A pars plana filtering procedure combined with lensectomy and vitrectomy for neovascular for neovascular glaucoma.
In 14 eyes undergoing a pars plana filtration procedure combined with pars plana lensectomy and vitrectomy, the most common complication was a severe sterile fibrinous vitritis. However, after a mean follow-up period of 6.3 months, intraocular pressure was controlled in five eyes (36%) after the procedure alone, in two (14%) after subsequent medical therapy, and in three (21%) after subsequent cyclocryotherapy. Preoperative visual acuity was maintained or improved in nine of the eyes (64%), whereas four eyes (28%) had no light perception.


Investigation on the structure-activity relationship of BaO promoting Pd/CeO2-ZrO2 catalysts for CO, HC and NOx conversions.
Four different synthetic routes (co-precipitation, oxidation-precipitation, citric acid sol-gel and reversed microemulsion) are adopted to prepare barium modified Pd/CeO2-ZrO2 catalysts and their catalytic activity towards CO, HC and NOx conversions is studied. The surface and bulk properties of these catalysts are characterized via XRD, N2 adsorption, XPS, UV-Raman, H2-TPR, and in situ DRIFTS. The catalyst prepared via the co-precipitation method exhibits the optimum three-way catalytic behavior, which is mainly due to its superior redox ability, whereas the oxidation-precipitation synthesis renders the catalyst with the best homogeneity and thermal resistance. However, for the catalyst prepared via the sol-gel route, its worst NOx reduction capacity is verified by the scarce appearance of negatively charged Pd0-N[double bond, length as m-dash]Oδ- species, which is related to the faster dissociation of NO based on in situ DRIFTS, and the abundance of surface CO-Pd+ species reveals its unsatisfactory deep oxidizability of the HC reactant.


Crystal structure of the MexR repressor of the mexRAB-oprM multidrug efflux operon of Pseudomonas aeruginosa.
MexR is a member of the MarR family of bacterial transcriptional regulators and is the repressor for the MexAB-OprM operon, which encodes a tripartite multidrug efflux system in Pseudomonas aeruginosa. Mutations in MexR result in increased resistance to multiple antibiotics due to overexpression of this efflux system. We have determined the crystal structure of MexR to 2.1-A resolution in the absence of effector. The four copies of the MexR dimer in the asymmetric unit are observed in multiple conformations. Analysis of these conformational states in the context of a model of the MexR-DNA complex proposed in this study suggests that an effector-induced conformational change may inhibit DNA binding by reducing the spacing of the DNA binding domains. The inhibited conformation is exhibited by one of the four MexR dimers, which contains an ordered C-terminal tail from a neighboring monomer inserted between its DNA binding domains and which we propose may resemble the MexR-effector complex. Our results indicate that MexR may differ from the other described member of this family, MarR, in the nature of its effector, mode of DNA binding, and mechanism of regulation.


Cellular and extracellular vesicular origins of miRNAs within the bovine ovarian follicle.
The ovarian follicle components must provide an ideal environment to ensure the success of reproductive processes, and communication between follicular cells is crucial to support proper oocyte growth. Recently, it has been demonstrated that the presence of extracellular vesicles (EVs) carrying microRNAs (miRNAs) in follicular fluid represents an important autocrine and paracrine communication mechanism inside the ovarian follicle. In this study, we tested the hypothesis that the miRNA content of EVs isolated from ovarian follicular (granulosa and cumulus-oocyte complexes) cell-conditioned culture media is dependent upon cell type. We initially screened bovine granulosa cells (GCs) and cumulus-oocyte complexes (COCs), as well as their derived EVs for 348 miRNAs using real-time PCR, and detected 326 miRNAs in GCs and COCs cells and 62 miRNAs in GCs and COCs EVs. A bioinformatics analysis of the identified cell-specific and differentially expressed miRNAs predicted that they likely modulate important cellular processes, including signalling pathways such as the PI3K-Akt, MAPK and Wnt pathways. By investigating the origins of miRNAs within the follicular fluid, the results of this study provide novel insights into follicular miRNA content and intercellular communication that may be of invaluable use in the context of reproductive technologies, diagnostic of ovarian-related diseases and/or the identification of biomarkers for oocyte and embryo quality.


Transcriptional synergy mediated by SAF-1 and AP-1: critical role of N-terminal polyalanine and two zinc finger domains of SAF-1.
Previously we determined that inflammation responsive transcription factors AP-1 and SAF-1 synergistically regulate transcriptional induction of the MMP-1 gene. The present study investigated the underlying molecular mechanism of cooperativity between these two different groups of transcription factors. We present evidence that knockdown of SAF-1 by small interfering RNAs inhibits AP-1-mediated increase of human MMP-1 expression. The two key members of the AP-1 family of proteins, c-Fos and c-Jun, and SAF-1 form a ternary protein complex, which has markedly higher DNA binding activity than either a SAF-1 homodimer or a c-Fos/c-Jun heterodimer. The increased DNA binding activity of the ternary complex is translated into a striking enhancement of their transcriptional activity by which synergistic transcriptional induction of MMP-1 expression is achieved. The SAF-1.c-Fos.c-Jun ternary complex efficiently promotes transcription from both SAF-1 and AP-1 sites of human MMP-1 promoter. The physical interaction between SAF-1 and AP-1 was demonstrated both in vitro by Far-Western and antibody pulldown assays with recombinant proteins and in vivo by chromatin immunoprecipitation (ChIP), re-ChIP, and co-immunoprecipitation analyses. Two distinct but adjacent domains in SAF-1 are involved in protein-protein contact with c-Fos and c-Jun; one domain resides within two N-terminal polyalanine tracts, and the other is present within the first two zinc finger motifs. Together these findings delineate the mechanism of synergy and the essential role of SAF-1 and AP-1 in up-regulating human MMP-1 expression under various inflammatory conditions.


Update of urethra-sparing approaches in cystectomy in women.
The emerging experience in urethra-sparing cystectomy in women undergoing subsequent orthotopic lower-urinary-tract reconstruction with regard to the anatomy of the remnant urethra, patient selection, refinements of the surgical technique, the patients' outcome with respect to the underlying disease, the risk for tumor recurrence, and postoperative urodynamics are the main focus of this report. In the present study, 30 carefully selected female patients underwent orthotopic reconstruction of the lower urinary tract. Surgical variations emerging from the first learning curve, including nerve-sparing anterior exenteration, vaginal reconstruction, omental support of the neobladder floor, and ureterointestinal anastomosis, were applied in 21 patients with lower-urinary-tract reconstruction. Of 24 patients followed for more than 6 months, 21 (87.5%) are continent at daytime, 19 (79%) have nocturnal continence, and only 1 (4%) requires self-catheterization; 3 patients with urinary retention were successfully treated for obstructed ileal valves. After a follow-up period of 2-41 (mean 15.4) months one patient each developed local recurrence (uterine adenosarcoma) after 13 months and distant metastasis transitional-cell cancer of the bladder after 3 months; all other patients are currently free of disease. Urethra-sparing surgery has established itself in selected women with bladder cancer. Refinements in the technique of radical cystectomy and orthotopic creation of a neobladder to the urethra may improve the continence, spontaneous micturition, and surgical oncological outcome of these patients.


Antisense Oligonucleotide Targeting Hepatic Serum Amyloid A Limits the Progression of Angiotensin II-Induced Abdominal Aortic Aneurysm Formation.
Obesity increases the risk for abdominal aortic aneurysms (AAA) in humans and enhances angiotensin II (AngII)-induced AAA formation in C57BL/6 mice. Obesity is also associated with increases in serum amyloid A (SAA). We previously reported that deficiency of SAA significantly reduces AngII-induced inflammation and AAA in both hyperlipidemic apoE-deficient and obese C57BL/6 mice. In this study, we investigated whether SAA plays a role in the progression of early AAA in obese C57BL/6 mice. Male C57BL/6J mice were fed a high-fat diet (60% kcal as fat) throughout the study. After 4 months of diet, the mice were infused with angiotensin II (AngII) until the end of the study. Mice with at least a 25% increase in the luminal diameter of the abdominal aorta after 4 weeks of AngII infusion were stratified into 2 groups. The first group received a control antisense oligonucleotide (Ctr ASO), and the second group received ASO that suppresses SAA (SAA-ASO) until the end of the study. Plasma SAA levels were significantly reduced by the SAA ASO treatment. While mice that received the control ASO had continued aortic dilation throughout the AngII infusion periods, the mice that received SAA-ASO had a significant reduction in the progression of aortic dilation, which was associated with significant reductions in matrix metalloprotease activities, decreased macrophage infiltration and decreased elastin breaks in the abdominal aortas. We demonstrate for the first time that suppression of SAA protects obese C57BL/6 mice from the progression of AngII-induced AAA. Suppression of SAA may be a therapeutic approach to limit AAA progression.


Sudden Death Due to Coronary Arteritis.
We report the case of a middle-aged man, without medical history, who suddenly died at his workplace. The autopsy highlighted a pathological heart macroscopically, with multiple small white areas on the left myocardium. Coronary dissection revealed a pseudotumoural fibromyxoid aspect within the anterior interventricular artery (AIVA) and the left main coronary trunk, including reduction in their diameter with tight stenosis. Microscopic examination of these arteries showed fibroinflammatory wall destruction. In the left myocardium, there were multiple focal ischemic areas at different stages of recovery. Our case is an illustration of primary ischemic heart disease due to coronary arteritis, with a pseudotumoural presentation, which was revealed by sudden death. We discuss the cause of death and the etiological diagnosis preceding coronary arteritis.


Lack of resolution in the animal phylogeny: closely spaced cladogeneses or undetected systematic errors?
A recent phylogenomic study reported that the animal phylogeny was unresolved despite the use of 50 genes. This lack of resolution was interpreted as "a positive signature of closely spaced cladogenetic events." Here, we propose that this lack of resolution is rather due to the mutual cancellation of the phylogenetic signal (historical) and the nonphylogenetic signal (due to systematic errors) that results from inadequate taxon sampling and/or model of sequence evolution. Starting with a data set of comparable size, we use 3 different strategies to reduce the nonphylogenetic signal: 1) increasing the number of species; 2) replacing a fast-evolving species by a slowly evolving one; and 3) using a better model of sequence evolution. In all cases, the phylogenetic resolution is markedly improved, in agreement with our hypothesis that the originally reported lack of resolution was artifactual.


Feasibility of thoracoscopic approach for retrosternal goitre (posterior mediastinal goitre): Personal experiences of 11 cases.
Posterior mediastinal goitres constitute of a unique surgical thyroid disorder that requires expert management. Occasionally, they require thoracic approach for the completion of thyroidectomy. In this paper, we describe the feasibility and utility of a novel thoracoscopic approach for such goitres. This is a retrospective study conducted at a tertiary care endocrine surgery department in South India over a period of 5 years from January 2010 to December 2014. We developed a novel thoracoscopic technique for posterior mediastinal goitres instead of a more morbid thoracotomy or sternotomy. All the clinical, investigative, operative, pathological and follow-up data were collected from our prospectively filled database. Statistical analysis was done with SPSS 15.0 version. Descriptive analysis was done. Operative Technique of Thoracoscopic Thyroidectomy: Single lumen endotracheal tube (SLETT) was used of anaesthetic intubation and general inhalational anaesthesia. Operative decubitus was supine with extension and abduction of the ipsilateral arm. Access to mediastinum was obtained by two working ports in the third and fifth intercostal spaces. Mediastinal extension was dissected thoracoscopically and delivered cervically. Out of 1,446 surgical goitres operated during the study period, 72 (5%) had retrosternal goitre. Also, 27/72 (37.5%) cases had posterior mediastinal extension (PME), out of which 11 cases required thoracic approach. We utilised thoracoscopic technique for these 11 cases. The post-operative course was uneventful with no major morbidity. There was one case of recurrent laryngeal nerve (RLN) injury and hoarseness of voice in the third case. Histopathologies in 10 cases were benign, out of which two had subclinical hyperthyroidism. One case had multifocal papillary microcarcinoma. We opine that novel thoracoscopic technique is a feasibly optimal approach for posterior mediastinal goitre, especially for benign and non-invasive malignant goitres.


Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain.
Imaging, electrophysiological studies, and lesion work have shown that the medial temporal lobe (MTL) is important for episodic memory; however, it is unclear whether different MTL regions support the spatial, temporal, and item elements of episodic memory. In this study we used fMRI to examine retrieval performance emphasizing different aspects of episodic memory in the context of a spatial navigation paradigm. Subjects played a taxi-driver game ("yellowcab"), in which they freely searched for passengers and delivered them to specific landmark stores. Subjects then underwent fMRI scanning as they retrieved landmarks, spatial, and temporal associations from their navigational experience in three separate runs. Consistent with previous findings on item memory, perirhinal cortex activated most strongly during landmark retrieval compared with spatial or temporal source information retrieval. Both hippocampus and parahippocampal cortex activated significantly during retrieval of landmarks, spatial associations, and temporal order. We found, however, a significant dissociation between hippocampal and parahippocampal cortex activations, with spatial retrieval leading to greater parahippocampal activation compared with hippocampus and temporal order retrieval leading to greater hippocampal activation compared with parahippocampal cortex. Our results, coupled with previous findings, demonstrate that the hippocampus and parahippocampal cortex are preferentially recruited during temporal order and spatial association retrieval--key components of episodic "source" memory.


Influence of arecoline on immune system: III. Suppression of B cell-mediated immune response in mice after short-term exposure.
Arecoline, a major alkaloid of arecanut was examined to explore its modulatory influence on B cell-mediated immune response in a murine model system. The in vivo and in vitro effects were evaluated at sub-toxic concentrations of arecoline. The number of primary antibody forming cells (AFC) and hemagglutinating and hemolysis antibody titers to Sheep Red Blood Cells (SRBC) were evaluated in male mice. Arecoline exposure for a week invoked dose-dependent effect on primary antibody forming cells to SRBC with a maximum reduction at the dosage of 20 mg/kg bw, a moderate reduction at 10 mg/kg bw and no effect at 5 mg/kg bw dose level. HA and HL antibody titers to SRBC were suppressed markedly at arecoline dosage of 20 mg/kg bw and moderately at a dose of 10 mg/kg bw, given daily for 1, 2 or 3 weeks. The inhibitory effect of arecoline was not dependent on the duration of treatment. Like the primary antibody response, the secondary HA and HL antibody titers were also decreased after arecoline exposure. The administration of arecoline dosages 10 and 20 mg/kg bw daily for 4 days following SRBC immunization also, exerted dose-dependent suppression of primary antibody response. Similarly, when treated after 12 h following immunization, significant reduction in response was observed with arecoline dosage of 20 mg/kg bw. While moderate suppression of antibody response was noticed at the dose level of 10 mg/kg bw, there was no alteration in response at a dosage of 5 mg/kg bw.(ABSTRACT TRUNCATED AT 250 WORDS)


Eutrophication, Ammonia Intoxication, and Infectious Diseases: Interdisciplinary Factors of Mass Mortalities in Cultured Nile Tilapia.
The present study was designed to assess the possible causes of the mass mortalities of Nile Tilapia Oreochromis niloticus at El-Behera Governorate, Egypt, in relationship to environmental and microbiotic factors. Water samples were collected from fish farms at different locations and from Lake Edku to analyze water temperature, water pH, salinity, biological oxygen demand, dissolved oxygen, total ammonia nitrogen, and un-ionized ammonia. A number of moribund and freshly dead fish were sampled and submitted to our laboratory for microbiological, molecular, and histopathological examination. Water analysis of the fish farms revealed noticeable increases in the previously mentioned physicochemical parameters. Clinical examinations of moribund fish showed severe gill rot and massive external and internal hemorrhages. Ordinary and molecular laboratory findings confirmed the presence of Branchiomyces sp. in gill tissue and mixed bacterial fish pathogens (Streptococcus agalactiae, Vibrio alginolyticus, V. parahaemolyticus, Pseudomonas anguilliseptica, and P. aeruginosa) in visceral organs. The histopathological and transmission electron microscopic examinations revealed severe necrosis of gill filaments and blockage of branchial blood vessels and lamellar capillaries with Branchiomyces sp. hyphae and spores mixed with different shapes of bacteria. Severe inflammations were detected in liver, kidney, heart, and brain tissues. Ultimately, we can conclude that the syndrome of mass fish kills in this area is a consequence of ecological damage to the aquatic environment, which is mainly related to natural and anthropogenic factors, as well as to the presence of infectious agents. Received September 30, 2015; accepted April 12, 2016.


Observation of microsecond time-scale protein dynamics in the presence of Ln3+ ions: application to the N-terminal domain of cardiac troponin C.
The microsecond time-scale motions in the N-terminal domain of cardiac troponin C (NcTnC) loaded with lanthanide ions have been investigated by means of a (1)H(N) off-resonance spin-lock experiment. The observed relaxation dispersion effects strongly increase along the series of NcTnC samples containing La(3+), Ce(3+), and Pr(3+) ions. This rise in dispersion effects is due to modulation of long-range pseudocontact shifts by micros time-scale dynamics. Specifically, the motion in the coordination sphere of the lanthanide ion (i.e. in the NcTnC EF-hand motif) causes modulation of the paramagnetic susceptibility tensor which, in turn, causes modulation of pseudocontact shifts. It is also probable that opening/closing dynamics, previously identified in Ca(2+)-NcTnC, contributes to some of the observed dispersions. On the other hand, it is unlikely that monomer-dimer exchange in the solution of NcTnC is directly responsible for the dispersion effects. Finally, on-off exchange of the lanthanide ion does not seem to play any significant role. The amplification of dispersion effects by Ln(3+) ions is a potentially useful tool for studies of micros-ms motions in proteins. This approach makes it possible to observe the dispersions even when the local environment of the reporting spin does not change. This happens, for example, when the motion involves a 'rigid' structural unit such as individual alpha-helix. Even more significantly, the dispersions based on pseudocontact shifts offer better chances for structural characterization of the dynamic species. This method can be generalized for a large class of applications via the use of specially designed lanthanide-binding tags.


[Lithium prophylaxis].
The author considers some difficulties and discrepancies in the diagnosis of schizophrenia, schizo-affective psychoses on the one hand and manic-depressive psychosis on the other in a group of out-patients receiving treatment with lithium for the prophylaxis of affective disorders. Factors common to both groups and being the basis for the selection of lithium prophylaxis are considered. Special attention in these cases is paid to the course of the disease.


Simple model for the mechanics of spider webs.
We propose a simple model to describe spider orb webs. The model has a formal analytical solution when no thread elements are broken. When the radial threads are sufficiently strong compared to the spiral threads, the model is free of stress concentrations even when a few spiral threads are broken. This is in contrast with what occurs in common elastic materials. According to our model, spiders can increase the number of spiral threads to make a dense web (to catch small insects) or adjust the number of radial threads (to adapt to environmental conditions or reduce the cost of making the web) without reducing the damage tolerance of the web.


Roccellatol, a new β-orcinol based metabolite from the lichen Roccella montagnei.
Roccellatol, a new (2'R,3'S)-erythrityl-2,6-dihydroxy-4-methylbenzoate was isolated along with nine known compounds from the fruticose lichen, Roccella montagnei Bel. em. D.D. Awasthi. The structure of the new compound was elucidated by detailed spectroscopic analysis (1H, 13C, DEPT and HRMS). The present isolation of roccellatol (10) assumes significance as the esters of p-orcellinic acid are rare in lichens. Interestingly, among the known compounds, (+)-montagnetol (9) was now isolated in very large quantity (4.66%).


Easy and inexpensive molecular detection of dengue, chikungunya and zika viruses in febrile patients.
Dengue (DENV), chikungunya (CHIKV) and zika (ZIKV) are arthropod-borne viruses (arboviruses) sharing a common vector, the mosquito Aedes aegypti. At initial stages, patients infected with these viruses have similar clinical manifestations, however, the outcomes and clinical management of these diseases are different, for this reason early and accurate identification of the causative virus is necessary. This paper reports the development of a rapid and specific nested-PCR for detection of DENV, CHIKV and ZIKV infection in the same sample. A set of six outer primers targeting the C-preM, E1, and E gene respectively was used in a multiplex one-step RT-PCR assay, followed by the second round of amplification with specific inner primers for each virus. The specificity of the present assay was validated with positive and negative serum samples for viruses and supernatants of infected cells. The assay was tested using clinical samples from febrile patients. In these samples, we detected mono and dual infections and a case of triple co-infection DENV-CHIKV-ZIKV. This assay might be a useful and an inexpensive tool for detection of these infections in regions where these arboviruses co-circulate.


The yurt: a mobile home of nomadic populations dwelling in the Mongolian steppe is still used both as a sun clock and a calendar.
The yurt is the traditional home of the nomadic Turkmen, the Kyrgyz, the Kazakhs, the Uzbeks, the Kalmyks, the Buryats and the Mongolians. As the impact of the western modern world, in terms of technological and behavioural changes, is slower than anywhere else, the use of the yurt is widespread in the Mongolian steppes, where nomadic life has been maintaining its traditional behaviour for at least 800 years. The Mongolian yurt entrance faces south and combines spatial and functional properties. An open circular hole named the "toon" can be found at the centre of the roof. On sunny days, a ray of sunshine revolves around its inner wall. Depending on the season, the light first appears between 5:40 am and 7:40 am and moves around the different inner walls (khana). The sundial enables the nomads to schedule their daily activities such as the herd milking and its processing, the drying of dung for fuel, the prayers and performing fighting games. The angle of the sun's light coming through the toon and lighting a space on the floor by the yurt entrance can vary according to the time of the year. Such clues are used to guess what time it is and which month it is, and thus help the Mongolians decide whether or not to start travelling from summer to winter pastures. The Mongolians pay special attention to the transhumances, seasonal movements based on a specific time, in order to prevent harming the livestock during the harsh Mongolian winter, and to choose the right time to move the yurt. They also pay attention not to offend the spirits of the wind, the earth and the sky. Regarded as the warrant of their ancestors' cultural traditions, nomadic people remain faithful to their heritage and respect their surrounding environment. Thus, the yurt has remained their reference to time in the heart of the Mongolian steppes.


[Recent advances in gene therapy of uveitis].
Uveitis is a group of common eye disease and is one of the major causes of blindness worldwide. Corticosteroids and immunosuppressive agents are commonly used for the treatment of uveitis. However, long-term application of these drugs frequently lead to numerous side effects. Recently, with the development of gene transfer techniques, viral vector mediated gene therapy has achieved remarkable success in experimental uveitis. Inhibition of ocular inflammation in animal models is obtained mainly by two ways: first, increase of the expression of different immune modulators including IL-10, IL-1Ra, IL-4 and IFN-alpha, or IL-27p28; secondly, induction of immune tolerance by transferring uveitis related antigens via viral vectors. Uveitis is characterized by long-lasting and recurrent, the unique properties of local administration, long-term effectiveness and minor side effects of gene therapy may provide a novel strategy for the treatment of the devastating uveitis.


Alzheimer's Disease and Sleep-Wake Disturbances: Amyloid, Astrocytes, and Animal Models.
Sleep-wake abnormalities are common in patients with Alzheimer's disease, and can be a major reason for institutionalization. However, an emerging concept is that these sleep-wake disturbances are part of the causal pathway accelerating the neurodegenerative process. Recently, new findings have provided intriguing evidence for a positive feedback loop between sleep-wake dysfunction and β-amyloid (Aβ) aggregation. Studies in both humans and animal models have shown that extended periods of wakefulness increase Aβ levels and aggregation, and accumulation of Aβ causes fragmentation of sleep. This perspective is aimed at presenting evidence supporting causal links between sleep-wake dysfunction and aggregation of Aβ peptide in Alzheimer's disease, and explores the role of astrocytes, a specialized type of glial cell, in this context underlying Alzheimer's disease pathology. The utility of current animal models and the unexplored potential of alternative animal models for testing mechanisms involved in the reciprocal relationship between sleep disruption and Aβ are also discussed.Dual Perspectives Companion Paper: Microglia-Mediated Synapse Loss in Alzheimer's Disease by Lawrence Rajendran and Rosa Paolicelli.


Flexible gating of contextual influences in natural vision.
Identical sensory inputs can be perceived as markedly different when embedded in distinct contexts. Neural responses to simple stimuli are also modulated by context, but the contribution of this modulation to the processing of natural sensory input is unclear. We measured surround suppression, a quintessential contextual influence, in macaque primary visual cortex with natural images. We found that suppression strength varied substantially for different images. This variability was not well explained by existing descriptions of surround suppression, but it was predicted by Bayesian inference about statistical dependencies in images. In this framework, surround suppression was flexible: it was recruited when the image was inferred to contain redundancies and substantially reduced in strength otherwise. Thus, our results reveal a gating of a basic, widespread cortical computation by inference about the statistics of natural input.


Addressing the needs of the high-risk prostate cancer patient.
For prostate cancer patients with a substantial risk of posttherapy progression, managing the disease with a risk-stratified approach and multimodal therapy is an evolving concept. Through an analysis of prostate-specific antigen (PSA) level, biopsy Gleason score, and clinical stage, investigators have been able to define low-, intermediate-, and high-risk disease in terms of the risk of progression after definitive local therapy. High-risk features include a PSA level greater than 20 ng/mL, a Gleason score of 8 to 10 or a clinical stage of T2c or higher. Because high-risk men treated by surgery or radiation therapy are at increased risk of progression and death from prostate cancer over the ensuing decade, various strategies have been used to improve their rates of disease-free progression and overall survival. Radiation therapy combined with hormonal therapy, radical prostatectomy combined with hormonal therapy or adjuvant radiation, and other approaches, such as chemo-hormonal therapy, are either under study or have been supported in randomized clinical trials. This review summarizes the current standard approaches to treating the man with high-risk disease.


A case of tularemia presenting as a dental abscess: case report.
The purpose of this report is to present a tularemia case accompanied by a neck mass that easily may be confounded with dental abscess. Francisella tularensis is a potential agent of biologic terrorism. Thirty percent of the symptoms seen in tularemia localize in the head and neck region and are sometimes mistaken for complications of a dental abscess. To our knowledge, reports of the differential diagnostic characteristics of tularemia are lacking in the dental literature and, to date, no dental journal articles have focused on the disease. In this present case, a 51-year-old woman arrived at the public health department with high fever and facial swelling. The findings suggested a dental origin and the patient was directed to dentistry. Radiology and a detailed intraoral and extraoral examination failed to reveal a dental problem. Fortunately, the patient was known to come from a tularemia region; with the suspicion of tularemia the patient was referred to the faculty of medicine. Serologic tests showed that the patient had a Francisella tularensis infection.


Quadrature subunits in directionally selective simple cells: counterphase and drifting grating responses.
Here we examine further the basis for directional selectivity (DS) in simple cells of the cat's striate cortex. We use a distinctly different input stimulus and different analysis of the output signal for the same type of space-time inseparable receptive field (RF) that was measured with flashing bars in the companion paper (Emerson, 1997). As in the companion paper, we have mimicked a popular "linear" model with a single "branch" that consists of a linear spatiotemporal filter followed by a soft threshold, which should mimic any simple cells that have a single subunit. Counterphase sinusoidal measurements of such a configuration always generate elliptically shaped polar plots of amplitude versus temporal phase, often pinched along the minor axis because of a high threshold. However, for many spatiotemporal frequencies, such polar phase plots, as measured in simple cells by others, show a consistent rotational phase skew. Here we apply counterphase analysis to the same 2-branch model as developed in the companion paper. We show that the model accounts for the skew as the summation of signals from linear filters separated spatially and temporally by approximately 90 deg (i.e. in spatiotemporal phase quadrature), each separated from the output stage by a soft-threshold nonlinearity. We also prove conclusively that such skew cannot be generated by a single-subunit configuration. This demonstration supports the proposed two-subunit structure for DS simple cells, such as in the example from the companion paper, which has strong linear contributions from its inseparable RF. The presence of at least two nonlinear subunits appears to be an obligatory concomitant of DS in all visual cortical cells. The primary function of these subunits may be to enhance the strength of responses to images moving in the preferred direction, as in complex cells. However, subunits may also aid in identifying the moving object through overcoming, at least partially, the phase-concealing properties of the neuron's threshold by generating a steady signal that effectively decreases the threshold for the preferred direction.


Risk Stratification Tool for Ischemic Stroke: A Risk Assessment Model Based on Traditional Risk Factors Combined With White Matter Lesions and Retinal Vascular Caliber.
Objective: This study aims to establish a risk assessment model based on traditional risk factors combined with the Fazekas classification of white matter lesions and retinal vascular caliber for screening the patients at high risk of ischemic stroke. Methods: This study included 296 patients (128 cases of ischemic stroke and 168 cases in the normal control group). The basic data of the patients were collected. Color fundus photography was performed after pupil dilation, and the retinal vascular caliber was measured using semiautomated vascular measurement software (IVAN Software, Sydney, Australia). The severity of white matter lesions (WML) on cranial nuclear magnetic fluid-attenuated inversion recovery images were assessed using the Fazekas scale. Moreover, logistic regression analysis was used to establish different risk assessment models for ischemic stroke. The effects of models were evaluated through the receiver operating characteristic (ROC) curve and the Delong test compared area under the curve. Results: The sensitivity and specificity of models 1 (the traditional risk factor model), 2 (the retinal vascular caliber model), 3 (the WML model), and 4 (the combined the traditional risk factor, WML and central retinal artery equivalent (CRAE) model) were 71 and 55%, 48 and 71%, 49 and 67%, and 68 and 68.5% with areas under the curve of 0.658, 0.586, 0.601, and 0.708, respectively. The area under the receiver operating characteristic curve in models 1, 2, 3, and 4 showed statistically significant differences. Moreover, no statistical significance exists in the pairwise comparison of other models. Conclusion: The risk assessment model of ischemic stroke combined with Fazekas grade of WML and CRAE is superior to the traditional risk factor and the single-index model. This model is helpful for risk stratification of high-risk stroke patients.


Functional reconstitution of ATP-dependent transporters from the solubilized hepatocyte canalicular membrane.
The hepatocyte canalicular membrane contains several primary-active ATP-dependent export carriers including one for bile salts and one for leukotriene C4 and related conjugates. The molecular identity of both transporters has not been fully elucidated. To establish a transport assay that allows the purification and identification of the proteins involved in ATP-dependent bile salt transport and in leukotriene C4 transport, we reconstituted solubilized hepatocyte canalicular membranes into phospholipid bilayers using a rapid dilution method. The proteoliposomes formed exhibited both [3H]taurocholate and [3H]leukotriene C4 uptake, which was much higher in the presence of ATP than in the presence of the non-hydrolyzable ATP-analog AdoPP[CH2]P or in the absence of nucleotides. Nucleotide requirement and osmotic sensitivity of [3H]taurocholate transport indicates true transport into the vesicle lumen. Optimized conditions for reconstitution included the addition of a high concentration of an osmolyte (glycerol) and the presence of exogenous phospholipids (0.3%) during solubilization. Highest transport rates were obtained by reconstitution into acetone/ether-precipitated Escherichia coli phospholipid supplemented with 20% cholesterol and by use of octylglucoside concentrations between 30 mM and 50 mM. Taurocholate transport was non-competitively inhibited by vanadate (Ki = 39 microM). The kinetic parameters of cyclosporin A inhibition (Ki = 2.6 microM for taurocholate and 4.3 microM for leukotriene C4 transport) as well as the affinities of taurocholate (Km = 12 microM) and leukotriene C4 (Km = 0.5 microM) in the proteoliposome system indicate that the reconstitution resulted in functionally active transport systems, which are representative of ATP-dependent transport in the intact plasma membrane.


Assessment of mental health literacy using a multifaceted measure among a Chinese rural population.
The present study aims to assess mental health literacy (MHL) using a standardised multifaceted 20-item instrument called Mental Health Knowledge Questionnaire (MHKQ) developed by the Chinese Ministry of Health, among a rural Chinese population. Four villages in Liuyang county of Hunan province, China. This was a cross-sectional study. A multistage cluster-sampling method was adopted, leading to a final sampling frame of 2377 residents aged 18-60 years from four villages of Liuyang county. Included in the study were residents aged 18-60 years living in their village for at least half a year; excluded were those not living in the areas during the research period, those with difficulty in communication due to serious physical or mental illness and those who were cognitively impaired or actively psychotic. Finally, 2052 participants completed the survey. Primary outcome was correct response rate of the MHKQ; secondary outcome measures were association between sociodemographics and MHL, and association between MHL and health outcomes. Correct response rates for the 20 MHKQ items ranged from 19% to 94%, with a mean rate of 58%. Younger age (r=-0.02, p<0.01), higher education (r: 1.38-2.69, p<0.01) and higher income (r=0.41, p<0.01), were independently associated with higher MHL. MHL was independently associated with self-rated general health (r=2.31, p<0.01), depression (r=-0.09, p<0.01) and anxiety (r=-0.07, p<0.05). MHL in the rural areas of Liuyang is lower than that reported in urban areas of China. There is much room for improvement with regard to MHL promotion in rural areas of China. Younger age, higher education and higher income are the three robust factors related to higher MHL, so cohort-specific educational intervention efforts may be indicated.


Health care access and use among male and female Canadian Armed Forces veterans.
Veterans are more likely than other Canadians to have chronic health conditions, making access to health care an important issue. However, little research has addressed health care access and use among veterans. This paper examines access and use among veterans compared with other Canadians. Health care access and use indicators were examined for Regular Force veterans using the 2016 Life After Service Survey. Information for male and female veterans was compared with information on the Canadian general population from the 2015 and 2016 Canadian Community Health Survey, using age-adjusted rates and 95% confidence intervals. More than 80% of male and female veterans reported having a regular medical doctor in the 12 months before the survey. The majority of veterans (71% of males and 81% of females) had consulted a family doctor, while a minority had been hospitalized (8% of males and females). These rates were similar to those in the Canadian general population. However, veteran consultation rates for mental health care and with audiologists, speech therapists or occupational therapists among both sexes were double to triple those of the Canadian general population. Among veterans, males reported lower rates of unmet needs compared with females. Veterans had similar rates of access to a regular medical doctor and higher rates of use compared with other Canadians. However, these may be comparatively low, given previous findings on higher rates of disability and some chronic conditions among veterans. Noted differences between males and females highlight the importance of research and services that account for sex and gender. The extent to which health care needs explain health care use and barriers to care requires further research.


Dysregulation of pulmonary endothelial protein C receptor and thrombomodulin in severe falciparum malaria-associated ARDS relevant to hemozoin.
To investigate the role of the protein C system, endothelial protein C receptor (EPCR) and thrombomodulin (TM) in the pathogenesis of malaria-associated acute respiratory distress syndrome (ARDS) in relation to hemozoin and proinflammatory cytokines-induced type II pneumocyte injury and -aggravated pulmonary resolution. A total of 29 left-over lung specimens that were obtained from patients who died from severe falciparum malaria were examined. Histopathological, immunohistochemical and electron microscopic analyses revealed that ARDS coexisted with pulmonary edema and systemic bleeding; the severity was dependent on the level of hemozoin deposition in the lung and internal alveolar hemorrhaging. The loss of EPCR and TM was primarily identified in ARDS patients and was related to the level of hemozoin, parasitized red blood cell (PRBC) and white blood cell accumulation in the lung. Moreover, an in vitro analysis demonstrated that interleukin-13 and -31 and hemozoin induced pneumocytic cell injury and apoptosis, as assessed by EB/AO staining, electron microscopy and the up-regulation of CARD-9 mRNA (caspase recruitment domain-9 messenger-ribonucleic acid). The dysregulation of EPCR and TM in the lung, especially in those with increased levels of hemozoin, may play an important role in the pathogenesis of malaria-associated ARDS through an apoptotic pathway.


Prevention and management of pressure ulcers.
Pressure ulcers represent a major health problem causing a considerable amount of suffering for patients and a high financial burden for healthcare systems. The geriatric population with an increased risk of pressure ulcer development is rising constantly as a result of chronic degenerative diseases that can lead to prolonged immobilization and poor nutrition. Evidence clearly indicates that preventive measures are essential to reduce the prevalence rates of pressure ulcers; therefore healthcare professionals must be able to identify the appropriate strategies to adopt, in order to meet the individual patient's requirements. Important advances have taken place in the world of pressure ulcer treatment during the past decade. These advances are reflected in the high rate of cures being obtained. This, together with the implementation of prevention guidelines, the excellent cost/effectiveness relationship of the techniques described, and other factors, means that the field of pressure ulcers management is no more an isolated and self-administered issue in medical practice. The areas discussed here are those in which there will be linear or, in some cases, exponential growth in the decades to come.


Association of pre-percutaneous coronary flow grade and clinical outcomes in patients with non-ST-segment elevation myocardial infarction: Data from the Korea Acute Myocardial Infarction Registry.
Because of a paucity of published data, we compared the 2-year major clinical outcomes between pre-percutaneous coronary intervention (pre-PCI) thrombolysis in myocardial infarction (TIMI) flow grade 0/1 (pre-TIMI flow grade [pre-TIMI] 0/1) group and pre-PCI TIMI flow grade 2/3 (pre-TIMI 2/3) group in patients with non-ST-segment elevation myocardial infarction (NSTEMI) who underwent successful implantation of newer-generation drug-eluting stent.A total of 7506 NSTEMI patients were divided into 2 groups: pre-TIMI 0/1 group (n = 3157) and pre-TIMI 2/3 group (n = 4349). The primary outcome was major adverse cardiac events defined as all-cause death, recurrent myocardial infarction, or any repeat revascularization. The secondary outcome was stent thrombosis (ST).After propensity score-matched (PSM) analysis, 2 PSM groups (2473 pairs, n = 4946, C-statistic = 0.684) were generated. Major adverse cardiac events (hazard ration [HR], 1.294; 95% confidence interval [CI]: 1.065-1.572; P = .009), all-cause death (HR, 1.559, P = .003), cardiac death (HR: 1.641, P = .005), and all-cause death or MI (HR: 1.531, P = .001) rates were significantly higher in the pre-TIMI 0/1 group than in the pre-TIMI 2/3 group. Moreover, these differences were more prominent during the first 1 month after the index PCI. However, the cumulative incidences of recurrent myocardial infarction, any revascularization, and ST were similar between the 2 groups.Among a contemporary cohort of NSTEMI, these data suggest that the presence of a pre-PCI patency of the infarct-related artery showed better mortality reduction capacity than those with a lack of patency.


Treatment of craniofacial asymmetry with dynamic orthotic cranioplasty.
Dynamic Orthotic Cranioplasty (DOC) was developed to treat craniofacial deformities associated with positional plagiocephaly. This investigation describes the treatment of more than 750 patients with the DOC Band since 1988. All patients undergoing DOC treatment were fit with a custom fabricated orthosis made from a plaster impression taken from the infant's head. When the orthosis was applied, the corrective pressure was directed to hold growth at the calvarial prominences and redirect symmetrical growth. A detailed medical history was obtained and anthropometric measurements were taken at start, exit, 12, 18, and 24 months follow-up. This information was recorded in a database created in Microsoft Excel. Mean length of treatment was 4.3 months with an average entrance age of 6.9 months. Analysis of anthropometric data showed significant reduction in mean cranial vault, skull base, and facial asymmetries. Correction of the more difficult skull base was documented with computed tomography. Our anthropometric and clinical observations document complete or near complete correction of asymmetry for a wide variety of head shapes. Based on the results of this investigation, we are able to support the earlier claims of our pilot study, which concluded that DOC is effective in the treatment of positional plagiocephaly.


The impact of inflationary cytomegalovirus-specific memory T cells on anti-tumour immune responses in patients with cancer.
Human cytomegalovirus (CMV) is a ubiquitous, persistent beta herpesvirus. CMV infection contributes to the accumulation of functional antigen-specific CD8+ T-cell pools with an effector-memory phenotype and enrichment of these immune cells in peripheral organs. We review here this 'memory T-cell inflation' phenomenon and associated factors including age and sex. 'Collateral damage' due to CMV-directed immune reactivity may occur in later stages of life - arising from CMV-specific immune responses that were beneficial in earlier life. CMV may be considered an age-dependent immunomodulator and a double-edged sword in editing anti-tumour immune responses. Emerging evidence suggests that CMV is highly prevalent in patients with a variety of cancers, particularly glioblastoma. A better understanding of CMV-associated immune responses and its implications for immune senescence, especially in patients with cancer, may aid in the design of more clinically relevant and tailored, personalized treatment regimens. 'Memory T-cell inflation' could be applied in vaccine development strategies to enrich for immune reactivity where long-term immunological memory is needed, e.g. in long-term immune memory formation directed against transformed cells.


Knowledge, perception, and confidence of healthcare workers about COVID-19 preventive measures during the first wave of the pandemic: a cross-sectional study from Egypt.
The ongoing coronavirus-disease-19 (COVID-19) pandemic had a variable history with differences in its various stages. This study evaluates the status of knowledge, perception, and confidence about COVID-19 preventive measures during the first wave of the COVID-19 pandemic among healthcare workers (HCWs) in Egypt. A cross-sectional study was conducted during the first wave of the COVID-19 pandemic, in July 2020, in Egypt. An-online-based questionnaire was used to collect data. It included items to record demographic data, and an assessment of knowledge, the perception of healthcare facilities preparedness, and HCW confidence about applying infection prevention measures. A total of 465 responses were analyzed. HCWs' mean age was 36.76 ± 9.57 years, 94.2% (n=438) had an adequate level of knowledge, 31% (n=144) had an adequate perception level, and 39.4% (n=183) had an adequate confidence level. The main source of information was international organizations' websites 46.5% (n=216). The main barriers to applying preventive measures were the overcrowding of patient care areas 73.1% (n=339), and limited infection control supplies 68% (n=316). Factors associated with COVID-19 among HCWs were COVID-19 infected family members (OR: 5.86), inability to protect themselves and their families (OR: 5.73), uncertainty about the available hand hygiene supplies (OR: 3.76), male gender (OR: 3.07), and single HCWs (OR: 2.88). Although the majority reported an adequate knowledge level, lower rates of adequate perception and confidence were observed. Revision of preparedness plans in different facilities should be further studied. Psychological support and gender differences should be considered in response programs.


Toward the design of ribonuclease (RNase) inhibitors: ion effects on the thermodynamics of binding of 2'-CMP to RNase A.
Ribonucleases (RNases) possess a variety of biological activities and, under certain conditions, are deleterious. Hence, design of selective inhibitors has been suggested as a strategy for treating RNase-related disorders. In the present study, isothermal titration calorimetry was used to measure ion effects on binding thermodynamics of the RNase A competitive inhibitor 2'-CMP as a representative system. The reaction cell (37 degrees C) contained dialyzed RNase A (0.04-0.05 mM) in buffered solution (pH 5.5) of 50 mM Na(+), K(+), Ca(2+), or Mg(2+) acetate, verified spectrophotometrically. Thirty-five sequential injections (4 microl each, 3 min apart) were made of 2'-CMP (1.2 mM) in ion-matching buffer. The data were corrected for heat of dilution. There was a 1:1 interaction in each case. The estimated parameters (+/-S.D.) were: K(d) = 4.84 +/- 0.29 microM (Na(+)); 5.62 +/- 0.98 microM (K(+)); 24.44 +/- 6.96 microM (Ca(2+)); 28.74 +/- 0.43 microM (Mg(2+)); DeltaG(o) = -7.541 +/- 0.037 kcal/mol (Na(+)); -7.458 +/- 1.03 kcal/mol (K(+)); -6.574 +/- 0.173 kcal/mol (Ca(2+)); -6.442 +/- 0.009 kcal/mol (Mg(2+)); DeltaH(o) = -22.357 +/- 1.189 kcal/mol (Na(+)); -21.917 +/- 0.891 kcal/mol (K(+)); -20.223 +/- 1.503 kcal/mol (Ca(2+)); -26.570 +/- 1.579 kcal/mol (Mg(2+)); and DeltaS(o) = -0.048 +/- 0.004 kcal/mol-K (Na(+)); -0.047 +/- 0.003 kcal/mol-K (K(+)); -0.044 +/- 0.005 kcal/mol-K (Ca(2+)); -0.065 +/- 0.005 kcal/mol-K (Mg(2+)). Thus, all reactions were enthalpy-driven. Despite a 5-fold difference in K(d) between mono- and divalent ions, the ratio of ion hydration DeltaG(o) to K(d) was constant. These data should be useful for molecular modeling and suggest that inhibitor activity will be a function of cellular conditions (normal or pathological).


Ultrasound-based relative elastic modulus imaging for visualizing thermal ablation zones in a porcine model.
The feasibility of using ultrasound-based elastic modulus imaging to visualize thermal ablation zones in an in vivo porcine model is reported. Elastic modulus images of soft tissues are estimated as an inverse optimization problem. Ultrasonically measured displacement data are utilized as inputs to determine an elastic modulus distribution that provides the best match to this displacement field. A total of 14 in vivo thermal ablation zones were investigated in this study. To determine the accuracy of delineation of each thermal ablation zone using elastic modulus imaging, the dimensions (lengths of long and short axes) and the area of each thermal ablation zone obtained from an elastic modulus image were compared to the corresponding gross pathology photograph of the same ablation zone. Comparison of elastic modulus imaging measurements and gross pathology measurements showed high correlation with respect to the area of thermal ablation zones (Pearson coefficient = 0.950 and p < 0.0001). The radiological-pathological correlation was slightly lower (correlation = 0.853, p < 0.0001) for strain imaging among these 14 in vivo ablation zones. We also found that, on average, elastic modulus imaging can more accurately depict thermal ablation zones, when compared to strain imaging (14.7% versus 22.3% absolute percent error in area measurements, respectively). Furthermore, elastic modulus imaging also provides higher (more than a factor of 2) contrast-to-noise ratios for evaluating these thermal ablation zones than those on corresponding strain images, thereby reducing inter-observer variability. Our preliminary results suggest that elastic modulus imaging might potentially enhance the ability to visualize thermal ablation zones, thereby improving assessment of ablative therapies.


Immunochemical measurement of serum prostatic acid phosphatase (PAP). Clinical evaluation of radioimmunoassay and counter immunoelectrophoresis.
Two radioimmunoassay procedures (RIA-1 and RIA-2) were evaluated for the quantitation of prostatic acid phosphatase in serum and compared with the enzymatic method and counter immunoelectrophoresis method for their specificity and sensitivity. Sera from 168 patients were analyzed and these included: normals, 27; untreated prostatic cancer patients Stage A, 2; Stage C, 3; Stage D, 17; cancer of prostate treated with different modalities, 42; sarcoma of prostate, 1; prostatitis, 3; nonprostatic carcinoma, 17; and benign prostatic hyperplasia (BPH), 56. RIA-1 procedure appeared more sensitive (82% sensitivity) and specific (94.5% specificity) than the RIA-2 procedure (68% sensitivity and 91.8% specificity), but the differences were not statistically significant. The enzymatic method was found to be least sensitive (63.6% sensitivity) but also the most specific (100% specificity). Only 69 of the specimens were analyzed by counter immunoelectrophoresis, which showed sensitivity of 87% and specificity of 51.4%. False positives were observed more often in patients with nonprostatic cancer and BPH. The variations in diagnostic specificity of immunologic assays suggest the need of characterization of each antibody specificity.


When can nurses refuse to care?
At the RCN Congress in Blackpool last year, one of the key topics discussed was the policy and practice implications which arise if nurses refuse to care for certain patients or if patients refuse to be cared for by a particular nurse. This article outlines the guidance by the RCN Ethics and Nursing Committee on when patients and nurses can exercise a right to refuse to be cared for or provide care.


Francisella tularensis proteome: low levels of ASB-14 facilitate the visualization of membrane proteins in total protein extracts.
Proteomic analysis of bacterial pathogens isolated from in vivo sources, such as infected tissues, provides many challenges not the least of which is the limited quantity of sample available for analysis. It is, therefore, highly desirable to develop a one-step cellular lysis and protein solubilization method that minimizes protein losses and allows the maximum possible coverage of the proteome. Here, we have used standard sample buffer constituents including urea, thiourea and DTT, but varied the detergent composition of the buffers in order to achieve the best quality of gels and the greatest spot resolution. We found that the most efficient solubilizing solution in this case consisted of 7 M urea, 2 M thiourea, 1% DTT, 0.5% amidosulfobetaine-14 (ASB-14) and 4% 3-[(3-Cholamidopropyl)dimethylammonio]-1-propanesulfonate (CHAPS). Inclusion of low levels of ASB-14 in solutions allowed visualization of a subset of 24 new protein spots in the Live Vaccine Strain (LVS) of Francisella tularensis and 21 spots in a virulent A-strain of the pathogen. Further investigation showed that 15 of the 24 enriched LVS spots were membrane or membrane-associated proteins suggesting that the optimized lysis and solubilization solution aids in the detection of more hydrophobic proteins. This methodology is now being applied to the analysis of Francisella obtained from in vivo sources.


Leiomyoma of the prostate--a rare mesenchymal tumor: a case report.
Prostatic enlargement due to benign adenomatous hyperplasia is very common in elderly males. However, benign mesenchymal tumors, especially true leiomyoma, are rare in prostate. True prostatic leiomyoma has been defined by Kaufman and Berneike as a smooth muscle tumor within the prostate or juxta-prostatic in position, devoid of glandular elements. The recognition of leiomyoma is important because of the potential of malignancy in such cases, and histopathology is the only tool to do so. We describe the case of a 65-year-old male presenting with urinary obstruction for eight months. Per rectal examination revealed an enlarged firm prostate, a trucut biopsy from which showed only stromal tissue. A suprapubic prostatectomy was performed, and histopathological examination revealed a benign smooth muscle tumor (confirmed by immunohistochemistry), in absence of glandular hyperplasia. Thus, a diagnosis of true leiomyoma of the prostate was made. True leiomyoma is a rare tumor in prostate, which can be diagnosed only on histopathological examination. In addition, careful intra-operative and extensive pathologic assessment is mandatory for predicting the potential behaviour.


Synergic use of chemical and ecotoxicological tools for evaluating multi-contaminated soils amended with iron oxides-rich materials.
Abandoned waste piles from ancient mining activities are potential hot spots for the pollution of the surrounding areas. A pot experiment was carried out to check the potential toxicity of the dumping material present in one of these scenarios, and several amendments were tested to attenuate the spread of the contamination events. The waste material had an acid pH and a large total concentration of As and Cu. A dose-response experiment was performed with this material following OCDE 208 test. A proportion 90:10 uncontaminated soil: dumping material (% w/w) was selected for the following experiment, in order to surpass the amount of dumping material that caused 50% reduction in plant growth. Pots were filled with the 90:10 mixture, planted with seeds of Brassica napus and amended with the following materials: three iron oxides of Bayoxide® E33 series, iron (II) sulphate in combination with de-inking paper sludge (Fe+PS), iron oxide-rich rolling mill scale (ROL) and iron oxide-rich cement waste (CEM). Amendment effectiveness evaluation was based on chemical and biological assays: extractable trace element concentration, soil enzymatic activities, inhibition of light emission of V. fischeri and Anabaena sp., B. napus L. fresh weight and screening test for emergence of B. napus L. seedlings. Amendments E33HCF and Fe+PS were the most effective in reducing extractable As and Zn concentration. B. napus weight and dehydrogenase and β-glucosidase activities were positively increased with the two above mentioned treatments but they triggered more toxic effects for V. fischeri luminescence. E33P treatment was the only in which the EC50 was higher than in the control. Anabaena sp. was less sensitive than V. fischeri as its luminescence was not hampered by any treatment. Trace element concentration did not significantly affect the failure in seed emergence. E33HCF and Fe+PS could act as proper amendments as they decreased extractable As and Zn. Further, plant fresh weight, enzymatic activities and some of the bioassays identified the latter treatments as the best ones among those tested here to this type of multi-contaminated soil.


Implementation of an in-reach rehabilitation program can increase the rate of discharge home from acute hospital care.
Objective This study describes how a model of early rehabilitation ('in-reach rehabilitation') can be integrated into acute care provision for hospitalised patients with high rehabilitation needs. This pragmatic evaluation aimed to assess service impact on home discharge rates from acute care. Methods An integrated early rehabilitation service was implemented at a tertiary teaching hospital in Sydney, Australia. Eligible patients were screened, placed on a waitlist, and treated in order of debility (six to eight patients concurrently). Routine data were collected and compared between those who received an in-reach rehabilitation program, and controls who remained on waitlist. Results From December 2021 to September 2022, 229 patients were identified as suitable for in-reach rehabilitation; of whom 100 received an in-reach program and the remaining 129 were waitlist controls. Patients who received in-reach rehabilitation achieved a significantly higher rate of discharge home from acute care compared to waitlist controls (46.0% vs 24.0%, P = 0.002) and lower rates of transfer to subacute inpatient rehabilitation (43.0% vs 62.0%). This was despite in-reach patients having high functional care needs (60% needed assistance from ≥two people to mobilise) and complex medical needs (median hospital length of stay 44.5 days, IQR 27.8-66.0). Conclusions It is feasible to deliver in-reach rehabilitation to hospitalised patients with heterogeneous diagnoses who have high rehabilitation needs. The rate of discharge home directly from acute wards is higher among those patients who received early in-reach rehabilitation compared to those on a waitlist.


The LiverSurgeryTrainer: training of computer-based planning in liver resection surgery.
The training of liver surgeons depends on local conditions such as the specialization of the clinic, the spectrum of cases, and the instructing surgeons. We present the LiverSurgeryTrainer a software application to support the training of prospective surgeons in preoperative decision making. The LiverSurgeryTrainer visualizes radiological images, volumetric information, and interactive 3D models of patients' liver anatomy. In addition, it provides special interaction techniques and tools to perform individual resections on the training data. To assess the correctness of decisions made by the learner, comments and decisions from experienced liver surgeons are provided for each case. To complete the case, additional material concerning the actual surgery (e.g., videos, reports) is presented. The application workflow is derived from a scenario-based design process and is based on an instructional design model. The LiverSurgeryTrainer was evaluated in several steps. A formative usability evaluation identified workflow and user interface flaws that were resolved in further development process. A summative evaluation shows the improvement of the LiverSurgeryTrainer in nearly all analyzed aspects. First results of a learning success evaluation show that learners experience a learning effect. Our training system allows surgeons to train procedures and interaction techniques for computer-based planning of liver interventions. The evaluations showed acceptance and usability.


Acute pain management for patients under opioid maintenance treatment: what physicians do in emergency departments?
The aim of this study was to analyze the current practices on acute pain management of patients under opioid maintenance treatment (OMT), that is, buprenorphine or methadone. A total of 706 physicians were solicited through a national network to answer a survey about pain perception and analgesic strategies. Among the prescribers, 323 (46%) answered the survey: 131 (40%) physicians estimated that patients under OMT when exposed to an acute painful event feel more pain than other patients and 170 (53%) estimated that the patients felt the same amount of pain. Use of WHO step 1 analgesics was reported by 283 (88%) prescribers [264 (82%) prescribers reported use of paracetamol and 178 (55%) reported use of NSAIDs]. Among the second-line analgesic drugs, the WHO step 3 analgesics (mainly morphine) were the most commonly reported [221 physicians (68%)]. Overall, the results demonstrate the misconceptions of physicians on the pain tolerance of patients under OMT. Clinical studies and evidence-based guidelines are necessary to improve the therapeutic strategies for such patients in an emergency setting.


Histone methyltransferase SETDB1 regulates liver cancer cell growth through methylation of p53.
SETDB1 is a histone H3K9 methyltransferase that has a critical role in early development. It is located within a melanoma susceptibility locus and facilitates melanoma formation. However, the mechanism by which SETDB1 regulates tumorigenesis remains unknown. Here we report the molecular interplay between SETDB1 and the well-known hotspot gain-of-function (GOF) TP53 R249S mutation. We show that in hepatocellular carcinoma (HCC) SETDB1 is overexpressed with moderate copy number gain, and GOF TP53 mutations including R249S associate with this overexpression. Inactivation of SETDB1 in HCC cell lines bearing the R249S mutation suppresses cell growth. The TP53 mutation status renders cancer cells dependent on SETDB1. Moreover, SETDB1 forms a complex with p53 and catalyses p53K370 di-methylation. SETDB1 attenuation reduces the p53K370me2 level, which subsequently leads to increased recognition and degradation of p53 by MDM2. Together, we provide both genetic and biochemical evidence for a mechanism by which SETDB1 regulates cancer cell growth via methylation of p53.


Bacterial Pathogen Indicator Transport from Livestock Mortality Biopiles.
Biopiles can be used to dispose of slaughterhouse residuals (SLRs); however, the fate of pathogenic bacteria (e.g., pathogenic strains of , ) in these systems is not well understood. The transport of these bacteria in water leaching from the biopile could represent a significant contamination source. This research examined the transport of Enterobacteriaceae and Enterococcaceae indicator bacteria from SLR biopiles. Three biopiles (2.6 m wide by 4.6 m long by 1.8 m high) were formed on soil layers in concrete cells that allowed for real-time monitoring of environmental parameters, hydrologic flux, and indicator bacteria levels in effluent leaching from the piles. In biopile effluent, indicator bacteria populations decreased exponentially following biopile formation. Indicator bacteria loads in effluent constituted <0.01% of the initial indicator bacteria levels in the biopiles, which was attributed to retention, inactivation, and death. Nearly 90% of the total indicator bacteria loads coincided with large precipitation events (>15 mm d). Movement of the indicator bacteria through the biopiles and underlying soil appeared to be consistent with preferential flow phenomena. The populations of the Enterobacteriaceae indicators remained low in conditions of higher soil water content and lower biopile temperatures, whereas the Enterococcaceae indicator appeared to regrow in these conditions. This indicated that bacterial pathogen transport from a biopile could be a concern after the disappearance of conventional bacterial indicators, such as . Management considerations should attempt to divert excess water from entering a biopile, such as locating a biopile under a roof. Unsaturated biopile and soil conditions should be maintained to impede water flow through preferential pathways in the soil underneath a biopile.


Implantation of the semicircular canals with preservation of hearing and rotational sensitivity: a vestibular neurostimulator suitable for clinical research.
It is possible to implant a stimulating electrode array in the semicircular canals without damaging rotational sensitivity or hearing. The electrodes will evoke robust and precisely controlled eye movements. A number of groups are attempting to develop a neural prosthesis to ameliorate abnormal vestibular function. Animal studies demonstrate that electrodes near the canal ampullae can produce electrically evoked eye movements. The target condition of these studies is typically bilateral vestibular hypofunction. Such a device could potentially be more widely useful clinically and would have a simpler roadmap to regulatory approval if it produced minimal or no damage to the native vestibular and auditory systems. An electrode array was designed for insertion into the bony semicircular canal adjacent to the membranous canal. It was designed to be sufficiently narrow so as to not compress the membranous canal. The arrays were manufactured by Cochlear, Ltd., and linked to a Nucleus Freedom receiver/stimulator. Seven behaviorally trained rhesus macaques had arrays placed in 2 semicircular canals using a transmastoid approach and "soft surgical" procedures borrowed from Hybrid cochlear implant surgery. Postoperative vestibulo-ocular reflex was measured in a rotary chair. Click-evoked auditory brainstem responses were also measured in the 7 animals using the contralateral ear as a control. All animals had minimal postoperative vestibular signs and were eating within hours of surgery. Of 6 animals tested, all had normal postoperative sinusoidal gain. Of 7 animals, 6 had symmetric postoperative velocity step responses toward and away from the implanted ear. The 1 animal with significantly asymmetric velocity step responses also had a significant sensorineural hearing loss. One control animal that underwent canal plugging had substantial loss of the velocity step response toward the canal-plugged ear. In 5 animals, intraoperative electrically evoked vestibular compound action potential recordings facilitated electrode placement. Postoperatively, electrically evoked eye movements were obtained from electrodes associated with an electrically evoked vestibular compound action potential wave form. Hearing was largely preserved in 6 animals and lost in 1 animal. It is possible to implant the vestibular system with prosthetic stimulating electrodes without loss of rotational sensitivity or hearing. Because electrically evoked eye movements can be reliably obtained with the assistance of intraoperative electrophysiology, it is appropriate to consider treatment of a variety of vestibular disorders using prosthetic electrical stimulation. Based on these findings, and others, a feasibility study for the treatment of human subjects with disabling Ménière's disease has begun.


Metabolic syndrome in Korean adolescents and young adult offspring and their parents.
Studies have investigated the associations between parental metabolic syndrome (MetS) and offspring MetS. This study aimed to uncover parental-offspring associations for MetS and its components according to offspring sex and age. A cross-sectional study in 1,403 fathers, 1,451 mothers, and 1,532 offspring (340 male and 404 female offspring aged 10-18 years; 283 male and 505 female offspring aged 19-25 years) using the Korea National Health and Nutrition Examination Survey data between 2010 and 2013. All categorized MetS components in fathers and mothers were significantly associated with the same components in male offspring, while high waist circumference, high triglycerides, and low high-density lipoprotein in fathers and mothers were associated with the same components in female offspring. The number of categorized MetS components which were significantly associated between parent-offspring pairs was greater in offspring aged 19-25 years than in those aged 10-18 years. All categorized MetS components were significantly associated between father-male offspring aged 19-25 years pairs, but not in other parent-offspring pairs. The MetS per se in fathers and mothers was significantly associated with that in male offspring aged 10-18 years. There were differential associations according to offspring sex and age group and parent's sex with respect to parental-offspring associations for MetS and its individual components. The associations for MetS and its components were stronger in young adult versus adolescent offspring, in male offspring versus female offspring.


Double-blind randomized controlled trial of low-level laser therapy in carpal tunnel syndrome.
Several studies have suggested that low-level laser therapy (LLLT) is effective in patients with carpal tunnel syndrome (CTS). In a double-blind randomized controlled trial of LLLT, 15 CTS patients, 34 to 67 years of age, were randomly assigned to either the control group (n = 8) or treatment group (n =7). Both groups were treated three times per week for 5 weeks. Those in the treatment group received 860 nm galium/aluminum/arsenide laser at a dosage of 6 J/cm2 over the carpal tunnel, whereas those in the control group were treated with sham laser. The primary outcome measure was the Levine Carpal Tunnel Syndrome Questionnaire, and the secondary outcome measures were electrophysiological data and the Purdue pegboard test. All patients completed the study without adverse effects. There was a significant symptomatic improvement in both the control (P = 0.034) and treatment (P =0.043) groups. However, there was no significant difference in any of the outcome measures between the two groups. Thus, LLLT is no more effective in the reduction of symptoms of CTS than is sham treatment.


T cell subpopulation phenotypes in filarial infections: CD27 negativity defines a population greatly enriched for Th2 cells.
Three-color flow cytometric analysis was used to define surface markers which identify the Th2-type CD4+ cells responsible for the eosinophilia and elevated serum IgE typical of tissue invasive helminth infections. A group of six mAbs to well known cell surface markers were screened for differential expression on CD4+ CD45RO+ lymphocytes from normal individuals (NL; n = 6) and filaria-infected patients (PT; n = 10). The majority of markers were expressed equally by both groups, but the CD4+ CD45RO+ cells in the PTs showed significantly higher levels of expression of HLA-DR than those of NLs (P = 0.014). This CD4+ HLA-DR+ subpopulation was then studied further for its expression of an additional 10 activation and adhesion molecules. CD27 showed a trend for lower intensities of expression on PT CD4+ HLA-DR+ cells than on those of NLs. Analysis of the serum from both NLs and PTs revealed that PTs had significantly higher levels of soluble CD27 and CD25 (IL-2R) in the serum than NLs (P < 0.01 and P = 0.022 respectively) indicating a general state of immune activation and differentiation. Functional analysis of the CD4+ HLA-DR+ and the CD4+ CD27- subpopulations revealed that the CD4+ HLA-DR+ cells produced significantly higher levels of IL-5 than the CD4+ HLA-DR- cells (P = 0.04), and the CD4+ CD27- cells produced significantly higher levels of both IL-4 and IL-5 than the CD4+ CD27+ cells (P < 0.05 and P < 0.001 respectively). Thus, while the CD4+ CD27- and CD27+ subpopulations contain Th1 and Th0 cells, only the CD4+ CD27- population contains the Th2 cells (producing both IL-4 and IL-5).


[The pathological, intestinal cockade sign].
The transabdominal ultrasonography is the most important imaging technique for intestinal diseases. The universal availability, the better imaging quality but also growing experience have definitely enlarged the spectrum of detectible diseases. The diagnostic accuracy of new techniques like "Tissue Harmonic Imaging" and Color and Power Doppler or the ultrasonography with contrast agents remains to be evaluated. Low costs and no side effects allow a generous use of the method in case of complications and in order to check the course of a disease. The sonomorphological signs of the most important diseases presenting as pathological cockade will be discussed.


Therapeutic effect of macular grid photocoagulation in treatment of nonexudative age-related macular degeneration.
To investigate the effect of prophylactic subthreshold laser macular grid photocoagulation on drusen area and to evaluate the visual outcome and incidence of choroidal neovascularization in patients with soft drusen maculopathy. In a nonrandomized nonmasked clinical trial, 18 patients (36 eyes) with bilateral soft drusen maculopathy were studied. For each patient, one eye was treated with 48 subthreshold (invisible end-point) applications of 532-nm KTP-laser in a macular grid pattern and the fellow eye was observed. Soft drusen areas were calculated and compared between the two groups at baseline and follow-up visits at 3, 6, 12, and 30 months of therapy. Best corrected visual acuity was also compared in observed and laser-treated eyes. Reduction of drusen area, change in visual acuity, and rate of CNV were assessed in both groups. At baseline, there was no significant difference in the mean drusen surface area between the two groups (P = 0.90). The mean surface area of soft drusen in treated eyes was 6.51 mm(2) after 30 months and 7.58 mm(2) (P = 0.50) in the control eyes. There was a trend towards reduction in the mean soft drusen area after 30 months from baseline in laser-treated eyes (6.51 vs. 6.97 mm(2)). In treated eyes, there was no statistically significant difference between the mean best corrected visual acuity at the baseline (0.28 logMAR) and after 30 months (0.32 logMAR) (P = 0.40). Subthreshold macular grid photocoagulation with 532-nm KTP-laser did not seem to reduce drusen surface area significantly and did not improve best corrected visual acuity after 30 months. No exudative lesion developed in laser-treated eyes.


Case Report: Residual Atrial Shunt Lesions in Aging Adults With Congenital Heart Disease: An Underestimated Risk of Stroke?
We report two cases of paradoxical cerebral embolism in adults with congenital heart disease (ACHD) with residual atrial shunt lesions, a 59 year-old male patient with partial detachment of a surgical ASD closure patch, and a 57 year-old male patient with Ebstein's anomaly and a large patent foramen ovale. Considering these mechanisms and the increasing incidence of venous thrombosis with age, a higher prevalence of paradoxical embolism in ACHD patients with residual atrial shunts may be suspected. Regular follow-up of patients with ACHD remains important throughout life even in seemingly stable lesions.


Calcium ion stimulated endogenous protein kinase catalyzed phosphorylation of peripheral and central nerve myelin proteins: comparison between normal and genetically dystrophic mouse.
Myelin isolated from the peripheral (PNS) and central nervous system (CNS) of mouse contained a protein kinase which catalyzed phosphorylation of myelin proteins. In the case of CNS myelin, small and large basic proteins were phosphorylated whereas in the case of PNS myelin, a glycoprotein (Po) as well as other basic proteins (P1 and P2) were phosphorylated. Ca2+, but not adenosine 3',5'-monophosphate (cyclic AMP), markedly (5- to 10-fold) stimulated phosphorylation of PNS and CNS myelin proteins. There was no difference between the normal and dystrophic mouse CNS myelin phosphorylation. However, a marked decrease in the cauda equina PNS myelin phosphorylation ofthe dystrophic mouse was observed. Interestingly, the dystrophic sciatic nerve myelin phosphorylation, compared to normal, was higher.


The Rising Costs of Alcohol-Associated Liver Disease in the United States.
Alcohol-associated liver disease (ALD) is rising in the United States because of an increase in high-risk drinking, but population-level ALD cost is unknown. Our aim was to project the direct and indirect costs associated with ALD in the US population through 2040. We used a previously validated microsimulation model of alcohol consumption and ALD with model parameters estimated from publicly available data sources, including the National Epidemiologic Survey Alcohol and Related Conditions-III, the Center for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research, the Bureau of Labor Statistics, and published studies informing the impact of alcohol consumption on ALD severity in the United States resident population. The simulated scenario included current and projected ALD-associated costs. From 2022 to 2040, the ALD is projected to cost $880 billion, $355 billion in direct healthcare-related costs, and $525 billion in lost labor and economic consumption. The annual cost of ALD is projected to increase from $31 billion in 2022 to $66 billion (118% increase) in 2040. Although the female population makes up 29% of these costs in 2022, by 2040 on a per annum basis, female costs would be 43% of the total annual expenditure. Increased consumption of alcohol in the US population, especially in females, will cause a steep rise in the economic burden of ALD in the United States. These findings highlight the need for planners and policymakers to plan for the increased impact of liver disease in the United States.


Functional and biochemical responses of skeletal muscle following a moderate degree of systemic iron loading in mice.
Excessive iron loading may cause skeletal muscle atrophy and weakness because of its free radical generating properties. To determine whether a clinically relevant degree of iron loading impairs skeletal muscle function, young male mice received injections of iron dextran (4 mg iron/200 µl) or 2 mM d-glucose (control) 5 days/week for 2 weeks ( n = 10/group). Systemic iron loading induced an approximate fourfold increase in the skeletal muscle nonheme iron concentration. Soleus specific tension (1, 30-250 Hz) was lower among iron-loaded animals compared with controls despite similar body mass and muscle mass. Soleus lipid peroxidation (4-hydroxynonenal adducts) and protein oxidation (protein carbonyls) levels were similar between groups. In gastrocnemius muscle, reduced glutathione (GSH) and glutathione peroxidase activity were similar but glutathione disulfide (GSSG) and the GSSG/GSH ratio were greater in iron-loaded muscle. A greater protein expression level of endogenous thiol antioxidant thioredoxin (TRX) was observed among iron-loaded muscle whereas its endogenous inhibitor thioredoxin-interacting protein (TXNip) and the TRX/TXNip ratio were similar. Glutaredoxin2, a thiol-disulfide oxidoreductase activated by GSSG-induced destabilization of its iron-sulfur [2Fe-2S] cluster, was lower following iron loading. Additionally, protein levels of α-actinin and αII-spectrin at 240 kDa were lower in the iron-loaded group. Ryanodine receptor stabilizing subunit calstabin1 was also lower following iron loading. In summary, the contractile dysfunction that resulted from moderate iron loading may be mediated by a disturbance in the muscle redox balance and from changes arising from an increased proteolytic response and aberrant sarcoplasmic reticulum Ca2+ release. NEW & NOTEWORTHY Although severe iron loading is known to cause muscle oxidative stress and dysfunction, the effects of a moderate degree of systemic iron loading on muscle contractile function and biochemical responses remain unclear. This study demonstrates that a pathophysiological elevation in the skeletal muscle iron load leads to force deficits that coincide with impaired redox status, structural integrity, and lower ryanodine receptor-associated calstabin1 in the absence of muscle mass changes or oxidative damage.


The relationship between airflow and lung sound amplitude in normal subjects.
Few investigators have examined the relationship between airflow and lung sound amplitude; the available data are contradictory. I measured airflow at the mouth and compared the peak flow (Vmax) to mean and peak lung sound amplitude (mean AMP and peak AMP) at four sites on the chest wall (right and left anterior apices and posterior bases) in four healthy young adults. At each site, the sounds produced by 20 breaths at Vmax ranging between 1.5 and 4 L/s (Vvar) were measured by an automated technique. Ten breaths during nearly constant Vmax breathing (Vcon) also were measured at each site. The lung sound amplitudes at the four sites in each subject were grouped and compared to Vmax by linear regression analysis. The same sounds were also submitted to an automated V-correction procedure to evaluate its adequacy in automatically adjusting for the effect of variations in Vmax on lung sound amplitude. The data showed that lung sound amplitude (mean or peak) was linearly related to V in all subjects (r for mean AMP vs Vmax:0.77, 0.85, 0.69, 0.89; r for peak AMP vs Vmax:0.80, 0.83, 0.79, 0.88), p less than 1 X 10(-7) in all cases. The average mean AMP vs Vmax regression line slope was 0.42, and the average peak AMP vs Vmax regression line slope was 0.45. V-correction decreased the coefficient of variation of the Vvar sounds by 61 percent and flattened the average regression line slopes to 0.128. For the Vcon series, V-correction diminished the coefficient of variation from 12.2 to 10.0 percent. The relationship between lung sound amplitude and airflow appears to be substantially linear and this relationship can be used to adjust effectively for variations in airflow.


Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite.
Sodium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Potassium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are inorganic salts that function as reducing agents in cosmetic formulations. All except Sodium Metabisulfite also function as hair-waving/straightening agents. In addition, Sodium Sulfite, Potassium Sulfite, Sodium Bisulfite, and Sodium Metabisulfite function as antioxidants. Although Ammonium Sulfite is not in current use, the others are widely used in hair care products. Sulfites that enter mammals via ingestion, inhalation, or injection are metabolized by sulfite oxidase to sulfate. In oral-dose animal toxicity studies, hyperplastic changes in the gastric mucosa were the most common findings at high doses. Ammonium Sulfite aerosol had an acute LC(50) of >400 mg/m(3) in guinea pigs. A single exposure to low concentrations of a Sodium Sulfite fine aerosol produced dose-related changes in the lung capacity parameters of guinea pigs. A 3-day exposure of rats to a Sodium Sulfite fine aerosol produced mild pulmonary edema and irritation of the tracheal epithelium. Severe epithelial changes were observed in dogs exposed for 290 days to 1 mg/m(3) of a Sodium Metabisulfite fine aerosol. These fine aerosols contained fine respirable particle sizes that are not found in cosmetic aerosols or pump sprays. None of the cosmetic product types, however, in which these ingredients are used are aerosolized. Sodium Bisulfite (tested at 38%) and Sodium Metabisulfite (undiluted) were not irritants to rabbits following occlusive exposures. Sodium Metabisulfite (tested at 50%) was irritating to guinea pigs following repeated exposure. In rats, Sodium Sulfite heptahydrate at large doses (up to 3.3 g/kg) produced fetal toxicity but not teratogenicity. Sodium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite were not teratogenic for mice, rats, hamsters, or rabbits at doses up to 160 mg/kg. Generally, Sodium Sulfite, Sodium Metabisulfite, and Potassium Metabisulfite were negative in mutagenicity studies. Sodium Bisulfite produced both positive and negative results. Clinical oral and ocular-exposure studies reported no adverse effects. Sodium Sulfite was not irritating or sensitizing in clinical tests. These ingredients, however, may produce positive reactions in dermatologic patients under patch test. In evaluating the positive genotoxicity data found with Sodium Bisulfite, the equilibrium chemistry of sulfurous acid, sulfur dioxide, bisulfite, sulfite, and metabisulfite was considered. This information, however, suggests that some bisulfite may have been present in genotoxicity tests involving the other ingredients and vice versa. On that basis, the genotoxicity data did not give a clear, consistent picture. In cosmetics, however, the bisulfite form is used at very low concentrations (0.03% to 0.7%) in most products except wave sets. In wave sets, the pH ranges from 8 to 9 where the sulfite form would predominate. Skin penetration would be low due to the highly charged nature of these particles and any sulfite that did penetrate would be converted to sulfate by the enzyme sulfate oxidase. As used in cosmetics, therefore, these ingredients would not present a genotoxicity risk. The Cosmetic Ingredient Review Expert Panel concluded that Sodium Sulfite, Potassium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are safe as used in cosmetic formulations.


Improved prediction of protein-protein interaction using a hybrid of functional-link Siamese neural network and gradient boosting machines.
In this paper, for accurate prediction of protein-protein interaction (PPI), a novel hybrid classifier is developed by combining the functional-link Siamese neural network (FSNN) with the light gradient boosting machine (LGBM) classifier. The hybrid classifier (FSNN-LGBM) uses the fusion of features derived using pseudo amino acid composition and conjoint triad descriptors. The FSNN extracts the high-level abstraction features from the raw features and LGBM performs the PPI prediction task using these abstraction features. On performing 5-fold cross-validation experiments, the proposed hybrid classifier provides average accuracies of 98.70 and 98.38%, respectively, on the intraspecies PPI data sets of Saccharomyces cerevisiae and Helicobacter pylori. Similarly, the average accuracies for the interspecies PPI data sets of the Human-Bacillus and Human-Yersinia data sets are 98.52 and 97.40%, respectively. Compared with the existing methods, the hybrid classifier achieves higher prediction accuracy on the independent test sets and network data sets. The improved prediction performance obtained by the FSNN-LGBM makes it a flexible and effective PPI prediction model.


The protective effect of ethyl pyruvate on lung injury after burn in rats.
To investigate the effects of administered ethyl pyruvate (EP), a novel anti-inflammatory agent, on oxidoinflammatory and apoptotic pathways in the lung tissue of rats in a full-thickness burn model. The study took place in Ankara Research and Training Hospital Animal Laboratory, Turkey in June 2006. Thirty-two rats were randomly divided into 4 groups in equal numbers as sham, burn, sham+EP, and burn+EP. The burn model, used produced a full thickness burn of the 30-35% of the total body surface area. Ethyl pyruvate was administered as 40 mg/kg intraperitoneally. Rats were sacrificed after 24 hours, acute lung injury (ALI) was evaluated by direct light microscopy and apoptosis was evaluated by caspase-3 staining. Oxidoinflammatory events were evaluated by determining the tissue levels of myeloperoxidase (MPO), lipid peroxidation products, and nitrite. No significant difference was observed in lung tissue nitrite and malondialdehyde levels among the study groups. Histopathological results revealed that ALI and apoptosis were significantly higher in the burn group and EP prevented this effect. Similar results were obtained in tissue MPO levels. Ethyl pyruvate is a novel, potent anti-inflammatory agent. This agent prevented leukocyte infiltration, ALI, and apoptotic loss of the lung tissue in thermal injury.


Silicene Flowers: A Dual Stabilized Silicon Building Block for High-Performance Lithium Battery Anodes.
Nanostructuring is a transformative way to improve the structure stability of high capacity silicon for lithium batteries. Yet, the interface instability issue remains and even propagates in the existing nanostructured silicon building blocks. Here we demonstrate an intrinsically dual stabilized silicon building block, namely silicene flowers, to simultaneously address the structure and interface stability issues. These original Si building blocks as lithium battery anodes exhibit extraordinary combined performance including high gravimetric capacity (2000 mAh g-1 at 800 mA g-1), high volumetric capacity (1799 mAh cm-3), remarkable rate capability (950 mAh g-1 at 8 A g-1), and excellent cycling stability (1100 mA h g-1 at 2000 mA g-1 over 600 cycles). Paired with a conventional cathode, the fabricated full cells deliver extraordinarily high specific energy and energy density (543 Wh kgca-1 and 1257 Wh Lca-1, respectively) based on the cathode and anode, which are 152% and 239% of their commercial counterparts using graphite anodes. Coupled with a simple, cost-effective, scalable synthesis approach, this silicon building block offers a horizon for the development of high-performance batteries.


Effects of Anaplasma phagocytophilum on host cell ferritin mRNA and protein levels.
Ferritin is a major intracellular iron storage protein and also functions as a cytoprotectant by sequestering iron to minimize the formation of reactive oxygen species. Anaplasma phagocytophilum, the causative agent of human granulocytic anaplasmosis, is an obligate intracellular bacterium that colonizes neutrophils. We have previously reported that human promyelocytic HL-60 cells infected with A. phagocytophilum demonstrate increased transcription of ferritin heavy chain and also that the bacterium stimulates neutrophil NADPH oxidase assembly and degranulation during the initial hours of infection (J. A. Carlyon, W. T. Chan, J. Galan, D. Roos, and E. Fikrig, J. Immunol. 169:7009-7018, 2002, and J. A. Carlyon, D. Abdel-Latif, M. Pypaert, P. Lacy, and E. Fikrig, Infect. Immun. 72:4772-4783, 2004). In this study, we assessed ferritin mRNA and protein levels during A. phagocytophilum infection in vitro using HL-60 cells and neutrophils and in vivo using neutrophils from infected mice. The addition of A. phagocytophilum, as well as Escherichia coli and serum-opsonized zymosan, to neutrophils results in a pronounced increase in ferritin light-chain transcription and a concomitant rise in ferritin protein levels. Neutrophils from A. phagocytophilum-infected mice demonstrate elevated ferritin heavy-chain mRNA expression, a phenomenon consistent with infections by intracellular pathogens. Notably, ferritin protein levels of infected HL-60 cells were markedly diminished in a dose- and time-dependent manner. These studies provide insight into the effects A. phagocytophilum has on the ferritin levels of its host cell.


Incidence and Risk Factors for Community and Hospital Acquisition of Clostridium difficile Infection in the Tel Aviv Sourasky Medical Center.
OBJECTIVES To estimate the incidence and identified risk factors for community-acquired (CA) and hospital-acquired (HA) Clostridium difficile infection (CDI) METHODS We conducted 2 parallel case-control studies at Tel Aviv Sourasky Medical Center from January 1, 2011, to December 31, 2014. We identified persons with CDI, determined whether infection was community or hospital acquired, and calculated incidence rates from 2007 to 2014. We collected demographic, clinical, and epidemiological information for CDI cases and hospitalized control cases and estimated the odds ratio with 95% confidence interval using conditional logistic regression. RESULTS In total, 1,563 CDI cases were identified in the study. The incidence rate of CA-CDI and HA-CDI increased by 1.6-fold and 1.2-fold, respectively, during 2012-2014. However, the incidence rate of CA-CDI was 0.84 per 100,000 (95% CI, 0.52-1.30), the rate for HA-CDI was 4.7 per 10,000 patient days (95% CI, 4.08-5.38), respectively, in 2014. We identified several factors as independent variables significantly associated with HA-CDI: functional disability, presence of nasogastric tube, antibiotic use, chemotherapy, infection by extended-spectrum β-lactamases, and mean of albumin values. Risk factors independently associated with CA-CDI were close contact with a family member who had been hospitalized in the previous 6 months, inflammatory bowel disease, and home density index (adjusted odds ratio, 25.7; 95% confidence interval, 3.99-165.54; P=.001). CONCLUSIONS The identification of the main modifiable risk factors for HA-CDI (antibiotic exposure and hypoalbuminemia) and for CA-CDI (close contact with a family member who had been hospitalized in the previous 6 months) is likely to optimize prevention efforts; these factors are critical in preventing the spread of CDI. Infect Control Hosp Epidemiol 2017;38:912-920.


Synthesis of peptides by the solid-phase method. V. Substance P and analogs.
We have synthesized a series of 12 analogs of the undecapeptide substance P in order to perform a structure-activity study of this peptide. In the present work, each residue was substituted by L-alanine, and the C-terminal amide was replaced by the free carboxyl in order to pinpoint biologically important side chains and functional groups. The synthesis of the analogs was carried out by the automatic solid-phase method. Couplings were performed by the symmetrical anhydride procedure. After cleavage with liquid HF, the peptides were purified by gel filtration and ion-exchange chromatography. Their purity was assessed by thin-layer chromatography, paper electrophoresis, amino acid and elemental analyses, and high pressure liquid chromatography. They were tested for biological activity in vitro on the ileum of the guinea pig, the mesenteric vein of the rabbit, and the vas deferens of the rat, and in vivo by measuring their effect on the blood pressure of the rat.