A Graphene Oxide-Based Sensing Platform for the Determination of Methicillin-Resistant Staphylococcus aureus Based on Strand-Displacement Polymerization Recycling and Synchronous Fluorescent Signal Amplification.
To develop new technology for detecting methicillin-resistant Staphylococcus aureus (MRSA), a novel fluorescent biosensor based on Klenow fragment (KF)-assisted target recycling amplification and synchronous fluorescence analysis was created. Carboxy-fluorescein (FAM)-labeled single-stranded DNA (ssDNA) containing a capture probe and a signal probe was adsorbed onto the surface of graphene oxide (GO) via π-stacking interactions, resulting in the fluorescence quenching of the dye. When target and primer were introduced, the fluorescence was restored due to P0 being completely released from the surface of the GO. Meanwhile, by using the KF and exploiting the synergistic effect of FAM and the double-stranded DNA (dsDNA)-SYBR Green I duplex structure, the fluorescence in this detection system was considerably amplified and the sensitivity was improved. The proposed strategy for mecA gene analysis showed a good linear range from 1 to 40 nmol/L, with a lower limit of detection of 0.5 nmol/L. In addition, a bacterial sample harboring the mecA gene was also detected, and its lower detection limit was up to 300 colony-forming units (CFU)/mL. Accordingly, this biosensor exhibits high sensitivity and selectivity and has great potential for early clinical diagnosis and treatment.


Comparative phylogeography reveals the demographic patterns of neotropical ancient mountain species.
Mountains are renowned for their bountiful biodiversity. Explanations on the origin of such abundant life are usually regarded to their orogenic history. However, ancient mountain systems with geological stability also exhibit astounding levels of number of species and endemism, as illustrated by the Brazilian Quartzitic Mountains (BQM) in Eastern South America. Thus, cycles of climatic changes over the last couple million years are usually assumed to play an important role in the origin of mountainous biota. These climatic oscillations potentially isolated and reconnected adjacent populations, a phenomenon known as flickering connectivity, accelerating speciation events due to range fragmentation, dispersion, secondary contact, and hybridization. To evaluate the role of the climatic fluctuations on the diversification of the BQM biota, we estimated the ancient demography of distinct endemic species of animals and plants using hierarchical approximate Bayesian computation analysis and Ecological Niche Modelling. Additionally, we evaluated if climatic oscillations have driven a genetic spatial congruence in the genetic structure of codistributed species from the Espinhaço Range, one of the main BQM areas. Our results show that the majority of plant lineages underwent a synchronous expansion over the Last Glacial Maximum (LGM, c. 21 thousand years ago), although we could not obtain a clear demographic pattern for the animal lineages. We also obtained a signal of a congruent phylogeographic break between lineages endemic to the Espinhaço Range, suggesting how ancient climatic oscillations might have driven the evolutionary history of the Espinhaço's biota.


Managing Patent Foramen Ovale (PFO) in Adults With Cryptogenic Stroke and Lymphoma: A Multidisciplinary Perspective.
Cryptogenic strokes are strokes with no clear underlying cause. Patent foramen ovale (PFO) is believed to be one of the causes of cryptogenic strokes. To manage such cases, closing the PFO is usually considered an option. We report a case of a middle-aged male with lymphoma who presented with an altered mental status due to a stroke, which, on investigation, was found to be due to an underlying PFO. This report explores the factors that must be considered when making the decision to close the PFO and emphasizes the vital role of a multi-disciplinary team in determining the best course of action for patients with cryptogenic strokes.


Effects of Educative Materials on Doctors' Intention to Initiate Life-Saving Procedures After a Suicide Attempt: Randomised Controlled Trial.
Introduction: The topic of euthanasia, assisted dying, and how to deal with death wishes has received strong public and media attention in many countries. Nevertheless, there is currently no research which has analysed if educative materials that favour or disfavour the initiation of life-saving measures after a suicide attempt impact on attitudes to initiate such procedures among physicians. Materials and Methods: A double-blind randomised controlled trial was conducted to test if educative materials that either support life-saving measures or rather recommend against it after a near-fatal suicide attempt has an effect on intentions to initiate such measures (trial registration: DRKS00024953, www.drks.de). N = 192 doctors from the Medical University Vienna (Austria) participated in the study and either read educative materials not recommending (n = 59), or recommending life-saving measures (n = 64), or were not reading educative materials (n = 69, control group). The primary outcome was intentions to initiate life-saving measures in an open case vignette featuring the case of a terminally ill cancer patient. Other variables assessed were demographics, experiences with terminally ill and dying patients, training or qualification in mental health, specialty, position, whether doctors worked in emergency medicine, and attitudes toward assisted dying. A logistic regression analysis was used. Results: There was no immediate effect of educative materials on intentions to initiate life-saving measures, χ2(2) = 0.94, p = 0.63. The adjusted model including all tested predictors was significant [χ2(15) = 37.82, df = 15, p < 0.001]. Attending position, male gender, low age, and more negative attitudes to assisted dying predicted a decision for life-saving measures. Higher agreement with life-saving measures was reported for a case vignette about a patient with schizophrenia than for a case vignette about a patient with Huntington's disease. Discussion: Educative materials either favouring or disfavouring the initiation of life-saving measures after a suicide attempt do not appear to immediately influence related decision-making processes. Related intentions appear mainly influenced by personal opinions on the topic and by the specific patient case. Good-quality in-depth discussions regarding end-of-life decisions and to develop well-founded and non-opinionated guidelines are highly warranted.


Short-term safety and efficacy of human GH replacement therapy in 595 adults with GH deficiency: a comparison of two dosage algorithms.
The aim of GH replacement therapy in GH-deficient adults is to optimize response with minimum incidence of adverse reactions, but optimal therapy regimens are still to be established. This two-arm parallel study examined effects of two GH dose algorithms in adults with GH deficiency of adult or childhood onset. Patients on low dose (LD; n = 302) received GH at 3 microg/kg per day for 3 months increasing to 6 microg/kg per day for 3 months, and those on conventional dose (CD; n = 293) started on 6 microg/kg per day for 3 months increasing to 12 microg/kg per day for 3 months. The proportion of patients completing therapy was greater for the LD group than the CD group for the first 3 months (93.0% vs. 88.1%; P = 0.037) and overall for the 6 months (90.7% vs. 84.0%; P = 0.013). Both dose groups showed significant increases in lean body mass and decreases in fat mass for all time points. Percent increase in lean body mass was less with LD than CD over the first 3 months (2.43 +/- 4.33 vs. 3.58 +/- 4.69%; P = 0.006) but not overall for the 6-month period (4.38% +/- 5.34% vs. 5.21% +/- 5.99%; P = 0.141). Percent decrease in fat mass was less with LD than CD for the first 3 months (-2.81% +/- 7.81% vs. -5.53% +/- 8.64%; P < 0.001) and overall for the 6-month period (-6.35% +/- 9.42% vs. -9.45% +/- 12.07%; P = 0.006). IGF-I SD score increased less with LD than CD for 0 to 3 and 0 to 6 months, although for IGF-binding protein-3 SD score, there was no significant difference between doses at any time. Arthralgia was the only adverse event that occurred significantly less frequently with LD than with CD. Calculated changes based on gender and onset indicated greater changes in males than females for body composition, but there was little difference in GH-related adverse events between males and females. The lower starting dose with dose titration appeared more favorable, but differences in response between genders and onset of GH deficiency need to be taken into account when setting an individual dose regimen.


Severe epilepsy: diagnostic and epidemiological aspects.
Epidemiological parameters of epilepsy have been estimated in a large number of studies. Reported annual incidence rates for recurrent seizures vary between 30 and 50/100,000, and prevalence rates in most studies between 500 and 1000/100,000. Varying findings are mostly due to different case ascertainment methods and definitions of epilepsy applied in different surveys. These aspects will be discussed in this paper. A special emphasis is laid on differential diagnosis of seizure disorders, and on the prevalence and causes of complex partial epilepsy. This epileptic disorder is one of the most common forms of epilepsy, and also difficult to treat in many cases. Many recent reports show that prognosis of seizures in patients with epilepsy is better than suggested in earlier studies. However, 25-30% of epileptics seem to have frequent (greater than 1/month) seizures. Our own study, in accordance with earlier findings suggests that prevalence of patients with severe complex partial epilepsy is about 80-90/100,000. Available literature provides several predictive factors for the prognosis of seizures and assessment of prognosis is possible quite early after the onset of seizures. Treatment choices for patients with intractable epilepsy will be discussed.


The potentiation of zinc toxicity by soil moisture in a boreal forest ecosystem.
Northern boreal forests often experience forest dieback as a result of metal ore mining and smelting. The common solution is to lime the soil, which increases pH, reducing metal toxicity and encouraging recovery. In certain situations, however, such as in Flin Flon, Manitoba, Canada, liming has yielded only moderate benefits, with some locations responding well to liming and other locations not at all. In an effort to increase the effectiveness of the ecorestoration strategy, the authors investigated if these differences in liming responsiveness were linked to differences in toxicity. Toxicity of metal-impacted Flin Flon soils on the oribatid mite Oppia nitens and the collembolan Folsomia candida was assessed, with a view toward identifying the metal of concern in the area. The effects of moisture content on metal sorption, uptake, and toxicity to the invertebrates were also investigated. Toxicity tests with the invertebrates were conducted using either Flin Flon soils or artificial soils with moisture content adjusted to 30%, 45%, 60%, or 75% of the maximum water-holding capacity of the soil samples. The Relative to Cd Toxicity Model identified Zn as the metal of concern in the area, and this was confirmed using validation tests with field contaminated soils. Furthermore, increasing the moisture content in soils increased the amount of mobile Zn available for uptake with the ion exchange resin. Survival and reproduction of both invertebrates were reduced under Zn exposure as moisture level increased. Thus, moisture-collecting landforms, which are often also associated with high Zn concentrations at Flin Flon, have, as a result, higher Zn toxicity to the soil ecosystem because of increases in soil moisture.


[Vesico-urethral lithiasis secondary to foreign body].
We report a case of vesico-urethral litiasis secondary to foreign body (gauze) calcificated, left in prostatic cell during prostate open surgery of performed twelve years ago. In the related literature we observe that most of foreign urinals bodies are secondary to the introduction through the urethra of objects with autoerotic finality in normal patients or more often with psychiatric disorders, and only a small proportion are of iatrogenic origin, mainly in the last ten years.


Steady-State EEG and Psychophysical Measures of Multisensory Integration to Cross-Modally Synchronous and Asynchronous Acoustic and Vibrotactile Amplitude Modulation Rate.
According to the temporal principle of multisensory integration, cross-modal synchronisation of stimulus onset facilitates multisensory integration. This is typically observed as a greater response to multisensory stimulation relative to the sum of the constituent unisensory responses (i.e., superadditivity). The aim of the present study was to examine whether the temporal principle extends to the cross-modal synchrony of amplitude-modulation (AM) rate. It is well established that psychophysical sensitivity to AM stimulation is strongly influenced by AM rate where the optimum rate differs according to sensory modality. This rate-dependent sensitivity is also apparent from EEG steady-state response (SSR) activity, which becomes entrained to the stimulation rate and is thought to reflect neural processing of the temporal characteristics of AM stimulation. In this study we investigated whether cross-modal congruence of AM rate reveals both psychophysical and EEG evidence of enhanced multisensory integration. To achieve this, EEG SSR and psychophysical sensitivity to simultaneous acoustic and/or vibrotactile AM stimuli were measured at cross-modally congruent and incongruent AM rates. While the results provided no evidence of superadditive multisensory SSR activity or psychophysical sensitivity, the complex pattern of results did reveal a consistent correspondence between SSR activity and psychophysical sensitivity to AM stimulation. This indicates that entrained EEG activity may provide a direct measure of cortical activity underlying multisensory integration. Consistent with the temporal principle of multisensory integration, increased vibrotactile SSR responses and psychophysical sensitivity were found for cross-modally congruent relative to incongruent AM rate. However, no corresponding increase in auditory SSR or psychophysical sensitivity was observed for cross-modally congruent AM rates. This complex pattern of results can be understood in terms of the likely influence of the principle of inverse effectiveness where the temporal principle of multisensory integration was only evident in the context of reduced perceptual sensitivity for the vibrotactile but not the auditory modality.


Propagation of the cardiac impulse in the diabetic rat heart: reduced conduction reserve.
Diabetes mellitus is a growing epidemic with severe cardiovascular complications. Although much is known about mechanical and electrical cardiac dysfunction in diabetes, few studies have investigated propagation of the electrical signal in the diabetic heart and the associated changes in intercellular gap junctions. This study was designed to investigate these issues, using hearts from control and diabetic rats. Diabetic conditions were induced by streptozotocin (STZ), given i.v. 7-14 days before experiments. Optical mapping with the voltage-sensitive dye di-4-ANEPPS, using hearts perfused on a Langendorff apparatus, showed little change in baseline conduction velocity in diabetic hearts, reflecting the large reserve of function. However, both the gap junction uncoupler heptanol (0.5-1 mM) and elevated potassium (9 mM, to reduce cell excitability) produced a significantly greater slowing of impulse propagation in diabetic hearts than in controls. The maximal action potential upstroke velocity (an index of the sodium current) and resting potential was similar in single ventricular myocytes from control and diabetic rats, suggesting similar electrical excitability. Immunoblotting of connexin 43 (Cx43), a major gap junction component, showed no change in total expression. However, immunofluorescence labelling of Cx43 showed a significant redistribution, apparent as enhanced Cx43 lateralization. This was quantified and found to be significantly larger than in control myocytes. Labelling of two other gap junction proteins, N-cadherin and beta-catenin, showed a (partial) loss of co-localization with Cx43, indicating that enhancement of lateralized Cx43 is associated with non-functional gap junctions. In conclusion, conduction reserve is smaller in the diabetic heart, priming it for impaired conduction upon further challenges. This can desynchronize contraction and contribute to arrhythmogenesis.


Effect of Custom-Made Foot Orthosis for Scoliosis with Pelvic Malalignment in a Patient with Myelomeningocele of Partial Neurological Deficit: A Case Report.
BACKGROUND The treatment of patients with spinal deformities, such as developmental scoliosis in children with myelomeningocele, poses a formidable challenge. We observed the effects of a custom-made foot orthosis in a case of mild scoliosis with pelvic malalignment, in a patient with myelomeningocele. CASE REPORT The patient was a 5-year-old female who was diagnosed with myelomeningocele and who had a partial neurological deficit. At the time of the first visit, the patient showed moderate pelvic rotation to the clockwise side during gait and severe left anterior pelvic tilting during the drooping upper body. Radiographic images revealed mild lumbar scoliosis and severe pelvic asymmetry. After applying a custom-made foot orthosis for 8 months, the patient showed moderate improvement of pelvic rotation and tilting. Clinical biomechanical changes were well correlated with radiographic images. CONCLUSIONS These results highlight that custom-made foot orthosis controlling 3 motion planes of the pelvis had a corrective effect on mild lumbar scoliosis in a patient with myelomeningocele.


Temperatures kept cool in Southampton.
According to Digitron, hospitals countrywide are seeing the benefits of DigiTrak, the company's automatic wireless temperature monitoring system. Katey McDonald, the company's marketing manager, outlines how the system replaces traditional methods of data collection by providing a single networked package, and describes its use at Southampton General Hospital for blood monitoring, with the help of advanced biomedical scientist and quality officer there Marie Cundall.


The properties of ion-water clusters. I. The protonated 21-water cluster.
The ab initio atom-centered density-matrix propagation approach and the multistate empirical valence bond method have been employed to study the structure, dynamics, and rovibrational spectrum of a hydrated proton in the "magic" 21 water cluster. In addition to the conclusion that the hydrated proton tends to reside on the surface of the cluster, with the lone pair on the protonated oxygen pointing "outwards," it is also found that dynamical effects play an important role in determining the vibrational properties of such clusters. This result is used to analyze and complement recent experimental and theoretical studies.


[A laboratory study of the possibility of benzpyrene penetration into wheat germ using different means of drying the products of combustion].
Possible accumulation of benzpyrene in wheat grain during its drying by means of a heat-carrying agent (air diluted combustion products) containing this carcinogen was studied in a laboratory set-up. With benzpyrene contained in the heat-carrier in an amount of 0.12 gamma/m3 this carcinogen was amassing in the grain with all conditions and methods of drying under study. An increased benzpyrene content in the grain by comparison with the background one was noted under optimal conditions of drying in a solid layer, boiling layer and in a suspended state by as much as 23, 11 and 3 times respectively. On the basis of these and literature data a conclusion is drawn that grain may be dried in suspended state (recirculation dryers) under definite, parctically realizable conditions without accumulation of benzpyrene therein.


Medrad Continuum MR infusion system components must remain secured in MR environment.
The infusion pump component of the Medrad Continuum MR infusion system contains ferromagnetic materials and may be pulled into the MR system's bore if not adequately secured. Users need to be aware that neither the pump nor any other components should be removed from the system within the scan room. Additionally, before bringing the system into the scan room, users should verify that the system is free of damage and that the pump and its mounting bracket are both firmly secured.


EGFR gene copy number as a prognostic marker in colorectal cancer patients treated with cetuximab or panitumumab: a systematic review and meta analysis.
The epidermal growth factor receptor (EGFR) gene copy number (GCN) has been previously demonstrated to correlate with the clinical outcome of colorectal cancer (CRC) treated with anti-EGFR monoclonal antibodies (mAbs), although it remains controversial. We conducted a systematic review and meta-analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs. We systematically identified articles investigating EGFR GCN by fluorescent or chromogenic in situ hybridization or other detection techniques in patients with metastatic CRC treated with panitumumab or cetuximab, (last search: 10 August 2012). Eligible studies had to report on overall survival (OS), progression-free survival (PFS) or time-to-progression (TTP), stratified by EGFR GCN. Summary hazard ratios (HRs) were calculated using random-effects models. Among 13 identified studies, 10 (776 patients, 302 with increased GCN), 8 (893 patients, 282 with increased GCN) and 3 (149 patients, 66 with increased GCN) were eligible for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR GCN was associated with increased OS (HR = 0.62; 95% CI 0.50-0.77; P<0.001), PFS (HR = 0.65; 95% CI 0.47-0.89; P = 0.008) but not TTP (HR = 0.71; 95% CI 0.44-1.14; P = 0.157). It was also shown that EGFR GCN is independent of other factors such as KRAS status. Among those populations received second-line or higher treatment, increased EGFR GCN was strongly associated with improved survival (for OS, HR = 0.60; 95% CI 0.47-0.75; P<0.001; for PFS, HR = 0.59; 95% CI 0.47-0.75; P<0.001), whereas it did not influence survival in patients that received first-line therapy. Among the anti-EGFR-treated patients, increased EGFR GCN appears to be associated with improved survival outcomes. The effect on survival appears to be related to patients receiving the line of treatment.


Ultrasound instrumentation.
Ultrasound is used in all areas of general surgery and many surgical subspecialties. The surgeon with ultrasound skills brings a number of advantages to clinical practice, including the ability to view dynamic images that are far superior to the interpretation of static ultrasound images. However, to obtain optimal ultrasound images, the surgeon sonographer must know the equipment well. This article provides an overview of the various types of ultrasound instrumentation, their settings, their care, and their uses ina variety of clinical situations.


Prevalence of Alzheimer's disease and apolipoprotein E allele frequencies in the Old Order Amish.
The authors examined the prevalence of Alzheimer's disease and apolipoprotein E allele frequencies in the Old Order Amish. A lower frequency of dementia in the Amish does not appear to be due to a reduced E4 frequency.


ACCUSA--accurate SNP calling on draft genomes.
Next generation sequencing technologies facilitate genome-wide analysis of several biological processes. We are interested in whole-genome genotyping. To our knowledge, none of the existing single nucleotide polymorphism (SNP) callers consider the quality of the reference genome, which is not necessary for high-quality assemblies of well-studied model organisms. However, most genome projects will remain in draft status with little to no genome assembly improvement due to time and financial constraints. Here, we present a simple yet elegant solution ('ACCUSA') that considers both the read qualities as well as the reference genome's quality using a Bayesian framework. We demonstrate that ACCUSA is as good as the current SNP calling software in detecting true SNPs. More importantly, ACCUSA does not call spurious SNPs, which originate from a poor reference sequence. ACCUSA is available free of charge to academic users and may be obtained from ftp://bbc.mdc-berlin.de/software. ACCUSA is programmed in JAVA 6 and runs on any platform with JAVA support. email@example.com Supplementary data are available at Bioinformatics online.


Practice-Based Approach to Assessing and Treating Non-Adherence in Pediatric Regimens.
With advances in medical care, youth with chronic illness have the potential for higher quality of life; however, these treatments often come with cost (i.e., burden, financial) that can result in non-adherence. Pediatric non-adherence, on average, is approximately 50% across chronic health conditions. Research has identified effective, evidence-based assessment measures and intervention strategies to promote regimen adherence in youth. Yet, these measures and strategies typically are designed for clinical trials and thus may not be feasible or practical in typical clinic settings. As the field of adherence assessment and intervention expands, it will be important to devise evidence-based tools that are pragmatic and can be translated easily into practice. To guide this future direction, the goals of this paper are to review evidence-based adherence assessment and intervention strategies that can be used with youth and families in clinical practice, to illustrate the complexities of addressing adherence concerns in routine practice, and to discuss the challenges of disseminating and implementing evidence-based strategies in the real world.


[Employment of the laser apparatus SL-30 in complex treatment of chronic recurrent herpetic stomatitis].
The purpose of the study was the estimation of complex treatment effectiveness of chronic recurrent herpetic stomatitis using portable laser device "Beurer" (Germany). Fifty patients 17 till 55 years of age were investigated. Among them 28 were women and 22 were men. They were divided into two groups. All patients were treated by standard algorithm according to the severity of the disease. In the patients from the second group laser therapy by means of SL-30, 15-30 min per day was administered. After the completion of the course of treatment positive therapeutic effect has been achieved in all patients from the second group. Disappearance of the subjective symptoms and the initiation of the reparative-regenerative processes has occurred much faster in this group which gave us an opportunity to reduce the number of sessions by 5-6 in comparison with the first group. Thus, it was shown that the use of apparatus SL-30 in complex treatment of the chronic recurrent herpetic stomatitis increases the efficiency of the treatment.


Viral-Induced Mortality of Prokaryotes in a Tropical Monsoonal Estuary.
Viruses are recognized as the most abundant and dynamic biological entities in the marine and estuarine environment. However, studies on the dynamics and activity of viruses in transient estuarine systems are limited. This study examines temporal and spatial variations in viral abundance (VA) and viral activity across the salinity gradient in a monsoon-driven tropical estuarine system (Cochin estuary, CE) along the southwest coast of India. Water samples were collected from five stations (with different hydrological settings) every 3 h for 24 h period during two distinct seasons, namely pre-monsoon (PRM, dry season) and monsoon (MON, wet season). Time series measurements were made for a spring and neap tidal cycle for each season at all the stations. The results showed marked spatial and seasonal variability with relatively low diel and tidal variations in VA and lytic activity. Viral activity was found to be distinct in five stations studied with the maximum activity in the mesohaline regions (salinity <20) of the estuary. This region was characterized by high VA, lytic infection and viral production, accompanied by low (BGE) and high bacterial respiration. Based on viral lytic production, lytic viruses were found to be responsible for the release of ca. 72.9 ± 58.5 μg C L-1d-1 of bacterial carbon. The contribution of the viral shunt to the dissolved organic carbon (DOC) pool was higher during the dry season (PRM) than MON. Statistical analysis confirmed a significant association of viruses with the host availability and salinity. This work demonstrates the spatiotemporal distribution of viruses in a tropical estuarine ecosystem and highlights their role in microbial mortality across different salinity gradients. This study forms the first report on viral processes from a monsoon-driven tropical estuarine ecosystem.


Histone deacetylase gene SlHDT1 regulates tomato fruit ripening by affecting carotenoid accumulation and ethylene biosynthesis.
Fruit development and ripening is a complicated biological process, that is not only regulated by plant hormones and transcription factors, but also affected by epigenetic modifications. Histone deacetylation is an important way of epigenetic modification, and little information about it is available. In this study, an RNAi vector was constructed and transferred successfully into wild-type tomato for further research on the detailed functions of the histone deacetylation gene SlHDT1. The expression level of PSY1 was upregulated, and the transcription levels of LCY-B, LCY-E and CYC-B were downregulated, which was consistent with the increased accumulation of carotenoids. In addition, the expression levels of ethylene biosynthetic genes (ACS2, ACS4 and ACO1, ACO3), ripening-associated genes (RIN, E4, E8, PG, Pti4 and LOXB) and fruit cell wall metabolism genes (HEX, MAN, TBG4, XTH5 and XYL) were significantly upregulated further strengthening the results, including an increased ethylene content, advanced fruit ripening time and a shortened shelf life of tomato fruits. In addition, the increased total histone H3 acetylation level also provides evidence of a connection between epigenetic regulation by histone deacetylation and fruit development and ripening. Hence, SlHDT1 is a negative regulator and plays an essential role in regulating ethylene and carotenoid biosynthesis during fruit ripening through influences on the acetylation level.


Influence of LTB4 on CD4-, CD8- thymocytes. Evidence that LTB4 plus IL-2 generate CD8+ suppressor thymocytes involved in tolerance to self. Effect of LTB4 and IL-2 on double negative thymocytes.
Leukotriene B4 (LTB4) is produced by a large variety of cells involved in immune response and it has been demonstrated that this arachidonic acid metabolite acts as an immunomodulator. Because LTB4 and IL-2 both influence the physiology of immature cells we studied the effects of the leukotriene on double negative thymocytes. For that purpose C57 Bl/6 double negative thymocytes were treated by LTB4 plus IL-2 in the presence of either autologous or allogenic red blood cells (RBC). Then, preincubated CD4- CD8- thymocytes were cocultured with red blood cells stimulated fresh splenocytes. We observed that fresh splenocytes responding to autologous RBC were CD4+ cells and that the proliferative response of spleen lymphocytes driven by RBC was inhibited by preincubated double negative thymocytes. On the other hand a majority of double negative thymocytes overnight preincubated in vitro in the presence of both IL-2 and LTB4 give rise to CD8+ CD4- cells. Therefore we speculate that LTB4 plus IL-2 generate CD8+ suppressor thymocytes among double negative thymocytes and that these suppressive T cells are involved in tolerance to self.


Characterization of patients in a medical endocrine-based center for male sexual dysfunction.
To characterize the patient population in a multidisciplinary sexual dysfunction clinic whose focal person is an endocrinologist and to summarize the initial manifestations, the demographics of the study group, and their associated medical conditions. We undertook a retrospective analysis of the medical records of all new consultations in a center for sexual function during a recent 2-year period. During the period from July 1995 to July 1997, 1,050 men were seen in new consultations for sexual dysfunction at our medical facility, and complete medical records could be retrieved for 990 of them. Of the overall study group of 990 men, most (93.2%) had erectile dysfunction (versus libido or ejaculatory problems), but combinations of problems were common. Most men had organic causes of their sexual dysfunction that correlated with increasing age; however, their dysfunction was more often the result of chronic medical conditions than of advancing age itself. Most men were married (72.1%) and in long-term relationships (mean duration, more than 20 years). Hypogonadism was the most common medical condition (36.3%), a finding that reflected an endocrine referral bias. Testosterone treatment alone corrected the complaints in a minority of patients. Hypertension was a more common diagnosis than diabetes (35.8% versus 23.1%), and pituitary tumors were rare. Successful outcomes were achieved in about two-thirds of men having a strong organic cause of sexual dysfunction, but treatments were less successful when pronounced psychologic factors were present. The patient dropout rate was substantial and was similar in each of the four 6-month quarters--an indication that even as newer therapies became available, dissatisfaction was still evident. Many patients have more than one manifestation of sexual dysfunction, which may have to be addressed separately. In a sexual dysfunction clinic managed by an endocrinologist, referral bias may direct more patients with hypogonadism and fewer patients who have had transurethral retropubic prostatectomy or a radical prostatectomy. Treatment of hypogonadism corrects sexual dysfunction in only a few men, and only when other medical problems are not present. Although the percentage of men with diabetes would be expected to be high in this study, the number of patients with hypertension was higher. A considerable dropout rate during evaluation and treatment persisted throughout this study.


Central retinal artery occlusion following cardiac catheterization.
We describe a 66-year-old Japanese man in whom central retinal artery occlusion followed cardiac catheterization. After the procedure, blurred vision was noted in the right eye, and ophthalmological examination revealed an occlusion. Central retinal artery occlusion is a very rare but serious complication of cardiac catheterization. We should anticipate this potential risk to ensure prompt detection and treatment.


Paenibacillus humicus sp. nov., isolated from poultry litter compost.
Two bacterial strains, PC-142 and PC-147(T), isolated from poultry litter compost, were characterized with respect to their phenetic and phylogenetic characteristics. The isolates were endospore-forming rods that were reddish in colour after Gram staining. They were catalase- and oxidase-positive, were able to degrade starch and gelatin and grew at 15-40 degrees C and pH 5.5-10.0. The predominant fatty acids were anteiso-C(15 : 0), iso-C(15 : 0) and iso-C(16 : 0), the major respiratory quinone was menaquinone MK-7, the cell-wall peptidoglycan was of the A1gamma type and the G+C content of the DNA was 58 mol%. The 16S rRNA gene sequence analysis and phenetic characterization indicated that these organisms belong to the genus Paenibacillus, with Paenibacillus pasadenensis SAFN-007(T) as the closest phylogenetic neighbour (97.5 %). Strains PC-142, PC-147(T) and P. pasadenensis SAFN-007(T) represent a novel lineage within the genus Paenibacillus, characterized by a high DNA G+C content (58-63 mol%). The low levels of 16S rRNA gene sequence similarity with respect to other taxa with validly published names and the identification of distinctive phenetic features in the two isolates indicate that strains PC-142 and PC-147(T) represent a novel species of the genus Paenibacillus, for which the name Paenibacillus humicus sp. nov. is proposed. The type strain is PC-147(T) (=DSM 18784(T) =NBRC 102415(T) =LMG 23886(T)).


Stability of the heme Fe-N-terminal amino group coordination bond in denatured cytochrome c.
In the denatured states of Hydrogenobacter thermophilus cytochrome c(552) (HT) and Pseudomonas aeruginosa cytochrome c(551) (PA), and their mutants, the N-terminal amino group of the polypeptide chain is coordinated to heme Fe in place of the axial Met, the His-N(term) form being formed. The coordination of the N-terminal amino group to heme Fe leads to loop formation by the N-terminal stretch preceding the first Cys residue bound to the heme, and the N-terminal stretches of HT and PA are different from each other in terms of both the sequence and the number of constituent amino acid residues. The His-N(term) form was shown to be rather stable, and hence it can influence the stability of the denatured state. We have investigated the heme Fe coordination structures and stabilities of the His-N(term) forms emerging upon guanidine hydrochloric acid-induced unfolding of the oxidized forms of the proteins. The Fe-N(term) coordination bond in the His-N(term) form with a 9-residue N-terminal stretch of HT proteins was found to be tilted to some extent away from the heme normal, as reflected by the great heme methyl proton shift spread. On the other hand, the small heme methyl proton shift spread of the His-N(term) form with an 11-residue stretch of PA proteins indicated that its Fe-N(term) bond is nearly parallel with the heme normal. The stability of the His-N(term) form was found to be affected by the structural properties of the N-terminal stretch, such as its length and the N-terminal residue. With a given N-terminal residue, the stability of the His-N(term) form is higher for a 9-residue N-terminal stretch than an 11-residue one. In addition, with a given length of the N-terminal stretch, the His-N(term) form with an N-terminal Glu is stabilized by a few kJ mol(-1) relative to that with an N-terminal Asn. These results provide a novel insight into the stabilizing interactions in the denatured cyts c that will facilitate elucidation of the folding/unfolding mechanisms of the proteins.


Migration of retained pacemaker electrodes.
Two cases of migration of retained pacemaker electrodes are described. The first presented as an unusual cause of deep vein thrombosis while the second was asymptomatic and detected by routine chest x-ray. Both made a good recovery, the first with surgery and the second with the fragment left in situ. A review of the world literature revealed only 13 other such cases. Of the total of 15 cases four are known to have died. In these patients no relationship was found between morbidity and the site of migration or associated infection and/or thrombosis. However surgical treatment appeared to be associated with a better prognosis.


A game-theoretic framework for landmark-based image segmentation.
A novel game-theoretic framework for landmark-based image segmentation is presented. Landmark detection is formulated as a game, in which landmarks are players, landmark candidate points are strategies, and likelihoods that candidate points represent landmarks are payoffs, determined according to the similarity of image intensities and spatial relationships between the candidate points in the target image and their corresponding landmarks in images from the training set. The solution of the formulated game-theoretic problem is the equilibrium of candidate points that represent landmarks in the target image and is obtained by a novel iterative scheme that solves the segmentation problem in polynomial time. The object boundaries are finally extracted by applying dynamic programming to the optimal path searching problem between the obtained adjacent landmarks. The performance of the proposed framework was evaluated for segmentation of lung fields from chest radiographs and heart ventricles from cardiac magnetic resonance cross sections. The comparison to other landmark-based segmentation techniques shows that the results obtained by the proposed game-theoretic framework are highly accurate and precise in terms of mean boundary distance and area overlap. Moreover, the framework overcomes several shortcomings of the existing techniques, such as sensitivity to initialization and convergence to local optima.


[Cannabis poisoning after eating salad].
We describe 4 patients who suffered gastrointestinal disorders and psychological effects after eating salad prepared with hemp seed oil. The concentration of tetrahydrocannabinol (THC) in this oil far exceeded the recommended tolerance dose. Our observations prompted the Swiss Federal Office of Public Health to publish warnings in the press concerning consumption of this oil. We describe the symptoms of orally ingested THC and point out unresolved problems connected with food containing hemp.


Epac1 Blocks NLRP3 Inflammasome to Reduce IL-1β in Retinal Endothelial Cells and Mouse Retinal Vasculature.
Inflammation is an important component of diabetic retinal damage. We previously reported that a novel β-adrenergic receptor agonist, Compound 49b, reduced Toll-like receptor 4 (TLR4) signaling in retinal endothelial cells (REC) grown in high glucose. Others reported that TLR4 activates high-mobility group box 1 (HMGB1), which has been associated with the NOD-like receptor 3 (NLRP3) inflammasome. Thus, we hypothesized that Epac1, a downstream mediator of β-adrenergic receptors, would block TLR4/HMGB1-mediated stimulation of the NLRP3 inflammasome, leading to reduced cleavage of caspase-1 and interleukin-1 beta (IL-1β). We generated vascular specific conditional knockout mice for Epac1 and used REC grown in normal and high glucose treated with an Epac1 agonist and/or NLRP3 siRNA. Protein analyses were done for Epac1, TLR4, HMGB1, NLRP3, cleaved caspase-1, and IL-1β. Loss of Epac1 in the mouse retinal vasculature significantly increased all of the inflammatory proteins. Epac1 effectively reduced high glucose-induced increases in TLR4, HMGB1, cleaved caspase-1, and IL-1β in REC. Taken together, the data suggest that Epac1 reduces formation of the NLRP3 inflammasome to reduce inflammatory responses in the retinal vasculature.


Is There a Critical Period for Amblyopia Therapy? Results of a Study on Older Anisometropic Amblyopes.
Amblyopia, a common cause of low vision, is rarely treated in adults. Improvement in vision has been seen beyond the critical period at times. Hence, this study was taken up to study the effect of minimal occlusion therapy (2-4 hours/day) in anisometropic amblyopic patients in the age group of 12-30 years. The study is a prospective, randomized case series of anisometropic amblyopia patients aged 12-30 years who reported in the outpatient department of Hakeem Abdul Hameed Centenary Hospital, New Delhi, from December 2011 to November 2013. Thorough ocular examination and cycloplegic refraction was done to rule out other ocular disease. Anisometropic Amblyopia was diagnosed only after four weeks of spectacle wear. The selected patients were then advised occlusion therapy of 2-4 hours per day of better eye with stress on near visual task. Videogames, computers, mobile phone gaming and colouring in especially designed patterns were used as vision training aids. The outcome measure selected was best corrected visual acuity (BCVA) achieved that remained stable for three consecutive months of occlusion. Sixty one patients of anisometropic amblyopia were included in the study (32 males and 29 females) aged 12-30 years (mean age 17 years). Mean BCVA at the start of treatment was 20/125 (0.8 log MAR units) and 20/32 (0.2 log MAR units) at the end of the treatment. Thirty three patients (54%) out of 61 had BCVA of 20/20, while 58 patients (95%) had ≥ 20/40 BCVA, 01(1.6%) had 20/50 and 02 (3.27%) had 20/80 BCVA at the end of therapy. The results were statistically significant (p- value <0.0001) with a 95% confidence interval. This study clearly proves that there is no critical period for the treatment in older (12-30 years) anisometropic amblyope. Even 2-4 hours per day of occlusion of better eye with vision training thorough near visual task of amblyopic eye is effective. However, counseling and patient compliance is important for successful outcome of therapy.


The Kinetic Chain Has a Brain: Could Adding Cognitive Demands in Lower Limb Injury Prevention Programs Improve Outcomes?
SYNOPSIS: The most effective lower limb injury prevention programs include strength training, balance exercises, and instructions on how to land safely from a jump or hop. Yet, the programs are not 100% effective-lower extremity noncontact injuries continue to be a significant problem. We suggest that adding cognitive training to motor tasks that currently comprise current lower limb injury prevention programs might help clinicians, athletes, and coaches continue to make inroads into preventing knee injuries. We ground our hypotheses in robust findings from cognitive neuroscience and rehabilitation, suggesting that when task demands exceed the attentional capacity of an individual, the risk for noncontact lower extremity injuries increases. In this editorial, we explain the concepts of attentional capacity and attentional demands, and the interplay of the two in sport, to justify including cognitive tasks to injury prevention programs to improve outcomes. J Orthop Sports Phys Ther 2023;53(4):1-3. doi:10.2519/jospt.2023.11403.


Three-Dimensionally Hierarchical Graphene Based Aerogel Encapsulated Sulfur as Cathode for Lithium/Sulfur Batteries.
A simple and effective method was developed to obtain the electrode for lithium/sulfur (Li/S) batteries with high specific capacity and cycling durability via adopting an interconnected sulfur/activated carbon/graphene (reduced graphene oxide) aerogel (S/AC/GA) cathode architecture. The AC/GA composite with a well-defined interconnected conductive network was prepared by a reduction-induced self-assembly process, which allows for obtaining compact and porous structures. During this process, reduced graphene oxide (RGO) was formed, and due to the presence of oxygen-containing functional groups on its surface, it not only improves the electronic conductivity of the cathode but also effectively inhibits the polysulfides dissolution and shuttle. The introduced activated carbon allowed for lateral and vertical connection between individual graphene sheets, completing the formation of a stable three-dimensionally (3D) interconnected graphene framework. Moreover, a high specific surface area and 3D interconnected porous structure efficiently hosts a higher amount of active sulfur material, about 65 wt %. The designed S/AC/GA composite electrodes deliver an initial capacity of 1159 mAh g-1 at 0.1 C and can retain a capacity of 765 mAh g-1 after 100 cycles in potential range from 1 V to 3 V.


CD3xCD19 DART molecule treatment induces non-apoptotic killing and is efficient against high-risk chemotherapy and venetoclax-resistant chronic lymphocytic leukemia cells.
Bispecific antibodies are promising new therapeutics in B cell malignancies. Whether they lead to potent T cell activation despite described T cell dysfunction in chronic lymphocytic leukemia (CLL), and are able to effectively target high-risk or venetoclax-resistant samples, is currently unknown. CD19+ cell lines or primary (high-risk) CLL were cocultured in vitro with healthy donor (HD) or CLL-derived T cells in the presence of a CD3xCD19 dual affinity retargeting molecule (CD3xCD19 DART). Cell cytotoxicity, T cell activation, proliferation and effector molecule production were analyzed using flow cytometry. Here, we report that a bispecific CD3xCD19 DART mediates efficient killing by HD T cells of CD19+ cell-lines and primary CLL cells, regardless of immunoglobulin heavy chain variable region (IGHV) mutational status TP53 status or chemotherapy, ibrutinib or venetoclax sensitivity. Whereas TCR stimulation of CLL-derived T cells resulted in dysfunctional T cell activation and proliferation, treatment with CD3xCD19 DART led to a similar activation profile in CLL-derived and HD-derived T cells. Consistently, co-culture of CLL derived T cells with JeKo-1 or CLL cells in the presence of CD3xCD19 DART resulted in significant cytotoxicity by both CD4+ and CD8+ T cells. On stimulation of CLL cells with CD40L, CLL cells become resistant to the specific inhibitor of anti-apoptotic Bcl-2 protein venetoclax, due to upregulation of Bcl-2 family members such as Bcl-XL. Nevertheless, CD40L stimulated CLL cells were as efficiently lysed on CD3xCD19 DART treatment as unstimulated CLL cells. Further examination of the mechanism of CD3xCD19 DART mediated killing showed that lysis was dependent on granules, but was independent of BAX/BAK or caspase activity, indicating non-apoptotic cell death. These data show that CD3xCD19 DART in CLL leads to robust T cell activation and lysis of high-risk venetoclax resistant CLL cells through a non-apoptotic mechanism.


Normal pregnancy and delivery following total hip joint replacement.
Total joint replacement procedures should be restricted to older individuals or persons with limited physical activities or life expectancy. However, on occasion a total joint replacement may be the only means to avoid serious disability in a young, otherwise healthy individual. This report of a 19-year-old woman who underwent a total hip joint replacement following unsuccessful treatment of a severely comminuted intracapsular hip fracture. Subsequent to the total hip joint replacement the patient experienced a normal pregnancy and delivery.


Reactivity of vitamin A derivatives and analogues with vitamin A antibodies.
Vitamin A antibodies were obtained using retinoic acid conjugated to human serum albumin as an immunogen. The following constraints governed the reactivity of vitamin A analogues with such an anti-serum. The stereochemistry of the side chain is relatively unimportant, and 9- and 13-cis retinal react almost as well as all-trans retinal. The nature of the ring is important; all of the compounds that react readily carry a beta-ionic ring; all of the compounds bearing an aromatic ring react poorly; the two compounds that display intermediate reactivity have non-aromatic 6- and 5-membered rings, respectively.


NAFLD Prevalence in a Young Cadaveric Organ Donor Population.
Liver transplantation is a critical survival point for patients with end stage liver diseases. It can dramatically increase patients' survival if the donor liver is intact. One aspect of liver health is absence of steatosis. Nonalcoholic Steato Hepatitis (NASH) and Nonalcoholic Fatty Liver Disease (NAFLD) are increasing among young adults and patients living with chronic liver diseases. In this study, we determined the prevalence of NALFD in livers of brain-dead donors in Imam-Khomeini hospital Complex, Tehran, Iran. We assumed that the calculated prevalence would represent NAFLD prevalence in Iranian population in the age range of 20-60 years. All eligible brain dead liver transplant donors were enrolled in the survey from March 21, 2011 to March 21, 2013 in Imam-Khomeini hospital Complex. Eligible participants were donors aged 20 to 60 years without any obvious history of liver disease. Liver needle biopsy was performed at the end of the transplant operation; time zero biopsy. We calculated the prevalence of NAFLD among brain-dead donors. Moreover, the frequency of NASH was calculated based on the NAS (NAFLD Activity Score). Among 116 cases, two were diagnosed as probable NASH. There was a significant association between NAFLD and male gender (P = 0.04). Moreover, we found a higher steatosis level in male gender. There was a significant association between NAFLD and BMI (P = 0.05). Those with BMI more than 27 had severe steatosis. Our comprehensive literature review showed that our study was the first investigation in Iran and the region, which determined the prevalence of NAFLD based on tissue diagnosis. We believe that the prevalence of NAFLD/NASH in our donors can represent the overall prevalence in this age group in Iran.


The interaction between parenting and children's cortisol reactivity at age 3 predicts increases in children's internalizing and externalizing symptoms at age 6.
Little is known about the role of stress reactivity in the emergence of psychopathology across early childhood. In this longitudinal study, we tested the hypothesis that child cortisol reactivity at age 3 moderates associations between early parenting and children's internalizing and externalizing symptoms from age 3 to age 6. One hundred and sixty children were assessed at age 3, and 135 children were reassessed at age 6. At age 3, we exposed children to stress-inducing laboratory tasks, during which we obtained four salivary cortisol samples, and parental hostility was assessed using an observational parent-child interaction task. At ages 3 and 6, child psychiatric symptoms were assessed using a clinical interview with parents. The results indicated that the combination of high child cortisol reactivity and high observed parental hostility at age 3 was associated with greater concurrent externalizing symptoms at age 3 and predicted increases in internalizing and externalizing symptoms from age 3 to age 6. Findings highlight that increased stress reactivity, within the context of hostile parenting, plays a role in the emergence of psychopathology from preschool to school entry.


Trace metal distribution in sediments of the Pearl River Estuary and the surrounding coastal area, South China.
Surface sediments and sediment cores collected at the Pearl River Estuary (PRE) and its surrounding coastal area were analysed for total metal concentrations, chemical partitioning, and Pb isotopic compositions. The distribution of Cu, Cr, Pb, and Zn demonstrated a typical diffusion pattern from the land to the direction of the sea. Two hotspots of trace metal contamination were located at the mixed zone between freshwater and marine waters. The enrichment of metals in the sediments could be attributed to the deposition of the dissolved and particulate trace metals in the water column at the estuarine area. The similar Pb isotopic signatures of the sediments at the PRE and its surrounding coastal area offered strong evidence that the PRE was a major source of trace metals to the adjacent coastal area. Slightly lower (206)Pb/(207)Pb ratios in the coastal sediments may indicate other inputs of Pb in addition to the PRE sources, including the inputs from Hong Kong and other parts of the region.


Determining Tpot in heterogeneous systems: a new approach illustrated with multicell spheroids.
Like many tumors, multicell spheroids from Chinese hamster V79-171b fibroblasts display karyotypic heterogeneity as they enlarge. This creates significant problems for analysis of univariate DNA content histograms of cells from spheroids, and even for bivariate bromodeoxyuridine (BrdUrd)/DNA flow histograms. While attempting to routinely measure spheroid cell kinetics with the latter approach, a simple alternative that overcomes many of the inherent problems emerged. The exit rate of BrdUrd-labelled cells from the S-phase compartment(s), determined using standard DNA analysis software, is used to define the duration of S-phase and ultimately the potential doubling time of the clonogenic cell population. This approach appears to offer several advantages over the conventional "relative movement" technique for heterogeneous samples, particularly since the subjective distinction between labelled/divided tetraploid G1 cells vs. labelled/undivided diploid G2 is no longer required. Further, the technique avoids some potential artifacts that might be expected for heterogeneous tumors where cell subpopulations proliferate with quite different cell kinetics.


Small-molecule inhibitors of JC polyomavirus infection.
The JC polyomavirus (JCPyV) infects approximately 50% of the human population. In healthy individuals, the infection remains dormant and asymptomatic, but in immuno-suppressed patients, it can cause progressive multifocal leukoencephalopathy (PML), a potentially fatal demyelinating disease. Currently, there are no drugs against JCPyV infection nor for the treatment of PML. Here, we report the development of small-molecule inhibitors of JCPyV that target the initial interaction between the virus and host cell and thereby block viral entry. Utilizing a combination of computational and NMR-based screening techniques, we target the LSTc tetrasaccharide binding site within the VP1 pentameric coat protein of JCPyV. Four of the compounds from the screen effectively block viral infection in our in vitro assays using SVG-A cells. For the most potent compound, we used saturation transfer difference NMR to determine the mode of binding to purified pentamers of JCPyV VP1. Collectively, these results demonstrate the viability of this class of compounds for eventual development of JCPyV-antiviral therapeutics.


Implication of KDM6A in bladder cancer.
Background: Bladder cancer is a common urogenital malignancy characterized by frequent genetic alterations. Histone demethylase gene KDM6A is commonly mutated in bladder cancer. Aim: To review the characteristics of KDM6A and its mutation consequences, and to introduce a potential KDM6A-targeted treatment. Methods: We conducted a comprehensive literature search using two electronic databases, MEDLINE and Cochrane Library, to retrieve topic-related articles from July 2013 to July 2022 using keywords 'KDM6A', 'bladder cancer', 'UTX', 'treatment' and 'mutation'. Five reviewers independently screened literature search results and abstracted data from included studies. Descriptive analysis was conducted and 30 articles were retained. Main Results: A total of 30 articles were retrieved. Experimental and clinical data were collected and grouped by theme. Therapeutic strategies are depicted and organized by tables for a better understanding. Conclusion: This review demonstrates that KDM6A has crucial implications in bladder cancer pathogenesis and treatment.


Artificial urinary sphincter, Part I: Overview.
Urinary incontinence has a tremendous impact on an individual's quality of life and self-esteem. A number of patients will fail both conservative medical as well as conservative surgical treatments in their pursuit to regain urinary control. The surgical implantation of an artificial urinary sphincter (AUS) is a definitive surgical option to reestablish continence. However, there are many challenges that may arise as a patient progresses through the rigorous preparation, surgical procedure, and recovery process. Understanding the history, various indications, and risks of AUS surgery will aid in counseling patients considering AUS.


Effect of Euterpe oleracea Mart. (Açaí) Oil on Dyslipidemia Caused by Cocos nucifera L. Saturated Fat in Wistar Rats.
Dyslipidemia is caused by disturbances in lipid metabolism that lead to chronic elevations of serum lipids, especially low-density lipoprotein (LDL)-cholesterol and triglycerides, increasing the risk of metabolic syndrome, obesity, diabetes, atherogenic processes, and cardiovascular diseases. The oil from the fruits of Euterpe oleracea (OFEO) is rich in unsaturated fatty acids with potential for treating alterations in lipid metabolism. In this study, we aimed to investigate the effect of OFEO on hyperlipidemia induced by Cocos nucifera L. saturated fat (GSC) in Wistar rats. Chromatographic profile showed that unsaturated fatty acids account for 66.08% in OFEO, predominately oleic acid (54.30%), and saturated fatty acids (palmitic acid 31.6%) account for 33.92%. GSC-induced dyslipidemia resulted in an increase in total cholesterol, LDL-cholesterol, triglycerides, glucose, and liver and abdominal fat, as well as atherogenic processes in the thoracic aorta. OFEO treatment did not reduce hypertriglyceridemia, but did reduce total cholesterol and LDL-cholesterol, thus contributing to the antiatherogenic action of OFEO. OFEO treatment inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats, as well as those who were treated with simvastatin. The results obtained suggest that OFEO has an antiatherogenic effect in a rat model of dyslipidemia.


Endodermal Sinus Tumor of the Neck: A Rare Presentation.
Germ cell tumors usually occur in the gonads. Extragonadal germ cell tumors (EGCTs) are uncommon, and the head and neck region is a rare primary location. In this region, endodermal sinus tumors are relatively uncommon; they are typically recorded alongside teratomas and infrequently by themselves. When an endodermal sinus tumor arises in the neck, it can present with unique clinical and radiographic features and can be challenging to diagnose and manage. We report the peculiar case of a 25-year-old young adult who was suffering from a painful left-sided neck swelling for a year. Fine needle aspiration cytology (FNAC) of neck mass was performed and the cytomorphological features were suggestive of germ cell tumor. After the diagnosis, the patient received chemotherapy and was posted for wide local excision of the tumor. On microscopic examination, the tumor mass showed histopathological features suggestive of an endodermal sinus tumor.


Bimodal intravascular volumetric imaging combining OCT and MPI.
Intravascular optical coherence tomography (IVOCT) is a catheter-based image modality allowing for high-resolution imaging of vessels. It is based on a fast sequential acquisition of A-scans with an axial spatial resolution in the range of 5-10 μm, that is, one order of magnitude higher than in conventional methods like intravascular ultrasound or computed tomography angiography. However, position and orientation of the catheter in patient coordinates cannot be obtained from the IVOCT measurements alone. Hence, the pose of the catheter needs to be established to correctly reconstruct the three-dimensional vessel shape. Magnetic particle imaging (MPI) is a three-dimensional tomographic, tracer-based, and radiation-free image modality providing high temporal resolution with unlimited penetration depth. Volumetric MPI images are angiographic and hence suitable to complement IVOCT as a comodality. We study simultaneous bimodal IVOCT MPI imaging with the goal of estimating the IVOCT pullback path based on the 3D MPI data. We present a setup to study and evaluate simultaneous IVOCT and MPI image acquisition of differently shaped vessel phantoms. First, the influence of the MPI tracer concentration on the optical properties required for IVOCT is analyzed. Second, using a concentration allowing for simultaneous imaging, IVOCT and MPI image data are acquired sequentially and simultaneously. Third, the luminal centerline is established from the MPI image volumes and used to estimate the catheter pullback trajectory for IVOCT image reconstruction. The image volumes are compared to the known shape of the phantoms. We were able to identify a suitable MPI tracer concentration of 2.5 mmol/L with negligible influence on the IVOCT signal. The pullback trajectory estimated from MPI agrees well with the centerline of the phantoms. Its mean absolute error ranges from 0.27 to 0.28 mm and from 0.25 mm to 0.28 mm for sequential and simultaneous measurements, respectively. Likewise, reconstructing the shape of the vessel phantoms works well with mean absolute errors for the diameter ranging from 0.11 to 0.21 mm and from 0.06 to 0.14 mm for sequential and simultaneous measurements, respectively. Magnetic particle imaging can be used in combination with IVOCT to estimate the catheter trajectory and the vessel shape with high precision and without ionizing radiation.


Transurethral resection of prostrate and suprapubic ballistic vesicolithotrity for benign prostatic hyperplasia with vesical calculi.
Bladder calculi associated with benign prostatic hyperplasia are fairly common, and a popular treatment is transurethral resection of the prostate (TURP) with endoscopic lithotripsy as a combined procedure. We have been routinely using a Reuter's suprapubic trocar and cannula for continuous irrigation during TURP for medium-size and large glands. Rather than performing the vesicolithotripsy per urethra, we have found it easier and faster to use the suprapubic route, especially because the suprapubic tract was already partly made by the Reuter's trocar and half sheath. We describe the technique in detail and explain why we find it easier to extract the stone by the suprapubic rather than the urethral route.


Elimination of Emergency Department Ambulance Divert during the COVID-19 Pandemic Was Not Associated with an Increase in the Average Number of Ambulance Arrivals per Day.
During the COVID-19 pandemic, ambulance divert in our EMS system reached critical levels. We hypothesized that eliminating ambulance divert would not be associated with an increase in the average number of daily ambulance arrivals. Our study objective was to quantify the EMS and emergency department (ED) effects of eliminating ambulance divert during the COVID-19 pandemic. Regional hospital divert data were obtained for the 10-county Twin Cities metro from MNTrac, a state-supported online system designed to allow hospitals to indicate their divert status to EMS. ED metrics are reported for a single Level I trauma center and were obtained by a deidentified data pull from our electronic medical record covering the 12 months prior to the elimination of divert (2021) and the 12 months after divert elimination (2022). The decision to eliminate divert occurred in November 2021, based on data available through October, with an implementation date of January 2022. The primary study outcome was to quantify the effect of the elimination of divert on the number of ambulances arriving per day at the study hospital. Regional utilization of ambulance divert increased steadily by 859% from January to October 2021 when 355 individual divert events occurred, totaling 809 h (34 days). There was no significant difference in the number of ambulances that arrived to the study hospital in 2021 (30,774) vs 2022 (30,421) p = 0.15. As compared to 2021, in 2022 there was no significant increase in mean ambulance arrivals per day (84/day vs 83/day, p = 0.08), time to room Emergency Severity Index level 2 (ESI) patients (28 min vs 28 min, p = 0.90), or time to obtain emergent head CT in acute "code stroke" patients (12 min vs 12 min, p = 0.15). Ambulance turnaround interval in the ED did not appreciably increase (16 min vs 17 min, p = 0.15). Elimination of ambulance divert was not associated with increases in the number of mean daily ambulance arrivals or EMS turnaround intervals, delays in ESI 2 patients being placed in beds, or prolonged time to head CT in stroke code patients.


How good are my data?: Information quality assessment methodology.
Quality assurance techniques used in software development and hardware maintenance/reliability help ensure that data in a computerized information management system are maintained well. However, information workers may not know the quality of data resident in their information systems. Knowledge of the quality of information and data in an enterprise provides managers with important facts for managing and improving the processes that impact information quality. This paper presents quality assessment methodology to assist information workers in planning and implementing an effective assessment of their information data and quality. The areas covered include: identifying appropriate information quality indicators; developing assessment procedures; conducting information quality assessments; reporting information assessment results; tracking improvements in information quality.


Dynamic light scattering microscopy sensing mitochondria dynamics for label-free detection of triple-negative breast cancer enhanced by deep learning.
We established a deep learning-based dynamic light scattering (DLS) microscopy sensing mitochondria dynamic for label-free identification of triple-negative breast cancer (TNBC) cells. The capacity of DLS microscopy to detect the intracellular motility of subcellular scatters was verified with the analysis of the autocorrelation function. We also conducted an in-depth examination of the impact of mitochondrial dynamics on DLS within TNBC cells, employing confocal fluorescent imaging to visualize the morphology of the mitochondria. Furthermore, we applied the DLS microscopy incorporating the two-stream deep learning method to differentiate the TNBC subtype and HER2 positive breast cancer subtype, with the classification accuracy achieving 0.89.


Surgical management of hereditary spherocytosis Current strategies.
Hereditary spherocytosis is a benign hematologic disease, which needs surgical treatment when medical therapy fails. Currently, the surgical strategies consist mainly in total or partial splenectomy, which can be performed either in open or in laparoscopic fashion. In this study, we analyzed our series of splenectomies for hereditary spherocytosis and we discuss about the surgical management, reviewing the Literature. Twenty-seven patients (mean age 16.5 years, range 8 - 30 years) affected by hereditary spherocytosis were retrospectively evaluated. Indication to surgery was based on hemolysis severity. Thirteen patients were submitted to laparoscopic splenectomy and 14 to open splenectomy, after preventive specific vaccinations. Cholecystectomy for associated cholelithiasis was performed during the same operation in 4 laparoscopic patients and in 6 open patients. Main reasons for performing splenectomy were anemia unresponsive to iron supplementation in 7 patients (42%), splenomegaly in 6 patients (37%), and jaundice in 4 cases (21%). All the patients had a severe disease with hemoglobin level below 80 g/L, median reticulocytes count 6,5%, median value of indirect bilirubin concentration 2,0 mg/dL. Indications to splenectomy were increased need for red cell transfusions in 11 patients (66%) and symptoms related to cholelithiasis in 6 patients (34%). A post-operative early complication was observed after open splenectomy, consisting in a pancreatic fistula, which was treated conservatively. No post-operative complications were observed after laparoscopic splenectomy. Neither intra-operative complications nor conversions to open surgery were recorded during the laparoscopic approach. In a long-term follow- up, no infective complications were recorded. According to our results, total splenectomy is associated with good results and few complications. In our opinion, it remains the best therapeutic option in selected adult patients non-responder to the medical treatment. Hereditary spherocytosis, Laparoscopic splenectomy, Partial splenectomy.


Locally reinforced polymer-based composites for elastic electronics.
A promising approach to fabricating elastic electronic systems involves processing thin film circuits directly on the elastic substrate by standard photolithography. Thin film devices are generally placed onto stiffer islands on the substrate surface to protect devices from excessive strain while still achieving a globally highly deformable system. Here we report a new method to achieve island architectures by locally reinforcing polymeric substrates at the macro- and microscale using magnetically responsive anisotropic microparticles. We demonstrate that the resulting particle-reinforced elastic substrates can be made smooth enough for the patterning and successful operation of thin film transistors with transfer characteristics comparable to state-of-the-art devices.


Water Bridges Substitute for Defects in Amine-Functionalized UiO-66, Boosting CO2 Adsorption.
The binary adsorption of CO2 and water on an amine-functionalized UiO-66 metal-organic framework (MOF) was studied experimentally and computationally. Grand canonical Monte Carlo simulations were used to investigate three additional UiO-66 MOFs with different functionalized linkers. Each MOF was studied in a defect-free form as well as two additional forms with precise linker defects. Binary adsorption isotherms are presented for CO2 at specific water loadings. While water loading in defect-free MOFs reduces the CO2 uptake, the defects slightly boost the CO2 uptake at low water loadings. It was found that water bridges form between the metal oxide cores, replacing the missing linkers. Effectively, this creates smaller pores that are more welcoming of CO2 adsorption. Experimental measurement of the binary isotherms for UiO-66-NH2 shows a behavior that is consistent with this enhancement.


A new activating role for CO in cardiac mitochondrial biogenesis.
To investigate a possible new physiological role of carbon monoxide (CO), an endogenous gas involved in cell signaling and cytotoxicity, we tested the hypothesis that the mitochondrial generation of reactive oxygen species by CO activates mitochondrial biogenesis in the heart. In mice, transient elevations of cellular CO by five- to 20-fold increased the copy number of cardiac mitochondrial DNA, the content of respiratory complex I-V and interfibrillar mitochondrial density within 24 hours. Mitochondrial biogenesis is activated by gene and protein expression of the nuclear respiratory factor 1 (NRF1) and NRF2, of peroxisome proliferator-activated receptor gamma co-activator-1alpha, and of mitochondrial transcription factor A (TFAM), which augmented the copy number of mitochondrial DNA (mtDNA). This is independent of nitric oxide synthase (NOS), as demonstrated by the identical responses in wild-type and endothelial NOS (eNOS)-deficient mice, and by the inhibition of inducible NOS (iNOS). In the heart and in isolated cardiomyocytes, CO activation involved both guanylate cyclase and the pro-survival kinase Akt/PKB. Akt activation was facilitated by mitochondrial binding of CO and by production of hydrogen peroxide (H(2)O(2)). Interference with Akt activity by blocking PI 3-kinase and by mitochondrial targeting of catalase to scavenge H(2)O(2) prevented binding of NRF1 to the Tfam promoter, thereby connecting mitochondrial H(2)O(2) to the pathway leading to mtDNA replication. The findings disclose mitochondrial CO and H(2)O(2) as new activating factors in cardiac mitochondrial biogenesis.


The Clinical Characteristics of 88 Patients with Total Anomalous Pulmonary Venous Connection and Risk Factors Associated with Early Postoperative Death.
This study aimed to analyze the outcomes and risk factors of early postoperative death (within 30 days after surgery) in a single-center after repair of total anomalous pulmonary venous connection (TAPVC). The clinical data of 88 children who had been diagnosed with TAPVC and underwent radical operation in the Shandong Provincial Hospital Affiliated with Shandong First Medical University (China) from January 2015 to July 2021 were retrospectively analyzed. All the patients were divided into the survival group (n = 81) and the death group (n = 7) for the analysis of preoperative and postoperative clinical data. The variables associated with early postoperative death were statistically analyzed to obtain the risk factors for early postoperative death of TAPVC. Of the 88 patients included in this study, 7 (7.95%) patients died early, including 4 supracardiac and 3 infracardiac cases. Recurrent pulmonary vein obstruction occurred in 2 patients after discharged from hospital, and both were intracardiac TAPVC. Delayed death occurred in 2 children, both of which were intracardiac TAPVC cases. According to univariate analysis, the risk factors statistically significantly associated with the early postoperative death included infracardiac type (P = 0.08), preoperative maximum pulmonary vein flow velocity (P = 0.031), preoperative mechanical ventilation (P = 0.043), preoperative maximum pulmonary artery pressure (P = 0.000), intraoperative cardiopulmonary bypass time (P = 0.003) and intraoperative aortic cross-clamp time (P = 0.000). Infracardiac type of TAPVC, preoperative maximum pulmonary vein flow velocity, preoperative mechanical ventilation, preoperative maximum pulmonary artery pressure, intraoperative cardiopulmonary bypass time and aortic cross-clamp time are the risk factors for early postoperative death.


Reactivity characterization of SiO2-coated nano zero-valent iron for iodoacetamide degradation: The effects of SiO2 thickness, and the roles of dehalogenation, hydrolysis and adsorption.
The effect of SiO2-layer thickness in SiO2-coated nano zero-valent iron (nZVI) particles on the reactivity characteristics of iodoacetamide (IAcAm) degradation was evaluated. SiO2-layer thicknesses ranging from 3.6 to 27.3 nm were obtained through varying tetraethyl orthosilicate dosages of 0.001-1 M. The crystallinity, surface chemical composition, and physicochemical properties were evaluated for their effects on synergetic degradation mechanisms, dehalogenation, hydrolysis, and adsorption. At a thickness of 3.6 nm, the SiO2 layer offered the highest observed pseudo-first-order rate (kobs) and higher rates of IAcAm degradation were maintained under pH fluctuations (pH 5-7) and aerobic conditions compared to pristine nZVI. At this SiO2-layer thickness (3.6 nm), the rate of iron oxide-layer formation was reduced and the migration of reactive iron species (Fe0 and Fe2+) for the dehalogenation and hydrolysis reactions was enabled. In a single-solute solution, IAcAm elimination was greater than bromoacetamide and chloroacetamide elimination due to the weak ionic I-C bond. In mixed solute conditions, the hydrophobicity of chloroacetamide played a more significant role in competitive degradation through greater adsorption. The proportion of dehalogenation relative to hydrolysis during IAcAm degradation by pristine nZVI and SiO2-coated nZVI was approximately 0.6:0.4. Iodoacetic acid and acetic acid were detected as intermediates in the degradation pathway of IAcAm by pristine nZVI. In contrast, the SiO2 layer on nZVI can accelerate the transformation of IAcAm to acetamide and iodoacetic acid. The electrolyte background of tap water exhibited a slight inhibitory effect on the degradation of IAcAm for both nZVI and SiO2-coated nZVI.


Occurrence, toxicity, and speciation analysis of arsenic in edible mushrooms.
Owing to the strong concentration and biotransformation of arsenic, the influence of some edible mushrooms on human health has attracted widespread attention. The toxicity of arsenic greatly depends on its species, so the speciation analysis of arsenic is of critical importance. The aim of the present review is to highlight recent advances in arsenic speciation analysis in edible mushrooms. We summarized the contents and distribution of arsenic species in some edible mushrooms, the methods of sample preparation, and the techniques for their identification and quantification. Stability of the arsenic species during sample pretreatment and storage is also briefly discussed.


Glomus intravagale tumour: aspects of management.
Glomus intravagale tumours are relatively rare tumours. A case is described and some aspects of its management are discussed with emphasis on the pre-operative investigation and diagnosis of this condition. Selective embolization of the lesion before operation is an important adjunct in treatment to reduce the vascularity of the tumour during operation. Intra-operative cardiac arrest due to traction of the vagus nerve was encountered. The methods to avoid this complication are discussed.


Aerobic exercise is an independent determinant of levels of inflammation and oxidative stress in middle-aged obese females.
The purpose of this study was to investigate the effects of a 4-week moderate-intensity aerobic exercise on changes of body composition and markers of inflammation and oxidative stress independent from weight loss in middle-aged obese females. Thity-five obese females were randomly assigned to either an exercise (EX, N=16) or control (CON, N=19) group. The EX performed moderate intensity aerobic exercise on the treadmill for 60 min at 55% of maximal oxygen consumption (VO2max) for 4 weeks (3 days/wk). Body composition measurement with dual-energy x-ray absorptiometry and blood collection were conducted before and after the 4-weeks intervention. Blood samples were used to measure levels of tumor necrosis factor-alpha (TNF-α), C-reactive protein, adiponectin, total antioxidant status (TAS), and 8-hydroxydeoxyguanosine. Four weeks of aerobic exercise intervention significantly increased VO2max in EX (P<0.001). EX also observed a decrease in TNF-α (P=0.033) and an increase in TAS (P=0.028) without changes in body weight and fat mass after 4 weeks of aerobic exercise training. No changes were observed in CON after the intervention. Results of this study indicate that moderate aerobic exercises may contribute, at least a part, to reductions of inflammation and oxidative stress independently from fat loss. Therefore, it may reduce risks of obesity-associated disorders in middle-aged obese females.


Hyperthyroidism: A Review.
Overt hyperthyroidism, defined as suppressed thyrotropin (previously thyroid-stimulating hormone) and high concentration of triiodothyronine (T3) and/or free thyroxine (FT4), affects approximately 0.2% to 1.4% of people worldwide. Subclinical hyperthyroidism, defined as low concentrations of thyrotropin and normal concentrations of T3 and FT4, affects approximately 0.7% to 1.4% of people worldwide. Untreated hyperthyroidism can cause cardiac arrhythmias, heart failure, osteoporosis, and adverse pregnancy outcomes. It may lead to unintentional weight loss and is associated with increased mortality. The most common cause of hyperthyroidism is Graves disease, with a global prevalence of 2% in women and 0.5% in men. Other causes of hyperthyroidism and thyrotoxicosis include toxic nodules and the thyrotoxic phase of thyroiditis. Common symptoms of thyrotoxicosis include anxiety, insomnia, palpitations, unintentional weight loss, diarrhea, and heat intolerance. Patients with Graves disease may have a diffusely enlarged thyroid gland, stare, or exophthalmos on examination. Patients with toxic nodules (ie, in which thyroid nodules develop autonomous function) may have symptoms from local compression of structures in the neck by the thyroid gland, such as dysphagia, orthopnea, or voice changes. Etiology can typically be established based on clinical presentation, thyroid function tests, and thyrotropin-receptor antibody status. Thyroid scintigraphy is recommended if thyroid nodules are present or the etiology is unclear. Thyrotoxicosis from thyroiditis may be observed if symptomatic or treated with supportive care. Treatment options for overt hyperthyroidism from autonomous thyroid nodules or Graves disease include antithyroid drugs, radioactive iodine ablation, and surgery. Treatment for subclinical hyperthyroidism is recommended for patients at highest risk of osteoporosis and cardiovascular disease, such as those older than 65 years or with persistent serum thyrotropin level less than 0.1 mIU/L. Hyperthyroidism affects 2.5% of adults worldwide and is associated with osteoporosis, heart disease, and increased mortality. First-line treatments are antithyroid drugs, thyroid surgery, and radioactive iodine treatment. Treatment choices should be individualized and patient centered.


Interface enhancement of glass fiber/vinyl ester composites with carbon nanotubes synthesized from ethanol flames.
Multi-walled carbon nanotubes synthesized from ethanol flames (F-MWCNTs) and nanotubes functionalized by n-hexadecylamine (H-MWCNTs) were applied to the preparation of glass fiber/vinyl ester composites by overcoating the original glass fiber. Scanning electron microscopy of the composites containing multi-walled carbon nanotubes (MWCNTs) showed better bonding between the glass fiber and the resin matrix which may be attributed to the existence of a flexible interphase introduced by the nanotubes. It was found that the bonding in the composites treated with H-MWCNTs was much stronger. Moreover, the dynamic mechanical properties and impact strengths of the resulting composites were investigated. The results revealed that treating glass fiber with MWCNTs effectively improved the mechanical properties of the composite materials. Furthermore, the dynamic properties showed that H-MWCNTs have become integral parts of the crosslinked polymer structure, rather than acting as separate fillers.


Critical role of human bisphosphoglycerate mutase Cys22 in the phosphatase activator-binding site.
The enzymatic activities catalyzed by bisphosphoglycerate mutase (BPGM, EC 18.104.22.168) have been shown to occur at a unique active site, with distinct binding sites for diphosphoglycerates and monophosphoglycerates. The physiological phosphatase activator (2-phosphoglycolate) binds to BPGM at an undetermined site. BPGM variants were constructed by site-directed mutagenesis of three amino acid residues in the active site to identify residues specifically involved in the binding of the monophosphoglycerates and 2-phosphoglycolate. Substitution of Cys22 by functionally conservative residues, Thr or Ser, caused a great decrease in 2-phosphoglycolate-stimulated phosphatase activity and in the Ka value of the activator, whereas it caused no change in other catalytic activities or in the Km values of 2,3-diphosphoglycerate (2,3-DPG) and glycerate 3-phosphate (3-PG, EC 184.108.40.206), indicating that Cys22 is specifically involved either directly or indirectly in 2-phosphoglycolate binding. Kinetic experiments showed that the Ka of the cofactor and the Km of 3-PG were affected by the substitution of Ser23 indicating that this residue is necessary for the fixation of both 3-PG and 2-phosphoglycolate. The R89K variant has previously been shown to have a modified Km value for monophosphoglycerates, however, its affinity for 2-phosphoglycolate is unaltered, suggesting that Arg89 is specifically involved in monophosphoglycerates binding. CD spectroscopic studies of substrates and cofactor binding showed that 2,3-DPG induced structural modifications of normal and mutated enzymes which could be due to protein phosphorylation. Addition of 2-phosphoglycolate to phosphorylated proteins with normal affinity for the cofactor produced spectra with the same characteristics as unphosphorylated species. In summary, monophosphoglycerates and 2-phosphoglycolate have partially distinct binding sites in human BPGM. The specific implication of the Cys22 residue in 2-phosphoglycolate binding is of great significance in the design of analogs of therapeutic benefit.


[Interleukin 13 and 18 serum concentration in children with cow milk hypersensitivity].
The aim of the study was the estimation of IL-13 and IL-18 concentration in serum of children with cow milk hypersensitivity and estimation of its usefulness in clinical practice. 30 children (14 boys, 16 girls) at the age 6-24 months, average 10.5 months. The children were divided into two groups. Group 1 included 18 children with elevated total IgE, group II, 12 children with normal IgE. In all children with suspected cow milk hypersensitivity, a diet based on strong milk hydrolysates or soy-milk formulas was advised. In 10 children IL-13 and IL-18 were examined three times: at the moment of diagnosis and after 3 and 6 months of dietary treatment. In 20 children IL-13 and IL-18 were estimated twice. Total IgE and specific IgE were performed by HYTER 288; IL-13 and IL-18 were measured by Bender Med System. The results were analysed statistically. in children with elevated IgE statistically significant higher IL-13 concentration was found and the mean IL-18 concentration in this group was lower but the difference was not statistically significant. We confirmed a positive correlation between elevated IgE and IL-13 concentration and a negative correlation between IgE and IL-18 before introducing the diet. In children with clinical improvement there was a nonsignificant decrease of IL-13 and increase of IL-18 concentration after diet introduction. In the group without clinical improvement, high IL-13 and low IL-18 concentration during diet were observed (p < 0,01). Highly positive correlation between serum IL-18 after 3 months of elimination diet and clinical improvement was observed. Highly negative correlation between mean IL-13 concentration after 6 months of diet and the clinical condition were observed. The correlation between IL-13 concentration and elevated IgE, indicates a connection of this cytokine with atopy. Negative correlation between IL-18 concentration and elevated IgE suggests a possibility of inhibiting IgE synthesis by this cytokine. A strong correlation between IL-18 concentration and clinical improvement after 3 months of elimination diet may imply a reduction of the allergic process. High negative correlation between IL-13 concentration and clinical improvement after 6 months of elimination diet may indicate a prolongation of the allergic process.


Application value of 3T ¹H-magnetic resonance spectroscopy in diagnosing breast tumors.
Assessment of breast lesions with magnetic resonance imaging (MRI) provides a means for lesion detection and diagnosis. Proton (hydrogen-1) magnetic resonance spectroscopy ((1)H-MRS) has been proposed as a useful diagnostic technique in providing metabolic information of suspicious breast lesions. To determine the clinical significance of in-vivo single voxel (1)H-MRS at 3T in the assessment of benign and malignant breast lesions in combination with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Twenty-four women with known breast abnormalities from conventional imaging (mammography, ultrasonography) underwent DCE-MRI at a 3T MR scanner and 26 breast lesions were detected. Breast lesions were assessed according BI-RADS classification. Single voxel (1)H-MRS was performed after gadolinium administration and choline peak was qualitatively evaluated. All lesions were confirmed histologically from the surgically excised specimens. Sensitivity, specificity, and accuracy of the (1)H-MRS, of the BI-RADS classification and of their combination (DCE-MRI + (1)H-MRS) were calculated. Fifteen out of 26 lesions proved to be malignant and 11 proved to be benign. In our study (1)H-MRS showed sensitivity 80%, specificity 81.8%, and accuracy 80.7%. DCE-MRI showed sensitivity 100%, specificity 63.6%, and accuracy 84.6%. The combination of DCE-MRI and (1)H-MRS provided higher accuracy (96.4%), as well as higher specificity 81.8% compared to BI-RADS classification. The combined use of (1)H-MRS and DCE-MRI found to have improved diagnostic performance in the assessment of equivocal breast lesions. (1)H-MRS can be used as a useful adjunct during lesion characterization in clinical routine in cases classified as BI-RADS 3 and 4.


Relation of macromolecular synthesis in streptococci to efficiency of transformation by markers of homospecific and heterospecific origin.
In previous studies with Streptococcus sanguis and S. pneumoniae as recipients and donors of transforming deoxyribonucleic acid (DNA), it was found that heating recipients just prior to exposure to DNA caused an increase in the number of transformants induced by heterospecific DNA relative to that induced by homospecific DNA. In the present studies, S. sanguis recipients were found to recover from this effect of heat (48 C, 15 min) when incubated at 37 C before exposure to DNA. Inhibitors of nucleic acid synthesis, such as rifampin, 5-fluorodeoxyuridine, actinomycin, and p-hydroxyphenylazo-uracil, but not inhibitors of protein synthesis, such as chloramphenicol and erythromycin, prevented recovery from the effect of heat. Inhibitors of nucleic acid synthesis caused changes in unheated cells similar to those observed with heat treatment; these changes included increased transformability by genetically hybrid DNA and by low-efficiency markers in homospecific DNA. The effect of a combination of heat and inhibitors on transformation by heterospecific DNA was greater than when single treatments were used. The most effective inhibitor used alone was rifampin: in treated recipient cells, the yield of transformants produced by a given amount of irreversibly bound heterospecific DNA was increased without a significant change in the yield of transformants produced by bound homospecific DNA. A cell being doubly transformed by homospecific and heterospecific DNA was enhanced specifically in its transformability with the latter as a consequence of rifampin treatment. Treatment with rifampin also increased co-transformation by linked heterospecific markers. The period during which recipient cells were sensitive to the effects induced by rifampin and fluorodeoxyuridine lasted from 10 to 20 min after DNA uptake.


Evaluation of combined therapy with chemoembolization and ethanol injection for advanced hepatocellular carcinoma.
To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) combined with percutaneous ethanol injection therapy (PEIT) for advanced hepatocellular carcinoma, we studied the effectiveness of TACE therapy combined with PEIT (50 cases) and TACE alone (50 cases). In both groups, patients had multiple lesions, or a single lesion with a diameter exceeding 2 cm or with vascular invasion (stages II, III, and IV in the tumor staging classification of the Liver Cancer Study Group of Japan). The clinical features in the two groups were comparable. The cumulative survival rates with TACE-PEIT were 95.0% for 1 year, 72.5% for 2 years, and 50.0% for 3 years, whereas the rates with TACE alone were 92.5% for 1 year, 57.5% for 2 years, and 20.0% for 3 years. The survival rate in the TACE-PEIT group was significantly higher than that in the TACE alone group. Moreover, the survival rate of patients with stage II or III disease in the TACE-PEIT group was significantly better than that in the TACE alone group, and the survival rate of patients with Child's classification B or C in the TACE-PEIT group was significantly higher than that in the TACE alone group. Multivariate analysis using Cox's proportional hazard regression model showed that the most significant prognostic factors in the TACE-PEIT group were tumor embolus in the portal vein and the number of tumors. These results suggest the effectiveness of combining TACE and PEIT for the treatment of advanced hepatocellular carcinoma.


Serotonergic Modulation of the BNST-CeA Circuit Promotes Sex Differences in Fear Learning.
Post-traumatic stress disorder (PTSD) is characterized by intense fear memory formation and is diagnosed more often in women than men. Here, we show that serotonin differentially affects fear learning and communication in the extended amygdala of male and female mice. Females showed higher sensitivity to the effects of pharmacologically increasing serotonin during auditory fear conditioning, which enhanced fear memory recall in both sexes. Optogenetic stimulation of dorsal raphe terminals in the anterior dorsal bed nucleus of the stria terminalis (adBNST) during fear conditioning increased c-Fos expression in the BNST and central nucleus of the amygdala (CeA), and enhanced fear memory recall via activation of adBNST 5-HT2C receptors in females only. Likewise, in females only, serotonin stimulation during learning enhanced adBNST-CeA high gamma (90-140Hz) synchrony and adBNST-to-CeA communication in high gamma during fear memory recall. We conclude that sex differences in the raphe-BNST-CeA circuit may increase risk of PTSD in women.


Trifluoromethylation of salicyl aldimines.
A method for the nucleophilic trifluoromethylation of salicyl aldimines, which do not contain an activating group at the nitrogen atom, has been described. The reaction proceeds through the initial generation of intramolecular boron complex followed by interaction with Me3SiCF3 activated by sodium acetate.


Effects of abiraterone acetate on chronic kidney disease in 2 patients with metastatic castration-resistant prostate cancer.
Prostate cancer is the second leading cause of cancer-related death in men in most Western countries. In this report, we present 2 cases of metastatic castration-resistant prostate cancer and chronic kidney disease. Both patients underwent and developed clinical resistance to androgen-deprivation therapy. Subsequently, the patients were treated with the conventional chemotherapeutic approach, which resulted in the worsening of renal function and performance status. Therefore, we opted for treatment with abiraterone acetate, and the patients exhibited improvements in renal function with good response of the disease.


Ampelopsis brevipedunculata (Vitaceae) extract stimulates collagen synthesis through superoxide generation in the serum-free cultures of rat dermal fibroblasts and Ito cells.
We describe the effects of an ethanol-extracted fraction of berries of Ampelopsis brevipedunculata (Maxim.) Trautv. (Vitaceae), a plant used in folk medicine to treat liver disease, on the synthesis of non-collagenous proteins and collagen by rat collagen-producible cells such as dermal fibroblasts and liver non-parenchymal Ito cells. The generation of superoxide and hydroxyl radical was assessed by measuring the reduction of cytochrome c and the formation of thiobarbituric acid-reactive substances from deoxyribose, respectively. The synthesis of non-collagenous proteins and collagen as evaluated by measuring the extent of [3H]tryptophan incorporation into a total protein fraction of culture products and the [3H]proline-incorporating rate into a collagenase-digestible protein fraction, respectively. Both types of cells promptly synthesized only collagen in response to a dialyzable fraction of the extract. Major activity to generate oxygen free radicals accumulated in the dialyzable fraction whereas activity to decrease ferrous iron-mediated generation of the radicals accumulated in an undialyzable fraction of the extract. Stimulation of collagen synthesis was caused by superoxide because addition of superoxide dismutase but not pyruvate, an antioxidant of hydrogen peroxide, or dimethyl sulfoxide, an antioxidant of the hydroxyl radical, abrogated the stimulatory effect. The extract may arrest the progress of liver injury mediated by oxygen free radicals generated in the presence of ferrous iron.