Replication and validation of a statewide linkage method to estimate incidence proportion of child maltreatment.
To study familial factors associated with child maltreatment in a birth population, Alaska piloted a mixed-design method that linked child welfare data with the Pregnancy Risk Assessment Monitoring System (PRAMS). We replicated this approach in Oregon and validated it in both states. We linked vital records, child welfare, and PRAMS data to create two 2009 birth cohorts for each state: one based on vital records (full birth cohort) and one on PRAMS (stratified random sample). For each cohort, we estimated the incidence proportions (IP) of child maltreatment before age 9 years and compared those estimated using PRAMS with those observed using the full birth cohort. The Oregon PRAMS cohort estimated that 28.7% (95% CI: 24.0, 33.4), 20.9% (17.1, 24.7), and 8.3% (6.0, 10.5) of children experienced an alleged, investigated, and substantiated maltreatment, respectively, versus 32.0%, 25.0%, and 9.9% from the birth cohort. The corresponding Alaska estimates were 29.1% (26.1, 32.0), 22.6% (19.9, 25.2), and 8.3% (6.7, 9.9) of children from the PRAMS cohort versus 29.1%, 23.5%, and 9.1% in the birth cohort. The IP of child maltreatment in two states was accurately estimated with PRAMS cohorts. Researchers can study a comprehensive set of factors that may influence child maltreatment by incorporating PRAMS into birth cohort linkages.


Liquid chromatographic determination of 2',3'-dideoxyguanosine in human plasma.
A rapid assay for 2',3'-dideoxyguanosine (ddG) in human plasma has been developed. The ddG was first extracted from human plasma using solid phase extraction. The extract containing ddG was then assayed with liquid chromatography using an ODS column and a mobile phase of 9% methanol in pH 6.8 phosphate buffer. The overall method had good accuracy (within 2%), linearity (r = 0.9998), sensitivity (LOD = 1.8 ng, S/N = 3) and recovery (greater than 99% for 5-50 micrograms ddG per ml plasma).


Effect of chronic GH overproduction on cardiac ANP expression and circulating ANP levels.
Sodium and water retention are common in acromegaly and upon GH administration. The underlying mechanisms, however, have not been clearly characterized as yet. Therefore, the aim of this study was to examine possible alterations of atrial natriuretic peptide (ANP), an endogenous regulator of volume homeostasis, in response to chronic elevated GH. We used GH-transgenic mice (GH-TM) as a model for chronic hypersomatotropinemia and moreover investigated 7 and 27 week old animals, respectively, in order to discriminate between short and long term effects of GH overexpression. Hematocrit values were reduced in GH-TM compared to control animals and it is known that plasma volume is increased in these animals. Structural lesions of the kidney were found in the GH-TM, however, in the animals studied there were no signs of renal insufficiency as evidenced by serum creatinine and urea levels. The serum concentration of immunoreactive ANP (IR-ANP) determined by RIA was significantly (P < 0.005) elevated in the young GH-TM as compared to control littermates (81.7+/-13.3 vs. 50.9+/-10.8 fmol/ml). The increase in serum IR-ANP of 27 week old GH-TM, however did not reach the level of significance (57.13+/-16.3 vs. 50.25+/-16.4 fmol/ml). Serum samples of control mice as well as of the 7 week old animals mainly contained ANP 99-126, known to be the circulating form of ANP. In contrast, serum of 27 week old GH-TM predominantly showed the cardiac storage form of ANP, ANP 1-126. Cardiac expression of ANP was quantified by Northern blot analysis. mRNA coding for ANP was found 1.2- and 2-fold increased in the atria of 7 and 27 week old GH-TM, respectively. In parallel, a 2.2-fold (7 week) and 2-fold (27 week) increase of IR-ANP was observed in transgenic atria compared to tissue of control animals. In contrast, no significant difference of ANP mRNA expression or of content of IR-ANP was observed in the ventricles of both groups of animals. In conclusion, GH-TM show various alterations in their ANP status suggesting an influence of the peptide on the effect of GH in fluid retention.


Horticultural Therapy in Patients With Dementia: A Systematic Review and Meta-Analysis.
World Health Organization has communicated that dementia as a public health priority in 2012. Behavioral and psychological symptoms of dementia are the main reason results in hospitalization of dementia patients. Horticulture is one of the favorite activity for many peoples to relax their minds. To investigate psychological health benefits of horticulture intervention in dementia patients. The databases including Cochrane Library, ProQuest, PubMed, EMBASE, EBSCO, Web of Science, and Ovid Medline were searched up to August 2017. Twenty-three articles for systematic review, whereas 8 articles were included in meta-analysis. Meta-analysis verified the beneficial effect of horticultural therapy (HT) on agitation level (standard mean difference: -0.59; P < .00001); increase time spent on activity engagement (mean differences [MD]: 45.10%, P < .00001); decrease time for doing nothing (MD: -29.36%, P = .02). Patients with dementia benefit from horticultural by alleviating their degrees of agitate behaviors, increasing time of engaging in activities and decrease time of doing nothing.


[Determination of haptoglobin by agglutination with anti-Hp on latex particles].
Human sera are able to agglutinate latex particles sensitized with antihaptoglobin serum produced from sheep. The agglutination depends on the haptoglobin types. Similar to the agglutination of T4-streptococci the titer of Hp 1-1 is very low and the titers of sera of the types Hp 2-1 and Hp 2-2 are 1:160 or higher.


Duck hepatitis B virus infection, aflatoxin B1 and liver cancer in ducks.
The association between chronic infection by hepadnaviruses isolated from human (HBV), woodchuck (WHV), ground squirrel (GSHV) and development of hepatocellular carcinoma (HCC) in their respective hosts is well established (reviewed in [11, 15, 17]). By contrast, the association of duck hepatitis B virus (DHBV) infection with HCC is less documented. Pekin ducks congenitally infected with DHBV and followed for several years throughout the world do not develop liver tumors: HCC has been found only in domestic ducks from a single area of China, Qidong. Several factors such as DHBV carrier rate, breed and age of ducks, subtype of DHBV and environmental carcinogens are suspected to contribute to this striking difference between the geographical repartition of liver cancer in DHBV-carrier ducks. In this brief review we will consider successively the role of these different factors in duck liver oncogenesis.


Effectiveness of ankle taping on ankle joint kinematics during walking on level ground.
Prescriptions for functional ankle instability are generally oriented to taping, which need to be validated as an efficient treatment. Therefore, the aim of this study was to investigate the effectiveness of ankle taping on the subject's foot pressure and gait pattern, including mediolateral analysis, according to tape application side. A sample of 20 right-handed healthy subjects volunteered to participate in this study, which was composed of 3 taping conditions: "with taping of the right ankle," "with taping of both ankles," and "with taping of the left ankle." Participants were asked to perform a walk on the walkway to get 2 footprints repeated 6 times. The variables measured were step length, step duration, double stance, and swing. The results clearly showed significant change in step duration and double phase when tape was applied to the left ankle, F(2, 54) = 12.03; P < .05. Significant changes were also observed for step length and swing when tape was applied to the both ankles, F(2, 54) = 10.71; P < .05]. This study showed that double stance and swing phase duration increases, and that the pressure is equalized on both feet when taping the unstable ankle. Taping a functionally unstable ankle is more likely to improve its stability. Therapeutic Level II: Prospective comparative trial.


Involvement of lactate in glucose metabolism and glucosensing function in selected tissues of rainbow trout.
The aim of this study was to obtain evidence in rainbow trout for a role of lactate in glucose homeostasis as well as in the function of glucosensing tissues. In a first set of experiments, trout were injected, either (1) intraperitoneally (N=8) with 5 ml kg(-1) of Cortland saline alone (control) or saline containing l-(+)-lactate (22.5 mg kg(-1) or 45 mg kg(-1)), oxamate (22.5 mg kg(-1)) or d-glucose (500 mg kg(-1)), or (2) intracerebroventricularly (N=11) with 1 microl 100 g(-1) body mass of Cortland saline alone (control) or containing d-glucose (400 microg microl(-1)) or l-(+)-lactate (400 microg microl(-1)), with samples being obtained 6 h after treatment. In a second set of experiments, hypothalamus, hindbrain and Brockmann bodies were incubated in vitro for 1 h at 15 degrees C in modified Hanks' medium containing 2, 4 or 8 mmol l(-1) l-(+)-lactate alone (control) or with 50 mmol l(-1) oxamate, 1 mmol l(-1) DIDS, 1 mmol l(-1) dichloroacetate, 10 mmol l(-1) 2-deoxy-d-glucose, 1 mmol l(-1) alpha-cyano-4-hydroxy cinnamate or 10 mmol l(-1) d-glucose. The response of parameters assessed (metabolite levels, enzyme activities and glucokinase expression) in tissues provided evidence for (1) a role for lactate in the regulation of glucose homeostasis through changes not only in brain regions but also in liver energy metabolism, which are further reflected in changes in plasma levels of metabolites; (2) the possible presence in trout brain of an astrocyte-neuron lactate shuttle similar to that found in mammals; and (3) the lack of capacity of lactate to mimic in vitro (but not in vivo) glucose effects in fish glucosensing regions.


[Bourgery and Jacob, Hirschfeld and Léveillé--masterpieces of anatomical iconography in the heyday of lithography].
The Traité de l'Anatomie by Bourgery and Jacob and the Néurologie by Hirschfeld and Léveillé are among the best works in medical iconography. They are considered to rank in importance with other magnificent atlases due to their excellent plates and precise descriptive text. They set an new standard in anatomical illustration and made the artist devoted to anatomy a scientific collaborator of his scientist in anatomy.


Multiple headspace-solid-phase microextraction: an application to quantification of mushroom volatiles.
Multiple headspace-solid phase microextraction (MHS-SPME) followed by gas chromatography/mass spectrometry (GC-MS) and flame ionization detection (GC-FID) was applied to the identification and quantification of volatiles released by the mushroom Agaricus bisporus, also known as champignon. MHS-SPME allows to perform quantitative analysis of volatiles from solid matrices, free of matrix interferences. Samples analyzed were fresh mushrooms (chopped and homogenized) and mushroom-containing food dressings. 1-Octen-3-ol, 3-octanol, 3-octanone, 1-octen-3-one and benzaldehyde were common constituents of the samples analyzed. Method performance has been tested through the evaluation of limit of detection (LoD, range 0.033-0.078 ng), limit of quantification (LoQ, range 0.111-0.259 ng) and analyte recovery (92.3-108.5%). The results obtained showed quantitative differences among the samples, which can be attributed to critical factors, such as the degree of cell damage upon sample preparation, that are here discussed. Considerations on the mushrooms biochemistry and on the basic principles of MHS analysis are also presented.


Electrocatalytic Reduction of CO2 to CO With Re-Pyridyl-NHCs: Proton Source Influence on Rates and Product Selectivities.
A series of four electron-deficient-substituted Re(I) pyridyl N-heterocyclic carbene (pyNHC) complexes have been synthesized, and their electrocatalytic reduction of CO2 has been evaluated by cyclic voltammetry and controlled potential electrolysis experiments. All of the catalysts were evaluated by cyclic voltammetry under inert atmosphere and under CO2 and compared to the known benchmark catalyst Re(bpy)(CO)3Br. Among the four Re-NHC catalysts, Re(pyNHC-PhCF3)(CO)3Br (2) demonstrated the highest catalytic rate (icat/ip)(2) at the first and second reduction events with a value of 4 at the second reduction potential (TOF = 0.8 s(-1)). The rate of catalysis was enhanced through the addition of proton sources (PhOH, TFE, and H2O; TOF up to 100 s(-1); (icat/ip)(2) = 700). Controlled potential electrolysis shows Faradaic efficiencies (FE) for CO production and accumulated charge for the Re(pyNHC-PhCF3)(CO)3Br catalyst exceed those of the benchmark catalyst in the presence of 2 M H2O (92%, 13 C at 1 h versus 61%, 3 C for the benchmark catalyst) under analogous experimental conditions. A peak FE of 100% was observed during electrolysis with Re(pyNHC-PhCF3)(CO)3Br.


Results of surgical management of 319 pituitary adenomas.
Of the 510 patients with pituitary adenoma treated surgically at our hospital in the period 1956-1984 319 were treated by the microsurgical technique, in the period 1973-1984, 235 by transsphenoidal approach and 84 by subfrontal-pterional approach. The transsphenoidal route was used almost exclusively in microadenomas, in intrasellar adenomas, in suprasellar adenomas with midline development, in adenomas invading the sphenoidal sinus and in haemorrhagic adenomas with considerable suprasellar development. In some giant adenomas the transsphenoidal route was used in a first stage operation for debulking the tumour, later removed by transcranial route. The latter route was preferred in large adenomas and especially in adenomas with laterosellar development. In some patients with PRL secreting adenomas post-operative treatment with bromocriptine proved useful when the hormone levels failed to normalize. Post-operative radiotherapy was of value in invasive adenomas and in cases in which tumour removal was not radical.


Cox regression and survival analysis from the tauro-urso-deoxycholic trial in amyotrophic lateral sclerosis.
Recent phase II pilot clinical trials suggested that tauro-urso-deoxycholic acid (TUDCA) might slow functional decline and increase survival in patients with amyotrophic lateral sclerosis (ALS). We performed a multivariate analysis of the original TUDCA cohort to better define the treatment effect and allow comparability with other trials. Linear regression slope analysis showed statistical differences in the decline rate, favoring the active treatment arm (p-value < 0.01; -0.262 for the TUDCA group and -0.388 for the placebo group). Mean survival time, estimated by the Kaplan-Meier analysis, showed a 1-month difference, favoring active treatment (log-rank test p-value = 0.092). Cox regression analysis demonstrated that placebo treatment was associated with a higher risk of death (p-value = 0.055). These data further support the disease-modifying effect of TUDCA monotherapy and raise the question of what could be the additional effect of combining TUDCA with sodium phenylbutyrate.


Thermal simulations in the human head for high field MRI using parallel transmission.
To investigate, via numerical simulations, the compliance of the specific absorption rate (SAR) versus temperature guidelines for the human head in magnetic resonance imaging procedures utilizing parallel transmission at high field. A combination of finite element and finite-difference time-domain methods was used to calculate the evolution of the temperature distribution in the human head for a large number of parallel transmission scenarios. The computations were performed on a new model containing 20 anatomical structures. Among all the radiofrequency field exposure schemes simulated, the recommended 39°C maximum local temperature was never exceeded when the local 10-g average SAR threshold was reached. On the other hand, the maximum temperature barely complied with its guideline when the global SAR reached 3.2 W/kg. The maximal temperature in the eye could very well rise by more than 1°C in both cases. Considering parallel transmission, the recommended values of local 10-g SAR may remain a relevant metric to ensure that the local temperature inside the human head never exceeds 39°C, although it can lead to rises larger than 1°C in the eye. Monitoring temperature instead of SAR can provide increased flexibility in pulse design for parallel transmission.


Variability of episodic ST segment depression in chronic stable angina: implications for individual and group trials of therapeutic efficacy.
This study was conducted to quantify the variability of episodic ST segment depression in chronic stable angina and enable assessment of the impact of interventions in individual patients and clinical trials. Episodic myocardial ischemia can be detected by ST segment depression on ambulatory electrocardiographic (ECG) monitoring and may be important for the assessment of outcome. Variability of the number and duration of episodes has important implications for monitoring and therapeutic strategies. We studied 36 patients, aged 37 to 77 years (median 60), with stable angina and coronary artery disease by serial ambulatory ECG monitoring for a total of 415 days. A nested analysis of variance was carried out to assess the sources of spontaneous variation, and power function analyses were performed. During 415 days of monitoring, 1,882 episodes of ST segment depression were detected (mean frequency +/- SD, 4.5 +/- 4.1/day, duration 67 +/- 87 min/day, 25% in association with pain). Considerable variability was found within and between patients for both the number and the duration of ischemic episodes. For a patient monitored for 24 h before and after treatment, an 81% reduction in the number of episodes would be required to show a significant benefit; if monitoring were performed for 4 days four times before and after therapy, a 46% decrease would be significant. In clinical trials, a true reduction of > or = 15% in ischemic episodes is required to have sufficient power to obtain statistical significance. The natural variability of transient myocardial ischemia in patients with chronic stable angina can be quantified and this information used to study the effectiveness of interventions in both individual patients and clinical trials.


The dynamic immune responses of Mandarin fish (Siniperca chuatsi) to ISKNV in early infection based on full-length transcriptome analysis and weighted gene co-expression network analysis.
Mandarin fish (Siniperca chuatsi) been seriously harmed by infectious spleen and kidney necrosis virus (ISKNV) in recent years, but the early immune response mechanism of infection is still unknown. Here, we performed RNA sequencing on the spleens of mandarin fish infected with ISKNV at 0, 12, 24, 48, and 72 h post-infection (hpi) using short-read Illumina RNA sequencing and long-read Pacific Biosciences isoform sequencing to generate a full-length transcriptome. The immune responses of mandarin fish infected with ISKNV at the molecular level were characterized by RNA-seq analysis and weighted gene co-expression network analysis (WGCNA). A total of 26,528 full-length transcript sequences were obtained. There were 2,729 (1,680 up-regulated and 1,112 down-regulated), 1,874 (1,136 up-regulated and 738 down-regulated), 2,032 (1,158 up-regulated and 847 down-regulated), and 4,176 (2,233 up-regulated and 1,943 down-regulated) differentially expressed genes (DEGs) in mandarin fish at 12, 24, 48, and 72 hpi, compared with uninfected fish, respectively. A total of four modules of co-expressed DEGs identified by WGCNA were significantly positively correlated to the four time points after infection, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the immune-related DEGs in all these modules were mainly enriched in Phagosome, Endocytosis, Herpes simplex infection, and Cytokine-cytokine receptor interaction pathways. Further analysis showed that oher signaling pathways, including CAMs, NOD-like receptor and ER protein processing, Intestinal immune network for IgA production, TLR pathway, and Apoptosis significantly enriched in four modules corresponding to 12, 24, 48, and 72 hpi respectively, had specifically participated in the immune response. Hub genes identified based on the high-degree nodes in the WGCN, including CAM3, IL-8, CCL21, STING, SNX1, PFR and TBK1, and some DEGs such as MHCI, MHCII, TfR, STING, TNF α, TBK1, IRF1, and NF-kB, BCR, IgA and Bcl-XL had involved in dynamic molecular response of mandarin fish to ISKNV infection. In sum, this study provides a set of full-length transcriptome of the spleen tissue of mandarin fish for the first time and revealed a group of immune genes and pathways involved in different temporal responses to ISKNV infection, which has implications for resource conservation and aiding the development of strategies to prevent virus early infection for mandarin fish.


Acceleration of peripheral nerve regeneration after crush injury in rat.
It the sciatic nerve of a rat is crushed in the thigh, axons from the proximal side of the crush will regenerate so that the toe-spreading reflex becomes observable again after 10.4 +/- 1.7 (mean +/- S.D.) days. If the nerve is electrically stimulated for 0.25-1.0 h at the crush site, just after the crush occurs, the toe-spreading reflex first becomes observable 4.14 +/- 1.6 (mean +/- S.D.) days after the crush. Stimulation is most effective if delivered immediately after the crush but can be delayed up to an hour and still cause significantly faster regeneration. This phenomenon could be useful in clinical management of crushed peripheral nerves.


Synaptic organization involving receptor, horizontal and on- and off-center bipolar cells in the catfish retina.
HRP-injected bipolar cells were analyzed electron microscopically in catfish retina. The dendrites of the two types of bipolar cells (on-center and off-center) invaginated into the photoreceptor terminals in distinct patterns. Those from off-center bipolars ended as the central element of triads in such a way that every synaptic ridge examined was contacted by a single process along its apex. In contrast, labeled processes from on-center bipolars never made direct contact with the synaptic ridges of any photoreceptors. In addition, chemical synapses made by external horizontal cells onto photoreceptors were observed. The postsynaptic sites was always a telodendrial process of a photoreceptor.


Renal Impairment Is Associated with Reduced Outcome After Associating Liver Partition and Portal Vein Ligation for Staged Hepatectomy.
Impaired postoperative renal function is associated with increased morbidity and mortality after liver resection. The role of impaired renal function in the two-stage hepatectomy setting of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is unknown. An international multicenter cohort of ALPPS patients captured in the ALPPS Registry was analyzed. Particular attention was drawn to the renal function in the interstage interval to determine outcome after stage 2 surgery. Interstage renal impairment (RI) was defined as an increase of serum creatinine of ≥ 0.3 mg/dl referring to a preoperative value or an increase of serum creatinine of ≥ 1.5× of the preoperative value on the fifth postoperative day after stage 1. A total of 705 patients were identified of which 7.5% had an interstage RI. Patients developing an interstage RI were significantly older. During stage 1, a longer operation time, higher rate of intraoperative transfusions, and additional procedures were observed in patients that developed interstage RI. After stage 1, interstage RI patients had more major complications and higher interstage mortality (1% vs. 8%, p < 0.001). Furthermore, these patients developed more and severe complications after completion of stage 2. Mortality of patients with interstage RI was 38% vs. 8% without interstage RI. In 41% of patients with interstage RI, the renal function recovered before stage 2; however, the mortality after stage 2 remained 28% in those patients. Risk factors for the development of an interstage RI were age over 67 years, prolonged operative time, and additional procedure during stage 1. This study shows that interstage RI is a predictor for interstage and post-stage 2 morbidity and perioperative mortality. The causality of impaired renal function on outcome, however, remains unknown. Interstage RI may directly cause adverse outcome but may also be a surrogate marker for major complications.


A miniaturised method for immunoglobulin allotype serology.
A modification of the classic haemagglutination inhibition method for immunoglobulin allotyping is described which employs reagent volumes of 2 microliters compared with the 25 microliter volumes commonly used in other serological allotyping methods. No loss of sensitivity or specificity was associated with the miniaturised method when compared to the standard tile technique. This method simplifies the large scale phenotyping and screening of sera and permits considerable savings of valuable reagents to be made.


Relationship between measurements of ipsilateral capitellum and prosthetic radial head size.
Selecting the correct size of head component is challenging in radial head arthroplasty, particularly in comminuted fractures. This study aimed to investigate the relationship between measurements of the ipsilateral capitellum and the prosthetic radial head size, which may be used to predict the size of the radial head prosthesis preoperatively. Our study enrolled all patients who underwent radial head arthroplasty at Beijing Jishuitan Hospital. Demographic, injury-related and radiographic data were collected. The prosthetic radial head size was recorded from the surgical notes. Three-dimensional models of preoperative CT scans were reconstructed, on which the lateral capitellar diameter, the capitellar width and the width between the capitellum and trochlea were measured. The correlations between measurements of the ipsilateral capitellum and the prosthetic radial head size were evaluated, and linear regression equations were established. The study enrolled 37 patients, with an average age of 42.8 ± 11.5 years and a male-female ratio of 20:17. The median diameter of the radial head prostheses was 22 (20, 22) mm. The average lateral capitellar diameter was 20.71 ± 1.93 mm, the mean capitellar width was 14.90 ± 1.40 mm, and the mean width between the capitellum and trochlea was 19.29 ± 1.78 mm. The lateral capitellar diameter (R = 0.820, P < 0.001), the capitellar width (R = 0.726, P < 0.001) and the width between the capitellum and trochlea (R = 0.626, P < 0.001) were significantly positively correlated with the size of the radial head prosthesis. The linear regression equation between the lateral capitellar diameter and the size of the radial head prosthesis was calculated and defined as follows: D = 7.44 + 0.67*d (D: diameter of radial head prosthesis; d: lateral capitellar diameter; and adjusted R2 = 0.719, P < 0.001). There are positive correlations between the anatomical parameters of the ipsilateral capitellum and the prosthetic radial head size. The lateral capitellar diameter can be measured on three-dimensional CT preoperatively to predict the size of the radial head prosthesis intraoperatively.


Serum concentrations of brain-derived neurotrophic factor as a potential biomarker of swine welfare.
Describe concentrations of brain-derived neurotrophic factor (BDNF) detectable in piglet sera before and after road transport, and evaluate the correlation of serum BDNF with other physiological parameters used to assess swine welfare. Commercial crosses of piglets that underwent weaning and transport at approximately 3 wk of age. Sixteen piglets were randomly selected from a larger study for complete blood counts, serum biochemistry testing, cortisol assays, and BDNF assays. Samples were collected 1 d before transport and immediately after transport (> 30 h) under commercial conditions. We assessed the change in serum BDNF concentration; and the correlations between serum BDNF and serum cortisol, neutrophil to lymphocyte ratios (N:L), glucose, and hematological indicators of muscle fatigue. Serum BDNF concentrations increased after transport (P < 0.05) and changed inversely compared to cortisol and N:L. Consistent correlations between BDNF and other physiological parameters were not observed. High inter-pig variation in serum BDNF was present at both sample times. Serum BDNF may be used as an additional indicator of swine welfare. Further research characterizing piglet BDNF concentrations in response to conditions promoting positive or negative affective states would be valuable. This communication discusses common hematological parameters used to quantify changes in pig welfare and introduces BDNF, which is a parameter of interest in human cognitive functioning research that may be useful for evaluating the effect of exposure to beneficial or aversive stimuli in animals. The implications of variation in sample collection, handling, and storage procedures for BDNF detection are highlighted.


Demonstration of kinetochores and centrioles in spermatocytes of two species of cockroaches by silver staining.
Light microscopy following silver staining of spermatocytes of German and Madagascar hissing cockroaches demonstrated: (1) the localization of a kinetochore in each autosomal synaptonemal complex during pachytene, and (2) visualization of centrioles in different stages of meiotic prophase. The presence of a "hairpin-like" twist and the nucleolus organizer region in the X-chromosome was observed only in the German cockroach.


Atypical B cells up-regulate costimulatory molecules during malaria and secrete antibodies with T follicular helper cell support.
Several infectious and autoimmune diseases are associated with an expansion of CD21-CD27- atypical B cells (atBCs) that up-regulate inhibitory receptors and exhibit altered B cell receptor (BCR) signaling. The function of atBCs remains unclear, and few studies have investigated the biology of pathogen-specific atBCs during acute infection. Here, we performed longitudinal flow cytometry analyses and RNA sequencing of Plasmodium falciparum (Pf)-specific B cells isolated from study participants before and shortly after febrile malaria, with simultaneous analysis of influenza hemagglutinin (HA)-specific B cells as a comparator. At the healthy baseline before the malaria season, individuals had similar frequencies of Pf- and HA-specific atBCs that did not differ proportionally from atBCs within the total B cell population. BCR sequencing identified clonal relationships between Pf-specific atBCs, activated B cells (actBCs), and classical memory B cells (MBCs) and revealed comparable degrees of somatic hypermutation. At the healthy baseline, Pf-specific atBCs were transcriptionally distinct from Pf-specific actBCs and classical MBCs. In response to acute febrile malaria, Pf-specific atBCs and actBCs up-regulated similar intracellular signaling cascades. Pf-specific atBCs showed activation of pathways involved in differentiation into antibody-secreting cells and up-regulation of molecules that mediate B-T cell interactions, suggesting that atBCs respond to T follicular helper (TFH) cells. In the presence of TFH cells and staphylococcal enterotoxin B, atBCs of malaria-exposed individuals differentiated into CD38+ antibody-secreting cells in vitro, suggesting that atBCs may actively contribute to humoral immunity to infectious pathogens.


Effects of propafenone on sinus nodal and ventricular automaticity: in vitro and in vivo correlation.
The electrophysiologic effects of the new antiarrhythmic drug, propafenone, were evaluated in anesthetized closed-chest dogs and on isolated cardiac tissues with the microelectrode technique. Propafenone (2 to 4 mg/kg intravenously) had no effect on sinus rate or on sinus nodal recovery time, but caused a dose-dependent significant decrease in the rate of idioventricular rhythm and increased the duration of ventricular overdrive suppression in dogs (n = 8) with complete atrioventricular block. On isolated canine Purkinje fibers (n = 8) manifesting automaticity with resting membrane potential less negative than -70 mV, propafenone reduced the slope of phase 4 depolarization and reduced the rate of automatic impulse initiation in a concentration-dependent manner (10(-6) M-4.10(-5) M). At these concentrations, propafenone had no effect on rabbit sinus nodal automaticity (n = 8) or on sinoatrial conduction. However, significant depression of sinus nodal automaticity occurred with propafenone concentrations above 5.10(-6) M in the presence of cholinergic or complete autonomic blockade with atropine (10(-6) M) and propranolol (5.10(-5) M). Propafenone caused a concentration-dependent decrease in the disparity of Purkinje fiber-ventricular muscle action potential duration (APD), mainly by shortening Purkinje fiber APD. We conclude: that propafenone suppresses idioventricular rhythm in the intact dog, most likely by depressing Purkinje fiber automaticity; the depressant effect of propafenone on sinus nodal automaticity is evident only during cholinergic receptor blockade; and the antiarrhythmic properties of propafenone may include removal of APD disparity by selective shortening of Purkinje fiber and not of ventricular muscle APD.


Renal stones and primary hyperparathyroidism: natural history of renal stone disease after successful parathyroidectomy.
The aim of the study was to evaluate the risk of renal stone recurrence after successful surgical treatment of primary hyperparathyroidism (pHPT). Of 297 consecutive patients with surgically verified pHPT, 151 patients had had renal stone disease; a total of 113 patients were eligible for follow-up; and of these, 107 patients remained normocalcemic during follow-up and formed the study group. The number of new stones were calculated by subtracting the stones present on preoperative urograms from the number of stones on urograms after 1, 3, and 5 years and the number of stones passed or eliminated by intervention. Among 107 patients, 32 (30%) formed one to four new stones within 5 years. This recurrence rate is comparable to the expected recurrence rate in idiopathic stone formers. Primary hyperparathyroidism and renal stone disease are common. As all renal stone formers are screened for pHPT by serum calcium analysis, the two diseases might by coincidence be found in the same patients. A considerable number of patients with pHPT and renal stone disease therefore experience recurrence of their stone disease irrespective of the presence of normocalcemia after successful parathyroidectomy.


Addressing the batch effect issue for LC/MS metabolomics data in data preprocessing.
With the growth of metabolomics research, more and more studies are conducted on large numbers of samples. Due to technical limitations of the Liquid Chromatography-Mass Spectrometry (LC/MS) platform, samples often need to be processed in multiple batches. Across different batches, we often observe differences in data characteristics. In this work, we specifically focus on data generated in multiple batches on the same LC/MS machinery. Traditional preprocessing methods treat all samples as a single group. Such practice can result in errors in the alignment of peaks, which cannot be corrected by post hoc application of batch effect correction methods. In this work, we developed a new approach that address the batch effect issue in the preprocessing stage, resulting in better peak detection, alignment and quantification. It can be combined with down-stream batch effect correction methods to further correct for between-batch intensity differences. The method is implemented in the existing workflow of the apLCMS platform. Analyzing data with multiple batches, both generated from standardized quality control (QC) plasma samples and from real biological studies, the new method resulted in feature tables with better consistency, as well as better down-stream analysis results. The method can be a useful addition to the tools available for large studies involving multiple batches. The method is available as part of the apLCMS package. Download link and instructions are at https://mypage.cuhk.edu.cn/academics/yutianwei/apLCMS/ .


The opsins of the vertebrate retina: insights from structural, biochemical, and evolutionary studies.
The vertebrate retina contains several classes of visual pigments responsible for such diverse functions as image- and nonimage-forming vision, the entrainment of circadian cycles, and the pupilary light response. With vision being vital to the survival of many species, the elucidation of the structural and biochemical properties of visual pigments has been the focus of a large body of research that has led to rapid advances in the field of photoreception. In this review, the current understanding of the structure, function, biochemistry, and evolution of the opsins that make up the photopigments in the vertebrate retina will be reviewed. These include the rod and cone opsins, melanopsin, RGR, peropsin, and VA-opsin. The goal is to highlight important questions that have been answered and to define some of the remaining questions in the field that will provide future directions for research.


Corticosteroid use in the intensive care unit: a survey of intensivists.
The efficacy of systemic corticosteroids in many critical illnesses remains uncertain. Our primary objective was to survey intensivists in North America about their perceived use of corticosteroids in clinical practice. Self-administered paper survey. Intensivists in academic hospitals with clinical trial expertise in critical illness. We generated questionnaire items in focus groups and refined them after assessments of clinical sensibility and test-retest reliability and pilot testing. We administered the survey to experienced intensivists practicing in selected North American centres actively enrolling patients in the multicentre Oscillation for ARDS Treated Early (OSCILLATE) Trial (ISRCTN87124254). Respondents used a four-point scale to grade how frequently they would administer corticosteroids in 14 clinical settings. They also reported their opinions on 16 potential near-absolute indications or contraindications for the use of corticosteroids. Our response rate was 82% (103/125). Respondents were general internists (50%), respirologists (22%), anesthesiologists (21%), and surgeons (7%) who practiced in mixed medical-surgical units. A majority of respondents reported almost always prescribing corticosteroids in the setting of significant bronchospasm in a mechanically ventilated patient (94%), recent corticosteroid use and low blood pressure (93%), and vasopressor-refractory septic shock (52%). Although more than half of respondents stated they would almost never prescribe corticosteroids in severe community-acquired pneumonia (81%), acute lung injury (ALI, 76%), acute respiratory distress syndrome (ARDS, 65%), and severe ARDS (51%), variability increased with severity of acute lung injury. Near-absolute indications selected by most respondents included known adrenal insufficiency (99%) and suspicion of cryptogenic organizing pneumonia (89%), connective tissue disease (85%), or other potentially corticosteroid-responsive illnesses (85%). Respondents reported rarely prescribing corticosteroids for ALI, but accepted them for bronchospasm, suspected adrenal insufficiency due to previous corticosteroid use, and vasopressor-refractory septic shock. These competing indications will complicate the design and interpretation of any future large-scale trial of corticosteroids in critical illness.


The B-domain lysine patch of pRB is required for binding to large T antigen and release of E2F by phosphorylation.
Cell cycle-dependent, site-specific phosphorylation of the retinoblastoma protein, pRB, is mediated by cyclin-dependent kinases (CDKs) and regulates the binding of pRB to many proteins. We previously showed that the interaction of pRB with E2F on DNA was regulated by the accumulation of phosphate groups on pRB. Here we show that positively charged lysine residues in the B domain of pRB are necessary for the release of pRB from E2F on DNA following phosphorylation by cyclin E-cdk2 kinase. These lysine residues are also important in the binding of the simian virus 40 large T antigen (TAg) to pRB, and mutation of these lysines to arginines alters the dependency of the pRB-TAg interaction on phosphorylation of pRB.


Health microplanning in the developing countries: a systems approach to appropriate technology.
A method of systematically planning the technical details of personal health care in the developing world is described. In contrast to national health plans of the traditional kind--"macroplans"--those for health technology have to be minutely detailed. They have therefore been termed "microplans". (They have also been called health care packages, but this term has other usages). A microplan is defined as an integrated set of components (instructions for technologies, equipment lists, teaching aids, evaluation instruments, etc.) prepared nationally to support a particular health care subsystem. The rationale for a microplan is that the whole is more than the sum of its parts. A microplan is itself a system in two senses. First, the technologies in a given microplan need to be organized so as to support one another. Second, the components in a microplan must themselves be integrated into a system. A microplan can be applied to induce change and so improve the technical quality of existing services. It can also be used to train new workers. More importantly, it ties educational programs to service needs. Since the technology for dealing with disease is so similar all over the developing world, once a "master microplan" for a particular subsystem has been prepared, it can be adapted readily to the needs of individual countries.


[Stem cells of dental pulp].
Any clinician dreams to obtain the regeneration of the destroyed organ for his patient. In the human being, the regeneration of complex structures is not possible, except the liver and the bone marrow, which can be regenerated because of the presence of adult stem cells in these tissues. The stem cells have two principal properties: they ensure their self-renewal and they have the ability to differentiate into several cellular types. Using specific markers allowing the identification of the stem cells in bone marrow, stem cells were observed in dental pulp tissues. Although the origin, the identification, and the localization of these stem cells of dental pulp remain under consideration, the optimism in research on stem cells permits to believe that the knowledge on dental stem cells will lead to their use in therapeutics.


Techniques for improving stereotaxic accuracy in Macaca fascicularis.
Sources of stereotaxic variability in long-tailed macaques (Macaca fascicularis) were examined by X-ray techniques. Accuracy in the vertical dimension can be improved significantly by measuring from the top of the brain rather than from the Frankfurt plane established by external bony landmarks. Even greater accuracy in both the vertical and anterior-posterior dimensions can be attained by rotating the cranium in the stereotaxic instrument to bring the intercommissural line, as defined by ventriculography, into a plane parallel to the horizontal stereotaxic plane, thus approximating the orientation of the brain as represented in both of the brain atlases currently available for this species. An adjustable eyebar spacer, which allows the cranium to be rotated in the stereotaxic instrument, is described.


Chromosome Level Genome Assembly and Annotation of Highly Invasive Japanese Stiltgrass (Microstegium vimineum).
The invasive Japanese stiltgrass (Microstegium vimineum) affects a wide range of ecosystems and threatens biodiversity across the eastern USA. However, the mechanisms underlying rapid adaptation, plasticity, and epigenetics in the invasive range are largely unknown. We present a chromosome-level assembly for M. vimineum to investigate genome dynamics, evolution, adaptation, and the genomics of phenotypic plasticity. We generated a 1.12-Gb genome with scaffold N50 length of 53.44 Mb respectively, taking a de novo assembly approach that combined PacBio and Dovetail Genomics Omni-C sequencing. The assembly contains 23 pseudochromosomes, representing 99.96% of the genome. BUSCO assessment indicated that 80.3% of Poales gene groups are present in the assembly. The genome is predicted to contain 39,604 protein-coding genes, of which 26,288 are functionally annotated. Furthermore, 66.68% of the genome is repetitive, of which unclassified (35.63%) and long-terminal repeat (LTR) retrotransposons (26.90%) are predominant. Similar to other grasses, Gypsy (41.07%) and Copia (32%) are the most abundant LTR-retrotransposon families. The majority of LTR-retrotransposons are derived from a significant expansion in the past 1-2 Myr, suggesting the presence of relatively young LTR-retrotransposon lineages. We find corroborating evidence from Ks plots for a stiltgrass-specific duplication event, distinct from the more ancient grass-specific duplication event. The assembly and annotation of M. vimineum will serve as an essential genomic resource facilitating studies of the invasion process, the history and consequences of polyploidy in grasses, and provides a crucial tool for natural resource managers.


Cytophagic histiocytic panniculitis. Case report with resolution after treatment.
This report describes a patient with cytophagic histiocytic panniculitis in which early diagnosis and therapy resulted in complete clinical remission of the disease.


Association of the careggi collateral score with radiological outcomes after thrombectomy for stroke with an occlusion of the middle cerebral artery.
We aimed to examine the association between Careggi Collateral Score (CCS) and radiological outcomes in a large multicenter cohort of patients receiving thrombectomy for stroke with occlusion of middle cerebral artery (MCA). We conducted a study on prospectively collected data from 1785 patients enrolled in the Italian Registry of Endovascular Treatment in Acute Stroke. According to the extension of the retrograde reperfusion in the cortical anterior cerebral artery-MCA territories, CCS ranges from 0 (absence of retrograde filling) to 4 (visualization of collaterals until the alar segment of the MCA). Radiological outcomes at 24 h were the presence and severity of infarct growth defined by the absolute change in ASPECTS from baseline to 24 h; presence and severity of cerebral bleeding defined as no ICH, HI-1, HI-2, PH-1, or PH-2; presence and severity of cerebral edema (CED) defined as no CED, CED-1, CED-2, or CED-3. Using CCS = 0 as reference, ORs of CCS grades were significantly associated in the direction of better radiological outcome on infarct growth (0.517 for CCS = 1, 0.413 for CCS = 2, 0.358 for CCS = 3, 0.236 for CCS = 4), cerebral bleeding grading (0.485 for CCS = 1, 0.445 for CCS = 2, 0.400 for CCS = 3, 0.379 for CCS = 4), and CED grading (0.734 for CCS = 1, 0.301 for CCS = 2, 0.295 for CCS = 3, 0.255 for CSS = 4) shift in ordinal regression analysis after adjustment for pre-defined variables (age, NIHSS score, ASPECTS, occlusion site, onset-to-groin puncture time, procedure time, and TICI score). Using CCS = 4 as reference, ORs of CCS grades were significantly associated in the direction of worse radiological outcome on infarct growth (1.521 for CCS = 3, 1.754 for CCS = 2, 2.193 for CCS = 1, 4.244 for CCS = 0), cerebral bleeding grading (2.498 for CCS = 0), and CED grading (1.365 for CCS = 2, 2.876 for CCS = 1, 3.916 for CCS = 0) shift. The CCS could improve the prognostic estimate of radiological outcomes in patients receiving thrombectomy for stroke with MCA occlusion.


A metaphor for epidemiology: The sea of person time.
Metaphors have had an important role to play in the theory and practice of epidemiology. Some well-known examples include "black boxes," the "web of causation," "shoe-leather epidemiology," the "ivory tower" and the ubiquitous "gold standard." Metaphors like these do not replace methods or principles but rather like memes can spark a creative response and thoughtful reflection. In this paper, I bring to the attention of epidemiologists a metaphor that originated forty years ago in a paper describing and explaining measures of disease incidence. The authors wrote about a "sea of population time" to represent how incident disease events-specifically, incidence density measures- occur in the two-dimensional space of person-time. A "sea of population time" or "sea of person time" seems ideally suited as a metaphor for creative and thoughtful development in epidemiology. The vast and varied characteristics of oceans provide a plethora of ideas that can potentially help us to think more deeply about the role and responsibilities of epidemiologists. As an example, consider the notion that epidemiologists' journey across this sea in their methodologically-laden and concept-heavy fishing boats searching for the causes of disease. At the same time, epidemiologists live in the sea itself subject to and thus at risk of all the same diseases that affect human populations. Storms on this imaginary sea could sink our boats causing us to rethink conceptual and methodological frameworks. Here I provide in lyric form examples that explore what might exist behind the sea of person time and on its shores.


Assessment of Hypertension, Guideline-Directed Counseling, and Outcomes in the ACHD Population.
Guidelines for the diagnosis and treatment of hypertension were published by the American Heart Association (AHA) in 2017. The prevalence of hypertension in adults with congenital heart disease (ACHD) under these guidelines has yet to be characterized. We sought to assess the prevalence, impact, and provider response to hypertension under current guidelines. Data were obtained retrospectively from records of routine clinic visits over a 10 year period. Potential hypertension-related adverse outcomes including stroke, myocardial infarction, surgical intervention for aortic aneurysm, aortic dissection, atrial fibrillation or flutter, cardiac transplantation and death were recorded. The 1070 patients who met inclusion criteria had a mean age of 30.8 ± 10.0 years. The prevalence of hypertension under the 2017 guidelines was 46.6%. Multivariate modeling identified cyanosis, male gender, older age, and overweight/obesity as independent risk factors for hypertension. Guideline-directed management of hypertension in ACHD patients occurred more frequently in ACHD and adult cardiology clinics than in pediatric cardiology clinics (44.1% and 45.1% vs. 24.0%, p < 0.01, respectively). Adverse outcomes were reported in 217 (20%) patients, the most prevalent of which was atrial fibrillation or flutter (11%). Multivariable modelling for any adverse outcome identified older age, hypertension, cyanosis, greater complexity ACHD, and obesity as risk factors. Modifiable risk factors for atherosclerotic cardiovascular disease are common and often under addressed in the ACHD population.


Comparison of Trends in Incidence, Revascularization, and In-Hospital Mortality in ST-Elevation Myocardial Infarction in Patients With Versus Without Severe Mental Illness.
Patients with severe mental illness (SMI), including schizophrenia and bipolar disorder, are at elevated risk of ST-elevation myocardial infarction (STEMI) but have previously been reported as less likely to receive revascularization. To study the persistence of these findings over time, we examined trends in STEMI incidence, revascularization, and in-hospital mortality for patients with and without SMI in the National Inpatient Sample from 2003 to 2012. We further used multivariate logistic regression analysis to assess the odds of revascularization and in-hospital mortality. SMI was present in 29,503 of 3,058,697 (1%) of the STEMI population. Patients with SMI were younger (median age 58 vs 67 years), more likely to be women (44% vs 38%), and more likely to have several co-morbidities, including diabetes, chronic pulmonary disease, substance abuse, and obesity (p <0.001 for all). Over time, STEMI incidence significantly decreased in non-SMI (p for trend <0.001) but not in SMI (p for trend 0.14). Revascularization increased in all subgroups (p for trend <0.001) but remained less common in SMI. In-hospital mortality decreased in non-SMI (p for trend = 0.004) but not in SMI (p for trend 0.10). After adjustment, patients with SMI were less likely to undergo revascularization (odds ratio 0.59, 95% CI 0.52 to 0.61, p <0.001), but SMI was not associated with increased in-hospital mortality (odds ratio 0.97, 95% CI 0.93 to 1.01, p = 0.16). In conclusion, in contrast to the overall population, the incidence of STEMI is not decreasing in patients with SMI. Despite changes in the care of STEMI, patients with SMI remain less likely to receive revascularization therapies.


An Overview of Nanoparticle Based Delivery for Treatment of Inner Ear Disorders.
Nanoparticles offer new possibilities for inner ear treatment as they can carry a variety of drugs, protein, and nucleic acids to inner ear. Nanoparticles are equipped with several functions such as targetability, immuno-transparency, biochemical stability, and ability to be visualized in vivo and in vitro. A group of novel peptides can be attached to the surface of nanoparticles that will enhance the cell entry, endosomal escape, and nuclear targeting. Eight different types of nanoparticles with different payload carrying strategies are available now. The transtympanic delivery of nanoparticles indicates that, depending on the type of nanoparticle, different migration pathways into the inner ear can be employed, and that optimal carriers can be designed according to the intended cargo. The use of nanoparticles as drug/gene carriers is especially attractive in conjunction with cochlear implantation or even as an inclusion in the implant as a drug/gene reservoir.


Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP.
Rap1 is a small, Ras-like GTPase that was first identified as a protein that could suppress the oncogenic transformation of cells by Ras. Rap1 is activated by several extracellular stimuli and may be involved in cellular processes such as cell proliferation, cell differentiation, T-cell anergy and platelet activation. At least three different second messengers, namely diacylglycerol, calcium and cyclic AMP, are able to activate Rap1 by promoting its release of the guanine nucleotide GDP and its binding to GTP. Here we report that activation of Rap1 by forskolin and cAMP occurs independently of protein kinase A (also known as cAMP-activated protein kinase). We have cloned the gene encoding a guanine-nucleotide-exchange factor (GEF) which we have named Epac (exchange protein directly activated by cAMP). This protein contains a cAMP-binding site and a domain that is homologous to domains of known GEFs for Ras and Rap1. Epac binds cAMP in vitro and exhibits in vivo and in vitro GEF activity towards Rap1. cAMP strongly induces the GEF activity of Epac towards Rap1 both in vivo and in vitro. We conclude that Epac is a GEF for Rap1 that is regulated directly by cAMP and that Epac is a new target protein for cAMP.


Controlled and targeted release of antigens by intelligent shell for improving applicability of oral vaccines.
Conventional oral vaccines with simple architecture face barriers with regard to stimulating effective immunity. Here we describe oral vaccines with an intelligent phase-transitional shielding layer, poly[(methyl methacrylate)-co-(methyl acrylate)-co-(methacrylic acid)]-poly(D,L-lactide-co-glycolide) (PMMMA-PLGA), which can protect antigens in the gastro-intestinal tract and achieve targeted vaccination in the large intestine. With the surface immunogenic protein (SIP) from group B Streptococcus (GBS) entrapped as the antigen, oral administration with PMMMA-PLGA (PTRBL)/Trx-SIP nanoparticles stimulated robust immunity in tilapia, an animal with a relatively simple immune system. The vaccine succeeded in protecting against Streptococcus agalactiae, a pathogen of worldwide importance that threatens human health and is transmitted in water with infected fish. After oral vaccination with PTRBL/Trx-SIP, tilapia produced enhanced levels of SIP specific antibodies and displayed durability of immune protection. 100% of the vaccinated tilapia were protected from GBS infection, whereas the control groups without vaccines or vaccinated with Trx-SIP only exhibited respective infection rates of 100% or >60% within the initial 5 months after primary vaccination. Experiments in vivo demonstrated that the recombinant antigen Trx-SIP labeled with FITC was localized in colon, spleen and kidney, which are critical sites for mounting an immune response. Our results revealed that, rather than the size of the nanoparticles, it is more likely that the negative charge repulsion produced by ionization of the carboxyl groups in PMMMA shielded the nanoparticles from uptake by small intestinal epithelial cells. This system resolves challenges arising from gastrointestinal damage to antigens, and more importantly, offers a new approach applicable for oral vaccination.


Staff rostering, split team arrangement, social distancing (physical distancing) and use of personal protective equipment to minimize risk of workplace transmission during the COVID-19 pandemic: A simulation study.
The recent global survey promoted by the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Taskforce on COVID-19 (coronavirus disease 2019) described staff rostering and organization as significant operational challenges during the COVID-19 pandemic. A discrete event simulation was used to explore the impact of different permutations of staff roster, including the number of shifts per day, the number of staff on duty per shift, overall number of staff accessible to work in the laboratory (i.e. overall staff pool), the frequency of shift changes (i.e. number of consecutive days worked), fixed work-rest days and split team arrangement on workplace transmission of COVID-19 by a simulated index staff who acquired the infection from the community over 21 days. Additionally, the impact of workplace social distancing (physical distancing) and use of personal protective equipment (PPE) were investigated. A higher rate of transmission was associated with smaller overall staff pool (expressed as multiples of the number of staff per shift), higher number of shifts per day, higher number of staff per shift, and longer consecutive days worked. Having fixed work-rest arrangement did not significantly reduce the transmission rate unless the workplace outbreak was prolonged. Social distancing and PPE use significantly reduced the transmission rate. Laboratories should consider organizing the staff into smaller teams/shift and reduce the number of consecutive days worked. Additionally, our observation aligns with the IFCC biosafety recommendation of monitoring staff health (to detect early infection), split team arrangement, workplace social distancing and use of PPE.


Evaluation of Aminoacetophenoneoxime derivatives of oxime Schiff bases as a new antimicrobial agent.
Schiff bases may be a core to synthesize different new chemical ligands. They also have many biological activities by its azomethine group. Antimicrobial activities of new synthetic oxime derivatives against bacteria and fungi were investigated. o-Aminoacetophenoneoxime (o-AAOX) and m- Aminoacetophenoneoxime (m-AAOX) were used as precursors in the synthesis of five oxime derived ligands (L1-5). Two tridentates (L1 and L4) were derived from o-AAOX and three bidentates (L2, L3, and L5) were derived from m-AAOX. The structure of prepared ligands was confirmed using FT-IR, NMR (1 H and 13 C), and UV-Visible spectral analysis as well as melting point and element analysis. Antimicrobial activities of five ligands were determined by the disk diffusion method. Only the m-AAOX ligands showed an antimicrobial action. The L2 was the most effective ligand on the tested microorganisms, especially against Staphylococcus aureus (MIC, 8 mg/ml) and Candida glabrata (MIC, 5.5 mg/ml). The L5 ligand showed only antifungal effect. Kocuria rosea was resistant to all ligands, while Candida albicans was susceptible to most of them. In conclusion; the m-AAOX derivatives are an active compound against bacteria and fungi than the o-AAOX derivatives. The ligand L2 has more inhibitory effects on bacteria, while fungi were inhibited by other m-AAOX derivatives. The new Schiff bases of the m-AAOX derivatives may be regarded as promising antimicrobial agents.


Retrospective evaluation and dating of non-accidental rib fractures in infants.
To describe the sequential appearance of healing rib fractures on initial and follow-up radiographs using published guidelines in approximating the age of rib fractures in infants with the aim of establishing a more objective method of dating rib fractures by measuring the thickness of the callous formation. This was a retrospective analysis of initial and follow-up digital skeletal surveys of infants less than 12 months of age performed between January 2008 and January 2012 at the University of California Davis Children's Hospital. Six radiological features of rib fractures evaluating the appearance of the callous formation (C stage) and fracture line (F stage) were assessed. Patients with osteogenesis imperfecta, known vitamin D deficiency, and skeletal or metabolic dysplasia were not included in the study. Thereafter, callous thickness was measured and recorded for each stage. Sixteen infants (age range 1-11 months, seven males and nine females) with 23 rib fractures were analysed. The thickness of the callous formation follows a predictable pattern advancing one stage after a 2-week follow-up with progressive callous thickening starting from stage 2, peaks at around stage 4, and then tapers and remodels until it almost disappears when the fracture is healed at stage 6. It appears that rib fractures in infants follow a predictable pattern of healing. Measuring the thickness of the callous formation is a more objective way of guiding the radiologist in estimating the age of the fracture.


Neurosurgery in Nepal: Past, Present, and Future.
Neurosurgery in Nepal is now more than half a century old. Though Nepalese neurosurgical roots can be traced back to ancient times, modern services began in Nepal only after 1990 following the arrival of Dr. Upendra Devkota-the father of Nepalese neurosurgery. Contributions from many reputable global advisors as well as local leaders have yielded many changes to the field ever since. Despite these advancements, neurosurgical care in Nepal is mostly limited to the capital city of Kathmandu, and there remains a deficit of qualified neurosurgeons. Geographical dissemination of neurosurgical care, reappraisal of residency training programs, and initiation of subspecialty-based neurosurgical practices are the next steps to further improve the field in Nepal.


Caught in Action - Evolving Emergent Large Vessel Occlusion and Collateral Failure During Alteplase Infusion for Acute Ischemic Stroke.
Published reports of acute deterioration during alteplase infusion for acute ischemic stroke due to development of partial to complete large vessel occlusion and collateral failure are sparce. We describe an 84-year-old patient with a fluctuating clinical course due to evolving emergent large vessel occlusion of right M1 segment of the middle cerebral artery and collateral failure during alteplase infusion. Potential mechanisms of acute deterioration within 24 h after thrombolysis are discussed. Urgent mechanical thrombectomy was performed with resultant partial recanalization and small volume residual infarcts at 72 h magnetic resonance imaging of brain. Progression from partial to complete occlusion may occur within minutes, even during administration of intravenous thrombolytics in hyper-acute stroke. In patients who deteriorate within 24 h of stroke onset, non-contrast CT of brain, followed by CT perfusion and angiography, is the imaging protocol of choice in the mechanical thrombectomy era.


Benchmarking ambulance call-to-needle times for thrombolysis after acute myocardial infarction in Australia: a pilot study.
Thrombolysis for patients with acute myocardial infarction (AMI) is of greatest benefit when treatment is commenced as soon as possible after symptom onset. The British Heart Foundation (BHF) recently set a benchmark recommending that eligible patients with AMI receive thrombolytic therapy less than 90 min after calling for medical assistance. The purpose of this study was to compare the performance of an urban emergency service to this benchmark. A secondary objective was to determine whether patients treated outside this time were at a greater risk of mortality. This study consisted of an explicit retrospective analysis of medical records for all patients who presented by ambulance to the Emergency Department (ED) of Western Hospital and received thrombolysis for AMI within 12 h of symptom onset. The study was conducted for the 18-month period between 1 January 1999 and 30 June 2000. Information collected included times of: (i) symptom onset, (ii) call for ambulance, (iii) ambulance response, (iv) transport to hospital and (v) thrombolysis, as well as final diagnosis and in-hospital mortality. For the purposes of this study, call-to-needle time (CTN) was defined as the time between calling the ambulance and commencement of thrombolytic therapy. One hundred and twenty-seven patients met the inclusion criteria. Median CTN was 81 min (range 42-279 min). Sixty-four per cent of patients were treated within the 90-min benchmark. The relative risk of mortality for patients treated outside the 90-min benchmark was 2.6 (95% CI 0.98-6.72). This study showed that the BHF benchmark for CTN was not being met for over one-third of patients in the study region, with potential impact on mortality after AMI. Further research is needed to establish: (i) whether there is relationship between longer transportation times and mortality, (ii) whether the findings of this study may be applied to other regions and (iii) what strategies might be employed to reduce CTN.


[Determination of aluminium in flour foods with photometric method].
To establish a determination method for aluminium in flour foods with photometric method. After samples being treated with microwave digestion and wet digestion, aluminium in staple flour foods was determined by photometric method. There was a good linearity of the result in the range of 0.25 - 5.0 microg/ml aluminium, r = 0.9998; limit of detection (LOD) : 2.3 ng/ml; limit of quantitation (LOQ) : 7 ng/ml. This method of determining aluminium in flour foods is simple, rapid and reliable.


Marked sequence diversity in the putative envelope proteins of hepatitis C viruses.
The nucleotide sequences of cDNAs (414 base pairs) encoding parts of putative envelope proteins (gp35 and gp70) of 40 isolates of hepatitis C virus (HCV-J) derived from 30 independent plasma or liver specimens from Japanese patients (13 with chronic hepatitis, 14 with hepatocellular carcinoma and 3 hemophiliacs who had received imported clotting factors), were analyzed using the polymerase chain reaction. Approximately 29-38% of the nucleotide sequences of the HCV-J isolates examined differed from those of isolates from the United States (HCV-US). Furthermore, 12-24% and 8-17% sequence diversities were found within the isolates of HCV-J and HCV-US, respectively. The diversities of the amino acid sequences were the same or greater than those of the nucleotide sequences. We confirmed that two hypervariable regions (HVR1 and HVR2) were present in this amplified region, as described in our previous report (Hijikata et al., 1991a) and we found that the HVR1 regions of HCV-J and HCV-US were 27 and 21 amino acids in length, respectively, and began from the N-terminal amino acid of gp70. HVR2 was found in HCV-J, but not in HCV-US isolates, in which the corresponding region of the genome was conserved. During the analysis, plural HCV genomes were found in 6 of 30 specimens. These plural HCV genomes in a single specimen were concluded to be derived from the same HCV ancestor, because of their relative low sequence diversities (about 10% in their nucleotide sequences).(ABSTRACT TRUNCATED AT 250 WORDS)


Publisher Correction: Effect of endogenous microbiota on the molecular composition of cloud water: a study by Fourier-transform ion cyclotron resonance mass spectrometry (FT-ICR MS).
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Liver transarterial embolizations in metastatic neuroendocrine tumors.
The management of patients with well-differentiated neuroendocrine tumors (NET) and non-resectable liver metastases is challenging. Liver-directed transarterial embolization (TAE), transarterial chemo-embolization (TACE) and selective internal radiation therapy (SIRT) have a place of choice among other treatment modalities. However, their utilization relies on a low level of proof, due to the lack of prospective data, the absence of comparative studies and considerable heterogeneity between local practices. TAE and TACE generally achieve average symptomatic, biological and radiological responses of 75%, 56% and 50%, with progression-free survival of 12-18 months, with acceptable tolerance. Although not clearly demonstrated, TACE may be more effective than TAE in pancreatic NET, but not in small-intestine NET. SIRT has been developed more recently and may achieve similar results, with improved tolerance, but decreased cost-effectiveness, although no prospective comparison has been published to date. There is currently no strong argument to choose between TAE, TACE and SIRT, and they have not been compared to other treatment modalities. The evaluation of their efficacy has mostly relied on criteria based on size variations, which do not take into account tumor viability and metabolism, and thus may not be relevant. These techniques may be especially effective when performed as first-line therapies, in patients with non-major liver involvement (<75%) and with hypervascular metastases. Finally, studies exploring their combination with systemic therapies are ongoing.


Deglycosylation by gaseous hydrogen fluoride of mucus glycoproteins immobilized on nylon membranes and in microtiter wells.
Strongly reacting antibodies specific for defined mucin gene products are often directed against the mucin protein backbone of the heavily glycosylated serine/threonine rich regions. A prerequisite for the use of such antibodies is often the complete removal of the oligosaccharides from the protein. This paper describes an efficient one-step deglycosylation method using gaseous hydrogen fluoride on nylon blotting membranes and microtiter wells.


Adding the spatial dimension to the social network analysis of an epidemic: investigation of the 2007 outbreak of equine influenza in Australia.
Equine influenza is a highly contagious and widespread viral respiratory disease of horses and other equid species, characterised by fever and a harsh dry cough. In 2007, in the first reported outbreak in Australia, the virus spread through the horse populations of two states within 4 months. Most of the geographic spread occurred within the first 10 days and was associated with the movement of infected horses prior to the implementation of movement controls. This study applies social network analysis to describe spread of equine influenza between horse premises infected in the early outbreak period, identifying spread occurring through a contact network and secondary local spatial spread. Social networks were constructed by combining contact-tracing data on horse movements with a distance matrix between all premises holding horses infected within the first 10 days of the outbreak. These networks were analysed to provide a description of the epidemic, identify premises that were central to disease spread and to estimate the relative proportion of premises infected through infected horse movements and through local spatial spread. We then explored the effect of distance on disease spread by estimating the range of local spread (through direct contact, transmission on fomites and windborne transmission) based on the level of fragmentation in the network and also by directly estimating the shape of the outbreak's spatial transmission kernel. During the first 10 days of this epidemic, 197 horse premises were infected; 70 of these were included in the contact-traced network. Most local spread occurred within 5 km. Local spread was estimated to have occurred up to a distance of 15.3 km - based on the contact-and-proximity network - and at a very low incidence beyond this distance based on the transmission kernel estimate. Of the 70 premises in the contact network, spread to 14 premises (95% CI: 9, 20 premises) was likely to have occurred through local spatial spread from nearby infected premises, suggesting that 28.3% of spread in the early epidemic period was 'network-associated' (95% CI: 25.6, 31.0%). By constructing a 'maximal network' of contact and proximity (based on a distance cut-off of 15.3 km), 44 spatial clusters were described, and the horse movements that initiated infection in these locations were identified. Characteristics of the combined network, incorporating both spatial and underlying contact relationships between infected premises, explained the high rate of spread, the sequence of cluster formation and the widespread dispersal experienced in the early phase of this epidemic. These results can inform outbreak control planning by guiding the imposition of appropriate control zone diameters around infected premises and the targeting of surveillance and interventions.


Unisexual broods and sex ratios in a polyembryonic encyrtid parasitoid (Copidosoma sp.: Hymenoptera).
We examined brood sex ratios of an undetermined species of Copidosoma. Most broods (65%) were unisexual, with a greater proportion of female broods. Some mixed broods contained extremely small proportions of wasps of the opposite sex. Our results imply that the female-biased sex rations in this species cannot be explained by local mate competition theory.


MOHS micrographic surgery for treating erosive adenoma of the nipple: a case report and review of the literature.
Erosive adenoma of the nipple (EAN) is a benign condition that involves major ducts of the nipple. Its clinical presentation may resemble other disorders. Complete removal of the nipple is often suggested because of frequent relapse. However, adverse cosmetic and functional results have prompted clinicians to look for other more conservative options. To present a case of EAN successfully treated using Mohs micrographic surgery (MMS) and summarize differential diagnosis and treatment. A 40-year-old woman with EAN was diagnosed by immunohistochemical markers after clinical suspicion. We have reviewed other cases treated with MMS in the literature. In this patient, lesion size was 0.8 cm and the margin specimen was 1 × 0.9 × 0.2 cm, with EAN as histopathologic diagnosis. No atypia or malignancy was reported. Final esthetic outcome was reached with only one session, under local anesthesia and on an outpatient basis. Dermatologic lesions appearing on the nipple's surface should be closely followed. Paget's disease, carcinoma or proliferative lesions like EAN have to be considered, and such conditions require different surgical approaches. Traditional complete removal of the nipple is performed in many cases, but it may result in over-treatment and unfavorable cosmetic outcome. MMS is frequently used in dermatologic surgery to treat malignant lesions with a high cure rate, avoiding excess tissue excision and leading to better patient satisfaction. EAN can be successfully treated by minimal resection, especially if early diagnosis is done. MMS offers a better aesthetic outcome than traditional total excision.


Leucocyte rheology in the early stages of ischaemic stroke.
Within 5 hours of the onset of ischaemic stroke the filterability patterns and the counts of the granulocyte, monocyte and lymphocyte subfractions were monitored. The results were compared to those of a healthy matched control group and to those of a matched group with cardiovascular risk factors. The granulocyte filterability rate was significantly impaired in the group at risk and even more so in the stroke group suggesting alterations in it may be a sign of latent ischaemia.


Fe2O3 micron particles are critical for electron transfer and the distribution of electrochemically active bacteria in soil MFCs.
Fe2O3 plays a complex role in soil electron transfer. A microbial fuel cell (MFC) was constructed to drive the directional transfer of electrons in soil, and the results revealed that Fe2O3 acts first as a capacitor, intercepting and reserving the electrons produced by electrochemically active bacteria (EAB) in the soil, which leads to a decrease in hexachlorobenzene (HCB) removal efficiency with increasing proportions of Fe2O3 dosing (R2 = 0.85). The Fe2O3 then exerted its semiconductor properties in synergy with dissolved Fe2+ as an electron mediator to promote the flow of electrons in the soil. Power generation by the MFC was significantly and positively correlated with the concentration of dissolved Fe2+ (r = 0.51) and the Fe2O3 dosing proportion (r = 0.97). The higher HCB removal efficiency, spatial distribution of intercepted electrons, and abundance of electron transfer metabolic pathways confirmed that Fe2O3 promoted electron-flow fluxes in soil. Additionally, Geobacter sp., (direct electron transfer) and Pseudomonas sp., (indirect electron transfer) were the dominant electrochemically active bacteria in the anode and soil of MFC, respectively. In this study, both dissolved (Fe2+) and solid state (Fe2O3) electron mediators functioned as electron transporters in soil, we propose an internal "electron internet" of soil consisting of points and lines.


Computational analysis of flow-cytometry antigen expression profiles in childhood acute lymphoblastic leukemia: an MLL/AF4 identification.
Precursor B-acute lymphoblastic leukemia (pB-ALL) is a heterogeneous disease and multiparameter flow cytometry, molecular genetics, and cytogenetic studies have all contributed to classification of subgroups with prognostic significance. Recently, gene expression microarray technology has been used to investigate lymphoblastic leukemias, demonstrating that known and novel pB-ALL subclasses can be separated on the basis of gene expression profiles. The strength of microarray technique lays in part in the multivariate nature of the expression data. We propose a parallel multiparametric approach based on immunophenotypic flow-cytometry expression data for the analysis of leukemia patients. Specifically, we tested the potential of this approach on a data set of 145 samples of pediatric pB-ALL that included 46 samples positive for mixed lineage leukemia (MLL) translocations (MLL+) and 99 control pB-ALLs, negative for this translocation (MLL-). The expression levels of 16 marker proteins have been monitored by four-color flow cytometry using a standardized diagnostic panel of antibodies. The protein expression database has been then analyzed using those univariate and multivariate computational techniques normally applied to mine and model large microarray data sets. Marker protein expression profiling not only allowed separating pB-ALL cases with an MLL rearrangement from other ALLs, but also demonstrates that MLL+ leukemias constitute a heterogeneous group in which MLL/AF4 leukemias represent a homogenous subclass described by a specific expression fingerprint.


Occurrence and risk assessment of pharmaceuticals in hospital wastewater in Costa Rica.
This work aims to determine the occurrence, hazard and prioritization of pharmaceuticals from hospital wastewater in Costa Rica through the monitoring of 70 compounds and assessing their environmental risk through a hazard quotient approach (HQ). Moreover, the quantification of selected antibiotic resistance genes (ARGs) was conducted for the first time in this matrix in this geographical location. Thirty-four pharmaceuticals were detected, being caffeine, 1,7-dimethylxanthine, acetaminophen, ibuprofen, naproxen, ciprofloxacin and ketoprofen the most frequent (>50% of the samples). Eighteen pharmaceuticals exhibited high hazard (HQ ≥ 1), while five more showed medium hazard (1 > HQ ≥ 0.1). Prioritization, which also included frequency parameters, revealed caffeine, lovastatin, diphenhydramine, acetaminophen, ibuprofen, ciprofloxacin, and sildenafil as the compounds of major concern. Similarly, cumulative hazard per sample (ΣHQ) estimated high hazard towards aquatic organisms in every sample. All selected ARGs, except mcr-1 (polymyxin resistance), were detected. Among genes conferring resistance to beta-lactams, blaCTX-M and blaKPC were the most abundant, related to resistance to cephalosporins and carbapenems. Ecotoxicological evaluation showed mostly low toxicity towards Daphnia magna and Vibrio fischeri, contrary to the marked effect observed towards Lactuca sativa. These findings provide relevant and novel information on the risk posed by hospital wastewater and their pharmaceutical content in the Latin American environmental context.


The Role of Classical and Novel Forms of Vitamin D in the Pathogenesis and Progression of Nonmelanoma Skin Cancers.
Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290-400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290-320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body's requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.


Assessing the influence of methanol-containing additive on biological characteristics of diesel exhaust emissions using microtox and mutatox assays.
Here we investigate the effect of the methanol-containing additive (MCA) on the biological characteristics of diesel exhaust emissions. Microtox and Mutatox assays, respectively, were used to evaluate the acute toxicity and genotoxicity of crude extracts from diesel engine exhaust. The engine was tested on a series of diesel fuels blended with five additive levels (0, 5, 8, 10 and 15% of MCA by volume). Emission tests were performed over the hot start portion of the transient Heavy-Duty-Federal Test Procedure (HD-FTP) and two selected steady-state modes. Microtox results show that MCA additive moderately lowers the toxicity levels of particle-associated (SOF) samples, but generally increase the vapor-phase (XOC) associated toxicity. A strong correlation was found between XOC-associated toxicity and total hydrocarbon (THC) concentrations, while only a slight link was found between SOF-associated toxicity and particulate matter (PM) concentrations. For Mutatox test results, when either 5 or 8% MCA used, XOC and SOF-associated genotoxicity in both steady-state and hot-start transient cycle tests were relatively lower compared to those of the base diesel. The genotoxic potential of XOC samples was significantly increased after treatment with an exogenous metabolic activation system (S9). On the contrary, the genotoxic potential of SOF samples without S9 metabolic activation was generally higher than those with S9. It is noteworthy that the total particle-associated (SOF) PAHs emissions showed trends quite similar to that of the genotoxic potential. As expected, the total particle-associated (SOF) PAHs correlated moderately with direct mutagenicity, and fairly well with indirect mutagenicity. Finally, the genotoxicity data did not parallel the Microtox results in this study, indicating that potentially long-term genotoxic agents may not be revealed by short-term toxicity assays.


The effect of fentanyl on the emergence characteristics after desflurane or sevoflurane anesthesia in children.
Desflurane and sevoflurane anesthesia are associated with emergence agitation in children. In this study, we examined the effect of a single intraoperative dose of fentanyl on emergence characteristics in children undergoing adenoidectomy. One hundred children, 2-7 yr old, were randomly assigned to receive desflurane or sevoflurane for maintenance of general anesthesia after an inhaled induction with sevoflurane and a 2.5 microg/kg dose of fentanyl. An observer blind-ed to the anesthetic technique assessed the times to achieve emergence, extubation and recovery criteria, as well as emergence behaviors. The results showed a similar incidence of severe emergence agitation after general anesthesia with desflurane (24%) and sevoflurane (18%). Times to achieve extubation and postanesthesia care unit discharge criteria were shorter with desflurane than with sevoflurane. With this technique, desflurane allows for a more rapid emergence and recovery than sevoflurane. In children receiving desflurane or sevoflurane, the concurrent use of fentanyl in a dose of 2.5 microg/kg results in a small incidence of emergence agitation. The concurrent use of fentanyl in a dose of 2.5 microg/kg in children receiving desflurane or sevoflurane results in a low incidence of emergence agitation. Desflurane allows for a more rapid emergence and recovery than sevoflurane.


Adventitious Shoot Regeneration from Leaf Explants in Sinningia Hybrida 'Isa's Murmur'.
As a valuable ornamental plant, Sinningia hybrida 'Isa's Murmur' (S. hybrida) has genetic flower diversity, which has great potential to develop different flower characters in the horticultural market. The present study focuses on establishing a practical approach for the sustainable propagation of S. hybrida. Compared with aseptic seeding leaves explants, field-grown leaves explants are more suitable for adventitious shoot regeneration. Adding 0.1 mg L-1 NAA and 2.0 mg L-1 TDZ could obtain the highest adventitious shoot proliferation coefficient (24.5), and the induction rate was 91.7%. The shoot proliferation coefficient (20.7) and the greatest shoot length and induction rate (95.3%) were achieved in 0.1 mg L-1 NAA and 2.0 mg L-1 BA medium, accompanied by rooting formation. Adding 0.5 mg L-1 GA3, 1.0 mg L-1 BA, and 0.2 mg L-1 IBA to MS medium can effectively prolong the regenerated buds for rooting. The best for rooting was 1/2 MS medium containing 0.3 mg L-1 IBA, with the maximum number of roots (13.4 per shoot) and survival rate for transplanting (100%). This work aims to build an efficient, definitive, and scalable protocol for S. hybrida regeneration useful for large-scale cultivation and even more protoplast fusion and genetic transformation to develop more colorful or fragrant flowers.


I-PreFer Study: A Questionnaire to Explore Patient, Caregiver and Pulmonologist Preferences of Idiopathic Pulmonary Fibrosis Treatment Options.
Idiopathic Pulmonary Fibrosis (IPF) is a rare disease that causes shortness of breath, dry cough, and tiredness. While there is no cure for IPF, current therapeutic treatments aim to slow lung degeneration while managing side effects. There is little known about patient experience and attitude with regards to their disease and medication. To understand the perceptions, behaviors and drivers of treatment decision-making among patients, caregivers and pulmonologists in IPF. Online surveys to patients with IPF, caregivers and pulmonologists were developed and administered in Belgium, Finland, France, Greece (pulmonologists only), the Netherlands, Ireland and the United Kingdom between November 2021 and January 2022. A total of 111 patients, 22 caregivers and 140 pulmonologists participated. Half (47%) of patients rated their disease as "severe", while pulmonologists reported that a quarter of their patients had a low Forced Vital Capacity (FVC) (below 50% of the predicted value). Between 21% and 42% of the patients do not take an IPF medication (patients' perception) or antifibrotic (physicians' perception). Pulmonologists reported that a total of 58% of their patients were receiving antifibrotic medication, any IPF medication, while around 53%, 55%, 35% and 73% of the patients limited their exposure (sometimes or often) to the sun due to IPF, considered taking medication against diarrhea, nausea/vomiting and heartburn, respectively. Treatment adherence was relatively high (81%), in line with the caregivers' view and the pulmonologists' expectations. Overall, cultural, clinical or socio-demographic factors impacted patients' perceptions or behaviors. This study shows there is a significant proportion of IPF patients who remain untreated, a misalignment of disease severity between patients and their physicians and patient background impacts behavior. Overall, more in-depth patient-physician communication is needed to improve treatment experience.


Molecular mechanism of lncRNA SNHG12 in immune escape of non-small cell lung cancer through the HuR/PD-L1/USP8 axis.
The pivotal role of long noncoding RNAs (lncRNAs) in cancer immune responses has been well established. This study was conducted with the aim of exploring the molecular mechanism of lncRNA small nucleolar RNA host gene 12 (SNHG12) in immune escape of non-small cell lung cancer (NSCLC). Expression of lncRNA SNHG12, programmed cell death receptor ligand 1 (PD-L1), ubiquitin-specific protease 8 (USP8), and human antigen R (HuR) in NSCLC tissues and cells was measured, and their binding relationship was determined. NSCLC cell proliferation and apoptosis were assessed. Peripheral blood mononuclear cells (PBMCs) were co-cultured with NSCLC cells. The ratio of CD8+ T cells, PBMC proliferation, and inflammatory factors were determined. lncRNA SNHG12 localization was assessed via subcellular fractionation assay. The half-life period of mRNA was determined using actinomycin D. Xenograft tumor models were established to confirm the role of lncRNA SNHG12 in vivo. LncRNA SNHG12 was found to be prominently expressed in NSCLC tissues and cells, which was associated with a poor prognosis. Silencing lncRNA SNHG12 resulted in the reduction in proliferation and the promotion of apoptosis of NSCLC cells, while simultaneously increasing PBMC proliferation and the ratio of CD8+ T cells. Mechanically, the binding of lncRNA SNHG12 to HuR improved mRNA stability and expression of PD-L1 and USP8, and USP8-mediated deubiquitination stabilized the protein level of PD-L1. Overexpression of USP8 or PD-L1 weakened the inhibition of silencing lncRNA SNHG12 on the immune escape of NSCLC. Silencing lncRNA SNHG12 restricted tumor growth and upregulated the ratio of CD8+ T cells by decreasing USP8 and PD-L1. LncRNA SNHG12 facilitated the immune escape of NSCLC by binding to HuR and increasing PD-L1 and USP8 levels.


Characterization of a germin-like protein gene expressed in somatic and zygotic embryos of pine (Pinus caribaea Morelet).
Germin-like proteins (GLPs) ionically bound to the walls of preglobular somatic embryos of Pinus caribaea Morelet are markers of this early developmental stage. In order to reveal the physiological implications of such markers during early embryo development, we isolated a cDNA clone from somatic embryos predicted to encode a protein with sequence similarity to GLPs. PcGER1 has an open reading frame corresponding to a 220 amino acid polypeptide with a putative N-glycosylation site on Asn-69. The presence of a 24 amino acid putative signal peptide supports the hypothesis of an apoplastic location. The N-terminal 20 amino acid sequence of the predicted mature protein is identical to the amino terminal sequence of GP111, one of the extracellular pine GLPs previously identified. Southern blot hybridizations indicate that PcGER1 is probably unique in the pine genome. Transcripts homologous to PcGER1 are abundant in all embryogenic lines, absent from nonembryogenic lines, and present in quiescent zygotic embryos but not in the female gametophyte, the haploid storage tissue of conifers. Their abundance sharply decreases during germination. Isolation of gf-0.8, a genomic fragment identical to PcGER1 cDNA sequence, confirms that no introns disrupt the coding region as it has been already described for wheat gf-2.8 and gf-3.8 genomic clones. Recombinant PcGER1, produced in Escherichia coli, is recognized by antibodies raised against the GP111 N-terminal nonapeptide and the unglycosylated wheat germin monomer. The implications of GLPs in pine embryogenesis are discussed.


The clinical and inflammatory relationships between periodontitis and chronic obstructive pulmonary disease.
To investigate associations between periodontitis and chronic obstructive pulmonary disease (COPD) with and without alpha-1 antitrypsin deficiency (AATD), including neutrophil functions implicated in tissue damage. The presence and severity of periodontitis (using two international criteria) and lung disease were assessed in 156 COPD patients with and without AATD accounting for common confounding factors. Saliva and systemic inflammatory markers were measured by ELISA together with neutrophil migration. COPD and AATD patients exhibited higher prevalence of periodontitis (COPD 95%; AATD 88%) than reported in unselected community-dwelling populations even when risk factors (age, smoking history, socio-economic status and dental habits) were considered. Periodontitis severity associated with lung disease severity (AATD, periodontitis versus no periodontitis; FEV1 = 56% versus 99% predicted; TLCO = 59% versus 81% predicted, p < .0001 for both). Neutrophil migratory accuracy declined in stage II-IV periodontitis patients with COPD or AATD compared to COPD or AATD with no or stage I periodontitis. Improved dental habits appeared to be associated with a reduction in exacerbation frequency in COPD. The results support shared pathophysiology between periodontitis and COPD, especially when associated with AATD. This may reflect an amplification of neutrophilic inflammation and altered neutrophil functions, already described in periodontitis, COPD and AATD.


Uptake, distribution, and elimination of sodium linear alkylbenzene sulfonate and sodium alkyl sulfate in carp.
Uptake, distribution, and elimination of labeled surfactants, 35S-labeled sodium laurylbenzenesulfonate (35S-C12-LAS) and 35S-labeled sodium lauryl sulfate (35S-C12-AS), were investigated in carp exposed to a low concentration level of the respective solutions found in river water in Japan by whole-body autoradiography and liquid scintillation counting. Whole-body autoradiograms showed that the fish absorbed 35S-C12-LAS and 35S-C12-AS from the solutions principally through gills and that the surfactants absorbed were rapidly distributed throughout the body tissues and organs. High concentrations were found in gills, blood, hepatopancreas, kidney, and gall bladder. The elimination in the fish that were kept in clean fresh water after exposure were relatively rapid in most tissues and organs except for gall bladder. These results suggest that the surfactants absorbed in fish may have an adverse effect on many tissues and organs of fish. What influenced the distribution profile and concentration factors of the surfactants in tissues and organs of carp were the exposure time and the molecular structure of the surfactants.


Formula-feeding and hypertrophic pyloric stenosis: is there an association? A case-control study.
The etiology of infantile hypertrophic pyloric stenosis (HPS) is not fully understood. The objective of this study was to determine whether formula-feeding is associated with increased incidence. This case-control study included HPS cases and controls admitted between 1992 and 2012. Demographic data including feeding method were collected from patient charts and analyzed. We identified 882 HPS cases and 955 controls. The highest incidence of HPS presentation was in summer (P=0.0028). Infants with HPS were more likely to have been exclusively formula-fed, have a family history of HPS, and be male compared to infants in the control group (P<0.001); they were also more likely to live in rural areas, although not significantly so. After adjusting for family history, sex, place of residence, and season of presentation, exclusively formula-fed infants were 1.36 times more likely to develop HPS compared with exclusively breastfed infants (RR 1.36, 95% CI 1.18-1.57, P<0.005). Formula-feeding is associated with significantly increased risk of HPS. Further investigation may help to determine the components of formula that simulate hypertrophy of the pylorus muscle, or the components of breast milk that are protective, as well as other influencing factors. 3b.