Prevalence and molecular characterization of Giardia duodenalis in dairy cattle in Central Inner Mongolia, Northern China.
Giardia duodenalis is a gastrointestinal protozoan ubiquitous in nature. It is a confirmed zoonotic pathogen, and cattle are considered a source of giardiasis outbreaks in humans. This study aimed to evaluate the prevalence and multilocus genotype (MLG) of G. duodenalis in dairy cattle in Central Inner Mongolia. This study was based on the small subunit ribosomal RNA (SSU rRNA), glutamate dehydrogenase (gdh), triosephosphate isomerase (tpi), and beta-giardin (bg) genes of G. duodenalis. DNA extraction, polymerase chain reaction (PCR), and sequence analysis were performed on 505 dairy cattle fecal samples collected in 2021 from six sampling sites and four age groups in Central Inner Mongolia to determine the prevalence and MLG distribution of G. duodenalis. The PCR results of SSU rRNA revealed that the overall prevalence of G. duodenalis was 29.5% (149/505) and that the overall prevalence of the diarrhea and nondiarrhea samples was 31.5% (46/146) and 28.5% (103/359), respectively; the difference was not significant (p > 0.05). SSU rRNA sequence analysis revealed that G. duodenalis assemblage E (91.1%, 133/146) was primarily detected and that assemblage A (8.9%, 13/146) was detected in 13 samples. The G. duodenalis-positive samples were PCR amplified and sequenced for gdh, tpi, and bg, from which 38, 47, and 70 amplified sequences were obtained, respectively. A combination of G. duodenalis assemblages A and E were detected in seven samples. Multilocus genotyping yielded 25 different assemblage E MLGs, which formed six subgroups. To the best of our knowledge, this is the first report regarding G. duodenalis infection in dairy cattle in Inner Mongolia, China. This study revealed that Inner Mongolian cattle pose a risk of giardiasis transmission to humans and that the distribution of local cattle G. duodenalis assemblage E MLGs is diverse. The findings of this study can bridge the knowledge gap in the molecular epidemiological investigation of giardiasis in Central Inner Mongolia.


Childhood schizophrenia. A review and comparison with adult-onset schizophrenia.
Childhood schizophrenia versus childhood autism and the phenomenology, epidemiology, and premorbid characteristics of childhood schizophrenia are reviewed, as well as pregnancy and birth complications, electroencephalographic studies, biochemistry, and genetic factors of this disorder. Treatment considerations and follow-up studies are outlined.


Enhancement of polyhydroxybutyrate production by introduction of heterologous phasin combination in Escherichia coli.
Phasin is a surface-binding protein of polyhydroxyalkanoate (PHA) granules that is encoded by the phaP gene. As its expression increases, PHA granules become smaller, to increase their surface area, and are densely packed inside the cell, thereby increasing the PHA content. A wide range of PHA-producing bacteria have phaP genes; however, their PHA productivity differs, although they are derived from the cognate bacterial host cell. Modulating phasin expression could be a new strategy to enhance PHA production. This study aimed to characterize the effect of heterologous phasins on the reconstitution of E. coli BL21(DE3) and determine the best synergistic phaP gene combination to produce polyhydroxybutyrate (PHB). We identified novel phasins from a PHB high-producer strain, Halomonas sp. YLGW01, and introduced a combination of phaP genes into Escherichia coli. The resulting E. coli phaP1,3 strain had enhanced PHB production by 2.9-fold, leading to increased cell mass and increased PHB content from 48 % to 65 %. This strain also showed increased tolerance to inhibitors, such as furfural and vanillin, enabling the utilization of lignocellulose biosugar as a carbon source. These results suggested that the combination of phaP1 and phaP3 genes from H. sp. YLGW01 could increase PHB production and robustness.


Analysis of the accuracy of determining average molecular weights of narrow polydispersity polymers by matrix-assisted laser desorption ionization time-of-flight mass spectrometry.
Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) can be used to determine number- and weight-average molecular weights of narrow polydispersity polymers. In this work, several possible sources of error in determining molecular weights of polymers with narrow polydispersity by MALDI-TOFMS are rigorously examined. These include the change in polymer distribution function, broadening or narrowing of the overall distribution, and the truncation of selected oligomer peaks within a distribution (i.e., the oligomer peaks at the high- and low-mass tails expected to be observed are not detected). These variations could be brought about by a limited detection sensitivity, background interference, and/or mass discrimination of oligomer analysis in MALDI-TOFMS. For narrow polydispersity polystyrenes, it is shown that by using an appropriate MALDI matrix and sample preparation protocol and a sensitive ion detection instrument, no systematic errors from these possible variations were detected within the experimental precision (0.5% relative standard deviation) of the MALDI method. It is concluded that MALDI mass spectrometry can provide accurate molecular weight and molecular weight distribution information for narrow polydispersity polymers, at least for polystyrenes examined in this work. The implications of this finding for polymer analysis are discussed.


Developing random forest based QSAR models for predicting the mixture toxicity of TiO2 based nano-mixtures to Daphnia magna.
During emission, TiO2 nanoparticles (NPs) might meet various chemicals, including metal ions and organic compounds in aquatic environments (e.g., surface water, sediments). At environmentally safe concentrations, combinations of both TiO2 NPs and those chemicals might cause cocktail effects (i.e., mixture toxicity) to aquatic organisms. Previous models such as concentration addition and independent action require dose-response curves of single components in the mixtures to predict the mixture toxicity. Structure-activity relationship (QSAR) models might predict the toxicity of nano-mixtures without dose-response curves of single components in the mixtures. However, current quantitative structure-activity relationship (QSAR) models are mainly focused on predicting cytotoxicity (i.e., cell viability) of heterogeneous metallic TiO2 nanoparticles (NPs) or mixtures of TiO2 NPs and four metal ions (Cu2+, Cd2+, Ni2+, and Zn2+). To minimize the experimental cost of nano-mixture risk assessment, in this study, we developed novel nano-mixture QSAR models to predict i) EC50 of 76 nano-mixtures containing TiO2 NPs and one of eight inorganic/organic compounds (i.e., AgNO3, Cd(NO3)2, Cu(NO3)2, CuSO4, Na2HAsO4, NaAsO2, Benzylparaben and Benzophenone-3), to Daphnia magna(D. magna), and ii) immobilization of D. magna exposed to one of 98 mixtures containing TiO2 NPs and one of eleven inorganic/organic compounds (i.e., AgNO3, Cd(NO3)2, Cu(NO3)2, CuSO4, Na2HAsO4, NaAsO2, Benzylparaben Benzophenone-3, Pirimicarb, Pentabromodiphenyl Ether and Triton X-100). The nano-mixture QSAR models were developed with mixture descriptors (Dmix) combing quantum descriptors of mixture components (e.g., TiO2 NPs and its partners) by using different machine learning techniques (i.e., random forest, neural network, support vector machine, and multiple linear regression). Nano-mixture QSAR models built with the random forest algorithm and proposed mixture descriptors exhibited good performance for predicting logEC50 (Adj.R2test = 0.955 ± 0.003, RMSEtest = 0.016 ± 0.002, and MAEtest = 0.008 ± 0.001) and immobilization (Adj.R2test = 0.888 ± 0.011, RMSEtest = 11.327 ± 0.730, and MAEtest = 5.933 ± 0.442). The models developed in this study were implemented in a user-friendly application for assessing the aquatic toxicity of TiO2 based nano-mixtures.


Systematic review of clinical trials of acupuncture-related therapies for primary dysmenorrhea.
Acupuncture-related therapies might be an effective intervention for primary dysmenorrhea. To evaluate the effects of acupuncture-related therapies for treating primary dysmenorrhea. A specified literature search was performed of the Cochrane Library, MEDLINE, EMBASE, CNKI, and CBM databases. All clinical controlled trials pertaining to acupuncture-related therapies for primary dysmenorrhea were included, and the quality of the trials was assessed. Two independent reviewers were responsible for data extraction and assessment. The original data of each trial were analyzed with software (Revman 4.2), but a meta-analysis could not be carried out because of the heterogeneity of the trials. Thirty randomized controlled trails (RCTs) and two controlled clinical trials (CCTs) were identified. Most of the trials were of low methodologic quality (six trials were Grade B and 26 trials were Grade C). Data analysis indicated that there were conflicting results regarding whether acupuncture-related therapies were more effective than control treatments. However, there was a small, methodologic sound trial of acupuncture which suggested that acupuncture was more effective than control groups (placebo acupuncture: WMD=-0.57 and 95% CI=-0.76-0.38; standard control: WMD=-.19 and 95% CI=-0.37-0.01; visitation control: WMD=-1.04 and 95% CI=-1.28-0.80). Because of low methodologic quality and small sample size, there is no convincing evidence for acupuncture in the treatment of primary dysmenorrhea. There is an urgent need for randomized, blinded, placebo-controlled trials to assess the effects of acupuncture.


Body mass index and primary chronic venous disease--a cross-sectional study.
This study aims to investigate whether overweight and obesity are related to the clinical (C) category of clinical, etiologic, anatomic and pathophysiologic (CEAP) classification of chronic venous disease (CVD). A cross-sectional study. The study was conducted in Serbia, in the year 2011. Men and women aged >18 years, consecutively coming to venous specialists because of venous problems in the legs, were included in the study. Patients demographic, anthropometric and clinical data were collected. For the analysis, univariate and multivariate logistic regressions were used. The study comprised 1116 subjects with primary CVD, 384 (34.4%) men and 732 (65.6%) women. Among them 464 (41.6%) were normal-weight patients (body mass index (BMI) < 25.0 kg m(-2)), 476 (42.7%) were overweight (BMI = 25.0-29.9 kg m(-2)) and 176 (15.8%) were obese (BMI ≥ 30.0 kg m(-2)). According to multivariate analysis, the CEAP C category of CVD was significantly more advanced in overweight and obese patients, the association being more pronounced in obese. Compared groups did not differ in the presence of venous reflux. In univariate analysis, venous obstruction was related to overweight and obesity but this association did not substantially affect the relationship between obesity and CEAP C categories of CVD. The CEAP C categories of CVD were significantly related to overweight and obesity, and this association was independent of age, sex and some other postulated risk factors.


Use of allografts in the management of ankle arthritis.
Reconstruction of articular cartilage defects of the tibiotalar joint remains a challenge. Although arthrodesis and total ankle arthroplasty are treatment options, we present fresh tibiotalar allografting as an alternative technique. The average age of 12 patients who underwent tibiotalar allografting was 43 years. The average follow-up was 21 months. All grafts healed at the host/donor interface. Complications included intraoperative fracture in one patient and graft collapse that required revision allografting in another. Most patients were relieved of preoperative pain and were satisfied with the procedure. Postoperative function was also significantly improved, based on questionnaire and physician assessment. Fresh tibiotalar allografting is an exciting and promising technique in the treatment of articular cartilage defects in young, active patients.


Light-driven hydrogen evolution catalyzed by a cobaloxime catalyst incorporated in a MIL-101(Cr) metal-organic framework.
A cobaloxime H2 evolution catalyst with a hydroxo-functionalized pyridine ligand, Co(dmgH)2(4-HEP)Cl [dmgH = dimethylglyoxime, 4-HEP = 4-(2-hydroxyethyl)pyridine] was immobilized on a chromium terephthalate metal-organic framework (MOF), MIL-101(Cr), to construct a MOF-catalyst hybrid which displays good photocatalytic H2 evolution activity. The longevity of the cobaloxime catalyst is increased by MOF incorporation, but limited by the stability of the cobalt-pyridine bond under turnover conditions.


Improvements to mechanical response tissue analysis.
Cortical Bone Mechanics Technology™ (CBMT) comprises certain improvements over a previous method known as Mechanical Response Tissue Analysis (MRTA). Both methods are dynamic 3-point bending tests intended for measuring the mechanical properties of cortical bone in living people. MRTA presented a theoretical potential for direct measurement of skeletal fragility, but it had acquired a reputation for error and fallen into disuse. We found sources of error in both MRTA data collection and data analysis. We describe here the fundamentals of MRTA, the major sources of error we found in MRTA, and our innovations for avoiding them. •Data collection at many sites across the mid-shaft of the ulna bone in the forearm.•Parameter estimation by fitting analytical complex compliance and stiffness transfer functions to empirical complex compliance and stiffness frequency response functions.•Optimization by selecting results from frequency response functions with the smallest deviations between fits to compliance and stiffness frequency response functions.


Early changes in iris blood vessels in exfoliation syndrome.
To look for possible changes in iris blood vessels that might precede the formation of true exfoliation material, and to correlate these changes, if present, to aging of the iris. Iris blood vessels of 10 clinically normal irises from 10 eyes (ages: 1 day-80 years), 4 irises with exfoliation (ages: 64-80 years) and 3 irises from primary open-angle glaucoma (POAG) (ages: 27-65 years) were examined with an electron microscope. Pronounced multilayering of the basal lamina around the vessels, abnormal excessive formation of microfibrils, presence of atrophic invaginations in the outer cell membranes of endothelial cells containing interlacing basal lamina, and an apparent decrease in the perivascular collagen fibers were evident in exfoliative iris vessels devoid of true exfoliation material. Similar, but much milder, changes were evident in normal aged and POAG irises. Abnormal elastic tissue and/or basal lamina production plays a role early in the formation of exfoliation material around iris blood vessels.


Topical capsaicin--a novel and effective treatment for idiopathic intractable pruritus ani: a randomised, placebo controlled, crossover study.
Pruritus ani is a common and embarrassing proctological condition which can be very difficult to treat. We report the results of a double blind placebo controlled study of treatment with capsaicin. Firstly, a pilot open study was carried out on five patients to establish which of two doses was the most acceptable by comparing effectiveness and side effects. Secondly, a double blind, placebo controlled, crossover study of topical capsaicin was performed. This study involved two four week treatment phases separated by a one week washout phase. Forty four patients were randomised to receive locally either active capsaicin (0.006%) or placebo (menthol 1%) ointment over a four week period (22 patients per group). After four weeks of treatment and a one week washout period, the placebo group began to receive capsaicin while the treated group received placebo (menthol 1%) for another four weeks. At the end of the controlled study, responders from both groups continued with capsaicin treatment in an open labelled manner. Thirty one of 44 patients experienced relief during capsaicin treatment periods and did not respond to menthol; all patients not responding to capsaicin also failed on menthol (p<0.0001). In 13 patients, treatment with capsaicin was unsuccessful: eight patients did not respond to capsaicin treatment, one responded equally to capsaicin and placebo, and four others dropped out because of side effects. During the follow up period (mean 10.9 (SD 5.8) months), 29 "responders" needed a mean application of capsaicin every day (1.6 (SD 1.2); range 0.5-7 days) to remain symptom free (or nearly symptom free). Capsaicin is a new, safe, and highly effective treatment for severe intractable idiopathic pruritus ani.


Cloning of a novel topramezone-resistant 4-hydroxyphenylpyruvate dioxygenase gene and improvement of its resistance through pressure acclimation.
Topramezone is a new 4-hydroxyphenylpyruvate dioxygenase (HPPD) inhibitor herbicide that is widely used on corn to control annual grass weeds and broadleaf weeds. Due to its broad-spectrum weed control capacity, improved activity, excellent crop selectivity, low mammalian toxicity and high environmental safety, topramezone is considered an ideal target herbicide for transgenic engineering of herbicide tolerance. In this study, a topramezone-resistant strain, Burkholderia sp. BW-1, was screened from soil, and a novel topramezone-resistant HPPD gene (Bkhppd) was cloned from this strain. Purified BkHPPD displayed relatively high HPPD activity and topramezone resistance with a half-maximal inhibitory concentration (IC50) of 572.0 nM. Two BkHPPD mutants designated as BkHPPDt31 and BkHPPDt76 were screened through pressure acclimation. BkHPPDt31 contained three amino acid substitutions (H65D, N160 T and N258S), whereas BkHPPDt76 contained four amino acid substitutions (H65D, N160 T, N258S and N343 T). The topramezone IC50 values of BkHPPDt31 and BkHPPDt76 were 1.1- and 2.3-fold higher, respectively, than that of wild-type BkHPPD. In addition, site-directed mutagenesis indicated that the increased resistance conferred by BkHPPDt31 resulted from the synergistic effects of the three site mutations rather than a single site mutation, and that substitution of asparagine 343 with threonine significantly decreased catalytic efficiency and affinity but increased topramezone resistance. In summary, this study provides a novel topramezone-resistant HPPD gene for the engineering of genetically modified herbicide-resistant crops and facilitates further elucidation of the resistance mechanism of BkHPPD and improvement of resistance through directed evolution.


Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs.
We evaluated the effectiveness of combination treatment using sumatriptan plus metoclopramide versus sumatriptan alone for the treatment of acute migraine. The patients who were treated had failed to respond to triptans in the past despite adequate doses on at least 2 separate trials of the same triptan or 2 trials involving different triptans. There is limited evidence that dopaminergic antagonists may benefit the migraineur by relieving migraine pain and associated symptoms. The exact mechanism of action in migraine is unknown. The postulated action is the inhibition of dopaminergic overactivity. A dopaminergic antagonist, metoclopramide, may improve the efficacy of a 5-HT1B/1D agonist, sumatriptan. In this double-blind, randomized, crossover study, 16 adult migraineurs fulfilling International Headache Society (IHS) criteria for migraine with or without aura who had failed to receive adequate relief from triptans treated one migraine with each treatment: sumatriptan 50 mg plus metoclopramide 10 mg or sumatriptan 50 mg plus placebo to match metoclopramide. Patients treated their migraines when they were moderate or severe in intensity and recorded pain severity and symptoms prior to treatment and 30, 60, 90, and 120 minutes and 24 hours after treatment. Thirteen women and 3 men (mean age, 40 years) completed the study; ie, treated 2 migraines (a total of 32 migraines), one attack with each treatment. Meaningful relief was attained in 10 (63%) of 16 migraines treated with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. Headache response (moderate or severe to mild or no pain at 2 hours) was achieved in 7 (44%) of 16 migraines with the combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated with sumatriptan 50 mg plus placebo. There did not appear to be a difference between treatment groups with respect to associated symptoms. The combination of sumatriptan 50 mg plus metoclopramide 10 mg was well tolerated. Combining sumatriptan with metoclopramide provided relief in some migraineurs who failed to achieve adequate relief with a triptan alone. It remains unknown whether initiating therapy when pain was mild or using a higher dose of sumatriptan (ie, 100 mg) would have provided additional benefit. Further studies are indicated.


Convolutional networks for the segmentation of intravascular ultrasound images: Evaluation on a multicenter dataset.
The delineation of the lumen contour and external elastic lamina (EEL) in intravascular ultrasound (IVUS) images is crucial for the quantitative analysis of coronary atherosclerotic plaques. However, the presence of ultrasonic shadows and anatomical structures (such as bifurcations and calcified plaque) complicates the automatic delineation of the lumen contour and EEL. The purpose of this paper is to evaluate the IVUS segmentation performances of different convolutional networks and the impact factors on a large-scale multiple-center dataset. A total of 6516 cross-sectional images from 175 IVUS pullbacks acquired in different centers by different IVUS imaging catheters were screened from a corelab to evaluate the segmentation methods. The IVUS images included bifurcation, side branch ostia, and various image artifacts to reflect the general image characteristics in routine clinical acquisition. We compared three generic fully convolutional networks (FCNs) and two FCNs specifically designed for the segmentation of IVUS images and explored the factors impacting the segmentation performance, including the training images and the input of consecutive images to the models. The performance of the FCNs was evaluated by using the Dice similarity coefficient (DSC), the Jaccard index (JI), the Hausdorff distance (HD), linear regression and Bland-Altman analysis. The 4-cascaded RefineNet and DeepLabv3+ outperformed U-net and IVUS-net in the segmentation of the lumen contour and EEL on IVUS images. DeepLabv3+ had the best segmentation performance, with DSCs of 0.927 and 0.944, JIs of 0.911 and 0.933, and HDs of 0.336 mm and 0.367 mm for delineation of the lumen and EEL, respectively. Excellent agreement between DeepLabv3+ and the manual delineation was found in the quantification of the coronary plaque area (r = 0.98). The convolutional network architecture is effective in the automatic segmentation of IVUS images. It might contribute to the clinical application of quantitative IVUS analysis in real-world as well as the efficient assessment of coronary atherosclerosis.


Pandemic and the state.
It has been argued the pandemic has brought back the state. The discussions on this return of the state have been concentrated, so far, around familiar themes: trade-off between freedom-privacy and security with the expansion of control and surveillance of our bodies by the state, efficiency-competency of the state in containing the spread of the virus, and exclusion of marginalised peoples from healthcare facilities and sacrifice of older people in the process of rational allocation of critical care. In this short essay, I will explore and engage with these debates, and enquire what the pandemic control measures and outcomes tell us about present nature of the Indian state.


Regulation of genes encoding cellulolytic enzymes by Pal-PacC signaling in Aspergillus nidulans.
Cellulosic biomass represents a valuable potential substitute for fossil-based fuels. As such, there is a strong need to develop efficient biotechnological processes for the enzymatic hydrolysis of cellulosic biomass via the optimization of cellulase production by fungi. Ambient pH is an important factor affecting the industrial production of cellulase. In the present study, we demonstrate that several Aspergillus nidulans genes encoding cellulolytic enzymes are regulated by Pal-PacC-mediated pH signaling, as evidenced by the decreased cellulase productivity of the palC mutant and pacC deletants of A. nidulans. The deletion of pacC was observed to result in delayed induction and decreased expression of the cellulase genes based on time course expression analysis. The genome-wide identification of PacC-regulated genes under cellobiose-induced conditions demonstrated that genes expressed in a PacC-dependent manner included 82 % of ClrB (a transcriptional activator of the cellulase genes)-regulated genes, including orthologs of various transporter and β-glucosidase genes considered to be involved in cellobiose uptake or production of stronger inducer molecules. Together with the significant overlap between ClrB- and PacC-regulated genes, the results suggest that PacC-mediated regulation of the cellulase genes involves not only direct regulation by binding to their promoter regions but also indirect regulation via modulation of the expression of genes involved in ClrB-dependent transcriptional activation. Our findings are expected to contribute to the development of more efficient industrial cellulase production methods.


Centrally programmed feeding in Helisoma: identification and chracteristics of an electrically coupled premotor neuron network.
(1) The oscillatory network underlying centrally programmed feeding in the fresh water pulmonate, Helisoma trivolvis, was studied using intracellular recording and staining techniques. These premotor neurons have been termed cyberchron neurons. (2) Intracellular staining with Procoin yellow has allowed the construction of a soma map and tentative identification of axonal projections of the cyberchron neurons. (3) Cyberchron neurons form a tightly electrically coupled network. Coupling coefficients range from 0.15 to 0.5, and electrotonic junctions allow the passage of Procion dye from cell to cell. Electrical synapses act as low pass filters, and allow spatial and temporal summation. (4) Burst generation within the network is the result of network interaction manifest as regeneration positive feedback from neuron to neuron via attenuating electrical synapses. (5) Decreased coupling between cyberchron neurons during and immediately following a burst is observed, and is discussed as a possible mechanism for burst termination.


Modulation of T lymphocyte function by the angiogenesis inhibitor AGM-1470.
The angiogenesis inhibitor AGM-1470 has recently been reported to inhibit collagen-induced arthritis in rats. To determine if the anti-arthritic effects of AGM-1470 might be due to T cell inhibition, we have studied its effects on T cell responses in vitro. Responses of human cells to tetanus toxoid (TT), and those of murine splenocytes to staphylococcal enterotoxin (SE), mitogens or a mls difference were inhibited by AGM-1470. Responses of human cells to SE, OKT3 and PHA were all partially inhibited on day 2 (d2) but not d3, and in fact were augmented on d6-8. The amount of IL-2 in SEA cultures was augmented on d4 and d5. There were no differences in the expression of CD3, CD4, CD8, CD25, CD45RA, CD45RO, LFA-1, VLA-4 or VLA-6 in inhibited cultures, except for slight decreases in CD25 and CD45RO in TT cultures. These results indicated that the angiogenesis inhibitor AGM-1470 also modulates human and murine lymphocyte function.


Elevated CO2 differentially alters the responses of coocurring birch and maple seedlings to a moisture gradient.
To determine the effects of elevated CO2 and soil moisture status on growth and niche characteristics of birch and maple seedlings, gray birch (Betula populifolia) and red maple (Acer rubrum) were experimentally raised along a soil moisture gradient ranging from extreme drought to flooded conditions at both ambient and elevated atmospheric CO2 levels. The magnitude of growth enhancement due to CO2 was largely contingent on soil moisture conditions, but differently so for maple than for birch seedlings. Red maple showed greatest CO2 enhancements under moderately moist soil conditions, whereas gray birch showed greatest enhancements under moderately dry soil conditions. Additionally, CO2 had a relatively greater ameliorating effect in flooded conditions for red maple than for gray birch, whereas the reverse pattern was true for these species under extreme drought conditions. For both species, elevated CO2 resulted in a reduction in niche breadths on the moisture gradient; 5% for gray birch and 23% for red maple. Species niche overlap (proportional overall) was also lower at elevated CO2 (0.98 to: 0.88: 11%). This study highlights the utility of of experiments crossing CO2 levels with gradients of other resources as effective tools for elucidating the potential consequences of elevated CO2 on species distributions and potential interactions in natural communities.


Is COVID-19 to Blame? Trends of Incidence and Sex Ratio in Youth-Onset Type 2 Diabetes in Germany.
We investigated the incidence of pediatric type 2 diabetes (T2D) in Germany during 2 years of the coronavirus disease 2019 (COVID-19) pandemic (2020-2021) compared with the control period 2011-2019. Data on T2D in children (aged 6 to <18 years) were obtained from the DPV (German Diabetes Prospective Follow-up) Registry. Poisson regression was used to estimate incidences for 2020 and 2021 based on data from 2011 to 2019, and these were compared with observed incidences in 2020 and 2021 by estimating incidence rate ratios (IRRs) with 95% CIs. Incidence of youth-onset T2D increased from 0.75 per 100,000 patient-years (PYs) in 2011 (95% CI 0.58, 0.93) to 1.25 per 100,000 PYs in 2019 (95% CI 1.02, 1.48), an annual increase of 6.8% (95% CI 4.1, 9.6). In 2020, T2D incidence increased to 1.49 per 100,000 PYs (95% CI 1.23, 1.81), which was not significantly higher than predicted (IRR 1.15; 95% CI 0.90, 1.48). In 2021, the observed incidence was significantly higher than expected (1.95; 95% CI 1.65, 2.31 vs. 1.38; 95% CI 1.13, 1.69 per 100,000 PYs; IRR 1.41; 95% CI 1.12, 1.77). Although there was no significant increase in incidence in girls in 2021, the observed incidence in boys (2.16; 95% CI 1.73, 2.70 per 100,000 PYs) significantly exceeded the predicted rate (IRR 1.55; 95% CI 1.14, 2.12), leading to a reversal of the sex ratio of pediatric T2D incidence. In Germany, incidence of pediatric T2D increased significantly in 2021. Adolescent boys were more affected by this increase, resulting in a reversal of the sex ratio of youth-onset T2D.


Cervical root compression by a traumatic pseudoaneurysm of the vertebral artery: case report.
We report the case of a patient with cervical monoradiculopathy secondary to a pseudoaneurysm of the vertebral artery caused by a knife wound to the neck.


Clinicopathologic risk factors for recurrence after a curative hepatic resection for hepatocellular carcinoma.
The long-term prognosis after resection for patients with hepatocellular carcinoma is still unsatisfactory because of the high recurrence rate. The survival of patients with multiple intrahepatic or extrahepatic recurrence is especially poor. Among the patients who underwent hepatic resection for hepatocellular carcinoma between 1981 and 2000, 216 patients with 3 or less than 3 intrahepatic recurrences (group B); 156 patients with more than 3 intrahepatic recurrences, extrahepatic recurrences, or both (group C); and 51 patients who survived more than 5 years without recurrence (group A) were clinicopathologically studied. The period to recurrence of group C was significantly earlier than that of group B and also showed a significantly poor prognosis after recurrence. Tumor factors, including size, portal venous invasion, intrahepatic metastasis, histologic grade, or the number of tumors at resection in group C was significantly worse than in groups A and B. Although no differences are recognized in the tumor factors between groups A and B, except for the alpha-fetoprotein level, liver function in group B was significantly worse than that in group A. In addition, the frequency of hepatitis B surface antigen in group B and that of hepatitis C virus in group B was significantly less and higher than that in group A, respectively. Similar to extrahepatic metastasis, multinodular recurrences are also mainly caused by metastatic recurrence from the main tumor by means of the portal system, and recurrences with up to 3 intrahepatic nodules are mainly caused by metachronous multicentric hepatocarcinogenesis. Because the mechanisms of recurrence differed, determining the patterns of recurrence on the basis of the clinicopathologic findings is important for selecting the optimal postoperative therapy for each individual patient.


Astrocytic nutritional dysfunction associated with hypoxia-induced neuronal vulnerability in stroke-prone spontaneously hypertensive rats.
Stroke-prone spontaneously hypertensive rats (SHRSP) is a valuable animal model to investigate human strokes. SHRSP Izumo strain (Izm) neurons are highly sensitive to blood supply changes. Furthermore, SHRSP/Izm astrocytes show various abnormalities upon hypoxic stimulation compared to control Wistar Kyoto (WKY/Izm) rats. This study aimed to describe stroke-related characteristics of SHRSP/Izm-derived neurons and astrocytes. In addition, we discuss the role of astrocytes in the development of stroke in SHRSP/Izm model. In SHRSP/Izm, neuronal death is induced upon reoxygenation after hypoxia. Furthermore, it was shown that SHRSP/Izm astrocytes show significantly reduced lactate production and supply ability to nerve cells when subjected to hypoxic stimulation. In particular, decreased lactate production and monocarboxylic acid transporter (MCT) expression in SHRSP/Izm astrocytes are factors that induce neuronal cell death. Remarkable differences in glial cell line-derived neurotrophic factor (GDNF) expression and L-serine production were also observed in SHRSP/Izm-derived astrocytes compared to WKY/Izm. Reduced production of both GDNF and L-serine contributes to diminished neuronal survival. The differences between SHRSP/Izm and WKY/Izm astrocyte cellular properties may contribute to compromised neuronal nutrition and induction of neuronal death. These properties are likely to be the factors that enhance stroke in SHRSP/Izm.


[Factors which influence cardiopulmonary resuscitation and medical information preferences in a geriatric population].
Whether or not performing cardiopulmonary resuscitation (CPR) is a complex decision that requires taking account of several factors. The aim of this study was to analyse the preferences of elderly people with regard to CPR. Survey administered to 181 elderly subjects from nursing homes and ambulatory care centres. 66.9% of them would request information if hospitalised. 80.7% would wish to undergo CPR. However, this figure decreased to 40.9% in case of serious sequeles as a result of the procedure and to 32.5% in case of previous dementia. Request information would be high. Age and functional status of the elderly person


The completed genome sequence of Pestalotiopsis versicolor, a pathogenic ascomycete fungus with implications for bayberry production.
The pathogenic fungus Pestalotiopsis versicolor is a major etiological agent of fungal twig blight disease affecting bayberry trees. However, the lack of complete genome sequence information for this crucial pathogenic fungus hinders the molecular and genetic investigation of its pathogenic mechanism. To address this knowledge gap, we have generated the complete genome sequence of P. versicolor strain XJ27, employing a combination of Illumina, PacBio, and Hi-C sequencing technologies. This comprehensive genome sequence, comprising 7 chromosomes with an N50 contig size of 7,275,017 bp, a GC content ratio of 50.16%, and a total size of 50.80 Mb, encompasses 13,971 predicted coding genes. By performing comparative genomic analysis between P. versicolor and the genomes of eleven plant-pathogenic fungi, as well as three closely related fungi within the same group, we have gained initial insights into its evolutionary trajectory, particularly through gene family analysis. These findings shed light on the distinctive characteristics and evolutionary history of P. versicolor. Importantly, the availability of this high-quality genetic resource will serve as a foundational tool for investigating the biology, molecular pathogenesis, and virulence of P. versicolor. Furthermore, it will facilitate the development of more potent antifungal medications by uncovering potential vulnerabilities in its genetic makeup.


Actinomycins as proteinase inhibitors.
A novel actinomycin (Act SG3) from a strain of Streptomyces galbus var. C-72, as well as actinomycin D (Act D) were found to act as competitive inhibitors of serine proteinases from microorganisms. The inhibitory properties of Act SG3 and Act D are compared with these of other peptide antibiotics, namely bacitracin A (Bac A) and gramicidin S (Gr S). The last compound has only a weak inhibitory effect. The following order of affinity for the four peptide antibiotics towards subtilisin DY and proteinase K was observed: Bac A > Act D > Act SG3 = Gr S. The affinity towards thermitase changes as follows: Act SG3 = Act D > Bac A > Gr S.


Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells.
Toll-like receptor (TLR) 2 and TLR4 play a pivotal role in recognition of Candida albicans. We demonstrate that TLR2(-/-) mice are more resistant to disseminated Candida infection, and this is associated with increased chemotaxis and enhanced candidacidal capacity of TLR2(-/-) macrophages. Although production of the proinflammatory cytokines TNF, IL-1alpha, and IL-1beta is normal, IL-10 release is severely impaired in the TLR2(-/-) mice. This is accompanied by a 50% decrease in the CD4+CD25+ regulatory T (Treg) cell population in TLR2(-/-) mice. In vitro studies confirmed that enhanced survival of Treg cells was induced by TLR2 agonists. The deleterious role of Treg cells on the innate immune response during disseminated candidiasis was underscored by the improved resistance to this infection after depletion of Treg cells. In conclusion, C. albicans induces immunosuppression through TLR2-derived signals that mediate increased IL-10 production and survival of Treg cells. This represents a novel mechanism in the pathogenesis of fungal infections.


Toward a Focused Conceptualization of Collateral Consequences Among Individuals Who Sexually Offend: A Systematic Review.
Despite speculation regarding the role of collateral consequences of sexual offender policies in psychosocial and criminogenic outcomes, there has been no empirical analysis in the extant literature examining these links. Lack of conceptual underpinnings and no psychometrically valid measure of collateral consequences has limited study in this area. A systematic literature review was conducted to assess the state of measurement in terms of conceptual and operational definitions, populations sampled, domains assessed, items used, and scale properties reported. Nineteen studies met inclusion criteria. Themes emerged regarding commonly assessed collateral consequences, the misconnect between legal and psychological conceptualizations of collateral consequences, the division between external (i.e., social) and internal (i.e., affective) collateral consequences, as well as a trend toward emphasizing the psychological damages (in addition to discrete experiences of loss) associated with a sexual offense. Findings are discussed, and a unifying definition of collateral consequences is proposed to guide future scale development.


Blockade of M1 muscarinic acetylcholine receptors modulates the methamphetamine-induced psychomotor stimulant effect.
Muscarinic acetylcholine receptors (M1-M5) regulate many key functions of the CNS and peripheral nervous system. In the present study, the role of M1 muscarinic receptors (M1R) in the psychomotor stimulant and sensitizing properties of methamphetamine (METH) is investigated using molecular, neurochemical, and behavioral approaches. Acute and repeated treatment with METH increased M1R mRNA expression in the frontal cortex and the CA2 region of the hippocampus. Repeated treatment with METH also increased M1R mRNA expression in the dentate gyrus. Dicyclomine, an M1R antagonist, did not affect the psychomotor effect of METH, but it attenuated METH-induced increases in the dopamine (DA) efflux in the nucleus accumbens (NAc). Dicyclomine enhanced the psychomotor effect of METH after repeated treatment with METH and 8.0 mg/kg of dicyclomine, and also augmented the increase in the NAc DA overflow evoked by repeated METH treatment. These results suggest that M1R plays a role in the METH-induced psychomotor stimulant effect by changing the release of DA in the NAc of mice.


Low-contact dynamic compression plating of the clavicle.
Internal fixation of the clavicle is rarely necessary. When it is warranted, the clavicle's complex three-dimensional morphology and functional anatomy, proximity to vital structures, and the multidirectional biomechanical forces acting upon it place considerable demands on any implant used for skeletal fixation. We treated nine clavicles with the recently-introduced 3.5 mm low contact-dynamic compression plate (LC-DCP). Surgery was performed for symptomatic non-union in six patients, shoulder dysfunction following a malunited fracture in one, for an open fracture in one, and for an acute fracture associated with brachial plexus injury in one. After an average follow-up period of 17 months union was secured in each case. The advantages afforded by the 3.5 mm LC-DCP in internal fixation of the clavicle with its uniquely demanding anatomical and biomechanical characteristics are discussed.


Significance of Fas and FasL protein expression in cardiac carcinoma and local lymph node tissues.
To investigate the relation of Fas and Fas ligand (FasL) protein expression with carcinogenesis and metastasis of cardiac carcinoma. Immunohistochemistry was used to detect Fas and FasL protein expression in 64 cardiac carcinoma tissue samples and 20 normal gastric tissue samples. Relation between FasL and Fas expression, age and gender of gastric cancer patients, and pathological subtype and lymph node metastasis of gastric cancer was analyzed. The Fas expression level was significantly higher in normal gastric tissue samples than in cardiac carcinoma tissue samples (85.0% vs. 25.0%, P<0.001), while the FasL expression level was significantly lower in normal gastric tissue samples than in cardiac carcinoma tissue samples (30.0% vs. 81.3%, P<0.001). The Fas expression level was significantly higher in invasive lymph nodes than in non-invasive lymph nodes (82.9% vs. 56.5%, P<0.003) and in well-differentiated gastric carcinoma tissue samples than in poorly-differentiated cardiac carcinoma tissue samples (50.0% vs. 18.0%, P=0.015). The FasL expression level was significantly lower in well-differentiated cardiac carcinoma tissue samples than in poorly- differentiated cardiac carcinoma tissue samples (42.9% vs. 84.0%, P=0.021). The Fas and FasL expression levels (25.0% and 81.3%) were significantly different in cardiac carcinoma tissue samples (P<0.001), but had a non-linear correlation (P=0.575). Abnormal Fas and FasL expressions in cardiac carcinoma and lymph node tissues are involved in carcinogenesis and metastasis of gastric cancer.


A triterpenoid saponin from Cucumaria frondosa.
The structure of a new triterpenoid saponin, frondoside D, isolated from Cucumaria frondosa has been determined principally by high field 1D and 2D NMR and FAB-MS spectrometry. Frondoside D was shown to be 3 beta-[3-O-methyl-O-beta-D-glucopyranosyl-(1-3)-O-beta-D- xylopyranosyl-(1-4)-[O-beta-D-xylopyranosyl-(1-2)]-O-beta-D- quinovopyranosyl-(1-2)-O-beta-D-4-sulfonatoxylo-pyranosyl]-1 6 beta-acetoxy-23S-hydroxy-holost-7-ene, sodium salt.


Spousal experiences of coping with and adapting to caregiving for a partner who has a stroke: a meta-synthesis of qualitative research.
This meta-synthesis was conducted to explore qualitative spousal accounts of coping and adaptation to caregiving when their partner experienced a stroke. Electronic databases were searched systematically and inclusion and exclusion criteria were applied. The meta-synthesis was conducted using guidance from Sandelowski and Barroso to extract salient data relating to coping and adaptation. Twelve papers were identified for inclusion and seven themes resultant themes were extracted: Seeking information; Searching for own space and well-being; Suffering in silence; Putting one's own needs aside; Adapting to a changed role; Social support and Hope and Optimism: instilling a positive focus. The findings suggested spouses adopt a range of adaptive coping strategies although several barriers to these were also identified and discussed in relation to a number of clinical implications. The limitations of this meta-synthesis were discussed, together with recommendations for future research.


Perception of whole-body motion during balance perturbations is impaired in Parkinson's disease and is associated with balance impairment.
In addition to motor deficits, Parkinson's disease (PD) may cause perceptual impairments. The role of perceptual impairments in sensorimotor function is unclear, and has typically been studied in single-joint motions. We hypothesized that perception of whole-body motion is impaired in PD and contributes to balance impairments. We tested (1) whether directional acuity to whole body perturbations during standing was worse in people with PD compared to neurotypical older adults (NOA), and (2) whether balance ability, as assessed by the MiniBESTest, was associated with poor directional acuity in either group. Participants were exposed to pairs of support-surface translation perturbations in a two-alternative forced choice testing paradigm developed previously in a young healthy population. The first perturbation of each pair that was to be judged by participants was directly backward, and the second perturbation deviated from the left or right from the backward direction by 1°-44°. Participants reported whether the perturbations in each pair were in the "same" or "different" direction. Judgements from 24 to 67 perturbation pairs were used to calculate directional acuity thresholds corresponding to "just-noticeable differences" in perturbation direction. Linear mixed models determined associations between directional thresholds and clinical variables including MDS-UPDRS-III score, age, and MiniBESTest score. 20 PD (64 ± 7 y, 12 male, ≥12 h since last intake of antiparkinsonian medications) and 12 NOA (64 ± 8, 6 male) were assessed. Directional thresholds were higher (worse) among PD participants (17.6 ± 5.9° vs. 12.8 ± 3.3°, P < 0.01). Linear mixed models further showed that higher thresholds were associated with MDS-UPDRS-III score (P < 0.01), and were associated with poorer balance ability among PD participants (P < 0.01), but not among NOA participants (P = 0.40). Perception of whole-body motion is impaired in PD and may contribute to impaired balance and falls.


Participation of the splanchnic nerves in the structure of the cranial mesenteric plexus of the rabbit.
In this study the branch points of the greater splanchnic nerve, lesser splanchnic nerve and lumbar splanchnic nerves from the sympathetic trunk of the rabbit were investigated and their participation in the structure of the cranial mesenteric plexus was estimated.


Superspreading - Has the mystery been unraveled?
Superspreading is a fascinating phenomenon first observed about 30 years ago with dilute solutions of trisiloxane surfactants on hydrophobic substrates. Although many groups all over the world have contributed considerably to solve the scientific challenges involved, the reasons why only some trisiloxane surfactants promote superspreading, whereas others of similar chemical structure behave more like ordinary surfactants, has remained a mystery up to now. A number of original papers and reviews on superspreading have been published in recent years. The driving force still proposed today is most often Marangoni flow. This is, however, in contradiction with recent results showing that superspreading only starts after a surface tension gradient between apex and leading edge has been eliminated. From foam film experiments unrelated to wetting, there is evidence for "dangling" bilayers attached to the air/water interface only in case of the superspreading trisiloxane surfactants. By combining this and other published experimental findings, a new hypothesis of the mode of action is put forward: Advancing by "rolling action" at the leading edge, and the supply of surfactant by "unzippering" of the dangling bilayers all over the surface of the drop; this hypothesis even fulfills basic thermodynamic requirements.


Editorial: Deep Remission in Eosinophilic Esophagitis With Long-Term Steroids: Difficult to Attain and Maintain.
The study by Greuter et al. entitled "Long-term treatment of eosinophilic esophagitis and swallowed topical corticosteroids: development and evaluation of a therapeutic concept" follows 351 patients over 6 years. This gives considerable insight into long-term topical steroid management of EoE and establishes the concept of deep remission in EoE.


Detection of hepatic amebic abscesses by infusion tomography.
The liver represents a major challenge for radiologic imaging. A simple method of diagnosing acute inflammatory lesions of the liver by infusion tomography is presented. Results of this technique in 48 consecutive patients with amebic abscesses of the liver are described, and their typical appearance is presented. The test also appears to aid in defining the acuteness of the lesion.


Hepatocellular carcinoma developing at the puncture site after percutaneous ethanol injection.
Percutaneous ethanol injection (PEI) is an option for hepatocellular carcinoma (HCC) treatment that is most effective for solitary lesions <or=5 cm or multiple lesions <or=3 cm. Malignant seeding along the needle tract is a rare complication of the procedure. We report a case of tumor seeding along the needle tract following PEI treatment for HCC arising 21 months after treatment.


Screening Families in Primary Care for Social and Economic Needs: Patients' Urgency and Activation for Social Care Navigation.
Social determinants of health (SDoH) screening and intervention in primary care aim to alleviate adverse influences on health, but its efficacy may be diluted when offered supports are not well matched to families' desire for such services. The purpose of this prospective cohort study was to provide guidance to social care navigation teams regarding which families would be most likely to make use of services. Analysis of registry data collected in April 1-September 30, 2021 from a social care navigation program embedded in a medical home was conducted. Multivariable regression models explored (1) whether family-reported urgency of needs, number of needs, and/or specific types of needs predicted completing program intake and (2) whether the degree of family activation regarding social needs predicted subsequent interactions with the navigation team. Of the 1,483 families reporting any social care needs (38% of all screens completed, mean of 2.5 needs per screen), 31% indicated that their needs were urgent. Accounting for program factors and the number and type of needs reported, families whose needs were urgent were more likely to complete intake (OR=1.34; 95% CI=1.01, 1.82; p=0.04) and remain engaged with the program over time (OR=2.25; 95% CI=1.62, 3.12; p<0.01). Those who were self-advocates were substantially less likely to desire follow-up or stay engaged (OR=0.40; 95% CI=0.17, 0.93; p<0.01). Family-reported urgency of needs and activation for social care assistance predicted engagement with the navigation team. SDoH interventions should prioritize outreach to those families expressing an interest in help with any of their identified needs.


Golgi apparatus analyzed by cryo-electron microscopy.
In 1898, the Golgi apparatus was discovered by light microscopy, and since the 1950s, the ultrastructure composition is known by electron microscopic investigation. The complex three-dimensional morphology fascinated researchers and was sometimes even the driving force to develop novel visualization techniques. However, the highly dynamic membrane systems of Golgi apparatus are delicate and prone to fixation artifacts. Therefore, the understanding of Golgi morphology and its function has been improved significantly with the development of better preparation methods. Nowadays, cryo-fixation is the method of choice to arrest instantly all dynamic and physiological processes inside cells, tissues, and small organisms. Embedded in amorphous ice, such samples can be further processed by freeze substitution or directly analyzed in their fully hydrated state by cryo-electron microscopy and tomography. Even though the overall morphology of vitrified Golgi stacks is comparable to well-prepared and resin-embedded samples, previously unknown structural details can be observed solely based on their native density. At this point, any further improvement of sample preparation would gain novel insights, perhaps not in terms of general morphology, but on fine structural details of this dynamic organelle.


[Bioligical aspects of cell fusion induced in vitro by sheep Visna virus].
Visna virus induced cell fusion of sheep choroid plexus cells was explored in vitro. Fusion is early rapid, and of exogenous origin for multiplicities of infection equal to or greater than 2 UFP per cell; whereas fusion is slow, late-occurring and of endogenous origin for multiplicities of infection less than or equal to 0.75 UFP per cell.


Implementing a Screening and Brief Intervention Protocol for Excessive Alcohol Use in a Trauma Center: A Healthcare Improvement Project.
The aim of this healthcare improvement project was to evaluate healthcare provider use of screening and brief interventions (SBIs) for patients screening positive for alcohol at an upper Midwestern adult trauma center transitioning from Level II to Level I. Trauma registry data for 2,112 adult patients with trauma who screened positive for alcohol were compared between three periods: pre-formal-SBI protocol (January 1, 2010, to November 29, 2011); first post-SBI protocol (February 6, 2012, to April 17, 2016) after protocol implementation, healthcare provider training, and documentation changes; and second post-SBI protocol (June 1, 2016, to June, 30, 2019) after additional training and process improvements. Data analysis included descriptive statistics and logistic regression for comparisons over time and between admitting services. For the trauma admitting service, SBI rates increased from 32% to 90% over time, compared with 18%-51% for other admitting services combined. Trauma-service-admitted patients screening positive for alcohol had higher odds of receiving a brief intervention than other admitting services in each period in adjusted models: pre-SBI (OR = 1.99, 95% CI [1.15, 3.43], p = .014), first post-SBI (OR = 2.89, 95% CI [2.04, 4.11], p < .001), and second post-SBI (OR = 11.40, 95% CI [6.27, 20.75], p < .001) protocol periods. Within trauma service admissions, first post-SBI protocol (OR = 2.15, 95% CI [1.64, 2.82], p < .001) and second post-SBI protocol (OR = 21.56, 95% CI [14.61, 31.81], p < .001) periods had higher rates and odds of receiving an SBI than the pre-SBI protocol period. The number of SBIs completed with alcohol-positive adult patients with trauma significantly increased over time through SBI protocol implementation, healthcare provider training, and process improvements, suggesting other admitting services with lower SBI rates could adopt similar approaches.


Biochemical markers of bone turnover in tibia fracture patients randomly assigned to growth hormone (GH) or placebo injections: Implications for detection of GH abuse.
It has been argued that increased levels of bone remodelling markers are not suitable indicators of GH abuse, as bone injuries per se increase the expression levels of these markers. To investigate the impact of a recovering tibia fracture on circulating bone markers in subjects receiving placebo or GH treatment. A randomised, double-blind, placebo-controlled trial of up to 16weeks GH treatment, followed by a 16-week washout. Subjects (406 adult males and females) with a tibia fracture were randomly allocated within three days after surgery, to either placebo or GH treatment (15, 30 or 60μg/kg daily) until fracture healing or 16weeks after treatment initiation. IGF-I, serum C-terminal telopeptide of type I collagen (CTX), osteocalcin (OST) and bone-specific alkaline phosphatase (BAP) were measured during and after treatment. Dose-dependent increases were observed in groups receiving GH, and mean levels in the highest GH dose group peaked at eight (IGF-I, CTX) or 12weeks (OST) after treatment initiation. Statistically significant differences between GH treatment and placebo were seen for IGF-I, CTX and OST in all GH dose groups throughout the treatment period, and persisted until eight (CTX) or 12 (OST) weeks after cessation of treatment. IGF-I, CTX and OST are suitable candidate markers of prolonged, illicit administration of GH. Furthermore, CTX and OST have potentials to serve as markers also after cessation of GH administration.


Early elevation of high-sensitivity C-reactive protein as a predictor for cardiovascular disease incidence and all-cause mortality: a landmark analysis.
We investigated the association between early elevation of high-sensitivity C-reactive protein (hsCRP) and cardiovascular disease (CVD) incidence, all-cause mortality, and CVD mortality. We analyzed 6567 participants from the Korean Genome and Epidemiology Study_Ansan_Ansung cohort between 2005 and 2018. The Kaplan-Meier curves and modified Cox regression by Fine and Gray were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD incidence, all-cause mortality, CVD mortality, cancer mortality, and mortality from other causes. Landmark analyses were performed at the first (2007-2008) and second (2009-2010) follow-up periods, with early elevation defined as hsCRP > 2 mg/L. At the first and second landmark points, the early hsCRP elevation group had a higher incidence of CVD and all-cause mortality. At first landmark point, the adjusted HRs (95% CIs) were 1.37 (1.08-1.74) for incident CVD and 1.26 (1.04-1.53) for all-cause mortality, respectively. At second landmark point, the adjusted HRs in the early hsCRP elevation group were 1.45 (1.12-1.89) for incident CVD and 1.34 (1.10-1.63) for all-cause mortality, respectively. However, there were no significant differences in CVD mortality and cancer mortality between the groups. In conclusion, early elevation of serum hsCRP is a predictor of incident CVD and all-cause mortality. The timing of hsCRP increase is also a significant predictor of incident CVD, even considering the competing risk. Regular hsCRP testing may help monitor hsCRP trends and develop individualized treatment plans for CVD prevention.


Multiple intrahepatic vascular shunts causing hyperammoniaemic encephalopathy in a patient without liver cirrhosis.
The very rare case of a non-cirrhotic patient with multiple intrahepatic portosystemic and arteriosystemic vascular shunts, presenting with hyperammoniaemic type B encephalopathy and hypoalbuminaemia due to proteinuria, is reported. The correct diagnosis, suspected by abdominal ultrasound and colour-Doppler imaging, was confirmed by hepatic and superior mesenteric angiography. A comparison with the few similar cases existing in the literature is offered.


Dual regulation of the cardiac L-type calcium channel in L6 cells by protein kinase C.
The role of protein kinase C (PKC) in the regulation of cardiac L-type Ca(2+) channel activity (LCC) was investigated in L6 rat neonatal myoblasts. Depolarization of fura-2 loaded cells with 140mM KCl activated a Ba(2+) influx pathway that was blocked by nifedipine and stimulated by (-) Bay K 8644. At least two splice variants of the alpha(1C) subunit of the cardiac LCC were identified by PCR; the alpha(1S) subunit of the skeletal muscle LCC was not detected. Peptides that specifically inhibit translocation of the novel, Ca(2+)-independent delta and epsilon PKC isozymes reduced Ba(2+) influx by 27% and 19%, respectively, whereas a corresponding peptide directed against translocation of classical PKC alpha had no effect. Ingenol 3,20-dibenzoate, an agent reported to selectively activate novel PKCs, increased Ba(2+) uptake by 31% while ethanol, a PKC epsilon agonist, enhanced uptake by 38%. In contrast, selective activation of classical PKCs with thymeleatoxin or an agonist peptide reduced Ba(2+) influx by 23-33%. Ba(2+) influx was reduced by 30-40% when cells were treated with either a PKC inhibitor (Gö 6983, bisindolylmaleimide) or the PKC activator phorbol-12-myristate-13-acetate. We propose that novel, Ca(2+)-insensitive PKC(s) enhance cardiac Ca(2+) channel activity in L6 cells under basal conditions while activation of the classical, Ca(2+)-sensitive PKC(s) inhibits channel activity. These findings provide the first evidence that different PKC isozymes exert class-specific opposing effects on cardiac L-type Ca(2+) channel activity in L6 myoblasts.


Extracorporeal shock wave lithotripsy using a new, compact and portable unit.
We report on the use of a new compact, inexpensive, portable shock wave lithotriptor. To date 40 treatments on 37 patients with different calculi in the upper urinary tract have been performed at our institution with excellent results and no complications. More patients currently are being treated with this machine at additional centers with equally good results.


Cardiac MR imaging of nonischemic cardiomyopathies.
Cardiomyopathies, diseases of the myocardium associated with cardiac dysfunction, include hypertrophic, restrictive, and dilated forms and rare entities, such as arrhythmogenic right ventricular dysplasia, ventricular noncompaction, and apical ballooning syndrome. Many have similar presentations, but the underlying condition determines prognoses and treatment. Cardiac MR imaging plays a role in characterizing the range of entities and is crucial for evaluation and management. In addition, delayed enhanced imaging can allow differentiation among the forms of cardiomyopathy and offer prognostic information. As the speed and technical ease of cardiac imaging improve, MR imaging will assume an increasing role in the care of patients who have cardiomyopathy.


Influence of pre-irradiation time employed in antimicrobial photodynamic therapy with diode laser.
The aim of the present study was to evaluate, in vitro, the effect of different pre-irradiation times of the photosensitizer in photodynamic therapy in biofilms formed by Streptococcus mutans and Candida albicans, through the evaluation of the microbial load. The factors under study were as follows: times of pre-irradiation of the photosensitizer in three levels (1, 2, or 5 min). For the control of the cariogenic dental biofilm with antimicrobial photodynamic therapy (aPDT), methylene blue (0.01%) was used in association with the diode laser (InGaAlP) with a wavelength of 660 nm. Chlorhexidine digluconate (0.12% CHX) and saline were used as positive and negative controls, respectively. The study design was carried out in complete and randomized blocks. The sample consisted of 15 S. mutans biofilms cultures, randomly divided into five groups and 15 C. albicans cultures, also divided into five groups. The experiment was performed in triplicate (n = 3) and the response variables were obtained through quantitative analysis of bacterial viability, expressed in colony-forming units (CFU) per square millimeter of the specimen area. The data were analyzed with the aid of the ANOVA one-way test and Tukey's post-test. All analyses were performed using the Graph Pad Prism 4.0 program, with a significance level of 5%. For the S. mutans group, only the saline solution presented a statistically significant difference when compared to the other treatments (p < 0.05), that is, the treatment with aPDT, irrespective of the irradiation time applied, was similar to the treatment with CHX and both were more effective in reducing cariogenic biofilm compared to saline. For the group of C. albicans, there was no statistical difference between the groups (p > 0.05). Therefore, it can be concluded that the treatment with aPDT reduced the number of CFUs of S. mutans in a similar way to CHX, independently of the pre-irradiation time applied. No effect of this therapy or of the different pre-irradiation times on the C. albicans biofilm could be observed. In this way, the pre-irradiation time of 1 min can be used to reduce the microbial load of S. mutans.


Circulating levels of TNF-like cytokine 1A correlate with the progression of atheromatous lesions in patients with rheumatoid arthritis.
Interactions between TNF-like Cytokine 1A (TL1A) and its receptors, death receptor-3 (DR3) and decoy receptor-3 (DcR3) may be important in atherogenesis. We hypothesized that dysregulation of this system predicts formation of new atheromatic plaques in rheumatoid arthritis (RA). Forty-five patients were prospectively followed up for 40.5 ± 3.6 months. Serum concentrations of TL1A and DcR3 were measured at baseline and carotid and femoral arteries examined by ultrasound at baseline and at the end of follow-up. Individual serum levels of TL1A correlated with the progression of carotid atheromatic plaque height (Spearman rho = 0.550, p = 0.003). Patients with low TL1A and undetectable DcR3 serum levels at baseline showed significantly fewer newly formed carotid plaques during the next 3.5 years than the remaining patients (P = 0.016). Univariate analysis showed that a "low TL1A/DcR3" immunophenotype predicted a preserved atherosclerosis profile in carotid (P = 0.026), or carotid and/or femoral arteries (P = 0.022). Dysregulated TL1A-induced signaling may be associated with risk for accelerated atherosclerosis in RA.


Pruritic dermatitis in asthmatic basenji-greyhound dogs: a model for human atopic dermatitis.
A recurrent, nonseasonal pruritic dermatitis manifested as lichenified plaques and as inflammatory nodules and papules in each of fourteen basenji-greyhound (B-G) crossbreed dogs, all of which demonstrated both nonspecific and Ascaris-specific airway hyperreactivity, with changes in pulmonary mechanics of the same order as those seen in symptomatic human asthma. Other features analogous to human atopic disease included blunted cyclic adenosine monophosphate (cAMP) responsiveness to beta adrenergic agents and in vivo release of histamine and slow-reacting substance of anaphylaxis in response to antigen aerosol challenge. The dermatitis appears to be a manifestation of the atopic state in these dogs and may provide an animal model for the study of human atopic dermatitis.


The effect of extruded breadfruit flour on structural and physicochemical properties of beef emulsion modeling systems.
The objective was to determine structural and physicochemical properties of beef emulsion modeling systems prepared with native breadfruit flour and four different extruded breadfruit flours. Extrusion conditions for the flours were summarized as two different specific mechanical energies (74 or 145 kJ/kg) and four unique melt temperatures (83 °C, 100 °C, 105 °C, or 126 °C). Meat emulsions formulated at 3% replacement of beef with native or extruded breadfruit flours were compared with control (no additional flour) formulations. Replacement of beef with breadfruit flour (either native or extruded) did not significantly change cooking loss or instrumental redness values of cooked meat emulsions. Interestingly, replacement of beef with the fully gelatinized extruded breadfruit flours altered viscosity during heating as indicated by lower values for storage modulus (44.75% to 62.53% decrease compared with control) and lower values for loss modulus (25.90% to 52.54% decrease compared with control). This resulted in meat emulsions with a significant reduction in textural hardness (28.78% to 37.62% decrease compared with control).


Regulatory T cell phenotype and function 4 years after GAD-alum treatment in children with type 1 diabetes.
Glutamic acid decarboxylase (GAD)(65) formulated with aluminium hydroxide (GAD-alum) was effective in preserving insulin secretion in a Phase II clinical trial in children and adolescents with recent-onset type 1 diabetes. In addition, GAD-alum treated patients increased CD4(+) CD25(hi) forkhead box protein 3(+) (FoxP3(+)) cell numbers in response to in-vitro GAD(65) stimulation. We have carried out a 4-year follow-up study of 59 of the original 70 patients to investigate long-term effects on the frequency and function of regulatory T cells after GAD-alum treatment. Peripheral blood mononuclear cells were stimulated in vitro with GAD65 for 7 days and expression of regulatory T cell markers was measured by flow cytometry. Regulatory T cells (CD4(+) CD25(hi) CD127(lo)) and effector T cells (CD4(+) CD25(-) CD127(+)) were further sorted, expanded and used in suppression assays to assess regulatory T cell function after GAD-alum treatment. GAD-alum-treated patients displayed higher frequencies of in-vitro GAD(65) -induced CD4(+) CD25(+) CD127(+) as well as CD4(+) CD25(hi) CD127(lo) and CD4(+) FoxP3(+) cells compared to placebo. Moreover, GAD(65) stimulation induced a population of CD4(hi) cells consisting mainly of CD25(+) CD127(+) , which was specific of GAD-alum-treated patients (16 of 25 versus one of 25 in placebo). Assessment of suppressive function in expanded regulatory T cells revealed no difference between GAD-alum- and placebo-treated individuals. Regulatory T cell frequency did not correlate with C-peptide secretion throughout the study. In conclusion, GAD-alum treatment induced both GAD(65) -reactive CD25(+) CD127(+) and CD25(hi) CD127(lo) cells, but no difference in regulatory T cell function 4 years after GAD-alum treatment.


Effect of a global alteration of running technique on kinematics and economy.
In this study, we examined the consequences of a global alteration in running technique on running kinematics and running economy in triathletes. Sixteen sub-elite triathletes were pre and post tested for running economy and running kinematics at 215 and 250 m.min-1. The members of the treatment group (n=8) were exposed to 12 weeks of instruction in the "pose method" of running, while the members of the control group (n=8) maintained their usual running technique. After the treatment period, the experimental group demonstrated a significant decrease in mean stride length (from 137.25+/-7.63 cm to 129.19+/-7.43 cm; P<0.05), a post-treatment difference in vertical oscillation compared with the control group (6.92+/-1.00 vs. 8.44+/-1.00 cm; P<0.05) and a mean increase in submaximal absolute oxygen cost (from 3.28+/-0.36 l.min-1 to 3.53+/-0.43 l.min-1; P<0.01). The control group exhibited no significant changes in either running kinematics or oxygen cost. The global change in running mechanics associated with 12 weeks of instruction in the pose method resulted in a decrease in stride length, a reduced vertical oscillation in comparison with the control group and a decrease of running economy in triathletes.


Generation and characterization of a human-mouse chimeric antibody against the extracellular domain of claudin-1 for cancer therapy using a mouse model.
Claudin-1 (CLDN-1), an integral transmembrane protein, is an attractive target for drug absorption, prevention of infection, and cancer therapy. Previously, we generated mouse anti-CLDN-1 monoclonal antibodies (mAbs) and found that they enhanced epidermal absorption of a drug and prevented hepatitis C virus infection in human hepatocytes. Here, we investigated anti-tumor activity of a human-mouse chimeric IgG1, xi-3A2, from one of the anti-CLDN-1 mAbs, clone 3A2. Xi-3A2 accumulated in the tumor tissues in mice bearing with human CLDN-1-expressing tumor cells. Xi-3A2 activated Fcγ receptor IIIa-expressing reporter cells in the presence of human CLDN-1-expressing cells, suggesting xi-3A2 has a potential to exhibit antibody-dependent cellular cytotoxicity against CLDN-1 expressing tumor cells. We also constructed a mutant xi-3A2 antibody with Gly, Ser, and Ile substituted with Ala, Asp, and Arg at positions 236, 239, and 332 of the Fc domain. This mutant antibody showed greater activation of Fcγ receptor IIIa and in vivo anti-tumor activity in mice bearing human CLDN-1-expressing tumors than xi-3A2 did. These findings indicate that the G236A/S239D/I332E mutant of xi-3A2 might be a promising lead for tumor therapy.


Poor blood pressure control following subarachnoid hemorrhage in patients with sleep apnea.
Retrospective studies indicate that obstructive sleep apnea occurs often after aneurysmal subarachnoid hemorrhage. We aim to investigate if obstructive sleep apnea is associated with impaired blood pressure control early after subarachnoid hemorrhage. Patients with subarachnoid hemorrhage were recruited and screened for sleep apnea using cardiorespiratory polygraphy within 48 h after intensive care unit admission, and 6 months after hospital discharge at home. Blood pressure was continuously measured using intra-arterial catheter within the first 24 h after admission. Time between hospital admission and first blood pressure below 140 mmHg, and time with elevated blood pressure within the first 24 h after admission were compared between patients with and without obstructive sleep apnea. Of 60 patients, 55 successfully completed the study. Obstructive sleep apnea (AHI > 5/h) was diagnosed in 32% of men and 24% of women. While the time to reach a blood pressure of 140 mmHg did not differ (60.0 ± 26.2 min vs. 49.7 ± 16.4 min; p = 0.74), obstructive sleep apnea patients spent more time with blood pressure above 140 mmHg (292.0 ± 114.0 vs. 96.9 ± 28.3 min per 24 h; p = 0.025, CI 95 -363.6 to -26.5) within the observational period. Only AHI and diagnosed hypertension were significant predictors for elevated blood pressure (R2 0.42; p = 0.03). Obstructive sleep apnea is associated in our study with poor blood pressure control early after subarachnoid hemorrhage. These patients may need advanced management for blood pressure including management for OSA following subarachnoid hemorrhage. Screening for sleep apnea in patients with subarachnoid hemorrhage is recommended. ClincalTrials.gov identifier: NCT02724215, registered on March 31, 2016.


Effect of aging on immunological memory in gastrointestinal tract induced by sheep red blood cells in mice.
Tolerance induction by oral administration of sheep red blood cells (SRBC) was investigated in young and aged mice. Two-month old C3H/He mice receiving oral administration of 8 X 10(9) SRBC a day for two weeks became tolerant to a subsequent SRBC challenge in the systemic immune system. In contrast, older C3H/He mice aged about 1 year old receiving the same treatment did not become tolerant but resisted tolerance induction and produced a prominent IgG memory in the systemic immune system. Autoimmune-prone NZB mice showed a similar resistance to tolerance induction even at 3 months of age. To investigate a possible role of the liver in the oral tolerance induction, young (2-month old) C3H/He mice received an injection of 1 X 10(8) SRBC via portal vein. The mice thus treated, were not tolerized at all but immunized. The results suggest that gut-associated local immune system play a key role in the induction of the oral tolerance and that the tolerance inducing function of the local immune system declines with aging. Antigens in the gut including denatured self antigens may immunize the systemic immune system of aged animals.


Discriminative stimulus effects of S(-)-methcathinone (CAT): a potent stimulant drug of abuse.
Methcathinone ("CAT") is a CNS stimulant that is a very significant drug of abuse in the former Soviet Union. It has also appeared on the clandestine market in the United States and has been recently classified as a Schedule I substance. In the present study, S(-)-methcathinone [S(-)-CAT, 0.50 mg/kg, IP] was employed as the training drug in a two-lever drug discrimination task in rats. Once established, the S(-)-CAT stimulus was shown to have a rapid onset to action (within 5 min) and a duration of effect of approximately 60-90 min. In tests of stimulus generalization (substitution), the S(-)-CAT (ED50 = 0.11 mg/kg) stimulus generalized to S(+)-methamphetamine (ED5 = 0.17 mg/kg), S(-)-cathinone (ED50 = 0.19 mg/kg), S(+)-amphetamine (ED50 = 0.23 mg/kg), aminorex (ED50 = 0.27 mg/kg), (+/-)-CAT (ED50 = 0.25 mg/kg), (+/-)-cathinone (ED50 = 0.41 mg/kg), R(+)-CAT (ED50 = 0.43 mg/kg), cis-4-methylaminorex (ED50 = 0.49 mg/kg), methylphenidate (ED50 = 0.83 mg/kg), and cocaine (ED50= 1.47 mg/kg). S(-)-CAT-stimulus generalization did not occur to fenfluramine, a structurally related nonstimulant anorectic. Lastly, haloperidol (AD50 = 0.18 mg/kg), a dopamine receptor antagonist, potently antagonized the S(-)-CAT stimulus. It is concluded that S(-)-methcathinone is a very potent CNS stimulant, which appears to produce its stimulus effect, at least in part, via a dopaminergic mechanism.


Retinal capillary degeneration and blood-retinal barrier disruption in murine models of Alzheimer's disease.
Extensive effort has been made studying retinal pathology in Alzheimer's disease (AD) to improve early noninvasive diagnosis and treatment. Particularly relevant are vascular changes, which appear prominent in early brain pathogenesis and could predict cognitive decline. Recently, we identified platelet-derived growth factor receptor beta (PDGFRβ) deficiency and pericyte loss associated with vascular Aβ deposition in the neurosensory retina of mild cognitively impaired (MCI) and AD patients. However, the pathological mechanisms of retinal vascular changes and their possible relationships with vascular amyloidosis, pericyte loss, and blood-retinal barrier (BRB) integrity remain unknown. Here, we evaluated the retinas of transgenic APPSWE/PS1ΔE9 mouse models of AD (ADtg mice) and wild-type mice at different ages for capillary degeneration, PDGFRβ expression, vascular amyloidosis, permeability and inner BRB tight-junction molecules. Using a retinal vascular isolation technique followed by periodic acid-Schiff or immunofluorescent staining, we discovered significant retinal capillary degeneration in ADtg mice compared to age- and sex-matched wild-type mice (P < 0.0001). This small vessel degeneration reached significance in 8-month-old mice (P = 0.0035), with males more susceptible than females. Degeneration of retinal capillaries also progressively increased with age in healthy mice (P = 0.0145); however, the phenomenon was significantly worse during AD-like progression (P = 0.0001). A substantial vascular PDGFRβ deficiency (~ 50% reduction, P = 0.0017) along with prominent vascular Aβ deposition was further detected in the retina of ADtg mice, which inversely correlated with the extent of degenerated capillaries (Pearson's r = - 0.8, P = 0.0016). Importantly, tight-junction alterations such as claudin-1 downregulation and increased BRB permeability, demonstrated in vivo by retinal fluorescein imaging and ex vivo following injection of FITC-dextran (2000 kD) and Texas Red-dextran (3 kD), were found in ADtg mice. Overall, the identification of age- and Alzheimer's-dependent retinal capillary degeneration and compromised BRB integrity starting at early disease stages in ADtg mice could contribute to the development of novel targets for AD diagnosis and therapy.


A NIR ratiometric fluorescent probe for the rapid detection of hydrogen sulfide in living cells and zebrafish.
Hydrogen sulfide (H2S) acts as a gas transporter and cell protector and plays a role in a number of disorders and signaling processes. Given that the half-life of H2S in biological systems is between seconds and minutes, the development of rapid and accurate technologies for reliable monitoring H2S levels and dynamics in organisms is critical. However, it is still difficult to design innovative near-infrared fluorescent probes that can quickly and accurately detect H2S. Here, we constructed a novel NIR ratiometric fluorescent probe based on the "aldehyde group auxiliary strategy", Cy-H2S, for the quantitative detection and precise imaging of H2S in living cells and zebrafish. Cy-H2S responded quickly (150 s) and was highly sensitive (0.179 μM) to H2S donor. Cy-H2S was further successfully employed to track endogenous H2S fluctuation in HCT116 cells and zebrafish and evaluated the release efficiency of the H2S prodrug in a NIR ratiometric imaging way. Cy-H2S has the potential to be used as a reliable indication of H2S levels in living cells and zebrafish, as well as an innovative and practical instrument for furthering the physiological research of H2S, which will encourage the creation of advanced NIR ratiometric probes for a variety of biological applications.


Dosimetric assessment of tumor control probability in intensity and volumetric modulated radiotherapy plans.
Radiobiological models have been used to calculate the outcomes of treatment plans based on dose-volume relationship. This study examines several radiobiological models for the calculation of tumor control probability (TCP) of intensity modulated radiotherapy plans for the treatment of lung, prostate, and head and neck (H&N) cancers. Dose volume histogram (DVH) data from the intensity modulated radiotherapy plans of 36 lung, 26 prostate, and 87 H&N cases were evaluated. The Poisson, Niemierko, and Marsden models were used to calculate the TCP of each disease group treatment plan. The calculated results were analyzed for correlation and discrepancy among the three models, as well as different treatment sites under study. The median value of calculated TCP in lung plans was 61.9% (34.1-76.5%), 59.5% (33.5-73.9%) and 32.5% (0.0-93.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in prostate plans was 85.1% (56.4-90.9%), 81.2% (56.1-88.7%) and 62.5% (28.2-75.9%) with the Poisson, Niemierko, and Marsden models, respectively. The median value of calculated TCP in H&N plans was 94.0% (44.0-97.8%) and 94.3% (0.0-97.8%) with the Poisson and Niemierko models, respectively. There were significant differences between the calculated TCPs with the Marsden model in comparison with either the Poisson or Niemierko model (p < 0.001) for both lung and prostate plans. The TCPs calculated by the Poisson and Niemierko models were significantly correlated for all three tumor sites. There are variations with different radiobiological models. Understanding of the correlation and limitation of a TCP model with dosimetric parameters can help develop the meaningful objective functions for plan optimization, which would lead to the implementation of outcome-based planning. More clinical data are needed to refine and consolidate the model for accuracy and robustness. This study has tested three radiobiological models with varied disease sites. It is significant to compare different models with the same data set for better understanding of their clinical applicability.


Patterns and outcomes of pediatric facial fractures in the United States: a survey of the National Trauma Data Bank.
Pediatric trauma involving the bones of the face is associated with severe injury and disability. Although much is known about the epidemiology of facial fractures in adults, little is known about national injury patterns and outcomes in children in the US. The epidemiology of facial injuries in children and adolescents (ages 0 to 18 years) was described using the National Trauma Data Bank (2001 to 2005) to examine facial fracture pattern, mechanism, and concomitant injury by age. A total of 12,739 (4.6%) facial fractures were identified among 277,008 pediatric trauma patient admissions. The proportion of patients with facial fractures increased substantially with age. The most common facial fractures were mandible (32.7%), nasal (30.2%), and maxillary/zygoma (28.6%). The most common mechanisms of injury were motor vehicle collision (55.1%), violence (11.8%), and falls (8.6%). These fracture patterns and mechanisms of injury varied with age. Compared with patients without facial fractures, patients with fractures exhibited substantial injury severity, hospital lengths of stay, ICU lengths of stay, ventilator days, and hospital charges. In addition, patients with facial fractures had more severe associated injury to the head and chest and considerably higher overall mortality. Causes and patterns of facial fractures vary with age. Cranial and central facial injuries are more common among toddlers and infants, and mandible injuries are more common among adolescents. Although bony craniofacial trauma is relatively uncommon among the pediatric population, it remains a substantial source of mortality, morbidity, and hospital resource use. Continued efforts toward injury prevention are warranted.


An application of Lacker's mathematical model for the prediction of ovarian response to superstimulation.
Introduction. A mathematical model of ovarian follicular growth is applied to the problem of predicting ovarian response in a superstimulation protocol. Methods. Fifty-four women enrolled in an ovarian superstimulation program of therapy for the amelioration of idiopathic infertility had their ovarian cycles synchronized by taking Demulen 30 for two weeks prior to the study. Daily ultrasonographic imaging, measurements of serum estradiol and doses of hMG began on day 5 after the patients stopped taking Demulen. The diameters of individual follicles were measured and followed daily. When the largest follicle attained a diameter of 19 mm, hCG was given to induce ovulation. Individual follicle growth data were fit to a mathematical model of ovarian follicle maturation and the resulting parameters were used to classify patients into low and high ovarian response groups. Results. The parameters computed from the mathematical model fit were found to be predictive of ovarian response with a sensitivity of 71% and a specificity of 70%. The parameters were also meaningful within the context of the original mathematical model and have value for determining how doses of hMG may be adjusted during the course therapy to increase the ovarian response in individuals. Conclusion. Mathematical modeling of ultrasonographically derived follicular growth data has significant potential for clinical application in ovarian superstimulation protocols. The method of fitting follicular growth data to a mathematical follicle maturation surface furthermore provides a straightforward approach for the characterization of ovarian follicular dynamics in general.


Correlation between running asymmetry, mechanical efficiency, and performance during a 10 km run.
Running asymmetry is considered a matter of concern for performance and injury, but the association between asymmetry and performance remain unclear. There are different strategies to address asymmetries and its relationship with performance. Here we investigated the correlation between global symmetry index and mechanical efficiency during 10 km running. Thirteen amateur trained athletes (8 men and 5 women) performed a 10 km running at a fixed pace while a 3D accelerometer attached to the pelvic region recorded position data throughout the course of the run and gas exchanges were monitored breath by breath. Global symmetry index was determined for 3 directions, and mechanical efficiency was calculated as the ratio of external work output to energy expenditure determined from gas analysis. Global Symmetry Index and mechanical efficiency decreased (-55.5% and -44.8%, respectively) during the course of the 10 km run (p < 0.01). A positive correlation was observed between global symmetry index and efficiency (r = 0.66, p = 0.01). Asymmetry in the vertical direction had a relatively higher impact on the global symmetry index. The global symmetry index accounted for 43.1% of the variance in mechanical efficiency (p = 0.015). Symmetry, evaluated by the global symmetry index, directly correlates with mechanical efficiency during a 10 km run.


Potential anticancer properties of calotropis procera: An investigation on breast and colon cancer cells.
Calotropis procera is a perennial flowering plant of the Apocynaceae family, traditionally used in medicine to treat various ailments. Recent investigations have revealed its potential therapeutic activities such as anti-inflammatory, gastroprotective, analgesic, anti-obesity, and anti-diabetic properties. RP-HPLC qualitatively and quantitatively evaluated the phenolic acids and flavonoids in the ethanolic extract at two different wavelengths, 280 and 330 nm. In addition, total phenolic and flavonoid contents were measured via spectrophotometric determination in addition to the antioxidant activity. The antiproliferative effects of C. procera were investigated on two cancer cell lines: human colon (HCT-116) and breast (MCF-7) cancer. Several methods were utilised to analyse the effectiveness of the plant extract on the cytotoxicity, apoptosis, cell cycle progression, genes involved in the cell cycle, and protein expression profiles of HCT-116 and MCF-7 cells. These included the MTT assay, Annexin V-FITC/PI, analysis of the cell cycle, and Western blot. Results indicated that ferulic and caffeic acids were the major compounds at λmax 280 nm (1.374% and 0.561%, respectively), while the major compounds at λmax 325 nm were kaempferol and luteolin (1.036% and 0.512%, respectively). The ethanolic extract had significantly higher antioxidant activity (80 ± 2.3%) compared to ascorbic acid (90 ± 3.1%). C. procera extract exhibited dose-dependent cell growth inhibition, with an estimated IC50 of 50 μg/mL for MCF-7 and 55 μg/mL for HCT-116 cells at 24 h. Annexin V-FITC/PI confirmed the induction of apoptosis. Remarkably, cell cycle arrest occurred at the sub-G1 phase in MCF-7 cells, while in HCT-116 cells, it was observed at the G2-M phase. The sub-G1 arrest was associated with dysregulation of Akt, p-AKT, mTOR, and p-mTOR proteins, as confirmed by the Western blot analysis, while downregulation of CDK1, cyclin B1, and survivin caused G2-M arrest.


Use of 1,2-bis(2-amino-5-fluorophenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA) in the measurement of free intracellular calcium in the brain by 19F-nuclear magnetic resonance spectroscopy.
We have applied the 19F-nuclear magnetic resonance (NMR) calcium indicator 1,2-bis(2-amino-5-fluoro-phenoxy)ethane-N,N,N',N'-tetraacetic acid (5FBAPTA) to the measurement of the free intracellular calcium concentration [( Ca2+]i) in superfused brain slices. A mean +/- SD control value of 380 +/- 71 nM (n = 18) was obtained at 37 degrees C using 2.4 mM extracellular Ca2+. Subcellular fractionation studies using [3H]5FBAPTA showed that after loading of its tetraacetoxymethyl ester, approximately 55% was de-esterified, with the other 45% remaining as the tetraester bound to membranes. Of the de-esterified 5FBAPTA, greater than 90% was in the cytosolic fractions, with less than 1% in the mitochondria or microsomes. The NMR-visible de-esterified 5FBAPTA slowly disappeared from the tissue with a t1/2 of 4 h. A time course after loading confirmed that the calculated [Ca2+]i was constant over a 5-h period, although the scatter of individual results was +/- 20%. The [Ca2+]i was increased by a high extracellular K+ concentration ([K+]e), by a low extracellular concentration of Na+, and by the calcium ionophore A23187. On recovery from high [K+]e, the [Ca2+]i "overshot" to values lower than the original control value. The [Ca2+]i was surpisingly resistant to changes in extracellular Ca2+ concentration.


Effects of excess weight on cancer incidences depending on cancer sites and histologic findings among men: Korea National Health Insurance Corporation Study.
The effects of excess weight on the development of cancers are controversial, and little is known for populations outside the United States and Europe. We conducted this study to assess the effects of excess weight with a large cohort of Koreans. We assessed the relationship between body mass index (BMI) and various cancers in a 10-year follow-up cohort of 781,283 Korean men who were free of prior cancer at baseline. Weight and height were measured, and questionnaires related to health behaviors and medical history were completed. Data on newly developed cancers were obtained from two organizations in Korea. A proportional hazards model was used to examine the relationship between BMI and cancer. Adenocarcinoma in the colon and rectosigmoid, hepatocellular carcinoma, cholangiocarcinoma, adenocarcinoma in the prostate, renal cell carcinoma, papillary carcinoma in the thyroid, small-cell carcinoma in the lung, non-Hodgkin's lymphoma, and melanoma had positive dose-dependent relationships with BMI (all P < .05). Although no linear trend was found (P = .267), obese men who never smoked with a BMI of >or= 30 kg/m(2) had an increased risk of developing gastric adenocarcinoma (relative risk = 1.73). Other cancers, such as leukemia, multiple myeloma, and gallbladder and pancreatic cancer, did not show significant associations. These findings show that, even in Koreans, obesity clearly increases the risk of many types of cancers and the strength of the associations varies with the organ and histologic type. Because these obesity-related cancers are reported to be rapidly increasing in Korea and many other Asian countries, controlling obesity epidemics could be an effective tool for preventing these cancers in these areas.


Supplementary Notes On An Abnormal Taenia Sp. With Double Genital Pores.
A complete but abnormal form of Taenia worm was obtained from an 18-year-old male student in Cheju Island, Korea, which has been known as a heavy endemic area of Taenia saginata and few of T. solium. There was an apical hookless eminence in the scolex, longitudinal white line along the middle portion of entire strobila, double genital pores and several lateral buddings from the strobila. It was considered an abnormal form of Taenia species, probably T. saginata.


Interaction of rat alveolar macrophages with pulmonary epithelial cells following exposure to lipopolysaccharide.
Because both alveolar macrophages and pulmonary epithelial cells are primary target cells of inhaled endotoxin, it is of interest to study the interaction of alveolar macrophages with epithelial cells following exposure to lipopolysaccharide (LPS). Repeated bronchoalveolar lavage suggested that rat alveolar macrophages became adhesive to epithelial cells in response to intratracheally instilled LPS at 0.5 h post-exposure in vivo. Adherence of alveolar macrophages to SV40T2 (rat type II pulmonary epithelial cells transformed by SV40) was also increased following 0.5-h stimulation with LPS in vitro. The adherence was increased with dose and reached a plateau at 2 micrograms/ml LPS. The transepithelial resistance of the SV40T2 monolayer was decreased by coculture with macrophages in the presence of LPS for 4 h. The transepithelial resistance was not changed by exposure of SV40T2 alone to LPS or conditioned medium obtained from LPS-stimulated macrophages, suggesting that the intercellular interaction between alveolar macrophages and epithelial cells or unstable products of LPS-exposed alveolar macrophages was associated with the decrease in transepithelial resistance. Following the decrease in transepithelial resistance, lysis of SV40T2 was observed in the LPS-exposed coculture system. However, the lysis of SV40T2 did not occur until 12 h after the addition of LPS, indicating that the junctional change of the monolayer preceded cell death in SV40T2. Cytotoxicity of LPS-stimulated macrophages was significantly reduced by NG-monomethyl-L-arginine (NMMA), an inhibitor of nitric oxide synthase, but NMMA did not reduce the decrease in transepithelial resistance. These results suggest that the greater adherence of alveolar macrophages to epithelial cells, the junctional change of the epithelial monolayer and the lysis of epithelial cells occur in this order in the LPS-exposed alveolar macrophage-SV40T2 coculture system, and the greater adherence of alveolar macrophages may play a role in LPS-induced inflammation in the rat lung.


Prognostic factors for survival in extensive-stage small cell lung cancer: An Italian real-world retrospective analysis of 244 patients treated over the last decade.
Potential relationships with the prognosis of patients with extensive-stage non-small cell lung cancer (ES-SCLC) have been investigated without valid results. A retrospective analysis of real-world data of consecutive patients with ES-SCLC admitted to our Medical Thoracic Oncology Unit was carried out from 2010 to 2020, focusing on identification of prognostic factors. Kaplan-Meier analysis was used to represent progression-free survival (PFS) and overall survival (OS). Univariable and multivariable Cox models were used to investigate prognostic factors. The analysis included 244 patients. The median OS was 8 months (95% confidence interval [CI]: 8-10) and the median PFS was 5 months (95% CI: 5-6). The univariable analysis showed that factors associated with shorter OS were older age (p = 0.047), TNM stage 4 versus 3 (p < 0.001), Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 and 2 versus 0 (p < 0.001), and >2 metastatic sites (p = 0.004). Mediastinal radiotherapy (RT) (p < 0.001), >1 irradiated site (p = 0.026), 3 and 4 chemotherapy (CT) lines versus 1 (p = 0.044 and 0.001, respectively), prophylactic cranial irradiation (PCI) (p < 0.001), and surgery (p = 0.001) correlated with longer OS. The multivariable analysis revealed statistically significant associations for TNM, ECOG PS 2 versus 0, number of CT lines, PCI, and surgery. A total of 23 patients (9.4%) survived ≥24 months, 39% of whom had received four CT lines and 48% had mediastinal RT. Our data suggest that tumor burden, PS, and mediastinal RT strongly correlate with outcome. With the addition of immunotherapy to CT, the identification of new biomarkers as predictive factors is urgently required.