Effect of acyclovir on mammalian embryonic development in culture.
Acyclovir [9-(2-hydroxyethoxymethyl)guanine] interfered with embryonic development in vitro when assessed with the "whole-embryo" culture technique. The "no-observed-effect level" was at 10 microM acyclovir; Minor impairment of embryonic development (retarded development of ear anlagen) was observed in vitro at 25 microM acyclovir in the culture medium. At high concentrations (100 or 200 microM) development of the ear anlagen was largely inhibited. At concentrations of 50 microM acyclovir or higher, additional disturbances of embryonic differentiation in vitro became obvious, resulting in gross structural abnormalities, especially of the brain (telencephalon); Histological examinations confirmed and extended these observations: at 100 microM acyclovir alterations of the neuroepithelium of the ventricles were pronounced, the telencephalon had developed poorly or was almost completely absent, and necroses were seen in the ear anlagen, the maxillary branch and within the somites; In a limb bud culture (mouse embryos, starting with day 11 of gestation) acyclovir interfered with the differentiation of cartilaginous bone anlagen at concentrations of 200 microM and more in the culture medium. A concentration of 100 microM induced no significant effect. Thus, this organ culture system is less sensitive to the action of acyclovir when compared with whole-embryo culture; Contrary to the results achieved with acyclovir, physiological nucleosides (2'-deoxyguanosine and 2'-deoxyadenosine) did not interfere with embryonic development in vitro even at the highest concentration tested (500 microM).


How do we diagnose syncope?
The Eastbourne Syncope Assessment Study aims to increase diagnostic yield in unexplained syncope while reducing investigational costs. The initial study phase was a retrospective analysis of every presentation to the Eastbourne General Hospital (a busy nontertiary center in the United Kingdom serving a population of 250,000; 24% are older than 65 years) with syncope for the year 1998. A total of 1,334 cases with syncopal codes were identified. Six hundred sixty patients (mean age 64 years) had actually suffered an episode of syncope. Forty percent had recurrent syncope, with a mean of 4.7 previous episodes. Twenty-nine percent of syncope cases remained undiagnosed. Forty-four percent were diagnosed as vasovagal, 12% neurologic, 6% due to an arrhythmia, 2% drug related, and 2% due to hemorrhage. Thirteen different types of investigation were undertaken, with an overall total of 3,264 investigations performed at a cost of Pound Sterling 104,285. Diagnosis was achieved by history and examination alone in 61% of cases. Excluding history and examination, the most cost-effective diagnostic tools were the 7-day patient-activated recorder (R test) and tilt testing (Pound Sterling 260 and Pound Sterling 401 per diagnosis, respectively). Investigations also were graded by their relative diagnostic power. Hospital admission alone accounted for 67% of the cost of investigating syncope. In syncope, diagnostic rates can be improved and investigational costs reduced by concentrating on the most specific, sensitive, and cost-effective investigations and by minimizing hospital stay. Such a protocol currently is under investigation at our institution.


Predictors of Long-Term Urinary Incontinence After Robot-Assisted Laparoscopic Prostatectomy.
Urinary incontinence is a major complication after radical prostatectomy. We analyzed the predictors of urinary incontinence after robot-assisted radical prostatectomy. One hundred twenty-one patients, whose urinary continence status was evaluable at 3 months, 6 months, and 12 months after robot-assisted radical prostatectomy, were included from October 2016 to September 2021. Data were retrospectively collected from electronic medical records. The continence status was evaluated by interviewing the patients about the number of urinary pads used per day. We compared the patients' age, body mass index, prostate volume, membranous urethral length on preoperative magnetic resonance imaging, surgeon experience, and pathological findings between patients with and without regained continence at 12 months after robot-assisted radical prostatectomy. The urinary continence rates were 30%, 57.8% and 79.3% at 3 months, 6 months, and 12 months, respectively, after robot-assisted radical prostatectomy. Twelve months after robot-assisted radical prostatectomy, 96 patients had regained continence and did not require urinary pads, whereas 25 patients had persistent urinary incontinence and required urinary pads. Membranous urethral length and surgeon experience were significantly different between patients with and without regained continence at 12 months after robot-assisted radical prostatectomy (P=0.05). However, no significant differences existed in age, body mass index, prostate volume, and pathological findings between patients with and without regained continence at 12 months after robot-assisted radical prostatectomy. Membranous urethral length and surgeon experience are predictors of urinary incontinence after robot-assisted radical prostatectomy. Measuring the membranous urethral length is recommended before performing the operation.


A new method for the simulation of electric fields, generated by electric fish, and their distorsions by objects.
Among the many species of fishes endowed with electric organs Mormyriformes and Gymnotoidei are known to emit and receive electric signals for the purposes of intraspecific communication and recognition of objects. Models which have been proposed for this electro-sensory system generally assume steady-state conditions. On the other hand, the very character of the signals itself and the idea that the cerebellum might be working as a clock point to the importance of the signal dynamics. Therefore a new approach to the simulation of electric fields is described in the paper. The basic idea is to superpose the fields of point charges in a way that the sum is in accordance with the fish's electric field. The same technique could be used to simulate the influence of objects on the electric field. Following a suggestion of Dr. E. Kasper I used a simpler but equal effective approach for object simulation consisting in the use of a dipole instead of point charges. The model described is easily applied to diverse situations and allows one to estimate the influence of various parameters (size, shape, and position) on the "electric image" of an object. Furthermore, the well-known behaviour of tailbending and its consequences in object recognition can be simulated. The results underline the importance of signal dynamics for species with pulse-type discharges.


Cerebellopontine angle epidermoids presenting with trigeminal neuralgia.
We studied the clinical characteristics of cerebellopontine angle (CPA) epidermoids presenting with trigeminal neuralgia (TN). Twenty-four patients were analyzed retrospectively and the literature reviewed with regard to clinical manifestation, imaging features, surgical procedures and prognosis. TN may be the initial symptom of CPA epidermoid, particularly in young patients. Epidermoids are characteristically hypodense nonenhancing lesions on CT scans, while on MRI they exhibit long T1 and T2 relaxation times. Although complete removal is ideal in the surgical management of CPA epidermoid, proximity to cranial nerves and the brain stem may pose technical difficulties in complete resection. In addition to complete resection of the tumour, arterial compression at the root entry zone (REZ) of the trigeminal nerve should be sought, and if found, a microvascular decompression (MVD) should be performed. Cranial nerve dysfunction and aseptic meningitis are the most common operative complications.


Congestive hepatopathy and acute pancreatitis as severe complications of mixed connective tissue disease.
Mixed connective tissue disease (MCTD) causes multiple organ dysfunctions, such as joint swelling, pulmonary fibrosis and hypertension, and serositis, but hepatopancreatic complications are rare. Here, we report a case of young man who exhibited acute severe liver dysfunction. He also had impaired cardiac function: both ventriculi were hypokinetic, but pulmonary hypertension and pericarditis were not observed. Since his liver and cardiac function markedly improved after commencing furosemide and carperitide, we considered congestive hepatopathy due to MCTD and accompanying heart failure. Heart failure and congestive hepatopathy recurred and he was treated with diuretics and prednisolone, but he passed away by co-occurrence of acute hemorrhagic pancreatitis. Necropsy revealed chronic hepatic congestion but not accompanying autoimmune hepatitis and hepatic vasculitis. We should consider congestive hepatopathy and hemorrhagic pancreatitis as serious complications of MCTD.


QUENCH: A software package for the determination of quenching curves in Liquid Scintillation counting.
In Liquid Scintillation Counting (LSC), the scintillating source is part of the measurement system and its detection efficiency varies with the scintillator used, the vial and the volume and the chemistry of the sample. The detection efficiency is generally determined using a quenching curve, describing, for a specific radionuclide, the relationship between a quenching index given by the counter and the detection efficiency. A quenched set of LS standard sources are prepared by adding a quenching agent and the quenching index and detection efficiency are determined for each source. Then a simple formula is fitted to the experimental points to define the quenching curve function. The paper describes a software package specifically devoted to the determination of quenching curves with uncertainties. The experimental measurements are described by their quenching index and detection efficiency with uncertainties on both quantities. Random Gaussian fluctuations of these experimental measurements are sampled and a polynomial or logarithmic function is fitted on each fluctuation by χ(2) minimization. This Monte Carlo procedure is repeated many times and eventually the arithmetic mean and the experimental standard deviation of each parameter are calculated, together with the covariances between these parameters. Using these parameters, the detection efficiency, corresponding to an arbitrary quenching index within the measured range, can be calculated. The associated uncertainty is calculated with the law of propagation of variances, including the covariance terms.


Serum metabolomic research of the anti-pulmonary fibrosis effects of Shuangshen Pingfei Formula on bleomycin-induced pulmonary fibrosis rats.
Our previous studies showed that Shuangshen Pingfei Formula (SSPF) exhibited anti-fibrosis effect, but its biochemical changes at the metabolic level remain unclear. In this study, an integrative approach of gas chromatography-mass spectrometry (GC-MS) and ultra performance liquid chromatography-Q Exactive-mass spectrometry (UPLC-QE-MS)-based non-targeted metabolomics and multivariate statistical analysis was employed to explore the metabolic changes of serum samples from different stages of bleomycin-induced pulmonary fibrosis (PF) rats (PFRs: M7, M14, M21 and M28) treated with SSPF extracts. Potential biomarkers for PF were screened. Benzenebutanoic acid, pyroglutamic acid, cholic acid, 1-monopalmitin, succinic acid and palmitoleic acid may be potential biomarkers of the early inflammation stage of PF (M7-M14). 3,4-dimethylbenzoic acid, glutamic acid, glycine, proline, serine, taurine, etc. may be potential biomarkers for the advanced pulmonary fibrosis stage (M21-M28) of PF. The disturbance was mainly related to the disorder of lipid, amino acid metabolism. After SSPF treatment, the disorder was regulated and 67 metabolites were restored to a certain extent. Serine, proline, glutamine, 4-guanidinobutyric acid, phosphatidylethanolamine, lecithin and 9,10-epoxyoctadecene acids may be useful as biomarkers of the anti-fibrosis effect of SSPF.


Modulator role of infliximab and methotrexate through the transient receptor potential melastatin 2 (TRPM2) channel in neutrophils of patients with rheumatoid arthritis: a pilot study.
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disease causing symmetric polyarthritis. In this study, we aimed to investigate the effects of infliximab (INF) and methotrexate (MTX) on apoptosis, oxidative stress, and calcium signaling in the neutrophils of RA patients. Neutrophils were isolated from 10 patients with newly diagnosed RA and 10 healthy controls. They were divided into four groups (control, RA, RA + MTX, RA + INF) and incubated with MTX and INF. In the cell viability (MTT) test, the ideal non-toxic dose and incubation time of MTX were found to be 0.1 mM and 1 h, respectively. The neutrophils were also incubated with the TRPM2 channel blocker N-(p-amylcinnamoyl) anthranilic acid (ACA). Intracellular free Ca2+ concentration, intracellular reactive oxygen species (ROS) production, mitochondrial depolarization, lipid peroxidation, apoptosis, and caspase 3 and caspase 9 activities were found to be significantly higher in the neutrophils of RA patients compared to controls. MTT, reduced glutathione (GSH) level, and glutathione peroxidase (GSHPx) activity were significantly lower in the neutrophils of RA patients. However, MTT, GSH and GSHPx values were detected to be significantly increased with INF and MTX therapies. The Ca2+ concentrations were further decreased by the ACA therapy. Our results suggest that INF and MTX are useful antagonists in apoptosis and mitochondrial oxidative stress in the neutrophils of RA patients. INF and MTX decreased the Ca2+ concentration through inhibition of the TRPM2 channel in the neutrophils of RA patients. It may be a new pathway in the mechanisms of anti-rheumatic drugs.


Infliximab as a novel therapy for pediatric ulcerative colitis.
The role of infliximab (anti-tumor necrosis factor alpha antibody) therapy in ulcerative colitis (UC) is not well defined. There are only two reports published describing its use in UC. The authors describe their experience with open-label use of infliximab in children with moderate to severe UC. The authors collected data on all consecutive pediatric patients with UC who received infliximab at The Children's Hospital of Philadelphia until July 2001. The primary measured outcome was clinical response at 2 days and 2 weeks after infliximab infusion, as measured by the Lichtiger colitis activity index (LCAI) score and the Physician Global Assessment (PGA). Tolerance of the infusions and adverse events were recorded. Nine patients qualified for clinical response analysis. The median Lichtiger colitis activity index score decreased from 11 before the infusion to 1 at 2 days and 2 weeks after the infusion, respectively (P = 0.01 for 2 days and 2 weeks). Seven of nine (77%) patients had decreased activity of their disease measured by the Physician Global Assessment. Corticosteroid therapy was discontinued in six (66%) patients. An infusion reaction developed (generalized pruritus and facial flushing) in two patients and an elevated anti-nuclear antibody (ANA) titer of 1:1280 developed in one patient. Infliximab is associated with short-term clinical improvement in children and adolescents with moderate to severe UC.


Prediagnostic Circulating Concentrations of Vitamin D Binding Protein and Survival among Patients with Colorectal Cancer.
Higher total 25-hydroxyvitamin D [25(OH)D] levels are associated with improved survival among patients with colorectal cancer, but the relationships between circulating vitamin D binding protein (VDBP), and bioavailable or free 25(OH)D, and colorectal cancer survival remain unknown. We examined the associations between prediagnostic plasma levels of vitamin D-related markers and survival among 603 White participants diagnosed with colorectal cancer from two prospective U.S. cohorts. Plasma VDBP and total 25(OH)D were directly measured, while bioavailable and free 25(OH)D was calculated using a validated formula on the basis of total 25(OH)D, VDBP, and albumin levels. Cox proportional hazards regression was used to estimate HRs for overall and colorectal cancer-specific mortality, with adjustment for other prognostic markers and potential confounders. Higher VDBP levels were associated with improved overall (P trend = 0.001) and colorectal cancer-specific survival (P trend = 0.02). Compared with patients in the lowest quartile, those in the highest quartile of VDBP had a multivariate HR of 0.58 [95% confidence interval (CI), 0.41-0.80] for overall mortality and 0.58 (95% CI, 0.37-0.91) for colorectal cancer-specific mortality. The results remained similar after further adjustment for total 25(OH)D levels. In contrast, neither bioavailable nor free 25(OH)D levels were associated with overall or colorectal cancer-specific mortality (all P trend > 0.15). Prediagnostic circulating concentrations of VDBP were positively associated with survival among patients with colorectal cancer. The clinical utility of VDBP as a prognostic marker warrants further exploration, as well as research into underlying mechanisms of action.


Population-based screening for prostate cancer by measuring free and total serum prostate-specific antigen in Sweden.
To report the initial results from Sweden of a large population-based randomized study of screening using prostate-specific antigen (PSA) to detect prostate cancer, as the efficacy of such screening to decrease prostate cancer mortality has not yet been proven. From the population registry men aged 50-66 years were randomized to screening (9973) and to future controls (9973). Men randomized to screening were invited to have their serum measured for free PSA (fPSA) and total PSA (tPSA) in serum using the Prostatus f/tPSA assay (Perkin-Elmer, Turku, Finland). Men with a tPSA of < 3.0 ng/mL were not further investigated, while those with a tPSA of > or = 3.0 ng/mL were investigated with a digital rectal examination (DRE), transrectal ultrasonography (TRUS) and sextant biopsies. Of those invited, 60% accepted PSA testing and 11.3% had a tPSA of > or = 3.0 ng/mL. Altogether 145 cancers were detected (positive predictive value, PPV, 24%); none were stage M1, two were stage N+ and 10 stage T3-4. Most (59%) cancers were impalpable and 39% were both impalpable and invisible on TRUS. At biopsy, 7% were Gleason score 2-4, 71% 5-6, 19% 7 and 2% Gleason score 8-10. A threshold tPSA of > or = 4.0 ng/mL would have detected 109 cancers in 366 biopsied men (PPV 30%) while cancer detection would have been 14% higher with a PPV of 36% using a threshold tPSA of > or = 3.0 ng/mL combined with a f/tPSA threshold of < or = 18%. PSA screening detects early-stage low-grade prostate cancer. Both the sensitivity and specificity can be increased by incorporating f/tPSA with a tPSA threshold of < 4 ng/mL.


Infants aren't biased toward fearful faces.
Grossmann's argument for the "fearful ape hypothesis" rests on an incomplete review of infant responses to emotional faces. An alternate interpretation of the literature argues the opposite, that an early preference for happy faces predicts cooperative learning. Questions remain as to whether infants can interpret affect from faces, limiting the conclusion that any "fear bias" means the infant is fearful.


Silver-catalyzed amidation of benzoylformic acids with tertiary amines via selective carbon-nitrogen bond cleavage.
A novel approach towards the synthesis of α-ketoamides using tertiary amines as nitrogen group sources via C-N bond cleavage has been developed. In the presence of Ag2CO3 and K2S2O8, α-keto acids reacted with tertiary amines to afford the corresponding α-ketoamides in good yields.


Functional expression of Kir 6.1/SUR1-K(ATP) channels in frog retinal Müller glial cells.
The retinae and brains of larval and adult amphibians survive long-lasting anoxia; this finding suggests the presence of functional K(ATP) channels. We have previously shown with immunocytochemistry studies that retinal glial (Müller) cells in adult frogs express the K(ATP) channel and receptor proteins, Kir6.1 and SUR1, while retinal neurons display Kir6.2 and SUR2A/B (Skatchkov et al., 2001a: NeuroReport 12:1437-1441; Eaton et al., in press: NeuroReport). Using both immunocytochemistry and electrophysiology, we demonstrate the expression of Kir6.1/SUR1 (K(ATP)) channels in adult frog and tadpole Müller cells. Using conditions favoring the activation of K(ATP) channels (i.e., ATP- and spermine-free cytoplasm-dialyzing solution containing gluconate) in Müller cells isolated from both adult frogs and tadpoles, we demonstrate the following. First, using the patch-clamp technique in whole-cell recordings, tolbutamide, a blocker of K(ATP) channels, blocks nearly 100% of the transient and about 30% of the steady-state inward currents and depolarizes the cell membrane by 5-12 mV. Second, inside-out membrane patches display a single-channel inward current induced by gluconate (40 mM) and blocked by ATP (200 microM) at the cytoplasmic side. The channels apparently show two sublevels (each of approximately 27-32 pS) with a total of 85-pS maximal conductance at -80 mV; the open probability follows a two-exponential mechanism. Thus, functional K(ATP) channels, composed of Kir6.1/SUR1, are present in frog Müller cells and contribute a significant part to the whole-cell K+ inward currents in the absence of ATP. Other inwardly rectifying channels, such as Kir4.1 or Kir2.1, may mediate the remaining currents. K(ATP) channels may help maintain glial cell functions during ATP deficiency.


Deep learning approach for prediction of exergy and emission parameters of commercial high by-pass turbofan engines.
Aviation emissions originated from the fuel burn have been hot topics by engineers and policy-makers due to their harmful effects on the environment and thereby human health as well as sustainability. In this study, it is tried that several emission indexes (EIs) involving CO, HC and NOx as well as fuel flow of several commercial aircraft engines (CAEs) are predicted using support vector regression (SVR) and long short-term memory (LSTM) approaches for take-off phase. Moreover, exergo-environmental parameters involving exergy efficiency (ExEFF), wasted exergy ratio (WExR) and environmental effect factor (EEF) pertinent to CAEs are computed employing thermodynamics laws. While establishing the models, rated thrust, by-pass ratio, overall pressure ratio and combustion type of the CAEs are utilized as the model inputs. According to the findings of emission modelling, the coefficient of determination (R2) of EI NOx and EI CO of the CAEs is found as 0.929074 and 0.960277 with SVR, whereas their R2 values are elevated to 0.954878 and 0.989283 with LSTM approach, respectively. However, R2 of EI HC is determined lower with 0.632280 (by SVR) and 0.651749 (by LSTM). On the other hand, exergo-environmental parameters for the CAEs are estimated with high correctness at both models. Namely, R2 of ExEFF and EEF regarding the CAEs are computed as 0.991748 and 0.989067 by SVR; however, these are calculated as 0.994785 and 0.992797 by LSTM method. To model these parameters with low error by using significant design variables as model inputs could help in predicting emission and environmental metrics for new engine designs.


Cortical suspensory button fixation has superior biomechanical properties to knotless anchor suture in anterior cruciate ligament repair: a biomechanical study.
The purpose of our biomechanical study was to assess load-to-failure, stiffness, gap formation following cyclic loading, and the failure mechanism for anterior cruciate ligament (ACL) repair comparing the cortical suspensory button and knotless anchor suture. Eight Thiel's embalmed paired cadaveric knees from four cadavers were dissected. The specimens were assigned to undergo ACL repair either with cortical suspensory button or with knotless anchor suture. The Instron machine replicates cyclic loading and then determines the gap formation. Traction was applied until failure. The load-to-failure, stiffness, and modes of failure in both groups were recorded. The load-to-failure, stiffness, and gap formation were compared between the two groups using the student's t-test. The mean load-to-failure in the cortical suspensory button group was significantly higher than the knotless anchor suture group (212.96 ± 54.57 vs 44.57 ± 20.80, p value < 0.01). No statistically significant difference was found regarding gap formation following cyclic loading and stiffness between the cortical suspensory button group and the knotless anchor suture group. This biomechanical study showed a higher load-to-failure for the ACL repair with cortical suspensory button compared to ACL repair with knotless anchor suture, while no statistically significant difference was found regarding the gap formation following cyclic loading and the stiffness. The load-to-failure in both cortical suspensory button and knotless anchor suture are below regular daily activity load. Thus, an internal brace or external support is recommended during rehabilitation.


CT features of low grade serous carcinoma of the ovary.
To evaluate the CT features of pathologically proven low grade serous carcinoma (LGSC) of the ovary. Patients with a pathologic diagnosis of LGSC and CT prior to oophorectomy were retrospectively identified. The CT scans in 14 patients were available and were analyzed for an adnexal mass, peritoneal mass and ascites. The adnexal mass was characterized as complex primarily cystic, mixed cystic solid, or primarily solid. Calcification in the adnexal and peritoneal masses and nodes was noted. Pathology revealed 6 patients had LGSC and 8 patients had a combined diagnosis of LGSC and serous borderline tumor (SBT) of the ovary. Of the 6 patients with only LGSC, 4 had primarily solid or mixed solid cystic adnexal masses and 5 had peritoneal masses. Calcification was present in the adnexal and peritoneal masses in 4 patients, and in nodes in 2 patients. Of the 8 patients with co-existing LGSC and SBT, 7 had complex primarily cystic adnexal masses and 6 had peritoneal masses. Calcification was present in the adnexal and peritoneal masses in 5 patients and in nodes in 2 patients. LGSC can appear as a solid, mixed solid cystic, or complex primarily cystic ovarian mass, and the appearance may be due to a co-existing SBT. Calcification of the adnexal and peritoneal masses appears to be common. LGSC is a diagnostic consideration in patients with a calcified adnexal mass and concurrent peritoneal masses or calcified nodes on CT.


Novel application of luciferase assay for the in vitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD).
KAL1 is implicated in 5% of Kallmann syndrome cases, a disorder which genotypically overlaps with septo-optic dysplasia (SOD). To date, a reporter-based assay to assess the functional consequences of KAL1 mutations is lacking. We aimed to develop a luciferase assay for novel application to functional assessment of rare KAL1 mutations detected in a screen of 422 patients with SOD. Quantitative analysis was performed using L6-myoblasts stably expressing FGFR1, transfected with a luciferase-reporter vector containing elements of the FGF-responsive osteocalcin promoter. The two variants assayed [p.K185N, p.P291T], were detected in three females with SOD (presenting with optic nerve hypoplasia, midline and pituitary defects). Our novel assay revealed significant decreases in transcriptional activity [p.K185N: 21% (p < 0.01); p.P291T: 40% (p < 0.001)]. Our luciferase-reporter assay, developed for assessment of KAL1 mutations, determined that two variants in females with hypopituitarism/SOD are loss-of-function; demonstrating that this assay is suitable for quantitative assessment of mutations in this gene.


Recombinant human growth hormone for children born small for gestational age: meta-analysis confirms the consistent dose-effect relationship on catch-up growth.
The optimal treatment regimen of recombinant human GH (r-hGH) for short children born small for gestational age (SGA) is still under discussion. A meta-analysis was performed of existing clinical trials that investigated the treatment of r-hGH in short children diagnosed SGA or with intrauterine growth retardation to determine the relationship between the daily r-hGH dose (placebo/no treatment; 0.033 mg/kg/day; 0.067 mg/kg/day) and the effect on growth [change in height-SD score (SDS) for chronological age]. A mathematical model describing the dose-response relationship was produced, and growth response (gain in height-SDS) to 2 yr of r-hGH 0.033 mg/kg/day [somatropin (rDNA origin) for injection; Serono] was estimated and compared with the response to other r-hGH formulations. The relationship between r-hGH dose and 2-yr growth response was described by an equation. The equation yielded a mean difference in height- SDS gain of 0.48 (0.35) between r-hGH 0.033 and 0.067 mg/kg/day in favor of the higher dose. The height-SDS gain after 2 yr of Serono r-hGH formulation, 0.033 mg/kg/day was estimated as 1.2. Comparison of this estimate to the growth response to 2-yr treatment at 0.033 mg/kg/day of other r-hGH formulations (mean difference in height-SDS 0.05, lower limit of the 95% confidence interval=-0.15) confirmed that growth response to Serono r-hGH formulation 0.033 mg/kg/day is an inferred response estimated to be within the range of observed responses to a (non-Serono formulation) r-hGH dose of 0.033 mg/kg/day. There is a clear dose-response relationship for r-hGH in the treatment of short children born SGA and the analysis confirmed that treatment with Serono r-hGH formulation 0.033 mg/kg/day should provide a meaningful therapeutic response.


The prognostic impact of seminal vesicle involvement found at prostatectomy and the effects of adjuvant radiation: data from Southwest Oncology Group 8794.
From the randomized study Southwest Oncology Group 8794 we evaluated the effect of seminal vesicle involvement on outcomes and whether those patients benefited from post-prostatectomy adjuvant radiation therapy. Southwest Oncology Group study 8794 randomized high risk patients (with seminal vesicle positive disease and/or capsular penetration and/or positive margins) to radiation vs observation after prostatectomy. A total of 431 subjects with pathologically advanced prostate cancer were randomized. Median followup was 12.2 years. Of the patients 139 had seminal vesicle involvement with or without capsular penetration and/or positive margins. Compared to the 286 patients with seminal vesicle negative disease there was poorer 10-year biochemical failure-free survival (33% for seminal vesicle negative and 22% for seminal vesicle positive, p = 0.04), metastasis-free survival (70% and 56%, respectively, p = 0.005) and overall survival (10-year overall survival 74% and 61%, respectively, p = 0.02) for those with seminal vesicle positive disease. Patients with seminal vesicle positive disease who received adjuvant radiation compared to observation realized an improvement in 10-year biochemical failure-free survival from 12% to 36% (p = 0.001), in 10-year overall survival from 51% to 71% (p = 0.08) and in metastasis-free survival from 47% to 66% (p = 0.09), respectively. Although seminal vesicle involvement is a negative prognostic factor, long-term control is possible especially if patients are given adjuvant radiation therapy. This therapy appears to be effective in patients with seminal vesicle involvement.


Regulation of the expression of a mammalian idiotype in chickens.
Id-1, an idiotype associated with rat anti-Group A streptococcal carbohydrate (anti-SACHO) antibodies has not been detected in any other tested species immunized with Group A streptococcal vaccine (GASV). The immunization of chickens with rat Id-1 prior to challenge with GASV, however, induced the production of Id-1 and anti-Id-1 in some chickens. The concentrations of both idiotype and anti-idiotype were regulated by challenges with GASV. Thus, it appears that this non-mammalian species has the genetic potential to express the mammalian Id-1 network but such a potential is normally masked by regulatory pressures.


The Farmer-Input Subsidy Program (FISP) Does not Service the Poor.
This article focuses on the Farmer Input Subsidy Program (FISP) in Southern Africa. The FISPs are part of agricultural support by governments providing input subsidies to small-scale farmers from public resources. FISPs are intended to reduce the production costs of small-scale farmers. Rural women members of the Rural Women's Assembly (RWA) in Southern Africa argue that the FISP is captured by the global agro-industry and that the FISP, far from providing real support to farmers, advances a green-revolution agenda and has become a tool of the political elites and MNCs.


Sex Differences in Long-term Outcome of Prenatal Exposure to Excess Glucocorticoids-Implications for Development of Psychiatric Disorders.
Exposure to prenatal insults, such as excess glucocorticoids (GC), may lead to pathological outcomes, including neuropsychiatric disorders. The aim of the present study was to investigate the long-term effects of in utero exposure to the synthetic GC analog dexamethasone (Dex) in adult female offspring. We monitored spontaneous activity in the home cage under a constant 12 h/12 h light/dark cycle, as well as the changes following a 6-h advance of dark onset (phase shift). For comparison, we re-analysed data previously recorded in males. Dex-exposed females were spontaneously more active, and the activity onset re-entrained slower than in controls. In contrast, Dex-exposed males were less active, and the activity onset re-entrained faster than in controls. Following the phase shift, control females displayed a transient reorganisation of behaviour in light and virtually no change in dark, while Dex-exposed females showed limited variations from baseline in both light and dark, suggesting weaker photic entrainment. Next, we ran bulk RNA-sequencing in the suprachiasmatic nucleus (SCN) of Dex and control females. SPIA pathway analysis of ~ 2300 differentially expressed genes identified significantly downregulated dopamine signalling, and upregulated glutamate and GABA signalling. We selected a set of candidate genes matching the behaviour alterations and found consistent differential regulation for ~ 73% of tested genes in SCN and hippocampus tissue samples. Taken together, our data highlight sex differences in the outcome of prenatal exposure to excess GC in adult mice: in contrast to depression-like behaviour in males, the phenotype in females, defined by behaviour and differential gene expression, is consistent with ADHD models.


The pathophysiology of lymphedema.
All edemas result from an imbalance between capillary filtration and tissue (lymph) drainage. This basic approach was adopted to investigate mechanisms for chronic arm edema following breast carcinoma treatment. A review of causes of lymphedema is presented plus the traditional pathophysiology of breast carcinoma related lymphedema (postmastectomy edema; PME). A summary of recent research that explored capillary filtration as a surrogate for lymph flow in the steady state is presented. A reduced interstitial protein concentration (relative to plasma) argues against lymphatic obstruction. Evidence exists that total arm blood flow (in some patients) and vascular bed size are increased in PME. The primary insult to the axillary lymphatic system by surgery and radiotherapy presumably is the root cause of PME; however, there is strong evidence to suggest that hemodynamic factors are contributory to the chronic swelling.


Cell death pathways and autophagy in the central nervous system and its involvement in neurodegeneration, immunity and central nervous system infection: to die or not to die--that is the question.
Death rules our lives. In this short paper, we summarize new insights into molecular mechanisms of neurodegeneration. Here we review the most important processes of cell death: apoptosis and oncosis. We focus on autophagy, which is pivotal for neuronal homeostasis, in the context of neurodegeneration, infection and immunity. Its dysfunction has been linked to several neurodegenerative diseases such as Parkinson's, Huntington's and Alzheimer's diseases. Our understanding is still incomplete, but may highlight attractive new avenues for the development of treatment strategies to combat neurodegenerative diseases.


The sequences of genes bordering oriT in the enterotoxin plasmid P307: comparison with the sequences of plasmids F and R1.
The nucleotide sequences of the enterotoxin plasmid P307 transfer genes traM, finP, traJ, traY, and gene 19 were determined. Gene 19 is highly conserved; its product is very similar to that coded by the F and R1 plasmids. The TraM protein is similar in P307 and in F; the R1 sequence shows differences in the 40 N-terminal amino acids. The traJ product is very different in P307, F, and R1. The traY gene from P307, which in F is almost twice as long, is similar in size to that from R1. The finP RNA shows a high degree of homology with that from R1 and F, except for the two loop regions where base changes were observed. The genes coding for proteins, except traY, could be expressed in minicell- and T7 promoter-driven expression systems, whereas traJ and gene 19 could be expressed only in the latter system.


Decoding continuous limb movements from high-density epidural electrode arrays using custom spatial filters.
Our goal was to identify spatial filtering methods that would improve decoding of continuous arm movements from epidural field potentials as well as demonstrate the use of the epidural signals in a closed-loop brain-machine interface (BMI) system in monkeys. Eleven spatial filtering options were compared offline using field potentials collected from 64-channel high-density epidural arrays in monkeys. Arrays were placed over arm/hand motor cortex in which intracortical microelectrodes had previously been implanted and removed leaving focal cortical damage but no lasting motor deficits. Spatial filters tested included: no filtering, common average referencing (CAR), principle component analysis, and eight novel modifications of the common spatial pattern (CSP) algorithm. The spatial filtering method and decoder combination that performed the best offline was then used online where monkeys controlled cursor velocity using continuous wrist position decoded from epidural field potentials in real time. Optimized CSP methods improved continuous wrist position decoding accuracy by 69% over CAR and by 80% compared to no filtering. Kalman decoders performed better than linear regression decoders and benefitted from including more spatially-filtered signals but not from pre-smoothing the calculated power spectra. Conversely, linear regression decoders required fewer spatially-filtered signals and were improved by pre-smoothing the power values. The 'position-to-velocity' transformation used during online control enabled the animals to generate smooth closed-loop movement trajectories using the somewhat limited position information available in the epidural signals. The monkeys' online performance significantly improved across days of closed-loop training. Most published BMI studies that use electrocorticographic signals to decode continuous limb movements either use no spatial filtering or CAR. This study suggests a substantial improvement in decoding accuracy could be attained by using our new version of the CSP algorithm that extends the traditional CSP method for use with continuous limb movement data.


Advances in Regional Vascular Injection Techniques for the Delivery of Stem Cells to Musculoskeletal Injury Sites.
Vascular injections of stem cells are a pertinent alternative to direct intralesional injections when treating multiple or extensive lesions or with lesions impossible to reach directly. Extensive research using stem cell tracking has shown that intra-arterial injections without the use of a tourniquet should be preferred over venous or arterial regional limb perfusion techniques using a tourniquet. The median artery is used for the front limbs and the cranial tibial artery for the hind limbs. Proper efficacy studies are still lacking but early clinical work seems promising.


Enhancing effects of food components on the production of interferon β from animal cells suppressed by stress hormones.
In today's 'modern' society, no one can escape from the stresses of daily life. Stress stimulates the secretion of stress hormones (e.g. cortisol or noradrenaline) which generally suppress the immune response system, thus rendering the body vulnerable to infectious diseases and cancer. Therefore finding anti-stress food components, which diminish and/or inhibit the stress related suppression of the immune response system would be helpful in maintaining and promoting the health of the human population. Here we established a screening system for anti-stress substances using the cultured human cell line MG-63. The production of interferon-β (IFN-β) by MG-63 cells super-induced by Poly (I): Poly (C) was shown to decrease in a dose dependent manner upon the addition of 0.01-10 μg/ml of cortisol or noradrenaline (NA). 1,2-Diacylglycerol (DG) was demonstrated to abrogate this suppression. Lipid from the fermented milk, kefir, also inhibited the influence of cortisol. Kefiran, a polysaccharide secreted from L. kafiranofasiens GKL-28 diminished the cortisol or NA influenced IFN-β production. But phosphatidylcholine had no significant effect in this system. These results suggest that DG, lipids from kefir and kefiran may be equated as anti-stress food component.Abbreviations DG - diacylglycerol; IFN-β - interferon-β; NA - noradrenaline; PC - phosphatidylcholine; Poly (I):Poly (C) - polyinosinic polycytidylic acid.


Medical supervision for contraception: too little or too much?
The need to provide medical supervision in contraceptive services is reviewed in the context of the situation existing in developing nations. The author contends that less rather than more medical supervision can be justified if one compares the relatively low incidence of complications from modern contraception with the inordinately high maternal death rates from pregnancy and its complications in these same countries.


Quantitative splenic embolization possible: application of 8Spheres conformal microspheres in partial splenic embolization (PSE).
To investigate the safety and efficacy of 8Spheres in partial splenic embolization. To explore the possibility of accurate control of splenic embolic volume by quantifying the number of microspheres used during PSE. The data of 179 patients who underwent PSE were collected. The patients were divided into two groups: 300-500 um microsphere group (N = 83) and 500-700 um microsphere group (N = 96). The spleen volume before PSE, infarct volume and infarct rate of the spleen after PSE, changes in peripheral blood cells after PSE, postoperative adverse events and incidence of infection were compared between the two groups. 300-500 um group vs 500-700 um group: postoperative spleen volume (cm3): 753.82 ± 325.41 vs 568.65 ± 298.16 (P = 0.008); spleen embolization volume (cm3): 525.93 ± 118.29 vs 630.26 ± 109.71 (P = 0.014); spleen embolization rate: 41.1 ± 12.3% vs 52.4 ± 10.1% (P = 0.021). Leukocytes and platelets were significantly increased after PSE in both groups; leukocyte, 1 month: 4.13 ± 0.91 vs 5.08 ± 1.16 (P = 0.026); 3 months: 4.08 ± 1.25 vs 4.83 ± 0.98 (P = 0.022); platelet, 1 month: 125.6 ± 20.3 vs 138.7 ± 18.4 (P = 0.019); 3 months: 121.8 ± 16.9 vs 134.3 ± 20.1 (P = 0.017). Incidence of abdominal pain after PSE, 72 (86.7%) vs 69 (71.9%), P = 0.027. The incidence of other adverse events and infections after PSE was not statistically different. PSE with 8Spheres is safe and effective. The use of 500-700 um microsphere for PSE can make the increase of peripheral blood cells more stable. Each vial of 8Spheres corresponds to a certain volume of splenic embolization, so it is possible to achieve quantitative embolization in PSE.


Intra-operative ultrasound assessment of the biliary tree during robotic cholecystectomy.
Image-guided assessment of bile ducts and associated anatomy during laparoscopic cholecystectomy can be achieved with intra-operative cholangiography (IOC) or laparoscopic ultrasound (LUS). Rates of robotically assisted cholecystectomy (RC) are increasing and herein we describe the technique of intra-corporeal biliary ultrasound during RC using the Da Vinci system. For intraoperative evaluation of the biliary tree during RC, in cases of suspected choledocholithiasis, the L51K Ultrasound Probe (Hitachi, Tokyo, Japan) is used. The extrahepatic biliary tree is scanned along its length, capitalising on the benefits of the full range of motion offered by the articulated robotic instruments and integrated ultrasonic image display using TileProTM software. Additionally, this technique avoids the additional time and efforts required to undock and re-dock the robot that would otherwise be required for selective IOC or LUS. The average time taken to perform a comprehensive evaluation of the biliary tree, from the hepatic ducts to the ampulla of Vater, is 164.1 s. This assessment is supplemented by Doppler ultrasound, which is used to fully delineate anatomy of the porta hepatis, and accurate measurements of the biliary tree and any ductal stones can be taken, allowing for contemporaneous decision making and management of ductal pathologies. Biliary tract ultrasound has been shown to be equal to IOC in its ability to diagnose choledocholithiasis, but with the additional benefits of being quicker and having higher completion rates. We have described our practice of using biliary ultrasound during robotically assisted cholecystectomy, which is ergonomically superior to LUS, accurate and reproducible.


Internet addiction and its association with quality of life in patients with major depressive disorder: a network perspective.
Depressive disorders and internet addiction (IA) are often comorbid. The aims of this study were to examine the network structure of IA in patients with major depressive disorders (MDD) and explore the association between IA and quality of life (QoL) in this population. This was a multicenter, cross-sectional survey. IA and QoL were assessed with the Internet Addiction Test (IAT) and the World Health Organization Quality of Life-brief version, respectively. Node expected influence (EI) was used to identify central symptoms in the network model, while the flow network of QoL was generated to examine its association with IA. A total of 1,657 patients with MDD was included. "Preoccupation with the Internet," "Job performance or productivity suffer because of the Internet," and "Neglect chores to spend more time online" were central symptoms. The symptom "Form new relationships with online users" had the strongest direct positive relation with QoL, while "Spend more time online over going out with others" and "Job performance or productivity suffer because of the Internet" had the strongest direct negative relations with QoL. Neglecting work caused by IA correlated with QoL, while making friends online appropriately was related to better QoL among MDD patients. Appropriate interventions targeting the central symptoms may potentially prevent or reduce the risk of IA in MDD patients.


Glutamatergic Projections from the Posterior Complex of the Anterior Olfactory Nucleus to the Amygdala Complexes.
Social buffering is a phenomenon where stress responses are ameliorated by an affiliative conspecific. Our previous findings suggest that the posterior complex of the anterior olfactory nucleus (AOP) is well positioned to participate in the neural mechanisms underlying social buffering. However, the lack of anatomical information prevents us from further estimating the role of the AOP. Here, we obtained anatomical information regarding the AOP in male rats. In Experiment 1 (n = 5), among 4',6-diamidino-2-phenylindole-positive cells in the AOP, the proportion of glutamic acid decarboxylase 67 (GAD67)-positive cells was 13.8% ± 1.2%. In Experiment 2 (n = 5), among the cells that were labeled by a retrograde tracer injected into the basolateral complex of the amygdala (BLA), the proportion of GAD67-positive cells was 18.6% ± 0.8%. In Experiment 3 (n = 5), we demonstrated the existence of cells that were labeled by the retrograde tracer injected into the posterior part of the medial amygdala (MeP), mostly into the ventral part of the MeP. In addition, the proportion of GAD67-positive cells among the tracer-labeled cells was 21.7% ± 1.7%. In Experiment 4 (n = 3), the retrograde tracers were injected into the BLA and MeP, mostly into the ventral part of the MeP. The proportion of double-labeled cells among the tracer-labeled cells was 2.1% ± 1.2%. Taken together, these results suggest that the AOP is predominantly composed of glutamatergic neurons. In addition, the AOP sends mutually independent glutamatergic-predominant projections to the BLA and MeP.


Spatial distribution of the adaptation field of the surround response mechanisms in type X cat retinal ganglion cells.
The surround response mechanism in on-center X-cells in cat retina was found to be bimodally distributed and weak or nonexistent in the receptive field middle. An on-inhibition measure was used to assess surround mechanism gain.


Mitogenome of Tolypocladium guangdongense.
Tolypocladium guangdongense is a high-value edible fungus with various medicinal and food safety properties. However, its evolutionary and genetic information is still limited. Mitochondrial genomes are potential models for molecular evolution and phylogenetic studies. In this study, we sequenced the complete mitogenome of T. guangdongense, demonstrating circular sequence of 46,102 bp, containing 14 standard protein-coding genes (PCGs), 2 ribosomal RNA subunit genes, and 28 tRNA genes. Phylogenetic analysis based on mitochondrial genes indicated that T. guangdongense was clustered into the Tolypocladium genus with high support value, based on the core PCG dataset. In addition, rps3 is also a suitable marker in the phylogenetic analysis in Hypocreales. Gene rearrangement analysis indicated that the gene order of PCGs was highly consistent in Hypocreales, and tRNA rearrangement events occurred in most species of Hypocreales; however, the rearrangement rates were not taxonomically correlated. Divergence time estimation based on the old fossil record and previous reports revealed that T. guangdongense originated approximately in the middle Cenozoic (42 Mya, 95% highest posterior density interval: 43-116) with the Tolypocladium genus differentiation. Our results provided more mitogenomic information of T. guangdongense and shed new insights into evolution of the Tolypocladium genus. KEY POINTS: • The general and unique features of T. guangdongense mitogenome are firstly reported. • Phylogenetic analysis further verified the taxonomic status of T. guangdongense. • Divergence time estimation provides more evolutionary information of T. guangdongense.


Reticulocytosis, increased mean red cell volume, and greater blood viscosity in altitude susceptible compared to altitude resistant rats.
We have identified two strains (H and M) of Sprague-Dawley rat with markedly different susceptibilities and cardiopulmonary responses to chronic hypobaria. To further characterize factors responsible for these differing cardiopulmonary responses to chronic hypobaria, the present study examined differences in hematologic responses between the strains and assessed the contribution of differences in blood viscosity to differences in pulmonary vascular resistance. Following a 4-5 week exposure to simulated high altitude (0.5 atm), hemoglobin, hematocrit, mean red cell volume, and reticulocyte count were all increased in the susceptible H compared to the resistant M rats, whereas red blood cell counts were similar. Sea level controls manifested no differences. Blood viscosity, measured in a capillary viscometer, was 53% greater in chronically hypoxic H than in M rats, and plasma viscosities were similar. Blood from high altitude H rats increased pulmonary vascular resistance more than blood from high altitude M rats when perfused into lungs isolated from high altitude rats of either strain. In conclusion, high altitude H rats have an increased population of immature red cells, leading to a greater mean red cell volume and hematocrit than in high altitude M rats. These hematologic differences contribute to the the increased blood viscosity and greater pulmonary vascular resistance of H compared to M rats after 4 weeks' high altitude exposure.


Auditory hair cell-afferent fiber synapses are specialized to operate at their best frequencies.
Auditory afferent fiber activity is driven by high-fidelity information transfer from the sensory hair cell. Presynaptic specializations, posited to maintain fidelity, are investigated at synapses with characteristic frequencies of 120 Hz and 320 Hz. Morphological data indicate that high-frequency cells have more synapses and higher vesicle density near dense bodies (DBs). Tracking vesicular release via capacitance changes identified three overlapping kinetic components of release corresponding to morphologically identified vesicle pools. High-frequency cells released faster; however, when normalized to release site number, low-frequency cells released faster, likely due to a greater Ca2+ load per synapse. The Ca(2+)-dependence of release was nonsaturating and independent of frequency, suggesting that release, not refilling, was rate limiting. A model of release derived from vesicle equilibration between morphologically defined pools reproduced the capacitance data, supporting a critical role in vesicle trafficking for DBs. The model suggests that presynaptic specializations enable synapses to operate most efficiently at their characteristic frequencies.


Pressure changes in spinal canal and evaluation of spinal cord injuries in spinal section subjected to impact.
To observe pressure changes in the spinal canal of the vertebrarium subjected to impact. From the point of view of impact, pressure changes and spinal cord injuries, the relationship between the type of spinal fracture and the severity of spinal cord injuries were analyzed and some experimental data were provided for early evaluation of severity of spinal cord injuries. An experimental model of spinal burst fracture was made with Type BIM-I bio-impact machine and techniques of high velocity vertical loading in static pattern and stress shielding were adopted. Vertebral sections T10-L4 taken from fresh cadavers were impacted and pressure changes in the spinal canal were observed. The types and severity of spinal fracture were studied with gross and radiography examination. Great positive pressure wave (wave A) in the spinal canal of the 4 vertebral specimens with burst fracture was recorded. The peak value of pressure was correlated with the severity of posterior column injuries. Generally, the peak value of pressure was low in the samples with posterior column injuries, but high in the samples without injuries. The predominant features of fractures were burst fractures of vertebral body and severe destruction of the skeletal and fiber structure of the spinal canal. Positive and negative pressure waves (wave B) were recorded in 2 vertebral samples in which no significant abnormal changes were found by radiography examination, however, a little liquid effusion in the vertebral body was found by gross examination. The type of pressure wave in the spinal canal is related to the deformation or the destruction of the spinal canal structure. The peak value of the pressure is non-linearly related to the obstruction in the spinal canal, but related to posterior column injuries.


Native tissue repair of cardinal/uterosacral ligaments cures overactive bladder and prolapse, but only in pre-menopausal women.
The aim of this article was to study the effect of native tissue cardinal/uterosacral ligament repair on overactive bladder (OAB) and pelvic organ prolapse (POP). Inclusion criteria included decrease of urge symptoms following insertion of a gauze tampon in the posterior fornix of vagina ('simulated operation'). Exclusion criteria included SUI, POP grades 3-4. The surgery consisted of plication of cardinal/uterosacral ligaments. Post-operative assessment was performed at3, 6, 12 and 18 months after surgery and included evaluation by stage of prolapse, Urinary Distress Inventory Short Form 6 (UDI-6), Overactive Bladder Questionnaire (OAB-q), Pelvic Floor Impact Questionnaire- Short Form 7 (PFIQ-7), and International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-SF) questionnaires and voiding diary. At 3 months, cure rates for frequency, urgency, nocturia and prolapse were comparable. By the 6-month review, catastrophic failure commenced in the postmenopausal group, parallel for all pa-rameters, starkly contrasting with premenopausal group. At 18 months, % cure rates for pre-menopausal (post-menopausal in brackets) were 79.6 (15.4) for POP, 67.3 (20.5) for urgency, 87.7 (20.5) for nocturia and 59.2 (15.4) for frequency. We hypothesize the stepwise parallel recurrence of POP and symptoms in the menopausal group was a consequence of collagen deficiency in the plicated ligaments. Nevertheless, plication of uterosacral-cardinal ligament complex is simple, inexpensive, effective, especially applicable pre-menopausally for POP and as an alternative treatment option in that difficult group of pre-menopausal women who have major OAB/nocturia symptoms but only minimal prolapse.


The accuracy in the control of the apical extent of rotary canal instrumentation using Root ZX II and ProTaper instruments: an in vivo study.
The accuracy of Root ZX II (J. Morita, Kyoto, Japan) to control the apical extent of rotary canal instrumentation in vivo was assessed. Twenty-four premolars with a single canal were selected. The roots were divided in two groups according to the calibration of the automatic apical reverse mechanism of Root ZX II, set at levels 1 and 2. After endodontic access, the preparation was performed with ProTaper instruments (Dentsply Maillefer, Ballaigues, Switzerland) connected to the device. Afterwards, the last file used was introduced into the canal and fixed in place with acrylic resin. The teeth were extracted and ground until exposure of the file. The distance from the instrument tip to the apical foramen was obtained. The percentage of acceptable measurements and the difference between means were submitted to statistical analysis. The differences of setting the reverse mechanism at 1 and 2 were not statistically significant. Both settings were not accurate for determining and controlling the apical extent of rotary instrumentation.


An efficient RNA-cleaving DNA enzyme can specifically target the 5'-untranslated region of severe acute respiratory syndrome associated coronavirus (SARS-CoV).
The worldwide epidemic of severe acute respiratory syndrome (SARS) in 2003 was caused by a novel coronavirus called SARS-CoV. We report the use of DNAzyme (catalytic DNA) to target the 5'-untranslated region (5'UTR) of a highly conserved fragment in the SARS genome as an approach to suppression of SARS-CoV replication. A mono-DNA enzyme (Dz-104) possessing the 10-23 catalytic motif was synthesized and tested both in vitro and in cell culture. SARS-CoV total RNA was isolated, extracted from the SARS-CoV-WHU strain and converted into cDNA. We designed a RNA-cleaving 10-23 DNAzyme targeting at the loop region of the 5'UTR of SARS-CoV. The designed DNAzyme, Dz-104, and its mutant version, Dz-104 (mut), as a control consist of 9 + 9 arm sequences with a 10-23 catalytic core. In vitro cleavage was performed using an in vitro transcribed 5'UTR RNA substrate. A vector containing a fused 5'UTR and enhanced green fluorescent protein (eGFP) was co-transfected with the DNAzyme into E6 cells and the cells expressing eGFP were visualized with fluorescence microscopy and analyzed by fluorescence-activated cell sorting (FACS). Our results demonstrated that this DNAzyme could efficiently cleave the SARS-CoV RNA substrate in vitro and inhibit the expression of the SARS-CoV 5'UTR-eGFP fusion RNA in mammalian cells. This work presents a model system to rapidly screen effective DNAzymes targeting SARS and provides a basis for potential therapeutic use of DNA enzymes to combat the SARS infection.


Factors influencing the excretion and relative physiological availability of pethidine in man.
Factors influencing the urinary excretion of pethidine, norpethidine and pethidine N-oxide have been examined. The proportion of a dose of pethidine excreted unchanged or as norpethidine depends on the urinary pH and the route of administration. Older people appear to metabolize more of the drug and therefore excrete less unchanged pethidine. The rate of excretion of pethidine in acid urine is directly proportional to the plasma pethidine concentration and under these conditions the relative physiological availability of pethidine has been determined. It has not been possible to explain variations in the amount of pethidine excreted as the N-oxide.


Computer-aided design and property prediction of novel insensitive high-energy heterocycle-substituted derivatives of cage NNNAHP.
A series of new derivatives of cage 2,4,6,8,10,12,13,14,15-nanonitro-2,4,6,8,10,12,13,14, 15-nanoazaheptacyclo[220.127.116.11,11,15,9] pentadecane (NNNAHP) were designed by incorporating combination of heterocyclic and non-heterocyclic substituents and studied by using density functional theory. The results indicate that the -tetrazine and -N(NO2)2 are very beneficial structural fragments to increase their heat of formation. The introduction of different heterocyclic and non-heterocyclic groups can produce different effects on different properties: large densities (1.88-2.06 g cm-3), high detonation velocities (8.17-9.83 km s-1), excellent detonation pressures (30.55-46.02GPa), and outstanding heat of detonations (1169.80-1637.19 cal g-1). The analysis of bond dissociation energy values show that the N(cage)-NO2 is the weakest bond, and it may turn into a trigger bond during detonation. Almost all the derivatives are thermally more stable than the parent compound. All the substituted derivatives are insensitive as compared with the parent compound. According to excellent detonation properties, high thermal stability, and good insensitivity, 10 compounds may be chosen as potential high-energy density compounds.


Biomechanical investigation into the role of the periodontal ligament in optimising orthodontic force: a finite element case study.
This paper aimed to precisely locate centres of resistance (CRe) of maxillary teeth and investigate optimal orthodontic force by identifying the effective zones of orthodontic tooth movement (OTM) from hydrostatic stress thresholds in the periodontal ligament (PDL). We applied distally-directed tipping and bodily forces ranging from 0.075 N to 3 N (7.5 g to 300 g) onto human maxillary teeth. The hydrostatic stress was quantified from nonlinear finite element analysis (FEA) and compared with normal capillary and systolic blood pressure for driving the tissue remodelling. Two biomechanical stimuli featuring localised and volume-averaged hydrostatic stresses were introduced to describe OTM. Locations of CRe were determined through iterative FEA simulation. Accurate locations of CRes of teeth and ranges of optimal orthodontic forces were obtained. By comparing with clinical results in literature, the volume average of hydrostatic stress in PDL was proved to describe the process of OTM more indicatively. The optimal orthodontic forces obtained from the in-silico modelling study echoed with the clinical results in vivo. A universal moment to force (M/F) ratio is not recommended due to the variation in patients and loading points. Accurate computational determination of CRe location can be applied in practice to facilitate orthodontic treatment. Global measurement of hydrostatic pressure in the PDL better characterised OTM, implying that OTM occurs only when the majority of PDL volume is critically stressed. The FEA results provide new insights into relevant orthodontic biomechanics and help establish optimal orthodontic force for a specific patient.


Resistance training using a novel robotic walker for over-ground gait rehabilitation: a preliminary study on healthy subjects.
Strength training is an aspect of gait rehabilitation, which complements balance control and weight-bearing training. However, conventional strength training does not show positive gait outcomes, due to lack of task specificity. Therefore, the aims of this study were to investigate the effects of a resistance force applied at the center of mass (CoM) and to investigate whether this exercise can be used for effective task-specific gait training. Using a novel robotic walker, a consistent resistive force was applied to the CoM of subjects in the posterior direction. Eleven healthy subjects were instructed to walk under five walking conditions with increasing forces, based on each subject's body weight (BW), at 0, 2.5, 5, 7.5, and 10% BW. Joint kinematics and mean amplitude and frequency of electromyography signals from nine major muscles were measured. The application of resistance resulted in significantly increased flexion angles at ankle, knee, and hip joints. A large amount of motor unit activation with lower firing rates was found at knee and hip joints, indicating that this type of resistance training can improve muscular strength and endurance in a task-specific manner. The long-term effects of the resistance training on neurologically challenged patients will be investigated in the future.


Identification and validation of risk score model based on gene set activity as a diagnostic biomarker for endometriosis.
The enigmatic nature of Endometriosis (EMS) pathogenesis necessitates investigating alterations in signaling pathway activity to enhance our comprehension of the disease's characteristics. Three published gene expression profiles (GSE11691, GSE25628, and GSE7305 datasets) were downloaded, and the "combat" algorithm was employed for batch correction, gene expression difference analysis, and pathway enrichment difference analysis. The protein-protein interaction (PPI) network was constructed to identify core genes, and the relative enrichment degree of gene sets was evaluated. The Lasso regression model identified candidate gene sets with diagnostic value, and a risk scoring diagnostic model was constructed for further validation on the GSE86534 and GSE5108 datasets. CIBERSORT was used to assess the composition of immune cells in EMS, and the correlation between EMS diagnostic value gene sets and immune cells was evaluated. A total of 568 differentially expressed genes were identified between eutopic and ectopic endometrium, with 10 core genes in the PPI network associated with cell cycle regulation. Inflammation-related pathways, including cytokine-receptor signaling and chemokine signaling pathways, were significantly more active in ectopic endometrium compared to eutopic endometrium. Diagnostic gene sets for EMS, such as homologous recombination, base excision repair, DNA replication, P53 signaling pathway, adherens junction, and SNARE interactions in vesicular transport, were identified. The risk score's area under the curve (AUC) was 0.854, as indicated by the receiver operating characteristic (ROC) curve, and the risk score's diagnostic value was validated by the validation cohort. Immune cell infiltration analysis revealed correlations between the risk score and Macrophages M2, Plasma cells, resting NK cells, activated NK cells, and regulatory T cells. The risk scoring diagnostic model, based on pathway activity, demonstrates high diagnostic value and offers novel insights and strategies for the clinical diagnosis and treatment of Endometriosis.


hGC33-Modified and Sorafenib-Loaded Nanoparticles have a Synergistic Anti-Hepatoma Effect by Inhibiting Wnt Signaling Pathway.
Delivery of tumor-specific inhibitors is a challenge in cancer treatment. Antibody-modified nanoparticles can deliver their loaded drugs to tumor cells that overexpress specific tumor-associated antigens. Here, we constructed sorafenib-loaded polyethylene glycol-b-PLGA polymer nanoparticles modified with antibody hGC33 to glypican-3 (GPC3 +), a membrane protein overexpressed in hepatocellular carcinoma. We found that hGC33-modified NPs (hGC33-SFB-NP) targeted GPC3+ hepatocellular carcinoma (HCC) cells by specifically binding to GPC3 on the surface of HCC cells, inhibited Wnt-induced signal transduction, and inhibited HCC cells in G0/1 by down-regulating cyclin D1 expression, thus attenuating HCC cell migration by inhibiting epithelial-mesenchymal transition. hGC33-SFB-NP inhibited the migration, cycle progression, and proliferation of HCC cells by inhibiting the Ras/Raf/MAPK pathway and the Wnt pathway in tandem with GPC3 molecules, respectively. hGC33-SFB-NP inhibited the growth of liver cancer in vivo and improved the survival rate of tumor-bearing mice. We conclude that hGC33 increases the targeting of SFB-NP to HCC cells. hGC33-SFB-NP synergistically inhibits the progression of HCC by blocking the Wnt pathway and the Ras/Raf/MAPK pathway.


[Development of emergency pediatric services].
The survey is undertaken to analyze the problems of children's applications for emergency and urgent medical care. The basic data on the functioning of urgent care units of territorial children's polyclinics and emergency care stations are presented. The study findings indicate the legitimate character and expediency of a separate system of urgent and emergency medical care delivery for children at the prehospital stage.


SARS-CoV-2 antibodies among people with cystic fibrosis prior to the vaccination campaign: A seroprevalence study in two specialized centres in Northern Italy.
The prevalence of anti-SARS-CoV-2 antibodies in people with cystic fibrosis (CF) is largely unknown. We carried out a cross-sectional study between March and June 2021 with the aim of estimating the seroprevalence of anti-SARS-CoV-2 antibodies in two CF centres in Northern Italy. Total serum anti-SARS-CoV-2 (spike) antibodies levels were measured and values ≥0.8 U/mL were considered positive. Among 434 patients aged >12 years, 64 patients had a positive result (14.7%, 95% CI: 11.5-18.4), 36 (56.3%) without experiencing any COVID-19-related symptoms. Three out of 49 transplanted patients tested positive with an odds ratio for a positive result among transplanted as compared to non-transplanted patients of 0.35 (95% CI: 0.07-1.14). No significant differences were observed between sexes, age groups, socioeconomic status and lung disease severity. In conclusion, SARS-CoV-2 has infected a relatively high proportion of our patients but in most cases the infection was asymptomatic.


Energy drinks consumption in Italian adolescents: preliminary data of social, psychological and behavioral features.
The aim of this study was to investigate the prevalence of energy drink (ED) consumption and the associations with social, psychological and behavioral features among an Italian adolescent sample. A cross-sectional prevalence study of 450 Italian adolescents attending middle school was conducted. The Italian versions of the European Food Safety Authority's adolescent Energy Drinks Questionnaire and of the Depression and Anxiety in Youth Scale (DAYS) were administered to evaluate ED use and its psychological correlates. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using a logistic model to estimate the associations between ED consumption and socio-demographic characteristics, psychological factors and risky behaviors. The prevalence of ED consumers was 57%, of whom 49% used alcohol mixed with ED. A total of 9% exhibited high chronic consumption, 31% average chronic consumption and 8% high acute consumption. Males were significantly more likely to use ED (OR=2.7, 95% CI: 1.8-4.0, P=0.00) and to engage in high acute consumption (OR=4.0, 95% CI: 1.1-13.8, P=0.03). Regular smoking was associated with ED use (OR=3.4, 95% CI: 1.2-9.1, P=0.02). No relationship was observed between ED use and depression (OR=1.6, 95% CI: 0.9-3.0, P=0.10) and anxiety (OR=0.8, 95% CI: 0.5-1.4, P=0.44), although those who were depressed with a suggestive but not statistically significant increased risk of acute ED use (OR=2.7, 95% CI: 1.0-7.4, P=0.06). The prevalence of ED consumption among middle school Italian students was high and it was associated with another risky behavior, smoking, but not with anxiety or depression. About half of ED consumers used alcohol mixed with ED.


How to select optimal maintenance intravenous fluid therapy.
Hyponatraemia is the commonest electrolyte abnormality in hospitalized patients. If the plasma sodium concentration (P(Na)) declines to approximately 120 mM in <48 h, brain cell swelling might result in herniation, with devastating consequences. The volume and/or the composition of fluids used for intravenous therapy often contribute to the development of acute hyponatraemia. Our hypothesis is that the traditional calculation of the daily loss of insensible water overestimates this parameter, leading to an excessive daily recommended requirement for water. We offer suggestions to minimize the risk of iatrogenic hyponatraemia.


The possible pathogenesis of macular caldera in patients with North Carolina macular dystrophy.
This study provides a detailed description of a Chinese family with North Carolina macular dystrophy (NCMD) and explores its possible pathogenesis. Five individuals from a three-generation family underwent general ophthalmic examination, multi-imaging examinations and visual electrophysiology examinations when possible. Genetic characterization was carried out by target region sequencing and high-throughput sequencing in affected patients. Despite severe fundus changes, patients had relatively good visual acuity. Genetic analysis showed that affected patients had PRDM13 gene duplication and heterozygous mutations of the ABCA4 gene. Optical coherence tomography (OCT) showed an abnormal retinal pigment epithelium (RPE) layer in patients with grade 2 lesions, while the neurosensory retina was relatively normal. In grade 3 patients, RPE and choroid atrophy were greater than that of the neurosensory retina, showing concentric atrophy. RPE and choroidal atrophy were found to play an important role in the development of macular caldera.


Unusual presentation of cholelithiasis on T1-weighted MR imaging.
Cholelithiasis usually appears on magnetic resonance as a signal void contrasting with the high signal of surrounding bile. We describe the appearance of two intraluminal gallstones as high-signal areas on a heavily T1-weighted scan and, based on infrared spectroscopic analysis of the stones, believe the fatty-acid content of the stones accounts for this unusual result. Increased focal intraluminal signal on strongly T1-weighted sequences does not, therefore, preclude a diagnosis of cholelithiasis.


Detection of immune effects of the Mannheimia haemolytica gamma irradiated vaccine in sheep.
Exposure to gamma rays from cobalt 60 (Co60) can induce a complete inactivation of Mannheimia haemolytica. The inactivated bacterial pathogen is a potential vaccine candidate for immunization of ruminants such as sheep. The subcutaneous administration of irradiated vaccine in a two-dose regimen (4.0 × 109 colony forming unit (CFU) per dose) results in no mortality in any of the vaccinated sheep during immunization and after subsequent challenge of the live bacteria of the same strain of M. haemolytica. A significant rise in serum IgG titer, detected through ELISA, is observed after the passage of two weeks from the inoculation of the first dose whereas, the peak of the mean serum antibody titer occurred after two weeks of booster dose. The vaccination does not bring significant change to the IFN-γ levels in serum. The bacterial challenge of the vaccinated sheep does not induce a further seroconversion relative to serum antibody titer. In conclusion, the vaccinated sheep are protected by the elevated IgG titer and increased levels of IL-4 (Th-2 response) compared to the non-vaccinated sheep. Radiation technology can provide the opportunity for mass production of immunologically safe vaccines against animal and zoonotic diseases. Ethics Approval by the National Research Center Ethics Committee (Trial Registration Number (TRN) no 13,602,023, 13/5/2023) was obtained.


[Nuclear magnetic resonance study of the conformation in nucleotides, oligonucleotides, and their analogs. I. Conformation of adenosine-3',5'-cyclic phosphate and its analogs in aqueous solutions].
Conformation in aqueous solution of adenosine-3',5'-cyclophosphate, 8-(beta-aminoethylamino) adenosine-3',5'-cyclophosphate, 8-(beta-oxiethylamino) adenosine-3',5'-cyclophosphate, 8-(carboxymethylamino) adenosine-3',5'-cyclophosphate and their non-cyclic analogs has been studied by NMR spectroscopy. The conformational situation in the model of dynamic equilibrium of sin- and anti-states has been described on the basis of spinlattice relaxation times and temperature dependences of chemical shifts. Adenosine-3',5'-cyclophosphate has been demonstrated to exist mainly in anti-conformation while 8-substituted analogs -- in sin-conformation. Equilibrium constants have been calculated for the compounds under study.


Dioxidomolybdenum(VI) complex featuring a 2,4-di-fluoro-substituted amine bis-(phenolate) ligand.
Synthetic complexes containing a cis-[MoO2]2+ core are well-established models for the molybdenum co-factor (Moco). Here we report the crystal structure of such a model complex bearing a tetra-dentate amine bis-(phenolate) ligand with fluorine substituents on the phenolate rings, namely, [2,2'-({[2-(di-methyl-amino)-eth-yl]aza-nedi-yl}bis-(methyl-ene))bis-(4,6-di-fluoro-phenolato)]dioxidomolybden-um(VI)), [Mo(C18H18F4N2O2)O2]. Distortion from idealized octa-hedral symmetry about the Mo center is evident in the large O=Mo=O angle [108.54 (4)°] and the small N-Mo-Ophenolate angles [79.79 (4), 81.21 (3), 77.83 (3), and 84.59 (3)°]. The dihedral angle between the phenolate rings is 60.06 (4)°, and π-π stacking is observed between aromatic rings related by inversion (1 - x, 1 - y, 1 - z). The lower data-collection temperature of 150 K vs room-temperature data collection reported previously [KOWXIF; Cao et al. (2014 ▸). Transit. Met. Chem. 39, 933-937] and larger 2θ range for data collection (5.8-66.6° versus 6-54.96°) led to a structure with lower R 1 and ωR 2 values (0.019 and 0.049 vs 0.0310 and 0.0566 for KOWXIF). Comparison of the metrical parameters with KOWXIF suggests that this dataset offers a more realistic depiction of bonding within the MoVI=O moiety.


"Right diet for the right person": a focus group study of nutritionist-dietitians' perspectives on nutritional genomics and gene-based nutrition advice.
Advances in nutritional genomics are intended to revolutionize nutrition practice. A basic understanding of nutritional genomics among nutritionist-dietitians is critical for such advancements to occur. As a precedent to the development and integration of gene-based nutrition advice, this study aimed to assess hospital-based nutritionist-dietitians' perceptions of nutritional genomics. A total of ten focus group discussions (FGDs) with sixty-one registered nutritionist-dietitians (RNDs) from hospitals in the National Capital Region (NCR), Philippines, were conducted from October to November 2019. Data were collected using a pretested semistructured discussion guide, and thematic analysis was subsequently performed. Diverging perceptions about nutritional genomics were noted among the FGD participants. Five themes emerged relating to the enablers and barriers of gene-based nutrition advice: training and capacity building, the extent of information to be disclosed, cost, ethical considerations, and government support. Themes related to the desired features of the gene-based nutrition advice included being consent-driven, cost-effective, technology-oriented, and guided by standards. The results of this study suggest that training and continued learning will equip RNDs to provide nutrition advice based on genetic information. However, other factors, such as cost and ethical considerations, are critical dimensions that need to be acknowledged and addressed before integrating gene-based advice into nutrition practice.


Optineurin modulates the maturation of dendritic cells to regulate autoimmunity through JAK2-STAT3 signaling.
Optineurin (OPTN) has important functions in diverse biological processes and diseases, but its effect on dendritic cell (DC) differentiation and functionality remains elusive. Here we show that OPTN is upregulated in human and mouse DC maturation, and that deletion of Optn in mice via CD11c-Cre attenuates DC maturation and impairs the priming of CD4+ T cells, thus ameliorating autoimmune symptoms such as experimental autoimmune encephalomyelitis (EAE). Mechanistically, OPTN binds to the JH1 domain of JAK2 and inhibits JAK2 dimerization and phosphorylation, thereby preventing JAK2-STAT3 interaction and inhibiting STAT3 phosphorylation to suppress downstream transcription of IL-10. Without such a negative regulation, Optn-deficient DCs eventually induce an IL-10/JAK2/STAT3/IL-10 positive feedback loop to suppress DC maturation. Finally, the natural product, Saikosaponin D, is identified as an OPTN inhibitor, effectively inhibiting the immune-stimulatory function of DCs and the disease progression of EAE in mice. Our findings thus highlight a pivotal function of OPTN for the regulation of DC functions and autoimmune disorders.


Effect of pH, sulphate concentration and total organic carbon on mercury accumulation in sediments in the Volta Lake at Yeji, Ghana.
In this study, pH, total organic carbon, sulphate concentration and mercury concentrations of sediment samples from the Volta Lake at Yeji in the northern part of Ghana were determined. The results indicate that pH ranged from 6.32 to 8.21, total organic carbon ranged from 0.17 to 3.02 g/kg and sulphate concentration from 10.00 to 57.51 mg/kg. Total mercury concentrations ranged from 32.61 to 700 ng/g which is below the International Atomic Energy Agency recommended value of 810 ng/g. Humic substance-bound mercury ranged from 81.15 to 481.31 mg/kg in sediments and its two fractions existed as humic acid-bound mercury > fulvic acid-bound mercury with the ratio of humic substance-bound mercury to fulvic acid-bound mercury as 1.62 on the average. Humic substance-bound mercury and the two fractions fulvic acid-bound mercury and humic substance-bound mercury in sediments were favorably determined and found to correlate significantly positive with total organic carbon (r = 0.538) and total mercury (r = 0.574). However, there were poor correlations between SO(4) (2-) concentrations and humic substance-bound mercury (r = -0.391) as well as the two fractions; fulvic acid (r = -0.406) and humic acid (r = -0.381). By assuming that methyl mercury is mostly formed in sediments, these significant relations suggest that the efficiency of mercury being methylated from a given inorganic form depends on the amount, and most likely biochemical composition of total organic carbon in the lake sediment but not the SO(4) (2-) concentration.


Prevention and control of influenza. Role of vaccine.
A major component in the prevention and control of influenza should be the use of killed influenza vaccines. These vaccines became possible after the first discovery of human strains of influenza virus in the 1930s. The ensuing decades have seen marked improvement in the available inactivated vaccines. Current vaccines have excellent reliability and assured potency, and they contain the proper antigens to match the frequent changes in circulating influenza viruses. Killed vaccines work by inducing serum antibodies against the hemagglutinin and neuraminidase of the vaccine strains, with sufficient antibodies ensuring protection against infection. The antibody responses to current vaccines appear to be adequate in all age groups. Although antibody responses are depressed in patients receiving chemotherapy or immunosuppressants, current vaccines do provide protection for most populations. Vaccines prevent the manifestations of disease by about 30 to 70 percent in all populations, and they reduce deaths in high-risk individuals by about 60 to 87 percent. Local adverse reactions to vaccine are quite common, but not severe. Fever, also somewhat common, usually does not last beyond 48 hours. Neurologic complications have not been observed since the use of the swine influenza vaccine of 1976. Killed vaccines should be given annually in the fall, but they can be given up to and during an outbreak. Target groups for vaccines have been defined by the Centers for Disease Control. In recent years, these groups have included physicians and nurses who give care to patients at risk for complications of influenza.


Molecular analysis of the Rett syndrome using cDNA synapsin I as a probe.
A cDNA encoding for rat synapsin I, a neuron-specific protein localized on the cytoplasmic surface of synaptic vesicles and probably involved in the regulation of neurotransmitter release from nerve terminals, has been used to map the human gene to the short arm of the X chromosome. We have screened, using this cDNA, the DNAs of six unrelated girls with the Rett Syndrome (RS) to test the hypothesis that mutations of the human synapsin I gene might cause RS. We found no alterations at the synapsin I (Syn I) locus in the vicinity of the probe sequence.


Imaging Features of the Whole Uterus Volume CT Perfusion and Influence Factors of Blood Supply: A Primary Study in Patients with Cervical Squamous Carcinoma.
To explore the imaging features of whole uterus volume CT perfusion (vCTP) and the influence factors of blood supply in cervical squamous carcinoma (CSC). vCTP was performed on a 640-slice computed tomography system in 43 patients with CSC diagnosed by biopsy, and 24 cases of them underwent magnetic resonance imaging. The size of the tumor was measured on vCTP and magnetic resonance (MR) images. Perfusion parameters, including arterial blood flow (AF), blood volume, and permeability surface (PS), were measured by two radiologists, using interclass correlation coefficient to evaluate the interobserver reliability. The difference of tumor size and perfusion data was analyzed by paired t test and rank sum test. The correlation of perfusion parameters with some factors was analyzed by Pearson or Spearman correlation analysis. Tumor sizes were not significantly different between vCTP and MR images. The interclass correlation coefficient of each parameter was 0.818-0.945. The AF value of CSC was significantly higher than normal uterine body, and the blood volume and PS values of CSC were not statistically different compared with those of normal uterine body. There was no significant difference in AF value of CSC among different FIGO stages and pathological grades. The AF and PS values of CSC were negatively correlated with the age of the patients. The vCTP could accurately shows the size of the CSC with use of MR as the reference standard, and its perfusion parameters have good measurement stability; the CSC was hypervascular, but this trend was less pronounced in older women.


Isolated skull fractures: trends in management in US pediatric emergency departments.
Previous studies have suggested that children with isolated skull fractures are at low risk of requiring neurosurgical intervention, suggesting that admission to the hospital may not be necessary in many instances. We seek to evaluate current practice for children presenting to the emergency department (ED) for isolated skull fractures in US children's hospitals. We conducted a retrospective multicenter cross-sectional study of children younger 19 years with a diagnosis of isolated skull fracture who were evaluated in the ED from 2005 to 2011, using the Pediatric Health Information System database. The primary outcome measure was the rate of hospital admission. Secondary outcomes were any neurosurgical procedure during hospitalization, repeated neuroimaging, duration of hospitalization, and cost of care. We identified 3,915 patients with isolated skull fractures, of whom 60% were male patients; 78% were hospitalized. Of hospitalized children, 85% were discharged within 1 day and 95% were discharged within 2 days. During hospitalization, 47 patients received repeated computed tomography imaging and 1 child required a neurosurgical procedure. Hospital costs were more than triple for hospitalized patients compared with patients discharged from the ED ($2,064 versus $619). Most children treated in EDs of US children's hospitals with isolated skull fractures are hospitalized. The rate of neurosurgical intervention is very low. A better understanding of current practice is necessary to assess whether these admissions are warranted or not.


Emotional salience changes the focus of spatial attention.
The interaction of emotional stimulus processing and attentional mechanisms has become a topic of intensive investigation. The present study combined aversive conditioning with a spatial attention paradigm that by simultaneously recording event-related potentials (ERPs) allowed for accessing the distribution of auditory spatial attention. In an initial conditioning phase, seven spatial locations (conditioned stimuli; CS-) were associated with an emotionally neutral and one additional location (CS+) with an emotionally aversive sound (US). Four locations were in the left and the four remaining locations were in the right hemifield. During the testing phase, either frequent single bursts of noise or infrequent double noise bursts were presented in a random sequence from these eight locations. Task of the participants was to attend to the most leftward (in half of the blocks) or the most rightward location (other half of the blocks) in order to press a button to any deviant sound at that location. Spatial attention elicited the well-known increased fronto-centrally distributed negativity in the ERPs. The presence of an aversively conditioned location in the vicinity of the spatially attended location resulted in a broadening of the attentional focus at processing stages as early as 100 ms after stimulus onset. These results suggest that emotional and attentional processing interact at early stages of stimulus processing and change sensory processing of environmental input.


Detection and Diagnostic Utilization of Cellular and Cell-Free Tumor DNA.
Because cancer is caused by an accumulation of genetic mutations, mutant DNA released by tumors can be used as a highly specific biomarker for cancer. Although this principle was described decades ago, the advent and falling costs of next-generation sequencing have made the use of tumor DNA as a biomarker increasingly practical. This review surveys the use of cellular and cell-free DNA for the detection of cancer, with a focus on recent technological developments and applications to solid tumors. It covers (a) key principles and technology enabling the highly sensitive detection of tumor DNA; (b) assessment of tumor DNA in plasma, including for genotyping, minimal residual disease detection, and early detection of localized cancer; (c) detection of tumor DNA in body cavity fluids, such as urine or cerebrospinal fluid; and (d) challenges posed to the use of tumor DNA as a biomarker by the phenomenon of benign clonal expansions.


Glycyrrhizin surface-modified chitosan nanoparticles for hepatocyte-targeted delivery.
The aim of the present work was to investigate the potential utility of chitosan nanoparticles surface modified with glycyrrhizin (CS-NPs-GL) as new hepatocyte-targeted delivery vehicles. For this purpose, chitosan nanoparticles (CS-NPs) were prepared previously by ionic gelation process and glycyrrhizin was oxidized by sodium periodate to be conjugated to the surface of CS-NPs. The CS-NPs-GL obtained were first characterized for their morphology, particle size, zeta potential, association efficiency and in vitro release of adriamycin (ADR), using as a model drug. The nanoparticles were also labeled with rhodamine B isothiocyanate and their interaction with rat hepatocytes was examined by flow cytometry (FCM) and confocal laser microscopy (CLSM). The spherical nanoparticles prepared with oxidized GL/CS ratio of 0.14:1 (w/w) were in the 147.2nm size range, and exhibited a positive electrical charge (+9.3mV), and associated ADR quite efficiently (association efficiency: 91.7%) and showed lower extent of release (28% over 72h) in vitro. FCM and CLSM studies showed that CS-NPs-GL were preferentially accumulated in hepatocytes and the cellular uptake amount were 4.9 times more than that in hepatic nonparenchymal cells, and the uptake process was dependent on incubation time and dose of nanoparticles, which indicated that the internalization of these nanoparticles into hepatocytes was mostly mediated by a ligand-receptor interaction. In conclusion, CS-NPs-GL as a promising hepatocyte-targeted delivery carrier holds promise for further effective studies.


The growth, lipid and hydrocarbon production of Botryococcus braunii with attached cultivation.
The green alga Botryococcus braunii is regarded as a potential source of renewable fuel due to its high lipid and hydrocarbon contents. However, the slow growth rate damaged its feasibility for biofuel production. In this study, a novel method of 'attached cultivation' was introduced to incubate B. braunii FACHB 357 (B race). A high biomass productivity of 6.5 gm(-2)d(-1) was achieved in single layer attached system at early stage of cultivation. At day 10, the biomass, lipid and hydrocarbon productivities were 5.5, 2.34 and 1.06 gm(-2)d(-1), respectively. Under nitrogen starvation condition, both of the contents of lipid and hydrocarbon were increased, whereas the profile of hydrocarbon kept almost unchanged, while the content for oleic acid (18:1) increased and linolenic acid (18:3) decreased. With a multi-layer photobioreactor, a biomass productivity of 49.1 gm(-2)d(-1) or a photosynthetic efficiency of 14.9% (visible light) were obtained under continuous illumination of 500 μmolm(-2)s(-1).


Complex lifestyle intervention among inactive older adults with elevated cardiovascular disease risk and obesity: a mixed-method, single-arm feasibility study for RESTART-a randomized controlled trial.
Physical inactivity and obesity are global public health challenges. Older adults are important to target for prevention and management of disease and chronic conditions. However, many individuals struggle with maintaining increased physical activity (PA) and improved diet. This feasibility study provides the foundation for the RESTART trial, a randomized controlled trial (RCT) to test a complex intervention to facilitate favourable lifestyle changes older adults can sustain. The primary objective of this study was to investigate study feasibility (recruitment, adherence, side-effects, and logistics) using an interdisciplinary approach. This 1-year prospective mixed-method single-arm feasibility study was conducted in Tromsø, Norway, from September 2017. We invited by mail randomly selected participants from the seventh survey of the Tromsø Study (2015-2016) aged 55-75 years with sedentary lifestyle, obesity, and elevated cardiovascular risk. Participants attended a 6-month complex lifestyle intervention program, comprising instructor-led high-intensive exercise and nutritionist- and psychologist-led counselling, followed by a 6-month follow-up. All participants used a Polar activity tracker for daily activity monitoring during the intervention. Participants were interviewed three times throughout the study. Primary outcome was study feasibility measures. We invited potential participants (n=75) by mail of which 27 % (n=20) agreed to participate. Telephone screening excluded four participants, and altogether 16 participants completed baseline screening. The intervention and test procedures of primary and secondary outcomes were feasible and acceptable for the participants. There were no exercise-induced injuries, indicating that the intervention program is safe. Participants experienced that the dietary and psychological counselling were delivered too early in the intervention and in too close proximity to the start of the exercise program. Minor logistic improvements were implemented throughout the intervention period. This study indicates that it is feasible to conduct a full-scale RCT of a multi-component randomized intervention trial, based on the model of the present study. No dropouts due to exercise-induced injury indicates that the exercises were safe. While minor improvements in logistics were implemented during the intervention, we will improve recruitment and adherence strategies, rearrange schedule of intervention contents (exercise, diet, and psychology), as well as improve the content of the dietary and behavioural counselling to maximize outcome effects in the RESTART protocol. ClinicalTrials.gov Identifier: NCT03807323 Registered 16 January 2019 - retrospectively registered.