Cushing syndrome and giant sterile abscess induced by self intramuscular injection of supra-therapeutic doses of triamcinolone.
Corticosteroid are among the most commonly used medications for a wide range of inflammatory, autoimmune and neoplastic disorders. Therefore, it is important for the physician to be aware of their side effects, in relation to different forms and delivery, that occur more often with oral therapy. A 33-year old professional drummer had been suffering from bilateral tenosynovitis of the wrists for three months. In order to accelerate the recovery and play drums again, he self-injected supra-therapeutic doses of triamcinolone acetonide (a total of injected drug > 2,400 mg was calculated) in his right gluteus. The intramuscular overuse of triamcinolone acetonide caused Cushing syndrome associated with a giant sterile abscess that involved the right gluteal muscles and the adjacent subcutaneous tissue. A large intramuscular sterile abscess can be a side effect of supra-therapeutic intramuscular triamcinolone dose and this should be explained to the patient prior to initiation of treatment with triamcinolone.


Comparison of fracture resistance of endodontically treated maxillary first premolar with mesio-occlusal-distal access restored with composite resin, fiber post, and prefabricated metal posts restored with/without full-coverage metal crowns.
A myriad of materials and procedures have been recommended for restoring the root-filled teeth with significant loss of tooth structure and the most common method being the use of "posts." A mesio-occluso-distal preparation was done on eighty intact maxillary first premolars, followed by access preparation and cleaning and shaping with rotary files. All samples were obturated and divided into four groups (n = 20). In Group 1, 3-mm gutta-percha was removed and restored using composite resin; Group 2 - Group 1 + crowns; Group 3 - prefabricated fiber post + crowns; and Group 4 - prefabricated metal post + crowns. All the groups were subdivided into eight groups (n = 10), fractured with 90° vertical and 45° oblique loading by a universal testing machine. Fracture resistance was analyzed and compared by means of two-factorial two-way analysis of variance and Scheffe's post hoc test. Under 90° loading, the fracture load of teeth restored with the Nayyar's composite resin core and crown was greatest. Under 45° loading, the fracture load of teeth restored with prefabricated metallic posts was significantly (P < 0.05) less than that in other groups. Under 45° load, group with fiber post exhibited significantly (P < 0.05) more number of favorable fractures than other groups. Under the conditions of vertical and oblique loadings, fiber post and composite resin core with a full-coverage crown is the most effective restorative modality for protecting the remaining tooth structure in pulpless teeth.


Interleukin-18 expression and modulation in human corneal epithelial cells.
The interferon-gamma-inducing factor Interleukin-18 (IL-18) is a recently described cytokine that appears to have multiple important pro-inflammatory effects including the induction of interferon-gamma (IFN-gamma) by activated T-cells. The expression of IL-18 by human cornea has not been previously reported. In the present study, we examine the possibility that human corneal epithelial cells are capable of producing this leukocyte-activating factor which may play an important role in IFN-gamma-dependent inflammation responses in the cornea. Northern blot analysis and ELISA were used to investigate the in vitro expression of IL-18 mRNA and protein respectively in primary (HCEC) and transformed human corneal epithelial cells (HCET). To determine if IL-18 expression was modulated by pro-inflammatory mediators, cells were treated with lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA) or synthetic double stranded RNA (poly dI : dC). IL-18 bioactivity was determined in a leukocyte interferon-gamma induction assay and IL-18 was immunolocalized in whole human cornea by immunohistochemistry using a specific anti-IL-18 antibody. IL-18 mRNA and bioactive protein was constitutively expressed by human corneal epithelial cells and upregulated by PMA, LPS and poly dI : dC. The constitutive expression of IL-18 protein immunoreactivity was also demonstrated in the epithelial cells of whole human cornea tissue. This is the first study demonstrating that corneal epithelial cells are capable of producing the IFN-gamma inducing factor IL-18. Increased bioactive corneal IL-18 production can be induced by a number of pro-inflammatory agents and may play an important role in initiating gamma-interferon-mediated inflammatory responses in the cornea.


TCR-induced FOXP3 expression by CD8+ T cells impairs their anti-tumor activity.
Adoptive cell transfer therapy using CD8+ T lymphocytes showed promising results eradicating metastatic malignancies. However, several regulatory mechanisms limit its efficacy. We studied the role of the expression of the transcription factor FOXP3 on CD8+ T cell function and anti-tumor immunity. Here we show that suboptimal T cell receptor stimulation of CD8+ T cells upregulates FOXP3 in vitro. Similarly, CD8 T cells transferred into tumor-bearing mice upregulate FOXP3 in vivo. Cell-intrinsic loss of FOXP3 by CD8+ T cells resulted in improved functionality after TCR stimulation and better antitumor responses in vivo. Inhibition of the FOXP3/NFAT interaction likewise improved CD8+ T cell functionality. Transcriptomic analysis of cells after TCR stimulation revealed an enrichment of genes implicated in the response to IFN-γ, IFN-α, inflammatory response, IL-6/JAK/STAT, G2M checkpoint and IL-2/STAT signaling in FOXP3-deficient CD8+ T cells with respect to FOXP3-wt CD8+ T cells. Our results suggest that transient expression of FOXP3 by CD8+ T cells in the tumor microenvironment restrains their anti-tumor activity, with clear implications for improving T cell responses during immunotherapy.


Necrotic tumor growth: an analytic approach.
The present paper deals with a free boundary problem modeling the growth process of necrotic multi-layer tumors. We prove the existence of flat stationary solutions and determine the linearization of our model at such an equilibrium. Finally, we compute the solutions of the stationary linearized problem and comment on bifurcation.


HEATR1 Deficiency Promotes Chemoresistance via Upregulating ZNF185 and Downregulating SMAD4 in Pancreatic Cancer.
To discover the correlated gene with HEATR1 in regulating chemoresistance of gemcitabine. Gene chip analysis was performed to find out differential genes between HEATR1-KD and control groups. The top 20 genes were subjected to high-content screening, and functional assay was implemented. Gene expression profiling was carried out to find the downstream target. Immunohistochemistry and survival analysis were performed. ZNF185 fold change (4.5285) was the most significant between the HEATR1-KD and control groups. Knocking down ZNF185 could promote the chemosensitivity, apoptosis, and proliferative inhibition, with SMAD4 significantly upregulated. Patients with high HEATR1 and SMAD4 or low ZNF185 exhibited better survival. HEATR1, ZNF185, and SMAD4 could affect the chemosensitivity of gemcitabine and may be the indicators of gemcitabine selection in the chemotherapy of pancreatic cancer.


Simple Strategy for Scalable Preparation Carbon Dots: RTP, Time-Dependent Fluorescence, and NIR Behaviors.
Transforming carbon dots (CDs) fluorescent materials into smart materials with complex functions is a topic of great interest to nanoscience. However, designing CDs with regulating fluorescence/phosphorescence that can be visually monitored with the environment changes in real-time remains a challenge. Here, a very simple strategy, one-step solvent-free catalytic assistant strategy, which is low cost, facile, environment-friendly, and high throughput, is put forward. Hydrogen bond is used to manipulate nanostructure of CDs, and the obtained carbon dots (M-CDs) show a series of attractive properties including matrix-free room-temperature phosphorescence, time-dependent fluorescence, and near-infrared emissive characteristics. Different from the traditional aggregation caused quenching or aggregation-induced emission fluorescent materials, M-CDs exhibit unprecedented and unique dispersion induced redshift fluorescence phenomenon, promoting the studies of fluorescence from static to dynamic. The causes of this phenomenon are further analyzed in detail. As a kind of intelligent fluorescent materials, this new designed CDs greatly enrich the basic recognition of CDs by illustrating the relationship between redshift fluorescence behaviors and the dispersion states, and may provide with an opportunity for solid-state fluorescent materials, anti-counterfeiting, cellular imaging, and hopefully many others.


Regulatory review: How do agencies ensure the quality of decision making?
The Centre for Innovation in Regulatory Science (CIRS) Workshop on Regulatory Review brought together international regulators and multinational pharmaceutical company representatives to focus on best practices that underlie regulatory decision making, thereby facilitating the transparent, timely, procedurally predictable, and good-quality evaluation of new medicines. Participants investigated frameworks used by agencies, discussed challenges for regulatory agencies in making quality decisions, investigated the role of other stakeholders, and made recommendations of activities and processes that agencies and companies can consider to enable quality decision making.


Prion protein immunohistochemical staining in the brains of monkeys with transmissible spongiform encephalopathy.
Prion protein (PrP) immunohistochemical staining of the brains of common marmosets (Callithrix jacchus) with experimental transmissible spongiform encephalopathy is described. The monkeys (n = 17) had been injected, intracerebrally, 17-49 months previously with homogenates of brain tissue taken post mortem from a cow with BSE (n = 2 monkeys), a sheep with natural scrapie (n = 2 monkeys), human cases of growth hormone related Creutzfeldt-Jakob disease (CJD) (n = 2 monkeys), sporadic CJD (n = 5 monkeys), or Gerstmann-Sträussler-Scheinker disease (GSS) (n = 4 monkeys), or from monkeys with spongiform encephalopathy resulting from injection with brain tissue from these last two cases (n = 1 monkey from each case). Only diffuse PrP-staining was seen in monkeys injected with CJD-material whereas more aggregated deposits of PrP were seen in monkeys injected with BSE-, scrapie--and GSS-brain tissue. There were no patterns of staining specific to the brains injected with BSE-material that could be used to identify the origin of that inoculum. BSE--and scrapie-injected monkey brains could be distinguished from each other because in BSE-injected monkey brain the spongiform vacuolation was largely confined to subcortical structures whereas in scrapie-injected monkey brain the spongiform vacuolation was also prominent in the neocortex. The patterns of PrP deposition differed markedly between those seen in monkey brains injected with BSE-material or CJD-material, but the patterns of PrP staining seen in monkey brains injected with BSE-material were also seen in monkey brains injected with scrapie--or GSS-material. Overall there was a correlation between the length of the incubation period and the amount of aggregated PrP-staining, but no correlation between the neuropathological picture and the clinical presentation of neurological signs.


Prediction of optimal injection protocol for tumor detection in contrast-enhanced dynamic hepatic CT using simulation of lesion-to-liver contrast difference.
The detection of hepatic lesions in computed tomography (CT) is improved when a contrasting material is administered intravenously, but it depends considerably on how this agent is injected. In this study, we constructed a compartment model for a liver containing a hepato-cellular carcinoma (HCC), and simulated the difference in lesion-to-liver contrast enhancement. Using this model, we simulated the effects of various injection factors on the detectability of a lesion and searched for the optimal injection protocol for detecting tumors in contrast-enhanced dynamic hepatic CTs. We found that the mass injection rate, or k-value (in mg/s), (which is the volume injection rate, in ml/s, multiplied by the contrast agent concentration, in mg/ml) plays a critical role in the injection protocol optimized for tumor detection, and has a unique value for a given body weight independent of the total injection dose.


Preclinical evaluation of a gene therapy treatment for transitional cell carcinoma.
Three drugs were compared for their efficacy in treating murine transitional cell carcinoma (TCC) of the bladder. Intravesical gene therapy treatments utilizing expression-targeted plasmids, where the murine cyclooxygenase-2 (Cox-2) promoter was used to drive the expression of exogenously inducible forms of caspases 3 and 9, were compared with treatment modalities employing Bacille Calmette-Guérin (BCG) and celecoxib. When administered via lavage, only the gene therapy regimen was found to be effective at restricting tumor progression following a 7-day incubation of tumor tissues. Celecoxib was also administered via the diet to allow for systemic delivery of the drug. The most efficacious celecoxib use tested yielded tumors with masses of (18.3±8.4 mg) versus the gene delivery method, which yielded tumors with masses of (3.6±7.7 mg). The difference was significant (t-test, n≥4, P<0.025). The results showed that the Cox-2 expression-targeted gene therapy system could efficiently bypass the bladder permeability barrier and more effectively inhibit tumor growth and development than either BCG or celecoxib treatments. Long-term data further demonstrated that the gene therapy system could effectively inhibit tumor growth and elongate life expectancy.


Let's get back to work: Preventive biological cycle management of COVID-19 in the workplace.
The primary response to the coronavirus (COVID-19) pandemic has been to minimize social contact through lockdown measures. The closure of non-essential businesses to tackle the spread of the coronavirus has had negative consequences for the global economy, production, and employment. To outline how known occupational health principles can be used for preventative management of the coronavirus in workplaces to support resumption of work. A discussion of current knowledge of COVID-19, the cost of the lockdown strategy, and preventative biological cycle management. The evidence-based literature indicates that biological cycle management can control the risk of coronavirus infection, provide a suitable and sufficient exit strategy from lockdown, and support getting employees back to work. Adherence to personal protective equipment standards has been insufficient, indicating a need for workplace investment and education. Imposed restrictions on workplace operations can be lifted without compromising worker health and safety when a workplace commits to practicing the three principles of biological cycle management.


MicroRNA-203-mediated posttranscriptional deregulation of CPEB4 contributes to colorectal cancer progression.
Elevated cytoplasmic polyadenylation element-binding 4 (CPEB4) is aberrantly expressed in several malignant cancers. However, its expression pattern, clinical significance, and biological function in colorectal cancer are still unknown. In this study, we demonstrated that CPEB4 is abundantly overexpressed in colorectal cancers and has the potential to be used for predicting clinical outcomes of colorectal cancer patients. We suppressed CPEB4 expression by small interfering RNA (siRNA) in SW480 and LOVO cells to clarify the role of CPEB4 on the cell apoptosis and proliferation in vitro. Further study revealed that knockdown of CPEB4 decreased the expression of anti-apoptotic protein B-cell lymphoma-extra large (Bcl-XL), but enhanced the expression of B-cell lymphoma-2-associated X (Bax). In addition, we indicated that CPEB4 is a novel target of miR-203, a tumor suppressive microRNA. Notably, restoration of CPEB4 in SW480 cells inhibited miR-203-induced apoptosis signaling pathway, which in turn enhanced cell proliferation and suppressed cell apoptosis. Taken together, our findings imply that posttranscriptional deregulation of CPEB4 contributes to the inhibited cell proliferation and the enhanced cell apoptosis in colorectal cancer, and directly targeting CPEB4 by miR-203 might be a novel strategy in colorectal cancer treatment.


An Approach to Peri-Fused Heterocycles: A Metal-Mediated Cascade Carbonylative Cyclization/Dearomatic Diels-Alder Reaction.
A short and efficient route to peri-fused heterocycles has been developed. The transition metal in cooperation with the imino directing group cleaves the C-P bond of the phosphirane, followed by 1,1-insertion of CO and reductive elimination to give a reactive azaphosphacyclohexone derivative. The further dearomatic Diels-Alder reaction of the in situ-generated azaphosphacyclohexone with alkenes provides an array of annulated heterodecalins with high molecular complexity and atomic utilization.


Temporal bone involvement of IgG4-related disease: a rare condition misleading to petrous apicitis causing lateral rectus palsy.
IgG4-related disease (IgG4-RD) of temporal bone is rare and clinical manifestation mimics infection. A 19-year-old female presented with progressive left earache and intermittent left nasal obstruction. Then, she rapidly developed left lateral rectus palsy. The physical examination revealed mild redness of left tympanic membrane and a small nasal polyp from the left middle meatus. CT scan showed left petrous apicitis and enhancing sinonasal mucosa. Therefore, Gradenigo's syndrome was first considered. The empirical intravenous antibiotic was immediately prescribed and surgery was performed. The intraoperative pale soft tissue mass in middle ear and polyp in the left nasal cavity were sent for pathological examination and found positive immunohistochemical stains for IgG4 in plasma cells. Systemic corticosteroid, the first-line treatment, was started and her symptoms were finally recovery.


[Psychological implications of sport and aging--a neglected research field].
Since the 1990s, sport and aging is increasingly in the focus of psychological research. Besides motivational aspects the main attention lies on the positive influence of sporting activity on physical and psychological health. Thus, ageing and sports is mostly considered under functional aspects. The aim to compensate deficits through sports in the elderly reflects the socially widespread pictures of age (frailness) and sport (capability, youthfulness). In this article the deficit model with the associated clichés is questioned on the background of the latest research. The author argues for a more differentiated and constructive view on sport and aging and to take into consideration the specific needs of older people.


The mechanism of synovial fluid retention in pressurized joint cavities.
Hyaluronan (HA) in synovial fluid is vital to fluid retention in joint cavities. This study aims to evaluate a HA concentration polarization hypothesis and to examine, quantitatively, the agreement between theoretical predictions and experimental results. A non-steady-state model was developed for HA ultrafiltration and concentration polarization on the synovial surface. The Kedem-Katchalsky equation was used to calculate the trans-synovial filtration rate Q as the HA concentration polarization layer built up. Model parameters were based on data from experiments. Effects of parameters on fluid filtration were investigated. The HA osmotic pressure at the synovial surface was found to approach the intra-articular pressure, P, during fluid infusion. The model simulated the experimentally observed decay in Q with the time at constant P, and predicted nonlinear P-Q relations in good agreement with experimental results over a range of bulk HA concentrations, from pathological (0.2 g L(- 1)) to physiological (4.0 g L(-1)). It gave quantitative insights into the development of the osmotic pressure and the significance of the HA reflection coefficient. The osmotic pressure of a HA concentration polarization layer on the synovial surface leads to outflow buffering. This provides the mechanism by which the vital lubricating synovial fluid is retained in a joint cavity under pressure.


Fungal liver abscesses in acute leukaemia--a report of two cases.
The radiological findings in two cases of hepatic fungal microabscesses (one with concomitant splenic involvement) occurring in children with acute leukaemia are presented, and the previous literature is reviewed. Usually both liver and spleen are involved, though either organ may be affected in isolation. Typical ultrasound features include hepatosplenomegaly with multiple hypoechoic areas throughout the liver and spleen, often with a 'target' configuration. Computed tomography shows these as multiple non-enhancing low attenuation lesions. These findings in a patient with acute leukaemia are strongly suspicious of fungal infection, and percutaneous fine-needle aspiration under ultrasound or computed tomography-guidance is indicated.


Neural Correlates of Boredom in Music Perception.
Music can elicit powerful emotional responses, the neural correlates of which have not been properly understood. An important aspect about the quality of any musical piece is its ability to elicit a sense of excitement in the listeners. In this study, we investigated the neural correlates of boredom evoked by music in human subjects. We used EEG recording in nine subjects while they were listening to total number of 10 short-length (83 sec) musical pieces with various boredom indices. Subjects evaluated boringness of musical pieces while their EEG was recording. Using short time Fourier analysis, we found that beta 2 rhythm was (16-20 Hz) significantly lower whenever the subjects rated the music as boring in comparison to non-boring. The results demonstrate that the music modulates neural activity of various parts of the brain and can be measured using EEG.


Value of lipopolysaccharide binding protein, interleukin-6 and C-reactive protein as biomarkers of severity in acute diverticulitis: a prospective study.
New biomarkers have the capability to predict severity and outcome of infectious diseases. Lipopolysaccharide binding protein (LBP) and Interleukin 6 (IL-6) were determined as new markers in patients with acute diverticulitis and were compared with standard markers such as C-reactive protein (CRP) and white blood cell count (WBC). CRP, IL-6, WBC and LBP were measured in 38 patients at hospital admission and every second day and after colonoscopy. Multi-slice CT scans, ultrasound and early colonoscopy were performed to confirm diagnosis and to detect complications (perforations, stenosis). CRP, IL-6 and LBP levels one correlated highly with each other and were equally influenced by antibiotic therapy. WBC changes were unremarkable. Severity of the disease (sealed- or non-perforation) was not reflected by the biomarkers. In non-perforated patients, colonoscopy was performed on day 6 (median) after admission with a success rate of 93%. Sealed-perforated patients were examined on median day 11 with a success rate of 60% (p > 0.001). Failure in all cases was due to sigmoidal stenosis requiring surgery. In a receiver-operating characteristic curve analysis (ROC), LBP on day one performed best in predicting colonic steno-sis with an area under the curve of 0.88 (95% CI 0.73 - 0.03 p < 0.02). CRP, IL-6, and LBP can be used to monitor diverticulitis. Initial LBP values in patients with acute diverticulitis may also be usefully in detecting candidates for surgical intervention.


Cotton-strip assays: Let's move on to eco-friendly biomonitoring!
There is increasing recognition that functional bioindicators are needed for ecosystem health assessments. In this perspective, cotton strip assays are widely considered as a standard method to account for organic matter decomposition in streams. However, cotton cultivation and manufacture raise both environmental and societal dramatic issues that are - in our opinion - irreconcilable with the objectives of bioindication. In this study, we assessed the relevance of four alternative - eco-friendly - textiles (made of organic cotton, hemp and linen) by comparing their chemical composition and degradation rates in six streams. Chemical composition exhibited low variations among textiles, but contrasted sharply with the expectation that cotton is mostly composed of cellulose. Moreover, surprisingly high nutrient (0.49% N) contents occurred in the conventional cotton strips compared with the organic textiles (N < 0.12%). All textiles provided similar degradation rates across the six streams, meaning that they could be interchangeably used as alternatives to conventional cotton strips. We thus call for the adoption of such ethical and eco-friendly tools as 'next-generation' indicators for the functioning of stream ecosystem.


Quarterly electricity consumption prediction based on time series decomposition method and gray model.
Accurately predicting electricity consumption is crucial for reducing power waste and maintaining power system stability. To address the non-linear and seasonal fluctuations of electricity consumption, this paper proposes a seasonal prediction method based on Seasonal and Trend decomposition using Loess (STL) algorithm and gray model by introducing time series decomposition method. The STL decomposition algorithm decomposes fluctuating electricity data into three components: trend, seasonal, and remainder. Then reasonable methods are used to predict components with different data characteristics. The novel model is employed to analyze the quarterly electricity consumption in Zhejiang province of China from 2014Q4 to 2022Q3. The experimental results show that the prediction accuracy of this model is superior to the state-of-the art models; the MAPE and RMSPE values are 1.77% and 2.37%, respectively. Our model that can effectively identify seasonal fluctuations in data sequences provides a new method for predicting seasonal fluctuation data and optimizing seasonal electricity supply schemes.


Time trends in the incidence of acute lymphoblastic leukemia among children 1976-2002: a population-based Nordic study.
We studied the incidence of childhood acute lymphoblastic leukemia in Denmark, Finland, Norway, and Sweden during 1976-2002, on the basis of data from national cancer registries. The incidence of acute lymphoblastic leukemia increased with the calendar period until 1983, and with the birth cohort until 1980, but incidence has been stable thereafter.


Methyl orange as a novel colorimetric iodide indicator with in situ generation of H2O2 by etching uncoated Ag-Ti3C2 nanohybrids.
Iodine intake remains a major public health concern, as both iodine excess and deficiency are related to adverse effects on health. Therefore, developing simple and economical methods to detect I- is still in great demand. Herein, we constructed a visual I- sensing platform based on the uncoated Ag-Ti3C2 nanohybrids using methyl orange (MO) as a colorimetric indicator. Plasmonic nanostructures are frequently employed in colorimetric analysis, but uncoated Ag nanoparticles (NPs) are unstable because their surface energies are usually high. Considering that Ag NPs can be etched by I- via forming Ag-I bond, we introduce Ag-Ti3C2 nanohybrids because uncoated Ag NPs with immaculate surfaces are more conducive to binding with I- and being etched. Dissolved O2 molecules adsorbed on Ti3+ of Ti3C2 MXenes enable the in situ generation of H2O2 by iodine-etching of uncoated Ag-Ti3C2 nanohybrids. ∙OH radicals promote the degradation of MO through a self-driven Fenton-like process, exhibiting the color variation from orange to transparent. Under optimal conditions, the absorbance of MO at 465 nm decreases linearly with the concentration of I- in the range of 0.5-300 μM, with a limit of detection as low as 0.31 μM. This work opens the feasibility of iodine-etching of Ag in developing novel probes for facile colorimetric determination of I-.


Differences in lethal response between male and female calanoid copepods and life cycle traits to cadmium toxicity.
This study determined the effect of cadmium (Cd) toxicity comparatively on two copepods, Eurytemora affinis (Poppe 1880) from a temperate region (Seine Estuary, France) and Pseudodiaptomus annandalei (Sewell 1919) from a subtropical region (Danshuei Estuary, Taiwan), according to their sex and reproductive stages. In addition, the effect of Cd to their life cycle traits was quantified. In the first experiment, both copepod sexes were exposed to 40, 80, 150, 220, and 360 µg/L of Cd and a control cultured in salinity 15, except that the temperature was 18 °C for E. affinis and 26 °C for P. annandalei. This allowed calculating median lethal concentration (LC50) of Cd after 96 h. This was 120.6 µg/L Cd for P. annandalei males which were almost twice as sensitive as P. annandalei females (LC50 = 239.5 µg/L Cd). For E. affinis females, the LC50 was 90.04 µg/L Cd, reflecting a 1.4 times higher sensitivity of females than of males (LC50 = 127.75 µg/L Cd). The males of both species were similarly sensitive; however, the E. affinis females were 2.7 times more sensitive than the P. annandalei females. We also compared the sensitivity of ovigerous females (OVF) and non-ovigerous females (NOF) of both species to Cd. Mortality was higher in NOF than in OVF of both copepod species in both the control and the 40 µg/L Cd treatment. Finally, the total population, fecundity and female morphology of both copepod species were estimated after exposing one generation cycle (nauplius to adult) to 40 μg/L Cd (for E. affinis) and 160 μg/L Cd (for P. annandalei). A significant decrease in cohort production, survival and clutch size but no significant difference in the prosome length of both copepod species exposed to Cd were detected. The ratio of OVF:NOF was high in both copepod species exposed to Cd. Cd toxicity did not significantly affect the M:F sex ratio and % OVF of E. affinis. However, the effect of Cd toxicity in P. annandalei was significant in the M:F sex ratio and was in favor of females and their reproductive activities due to an increase in % OVF. Moreover, there was a significant decrease in total production of P. annandalei due to high mortality in their nauplii and copepodid developmental stages. Toxicity to Cd appears to be affected by multiple factors including sex, reproductive life stage and species. The ecological implication of Cd toxicity on E. affinis and P. annandalei copepod ecology is more related to a skewed sex ratio, low egg production, reduced hatchability and reduced survival that affects the recruitment potential of the copepod nauplii resulting in a decreasing copepod population. Mortality, reproduction and population growth of model species may provide important bio-indicators for environmental risk assessment.


Statistical analysis plan for the Urodynamics for Prostate Surgery Trial; Randomised Evaluation of Assessment Methods (UPSTREAM).
Current management for men with lower urinary tract symptoms (LUTS) is a pathway that results in prostate surgery in a significant proportion. While helpful in relieving benign prostatic obstruction (BPO), surgery may be ineffective for men suffering from difficulties not relating to BPO. The UPSTREAM trial started recruitment in October 2014 with the aim of establishing whether a care pathway including urodynamics (a diagnostic tool for BPO and thus an indication of whether surgery is needed) is no worse for men, in terms of symptomatic outcome, than one without (routine care). This analysis plan outlines the main outcomes of the study and specific design choices, such as non-inferiority margins. The trial is currently recruiting in 26 hospitals across the UK, randomising men to either urodynamics or routine care, with recruitment set to end on the 31 December 2016. All outcomes will be measured 18 months after randomisation to allow sufficient time for surgical procedures and recovery. The primary outcome is based on a non-inferiority design with a margin of 1 point on the International Prostate Symptom Score (IPSS) scale. The key secondary outcome for this trial is surgery rate per arm, which is estimated to be at least 18% lower in the urodynamics arm. Surgery rates, adverse events, flow rate, urinary symptoms and sexual symptoms are secondary outcomes to be assessed for superiority. This is an update to the UPSTREAM protocol, which has already been published in this journal. This a priori statistical analysis plan aims to reduce reporting bias by allowing access to the trial's objectives and plans in advance of recruitment end. The results of the trial are expected to be published soon after the trial end date of 30 September 2018. ISRCTN registry, ISRCTN56164274 . Registered on 8 April 2014.


Resistance to aspirin in patients after coronary artery bypass grafting is transient: impact on the monitoring of aspirin antiplatelet therapy.
The aim of the present study was to assess the responsiveness of blood platelets to aspirin in patients following coronary artery bypass grafting (CABG) surgery. Aspirin was administered following CABG in 24 operated patients (aged 63.2 +/- 6.3 years). Platelet function was monitored on the 10th postoperative day (A) and 1 month after CABG (B) with the use of whole-blood aggregometry (WBEA) and PFA-100 closure time (PFA-100 CTCEPI). Normal platelet response to aspirin was defined by 3 criteria: the complete inhibition of WBEA induced by arachidonic acid (0.5 mmol/L), partial inhibition of collagen (1 microg/mL)-induced aggregation (WBEA < 14 Omega), and prolongation of PFA-100 CTCEPI (>150 seconds) ("good responders"). Depending on whether 0, 1, 2, or 3 of these 3 criteria were fulfilled, patients were classified as "nonresponders," "weak responders," "incomplete responders," or "good responders," respectively. On the 10th postoperative day, there were 3 good responders, 6 incomplete responders, 11 weak responders, and 4 nonresponders among 24 patients. In contrast, 1 month after CABG within the same group of 24 patients there were 18 good responders, 5 incomplete responders, and 1 weak responder. Using a new methodology to assess impaired platelet responsiveness to aspirin ex vivo, we describe here the transient nature of "aspirin resistance" following CABG. These results indicate the necessity for the prolonged monitoring of the antiplatelet effectiveness of aspirin in the postoperative period after CABG.


Thoracoscopy: new method of early diagnosis of cardiac herniation.
Cardiac herniation is an uncommon but rapidly fatal complication of radical pneumonectomy. Although operative correction is simple, a successful clinical outcome requires early diagnosis and thoracotomy. A patient is described in whom a left-sided cardiac herniation through a pericardial defect occurred following radical pneumonectomy. The diagnosis was suspected by persistent hypotension and radiographic changes. Confirmation of the diagnosis was achieved by thoracoscopy, performed with local anesthesia in the operating room. Immediate thoracotomy resulted in a successful outcome.


Disorders of carbohydrate digestion and absorption.
The carbohydrate malabsorptive syndromes are frequently seen by pediatricians. The congenital deficiency states are quite rare, but adult type hypolactasia and lactose intolerance following rotavirus infection are recognized with increasing frequency by primary care physicians. Therapy for these disorders involves identification of the offending carbohydrate, removal of the carbohydrate from the diet, and exclusion of other entities that may result in carbohydrate malabsorption but not respond to its removal from the diet. Prognosis for both the primary and secondary carbohydrate malabsorption syndromes is excellent. Compliance with diets for those pediatric patients who will require lifelong therapy remains problematic.


"Systematic review and meta-analysis of ceramic coated implants in total knee arthroplasty. Comparable mid-term results to uncoated implants."
Nitride-based ceramic coatings, such as titanium nitride (TiN) and titanium niobium nitride (TiNbN), have been introduced in total knee arthroplasty (TKA) to enhance the mechanical properties and biocompatibility of knee components, harden the metal surface and reduce CoCrMo exposure and metal ion release. However, the theoretical advantages of these ceramic coatings in TKA have yet to be fully elucidated. This systematic review aimed to provide clinical evidence on mid-term outcomes of ceramic-coated knee prostheses in comparison with uncoated standard CoCrMo knee prostheses in primary TKA. The hypothesis was that ceramic-coated implants can be used in primary TKA with no inferior outcomes compared to uncoated CoCrMo implants. A systematic review of the literature was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to find all clinical studies regarding primary TKA with ceramic-coated knee prostheses. MEDLINE (PubMed), Embase and Cochrane Library were searched from 1990 to October 2020 to identify relevant studies for the first qualitative analysis. Using PICOS eligibility criteria, a subgroup of the selected studies was used to perform a meta-analysis. Fifteen studies were included in this systematic review, of which six were included in the meta-analysis: 3 randomized controlled trials, 2 retrospective comparative studies and 1 prospective cross-sectional study. Pooled data overall included 321 coated TKAs vs. 359 uncoated TKAs and a mean follow-up of 4.6 years (range, 2-10 years). No significant difference in the implant survival risk ratio with revision or reoperation due to any reason was found between coated and uncoated TKAs, even considering the RCT study subgroup with a risk ratio of 1.02 (P = 0.34). No significant differences were found for postoperative complications, clinical scores, or metal blood concentrations at 1 year. The findings of this systematic review and meta-analysis support the statement that ceramic-coated TKAs are not inferior to uncoated TKAs, showing comparable survival rates, complication rates and clinical outcomes. There is strong evidence that ceramic-coated TKA does not improve the clinical results or survival rate in comparison with uncoated TKA. II, Therapeutic.


Apolipoprotein B 5'-Ins/Del and 3'-VNTR polymorphisms in Chinese, malay and Indian singaporeans.
The allele frequencies for the apolipoprotein B (apo B) 5'-Ins/Del and 3'-VNTR polymorphisms varied significantly (p < 0.01) among Singaporeans of Chinese, Malay and Indian descent. We calculated the unbiased expected heterozygosities for the 5'-Ins/Del polymorphism as 0.3357, 0.1984 and 0.2418, and for the 3'-VNTR as 0.5980, 0.5260 and 0.6749, respectively, in the Chinese, Malays and Indians. Compared to heterozygosities reported for other populations, the Singaporeans differed from most Caucasians in having significantly lower values but were closely related to other non-Caucasians. Thirteen alleles, with a bimodal distribution, were observed at the 3'-VNTR polymorphic locus; the alleles occurring most frequently among the Chinese and Malays were of 35 or 53 repeats, and among the Indians, of 37 or 47 repeats. The Del allele was associated with elevated serum cholesterol (p = 0.023), LDL-cholesterol (LDL-C) (p = 0.001) in the Chinese, and apo B (p = 0.007) in the Indians. Likewise, the larger 3'-VNTR alleles (> 41 repeats) were associated with raised cholesterol (p = 0.018), LDL-C (p = 0.025), and triglyceride (p = 0.001) in the Chinese. The two polymorphisms were not in significant linkage disequilibrium (D = -0.0029, p = 0.494) in the three ethnic groups.


Predictors of relapse, death or heart transplantation in myocarditis before the introduction of immunosuppression: negative prognostic impact of female gender, fulminant onset, lower ejection fraction and serum autoantibodies.
Outcome predictors in myocarditis are not well defined; we aimed at identifying predictors of death, heart transplantation (HTx) and relapse before the introduction of immunosuppression. From 1992 to 2012, 466 consecutive patients (68% male, mean age 37 ± 17 years, single centre recruitment, median follow-up 50 months) were included, of whom 216 had clinically suspected and 250 biopsy-proven myocarditis. Serum anti-heart (AHA) and anti-intercalated disk (AIDA) autoantibodies were measured by indirect immunofluorescence. Univariable and multivariable analyses of clinical and diagnostic features at diagnosis were performed. Survival free from death or HTx at 10 years was 83% in the whole study population and was lower in biopsy-proven versus clinically suspected myocarditis (76% vs. 94%, p < 0.001). Female gender (hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1-6.5), fulminant presentation (HR 13.77, 95% CI 9.7-261.73), high-titre organ-specific AHA (HR 4.2, 95% CI 1.2-14.7) and anti-nuclear antibodies (ANA) (HR 5.2, 95% CI 2.1-12.8) were independent predictors of death or HTx; higher echocardiographic left ventricular ejection fraction (LVEF) at diagnosis was protective, with a 0.93-fold risk reduction for each 1% LVEF increase (95% CI 0.89-0.96). History of myocarditis at diagnosis (HR 8.5, 95% CI 3.5-20.7) was an independent predictor of myocarditis relapse at follow-up; older age was protective (HR 0.95, 95% CI 0.91-0.99). Predictors of death, HTx and relapse did not differ in biopsy-proven versus clinically suspected myocarditis. Young age and a previous myocarditis were independent relapse predictors; female gender, fulminant onset, lower LVEF at presentation and high-titre organ-specific AHA and ANA were independent predictors of death and HTx, suggesting that autoimmune features predict worse prognosis.


Cocaine self-administration in rats: discrete trials procedures.
A discrete trials procedure involves splitting up a self-administration session so that there are multiple distinct trials and inter-trial-intervals. This schedule is well suited to be used over 24 h periods which allows insight into diurnal variability in self-administration behavior. DT is also well suited for investigations using pretreatments for increasing or decreasing both high and low probability behavior.


Inhibition of ABCG2 transporter by lapatinib enhances 5-aminolevulinic acid-mediated protoporphyrin IX fluorescence and photodynamic therapy response in human glioma cell lines.
5-Aminolevulinic acid (ALA) is an intraoperative molecular probe approved for fluorescence-guided resection (FGR) of high-grade gliomas to achieve maximal safe tumor resection. Although ALA has no fluorescence on its own, it is metabolized in the heme biosynthesis pathway to produce protoporphyrin IX (PpIX) with red fluorescence for tumor detection and photosensitizing activity for photodynamic therapy (PDT). The preferential tumor accumulation of PpIX following ALA administration enables the use of ALA as a prodrug for PpIX FGR and PDT of gliomas. Since intracellular PpIX in tumor cells after ALA treatment is influenced by biological processes including PpIX bioconversion catalyzed by ferrochelatase (FECH) and PpIX efflux by ATP-binding cassette subfamily G member 2 (ABCG2), we determined the activity of FECH and ABCG2 in a panel of human glioma cell lines and correlated with intracellular and extracellular PpIX levels and PDT response. We found that glioma cell lines with ABCG2 activity exhibited the trend of low intracellular PpIX, high extracellular PpIX and low PDT response, whereas no particular correlation was seen with FECH activity. Inhibition of PpIX efflux with ABCG2 inhibitors was more effective in enhancing ALA-PpIX fluorescence and PDT response than blocking PpIX bioconversion with iron chelator deferoxamine. We also showed that a clinically used kinase inhibitor lapatinib could be repurposed for therapeutic enhancement of ALA due to its potent ABCG2 inhibitory activity. Our study reveals ABCG2 as an important biological determinant of PpIX fluorescence in glioma cells and suggests ABCG2 inhibition with lapatinib as a promising therapeutic enhancement approach.


Progress in Alzheimer's disease research in the last year.
Alzheimer's disease (AD) is the most common cause of dementia in the elderly, with a prevalence of 5 % after 65 years of age, increasing to about 30 % in people aged 85 years or older. It is characterized by progressive cognitive impairment, including impaired judgment, decision-making and orientation, and in some cases accompanied by psycho behavioral disturbances or language impairment. Herein, we summarize and discuss the main articles describing novel findings in AD published over the last year, including clinical, therapeutic, and research issues.


The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer.
Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches. Cytotoxicity testing (MTT) and cell cycle blockade assessed drug responsiveness. Methylation specific PCR and pyrosequencing identified sites of promoter methylation in p57(Kip2). siRNA to p57(Kip2) was used to look at the changes in apoptosis of carboplatin treated EOC cells. EOC tissues (20 cases) were assessed for mRNA levels of p57(Kip2). Carboplatin resistance was reversed using 5-aza-cytidine in vitro. Promoter methylation sites and preferential sensitivity to seliciclib were seen in PEO1CarbR cells. Silencing p57(Kip)2 decreased the apoptotic response to the effects of platinum but produced sensitisation to seliciclib. EOC biopsies indicated an association of high levels of p57(Kip2)mRNA with complete responses to chemotherapy and improved outcome. We conclude that p57(Kip2) is a candidate biomarker of platinum sensitivity/resistance in EOC and such cases may show preferential response to the cyclin-dependent kinase inhibitor seliciclib.


Protective effects of Zishen Huoxue recipe against neuronal injury in the neurovascular unit of rats with vascular dementia by interfering with inflammatory cascade-induced pyroptosis.
Chinese herbal formulas show considerable therapeutic benefits in dementia. This study specifically explored the protective action of Zishen Huoxue recipe on the neurovascular unit (NVU) of rats with vascular dementia (VD). VD rat models were established by permanent bilateral common carotid artery occlusion and treated with Zishen Huoxue recipe. In vitro glucose‑oxygen deprivation (OGD)-injured NVU models were established and treated with miR-124-3p agomir or rat medicated serum. The neurological damage, histopathological changes, and neuronal injury in the rat hippocampus were assessed using Morris water maze test and histological stainings. Expression of miR-124-3p was determined using RT-qPCR. The blood-brain barrier/NVU injury, cell pyroptosis, NLRP3 inflammasome activation, and release of inflammatory factors were analyzed mainly by immunofluorescence analysis, TUNEL staining, Western blot, and ELISA. QS-21 (an NLRP3 activator) was used to verify the role of miR-124-3p/NLRP3. Zishen Huoxue recipe ameliorated the learning/memory deficits, neuronal injury, NVU insults, cell pyroptosis, activation of NLRP3 inflammasome, and extensive secretion of lactate dehydrogenase/IL-1β/IL-18 in VD rats. miR-124-3p was downregulated in VD rats but upregulated after treatment of this recipe. miR-124-3p overexpression ameliorated NVU insults, reduced cell pyroptosis, lowered NLRP3 inflammasome activation, and suppressed inflammatory responses in OGD-injured NVU models. NLRP3 inflammasome activation partly counteracted the amelioration effect of miR-124-3p on pyroptosis. Zishen Huoxue recipe could upregulate miR-124-3p to suppress pyroptosis and protect NVU function. Zishen Huoxue recipe can upregulate miR-124-3p expression to repress the inflammatory cascade-evoked pyroptosis, thereby protecting against neuronal injury in the NVU of VD rats.


Alarm bells over MERS coronavirus.
Middle East coronavirus is causing alarm among researchers and international health officials. Neil Bennet looks at the unfolding situation.


Facial Animation With Free Functional Gracilis Transfer Innervated by the Cross-Facial Nerve Graft.
The treatment of long-standing facial paralysis has always been a challenge for plastic surgery. The purpose of this study was to demonstrate that the free functional gracilis transfer innervated by the cross-facial nerve graft (CFNG) is still an ideal option, even though there are many new surgical options available. A retrospective survey was made on 12 patients who received free functional gracilis transfer innervated by the CFNG. A modified version of the House-Brackmann scale was used to evaluate the movement of the corners of mouth after surgery. Patients were also asked about their satisfaction with the operation. In addition, an objective test was performed to assess the postoperative angle improvement by measuring the angle formed between the horizontal line of both corners of the lips and the vertical midline. All grafts survived well. No severe complication occurred. Three patients received further surgical operations for aesthetic reasons. The movement of the corners of mouth was classified as excellent in 8 cases, good in three cases, and fair in one cases. The static angle and dynamic angle of postoperation improved and the range of dynamic angle improvement was larger than that of static angle. Free functional gracilis transfer innervated by the CFNG is an ideal technique for facial paralysis. It can effectively improve the facial dynamic of the affected side.


Synthesis and morphological reversion activity on srctsNRK cells of pyrimidinylpropanamide antibiotics, sparsomycin, sparoxomycin A1, A2, and their analogues.
Three pyrimidinylpropanamide antibiotics sparsomycin (1), sparoxomycins A1, A2 (2, 3), and also six analogues (4-9) have been synthesized by employing asymmetric sulfide oxidation conditions as a key step. Sparsomycin (1) and its alkyl analogues (5-7) showed higher morphological reversion activities on srctsNRK cells than 2 and 3.


Unexpected divergence and lack of divergence revealed in continental Asian Cyornis flycatchers (Aves: Muscicapidae).
The flycatcher genus Cyornis (Aves: Muscicapidae) comprises 25 species with Oriental distributions. Their relationships are poorly known. We analyzed the phylogenetic relationships of 70 individuals from 12 species and several subspecies of Cyornis based on three mitochondrial genes and five nuclear introns, with special focus on Chinese and Vietnamese populations of the monotypic C. hainanus and polytypic C. rubeculoides. We found no support for inclusion of C. concretus in Cyornis. Deep divergences were observed among different subspecies of C. banyumas and C. rubeculoides. C. rubeculoides glaucicomans was also shown to have a highly distinctive song, and we propose that it is treated as a distinctive Chinese endemic species, C. glaucicomans. In contrast, the south Vietnamese C. rubeculoides klossi, which has a disjunct distribution from the other subspecies of C. rubeculoides, along with a recently discovered population in Guangdong Province (China) with several plumage features reminiscent of C. r. klossi, were indistinguishable in all loci analyzed from the phenotypically markedly different C. hainanus. More research is needed to elucidate the reasons for this unexpected pattern.


Effect of Intraoperative Imprint Cytology Followed by Frozen Section on Margin Assessment in Breast-Conserving Surgery.
Intraoperative margin assessment can reduce positive margins in patients undergoing breast-conserving surgery. However, reports on intraoperative margin assessment have described only the use of either imprint cytology or frozen section. This study was designed to elucidate the effect of intraoperative margin assessment using imprint cytology followed by frozen section. Overall, 522 patients were enrolled. First, the entire surgical margin was subjected to imprint cytology. Frozen section was performed only in cases with "positive" or "suspicious" imprint cytology results. An additional intraoperative excision was performed in patients with frozen section-positive lesion sites. All margins were evaluated using postoperative permanent sections after excision. Among 522 patients, 136 (26.1%) were imprint cytology-positive, and 386 (73.9%) were imprint cytology-negative. Among the 386 imprint cytology-negative patients not subjected to frozen section, 11 (2.1%) were permanent sections-positive (imprint cytology-false-negative). In 47 of the 136 imprint cytology-positive patients, additional intraoperative excision was unnecessary due to the frozen section-negative diagnosis. Moreover, these patients could avoid reoperation, because they were permanent section-negative. The false-positive rate of imprint cytology alone was 13.4%, but adding frozen section to imprint cytology decreased the overall false-positive rate to 2.5%. After undergoing excision, four patients still had positive margins. The overall positive margin rate in the final pathology based on permanent sections was 2.9% (15/522). Imprint cytology followed by frozen section led to a markedly decreased positive margin rate. This is considered the best method for intraoperative margin assessment, as it can overcome the limitations of cytology and histology performed individually.


Rabphilin3A reduces integrin-dependent growth cone signaling to restrict axon regeneration after trauma.
Neural repair after traumatic spinal cord injury depends upon the restoration of neural networks via axonal sprouting and regeneration. Our previous genome wide loss-of-function screen identified Rab GTPases as playing a prominent role in preventing successful axon sprouting and regeneration. Here, we searched for Rab27b interactors and identified Rabphilin3A as an effector within regenerating axons. Growth cone Rabphilin3a colocalized and physically associated with integrins at puncta in the proximal body of the axonal growth cone. In regenerating axons, loss of Rabphilin3a increased integrin enrichment in the growth cone periphery, enhanced focal adhesion kinase activation, increased F-actin-rich filopodial density and stimulated axon extension. Compared to wild type, mice lacking Rabphilin3a exhibited greater regeneration of retinal ganglion cell axons after optic nerve crush as well as greater corticospinal axon regeneration after complete thoracic spinal cord crush injury. After moderate spinal cord contusion injury, there was greater corticospinal regrowth in the absence of Rph3a. Thus, an endogenous Rab27b - Raphilin3a pathway limits integrin action in the growth cone, and deletion of this monomeric GTPase pathway permits reparative axon growth in the injured adult mammalian central nervous system.


A shrewd and ethical approach to xenotransplantation.
Policies surrounding xenotransplantation, and many other emerging high-technology interventions, must balance opportunity and risk. Whereas traditional stakeholders, such as the researcher community, government agencies and the commercial sector, readily contribute to the debates that influence policies, the voice of the public is seldom heard. Not only does this raise ethical concerns but also it might ultimately prove to be shortsighted. Before any country settles unilaterally on comprehensive policies governing the practice of xenotransplantation, well-informed public opinions need to be taken into account.


[Improvement of the process of producing pseudoephedrine hydrochloride].
To improve the design of the technological process so as to solve the long existing quality problem in the process of producing pseudoephedrine hydrochloride. Pseudoephedrine hydrochloride was developed on basis of developing pseudoephedrine. And its preparation condition was observed. Pseudoephedrine hydrochloride obtained in the improved process didn't show tendency to agglomerate, which solves the quality problem of the product and the rate of production was raised. The improved process of producing pseudoephedrine hydrochloride has great application value.


Local oral immunization with synthetic peptides induces a dual mucosal IgG and salivary IgA antibody response and prevents colonization of Streptococcus mutans.
A small cell surface antigen of Streptococcus mutans was partially sequenced and the amino terminal peptides of 11, 15 and 20 amino acid residues and a dimer of the 15 and 20 residues peptides were synthesized. The synthetic peptides (SP) were used in topical oral immunization of the gingivomucosal epithelium of macaque monkeys. Sequential examination for antibodies over a period of up to 30 weeks revealed that six applications of the linear or cyclized SP11 and a random SP11 induced negligible or very low antibody levels. In contrast, the SP17 (SP15 with added cysteine at each terminus), SP21 (SP20 with one cysteine) and the dimer (SP35) induced significant anti-SP as well as anti-native streptococcal antibodies in the gingival fluid and in saliva. The functional significance of this immune response was examined by studying its effect on oral colonization of S. mutans following feeding of a carbohydrate-rich diet. Whereas control animals, sham-immunized with a random SP of 11 residues, showed increased colonization of the teeth by S. mutans, there was no colonization or a significant reduction in colonization of animals immunized with the cyclized SP17, linear SP21 or dimerized SP35. These experiments suggest that local immunization with SP derived from the sequences of a streptococcal cell surface antigen induce a dual local immune response of gingival IgG and salivary IgA antibodies against the SP and native SA. These antibodies may be involved in preventing colonization of S. mutans, which is the principal agent in the development of dental caries.


Terrestrial mosses as bioindicators of SO2 pollution stress : Synecological analysis and the index of atmospheric purity.
The turf structure of terrestrial mosses was analysed in the understory of white spruce associations along two SO2 stress gradients associated with a single SO2 source. Changes in coverage, turf depth, biomass and percent living moss were followed. SO2 stress initially caused changes in turf structure in the vertical plane (green turf depth, percentage and biomass) whereas changes in the horizontal plane (coverage) were most noticeable in areas of severe stress. The Index of Atmospheric Purity (IAP) reflected SO2 stress only in these latter areas. Intrusion of weeds and increased prominence of subordinate species occurred in lightly stressed areas, but these perturbations were not reflected by the IAP. The effect of Q i, frequency, and coverage factors in the IAP are discussed and the criteria of the Index of Community Vigor are proposed.


Multigene phylogenetic reconstruction of the Tubulinea (Amoebozoa) corroborates four of the six major lineages, while additionally revealing that shell composition does not predict phylogeny in the Arcellinida.
Tubulinea is a phylogenetically stable higher-level taxon within Amoebozoa, morphologically characterized by monoaxially streaming and cylindrical pseudopods. Contemporary phylogenetic reconstructions have largely relied on SSU rDNA, and to a lesser extent, on actin genes to reveal the relationships among these organisms. Additionally, the test (shell) forming Arcellinida, one of the most species-rich amoebozoan groups, is nested within Tubulinea and suffers from substantial under-sampling of taxa. Here, we increase taxonomic and gene sampling within the Tubulinea, characterizing molecular data for 22 taxa and six genes (SSU rDNA, actin, α- and β-tubulin, elongation factor 2 and the 14-3-3 regulatory protein). We perform concatenated phylogenetic analyses using these genes as well as approximately unbiased tests to assess evolutionary relationships within the Tubulinea. We confirm the monophyly of Tubulinea and four of the six included lineages (Echinamoeboidea, Leptomyxida, Amoebida and Poseidonida). Arcellinida and Hartmanellidae, the remaining lineages, are not monophyletic in our reconstructions, although statistical testing does not allow rejection of either group. We further investigate more fine-grained morphological evolution of previously defined groups, concluding that relationships within Arcellinida are more consistent with general test and aperture shape than with test composition. We also discuss the implications of this phylogeny for interpretations of the Precambrian fossil record of testate amoebae.


Comparison of thrice daily biphasic human insulin (30/70) versus basal detemir & bolus aspart in patients with poorly controlled type 2 diabetes mellitus - a pilot study.
Conventionally, biphasic human insulin (30/70, BHI) is used twice daily for the management of patients with diabetes. However, this regimen is suboptimal to control post-lunch and/or pre-dinner hyperglycaemia in some patients. This study was undertaken to compare the efficacy and safety of thrice-daily biphasic human insulin (30/70, BHI) versus basal detemir and bolus aspart (BB) in patients with poorly controlled type 2 diabetes mellitus (T2DM). In this open labelled randomized pilot study, 50 patients with uncontrolled T2DM on twice-daily BHI and insulin sensitizers were randomized either to BHI thrice-daily or BB regimen. HbA1c, six point plasma glucose profile, increment in insulin dose, weight gain, hypoglycaemic episodes and cost were compared between the two treatment groups at the end of 12 wk. Mean HbA l c (± SD) decreased from 9.0 ± 0.9 per cent at randomization to 7.9 ± 0.8 per cent in BHI (P<0.001) and from 9.4 ± 1.3 to 8.2 ± 1.0 per cent in BB regimen (P<0.001) after 12 wk of treatment. The mean (± SEM) weight gain in patients in the BHI regimen was 1.5 ± 0.33 kg compared to 1.4 ± 0.34 kg in the BB regimen. Insulin dose increment at 12 wk was significantly more in the BB regimen 0.46 ± 0.32 U/kg/day compared to 0.15 ± 0.21 U/kg/day in the BHI regimen (P<0.001). The incidence of major as well as minor hypoglycaemic episodes was not different in both the regimen. The BB regimen was more expensive than the BHI regimen (P<0.001). The thrice daily biphasic human insulin regimen is non-inferior to the basal bolus insulin analogue regimen in terms efficacy and safety in patients with poorly controlled T2DM. However, these data require further substantiation in large long term prospective studies.


Isolation and genetic characterization of swinepox virus from pigs in India.
Swinepox virus (SWPV), a member of the genus Suipoxvirus causes generalized pock-like lesions on the body of domestic and wild pigs. Although outbreak has been reported in India since 1987, virus isolation and genetic characterization remained elusive. In September 2013, an outbreak of acute skin infection occurred in piglets in a commercial piggery unit at Rohtak district in Haryana, India. The presence of SWPV in scab samples collected from piglets succumbed to infection was confirmed by virus isolation, PCR amplification of SWPV-specific gene segments and nucleotide sequencing. Phylogenetic analysis of host-range genes of the SWPV revealed that the Indian isolate is genetically closely related to reference isolate SWPV/pig/U.S.A/1999/Nebraska. To the best of our knowledge this is the first report on isolation and genetic characterization of SWPV from pigs in India.


The multimolecular cascade of spinal cord injury. Studies on prostanoids, calcium, and proteinases.
Experimental spinal cord injury in animals induced by weight drop produces neurological deficit and paralysis. Correlation of the progressive morphological changes in the lesion by both light and electron microscopy with the biochemical alterations revealed ischemia, edema, hemorrhage, tissue necrosis, granular changes in axons, vesicular degeneration of myelin and axonal calcification. The biochemical pathology was that of degradation of axonal (neurofilaments) and myelin proteins (MBP and PLP) with increased activities of proteolytic enzymes and particularly the neutral proteinase. The level of total calcium increased progressively in the lesion to a peak at 8 hrs. and subsequently remained constant thereafter. The capacity of calcium for activating proteinases and lipases and fostering the degradation of axon and myelin proteins as well as the liberation of arachidonic acid required for the synthesis of prostanoids must be relevant. An increased production of prostanoids is indicated by elevation of thromboxane (TxB2), a stable metabolite of TXA2 at 1 hour after injury. The 6-keto-PG1(1)a was also increased but to a lesser extent. We suspect that the activation of arachidonic acid metabolism contributes to post-traumatic vascular injury and the progressive ischemia. These putative roles for calcium in proteolysis and lipolysis, inducing degradation of macromolecules and production of prostanoids which initiate edema, lysolecithin a myelinolytic factor and mitochondrial dysfunction in spinal cord injury are discussed.


Effects of the Use of a Combination of Two Bacillus Species on Performance, Egg Quality, Small Intestinal Mucosal Morphology, and Cecal Microbiota Profile in Aging Laying Hens.
Sixty-week-old Hy-Line brown laying hens were randomly divided into five groups and fed different diets over a period of 84 days. Experimental treatments included a basal diet (control); the basal diet supplemented with 1.0 × 106B. licheniformis yb-214245; the basal diet supplemented with 1.0 × 106B. subtilis yb-114246; a combination of both strains in a 2:1 ratio (6.6 × 105:3.3 × 105B. licheniformis yb-214245:B. subtilis yb-114246); and the latter, added with 5 mg/kg flavomycin. Basal diet supplementation with the combined Bacillus species improved egg-laying performance in aging hens significantly (P < 0.05). Eggshell strength improved significantly with this treatment, compared to the control or the antibiotic-supplemented groups (P < 0.05). The levels of total cholesterol, triglycerides, and very low-density lipoprotein cholesterol in egg yolk declined significantly more in the Bacillus-treated group than in the control or the antibiotic-supplemented groups (P < 0.01). Small intestinal morphology was better in the hens treated with the Bacillus combination than in the hens in the control group (P < 0.05). The total number of aerobic bacteria (Bacillus, Lactobacillus, and Bifidobacterium) in the cecum was significantly higher in all the Bacillus-supplemented hens than either in the control or the antibiotic-supplemented hens (P < 0.01); additionally, the number of E. coli and Salmonella was significantly lower than in the control group (P < 0.01). In conclusion, diet supplementation with the combination of Bacillus species used here for aging laying hens improved their growth performance, cecal bacterial composition, egg quality, and small intestine morphology.


Clinical characteristics and outcomes of patients with community-acquired, health-care-associated and hospital-acquired empyema.
Patients with pneumonia, a common cause of empyema, are stratified based on their risk factors, and the treatment of empyema might benefit from this risk stratification. The etiology, bacteriologic profile and outcome of patients diagnosed with empyema in Shinko Hospital between May 2005 and October 2013 were retrospectively studied. The patients were stratified according to whether they had community-acquired empyema (CAE), health-care-associated empyema (HCAE) or hospital-acquired empyema (HAE). The study included 81 patients, 25 CAE, 40 HCAE and 16 HAE. The comorbidity rate was highest among HAE patients (100%), followed by 95% of HCAE and 72% of CAE patients (P = 0.005). The rates of cancer and central nervous system (CNS) disease were higher in patients with HCAE and HAE than in patients with CAE (P = 0.030, P = 0.018, respectively). Pleural fluid cultures were positive in 58/81 patients. Streptococcus species were the most common organisms cultured from CAE (12/15) and HCAE patients (17/30), but not from HAE patients (3/13). Anaerobic organisms were cultured from 3 CAE, 5 HCAE and 3 HAE patients. Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were only cultured from HCAE and HAE patients. The mortality rates were higher in HCAE (18%) and HAE (50%) than in CAE (4%) patients (log-rank test: P = 0.0012). Half of patients with empyema were HCAE patients, who had comorbidities, bacteriological profile and outcome different from CAE patients. The patient with HCAE should be differentiated from CAE patient, and the stratification of patients based on risk factors may be useful for treatment strategy.


Surgical and endovascular treatment of pelvic venous disorder: Results of a multicentre retrospective cohort study.
In the present study, we investigated the clinical outcomes after gonadal vein resection (GVR) and gonadal vein embolization (GVE) with coils in patients with pelvic venous disorder (PeVD). We also assessed the rates of procedural complications and disease recurrence. Our multicenter retrospective cohort study included 361 female patients with PeVD-related chronic pelvic pain (CPP) and gonadal vein reflux who underwent GVR (n = 184) or GVE with coils (n = 177) from 1999 to 2020. The clinical outcomes (ie, presence and severity of CPP, procedural complications, disease recurrence) were assessed at 1 month and 1, 3, and 5 years after intervention. The pain intensity before and after treatment was assessed using a visual analog scale. All the patients underwent duplex ultrasound after GVR and GVE, and those with persistent CPP and suspected perforation of the gonadal vein by the coils were also evaluated by multiplanar pelvic venography. GVR and GVE was associated with the reduction or elimination of CPP at 1 month after treatment in 100% and 74% of patients and postprocedural complications in 14% and 37% of patients, respectively (Р < 0.01 for both). The most common complication after either GVR or GVE was pelvic vein thrombosis (11% and 22% patients, respectively; P < .01 between groups). GVE was associated with postembolization syndrome in 20%, coil protrusion in 6%, and coil migration in 1% of patients. The long-term recurrence rate after GVR and GVE was 6% and 16%, respectively (P < .01). Both GVR and GVE were found to be effective in treating patients with PeVD. However, GVR was associated with better efficacy in the relief of CPP and lower rates of procedural complications and disease recurrence.


The Association Between new Nurses' Gerontological Education, Personal Attitudes Toward Older Adults, and Intentions to Work in Gerontological Care Settings in Ontario, Canada.
The older adult population in Canada is increasing, and many will require care within an acute geriatric unit (AGU) or long-term care facility (LTCF). However, the nursing workforce is not growing at the same pace as the population is aging. New graduate nurses may be able to fill this gap; therefore, it is important to understand their intentions of working in gerontological care settings (i.e., AGU or LTCF). To examine if nursing education and personal attitudes toward older adults influence newly registered nurses'(RNs) intentions to work in a gerontological care setting. Nurses (n= 1,103) who registered with the College of Nurses of Ontario for the first time in 2018 were invited to complete a questionnaire. The majority of participants (n = 181) reported a positive attitude toward older adults. However, only 14% reported an intention to work in a gerontological care setting. Participants who completed multiple geriatric focused clinical placements were more likely to report an intention to work in these settings. This study provides some information regarding the attitudes and intentions of newly RNs toward a career in gerontological care settings. Further research is needed to understand nurses' intentions regarding working in AGUs or LTCFs.


The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic β-cells.
Hormone secretion from metabolically active tissues, such as pancreatic islets, is governed by specific and highly regulated signaling pathways. Defects in insulin secretion are among the major causes of diabetes. The molecular mechanisms underlying regulated insulin secretion are, however, not yet completely understood. In this work, we studied the role of the GTPase ARFRP1 on insulin secretion from pancreatic β-cells. A β-cell-specific Arfrp1 knockout mouse was phenotypically characterized. Pulldown experiments and mass spectrometry analysis were employed to screen for new ARFRP1-interacting proteins. Co-immunoprecipitation assays as well as super-resolution microscopy were applied for validation. The GTPase ARFRP1 interacts with the Golgi-associated PDZ and coiled-coil motif-containing protein (GOPC). Both proteins are co-localized at the trans-Golgi network and regulate the first and second phase of insulin secretion by controlling the plasma membrane localization of the SNARE protein SNAP25. Downregulation of both GOPC and ARFRP1 in Min6 cells interferes with the plasma membrane localization of SNAP25 and enhances its degradation, thereby impairing glucose-stimulated insulin release from β-cells. In turn, overexpression of SNAP25 as well as GOPC restores insulin secretion in islets from β-cell-specific Arfrp1 knockout mice. Our results identify a hitherto unrecognized pathway required for insulin secretion at the level of trans-Golgi sorting.


Complete Genome Sequence Resource for Cercospora apii Causing Leaf Spot of Celery.
Cercospora apii is an important seedborne pathogenic fungus causing severe Cercospora leaf spot of celery worldwide. Here, we first present a complete genome assembly of C. apii QCYBC from celery, based on Illumina paired-end and PacBio long-read sequencing data. The high-quality genome assembly contains 34 scaffolds with a 34.81 Mb genome size, 330 interspersed repeat genes, 114 noncoding RNAs, and 12,631 protein-coding genes. The benchmarking universal single-copy ortholog (BUSCO) analysis indicated that 98.2% of the BUSCOs were complete, whereas 0.3, 0.7, and 1.1% were duplicated, fragmented, and missing, respectively. Based on annotation, 508 carbohydrate-active enzymes, 243 cytochromes P450 enzymes, 1,639 translocators, 1,358 transmembrane proteins, and 1,146 virulence genes were identified. This genome sequence provides a valuable reference for future studies to improve understanding of the C. apii-celery pathosystem. [Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Comparison of hemoglobin A1C results by two different methods on patients with structural hemoglobin variants.
The objective was to compare hemoglobin A1C (HbA1C) results obtained by two methods based on different analytical principles for individuals with a structural hemoglobin variant. Hemoglobin A1C results were obtained using the Bio-Rad Variant (based on cation exchange chromatography) and the Bayer DCA 2000 (based on an immunological reaction) on individuals with a structural hemoglobin variant. The identity of the hemoglobin variant was confirmed by high pressure liquid chromatography (HPLC) and electrophoresis. Hemoglobin A1C results obtained by the two methods on individuals with S, C, D, and E trait were in close agreement. The Bio-Rad Variant and Bayer DCA 2000 produce equivalent hemoglobin A1C results on patients with S, C, and E trait. With appropriate correction, correlation of hemoglobin A1C results from the Bio-Rad Variant for individuals with D trait was good (r = 0.927). Glycohemoglobin results obtained by the two methods for some unusual structural hemoglobin variants were in close agreement.


High and low neurobehavior disinhibition clusters within locales: implications for community efforts to prevent substance use disorder.
Knowledge of where substance use and other such behavioral problems frequently occur has aided policing, public health, and urban planning strategies to reduce such behaviors. Identifying locales characterized by high childhood neurobehavioral disinhibition (ND), a strong predictor of substance use and consequent disorder (SUD), may likewise improve prevention efforts. The distribution of ND in 10-12-year olds was mapped to metropolitan Pittsburgh, PA, and tested for clustering within locales. The 738 participating families represented the population in terms of economic status, race, and population distribution. ND was measured using indicators of executive cognitive function, emotion regulation, and behavior control. Innovative geospatial analyzes statistically tested clustering of ND within locales while accounting for geographic barriers (large rivers, major highways), parental SUD severity, and neighborhood quality. Clustering of youth with high and low ND occurred in specific locales. Accounting for geographic barriers better delineated where high ND is concentrated, areas which also tended to be characterized by greater parental SUD severity and poorer neighborhood quality. Offering programs that have been demonstrated to improve inhibitory control in locales where youth have high ND on average may reduce youth risk for SUD and other problem behaviors. As demonstrated by the present results, geospatial analysis of youth risk factors, frequently used in community coalition strategies, may be improved with greater statistical and measurement rigor.


Relative sensitivity of one freshwater and two marine acute toxicity tests as determined by testing 30 offshore E & P chemicals.
Acute toxicity of 30 offshore E & P (Exploration and Production) chemicals was measured using the three standard test organisms Daphnia magna (freshwater cladoceran), Acartia tonsa (marine copepod) and Skeletonema costatum (marine diatom alga). Test chemicals included 20 water-soluble and 10 (partially) non-soluble products. For 22 out of the 30 chemicals, the difference in sensitivity between the three tests varied within one order of magnitude. A very good correlation was found between the two marine tests (r = 0.96, P < 0.01, n = 30), and a correlation coefficient of r = 0.78 (P < 0.01, n = 30) was found between D. magna and both A. tonsa and S. costatum, individually. When the comparison of D. magna and A. tonsa sensitivity was based only on the water-soluble chemicals, a significantly higher correlation was obtained (r = 0.84, n = 20), indicating that the sample preparation method used for the (partially) non-soluble chemicals (the water accommodated fraction (WAF) method) induces additional variation between tests performed with different test media. (Partially) non-soluble chemicals are characterised by phase separation or precipitation at the concentrations used for testing. In a WAF-based test, each test concentration/exposure level is prepared separately, and following mixing and separation, only the water phase is used for testing. Toxicity is related to the amount of substance originally added to the mixing vessels. For 25 of the 30 chemicals, D. magna was found to be less sensitive than the marine copepod by a factor >2. The generally higher sensitivity of the marine toxicity tests compared to the Daphnia test emphasise the importance of using marine data for environmental hazard classification as well as for environmental risk assessment purposes.


Trigeminal antidromic vasodilatation and plasma extravasation in the rat: effects of sensory, autonomic and motor denervation.
The cutaneous vasodilatation and plasma extravasation observed following antidromic stimulation of trigeminal sensory branches in the rat are reduced by atropine. The atropine-sensitive component does not originate from the seventh cranial nerve (facial nerve) or from the mental nerve, because after chronic section of these nerves an atropine-sensitive component persists. The cholinergic component of the plasma extravasation is abolished by chronic bilateral extirpation of the superior cervical ganglia but this is not the case for the vasodilatation. Our data suggest that trigeminal sensory fibres are not the only fibres involved in these vascular responses seen in the lower lip of the rat after electrical stimulation of the mental nerve.


Prescription errors in older individuals with an intellectual disability: prevalence and risk factors in the Healthy Ageing and Intellectual Disability Study.
Prescribing pharmacotherapy for older individuals with an intellectual disability (ID) is a complex process, possibly leading to an increased risk of prescription errors. The objectives of this study were (1) to determine the prevalence of older individuals with an intellectual disability with at least one prescription error and (2) to identify potential risk factors for these prescription errors (age, gender, body mass index (BMI), frailty index, level of intellectual disability and living situation). The study population consisted of 600 older (≥ 50 years) individuals with an ID using one or more drugs who were randomly selected from the study cohort of the Healthy Ageing and Intellectual Disability (HA-ID) Study. The medication used at the time of measurement was screened for errors by a hospital pharmacist/clinical pharmacologist and a Master's student pharmacy using consensus methodology. Participants with one or more prescription errors were compared to participants without prescription errors by multivariate logistic regression to identify potential risk factors. The prevalence of individuals with one or more prescription errors was 47.5% (285 of 600 individuals; 95% confidence interval (CI) 43-52%). Relevant errors, defined as errors that actually do require a change of pharmacotherapy, were identified in 26.8% of the individuals (161 of 600 individuals; 95% CI 23-30%). Higher age (adjusted odds ratio (OR adj) 1.03; 95% CI 1.01-1.06), less severe intellectual disability (moderate: OR adj 0.48; 95% CI 0.31-0.74 and severe: OR adj 0.56; 95% CI 0.32-0.98), higher BMI (OR adj 1.04; 95% CI 1.01-1.08), higher frailty index (0.39-0.54: OR adj 2.4; 95% CI 1.21-4.77 and ≥ 0.55: OR adj 3.4; 95% CI 1.03-11.02), polypharmacy (OR adj 8.06; 95% CI 5.59-11.62) and use of medicines acting on the central nervous system (OR adj 3.34; 95% CI 2.35-4.73) were independently associated with the occurrence of prescription errors. Interventions targeted to high risk patients should be designed and implemented to improve pharmacotherapy in older individuals with an intellectual disability.


Biceps Tenotomy Versus Tenodesis.
Long head biceps tendon is a common cause of anterior shoulder pain. Failure of conservative treatment may warrant surgical intervention. Surgical treatment involves long head biceps tenotomy or tenodesis. Several different techniques have been described for biceps tenodesis, including arthroscopic versus open and suprapectoral versus subpectoral. Most studies comparing tenodesis to tenotomy are limited by the level of evidence and confounding factors, such as concomitant rotator cuff tear. Many studies demonstrate similar outcomes for both procedures. Surgeon preference is likely more influential in choosing between tenotomy and tenodesis. Higher-powered studies are necessary to elucidate any differences in outcomes if present.


Circulating levels of tissue inhibitor of metalloproteinase 3, a protein with inhibitory effects on angiogenesis, are increased in pre-eclampsia.
To assess and compare circulating tissue inhibitor of metalloproteinase 3 (TIMP-3) concentrations between women with pre-eclampsia and healthy pregnant women. We also aimed to determine the relationships between circulating TIMP-3 and matrix metalloproteinase 2 (MMP-2), MMP-9, TIMP-1, and TIMP-2 concentrations in pre-eclampsia. A primary case-control study included patients with pre-eclampsia (n = 219) and gestational hypertension (n = 118), healthy pregnant women (n = 214), and non-pregnant women (n = 66), and a replication case-control study included patients with pre-eclampsia (n = 177) and healthy pregnant women (n = 124), all from southeastern Brazil. Plasma TIMP-3, MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations were assessed using commercially available enzyme-linked immunosorbent assay kits, and the relationships between them were analyzed using Spearman's correlation. In our primary study, patients with pre-eclampsia and gestational hypertension exhibited increased TIMP-3 concentrations compared with healthy pregnant women (both P < 0.0001) and non-pregnant women (both P < 0.001). These findings were confirmed in the replication study, showing elevated TIMP-3 concentrations in women with pre-eclampsia versus healthy pregnant women (P < 0.001). We found no difference in TIMP-3 concentrations between early-onset and late-onset pre-eclampsia. Moreover, TIMP-3 concentrations were significantly correlated with plasma concentrations of TIMP-1 (r = 0.2333; P = 0.0086) and MMP-2 (r = 0.2159; P = 0.0156) in pre-eclampsia. Circulating TIMP-3 concentration is increased in women with pre-eclampsia compared with healthy pregnant women, and it is positively correlated with plasma MMP-2 and TIMP-1 concentrations in pre-eclampsia.


A proteome database of human primary T helper cells.
We have established the first public database of human primary T helper cell proteome using two-dimensional electrophoresis (2-DE) and matrix assisted laser desorption/ionization-time of flight-mass spectrometry. For the database, CD4+ human T cells were activated with anti-CD3+anti-CD28 antibodies and metabolically labeled with [35S]methionine for 24 h. Cells were lysed and proteins were separated by 2-DE. About 1500 protein spots were detected in the resulting 2-DE gels with silver staining, and 2000 spots with autoradiography. We have identified 91 proteins from the 2-DE gels using peptide mass fingerprinting, and annotated them to our database. The identified proteins are also linked to SWISS-PROTand NCBI protein databases. Our database is available via the Internet at http://www3.btk.utu.fi:8080/Genomics/Proteomics/Database.


Deoxy derivatives of butirosin A and 5"-amino-5"-deoxybutirosin A, aminoglycoside antibiotics resistant to bacterial 3'-phosphorylative enzymatic inactivation. Synthesis and NMR studies.
3'-Deoxybutirosin A (4), 5"-amino-3', 5"-dideoxybutirosin A (6), and 5"-amino-4', 5"-dideoxybutirosin A (7) were prepared by deoxygenation of the appropriate hydroxyl in suitably protected derivatives of butirosin A, using sequentially trifluoromethylsulfonylation, displacement with benzenethiolate, and hydrogenolysis. The structures of the compounds were confirmed by NMR spectroscopy, using 13C NMR and 1H NMR at up to 600 MHz. The compounds are broad-spectrum antibiotics active against resistant microorganisms which inactivate butirosin and related aminoglycosides by 3'-phosphorylation.


Spectroscopic technique for measuring the temperature and pressure cycle of a pressure modulator radiometer.
Precise spectral line measurements of carbon monoxide in an operating pressure modulator cell permit independent determinations of the instantaneous gas temperature and pressure.


Frailty.
The increasingly common awareness of frailty in human affairs seeks deeper explanation. Several reports employ non-traditional platforms to generate a framework which accommodates a range of experimental findings. Consideration of thermodynamic processes underlies much of this approach.


Schistosomatium douthitti: biochemical and morphological effects of an experimental infection in mice.
The pathophysiological changes that occur in mice experimentally infected with Schistosomatium douthitti were studied. Male ICR mice, 6-8 weeks in age, were exposed to 100 cercariae of S. douthitti from infected snails (Lymnaea catascopium) and sacrificed weekly for a total of 13 weeks. Liver homogenates, serum samples, and histological sections of liver tissue were examined. Results showed that body weights of animals with prepatent infections were higher than those of corresponding controls. After patency, which occurred at 5 weeks, body weights were lower and liver weights were higher resulting in significantly increased liver weight/body weight ratios. Hematocrit values declined progressively in patent infections. Total cholesterol in liver was generally higher in the parasitized groups reaching significance during patency. Values rose with age in both control and parasitized groups, but sooner in the latter. Free cholesterol was increased in the liver of animals with patent infections. Total lipid content of the liver was reduced in the infected animals throughout the study. Both liver glycogen and serum glucose levels in the infected animals rose over the control values. The activity of alkaline phosphatase (E.C.220.127.116.11) was elevated in liver tissue of infected mice. Glutamic-pyruvic transaminase (E.C.184.108.40.206) activity was higher in serum but lower in the livers of animals harboring patent infections. Total bile salt concentration in parasitized animals did not differ appreciably from control values; however, gallbladders were enlarged five times in the infected animals. Histologically, liver sections from infected mice showed granulomas in various stages of formation and degeneration. Granulomas contained from 1 to 40 schistosome eggs. After 6 weeks of infection, granulomas were characterized by many neutrophils and monocytes. Few lymphocytes and eosinophils were present. As the granulomas developed, fibroblasts and connective tissue became more prominent. Glycogen deposits were observed surrounding granulomas and were increased in older infections. Adult worms contained abundant amounts of glycogen and cholesterol in their parenchymal tissues.


Mitochondrial events responsible for morphine's cardioprotection against ischemia/reperfusion injury.
Morphine may induce cardioprotection by targeting mitochondria, but little is known about the exact mitochondrial events that mediate morphine's protection. We aimed to address the role of the mitochondrial Src tyrosine kinase in morphine's protection. Isolated rat hearts were subjected to 30 min ischemia and 2h of reperfusion. Morphine was given before the onset of ischemia. Infarct size and troponin I release were measured to evaluate cardiac injury. Oxidative stress was evaluated by measuring mitochondrial protein carbonylation and mitochondrial ROS generation. HL-1 cells were subjected to simulated ischemia/reperfusion and LDH release and mitochondrial membrane potential (ΔΨm) were measured. Morphine reduced infarct size as well as cardiac troponin I release which were aborted by the selective Src tyrosine kinase inhibitors PP2 and Src-I1. Morphine also attenuated LDH release and prevented a loss of ΔΨm at reperfusion in a Src tyrosine kinase dependent manner in HL-1 cells. However, morphine failed to reduce LDH release in HL-1 cells transfected with Src siRNA. Morphine increased mitochondrial Src phosphorylation at reperfusion and this was abrogated by PP2. Morphine attenuated mitochondrial protein carbonylation and mitochondrial superoxide generation at reperfusion through Src tyrosine kinase. The inhibitory effect of morphine on the mitochondrial complex I activity was reversed by PP2. These data suggest that morphine induces cardioprotection by preventing mitochondrial oxidative stress through mitochondrial Src tyrosine kinase. Inhibition of mitochondrial complex I at reperfusion by Src tyrosine kinase may account for the prevention of mitochondrial oxidative stress by morphine.


[Measurement of endogenous carbon monoxide increase in the blood as a criterion of systemic hemolysis].
Using a closed to-and-from respiratory system and measuring the COHb level in capillary blood the rise in endogenous carbon monoxide level in the blood was determined in 15 patients with haemolytic anaemia and in 6 healthy subjects. An evident rise in CO concentration with raised COHb level in the blood was found in all patients with haemolytic anaemia.


Characterization of basolateral Na/H exchange (Na/H-1) in MDCK cells.
MDCK cells were grown to confluent monolayers on permeant filter supports; pH was analysed by using the pH-sensitive fluorescent probe 2'7'-biscarboxyethyl-5,6-carboxyfluorescein and a routine spectrofluorometer equipped with a perfusion cuvette [Krayer-Pawlowska et al. (1990) J Membr Biol 120:173-183]. Superfusion of the basolateral (but not apical) cell surface with Na(+)-containing solutions led to immediate recovery of pHi from an acid load (NH4 prepulse). This pHi recovery was reversibly inhibited by ethylisopropylamiloride indicating Na/H exchange activity. Na/H exchange activity showed an apparent Km for Na+ of about 25 nM Na+ and an apparent Ki for inhibition by dimethylamiloride of around 0.2 microM; inhibition by dimethylamiloride was competitive with Na+ interaction. Lowering pHi prior to analysis of Na/H exchange leads to sharp activation of Na/H exchange; the apparent Vmax for Na/H exchange is increased more than tenfold by lowering the pHi from 7.0 to 6.7 without an effect on apparent Km values for Na+ interaction. It is concluded that MDCK cells (strain I) grown on a permeant support contain only basolateral Na/H exchange activity, most likely Na/H-1 [for nomenclature see Igarashi et al. (1991) Kidney Int 40:S84-S89].


[Immunohistochemical detections of EGFR status in NSCLC].
Patients with non-small cell lung cancer (NSCLC) harboring mutations of the epidermal growth factor receptor (EGFR) respond well to EGFR-tyrosine kinase inhibitor therapy. Immunohistochemistry (IHC) is a simple and widely used technique in clinical pathology laboratories. IHC also features cost effectiveness and rapid detection of EGFR mutations compared with molecular methods. This study aims to determine the accuracy of IHC for EGFR mutation detection in NSCLC. Specimens (obtained from surgery or biopsy) from 97 NSCLC cases were stained through IHC with mutation-specific antibodies. The clinicopathological features of patients with positive immunostaining results were analyzed. Positive specimens were subjected to liquid chip technology to detect the actual EGFR status. Forty NSCLC specimens obtained from surgery and confirmed to have EGFR mutations through liquid chip technology were collected. These specimens were then subjected to IHC analyses with mutation-specific antibodies. The sensitivity of IHC in detecting EGFR mutations was calculated. Seventeen of the 97 NSCLC specimens were stained positive, and positive results were mostly observed in females, patients with adenocarcinoma, and non-smokers. About 76.9% of specimens with positive IHC results harbored mutations. The sensitivity of IHC was 40% among the 40 cases identified as containing EGFR mutations through liquid chip technology. The strong positive immunostaining result is accurate, but the sensitivity of the method may not be optimal and significantly varies in different studies. The widespread application of IHC in clinics must be further investigated.


The significance of epithelial rests of Malassez in the periodontal ligament.
The purpose of this review was to describe the function of epithelial rests of Malassez (ERMs) in a variety of physiologic and pathologic conditions. The authors performed a PubMed search on the term "epithelial rests" alone or in combination with "Malassez." Relevant articles were categorized into primary subtopics and related to current and historic literature. The review was divided into 7 subtopics. Those sections discuss possible roles for ERM in a variety of physiologic and pathologic processes. ERMs have a fundamental role in root development, protect against root resorption, and are involved in reparative and regenerative functions of the pulp and periodontal tissues including apexogenesis and periodontal healing. They also appear to be involved in pathologic processes such as the development of oral cysts and tumors.


Pharmacological Activation of Peroxisome Proliferator-Activated Receptor {Delta} Increases Sphingomyelin Synthase Activity in THP-1 Macrophage-Derived Foam Cell.
Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which mediate glucose and lipid homeostasis by regulating the expression of a large number of transcription factors. Sphingomyelin synthase (SMS) is a key enzyme in the synthesis of sphingomyelin (SM), and its expression and activity have been reported to be associated with atherosclerosis (AS). Although there have been many functional PPAR and SMS studies on atherosclerosis in recent years, few have investigated the correlation between the activation of PPARδ and the activity of SMS. In his study, macrophage-induced foam cells were utilized to model important pathological changes that occur in AS. The influence of PPARδ agonism by GW501516 on SMS and its product molecule SM were measured. Results indicated that the activation of PPARδ was correlated in a positive manner with the activity of SMS2, and the content of SM was dose dependently increased by GW501516. Together, this study represents the first to suggest that PPARδ activation may be a potential risk of AS through enhancing activity of SMS2.


Chronic obstructive pulmonary disease in the United Kingdom: trends in mortality, morbidity, and smoking.
Current trends in chronic obstructive pulmonary disease (COPD) in the UK differ from those in many other countries because, in the past, COPD was much more common than in other countries undergoing a smoking epidemic at the same time, and peak cigarette consumption in men and women occurred more 25 years ago. Male mortality from COPD has been falling for 30 years, while female mortality has risen steadily during the same period. A strong socioeconomic gradient in morbidity and mortality persists. Emergency hospital admissions for exacerbations and home oxygen account for a large proportion of the healthcare costs.