Approach to Diagnostic Cytopathology of Serous Effusions.
Collection of most serous fluids from various effusions is a relatively simple procedure. Because of this, serous fluids are commonly submitted for pathologic examination including cytopathologic evaluation by various clinical institutions. As a consequence, even a general pathology laboratory which may not have expertise with highly trained cytopathologist would be confronted with serous fluids for cytologic evaluation. However, cytopathologic evaluation of serous fluids is complex as compared to evaluation of fine needle aspiration cytology. This signifies the fact that all pathologists, irrespective of subspeciality cytopathology training and level of subspeciality expertise, should be conversant with the diagnostic challenges and pitfalls of effusion fluid cytology. Although, majority of effusions are due to reactive and non-neoplastic etiologies, cancer is one of the causes of an effusion as a manifestation of advanced cancer. Detecting neoplastic cells in effusion specimens in most of clinical settings is related to the advanced status of the disease, which usually is equivalent to incurable stage. Thus, interpretation of cytopathology as positive for cancer cell is highly critical in planning the trajectory of the clinical management with an obvious negative impact of false positive interpretation. Apart from cancer, effusions may be secondary to hemodynamic pathologies such as heart failure, hypoalbuminemia, cirrhosis etc. in addition to the different inflammatory conditions including parasitic infestations, bacterial, fungal, or viral infections, and other non-neoplastic etiologies including collagen diseases. Due to the cytomorphologic overlap of reactive mesothelial cells with malignant cells, general cytologic criteria for diagnosis of malignancy in single cells cannot be applied in most of the effusion specimens. This challenge is further amplified because of surface tension related phenomenon which 'round up' the cells after exfoliation in serous fluids. As a result, the native shapes of cancer cells cannot be a guiding feature. Thus the cytomorphologic features of cancer cells in serous fluids may not be same as seen in routine cytopathology of exfoliative, brushing, and fine-needle aspiration specimens. The cancer cells may continue to proliferate after exfoliation in the nutrient rich effusion fluids and may form proliferation spheres. It is crucial to consider these factors when interpreting effusion cytology. Amongst malignant effusions, adenocarcinomas are the most common cause of metastatic cancers, but almost any type of malignancy including melanomas, hematopoietic neoplasms, sarcomas, and mesotheliomas may involve serous cavities. The interpreter must be aware of the wide range of the cytomorphologic appearances of reactive mesothelial cells in effusion fluids. It is essential to understand these and other nuances related to effusion fluid cytology. Understanding potential pitfalls during various stages from processing to application of ancillary studies would increase the diagnostic accuracy and minimize atypical interpretations and false positivity.


Handling limited datasets with neural networks in medical applications: A small-data approach.
Single-centre studies in medical domain are often characterised by limited samples due to the complexity and high costs of patient data collection. Machine learning methods for regression modelling of small datasets (less than 10 observations per predictor variable) remain scarce. Our work bridges this gap by developing a novel framework for application of artificial neural networks (NNs) for regression tasks involving small medical datasets. In order to address the sporadic fluctuations and validation issues that appear in regression NNs trained on small datasets, the method of multiple runs and surrogate data analysis were proposed in this work. The approach was compared to the state-of-the-art ensemble NNs; the effect of dataset size on NN performance was also investigated. The proposed framework was applied for the prediction of compressive strength (CS) of femoral trabecular bone in patients suffering from severe osteoarthritis. The NN model was able to estimate the CS of osteoarthritic trabecular bone from its structural and biological properties with a standard error of 0.85MPa. When evaluated on independent test samples, the NN achieved accuracy of 98.3%, outperforming an ensemble NN model by 11%. We reproduce this result on CS data of another porous solid (concrete) and demonstrate that the proposed framework allows for an NN modelled with as few as 56 samples to generalise on 300 independent test samples with 86.5% accuracy, which is comparable to the performance of an NN developed with 18 times larger dataset (1030 samples). The significance of this work is two-fold: the practical application allows for non-destructive prediction of bone fracture risk, while the novel methodology extends beyond the task considered in this study and provides a general framework for application of regression NNs to medical problems characterised by limited dataset sizes.


Functional and effective connectivity in subthalamic local field potential recordings of patients with Parkinson's disease.
In Parkinson's disease (PD) levodopa-associated changes in the power and long-range temporal correlations of beta oscillations have been demonstrated, yet the presence and modulation of genuine connectivity in local field potentials (LFP) recorded from the subthalamic nucleus (STN) remains an open question. The present study investigated LFP recorded bilaterally from the STN at wakeful rest in ten patients with PD after overnight withdrawal of levodopa (OFF) and after a single dose levodopa administration (ON). We utilized connectivity measures being insensitive to volume conduction (functional connectivity: non-zero imaginary part of coherency; effective connectivity: phase-slope index). We demonstrated the presence of neuronal interactions in the frequency range of 10-30 Hz in STN-LFP without a preferential directionality of interactions between different contacts along the electrode tracks. While the direction of neuronal interactions per se was preserved after levodopa administration, functional connectivity and the ventral-dorsal information flow were modulated by medication. The OFF-ON differences in functional connectivity were correlated with the levodopa-induced improvement in clinical Unified Parkinson's Disease Rating Scale scores. We hypothesize that regional neuronal interactions, as reflected in STN-LFP connectivity, might represent a basis for the intra-nuclear spatial specificity of deep brain stimulation. Moreover, our results suggest the potential use of volume conduction-insensitive measures of connectivity in STN-LFP as a marker of clinical motor symptoms in PD.


Over-expression of PPAR-γ2 gene enhances the adipogenic differentiation of hemangioma-derived mesenchymal stem cells in vitro and in vivo.
Most of infantile hemangiomas involute into fibrofatty tissue in childhood, which indicates adipogenesis during this period. Mesenchymal stem cells (MSCs) contribute to the adipogenesis in IH. In this study, we investigated the effects of overexpression of PPAR-γ2 gene on the adipogenic differentiation of Hemangioma-derived MSCs (Hem-MSCs), and discussed the possibility of targeted therapy via PPAR-γ pathway. MSCs were isolated from proliferating hemangioma by their selective adhesion to plastic culture dishes. Recombinant lentivirus with PPAR-γ2 gene were prepared, and used to transfect Hem-MSCs. Transfected cells were cultured in adipogenic medium to observe the differentiation in vitro. And the cells were mixed with Matrigel, then subcutaneously injected into the back of nude mice to observe the differentiation in vivo. In the in vitro tests, Hem-MSCs with overexpression of PPAR-γ2 gene showed enhanced adipogenic differentiation with increased expression of adipogenic-related genes, including PPAR-γ2, ADD1, LPL, and CEBPA genes. In the in vivo tests, Hem-MSCs/Matrigel plugs with overexpression of PPAR-γ2 gene also showed accelerated adipogenesis and time-phased changes of above genes. Overexpression of PPAR-γ2 gene enhances and accelerates the adipogenic differentiation of Hem-MSCs in vitro and in vivo. The results may provide the preliminary evidences for the targeted therapy of IH via PPAR-γ signal pathway.


Upregulated in Hepatitis B virus-associated hepatocellular carcinoma cells, miR-331-3p promotes proliferation of hepatocellular carcinoma cells by targeting ING5.
Hepatitis B virus (HBV) is a major risk factor for development and progression of hepatocellular carcinoma (HCC). It has been reported that viral infection can interfere with cellular microRNA (miRNA) expression and participate in the pathogenesis of oncogenicity. Our miRNAs array data indicated that miR-331-3p expression in HCC cell lines increased, but the relationship between miR-331-3p expression and HBV activity is unclear. Here, we observed elevated expression of miR-331-3p in different HCC cell lines expressing HBV. HBV, especially HBx, promotes miR-331-3p expression by enhancing its promoter activity. Using a miRNA target prediction database miRBase, we identified ING5 to be a novel target gene of miR-331-3p. miR-331-3p could inhibit ING5 expression by directly targeting its 3'-untranslated region (3'-UTR). As predicted, HBV was confirmed to repress ING5 at both mRNA and protein levels by promoting miR-331-3p expression. Our result indicated that miR-331-3p expression promotes proliferation of SMMC7721 cells by inhibiting ING5. ING5 overexpression promoted cell apoptosis in HCC cell lines. We also found ING5 expression was decreased in tumor tissue of HCC patient with HBV infection compared to its expression in para-carcinoma tissues. These results showed that miR-331-3p is upregulated by HBV and promotes proliferation of HCC cells though repression of ING5 expression. These data provide new insights for understanding the mechanisms of HBV-related HCC pathogenesis.


Echinostoma luisreyi n. sp. (Platyhelminthes: Digenea) by light and scanning electron microscopy.
The entire life cycle of the Brazilian Echinostoma luisreyi n. sp., of the 37-collar spine E. revolutum group, has been observed under experimental conditions. The snail Physa marmorata serves as its first natural intermediate host. This species and the planorbid Biomplalaria glabrata act as experimental second intermediate hosts. The worm recovery rate was 51.3 and 0.6% for mice and hamsters, respectively, but the infection did not develop in the quail Coturnix coturnix. The natural vertebrate host is not known. The most important morphological character of the new species separating it from the other Echinostoma species studied is the oral corner spines that increase in size from the latero-oral to the ventro-oral regions. The ratio of the sizes of the smaller oral spines and the larger aboral ones was 1.7:1.0. Also, the excretory pore is radially wrinkled and dorsally subterminal. Images obtained by scanning electron microscopy confirmed the characters that differentiate the new species and the most closely related species.


A computer study and photoelectric property analysis of potassium-doped lithium niobate single crystals.
First-principles theory was used to design a potassium-doped lithium niobate single crystal. The structural, electronic, optical and ferroelectric properties of the potassium-doped LiNbO3 single crystal model have been investigated using a generalized gradient approximation within density functional theory. It was found that substitution with potassium drastically changed the optical and electronic nature of the crystal and that the band gap slightly decreases. A series of LiNbO3 single crystals doped with x mol% K (x = 0, 3, 6, 9, 12 mol%) were successfully grown using the Czochralski method. The crystals were characterized using powder X-ray diffraction, UV-vis-infrared absorption spectroscopy and a ferroelectric property test. The experimental test results were consistent with the calculated predictions.


Protonation and H/D exchange reactions promoted by a sulfur-rich osmium hydride complex: identification of a labile dihydrogen complex.
The sulfur-rich osmium nitrosyl complexes Bu(4)N[Os(NO)((bu)S(2))(2)] (1) [(bu)S(2)(2-) = 3,5-tert-butyl-1,2-benzenedithiolate(2-)] and [Os(NO)(py(bu)S(4))]Br ()[py(bu)S(4)(2-) = 2,6-bis(2-sulfanyl-3,5-di-tert-butylphenylthio)dimethylpyridine(2-)] have been synthesized. The molecular structure of 1 exhibits a square-pyramidal geometry with the NO group at the apical position. A pseudo-octahedral geometry with two thiolate and two thioether donors in trans configuration is found for 2. Compound 2 shows two quasi-reversible one-electron redox waves at E(1/2) = 0.51 and -0.46 V vs. NHE for the redox couples [Os(NO)(py(bu)S(4))](+1/0) and [Os(NO)(py(bu)S(4))](0/-1), respectively. 2 reacts with NaAlH(4) to produce Na[Os(H)(py(bu)S(4))] (3), which exhibits a typical hydride resonance in the (1)H NMR spectrum at delta =-15.03 ppm. Protonation of 3 with HBF(4)/CD(3)OD at 20 degrees C rapidly releases H(2)/HD to afford the dinuclear complex [Os(py(bu)S(4))](2) (4). Low temperature (1)H and (2)H NMR spectra of in [D(8)]THF with CH(3)OH or CD(3)OD at -80 degree C allow the observation of the formation of [Os(H(2)/HD)(py(bu)S(4))]. A 1 : 1 : 1 triplet at delta = -7.84 ppm [J(HD) = 31.2 Hz] and a relaxation time of T(1)(min) = 6 ms (-65 degrees C, 270 MHz) firmly establish the presence of eta(2)-H(2)/HD ligand. At room temperature, 3 interacts with D(2) (1 atm) and undergoes heterolytic D(2) cleavage followed by H/D exchange to form Na[Os(D)(py(bu)S(4))] (3a). A plausible cyclic mechanism has been proposed.


Results of 1 year of clinical experience with independent dose calculation software for VMAT fields.
It is widely accepted that a redundant independent dose calculation (RIDC) must be included in any treatment planning verification procedure. Specifically, volumetric modulated arc therapy (VMAT) technique implies a comprehensive quality assurance (QA) program in which RIDC should be included. In this paper, the results obtained in 1 year of clinical experience are presented. Eclipse from Varian is the treatment planning system (TPS), here in use. RIDC were performed with the commercial software; Diamond(®) (PTW) which is capable of calculating VMAT fields. Once the plan is clinically accepted, it is exported via Digital Imaging and Communications in Medicine (DICOM) to RIDC, together with the body contour, and then a point dose calculation is performed, usually at the isocenter. A total of 459 plans were evaluated. The total average deviation was -0.3 ± 1.8% (one standard deviation (1SD)). For higher clearance the plans were grouped by location in: Prostate, pelvis, abdomen, chest, head and neck, brain, stereotactic radiosurgery, lung stereotactic body radiation therapy, and miscellaneous. The highest absolute deviation was -0.8 ± 1.5% corresponding to the prostate. A linear fit between doses calculated by RIDC and by TPS produced a correlation coefficient of 0.9991 and a slope of 1.0023. These results are very close to those obtained in the validation process. This agreement led us to consider this RIDC software as a valuable tool for QA in VMAT plans.


The rise of mammals.
Mammalian synthetic biology represents a vibrant and growing technical discipline. As this nascent field matures, technologies for engineering sophisticated mammalian cell functions are enabling the development of novel therapies that address unmet medical needs. These transformative capabilities are likely to impact clinical practice in ways that have yet to be identified.


Fibronectin enhances in vitro lipopolysaccharide priming of polymorphonuclear leukocytes.
We investigated the role of humoral factors in lipopolysaccharide (LPS) priming of polymorphonuclear leukocytes (PMN) using cells isolated from adults and from neonates. Plasma from newborn infants had decreased priming activity of adult plasma when mixed with LPS in studies measuring oxidative radical production of PMN after stimulation with a formyl bacterial oligopeptide (fMLP). This marked difference was not caused by LPS binding protein (LBP) because the LBP concentration in newborn and adult plasma were similar (138.4 +/- 12.9 U for adults, and 126.9 +/- 12.1 U for neonates, P = .53). Therefore, we attempted to identify other plasma factors that may contribute to LPS priming of PMN. We identified an LPS priming factor for PMN that is present in plasma, heat stable (56 degrees C for 30 minutes), enhanced by heparin, and concentrated in cold precipitates of plasma. Because these properties resemble those of plasma fibronectin, we assessed the role of fibronectin in LPS priming of PMN. Although fibronectin in phosphate-buffered saline (PBS) had little effect on LPS priming of PMN, fibronectin in combination with other plasma factors appeared to play a role in LPS priming of PMN because (1) removing fibronectin from adult plasma dramatically decreased LPS priming activity from plasma (P < .005), (2) addition of fibronectin to fibronectin-depleted plasma restored its LPS plasma priming activity (P < .05), and (3) neutralizing fibronectin with antibody decreased the LPS priming activity of plasma (60.3 +/- 1.3 v 30.2 +/- 2.2, P < .01). Thus, plasma fibronectin plays a role in LPS priming of PMN in the presence of other factors in plasma.


Micranoic acids A and B: two new octanortriterpenoids from Schisandra micrantha.
Two novel octanortriterpenoids, micranoic acids A (1) and B (2), along with three known compounds, kadsuric acid (3), 3beta-hydroxy-lanost-9(11),24(25)-dien-26-oic acid (4) and schizandronic acid (5), were isolated from the leaves and stems of Schisandra micrantha. The structures of 1 and 2 were determined by 1D and 2D NMR spectroscopic analysis. Micranoic acids A and B represent a new group of triterpenes in which the entire C-17 side chain has lost. This is the first report of octanortriterpenoids isolated from the family Schisandraceae.


[Ophthalmological aspects of systemic vasculitis].
Ocular findings of systemic vasculitis, such as polyarteritis nodosa, giant cell angitis, and aortitis syndrome were reviewed. Systemic lupus erythematosus is not categorized as systemic vasculitis, however its ocular findings are microangiopathic. Therefore review of its ocular findings was included in this paper. The most common fundus finding in these diseases is ischemic optic neuropathy or retinal vascular occlusions. Therefore several points in diagnosis or pathogenesis of optic neuropathy and retinal and choroidal vaso occlusion were discussed. Choroidal ischemia has come to be able to diagnosed clinically, since fluorescein angiography was applied in these lesions. When choroidal arteries are occluded, overlying retinal pigment epithelium is damaged. This causes disruption of barrier function of the epithelium and allows fluid from choroidal vasculatures to pass into subsensory retinal spaces. This is a pathogenesis of serous detachment of the retina. The retinal arterial occlusion formed non-perfused retina. Such hypoxic retina released angiogenetic factors which stimulate retinal and iris neovascularizations and iris neovascularization may cause neovascular glaucoma.


Social norms and women's risk of intimate partner violence in Nepal.
Social norms increasingly are the focus of intimate partner violence (IPV) prevention strategies but are among the least examined contextual factors in quantitative violence research. This study assesses the within-community, between-community, and contextual effect of a new measure of social norms (PVNS: Partner Violence Norms Scale) on women's risk of IPV. Data come from baseline surveys collected from 1435 female, married, reproductive-age participants, residing in 72 wards in three districts (Chitwan, Kapilvastu, Nawalparasi) in Nepal who were enrolled in a cluster randomized trial testing the impact of a social behavioral change communication intervention designed to prevent IPV. Results of unconditional multilevel logistic regression models indicated that there was cluster-level variability in the 12-month prevalence of physical (ICC = 0.07) and sexual (ICC = 0.05) IPV. Mean PVNS scores also varied across wards. When modeled simultaneously, PVNS scores aggregated to the ward-level and at the individual-level were associated with higher odds of physical (ORind = 1.12, CI = 1.04, 1.20; ORward = 1.40, CI = 1.15, 1.72) and sexual (ORind = 1.15, CI = 1.08, 1.24; ORward = 1.47, CI = 1.24, 1.74) IPV. The contextual effect was significant in the physical (0.23, se = 0.11, t = 2.12) and sexual (0.24, se = 0.09, t = 2.64) IPV models, suggesting that the ward-level association was larger than that at the individual-level. Adjustment for covariates slightly attenuated the ward-level association and eliminated the contextual association, suggesting that individual perceptions and the collective community phenomena were equally strong predictors of women's risk of IPV and should be taken into consideration when planning interventions. PVNS is a promising measure of social norms underpinning women's risk of IPV and warrants further psychometric testing.


MicroRNA-505-5p functions as a tumor suppressor by targeting cyclin-dependent kinase 5 in cervical cancer.
MicroRNAs (miRs) are considered to be tumor suppressors or oncogenes as they regulate cell proliferation, migration, invasion, and differentiation. Recently, microRNA-505 (miR-505) has been reported as being involved in the progression of several human cancers. In the present study, we aim to investigate the expression rate and functional role of miR-505-5p in cervical cancer (CC) to determine its significance regarding the disease's development.The expression of miR-505-5p and cyclin-dependent kinase 5 (CDK5) in specimens of patients with CC and CC cell lines was examined by quantitative real-time PCR (qRT-PCR) and Western Blot. The relationship between miR-505-5p and CDK5 was verified by luciferase reporter assay. Cell counting kit-8 (CCK-8) assay, Scratch wound healing assay and transwell assay were used to detect the roles of miR-505-5p and CDK5 in CC cell functions. Western Blot was utilized to explore the epithelial-mesenchymal transition (EMT) markers.The result showed that in CC tissues and CC cell lines miR-505-5p was down-regulated while CDK5 level was up-regulated. MiR-505-5p was closely correlated with the metastasis-associated clinicopathological features. Overexpression of miR-505-5p inhibited cell viability, cell metastasis and EMT in CC cells. CDK5 was confirmed as a direct target of miR-505-5p and inverse relationship between them was also observed. Overexpression of CDK5 reduces the inhibitory effects of miR-505-5p in CC.Taken together, these results determine that miR-505-5p is a tumor suppressor miRNA which regulates tumor cell proliferation, migration, and invasion via binding to the functional target CDK5 and demonstrates its potential for future use in the treatment of CC.


[The Stepanik arteriotonograph (author's transl)].
A pressure-sensitive probe, specially developed for this purpose, is built into a contact lens in such a manner that when adjusted to the patient's eye the probe registers the intraocular pressure whilst the observer compresses the eyeball and observes the arterial collapse phenomenon on the disc over the contact lens on the slit-lamp microscope. The standard deviation of a clinical measurement is 1.5 mm Hg. Derived from measurements on 65 eyes of patients without signs of vascular disorder, the correlation of the systolic and diastolic ophthalmic artery-pressure (y) to that of the ipsilateral brachial artery (x) is given by Y =0.79x-1.33 (r=0.96) and the correlation of their median pressure by Y=0.93x-17.2 (r=0.94).


Dual-TRACER: High resolution fMRI with constrained evolution reconstruction.
fMRI with high spatial resolution is beneficial for studies in psychology and neuroscience, but is limited by various factors such as prolonged imaging time, low signal to noise ratio and scarcity of advanced facilities. Compressed Sensing (CS) based methods for accelerating fMRI data acquisition are promising. Other advanced algorithms like k-t FOCUSS or PICCS have been developed to improve performance. This study aims to investigate a new method, Dual-TRACER, based on Temporal Resolution Acceleration with Constrained Evolution Reconstruction (TRACER), for accelerating fMRI acquisitions using golden angle variable density spiral. Both numerical simulations and in vivo experiments at 3T were conducted to evaluate and characterize this method. Results show that Dual-TRACER can provide functional images with a high spatial resolution (1×1mm2) under an acceleration factor of 20 while maintaining hemodynamic signals well. Compared with other investigated methods, dual-TRACER provides a better signal recovery, higher fMRI sensitivity and more reliable activation detection.


[Update on current care guidelines: spinal cord injury].
Traumatic spinal cord injury is most common among men between 16 and 30 years. Prevention should be targeted both on traffic safety and individual behaviour Key issues in patient care are safe transfer from the place of injury to a hospital, diagnostic imaging (primarily CT, MRI if needed) and assessment of neurological injury by AIS-questionnaire, early surgical decompression and stabilisation for most cases, and treatment and rehabilitation starting from the emergency room and extending to life-long care carried out by a multi-professional team.


Visual deficits following stroke: maximizing participation in rehabilitation.
This article reviews the literature regarding the prevalence, etiology, and clinical symptoms of various visual deficits including those that are age related and those that are a result of neurological damage to the brain, such as in traumatic brain injury or stroke. It discusses treatment options provided by an occupational therapist, along with other members of the rehabilitation team, to educate the patient and family members regarding vision loss, to accommodate for visual loss, and to optimize independence with activities of daily living. This article also briefly reviews the literature and discusses possibilities for individuals who identify computer access and return to driving as goal areas.


MARSIPAN and the deadly triad: management of malnourished patients.
A 44-year-old gentleman was admitted with a deliberate overdose of olanzapine, paracetamol and bisoprolol. On admission, he was hypothermic, bradycardic and hypotensive and his body mass index was 12 kg/m(2). Problems identified on admission included polypharmacy overdose, risk of refeeding syndrome and sepsis. Despite careful reintroduction of feeding and generous electrolyte replacement, he developed persistent hypophosphataemia, hypokalaemia and a marked transaminitis. Several days later, he was noted to be hypothermic and hypoglycaemic. No increase in white cell count or C reactive protein was noted and his clinical appearance was otherwise unremarkable. Nevertheless, given these signs he was started on broad spectrum antibiotics for possible sepsis, which was subsequently confirmed on chest radiograph in addition to a further finding of likely aspergilloma on a later chest CT. His metabolic function stabilised after 3 weeks of carefully titrated nutrition and the sepsis responded to antibiotics and antifungal therapy.


Glucose intolerance and reduced islet blood flow in transgenic mice expressing the FRK tyrosine kinase under the control of the rat insulin promoter.
The FRK tyrosine kinase has previously been shown to transduce beta-cell cytotoxic signals in response to cytokines and streptozotocin and to promote beta-cell proliferation and an increased beta-cell mass. We therefore aimed to further evaluate the effects of overexpression of FRK tyrosine kinase in beta-cells. A transgenic mouse expressing kinase-active FRK under control of the insulin promoter (RIP-FRK) was studied with regard to islet endocrine function and vascular morphology. Mild glucose intolerance develops in RIP-FRK male mice of at least 4 mo of age. This effect is accompanied by reduced glucose-stimulated insulin secretion in vivo and reduced second-phase insulin secretion in response to glucose and arginine upon pancreas perfusion. Islets isolated from the FRK transgenic mice display a glucose-induced insulin secretory response in vitro similar to that of control islets. However, islet blood flow per islet volume is decreased in the FRK transgenic mice. These mice also exhibit a reduced islet capillary lumen diameter as shown by electron microscopy. Total body weight and pancreas weight are not significantly affected, but the beta-cell mass is increased. The data suggest that long-term expression of active FRK in beta-cells causes an in vivo insulin-secretory defect, which may be the consequence of islet vascular abnormalities that yield a decreased islet blood flow.


Role of SHP-2 in fibroblast growth factor receptor-mediated suppression of myogenesis in C2C12 myoblasts.
Ligand activation of the fibroblast growth factor receptor (FGFR) represses myogenesis and promotes activation of extracellular signal-regulated kinases 1 and 2 (Erks). The precise mechanism through which the FGFR transmits both of these signals in myoblasts remains unclear. The SH2 domain-containing protein tyrosine phosphatase, SHP-2, has been shown to participate in the regulation of FGFR signaling. However, no role for SHP-2 in FGFR myogenic signaling is known. In this study, we show that stimulation of C2C12 myoblasts with FGF-2 induces SHP-2 complex formation with tyrosyl-phosphorylated FGFR substrate 2 alpha (FRS-2 alpha). Both the catalytic activity and, to a much lesser extent, the Grb2 binding-tyrosyl phosphorylation sites of SHP-2 are required for maximal FGF-2-induced Erk activity and Elk-1 transactivation. When overexpressed in C2C12 myoblasts, wild-type SHP-2, but not a catalytically inactive SHP-2 mutant, potentiates the suppressive effects of FGF-2 on muscle-specific gene expression. In addition, expression of a constitutively active mutant of SHP-2 is sufficient to prevent myogenesis. The constitutively active mutant of SHP-2 induces hyper-tyrosyl phosphorylation of FRS-2 alpha but fails to stimulate or potentiate either FGF-2-induced Erk activation or Elk-1 transactivation. These data suggest that in myoblasts, SHP-2 represses myogenesis via a pathway that is independent of the Erks. We propose that SHP-2 plays a pivotal role in FGFR signaling in myoblasts via both Erk-dependent and Erk-independent pathways.


HER2-positive apocrine carcinoma of the breast: a population-based analysis of treatment and outcome.
Apocrine carcinoma of the breast (APO) expresses HER2 in 30-50% of cases. This study explored the clinicopathological features and outcome of HER2+/APO and matched HER2+/NST cohort. We used the SEER database to explore the cohorts. Univariate and multivariate analyses were used to assess the survival. Based on ER and PR [steroid receptors/SR/] and HER2 status, we divided the cohorts to match the intrinsic molecular subtypes for comparisons. We retrieved 259 cases of HER2+/APO. Most HER2+/APO were SR negative (65%). HER2+/APO were more prevalent in the 80+ age group (24.7% vs. 15.7%, p < 0.001). HER2+/SR-/APO had a significantly lower histological grade than the HER2+/SR-/NST (p < 0.001). Breast cancer-related deaths were more prevalent in HER2+/NST (7.8% vs. 3.9%, p = 0.019). This was particularly evident between SR- subgroups (10.4% in HER2+/SR-/NST vs. 4.2% in HER2+/SR-/APO, p = 0.008) and was reaffirmed in breast cancer-specific survival in univariate analysis (p = 0.03). Other than race and SR status, HER2+/APO subgroups did not differ in clinicopathological parameters. Our study confirms the rarity of the APO and reveals that SR status in APO does not affect these patients' prognosis. HER2+/APO tumors tend to have a less aggressive phenotype and a more favorable outcome despite a markedly lower ER/PR positivity.


Phytolith-occluded carbon in leaves of Dendrocalamus Ronganensis influenced by drought during growing season.
Being an important carbon (C) sink, phytolith-occluded carbon (PhytOC) has been investigated in various soil-plant systems. However, the effects of environmental factors (i.e., drought) on phytoliths, including altered deposition in plant tissues, morphological variation, and amounts of carbon occluded within phytoliths, are less studied. In this study, we analyzed the monthly variations of phytolith production and PhytOC in the leaves of Dendrocalamus ronganensis grown on a karst mountain in southwestern China during a drought year. This study thus sought to understand the effects of drought on phytolith formation, morphological variations and carbon sequestration within phytoliths in plants. Our results showed that the phytolith assemblages and PhytOC between new and old leaves differed significantly and varied with plant growth stages. The average PhytOC values of old leaves and tip leaves were 3.2% and 2.2%, respectively. In particular, both PhytOC and proportions of ELONGATE, BULLIFORM FLABELLATE, and STOMA phytoliths in tip leaves significantly decreased from September to January the following year because of drought effects. This study suggests that PhytOC in plants varies between phytolith morphotypes and is significantly affected by plant growth stage and hydrologic conditions. This indicates that we can improve the efficiency of phytolith carbon sequestration in plants by improving the soil water conditions required for plant growth.


The Natural Polypeptides as Significant Elastase Inhibitors.
Human neutrophil elastase (HNE) is a major cause of the destruction of tissues in cases of several different chronic andinflammatory diseases. Overexpression of the elastase enzyme plays a significant role in the pathogenesis of various diseases including chronic obstructive pulmonary disease (COPD), acute respiratory distress syndrome, rheumatoid arthritis, the rare disease cyclic hematopoiesis (or cyclic neutropenia), infections, sepsis, cystic fibrosis, myocardial ischemia/reperfusion injury and asthma, inflammation, and atherosclerosis. Human neutrophil elastase is secreted by human neutrophils due to different stimuli. Medicine-based inhibition of the over-activation of neutrophils or production and activity of elastase have been suggested to mend inflammatory diseases. Although the development of new elastase inhibitors is an essential strategy for treating the different inflammatory diseases, it has been a challenge to specifically target the activity of elastase because of its overlapping functions with those of other serine proteases. This review article highlights the reported natural polypeptides as potential inhibitors of elastase enzyme. The mechanism of action, structural features, and activity of the polypeptides have also been correlated wherever they were available.


Effectiveness of Evenup™ Shoe-Lift Use Among Individuals Prescribed a Walking Boot.
Walking boots are prescribed after foot and ankle injuries, allowing immediate ambulation for patients. However, temporary limb-length inequality (LLI) may result, causing dysfunction and pain, including low back pain. The Evenup™ shoe-lift was designed to eliminate joint pathology, pain, and gait deviations resulting from walking-boot-induced LLI, yet no clinical trials have been reported on its effectiveness. Thirty-four subjects undergoing unilateral lower-extremity orthopedic medical and rehabilitative care were recruited for this study. Seventeen subjects were assigned to an intervention group using a walking boot on the foot of their involved side and the Evenup™ on the other foot, while the control group used a walking boot only on the involved side. Outcome measures included the lower extremity functional scale (LEFS), modified Oswestry low back pain disability questionnaire (OSW), numeric pain rating scale, ankle range of motion (ROM) and strength. All subjects, regardless of the intervention, demonstrated improved function, decreased pain, increased ROM, and increased strength. Additionally, a clinically relevant difference was found between the intervention and control groups for the OSW and LEFS. LEFS and OSW results suggest Evenup™ use added value in the form of improved patient function.


Protein Intakes during Weaning from Parenteral Nutrition Drive Growth Gain and Body Composition in Very Low Birth Weight Preterm Infants.
Weaning from parenteral to enteral nutrition is a critical period to maintain an adequate growth in very low birth weight preterm infants (VLBWI). We evaluated the actual daily nutritional intakes during the transition phase (TP) in VLBWI with adequate and inadequate weight growth velocity (GV ≥ 15 vs. GV < 15 g/kg/day). Fat-free mass (FFM) at term-corrected age (TCA) was compared between groups. Based on actual nutritional intakes of infants with adequate growth, we defined a standardized parenteral nutrition bag (SPB) for the TP. One hundred and six VLBWI were categorized as group 1 (G1): [GV < 15 (n = 56)] and group 2 (G2): [GV ≥ 15 (n = 50)]. The TP was divided into two periods: main parenteral nutritional intakes period (parenteral nutritional intakes >50%) (M-PNI) and main enteral nutritional intakes period (enteral nutritional intakes >50%) (M-ENI). Anthropometric measurements were assessed at discharge and TCA, FFM deposition at TCA. During M-PNI, G2 showed higher enteral protein intake compared to G1 (p = 0.05). During M-ENI, G2 showed higher parenteral protein (p = 0.01) and energy intakes (p < 0.001). A gradual reduction in SPB volume, together with progressive increase in enteral volume, allowed nutritional intakes similar to those of G2. At TCA, G2 had higher FFM compared to G1 (p = 0.04). The reasoned use of SPB could guarantee an adequate protein administration, allowing an adequate growth and higher FFM deposition.


Motion of localized disturbances in scalar harmonic lattices.
We present analytical and numerical investigations of energy propagation in systems of massive particles that interact via harmonic (linear) forces. The particle motion is described by a scalar displacement, and the particles are arranged in a simple crystal lattice. For the systems under consideration we prove the conservation of the total energy flux analytically. Then, using a sample case of a square lattice, we confirm the analytical results numerically. We create disturbances of a special kind which can move with a predefined velocity with a minor change in their shape. We show that a clot of energy, associated with each disturbance, moves similarly to a free body of matter in classical mechanics. We also numerically study a simultaneous propagation of a number of energy clots as an analogy to the motion of point masses in the conventional mechanics of particles. The obtained results demonstrate that an energy flow in lattices can be described in terms of numerous separated energy bodies, making a step towards a linkage between lattice dynamics and the kinetic theory of heat transfer in solids.


Determination of the Global Pattern of Gene Expression in Yeast Cells by Intracellular Levels of Guanine Nucleotides.
Correlations between gene transcription and the abundance of high-energy purine nucleotides in Saccharomyces cerevisiae have often been noted. However, there has been no systematic investigation of this phenomenon in the absence of confounding factors such as nutrient status and growth rate, and there is little hard evidence for a causal relationship. Whether transcription is fundamentally responsive to prevailing cellular energetic conditions via sensing of intracellular purine nucleotides, independently of specific nutrition, remains an important question. The controlled nutritional environment of chemostat culture revealed a strong correlation between ATP and GTP abundance and the transcription of genes required for growth. Short pathways for the inducible and futile consumption of ATP or GTP were engineered into S. cerevisiae, permitting analysis of the transcriptional effect of an increased demand for these nucleotides. During steady-state growth using the fermentable carbon source glucose, the futile consumption of ATP led to a decrease in intracellular ATP concentration but an increase in GTP and the guanylate energy charge (GEC). Expression of transcripts encoding proteins involved in ribosome biogenesis, and those controlled by promoters subject to SWI/SNF-dependent chromatin remodelling, was correlated with these nucleotide pool changes. Similar nucleotide abundance changes were observed using a nonfermentable carbon source, but an effect on the growth-associated transcriptional programme was absent. Induction of the GTP-cycling pathway had only marginal effects on nucleotide abundance and gene transcription. The transcriptional response of respiring cells to glucose was dampened in chemostats induced for ATP cycling, but not GTP cycling, and this was primarily associated with altered adenine nucleotide levels.IMPORTANCE This paper investigates whether, independently of the supply of any specific nutrient, gene transcription responds to the energy status of the cell by monitoring ATP and GTP levels. Short pathways for the inducible and futile consumption of ATP or GTP were engineered into the yeast Saccharomyces cerevisiae, and the effect of an increased demand for these purine nucleotides on gene transcription was analyzed. The resulting changes in transcription were most consistently associated with changes in GTP and GEC levels, although the reprogramming in gene expression during glucose repression is sensitive to adenine nucleotide levels. The results show that GTP levels play a central role in determining how genes act to respond to changes in energy supply and that any comprehensive understanding of the control of eukaryotic gene expression requires the elucidation of how changes in guanine nucleotide abundance are sensed and transduced to alter the global pattern of transcription.


Tissue non-linearity.
The propagation of acoustic waves is a fundamentally non-linear process, and only waves with infinitesimally small amplitudes may be described by linear expressions. In practice, all ultrasound propagation is associated with a progressive distortion in the acoustic waveform and the generation of frequency harmonics. At the frequencies and amplitudes used for medical diagnostic scanning, the waveform distortion can result in the formation of acoustic shocks, excess deposition of energy, and acoustic saturation. These effects occur most strongly when ultrasound propagates within liquids with comparatively low acoustic attenuation, such as water, amniotic fluid, or urine. Attenuation by soft tissues limits but does not extinguish these non-linear effects. Harmonics may be used to create tissue harmonic images. These offer improvements over conventional B-mode images in spatial resolution and, more significantly, in the suppression of acoustic clutter and side-lobe artefacts. The quantity B/A has promise as a parameter for tissue characterization, but methods for imaging B/A have shown only limited success. Standard methods for the prediction of tissue in-situ exposure from acoustic measurements in water, whether for regulatory purposes, for safety assessment, or for planning therapeutic regimes, may be in error because of unaccounted non-linear losses. Biological effects mechanisms are altered by finite-amplitude effects.


Tachyphylaxis of intravenous immunoglobulin in refractory inflammatory myopathy.
We describe 2 patients with refractory inflammatory myositis who had an initial favorable response to intravenous immunoglobulin (IVIG) therapy. In contrast to all other reported cases, our patients reached a nadir in creatine phosphokinase (CPK) levels at 6 and 14 weeks after initiation of therapy, respectively, then experienced a relentless rise in CPK levels as well as a return of muscle weakness while still receiving IVIG. While IVIG may benefit some patients with refractory myositis, future studies must address the sustained efficacy of this agent.


[Action of imipenem on Enterobacter cloacae].
Most of Enterobacter cloacae strains produce chromosomally determined class I beta-lactamases when they are exposed to beta-lactams. Imipenem is a strong inducer of these enzymes but is poorly affected by them. We compared the effect of imipenem on inducible, non-inducible and stably derepressed strains of E. cloacae using the killing curve system. With antibiotic concentrations of 0.5 mg/l or more, an intense dose-dependent bactericidal effect was observed within 4 to 6 hours. However the bactericidal activity was incomplete. With an inoculum as low as 10(5) bacteria/ml a regrowth was observed after 24 hours. Among the surviving bacteria imipenem had the same bactericidal kinetic than on the parental strain. Similar results were observed with inducible, non-inducible and stably derepressed strains.


Frailty is an independent prognostic marker in elderly patients with myocardial infarction.
Acute coronary syndrome (ACS) patients are increasingly older. Conventional prognostic scales include chronological age but do not consider vulnerability. In elderly patients, a frail phenotype represents a better reflection of biological age. This study aims to determine the prevalence of frailty and its influence on patients age ≥75 years with ACS. Patients age ≥75 years admitted due to type 1 myocardial infarction were included in 2 tertiary hospitals, and clinical data were collected prospectively. Frailty was defined at admission using the previously validated Survey of Health Ageing and Retirement in Europe Frailty Index (SHARE-FI) tool. The primary endpoint was the combination of death or nonfatal myocardial reinfarction during a follow-up of 6 months. Major bleeding (hemoglobin decrease ≥3 g/dL or transfusion needed) and readmission rates were also explored. A total of 234 consecutive patients were included. Frail patients (40.2%) had a higher-risk profile, based on higher age and comorbidities. On multivariate analysis, frailty was an independent predictor of the combination of death or nonfatal myocardial reinfarction (adjusted hazard ratio [aHR]: 2.54, 95% confidence interval [CI]: 1.12-5.79), an independent predictor of the combination of death, nonfatal myocardial reinfarction, or major bleeding (aHR: 2.14, 95% CI: 1.13-4.04), and an independent predictor of readmission (aHR: 1.80, 95% CI: 1.00-3.22). Frailty phenotype at admission is common among elderly patients with ACS and is an independent predictor for severe adverse events. It should be considered in future risk-stratification models.


Specific distribution of short-chain fatty acids in molecular distillates of bovine milk fat.
Triglycerides with a total of 34-44 acyl carbon atoms have previously been shown to account for nearly 50% of bovine milk fat. About 80% of this material was isolated by molecular distillation and a representative fraction of these glycerides was subjected to a stereospecific analysis. Of the 29 moles % of C(4)-C(8) fatty acids present in the analyzed fraction, at least 95% were specifically attached to the glycerol molecule in the position corresponding to carbon 3 of sn-glycerol 3-(dihydrogen phosphate) (L-alpha-glycerophosphate). The distribution of the other fatty acids (C(10) or greater) did not show such marked specificity for either the 1- or the 2-position. The data support the hypothesis that the short-chain fatty acids are esterified with long-chain diglycerides, or are substituted in glycerophosphatide intermediates, during the final step in the biosynthesis of milk fat triglycerides.


Molecular identification of the dominant-negative, splicing isoform of the two-pore domain K(+) channel K(2P)5.1 in lymphoid cells and enhancement of its expression by splicing inhibition.
The two-pore domain background K(+) channel K2P5.1 is expected as a possible therapeutic target for autoimmune and inflammatory disorders and cancers because it plays an important role in maintaining the resting membrane potential and regulation of Ca(2+) signaling in T lymphocytes and cancer cells. However, the lack of selective K2P5.1 blockers has led to difficulties conducting experimental studies on this K(+) channel. We identified a novel splicing isoform of K2P5.1, K2P5.1B from the mammalian spleen, which lacked the N-terminus of full-length K2P5.1A. A co-immunoprecipitation assay using mice spleen lysates revealed an interaction between K2P5.1A and K2P5.1B in the cytoplasmic C-terminal domain. In a heterologous HEK293 expression system, K2P5.1B inhibited the trafficking of K2P5.1A to the plasma membrane. The alkaline pHe-induced hyperpolarizing response was significantly suppressed in K2P5.1B-transfected human leukemia K562 cells. Enhancement in cell proliferation by the overexpression of K2P5.1A in K562 was significantly prevented by the transfection of K2P5.1B. The spliceosome inhibitor pladienolide B significantly enhanced the relative expression of K2P5.1B in K562, resulting in decreases in the activity of K2P5.1A. K2P5.1B suppresses the function of the K2P5.1 K(+) channel in a dominant-negative manner, suggesting that the mRNA splicing mechanisms underlying the transcriptional regulation of K2P5.1B may be a new therapeutic strategy for autoimmune and inflammatory disorders and cancers.


Determination of sample sizes for epidemiological surveys using cluster sampling technique.
Cluster sampling often provides a convenient and low cost device, in epidemiological surveys. The sample size needed under cluster sampling is generally larger than that in an individual based scheme due to the intra-class correlation existing in a cluster. This intra-class correlation coefficient is usually not known and some assumptions or estimates are essential. The strengths and weaknesses of cluster sampling over other sampling plans are presented and briefly discussed in this paper with particular reference to leprosy control programmes. One particular model of multistage cluster sampling technique is suggested in the evaluation of a District level programme, which includes determining the effectiveness of Multi-Drug Therapy, monitoring efficiency of paramedical workers and estimating the incidence of leprosy.


Expression of GnRH type II is regulated by the androgen receptor in prostate cancer.
GnRH II has important functional effects in steroid hormone-dependent tumours. Here we investigated the expression and regulation of GnRH II in prostate cancer. GnRH II protein was equally expressed in benign (73%) and malignant (78%) biopsies studied in a prostate tissue microarray (P = 0.779). There was no relationship between expression and clinical parameters in the cancer cohort. GnRH II was, however, significantly reduced in tumour biopsies following hormone ablation. This was further investigated in a prostate xenograft model where androgens increased GnRH II levels, while their withdrawal reduced it. In cell lines, we confirmed high levels of GnRH II in androgen receptor (AR)-positive LNCaP cells but low levels in AR-negative PC3 cells. In LNCaP cells, GnRH II induction by androgens was blocked by the AR inhibitor casodex, but not by cycloheximide treatment. Sequence analysis subsequently revealed a putative androgen response element in the upstream region of the GnRH II gene and direct interaction with the AR was confirmed in chromatin immunoprecipitation experiments. Finally, to test whether the effects of GnRH II were dependent on AR expression, LNCaP and PC3 cells were exposed to exogenous peptide. In both cell lines, GnRH II inhibited cell proliferation and migration, suggesting that its function is independent of AR status. These results provide evidence that GnRH II is widely expressed in prostate cancer and is an AR-regulated gene. Further studies are warranted to characterise the effects of GnRH II on prostate cancer cells and investigate its potential value as a novel therapy.


A perspective on public concerns about exposure to fallout from the production and testing of nuclear weapons.
Exposures of the American public occurred nationwide from the testing of nuclear weapons in the United States, the Pacific, and the former Soviet Union. After decades of diminished public awareness on the subject of health risks resulting from exposure to fallout, the release of the National Cancer Institute's 1997 report on nationwide exposure to 131I from the Nevada Test Site (NTS) has led to renewed interest. Public requests for information are focused on individual and family health problems, the right to credible and full disclosure of information, and the need for medical care and assistance for exposure-related health problems. Public concerns have been raised regarding: (a) the lack of information on the potential health risks from exposure to all biologically significant radionuclides in fallout; (b) the lack of independent oversight that includes public participation; (c) governmental portrayal of exposures averaged over very large segments of the population without identification of much larger values for individuals or population subgroups likely to be at highest risk; and (d) a governmental response to known or suspected human exposures that consumes large periods of time and devotes considerable funding to various research-related activities before serious consideration is given to addressing health care responsibilities to exposed individuals. To some extent, these complaints and concerns are rooted in the legacy of government secrecy surrounding the development and testing of nuclear weapons, public distrust of government sources of information about radiation exposures and health risks, and the imposition of past exposures without informed consent. Members of the public participating in the oversight of dose reconstruction projects and epidemiologic studies are requesting information on the total impact from all relevant sources of exposure at each site that might contribute significantly to an individual's risk, including exposure to local releases and to NTS and global fallout. Information is being requested on individual doses and risks from these cumulative exposures, with estimates of uncertainty, including estimates of the absorbed organ dose (as opposed to the effective dose), the risk of disease incidence as opposed to the risk of a cancer fatality, and the chance that a person's diagnosed disease was caused by past exposure (i.e., the probability of causation). This paper attempts to address some of these concerns. We conclude by noting that many individuals exposed in childhood during the 1950's to 131I in fallout from nuclear weapons production and testing would qualify for compensation and medical care if the present rules for the adjudication of claims for atomic veterans and radiation workers at DOE sites were to be extended to the public.


The effect of repellents Ocimum forskolei and deet on the response of Anopheles stephensi to host odours.
The behavioural response of Anopheles stephensi Liston (Diptera: Culicidae) to incubated host odours (from human and goat) and to human odour in combination with a repellent plant, Ocimum forskolei (Labiatae), or deet (N, N, diethyl-toluamide) (20%) was tested in a dual-port olfactometer. An. stephensi was significantly attracted to both host odours compared with air alone, but showed no preference when given a choice between both host odours simultaneously. In choice tests, the addition of deet to human odour did not significantly divert mosquitoes to human odour alone, but did divert them to goat odour. O. forskolei combined with human odour diverted mosquitoes to goat or human odour alone. Combinations of human odour and O. forskolei, and human odour and deet were both as unattractive as air alone, and attracted mosquitoes equally when offered simultaneously. The results indicate that use of O. forskolei as a repellent would be beneficial in reducing vector biting if used in communities in areas with partially zoophilic mosquito species such as An. stephensi, and where animals are present.


[Effect of interleukin-1 on animals with a fibrinolytic dysfunction].
Activating effect of the interleukin-1 on the fibrinolytic system was shown in hypofibrinolysis models. This polypeptide exerted an opposite effect on the fibrinolysis which had been activated with i.v. administration of dihydroergotoxine and thrombin.


Synthesis and Evaluation of Metal Lipoate Adhesives.
The development of new bioadhesives with integrated properties remains an unmet clinical need to replace staples or sutures. Current bioadhesives do not allow electronic activation, which would allow expansion into laparoscopic and robotic surgeries. To address this deficiency, voltage-activated adhesives have been developed on both carbene- and catechol-based chemical precursors. Herein, a third platform of voltage-activated adhesive is evaluated based on lipoic acid, a non-toxic dithiolane found in aerobic metabolism and capable of ring-opening polymerization. The electro-rheological and adhesive properties of lithium, sodium, and potassium salts of lipoic acid are applied for wet tissue adhesion. At ambient conditions, potassium lipoate displays higher storage modulus than lithium or sodium salt under similar conditions. Voltage stimulation significantly improves gelation kinetics to Na- and K-lipoates, while Li-lipoate is found to not require voltage stimulation for gelation. Lap shear adhesion strength on wetted collagen substrates reveals that the synthetic metal lipoates have comparable adhesion strength to fibrin sealants without viral or ethical risks.


Serum resistin levels and resistin gene polymorphism in patients with acne vulgaris: does it correlate with disease severity?
Acne vulgaris is a disease that inflames the sebaceous gland with multiple etiologies. Many proinflammatory adipokines contribute to this pathogenesis. Resistin is a proinflammatory mediator that activates kappa B, a nuclear factor, and c-Jun N-terminal kinases pathways inducing toll-like receptor-2, interleukin-1, 6, and tumor necrosis factor alpha. Resistin gene affects the promoter and intron regions' polymorphisms' expression levels. We aimed to study the association of resistin gene polymorphisms (RETN -420 C/G) and the development of acne vulgaris and whether it is associated with serum resistin levels and disease severity. Resistin (RETN) gene (rs1862513) genotypes were identified using restriction fragment length polymorphism (RFLP), and serum resistin presence was assessed by enzyme-linked immunosorbent assay in 40 patients with acne vulgaris and 40 age- and sex-matched healthy controls as a cross-reference. Patients were divided into mild, moderate, and severe groups. Global Acne Grading System (GAGS) was used to assess the severity of acne vulgaris. CG and GG genotypes were present in cases (P = 0.006) odds ratio (OR)1 = 4.43; 95% confidence interval (CI) (1.53, 12.7) and OR2 = 5.47; 95% CI (0.99, 30.1); G-allele statistically dominated in the patient group where P = 0.001 and OR = 3.57; 95% CI (1.63, 7.80). A positive significant relationship between RETN genotypes and serum resistin levels and GAGS score was present. RETN genes rs1862513 GG and G allele are correlated to acne vulgaris development and severity in a sample of the Egyptian population. This study comprised a small sample size. The cases may not accurately represent the general population; only one clinic was enrolled in the study.


Fish immune responses against endoparasitic nematodes - experimental models.
Vertebrates mount a series of immune reactions when invaded by helminths but antihelmintic immune strategies allow, in many cases, the first invaders of the non-immune host to survive for prolonged periods, whereas subsequent larval invaders of the same parasite species face increased host resistance and thereby decreased colonization success. This concomitant immunity may represent a trade-off between adverse side effects (associated with killing of large helminths in the host tissue) and the need for future protection against invasion. Encapsulation and isolation of large live endoparasitic larvae may be associated with less pathology compared to coping with excess dead parasite tissue in host organs. Likewise, live adult nematodes may be accepted in tissues at a certain activity level for the same reasons. Various host cell receptors bind helminth molecules after which signal-transducing events lead to mobilization of specific reaction patterns depending on the combination of receptors and ligands involved. Both innate and adaptive responses (humoral and cellular) are prominent actors, but skewing of the Th1 lymphocyte response towards a Th2 type is a characteristic element of antihelminthic responses in mammalian hosts. Similar patterns may be expected also to occur in at least some fish species, such as salmonids, producing relevant cytokines, MHCII and CD4+ cells required for these lymphocyte subpopulations. Atlantic cod, Gadus morhua L., is without these immunological elements that indicate that alternative reaction pathways exist in at least some fish groups. Recent achievements within teleost immunology have made it possible to track these host responses in fish and the present work outlines the main immune reactions in fish against helminths and suggests three experimental fish models for exploration of these immune pathways in fish infected with nematodes.


Indoor secondhand tobacco smoke emission levels in six Lebanese cities.
To date, Lebanon has failed to enact comprehensive clean indoor air laws despite ratification of the Framework Convention on Tobacco Control (FCTC), which calls for the protection of non-smokers from exposure to secondhand tobacco smoke (SHS). Complicating the problem of SHS exposure in Lebanon is the widespread use of the tobacco water-pipe. While most research on SHS has involved cigarette smoking as a source of emissions, other sources, including tobacco water-pipes, may be an important contributor. PM(2.5) concentrations (microg/m(3)) were measured in a sample of 28 public venues located in six major Lebanese cities. Active smoker density (number of smokers/100 m(3)) was calculated for both water-pipe and cigarette smokers. Venues were then categorised as having higher density of water-pipe smokers or higher density of cigarette smokers, and resultant emission levels were compared between the two groups. Cigarette and water-pipe smoking was observed in 14 venues, while cigarette smoking only and water-pipe smoking only were found in 12 venues and one venue, respectively. Among all smoking-permitted venues, the mean PM(2.5) concentration was 342 microg/m(3). Venues with a higher density of water-pipe smokers (n =14) showed a similar median PM(2.5) concentration (349 microg/m(3)) compared with venues with a higher density of cigarette smokers (n =13; 241 microg/m(3); p=0.159). The mean PM(2.5) concentration in the single venue with a voluntary smoke-free policy was 6 microg/m(3). Despite ratification of the FCTC in 2005, both cigarette and water-pipe smoking are commonly practised in enclosed public places throughout Lebanon, leading to unsafe levels of indoor particulate pollution. Smoke-free policies are needed in Lebanon to protect the public's health, and should apply to all forms of tobacco smoking.


Coronary artery disease in women: the myth still exists.
There is a large media effort currently available to increase awareness of coronary artery disease in women. Despite this, there is still a misconception among some people, and unfortunately, some healthcare providers, that heart disease is a man's disease. This article will review some of the information about women and coronary artery disease; a short review of the literature, symptoms, diagnostic tests, and treatment pertinent to women; and the action nurses can take to help educate the public, and other healthcare providers, about this deadly threat.


Facile Controlled Synthesis of Spinel LiMn2O4 Porous Microspheres as Cathode Material for Lithium Ion Batteries.
Although the electrochemical properties of porous LiMn2O4 microspheres are usually improved compared to those of irregular LiMn2O4 particles, the effects of the different synthesis conditions on the preparation of the porous LiMn2O4 microspheres are rarely discussed in detail. In the present work, porous LiMn2O4 microspheres were successfully synthesized by using molten LiOH and porous Mn2O3 spheres as a template. Multiple factors were considered in the preparation process, including reagent concentration, pH, adding mode, heating time, etc. The morphology of the MnCO3 template was crucial for the preparation of porous LiMn2O4 microspheres and it was mainly affected by the concentration of reactants and the pH value of the solution during the precipitation process. During the lithiation of Mn2O3 microspheres, the heating temperature and the ratio between Mn2O3 and lithium salt were the most significant variables in terms of control over the morphology and purity of the LiMn2O4 microspheres. Furthermore, we demonstrated that the porous LiMn2O4 microspheres presented better rate capability and cyclability compared to commercial LiMn2O4 powder as cathode materials for lithium-ion batteries (LIBs). This study not only highlights the shape-controllable synthesis of LiMn2O4 microspheres as promising cathode materials, but also provides some useful guidance for the synthesis of porous LiMn2O4 microspheres and other LIB' electrode materials.


[Recombinant HBcAg promotes secretion of IL-15 in myeloid dendritic cells via p38MAPK signaling pathway].
Objective To study the mechanism by which recombinant human hepatitis B virus core antigen (rhHBcAg) induces interleukin-15 (IL-15) secretion in myeloid dendritic cells (mDCs). Methods Human peripheral blood monocytes were isolated from peripheral blood of healthy volunteers by Dynabeads Untouched Human monocytes kit. We obtained mDCs by culturing the monocytes in the presence of GM-CSF, IL-4 and TNF-α. In one group, mDCs were cultured in RPMI1640 and stimulated by rhHBcAg at the final concentration of 10 μg/mL for 1, 2, 3, 4, 5, 6 days. In another group, mDCs were incubated with 25 μmol/L LY294002 (PI3K/Akt inhibitor), 1 μmol/L SB203580 (p38MAPK inhibitor), 100 nmol/L SP600125 (JNK inhibitor) and 150 nmol/L U0126 (ERK inhibitor) for 1 hour separately, and then stimulated by 10 μg/mL rhHBcAg for another 48 hours. Cells and supernatants were collected, and IL-15 mRNA expression level, IL-15 protein level, phosphorylation rate of MAPK and PI3K/Akt signaling pathway were detected by real-time qPCR, ELISA and Western blotting, respectively. Results IL-15 mRNA and protein levels significantly increased in rhHBcAg stimulation group compared with non-stimulated group. IL-15 protein level in p38 inhibitor pretreatment group was significantly lower than that in rhHBcAg stimulation group, but that in PI3K/Akt-, JNK- and ERK-inhibitor pretreatment groups were not obviously changed. Conclusion rhHBcAg promotes IL-15 expression in mDCs via p38 MAPK signaling pathway.


Cannabis-impaired driving and Canadian youth.
Acute cannabis use results in inattention, delayed information processing, impaired coordination, and slowed reaction time. Driving simulator studies and epidemiologic analyses suggest that cannabis use increases motor vehicle crash risk. How much concern should we have regarding cannabis associated motor vehicle collision risks among younger drivers? This article summarizes why young, inexperienced drivers may be at a particularly high risk of crashing after using cannabis. We describe the epidemiology of cannabis use among younger drivers, why combining cannabis with alcohol causes significant impairment and why cannabis edibles may pose a heightened risk to traffic safety. We provide recommendations for clinicians counselling younger drivers about cannabis use and driving.


Nonrandom, diversifying processes are disproportionately strong in the smallest size classes of a tropical forest.
A variety of ecological processes influence diversity and species composition in natural communities. Most of these processes, whether abiotic or biotic, differentially filter individuals from birth to death, thereby altering species' relative abundances. Nonrandom outcomes could accrue throughout ontogeny, or the processes that generate them could be particularly influential at certain stages. One long-standing paradigm in tropical forest ecology holds that patterns of relative abundance among mature trees are largely set by processes operating at the earliest life cycle stages. Several studies confirm filtering processes at some stages, but the longevity of large trees makes a rigorous comparison across size classes impossible without long-term demographic data. Here, we use one of the world's longest-running, plot-based forest dynamics projects to compare nonrandom outcomes across stage classes. We considered a cohort of 7,977 individuals in 186 species that were alive in 1971 and monitored in 13 mortality censuses over 42 y to 2013. Nonrandom mortality with respect to species identity occurred more often in the smaller rather than the larger size classes. Furthermore, observed nonrandom mortality in the smaller size classes had a diversifying influence; species richness of the survivors was up to 30% greater than expected in the two smallest size classes, but not greater than expected in the larger size classes. These results highlight the importance of early life cycle stages in tropical forest community dynamics. More generally, they add to an accumulating body of evidence for the importance of early-stage nonrandom outcomes to community structure in marine and terrestrial environments.


Integrating Social Presence With Social Learning to Promote Purchase Intention: Based on Social Cognitive Theory.
Consumers mainly acquire information through social learning in online shopping environment, and social presence as a media attribute generated by real-time interactions in live streaming commerce is more conducive for consumers' social learning. Therefore, it is worth investigating the roles of social presence and social learning on consumers' purchase intention (PI) in the strong interactive environment. Based on social cognitive theory (SCT) framework and drawing on social presence theory and social learning theory, this study investigates the relationships among social presence, social learning process, and PI. Social presence is operationalized into social presence of others (SPO) and social presence of interactions (SPI), whereas social learning process contains external interaction process [exploitative learning (ETL) and exploratory learning (ERL)] and internal psychological process [cognitive appraisal (CAP) and affective appraisal AAP)]. The results from a survey of 372 consumers of live streaming commerce indicate that SPO and SPI positively affect ETL and ERL and then contribute significantly to the building of CAP and AAP, which can lead to PI. The findings also provide guidance for brand managers and retailers in building more effective interactive atmosphere and promoting consumers' positive attitude toward brands in live streaming marketing.


Aripiprazole prevents renal ischemia/reperfusion injury in rats, probably through nitric oxide involvement.
Renal ischemia/reperfusion (I/R) injury is strongly related to morbidity and mortality. Oxidative stress, inflammation, and apoptosis play key roles in renal dysfunction following renal I/R. Aripiprazole is an atypical antipsychotic which used for the treatment of schizophrenia and bipolar disorder. Recent studies have reported aripiprazole as displaying certain anti-inflammatory effects. Regarding the underlying mechanisms of renal ischemia-reperfusion, therefore, nephroprotective effects might be predicted to be seen with aripiprazole. I/R injury was induced by bilateral clamping of the renal pedicles (45min) followed by reperfusion (24h). The mechanism of aripiprazole-mediated nephroprotection was explored by a combined use of aripiprazole and L-NAME (non-selective nitric oxide synthase inhibitor). Animals were given aripiprazole (2.5, 5, 10 and 20mg/kg) intraperitoneally, 30min before ischemia. L-NAME was administered before the aripiprazole injection. Serum creatinine and blood urea nitrogen were assessed after 24h of reperfusion. Serum levels of malondialdehyde (MDA), TNF-α and IL-1β were measured for rats treated with aripiprazole. The extent of necrosis was measured by the stereology method. Ischemia/reperfusion caused significant renal dysfunction and marked renal injury. Aripiprazole reduced creatinine and blood urea nitrogen. Serum levels of MDA, IL-1β and TNF-α were significantly lower in the aripiprazole group. Aripiprazole treatment also decreased the volume of kidney necrosis. The administration of L-NAME reversed the renoprotective effect of aripiprazole on BUN and creatinine, but enhanced the anti-necrotic effect of aripiprazole. The results show that a single dose of aripiprazole significantly improved renal function following ischemia/reperfusion injury - probably through the involvement of nitric oxide.


Association between physician characteristics and practice-level uptake of paediatric virtual mental healthcare: a population-based study.
To examine physician factors associated with practice-level uptake of virtual mental healthcare for children and adolescents. A population-based data linkage study of a cohort of all physicians (n=12 054) providing outpatient mental healthcare to children and adolescents (aged 3-17 years, n=303 185) in a single-payer provincial health system in Ontario, Canada from 1 July 2020 to 31 July 2021. Physician characteristics including gender, age, specialty, location of training, practice region, practice size and overall and mental health practice size. Practice-level proportion of outpatient virtual care provided: (1) mostly in-person (<25% virtual care), (2) hybrid (25%-99% virtual care) or (3) exclusively virtual (100% virtual care). Multinomial logistic regression models tested the association between practice-level virtual care provided and physician characteristics. Among physicians, 1589 (13.2%) provided mostly in-person mental healthcare with 8714 (67.8%) providing hybrid care, and 2291 (19.0%) providing exclusively virtual care. The provision of exclusive virtual care (vs mostly in-person) was associated with female sex (adjusted OR (aOR) 1.97, 95% CI 1.70 to 2.27 (ref: male)), foreign training (aOR 1.27, 95% CI 1.07 to 1.50 (ref: Canadian-trained)), family physicians (aOR 2.05, 95% CI 1.56 to 2.69 (ref: psychiatrist)) and reversely associated with large practice size (aOR 0.32, 95% CI 0.25 to 0.40 (ref smallest quintile)). Mostly in-person care was associated with older age physicians (71+ years) and practice outside the Toronto region. In a single-payer universal healthcare system that remunerates physicians using the same fee structure for in-person and virtual outpatient care, there is heterogeneity in utilisation of virtual care that is associated with provider factors. This practice variation, with limited evidence on effectiveness and appropriate contexts for virtual care use, suggests there may be opportunity for further outcomes research and guidance on appropriate context for paediatric virtual mental healthcare delivery.


Application of Neural Network Based on Visual Recognition in Color Perception Analysis of Intelligent Vehicle HMI Interactive Interface under User Experience.
As a bridge of human-computer communication, the color design of intelligent vehicle HMI interactive interface is particularly important. It is also the first guide to the driver during the driving process. The quality of its design will also directly affect the driver's senses and the driving safety of the vehicle. Therefore, this paper introduces the current situation, design principle, and future development of the vehicle interaction interface from multiple perspectives. Through the neural network system (condition generation countermeasure network model) of visual recognition, the color of the intelligent vehicle HMI interactive interface under the user experience is analyzed. According to the analysis of the psychological cognition and behavior operation of the automobile user, the correlation analysis of the human, vehicle, environment, and various elements of the interface is carried out, and how the vehicle interactive interface can meet the expected physiological and psychological needs of the user more and improve the operability is discussed in order to design an on-board HMI interactive interface that can be intelligently perceived according to weather, driver's interests, and other factors and then improve the current backward operation mode of the on-board interactive interface, so that the interaction between people and vehicles is more smooth and pleasant.


MicroRNA-761 inhibits Angiotensin II-induced vascular smooth muscle cell proliferation and migration by targeting mammalian target of rapamycin.
Aberrant vascular smooth muscle cell (VSMC) proliferation and migration are a major pathological phenomenon in vascular disease characterized by intimal thickening. The important role of the mammalian target of rapamycin (mTOR) signaling in VSMC proliferation has been previously reported. Consequently, down-regulation of mTOR pathway may be an effective way of controlling excessive VSMC proliferation. Since microRNAs (miRNA) are newly emerging regulators of virtually all the biological processes including cellular proliferation, miRNAs targeting mTOR pathway may be utilized to suppress aberrant VSMC proliferation during pathologic conditions. Thus, in the present study, we screened miRNAs targeting mTOR, and we identified miR-761 as a new mTOR targeting miRNA. Luciferase assay using luciferase vector containing 3'UTR of mTOR indicated that miR-761 directly targets mTOR mRNA leading to suppression of mTOR protein expression. Our data also indicate that miR-761 expression decreases during angiotensin II (AngII)-induced proliferation of VSMCs, and exogenous miR-761 delivery effectively inhibit the AngII-induced VSMC proliferation. Additionally, the results of migration tests demonstrate that down-regulation of mTOR using exogenous miR-761 suppresses AngII-induced migration of VSMCs as well. Taken together, the present study provided evidence that miR-761 can be a potent anti-proliferative agent for vascular diseases such as atherosclerosis and restenosis, and warrants further studies to validate the effectiveness of miR-761 in vivo.


Development of a protein chip: a MS-based method for quantitation of protein expression and modification levels using an immunoaffinity approach.
Protein chip technology permits analysis of the expression and modification status of numerous targeted proteins within a single experiment, mainly through the use of antibody-based microarrays. Despite recent improvements in these protein chips, their applications are still limited for a variety of reasons, which include technical challenges in fabrication of the antibody chips as well as the very low specificity achieved by current detection methods. We have developed a unique approach for relative and/or absolute quantitation of protein expression and modification based on the capture of epitope peptides on affinity beads, which can be used to develop a mass-spectrometry-based protein chip technology. This new method, which utilizes antibodies immobilized on beads for the capture of target peptides, instead of proteins, eliminates many of the problems previously associated with protein chips. We present here several proof-of-principle experiments examining model peptides by this technique. These experiments show that the method is capable of (i). detecting peptides bound to a single antibody bead, (ii). detecting peptides at low (fmol) levels, (iii). producing MS/MS data of suitable quality for protein identification via database searching or de novo sequencing, (iv). quantitating peptides affinity-bound to antibody beads, (v). specifically detecting target peptides in complex mixtures over wide dynamic ranges, and (vi) is compatible with a microarray format for high-throughput analysis. Because our novel method uses antibody beads instead of a derivatized capture surface, and peptides instead of proteins for affinity capture, it can overcome many of the pitfalls of previous protein chip fabrications. Therefore, this method offers an improved approach to protein chip technology that should prove useful for diagnostics and drug development applications.


Sexually transmitted disease and family planning counselling of psychiatric patients in New Zealand.
We aimed to determine the attitudes and behaviours of mental health professionals (MHPs) including psychiatrists towards identifying and reducing their own patients' risk for sexually transmitted diseases and unwanted pregnancies. 102 of all of the 162 mental health professionals serving predominantly chronically psychiatrically ill adult outpatients and inpatients in Waitemata district responded to an anonymous questionnaire (response rate = 63%), concerning their own attitudes and behaviours towards identifying and counselling patients on their risk for sexually transmitted diseases and unwanted pregnancies. Mental health professionals reported that, on average, they had counselled 14% of their own male patients and 21% of their own female patients on sexually transmitted diseases, including AIDS prevention, and that more of their own patients were at risk than were counselled. They also reported that they had counselled 5% of their own male patients and 17% of their own female patients about family planing. Forty-two per cent of mental health professionals indicated that they had insufficient knowledge about sexually transmitted diseases to educate patients, 72% indicated that when it came to risky sexual behaviours chronic psychiatric patients were much the same as other people, and 33% or more felt uncomfortable discussing topics of condom use and patients' sexual preferences. These results suggest that family planning and sexually transmitted diseases risk preventive interventions for psychiatric patients need to overcome mental health professionals' own barriers to risk prevention.


Loss of Endometrial Plasticity in Recurrent Pregnancy Loss.
Menstruation drives cyclic activation of endometrial progenitor cells, tissue regeneration, and maturation of stromal cells, which differentiate into specialized decidual cells prior to and during pregnancy. Aberrant responsiveness of human endometrial stromal cells (HESCs) to deciduogenic cues is strongly associated with recurrent pregnancy loss (RPL), suggesting a defect in cellular maturation. MeDIP-seq analysis of HESCs did not reveal gross perturbations in CpG methylation in RPL cultures, although quantitative differences were observed in or near genes that are frequently deregulated in vivo. However, RPL was associated with a marked reduction in methylation of defined CA-rich motifs located throughout the genome but enriched near telomeres. Non-CpG methylation is a hallmark of cellular multipotency. Congruently, we demonstrate that RPL is associated with a deficiency in endometrial clonogenic cell populations. Loss of epigenetic stemness features also correlated with intragenic CpG hypomethylation and reduced expression of HMGB2, coding high mobility group protein 2. We show that knockdown of this sequence-independent chromatin protein in HESCs promotes senescence and impairs decidualization, exemplified by blunted time-dependent secretome changes. Our findings indicate that stem cell deficiency and accelerated stromal senescence limit the differentiation capacity of the endometrium and predispose for pregnancy failure.


Intravenous immunoglobulin for the treatment of autoimmune encephalopathy in children with autism.
The identification of brain-targeted autoantibodies in children with autism spectrum disorder (ASD) raises the possibility of autoimmune encephalopathy (AIE). Intravenous immunoglobulin (IVIG) is effective for AIE and for some children with ASD. Here, we present the largest case series of children with ASD treated with IVIG. Through an ASD clinic, we screened 82 children for AIE, 80 of them with ASD. IVIG was recommended for 49 (60%) with 31 (38%) receiving the treatment under our care team. The majority of parents (90%) reported some improvement with 71% reporting improvements in two or more symptoms. In a subset of patients, Aberrant Behavior Checklist (ABC) and/or Social Responsiveness Scale (SRS) were completed before and during IVIG treatment. Statistically significant improvement occurred in the SRS and ABC. The antidopamine D2L receptor antibody, the anti-tubulin antibody and the ratio of the antidopamine D2L to D1 receptor antibodies were related to changes in the ABC. The Cunningham Panel predicted SRS, ABC, parent-based treatment responses with good accuracy. Adverse effects were common (62%) but mostly limited to the infusion period. Only two (6%) patients discontinued IVIG because of adverse effects. Overall, our open-label case series provides support for the possibility that some children with ASD may benefit from IVIG. Given that adverse effects are not uncommon, IVIG treatment needs to be considered cautiously. We identified immune biomarkers in select IVIG responders but larger cohorts are needed to study immune biomarkers in more detail. Our small open-label exploratory trial provides evidence supporting a neuroimmune subgroup in patients with ASD.


Long-term quality of life for surgical and nonsurgical treatment of head and neck cancer.
To compare the long-term, health-related quality-of-life outcomes in patients with advanced head and neck cancer (HNC) treated with surgery and postoperative radiation therapy (SRT) or concurrent chemotherapy and radiation therapy (CRT). Matched-pair study comparing patients with advanced HNC treated with SRT or CRT at least 12 months after treatment. Patients completed 2 validated surveys addressing HNC-specific outcomes and depressive symptoms and provided information on employment and tobacco and alcohol use. Results for the 2 groups were compared using paired-sample t test and chi2 analysis. University-based study. Patients with stage III or IV squamous cell carcinoma of the oropharynx, hypopharynx, and larynx who underwent SRT or received CRT. Head and neck cancer-specific health-related quality of life from the Head and Neck Cancer Inventory and level of depressive symptoms from the Beck Depression Inventory. The matching process resulted in 27 patients in each treatment group. The HNC-specific domain scores (with higher scores representing better outcomes) for CRT vs SRT were eating, 37.8 vs 40.8 (P = .69); speech, 65.1 vs 56.0 (P = .23); aesthetics, 80.3 vs 69.2 (P = .14); and social disruption, 69.7 vs 70.6 (P = .90). Overall health-related quality of life was 64.0 with SRT and 55.0 with CRT (P = .142). For the Beck Depression Inventory (with higher scores representing worse outcomes), patients who underwent SRT had a mean score of 9.6 compared with 11.6 for patients who received CRT (P = .42). As nonsurgical means of treating HNC have become more aggressive and surgical techniques have become more focused on function preservation and rehabilitation, the overall health-related quality of life resulting from these different approaches is similar.


The mechanism of successful colposuspension in genuine stress incontinence.
Colposuspension (Burch procedure) is one of the most effective surgical procedures for the cure of genuine stress incontinence in women. The aim of the current study was to understand the mechanism of successful colposuspension for treatment of this condition. Thirty-five patients with primary genuine stress incontinence underwent colposuspension. Preoperative investigation included detailed history taking, urinalysis, pelvic floor relaxation assessments, one-hour pad test, Q-tip test, urodynamic study and perineal ultrasound urethrocystography. Follow-up results were estimated after one year. Twenty-five (71.4%) patients were completely cured; four (11.4%) patients showed significant improvement and six (17.1%) had recurrence of incontinence. The overall success rate was 82.9%. The complication rate was 20%. Urodynamic data revealed a significant increase in the maximal stress urethral closure pressure and proximal urethral transmission ratios. Perineal ultrasound urethrocystography and Q-tip test revealed a significant anatomic correction in bladder neck descent. This study confirmed that surgical cure of urinary incontinence can be achieved by restoration of the vesical neck from a dependent position in the pelvis to a position high behind the symphysis pubis, with subsequent improved pressure transmission ratios.


Expression of the erbB-2 family of growth factor receptors and their ligands in breast cancers. Implication for tumor biology and clinical behavior.
Transmembrane receptor tyrosine kinases that bind to growth factors transmit signals that are essential to growth and differentiation. These receptors can be classified into groups based on their structure. One group implicated in the pathogenesis of breast cancer contains receptors belonging to the erbB family. This group includes the epidermal growth factor receptors, the HER-2/neu (erbB-2), HER-3, and HER-4. Despite the structural similarity of these receptors, HER-2/neu, HER-4, and HER-3 do not bind to any ligand of the epidermal growth factor receptor. However, a 44-kD glycoprotein called neu differentiation factor (neu differentiation factor/heregulin) has been isolated. This ligand phosphorylates the HER-2/neu receptor and binds directly to HER-4 and HER-3. The abundance of erbB receptors and their ligands in breast cancers points to their functional importance in the pathogenesis and biological behavior of breast cancers. Furthermore, these receptors and ligands may hold a promise for targeted therapy for breast cancer in the future.


Distribution and Feeding Behavior of Omorgus suberosus (Coleoptera: Trogidae) in Lepidochelys olivacea Turtle Nests.
Omorgus suberosus (Fabricius, 1775) has been identified as a potential predator of the eggs of the turtle Lepidochelys olivacea (Eschscholtz, 1829) on one of the main turtle nesting beaches in the world, La Escobilla in Oaxaca, Mexico. This study presents an analysis of the spatio-temporal distribution of the beetle on this beach (in areas of high and low density of L. olivacea nests over two arrival seasons) and an evaluation, under laboratory conditions, of the probability of damage to the turtle eggs by this beetle. O. suberosus adults and larvae exhibited an aggregated pattern at both turtle nest densities; however, aggregation was greater in areas of low nest density, where we found the highest proportion of damaged eggs. Also, there were fluctuations in the temporal distribution of the adult beetles following the arrival of the turtles on the beach. Under laboratory conditions, the beetles quickly damaged both dead eggs and a mixture of live and dead eggs, but were found to consume live eggs more slowly. This suggests that O. suberosus may be recycling organic material; however, its consumption of live eggs may be sufficient in some cases to interrupt the incubation period of the turtle. We intend to apply these results when making decisions regarding the L. olivacea nests on La Escobilla Beach, one of the most important sites for the conservation of this species.


Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction.
We evaluated the efficacy and tolerability of a dual therapy with rabeprazole and amoxicillin (AMX) as an empiric third-line rescue therapy. In patients with failure of first-line treatment with a proton pump inhibitor (PPI)-AMX-clarithromycin regimen and second-line treatment with the PPI-AMX-metronidazole regimen, a third-line eradication regimen with rabeprazole (10 mg q.i.d.) and AMX (500 mg q.i.d.) was prescribed for 2 wk. Eradication was confirmed by the results of the ¹³C-urea breath test (UBT) at 12 wk after the therapy. A total of 46 patients were included; however, two were lost to follow-up. The eradication rates as determined by per-protocol and intention-to-treat analyses were 65.9% and 63.0%, respectively. The pretreatment UBT results in the subjects showing eradication failure; those patients showing successful eradication comprised 32.9 ± 28.8 permil and 14.8 ± 12.8 permil, respectively. The pretreatment UBT results in the subjects with eradication failure were significantly higher than those in the patients with successful eradication (P = 0.019). A low pretreatment UBT result (≤ 28.5 permil) predicted the success of the eradication therapy with a positive predictive value of 81.3% and a sensitivity of 89.7%. Adverse effects were reported in 18.2% of the patients, mainly diarrhea and stomatitis. Dual therapy with rabeprazole and AMX appears to serve as a potential empirical third-line strategy for patients with low values on pretreatment UBT.


SHED-exos promote saliva secretion by suppressing p-ERK1/2-mediated apoptosis in glandular cells.
Confirm that stem cells from human exfoliated deciduous teeth-derived exosomes (SHED-exos) can limit inflammation-triggered epithelial cell apoptosis and explore the molecular mechanism. SHED-exos were injected into the submandibular glands (SMGs) of non-obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. SHED-exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase-3 levels and apoptotic cell numbers in SMGs. SHED-exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS-damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p-ERK1/2 was upregulated in SMGs, and this change was blocked by SHED-exos treatment. In vitro, SHED-exos suppressed p-ERK1/2 activation and increased cleaved caspase-3 and apoptotic cell numbers, which were induced by IFN-γ. SHED-exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED-exos inhibited inflammation-triggered epithelial cell apoptosis by suppressing p-ERK1/2 activation, which is involved in these effects.


The liver in long-term survivors of marrow transplant--chronic graft-versus-host disease.
We have studied five long-term survivors of allogeneic bone marrow transplantation. All exhibited prolonged serum biochemical evidence of hepatic dysfunction during 2- to 5-year periods of follow-up. Two patients developed chronic cholestasis without pruritus. The serum of a third patient became chronically positive for HBsAg. A fourth patient developed an acute hepatic syndrome and high titers of antibody to cytomegalovirus. Nuclear, mitochondrial, and smooth muscle antibodies were not detected. Seven liver biopsies, obtained from three of the patients, all revealed a hepatocellular necroinflammatory lesion suggestive of chronic active hepatitis, a paucity of interlobular bile ducts, and intrahepatic cholestasis. Possible etiologies for these hepatic changes include reactivation of chronic non-A, non-B hepatitis and chronic graft-versus-host disease per se. Our study emphasizes the diagnostic problems posed by hepatic dysfunction occurring in an immunosuppressed multiply-transfused patient after bone marrow transplantation.


APE1/Ref-1 facilitates recovery of gray and white matter and neurological function after mild stroke injury.
A major hallmark of oxidative DNA damage after stroke is the induction of apurinic/apyrimidinic (AP) sites and strand breaks. To mitigate cell loss after oxidative DNA damage, ischemic cells rapidly engage the base excision-repair proteins, such as the AP site-repairing enzyme AP endonuclease-1 (APE1), also named redox effector factor-1 (Ref-1). Although forced overexpression of APE1 is known to protect against oxidative stress-induced neurodegeneration, there is no concrete evidence demonstrating a role for endogenous APE1 in the long-term recovery of gray and white matter following ischemic injury. To address this gap, we generated, to our knowledge, the first APE1 conditional knockout (cKO) mouse line under control of tamoxifen-dependent Cre recombinase. Using a well-established model of transient focal cerebral ischemia (tFCI), we show that induced deletion of APE1 dramatically enlarged infarct volume and impaired the recovery of sensorimotor and cognitive deficits. APE1 cKO markedly increased postischemic neuronal and oligodendrocyte degeneration, demonstrating that endogenous APE1 preserves both gray and white matter after tFCI. Because white matter repair is instrumental in behavioral recovery after stroke, we also examined the impact of APE1 cKO on demyelination and axonal conduction and discovered that APE1 cKO aggravated myelin loss and impaired neuronal communication following tFCI. Furthermore, APE1 cKO increased AP sites and activated the prodeath signaling proteins, PUMA and PARP1, after tFCI in topographically distinct manners. Our findings provide evidence that endogenous APE1 protects against ischemic infarction in both gray and white matter and facilitates the functional recovery of the central nervous system after mild stroke injury.