurons and suppressed spontaneous activity in 58% of Po neurons. The majority of MCS-enhanced ZI neurons (81%) were located in the ventrorateral subdivision of ZI-the area containing Po-projecting ZI neurons. In addition, we found that inactivation of ZI using muscimol (GABAA receptor agonist) blocked the effects of MCS in 73% of Po neurons. Although we cannot eliminate the possibility that muscimol spread to areas adjacent to ZI, these findings support our hypothesis and suggest that MCS produces antinociception by activating the incertothalamic pathway. This article describes a novel brain circuit that can be manipulated, in rats, to produce antinociception. These results have the potential to significantly impact the standard of care currently in place for the treatment of patients with intractable pain.


DREAM--a novel approach for robust, ultrafast, multislice B₁ mapping.
A novel multislice B₁-mapping method dubbed dual refocusing echo acquisition mode is proposed, able to cover the whole transmit coil volume in only one second, which is more than an order of magnitude faster than established approaches. The dual refocusing echo acquisition mode technique employs a stimulated echo acquisition mode (STEAM) preparation sequence followed by a tailored single-shot gradient echo sequence, measuring simultaneously the stimulated echo and the free induction decay as gradient-recalled echoes, and determining the actual flip angle of the STEAM preparation radiofrequency pulses from the ratio of the two measured signals. Due to an elaborated timing scheme, the method is insensitive against susceptibility/chemical shift effects and can deliver a B₀ phase map and a transceive phase map for free. The approach has only a weak T₁ and T₂ dependence and moreover, causes only a low specific absorption rate (SAR) burden. The accuracy of the method with respect to systematic and statistical errors is investigated both, theoretically and in experiments on phantoms. In addition, the performance of the approach is demonstrated in vivo in B₁-mapping and radiofrequency shimming experiments on the abdomen, the legs, and the head on an eight-channel parallel transmit 3 T MRI system.


Transbronchial Biopsy and Cryobiopsy in the Diagnosis of Hypersensitivity Pneumonitis among Patients with Interstitial Lung Disease.
Rationale: Hypersensitivity pneumonitis (HP) is an interstitial lung disease (ILD) with a diagnosis based on clinical, radiological, and pathological findings. The evidence supporting transbronchial forceps lung biopsy (TBBx) and transbronchial lung cryobiopsy (TBLC) as sampling techniques to diagnose HP in patients with newly detected ILD has not been reviewed systematically.Objectives: A systematic review was performed to assess the diagnostic yield and complication rates of TBBx or TBLC in patients with newly detected ILD whose differential diagnosis includes HP and to inform the development of the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of HP.Methods: Medline, Excerpta Medica Database, and the Cochrane Library were searched through October 2019. Studies that enrolled patients with ILD and reported the diagnostic yield of TBBx or TBLC were selected for inclusion. Data related to diagnostic yield and safety outcomes were extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation (GRADE) approach.Results: The histopathologic diagnostic yields (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBBx and TBLC were 37% (95% confidence interval [CI], 32-42%) and 82% (95% CI, 78-86%), respectively, among patients with ILD. Among those diagnosed by TBBx, the proportion with HP could not be determined. However, among those diagnosed by TBLC, 13.4% had HP. TBBx was complicated by moderate to severe bleeding, severe bleeding, and pneumothorax in 4% (95% CI, 0-8%), 0% (95% CI, 0-1%), and 7% (95% CI, 2-13%) of patients, respectively. TBLC was complicated by any bleeding, severe bleeding, and pneumothorax in 11% (95% CI, 7-15%), 0% (95% CI, 0-1%), and 11% (95% CI, 9-14%) of patients, respectively. The quality of the evidence was very low because of the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results.Conclusions: Very low-quality evidence indicated that TBLC had a higher diagnostic yield than TBBx among patients with ILD, although complications were similar.


Determinants of health-related quality of life among patients with systemic lupus erythematosus in Hanoi, Vietnam.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease which impacts patients' lives. Many studies in high-income countries have focused on their health-related quality of life (HRQoL). However, evidence of awareness of SLE and HRQoL in low- and middle-income countries is lacking. Therefore, this study aimed to identify the determinants of HRQoL of SLE patients in Vietnam, a lower-middle income country. This cross-sectional study was conducted at the National Hospital of Dermatology and Venereology in 2019. A pre-tested structured questionnaire was used to collect data. It consisted of Short Form-36 to assess HRQoL which comprised physical and mental component summaries, Multidimensional Scale of Perceived Social Support, Satisfaction with Life Scale, and Mental Adjustment to SLE. Multiple linear regression was used to identify the determinants of HRQoL. One hundred thirty four patients with SLE participated in this study. The majority of the patients were women (n = 126, 94.0%). The mean age of all participants was 37.9 years old (standard deviation [SD] 12.5). Of 134 participants, 104 (77.6%) were married. Older patients were more likely to have a lower score of mental component summary (B=-0.45, 95% CI -0.73, -0.17). Patients with more children were more likely to have a lower score of physical component summary (B=-5.14, 95% CI -9.27, -1.00). Patients who felt more helplessness or hopelessness were more likely to have lower scores of physical and mental component summaries (B=-1.85, 95% CI -2.80, -0.90; B=-1.69, 95% CI -2.57, -0.81). Also, patients who felt more anxious were more likely to have a lower score of mental component summary (B=-1.04, 95% CI -1.77, -0.32). Patients who were more satisfied with their lives were more likely to have higher scores of physical and mental component summaries (B = 1.07, 95% CI 0.50, 1.64; B = 1.08, 95% CI 0.55, 1.61). Factors associated with lower HRQoL in Vietnam were feelings of helplessness or hopelessness, and burdens of parenting roles. However, social support can contribute to a higher HRQoL, such as information support, self-support groups, and daycare services provided at the community level.


The Effects of Autologous Fat Transfer in an In Vitro Model of Basal Joint Osteoarthritis.
Basal joint osteoarthritis (OA) is a highly prevalent and debilitating condition. Recent clinical evidence suggests that autologous fat transfer (AFT) may be a promising, minimally invasive treatment for this condition. However, the mechanism of action is not fully understood. It is theorized that AFT reduces inflammation in the joint, functions to regenerate cartilage, or acts as a mechanical buffer. The purpose of this study was to better understand the underlying mechanism of AFT using an in vitro model. We hypothesize that the addition of stromal vascular fraction (SVF) cells will cause a reduction in markers of inflammation. Articular chondrocytes were expanded in culture. Liposuction samples were collected from human subjects and processed similarly to AFT protocols to isolate SVF rich in adipose-derived stem cells. A control group was treated with standard growth media, and a positive control group (OA group) was treated with inflammatory cytokines. To mimic AFT, experimental groups received inflammatory cytokines and either a low or high dose of SVF. Expression of relevant genes was measured, including interleukin (IL)-1ß, IL-1 receptor antagonist, and matrix metalloproteinases (MMP). Compared to the OA group, significant decreases in IL-1ß, MMP3, and MMP13 expression on treatment day 3 were found in the high-dose SVF group, while MMP13 expression was also significantly decreased in the low-dose SVF group on day 3. In this study, we found that SVF treatment reduced expression of IL-1ß, MMP3, and MMP13 in an in vitro model of OA. These results suggest that an anti-inflammatory mechanism may be responsible for the clinical effects seen with AFT in the treatment of basal joint OA. An anti-inflammatory mechanism may be responsible for the clinical benefits seen with AFT for basal joint arthritis.


Assessment of the viability of human periodontal ligament cells in black tea, lime juice, and passion fruit concentrate - A comparative in vitro study.
Tooth avulsion is considered as a severe form of dental trauma, causing damage to the periodontium. Hence, the preservation of healthy periodontal ligament (PDL) cells in the storage medium are pivotal for the success of replantation. The aim of this study is to assess the viability of human PDL cells in black tea, lime juice, and passion fruit concentrate. Human periodontal cells were cultured and stored in three experimental media - black tea, lime juice, and passion fruit concentrate and subjected to 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay for 1 h and the cell viability was determined. Mean and standard deviation were statistically analyzed using one-way analysis of variance to identify the significant groups. The human PDL cells showed 100% viability in lime juice and passion fruit concentrate, followed by 98% viability in black tea. Black tea, lime juice, and passion fruit concentrate can be used effectively as storage media for maintaining PDL cells viability in avulsed teeth, with 100% viability exhibited by lime juice and passion fruit concentrate.


Intramolecular translocation of the protein radical formed in the reaction of recombinant sperm whale myoglobin with H2O2.
A sperm whale myoglobin gene containing multiple unique restriction sites has been constructed in pUC 18 by sequential assembly of chemically synthesized oligonucleotide fragments. Expression of the gene in Escherichia coli DH5 alpha cells yields protein that is identical to native sperm whale myoglobin except that it retains the terminal methionine. Site-specific mutagenesis has been used to prepare all the possible tyrosine----phenylalanine mutants of the recombinant myoglobin, including the three single mutants at Tyr-103, -146, and -151, the three double mutants, and the triple mutant. All of the mutant proteins are stable except the Tyr-103 mutant. Introduction of a second mutation (Lys-102----Gln) stabilizes the Tyr-103 mutant. Absorption spectroscopy suggests that the active sites of the mutant proteins are intact. EPR and absorption spectroscopy show that all the proteins, including the triple mutant devoid of tyrosine residues, react with H2O2 to give a ferryl species and a protein radical. The presence of a protein radical in all the mutants suggests that the radical center is readily transferred from one amino acid to another. Cross-linking studies show, however, that protein dimers are only formed when Tyr-151 is present. Tyr-103, shown earlier to be the residue that primarily cross-links to Tyr-151 (Tew, D., and Ortiz de Montellano, P. R. (1988) J. Biol. Chem. 263, 17880-17886), is not essential for cross-linking. Electron transfer from Tyr-151 to the heme, which are 12 A apart, occurs in the absence of the intervening tyrosines at positions 103 and 146. The present studies show that the peroxide-generated myoglobin radical readily exchanges between remote loci, including non-tyrosine residues, but protein cross-linking only occurs when radical density is located on Tyr-151.


The utility of the AusEd driving simulator in the clinical assessment of driver fatigue.
Several driving simulators have been developed which range in complexity from PC based driving tasks to advanced "real world" simulators. The AusEd driving simulator is a PC based task, which was designed to be conducive to and test for driver fatigue. This paper describes the AusEd driving simulator in detail, including the technical requirements, hardware, screen and file outputs, and analysis software. Some aspects of the test are standardized, while others can be modified to suit the experimental situation. The AusEd driving simulator is sensitive to performance decrement from driver fatigue in the laboratory setting, potentially making it useful as a laboratory or office based test for driver fatigue risk management. However, more research is still needed to correlate laboratory based simulator performance with real world driving performance and outcomes.


Syndromology: an updated conceptual overview. X. References.
Part X is the reference section for Parts I through VIII which appeared in the four previous issues of the journal and Part IX which appears in this issue. The reference section itself is divided into two parts. The first part provides general references of selected topics for the interested reader. The second part consists of an alphabetical listing of all references cited in Parts I through IX.


[Postsurgical family information: an improvement area. Prospective study after urologic surgery].
Analyzing and quantifying the postoperative retention of information, checking if it could be improved been delivered in an organized way. After the basic information to relatives of 50 post-surgical patients operated for bladder or prostate, we deliver a questionnaire about what has just been told. It must be completed by a family member. The information is distributed differently: group 1 (30 patients) reported to the family following a script designed by us, written in simple and natural language. In group 2 (20 patients) the doctor informed as usual, not knowing that he is participating in the research. Then the relative is interviewed by one of the researchers. Only 3 (6%) family members matched all the right answers, and 25 (50%) did not hit more than 70% of the issues. The best known concept was the organ involved: 46 (92%). 21(42%) of respondents did not know if the process is basically benign or malignant, getting better results in group 1 but without significance: 20/30 (66.7%) vs 9/20 (45%) (p>0.05). The only item in which there are differences in success rate depending on the group is if a catheter have been set: 29 (96.7%) of successes in group 1, 13(65%) in 2. We found no difference in success rate according to number of family members informed, education, age or number of previous interventions. Relatives do not retain everything that was said. Organizing the information provided may improve, but other factors have influence. We must improve issues such as personal identification. It may be useful to repeat the information later.


Agaricus subrufescens: A review.
Medicinal mushrooms have currently become a hot issue due to their various therapeutic properties. Of these, Agaricus subrufescens, also known as the "almond mushroom", has long been valued by many societies (i.e., Brazil, China, France, and USA). Since its discovery in 1893, this mushroom has been cultivated throughout the world, especially in Brazil where several strains of A. subrufescens have been developed and used as health food and alternative medicine. This article presents up-to-date information on this mushroom including its taxonomy and health promoting benefits. Medicinal properties of A. subrufescens are emphasized in several studies which are reviewed here. In addition, safety issues concerning the use of this fungus will be discussed.


[Scintigraphic bone scans in evaluation of aseptic and septic hip prosthesis loosening].
The results of clinical examination, three-phase bone scintigraphy and intraoperative findings were compared in 29 patients. Scintigraphic criteria of infection or aseptic loosening have been presented. The method proved to be highly useful with sensitivity, specificity and accuracy being 100, 73 and 90 per cent respectively.


Risks of seawater ozonation in recirculation aquaculture--effects of oxidative stress on animal welfare of juvenile turbot (Psetta maxima, L.).
Ozone is frequently used for water treatment and disinfection in recirculating aquaculture systems. However, due to the fragmentary data on chronic toxicity of ozone produced oxidants (OPO) and its safe concentrations, the daily application of ozone in aquaculture is challenging. To evaluate the chronic effects of sublethal OPO concentrations, juvenile turbot (Psetta maxima, L.) were exposed to OPO concentrations of 0.06, 0.10 and 0.15 mg/l for 21 days. Gills were analysed for histopathological alterations and mRNA expression of heat shock protein 70 (hsp70), hsp90 as well as glutathione-S-transferase (gst) were determined in the gills and the liver after 1d, 7d and 21 d. Histopathologic findings confirmed adverse effects at 0.10-0.15 mg/l, but these (necrosis, lamellar clubbing, hypertrophy, hyperplasia) could only be observed after an extended exposure (mostly 21 d), and were considered as irreversible tissue damage. Hsp70 expression in the gills was only significantly increased at the highest OPO concentration (0.15 mg/l) on 1d and 7d, and returned to basic levels until day 21. Hsp90 mRNA was already increased at 0.10mg/l after 1 and 7 days of exposure, and again was comparable to the control group on day 21. In contrast, elevated gst mRNA expression was only observed on day 7 at 0.10mg and 0.15 mg/l. Although similar trends were observed in the liver for all markers, differences were only significant in exceptional cases due to the high individual variation observed. Thus, mRNA expression in the gills rather than in the liver is recommended as a marker to characterize OPO-induced oxidative stress in turbot. It has to be noted that mRNA expression returned to basic levels on day 21 regardless the actual OPO concentration, suggesting a collapse of adaptive mechanisms as a possible explanation for the observed tissue damage.


Negative affect as a mediator of the relationship between weight-based teasing and binge eating in adolescent girls.
Previous research has established a link between weight-based teasing and binge eating, though the precise mechanisms that drive this relationship remain unknown. This study examined negative affect as a mediator of the relationship between weight-based teasing and binge eating. Participants included 265 adolescent female twins (aged 10-15 years). Self-report measures assessed binge eating, weight-based teasing, and negative affect. Mediation was tested within hierarchical linear models to control for the non-independence of the twin data. Significant positive associations were observed between binge eating, teasing, and negative affect. In the regression analyses, negative affect partially mediated associations between weight-based teasing and binge eating. Results suggest that increases in negative affect are one way in which weight-based teasing leads to binge eating in girls. Future studies should examine additional mediators and assess possible clinical applications of these findings.


Tracheobronchial abnormalities in infants with bronchopulmonary dysplasia.
Twelve preterm infants with bronchopulmonary dysplasia underwent bronchoscopy to determine if airway abnormalities were contributing to persistent pulmonary problems. Indications for bronchoscopy were persistent atelectasis, lobar hyperinflation, or both on chest radiograph (11 patients), unexplained respiratory distress (three patients), and aspiration of tissuelike material from a tracheostomy (one patient). Bronchoscopy revealed abnormalities of the trachea, bronchi, or both in all infants, including partial or near total airway occlusion by abnormal growth of tissue (10 patients); tracheomalacia, bronchomalacia, or both (three patients); and inspissated secretions (two patients). Seven infants died during initial hospitalization. Tracheobronchial abnormalities should be considered as a cause of persistent pulmonary problems in infants with bronchopulmonary dysplasia.


Effects of feed systems on growth performance, carcass characteristics, organ index, and serum biochemical parameters of pigeon.
This study aimed to investigate the effects of feed systems in parent pigeons on the growth performance, carcass characteristics, organ index, and serum biochemical parameters of squabs. A total of 60 pairs of parent pigeons were selected and divided into 2 groups randomly. The parent pigeons were fed with two feed systems that were whole grains plus granulated feed (WGG) and complete-formula granulated feed (CFG) for 21 d. The results showed that CFG diet could increase carcass yield, heart index, content of trypsin, and growth hormone of squabs (P < 0.05), but decrease feed intake, gizzard index, b* value, malondialdehyde concentration, and uric acid concentration significantly (P < 0.05) comparing with WGG diet. There were no significant differences among the 2 groups in feed intake from d 1 to d 21, abdominal fat yield and body weight changes of squabs and parent pigeons (P > 0.05). It can be concluded from these observations that CFG was beneficial to squab which could improve digestive enzyme and antioxidant ability in the serum, so the CFG should be suggested in practice.


1-Aminobenzotriazole: A Mechanism-Based Cytochrome P450 Inhibitor and Probe of Cytochrome P450 Biology.
1-Aminobenzotriazole (1-ABT) is a pan-specific, mechanism-based inactivator of the xenobiotic metabolizing forms of cytochrome P450 in animals, plants, insects, and microorganisms. It has been widely used to investigate the biological roles of cytochrome P450 enzymes, their participation in the metabolism of both endobiotics and xenobiotics, and their contributions to the metabolism-dependent toxicity of drugs and chemicals. This review is a comprehensive evaluation of the chemistry, discovery, and use of 1-aminobenzotriazole in these contexts from its introduction in 1981 to the present.


High-resolution pulmonary ventilation and perfusion PET/CT allows for functionally adapted intensity modulated radiotherapy in lung cancer.
To assess the utility of functional lung avoidance using IMRT informed by four-dimensional (4D) ventilation/perfusion (V/Q) PET/CT. In a prospective clinical trial, patients with non-small cell lung cancer (NSCLC) underwent 4D-V/Q PET/CT scanning before 60Gy of definitive chemoradiation. Both "highly perfused" (HPLung) and "highly ventilated" (HVLung) lung volumes were delineated using a 70th centile SUV threshold, and a "ventilated lung volume" (VLung) was created using a 50th centile SUV threshold. For each patient four IMRT plans were created, optimised to the anatomical lung, HPLung, HVLung and VLung volumes, respectively. Improvements in functional dose volumetrics when optimising to functional volumes were assessed using mean lung dose (MLD), V5, V10, V20, V30, V40, V50 and V60 parameters. The study cohort consisted of 20 patients with 80 IMRT plans. Plans optimised to HPLung resulted in a significant reduction of functional MLD by a mean of 13.0% (1.7Gy), p=0.02. Functional V5, V10 and V20 were improved by 13.2%, 7.3% and 3.8% respectively (p-values<0.04). There was no significant sparing of dose to functional lung when adapting to VLung or HVLung. Plan quality was highly consistent with a mean PTV D95 and D5 ranging from 60.8Gy to 61.0Gy and 63.4Gy to 64.5Gy, respectively, and mean conformity and heterogeneity index ranging from 1.11 to 1.17 and 0.94 to 0.95, respectively. IMRT plans adapted to perfused but not ventilated lung on 4D-V/Q PET/CT allowed for reduced dose to functional lung whilst maintaining consistent plan quality.


The endocrine control of embryonic lung maturation in the chicken. I. Morphological and biochemical differentiation of lungs after "in ovo" decapitation.
The effects of "in ovo" hypophysectomy on lung maturation of the chick embryo were investigated. Both biochemical and morphological aspects of differentiation were markedly delayed in experimental embryos: the phospholipid content of lungs was lower than in controls at all stages, whereas the water content remained very high. The type II pneumocytes, which normally appear within the epithelium on day 16 of incubation, started to differentiate only between days 18 and 20 of incubation in the decapitated embryos. The differentiation of type I pneumocytes leading to the formation of air capillaries was also slowed down: they did not appear until the end of incubation in decapitated embryos, whereas they normally start to appear on day 19. The presence of an intact hypophysis is thus essential for normal lung maturation in the chicken.


Dynein at kinetochores: Making the connection.
Dynein removes the checkpoint proteins from kinetochores once chromosomes are bioriented. In this issue, Gama et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201610108) and Mosalaganti et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201611060) reveal the molecular basis for how dynein and its adaptor protein Spindly are recruited to the ROD-Zw10-Zwilch complex in the fibrous corona of unattached kinetochores.


Carcinogen-induced activation of SV40 gene expression in a semi-permissive environment.
Carcinogen-induced expression of the integrated viral genome was examined on SV40-transformed Chinese hamster cells. Carcinogen treatment markedly increased the transcription rate and the steady state mRNA level of both early and late viral transcripts. Carcinogen-induced transcription was mediated by RNA polymerase II. The increase in viral gene expression was also detected at the protein level, although at a reduced amplitude. Enhanced transcription was apparent as early as 12 hr postexposure and was considerably elevated after 24-36 hr. The increased gene expression depended on the existence of a functional replication machinery, as indicated by two lines of evidence. First, a cell line that harbors origin-deleted SV40 failed to respond to carcinogen treatment by increasing transcription and expression of T antigen. Furthermore, carcinogen-induced overtranscription was inhibited by aphidicolin, an inhibitor of DNA polymerase alpha. The involvement of the replication apparatus in the enhanced expression points to mechanistic similarities between the carcinogen-induced viral gene expression in the drug-treated semipermissive cells and the SV40 lytic pathway under permissive conditions. It is therefore suggested that cellular permissivity to viral development is enhanced following exposure to carcinogens. The implications of these findings for the nature of cellular permissivity to viral infection and the synergistic effects of carcinogens and tumor viruses are discussed.


A new interference-free lysine biosensor using a non-conducting polymer film.
An electrochemical biosensor for the determination of lysine to be used for rapid evaluation of food quality has been developed. Platinum electrodes have been coated by electropolymerisation with 1,2-diaminobenzene (1.2-DAB) using cyclic voltammetry. The reduction in the oxidation of interferents compared with the bare platinum electrode was 100% for ascorbic acid, 99% for acetaminophen and 99% for cysteine. The enzyme L-lysine-alpha-oxidase was then immobilised onto the polymer layer by passive adsorption and a calibration curve for lysine constructed. This gave a linear range of 1 x 10(-5) mol/l to 1 x 10(-3) mol/l and a limit of detection of 2 x 10(-7) mol/l.


Application of orthogonal sampling to incomplete data interferometric tomography: numerical simulation and experimental analysis.
Orthogonal projection sampling mode was proposed to reconstruct the incomplete-data flow field in optical computerized tomography (OCT). With numerical simulation technique, a two-peak plane symmetric flow field was reconstructed in different sampling modes and discussed in simulated results is the reconstructive accuracy with error indexes, such as mean square error (MSE) and peak error (PE). The corresponding experiments were researched with a Fabry-Perot rotary interferometer. The results indicated that the errors were drastically reduced and the precision was improved when orthogonal projection sampling mode was adopted in the reconstruction of the incomplete data field. The MSE obtained with orthogonal sampling mode was decreased 72.81% from that of the sequential projection sampling mode (the difference between the MSE obtained with the orthogonal sampling mode and that with the sequential sampling mode divided by the MSE of the sequential sampling mode) and the PE was decreased by 73.97%. The precision obtained from the experimental results reached 10%, which showed the orthogonal projection sampling could be a practicable sampling mode for the incomplete data field reconstruction in OCT and could provide some guidance for the flow-field measurement and apparatus design in the practical situation.


Traumatic osteonecrosis of the femoral head following intracapsular fracture: incidence and earliest radiological features.
A sub-capital fracture of the femoral neck is common particularly in the elderly female with non-union occurring in 25% and osteonecrosis in up to 24% of united fractures. Assessment of the viability of the femoral head in the early stages is unreliable and initial diagnosis of osteonecrosis depends on recognition of radiological features. Many reports imply that structural failure of the joint surface is the initial abnormality. 121 patients with a sub-capital fracture have been followed up for at least a year and as long as three and a half years. The incidence of osteonecrosis was 8% in Grade I fractures; 4% in Grade II and 21% and 30% in the more severe Grade III and Grade IV fractures. Of the 24 patients with osteonecrosis, increased radiological density developed in 13 at a time interval of 3 months to 36 months after the fracture with a mean time of 10 months and seven subsequently developed structural failure. Eleven patients developed structural failure as an initial feature at a time interval of 5 months to 24 months with a mean of 13 months. From this it is clear that either an absolute increase in radiographic density or structural failure are the earliest radiological features. Good quality radiographs, clearly demonstrating trabecular detail, are essential for the recognition of osteonecrosis.


A novel alignment-free method for HIV-1 subtype classification.
HIV-1 is the most common and pathogenic strain of human immunodeficiency virus consisting of many subtypes. To study the difference among HIV-1 subtypes in infection, diagnosis and drug design, it is important to identify HIV-1 subtypes from clinical HIV-1 samples. In this work, we propose an effective numeric representation called Subsequence Natural Vector (SNV) to encode HIV-1 sequences. Using the representation, we introduce an improved linear discriminant analysis method to classify HIV-1 viruses correctly. SNV is based on distribution of nucleotides in HIV-1 viral sequences. It not only computes the number of nucleotides, but also describes the position and variance of nucleotides in viruses. To validate our alignment-free method, 6902 complete genomes and 11,668 pol gene sequences of HIV-1 subtypes were collected from the up-to-date Los Alamos HIV database. SNV outperforms the three popular methods, Kameris, Comet and REGA, with almost 100% Sensitivity and Specificity, also with much less time. Our subtyping algorithm especially works better for circulating recombinant forms (CRFs) consisting of a few sequences. Our approach is also powerful to separate unique recombinant forms (URFs) from other subtypes with 100% Sensitivity and Specificity. Moreover, phylogenetic trees based on SNV representation are constructed using full-length HIV-1 genomes and pol genes respectively, where viruses from the same subtype are clustered together correctly.


[Romanowsky dyes and Romanowsky-Giemsa effect. 2. Eosin Y, erythrosin B, tetrachlorofluorescein, spectroscopic characterization of pure dyes, association of eosin Y].
Analytically pure samples of the Romanowsky dyes eosin y, erythrosin b and tetrachlorofluorescein are prepared. DC of the dye samples shows no contaminations. We measured the absorption spectra of the dye dianions in alkaline aqueous solution and of the dye acids in 95% ethanol at very low dye concentrations. The molar extinction coefficients of the long wavelength absorption of the monomeric dye species are determined (Table 1). The extinction coefficients may be used for standardisation of dye samples. The absorption spectra of eosin y in aqueous solution are dependent on concentration. Using a new very sensitive method it was possible to identify two association equilibria from the concentration dependency of the spectra. Dimers are formed even in very dilute solutions, at higher concentrations tetramers. The dissociation constant of the dimers D in monomers M at 293 K, pH = 12, is K21 = 2,9 X 10(-5) M; of the tetramers Q in dimers D K42 = 2,4 X 10(-3) M. From the experimental spectra of eosin solutions at various concentrations, pH = 12, and the equilibrium constants K21, K42 the absorption spectra of the pure monomers, dimers and tetramers are calculated. M has one long wavelength absorption band, VM = 19300 cm-1, epsilon M = 1,03 X 10(5) M-1 cm-1; D also one absorption band, VD = 19300 cm-1, epsilon D = 1,74 X 10(5) M-1 cm-1; Q two absorption bands, VQ1 = 19100, VQ2 = 20200 cm-1, epsilon Q1 = 1,65 X 10(5), epsilon Q2 = 1,96 X 10(5) M-1 cm-1. The absorption spectrum of the dimers is discussed by quantum mechanics.


3-O-substituted benzyl pyridazinone derivatives as COX inhibitors.
New 3-O-substituted benzyl pyridazinone compounds have been synthesised and evaluated for their cyclooxygenase inhibitory activity and COX-2 selectivity. Among the compounds synthesised, three compounds (11b-11d) have shown in vitro COX-2 selectivity. These compounds have been evaluated for their in vivo potential using carrageenan-induced rat paw edema assay. One compound (11b) showed 32% anti-inflammatory activity at 30 mgkg(-1) dose.


Injury-related causes of acute knee pain.
This detailed overview covers the anatomy, function, and examination of the knee and describes the phases of treatment for acute knee pain secondary to injury.


Use of microvena snare catheter in non-ST elevation myocardial infarction due to saphenous vein graft occlusive thrombi.
A 75-year-old man presented with acute coronary syndrome; he had a saphenous vein graft thrombosis. Percutaneous coronary intervention of bypass graft vessels is more challenging due to a higher incidence of periprocedural distal micro-emobilization and myocardial infarction. Current guidelines for percutaneous coronary intervention advocate the use of distal embolic protection devices, especially in patients with large thrombus burden, undergoing percutaneous intervention for vein graft disease. This patient was treated by manual aspiration of graft thrombus using a microvena catheter and successful clot removal was achieved. There are yet no best available therapeutic options for patients undergoing percutaneous coronary intervention of saphenous vein graft lesions.


Effectiveness of Substance Use Navigation for Emergency Department Patients With Substance Use Disorders: An Implementation Study.
We implemented a whole person care-informed intervention delivered by substance use navigators (SUN) for emergency department (ED) patients with substance use disorders. This was an implementation study of adult patients discharged from 3 public hospital EDs between September 1, 2021 through January 31, 2022 with cocaine, methamphetamine, alcohol, and opioid use-related diagnoses. The primary effectiveness outcome was treatment engagement within 30 days of ED discharge among patients with and without the SUN intervention. We used logistic regression and nearest neighbor propensity score matching without replacement to control for confounding effects. There were 1,328 patients in the cohort, and 119 (9.0%) received the SUN intervention; 50.4% of patients in the SUN intervention group and 15.9% of patients without the SUN intervention were engaged in outpatient treatment within 30 days of ED discharge (difference in proportions: 34.5%, 95% confidence interval [CI] 25.3% to 43.8%). In the unadjusted analysis, the SUN intervention was associated with higher rates of treatment engagement after ED discharge for patients with alcohol, opioid, and cocaine-related diagnoses; patients with methamphetamine-related diagnoses had low engagement rates with or without the SUN intervention. In addition, the SUN intervention was associated with higher odds of treatment engagement in the multivariable model (aOR 3.7, 95% CI 2.4 to 5.8) and in the propensity score-matched analysis (OR 2.1, 95% CI 1.2 to 3.5). A whole person care-informed intervention delivered by SUNs for ED patients with substance use disorders was strongly associated with higher engagement rates in addiction treatment after discharge.


HIGLE is a bifunctional homing endonuclease that directly interacts with HYL1 and SERRATE in Arabidopsis thaliana.
A highly coordinated complex known as the microprocessor precisely processes primary transcripts of MIRNA genes into mature miRNAs. In plants, the microprocessor minimally consists of three components: Dicer-like protein 1 (DCL1), HYPONASTIC LEAF 1 (HYL1), and SERRATE (SE). To precisely modulate miRNA maturation, the microprocessor cooperates with at least 12 proteins in plants. In addition, we here show the involvement of a novel gene, HYL1-interacting GIY-YIG-like endonuclease (HIGLE). The encoded protein has a GIY-YIG domain that is generally found within a class of homing endonucleases. HIGLE directly interacts with the microprocessor components HYL1 and SE. Unlike the functions of other GIY-YIG endonucleases, the catalytic core of HIGLE has both DNase and RNase activities that sufficiently processes miRNA precursors into short fragments in vitro.


[Genetic analysis of a rare case with Kallman syndrome and steroid sulfatase deficiency].
To explore the pathogenesis of a patient featuring azoospermia and steroid sulfatase deficiency. Polymerase chain reaction (PCR), G-banded karyotyping and Illumina Human CytoSNP-12 Beadchip analysis were conducted. STS sites PCR showed that there was no deletion in the AZF zone. G-banding analysis indicated an unknown structural change in chromosome X, which was verified by single nucleotide polymorphism array (SNP array) as a 5.4 Mb deletion in Xp22.31-p22.33. The Xp22.31-p22.33 deletion probably underlies the Kallman syndrome and steroid sulfatase defect in the patient.


Prognostic impact of HIF-1alpha expression in patients with definitive radiotherapy for cervical cancer.
To investigate the relationship between the hypoxia-inducible factor-(HIF-)1alpha expression in tumor tissue, tumor oxygenation and hemoglobin levels in patients with advanced cervical cancers prior to radiotherapy and the effect on clinical outcome. The investigation included 44 patients who underwent definitive radiotherapy for advanced cervical cancers between May 1995 and March 1999. Tumor biopsies were taken prior to treatment, and HIF-1alpha expression was determined by immunohistochemistry. In the same tumor area, tumor tissue oxygenation (pO2) was measured using the Eppendorf device. The 5-year cancer-specific survival of all patients was 60%. Twelve of 44 tumor specimens were HIF-1alpha-negative with a significantly better 5-year survival (92 +/- 8%) versus 32 patients who were HIF-1alpha-positive (45 +/- 10%; p < 0.02). There was no correlation between HIF-1alpha expression and tumor oxygenation (p = 0.57 both for pO2 median and hypoxic fraction < 5 mmHg vs. HIF-1alpha expression). However, patients with hemoglobin levels < 11 g/dl showed elevated HIF-1alpha expression compared to patients with hemoglobin levels > 12.5 g/dl (p = 0.04). Furthermore, HIF-1alpha correlated with vascular endothelial growth factor expression (p = 0.002). In a multivariate Cox regression model, HIF-1alpha expression (relative risk [RR] = 7.5; p = 0.05) revealed an increased risk of tumor-related death. The study indicates, that endogenous tumor markers such as HIF-1alpha may serve as prognostic markers of clinical outcome concerning cervical cancer after primary radiotherapy.


Intracellular pH regulation by Na⁺/H⁺ exchanger-1 (NHE1) is required for growth factor-induced mammary branching morphogenesis.
Regulation of intracellular pH (pHi) and protection against cytosolic acidification is primarily a function of the ubiquitous plasma membrane Na+/H+exchanger-1 (NHE1), which uses a highly conserved process to transfer cytosolic hydrogen ions (H+) across plasma membranes in exchange for extracellular sodium ions (Na+). Growth factors, which are essential regulators of morphogenesis, have also been found to be key activators of NHE1 exchanger activity; however, the crosstalk between both has not been fully evaluated during organ development. Here we report that mammary branching morphogenesis induced by transforming growth factor-alpha (TGFα) requires PI3K-dependent NHE1-activation and subsequent pHi alkalization. Inhibiting NHE1 activity after TGFα stimulation with 10 μM of the NHE1-specific inhibitor N-Methyl-N-isobutyl Amiloride (MIA) dramatically disrupted branching morphogenesis, induced extensive proliferation, ectopic expression of the epithelial hyper-proliferative marker Keratin-6 and sustained activation of MAPK. Together these findings indicate a novel developmental signaling cascade involving TGFα>PI3K>NHE1>pHi alkalization, which leads to a permissible environment for MAPK negative feedback inhibition and thus regulated mammary branching morphogenesis.


Gainful employment and risk of mortality after spinal cord injury: effects beyond that of demographic, injury and socioeconomic factors.
To evaluate the association of three levels of gainful employment with the risk of mortality after traumatic spinal cord injury (SCI) while controlling for known predictors of mortality status (including education and income). Prospective cohort study. A total of 20 federally funded SCI Model Systems of care in the United States. Participants included 7955 adults with traumatic SCI. Preliminary assessments were conducted between 1995 and 2006. Mortality status was determined by the Social Security Death Index (1308 deaths). A two-stage logistic regression model was used to estimate the chance of dying in any given year. Life expectancy was calculated under different economic assumptions. Compared with those who were working 30+ h per week, the odds of mortality was 1.37 for those who worked 1-29 h and 1.67 for those who were unemployed. The addition of gainful employment only modestly reduced the effects of household income and education, both of which remained significant. For instance, the odds of mortality for household income (referent $75 000+) decreased from 1.50 to 1.38 for $25 000-$75 000 and from 2.10 to 1.82 for < $25 000. Life expectancy varied widely depending on socioeconomic characteristics more than doubling under certain assumptions. Substantial variation in mortality is attributable to employment, above and beyond the effects of previously established demographic, injury and socioeconomic predictors. Although some excess mortality may be the inevitable consequence of SCI, risk is substantially increased with poor socioeconomic characteristics.


Update of carcinogenicity studies in animals and humans of 535 marketed pharmaceuticals.
This survey is a compendium of information retrieved on carcinogenicity in animals and humans of 535 marketed pharmaceuticals whose expected clinical use is continuous for at least 6 months or intermittent over an extended period of time. Of the 535 drugs, 530 have the result of at least one carcinogenicity assay in animals, and 279 (52.1%) of them gave a positive response in at least one assay. Only 186 drugs (34.8%) have retrievable information on carcinogenicity in humans, and 104 of them gave to a variable extent evidence of a potential carcinogenic activity. Concerning the correlation between results obtained in animals and epidemiological findings, 58 drugs gave at least one positive result in carcinogenicity assays performed in animals and to a variable extent displayed evidence of carcinogenicity in humans, but 97 drugs tested positive in animals and were noncarcinogenic in humans or vice versa. Our findings, which are in agreement with previous studies, indicate that the evaluation of the benefit/carcinogenic risk ratio should be always made in prescribing a drug.


Customised fragments libraries for protein structure prediction based on structural class annotations.
Since experimental techniques are time and cost consuming, in silico protein structure prediction is essential to produce conformations of protein targets. When homologous structures are not available, fragment-based protein structure prediction has become the approach of choice. However, it still has many issues including poor performance when targets' lengths are above 100 residues, excessive running times and sub-optimal energy functions. Taking advantage of the reliable performance of structural class prediction software, we propose to address some of the limitations of fragment-based methods by integrating structural constraints in their fragment selection process. Using Rosetta, a state-of-the-art fragment-based protein structure prediction package, we evaluated our proposed pipeline on 70 former CASP targets containing up to 150 amino acids. Using either CATH or SCOP-based structural class annotations, enhancement of structure prediction performance is highly significant in terms of both GDT_TS (at least +2.6, p-values < 0.0005) and RMSD (-0.4, p-values < 0.005). Although CATH and SCOP classifications are different, they perform similarly. Moreover, proteins from all structural classes benefit from the proposed methodology. Further analysis also shows that methods relying on class-based fragments produce conformations which are more relevant to user and converge quicker towards the best model as estimated by GDT_TS (up to 10% in average). This substantiates our hypothesis that usage of structurally relevant templates conducts to not only reducing the size of the conformation space to be explored, but also focusing on a more relevant area. Since our methodology produces models the quality of which is up to 7% higher in average than those generated by a standard fragment-based predictor, we believe it should be considered before conducting any fragment-based protein structure prediction. Despite such progress, ab initio prediction remains a challenging task, especially for proteins of average and large sizes. Apart from improving search strategies and energy functions, integration of additional constraints seems a promising route, especially if they can be accurately predicted from sequence alone.


Bias effects on magnitude and ratio estimation power function exponents.
A bias model of relative judgment was used to derive a ratio estimation (RE) power function, and its effectiveness in providing estimates of exponents free of the effects of standards was evaluated. The RE bias model was compared with the simple RE power function that ignores bias. Results showed that when bias was not taken into account, estimates of exponents exhibited the usual effects of standards observed in previous research. However, the introduction of bias parameters into the RE power function virtually eliminated these effects. Exponents calculated from "equal-range segments" (e.g., low stimulus range vs. high stimulus range) judged by magnitude estimation (ME) were examined: the effects of equal-range segments on exponents were much stronger for ME than standards were for RE, using the bias model.


Successful treatment of infertile women with hypothalamic primary and secondary protracted amenorrhoea using gonadotrophin releasing hormone analogue and human menopausal gonadotrophin.
Thirty-one women with hypothalamic primary or protracted secondary amenorrhoea were treated with human menopausal gonadotrophin (HMG) in 89 cycles, but adequate follicular growth failed to occur. They were then treated with a gonadotrophin releasing hormone analogue (GnRHa) and HMG in 91 cycles. An adequate ovarian response occurred in 68 cycles (74.7%) and pregnancy occurred in 26 cycles (28.6%). GnRHa and HMG produced an adequate ovarian response in hypothalamic amenorrhoeic patients who failed to respond to HMG alone. The strong initial agonistic effect of GnRHa produced sudden high levels of FSH that might possibly have initiated folliculogenesis which was continued by HMG.


NRASQ61R mutation in human endothelial cells causes vascular malformations.
Somatic mutations in NRAS drive the pathogenesis of melanoma and other cancers but their role in vascular anomalies and specifically human endothelial cells is unclear. The goals of this study were to determine whether the somatic-activating NRASQ61R mutation in human endothelial cells induces abnormal angiogenesis and to develop in vitro and in vivo models to identify disease-causing pathways and test inhibitors. Here, we used mutant NRASQ61R and wild-type NRAS (NRASWT) expressing human endothelial cells in in vitro and in vivo angiogenesis models. These studies demonstrated that expression of NRASQ61R in human endothelial cells caused a shift to an abnormal spindle-shaped morphology, increased proliferation, and migration. NRASQ61R endothelial cells had increased phosphorylation of ERK compared to NRASWT cells indicating hyperactivation of MAPK/ERK pathways. NRASQ61R mutant endothelial cells generated abnormal enlarged vascular channels in a 3D fibrin gel model and in vivo, in xenografts in nude mice. These studies demonstrate that NRASQ61R can drive abnormal angiogenesis in human endothelial cells. Treatment with MAP kinase inhibitor U0126 prevented the change to a spindle-shaped morphology in NRASQ61R endothelial cells, whereas mTOR inhibitor rapamycin did not.


Evaluation of Postnatal Complications in Clinical and Histological Chorioamnionitis in Extremely Preterm Infants: A Japanese Cohort Study.
Terminating pregnancy appropriately before the intrauterine infection has progressed may have an improved prognosis for preterm infants. We evaluate how the combination of histological chorioamnionitis (hCAM) and clinical chorioamnionitis (cCAM) affects the short-term prognosis of infants. This retrospective multicenter cohort study based on the Neonatal Research Network of Japan included extremely preterm infants born weighing <1,500 g between 2008 and 2018. Demographic characteristics, morbidity, and mortality were compared between the cCAM(-)hCAM(+) and cCAM(+)hCAM(+) groups. We included 16,304 infants. The progression to cCAM in infants with hCAM was correlated with the increase in home oxygen therapy (HOT) (adjusted odds ratio [aOR], 1.27; 95% confidence interval [CI], 1.11-1.44) and persistent pulmonary hypertension of the newborn (PPHN) (1.20, 1.04-1.38). Furthermore, increased progression of the hCAM stage in infants with cCAM correlated with an increase in bronchopulmonary dysplasia (BPD; 1.05, 1.01-1.11), HOT (1.10, 1.02-1.18), and PPHN (1.09, 1.01-1.18). However, it had a negative impact on hemodynamically significant patent ductus arteriosus (hsPDA; 0.87, 0.83-0.92) and death before discharge from the neonatal intensive care unit (NICU; 0.88, 0.81-0.96). Progression to cCAM in infants with hCAM positively correlated with HOT and PPHN. Progression of hCAM staging in infants with cCAM further increases the prevalence of BPD and the need for HOT and PPHN while reducing the prevalence of hsPDA and death before discharge from the NICU. The effects of the progressive hCAM stage in infants with cCAM vary from positive to negative by disease. · Retrospective multicenter cohort study based on the Neonatal Research Network of Japan.. · Clinical and histological chorioamnionitis increases the prevalence of BPD, HOT, and PPHN.. · Progression of histological chorioamnionitis in infants reduces the prevalence of hsPDA and death..


What complete mitochondrial genomes tell us about the evolutionary history of the black soldier fly, Hermetia illucens.
The Black Soldier Fly (BSF) Hermetia illucens is a cosmopolitan fly massively used by industrial companies to reduce biowaste and produce protein and fat for poultry and aquaculture feed. However, the natural history and the genetic diversity of the BSF are poorly known. Here, we present a comprehensive phylogeny and time tree based on a large dataset of complete mitochondrial genomes better to understand the evolution and timing of the BSF. In this study, we analyzed 677 CO1 sequences derived from samples found all over the five continents, leading us to discover 52 haplotypes, including ten major haplotypes. This worldwide cryptic genetic and genomic diversity is mirrored at a local scale in France, in which we found five major haplotypes sometimes in sympatry. Phylogenetic analyses of 60 complete mitochondrial genomes robustly resolved the phylogeny of the major BSF haplotypes. We estimate the separation events of the different haplotypes at more than 2 million years for the oldest branches characterizing the ancestral split between present North American lineages and the other highly diverse south-central American clades, possibly the following radiation beyond the isthmus of Panama northwards. Our data confirm that this North American lineage ultimately gave birth to almost all commercial BSF stocks that participated in the worldwide BSF dissemination through farm escapements. Our data resolve the phylogenetic relationships between the major lineages and give insights into the BSF's short and long-term evolution. Our results indicate that commercial BSF stock's genetic and genomic diversity is very low. These results call for a better understanding of the genomic diversity of the BSF to unravel possible specific adaptations of the different lineages for industrial needs and to initiate the selection process.


Ultrasound-guided sub-multifidus block for postoperative pain after lumbar spine surgery - a prospective case series.
We describe this series of 15 cases who were scheduled for single level lumbar spine decompression with instrumentation. Here we describe ultrasound (US) guided sub-multifidus block (SMFB). Injections of local anesthetic deep to the multifidus muscle provided reliable block of dorsal rami of spinal nerves at multiple levels in this series. With US the multifidus muscle can be identified both in axial and parasagittal planes. Needle tip is easily visualized beneath the multifidus and medial to transverse process. A good quality analgesia was documented by pain scores. There were no adverse events. This block needs to be compared with routine multimodal analgesia or with the recently describe thoracolumbar interfascial plane block to compare safety and analgesic efficacy.