[HELLP syndrome in the postpartum period].
The HELLP syndrome was described by Weinstein as a complication of pregnancy induced hypertension (PIH). There are few clinical reports about HELLP during postpartum period. We present the history of 31 years old pregnant patient, who developed in 36 week of her first pregnancy PIH, pregnancy was terminated in 39 week by cesarean section and postpartum period was complicated with HELLP syndrome (class I). The patient was treated surgically (hysterectomy), than continue at ICU. The treatment was successful without any late organ complications.


Malignant melanoma and histiocytofibroma.
In patients with malignant melanoma, histiocytofibromas often appeared to be present. The frequency of this association has been determined in 60 female and 40 male patients, and compared with age- and sex-matched controls. Histiocytofibromas are significantly more common in females with malignant melanoma than in controls. This relationship is not found in males. Therefore, it would seem important to make a careful examination of nevocytic nevi in women having this benign tumour because of the high risk of developing a malignant melanoma.


Inhibitory effects of a sulfated polysaccharide isolated from edible red alga Bangia fusco-purpurea on α-amylase and α-glucosidase.
In this study, a sulfated polysaccharide (BFP) was isolated from the edible red alga Bangia fusco-purpurea. Gel-filtration and thin layer chromatographically analyses suggested that BFP was a homogenous polysaccharide. The chemical structural analysis revealed that BFP mainly consisted of galactose together with a small amount of uronic acid, mannose, and glucose. Its molecular mass was estimated to be 133.18 kDa by high-performance liquid chromatography (HPLC) analysis. BFP inhibited α-amylase and α-glucosidase in a concentration-dependent manner. The IC50 values of BFP against α-amylase and α-glucosidase were estimated to be 1.26 ± 0.11 mg/mL and 1.34 ± 0.07 mg/mL, respectively. Kinetic analyses suggested that BFP showed competitive and non-competitive inhibition against α-amylase and α-glucosidase, respectively. Circular dichroism spectral and fluorescence spectral analyses suggested that BFP affects the conformational structures of these enzymes, which may lead to the inhibition of the enzymatic activities. Abbreviations: Ara: D-arabinose; AnGal: anhydro-L-galactose residues; CD spectroscopy: Circular Dichroism spectroscopy; DNS: dinitrosalicylic acid; FT-IR: fourier transform infrared spectra; Fuc: L-fucose; Gal: D-galactose; Glc: D-glucose; GlcA: D-Glucuronic acid; HPLC: high performance liquid chromatography; Man: D-mannose; pNPG: p-nitrophenyl-α-D-glucoside; TFA: trifluoroacetic acid; TLC: thin-layer chromatography; PMP: 1-phenyl-3-methyl-5-pyrazolone; Xyl: D-xylose.


LncRNA SNHG3 is activated by E2F1 and promotes proliferation and migration of non-small-cell lung cancer cells through activating TGF-β pathway and IL-6/JAK2/STAT3 pathway.
Recently, long noncoding RNAs (lncRNAs) have been widely reported to play pivotal roles in the regulation of human cancers. Although the oncogenic property of lncRNA small nucleolar RNA host gene 3 (SNHG3) has been revealed in a variety of cancers, functions and regulatory mechanism of SNHG3 in non-small-cell lung cancer (NSCLC) remain to be investigated. In this study, we detected the upregulated expression of SNHG3 in NSCLC tissues as well as cells through quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis. Using Kaplan-Meier analysis, we determined that a high-level of SNHG3 was associated with a low overall survival rate of patients with NSCLC. Through gain and loss of function experiments, we demonstrated that SNHG3 had a significantly positive effect on NSCLC cell proliferation and migration. Mechanistic investigations revealed that SNHG3 was a predicted direct transcriptional target of E2F1. We observed that the transcriptional activation of SNHG3 could be induced by E2F1. To explore the mechanism, rescue experiments were carried out, which revealed that the cotreatment with SB-431542, JSI-124, or JSI-124 + SB-431542 rescued the effects brought by the overexpression of SNHG3 on NSCLC cell proliferation, migration, and epithelial-mesenchymal transition process. Our results suggested that E2F1 activated SNHG3 and promoted cell proliferation and migration in NSCLC via transforming growth factor-β pathway and interleukin-6/janus-activated kinase 2/signal transducer and activator of transcription 3 pathway, which implied that SNHG3 may be a biomarker for the treatment of patients with NSCLC.


The WUSCHEL gene promotes vegetative-to-embryonic transition in Arabidopsis.
Formation of somatic embryos in plants is known to require high concentrations of auxin or 2,4-dichlorophenoxyacetic acid (2,4-D), which presumably acts to trigger a signalling cascade. However, very little is known about the molecular mechanism that mediates the vegetative-to-embryogenic transition. We have employed a genetic approach to dissect the signal transduction pathway during somatic embryogenesis. In a functional screen using a chemical-inducible activation-tagging system, we identified two alleles of Arabidopsis gene PGA6 whose induced overexpression caused high-frequency somatic embryo formation in all tissues and organs tested, without any external plant hormones. Upon inducer withdrawal, all these somatic embryos were able to germinate directly, without any further treatment, and to develop into fertile adult plants. PGA6 was found to be identical to WUSCHEL (WUS), a homeodomain protein previously shown to be involved in specifying stem cell fate in shoot and floral meristems. Transgenic plants carrying an estradiol-inducible XVE-WUS transgene can phenocopy pga6-1 and pga6-2. Our results suggest that WUS/PGA6 also plays a key role during embryogenesis, presumably by promoting the vegetative-to-embryogenic transition and/or maintaining the identity of the embryonic stem cells.


Antibacterial Chemodynamic Therapy: Materials and Strategies.
The wide and frequent use of antibiotics in the treatment of bacterial infection can cause the occurrence of multidrug-resistant bacteria, which becomes a serious health threat. Therefore, it is necessary to develop antibiotic-independent treatment modalities. Chemodynamic therapy (CDT) is defined as the approach employing Fenton and/or Fenton-like reactions for generating hydroxyl radical (•OH) that can kill target cells. Recently, CDT has been successfully employed for antibacterial applications. Apart from the common Fe-mediated CDT strategy, antibacterial CDT strategies mediated by other metal elements such as copper, manganese, cobalt, molybdenum, platinum, tungsten, nickel, silver, ruthenium, and zinc have also been proposed. Furthermore, different types of materials like nanomaterials and hydrogels can be adopted for constructing CDT-involved antibacterial platforms. Besides, CDT can introduce some toxic metal elements and then achieve synergistic antibacterial effects together with reactive oxygen species. Finally, CDT can be combined with other therapies such as starvation therapy, phototherapy, and sonodynamic therapy for achieving improved antibacterial performance. This review first summarizes the advancements in antibacterial CDT and then discusses the present limitations and future research directions in this field, hoping to promote the development of more effective materials and strategies for achieving potentiated CDT.


Syndecan-1 expression in laryngeal cancer.
Syndecan-1 is a member of the syndecan family of cell surface heparan sulphate proteoglycans. The aim of this study was the evaluation of syndecan-1 expression in laryngeal cancer. The findings were correlated both with the clinico-pathological parameters of the tumours and with patient survival. Paraffin-embedded samples from 48 patients with laryngeal cancer selected from the files of the ENT Department of the Medical Academy in Lublin were immunostained with anti-syndecan-1 monoclonal antibody. The patients' mean age was 56 years, and 69% survived for over 3 years. Syndecan-1 immunoreactivity was observed in 48 (100%) of carcinomas. In our study, statistically significant correlations were observed both between syndecan-1 expression and patient survival (Chi-square = 4.364; P<0.05) and between syndecan-1 expression and clinical stage of disease (Chi-square = 4.363; P<0.05). Significant differences in syndecan-1 expression were also observed with various stages of histological differentiation of the carcinomas (Chi-square = 6.588; P<0.05), and also according to the presence or absence of metastatic changes in the regional lymph nodes (Chi-square = 6.289; P<0.05). Our results indicate that syndecan-1 could be used as a prognostic marker in laryngeal cancer.


Low renin hypertension.
Low renin hypertension comprises a spectrum of disorders ranging from primary aldosteronism to obvious disorders of other mineralocorticoids, as well as a variety of miscellaneous disorders. The largest group of patients with low renin hypertension have no clear abnormality in mineralocorticoid production. However, many lines of evidence suggest the critical role of volume excess in the pathogenesis of hypertension in these patients. More detailed physiological studies must be performed in order to totally understand the spectrum of pathophysiology in low renin hypertension. However, while such studies are in progress the evidence from the literature suggests that these patients must be treated and that in most of these patients diuretic administration, either spironolactone or the thiazide group of diuretics, is usually effective in achieving a reduction of blood pressure to normal.


Pretreatment neutrophil-to-lymphocyte ratio as a marker of outcomes in nivolumab-treated patients with advanced non-small-cell lung cancer.
Efficient use of nivolumab in non-small-cell lung cancer (NSCLC) has been limited by the lack of a definitive predictive biomarker. In patients with metastatic melanoma treated with ipilimumab, a pretreatment neutrophil-to-lymphocyte ratio (NLR)<5 has been associated with improved survival. This retrospective cohort study aimed to determine whether the pretreatment NLR was associated with outcomes in NSCLC patients treated with nivolumab. We reviewed the medical records of all patients with previously treated advanced NSCLC who received nivolumab between March 2015 and March 2016 outside of a clinical trial at the University of Pennsylvania. Patients were dichotomized according to pretreatment NLR<5 vs. ≥5. Multivariable logistic regression and Cox proportional hazards models were used to assess the impact of pretreatment NLR on overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). 175 patients were treated. Median age was 68 (range, 33-88); 54% were female. Twenty-five percent of patients had an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2; 46% had received ≥2 prior systemic therapies. In multivariate analyses, pretreatment neutrophil-to-lymphocyte ratio (NLR) ≥5 was independently associated with inferior OS (median 5.5 vs. 8.4 months; HR 2.07, 95% CI 1.3-3.3; p=0.002) and inferior PFS (median 1.9 vs. 2.8 months; HR 1.43, 95% CI 1.02-2.0; p=0.04). In a cohort of patients with NSCLC treated with nivolumab in routine practice, pretreatment NLR≥5 was associated with inferior outcomes. It is unclear whether this marker is predictive or prognostic. Prospective studies are warranted to determine the utility of NLR in the context of other biomarkers of programmed death-1 (PD-1) therapy.


Reactivity of the bis(pentafluorophenyl)boranes ClB(C6F5)2 and [HB(C6F5)2]n towards late transition metal reagents.
The reactivities of the highly electrophilic boranes ClB(C(6)F(5))(2) (1) and [HB(C(6)F(5))(2)](n) (2) towards a range of organometallic reagents featuring metals from Groups 7-10 have been investigated. Salt elimination chemistry is observed 1 between and the nucleophilic anions eta(5)-C(5)R(5))Fe(CO)(2)](-)(R = H or Me) and [Mn(CO)(5)](-), leading to the generation of the novel boryl complexes (eta(5)-C(5)R(5))Fe(CO)(2)B(C(6)F(5))(2)[R = H (3) or Me (4)] and (OC)(5)MnB(C(6)F(5))(2) (5). Such systems are designed to probe the extent to which the strongly sigma-donor boryl ligand can also act as a pi-acceptor; a variety of spectroscopic, structural and computational probes imply that even with such strongly electron withdrawing boryl substituents, the pi component of the metal-boron linkage is a relatively minor one. Similar reactivity is observed towards the hydridomanganese anion [(eta(5)-C(5)H(4)Me)Mn(CO)(2)H](-), generating a thermally labile product identified spectroscopically as (eta(5)-C(5)H(4)Me)Mn(CO)(2)(H)B(C(6)F(5))(2) (6). Boranes 1 and 2 display different patterns of reactivity towards low-valent platinum and rhodium complexes than those demonstrated previously for less electrophilic reagents. Thus, reaction of 1 with (Ph(3)P)(2)Pt(H(2)C=CH(2)) ultimately generates EtB(C(6)F(5))(2) (10) as the major boron-containing product, together with cis-(Ph(3)P)(2)PtCl(2) and trans-(Ph(3)P)(2)Pt(C(6)F(5))Cl (9). The cationic platinum hydride [(Ph(3)P)(3)PtH](+) is identified as an intermediate in the reaction pathway. Reaction of with [(Ph(3)P)(2)Rh(mu-Cl)](2), in toluene on the other hand, appears to proceed via ligand abstraction with both Ph(3)P.HB(C(6)F(5))(2) (11) and the arene rhodium(I) cation [(Ph(3)P)(2)Rh(eta(6)-C(6)H(5)Me)](+) (14) ultimately being formed.


3-Amino-1,2,4-triazole Limits the Oxidative Damage in UVA-Irradiated Dysplastic Keratinocytes.
Reactive oxygen species (ROS) generated by UVA irradiation affect the keratinocyte cell membrane, DNA, and proteins and may cause serious injury to the skin. Treating human dysplastic keratinocytes (DOK) with 3-amino-1,2,4-triazole (AMT), a common catalase inhibitor, induced a compensatory mechanism for the hydrogen peroxide detoxification, which included a rise in glutathione peroxidase and glutathione reductase activities. Here, we examined a possible role of AMT in protecting a human DOK cell line against UVA-induced damage. In DOK cells exposed to UVA irradiation, we observed a substantial decrease in antioxidant enzymatic activities, such as catalase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase and an increase in lipid peroxidation and protein oxidation levels. Treating DOK cells with AMT prior to UVA exposure enhanced the activities of glutathione peroxidase, glutathione reductase, and glutathione-S-transferase, relative to nontreated cells. The enhanced antioxidant activities were correlated with decreased protein oxidation levels. Based on these results, we suggest that AMT may protect dysplastic keratinocytes against the harmful effects of UVA radiation.


Anterior Interosseous Nerve Neuropraxia Secondary to Shoulder Arthroscopy and Open Subpectoral Long Head Biceps Tenodesis.
Arthroscopic rotator cuff tendon repair is a common elective procedure performed by trained orthopaedic surgeons with a relatively low complication rate. Specifically, isolated neuropraxia of the anterior interosseous nerve (AIN) is a very rare complication of shoulder arthroscopy. An analysis of peer-reviewed published literature revealed only three articles reporting a total of seven cases that describe this specific complication following standard shoulder arthroscopic procedures. This article reports on three patients diagnosed with AIN neuropraxia following routine shoulder arthroscopy done by a single surgeon within a three-year period. All three patients also underwent open biceps tenodesis immediately following completion of the arthroscopic procedures. The exact causal mechanism of AIN neuropraxia following shoulder arthroscopy with biceps tenodesis is not known. This case report reviews possible mechanisms with emphasis on specific factors that make a traction injury the most likely etiology in these cases. We critically analyze our operating room setup and patient positioning practices in light of the existing biomechanical and cadaveric research to propose changes to our standard practices that may help to reduce the incidence of this specific postoperative complication in patients undergoing elective shoulder arthroscopy with biceps tenodesis.


Potential toxic effects associated to metals and endotoxin present in PM10: an ancillary study using multivariate analysis.
In the evaluation of particulate matter (PM) toxicity, one faces the challenge of identifying components that could be addressed as markers of toxicity. This study examines the use of statistical methods to determine which components present in the complex mixtures are related to toxic effects. The work is based on data previously published, where we demonstrated that particles collected in different zones of Mexico City showed different ability of inducing cell death, causing DNA damage, or creating proinflammatory effects. Empirically, we correlated those differences to variations in the concentration of transitional metals or endotoxin. In order to test those correlations, in this study we evaluated the role of the concentration of six transitional metals (Ni, V, Zn, Cu, Fe, and Pb) and endotoxin using the following tools: Pearson's regression analysis, correlation matrix between components, and multiple regression followed by a stepwise analysis. Due to collinearity found among several of the components, only Ni, Zn, and Pb were considered as independent variables. Among these, Ni and Zn show better correlations and help to explain the loss in viability, whereas Pb is the component that betters explains the proinflammatory effects. The statistical identification of composition markers facilitates the generation of a hypothesis relating the role played by the composition of PM and its biological effects.


[Dr. Eiichi Tanaka's Achievement in the Research of Image Reconstruction].
In memoriam of Dr. Eiichi Tanaka who passed away on August 21, 2021, I review his achievement in the research of tomographic image reconstruction. Tomographic image reconstruction is an important research area which has wide applications including X-ray CT, nuclear medicine imaging such as PET and SPECT, and electron microscopy. Since 1970's, Dr. Tanaka has worked on numerous important topics in tomographic reconstruction fields aiming at using them in image reconstruction for PET and SPECT. Among them, in this paper, I will introduce his research on Filtered BackProjection (FBP) method, analytical attenuation correction in SPECT, image reconstruction in Time-of-Flight PET, image reconstruction for 3-D PET imaging, and iterative image reconstruction method called Dynamic Row-Action Maximum Likelihood Algorithm (DRAMA).


Treatment with lithium as a tool for the study of animal-vegetal interactions in sea urchin embryos.
The question about the nature of the effect of lithium on early sea urchin development is reexamined. Essential features of the morphogenetic changes of lithium treated embryos are followed with continuous comparisons with control embryos. The key to the lithium effect is the greater cytoplasmic susceptibility in the animal polar region as compared with the vegetal one. This is diagrammed in Fig. 23a-c on the basis of the double gradient concept. There is a decline of the animal gradient with increasing lithium concentration. As a consequence the level of differentiation of the terminal region becomes more and more vegetal, seean/veg-values in Fig. 23. The region suppressed by a prolonged exposure to lithium, e.g. 9-16 hours, cannot be restored. Nevertheless, there are data from previous research supporting the view that the primary effects of lithium are reversible within certain limits. However, when the normal balance is disturbed by decline of the animal gradient and particularly by suppression of its higher levels, there is a compensatory enhancement of the vegetal gradient system which stabilizes the suppression. As a consequence of the suppression of the higher animal levels, a certain accumulation of cells in an anterior direction has taken place in the blastula stage. The degree of accumulation reflects the degree of vegetalization. Later there is to varying extent a backflow of cells in the vegetal direction. It was shown how a great part of the blastula wall may have the aspect of an attachment zone (Fig. 7). The primary mesenchyme cells attach themselves only to a certain level of the ectoderm in which the relativean/veg-value is around 0.7 according to the conventions behind Fig. 23.Sections of Carnoy fixed embryos were exposed to trypsin. It proved that the external cytoplasm of blastodermic cells in lithium treated embryos was more strongly attacked than the internal one. The latter showed a strong resistance to tryptic action. On the other hand, in the control embryos the inner part of blastodermic cells was completely digested with exception of the vegetal region including the attachment zone. The trypsin resistant structure may be preformed and may be responsible for the higher rigidity of the cytoplasm in lithium treated embryos (section IIIf).It is proposed that in the period of lithium susceptibility, the colloidal state is most affected in the animal region, thereby creating a block to the diffusion of the animalizing substances which results in the shifts diagrammed in Fig. 23.


[Acute abdomen as form of presentation of hepatic adenoma].
We report the case of a woman aged 33 years old who was admitted with an acute abdomen. She referred oral contraceptives intake. Physical findings were abdominal tenderness, involuntary guarding and right upper quadrant rigidity. The following studies were performed: laboratory tests excluded hydatidosis and amebiasis. Ultrasonography showed a nodular image in the right hepatic lobe and a normal biliary tract. A low-density mass was observed with the computed tomographic scanning. A tomographic guided needle biopsy was informed as normal liver cells. Angiography showed tortuous hepatic arteries. Laparoscopy revealed a solid formation blood was obtained when it was punctured. Laparotomy was indicated. A tumor in the right hepatic lobe was found but a surgeon did not resect the lesion because a congelation biopsy failed to demonstrate tumoral cells. The diagnosis of hepatic adenoma was reached with the definitive biopsy. Our patient had a good evolution with the contraceptives withdrawal and a tomographic scanning one year after surgery showed the almost complete remission of the tumor. Pain as the initial symptom was observed in 12-52% of patients with an hepatic adenoma an audden onset in 33% of them. However this tumor is not frequently considered as a cause of acute abdomen.


NuSegDA: Domain adaptation for nuclei segmentation.
The accurate segmentation of nuclei is crucial for cancer diagnosis and further clinical treatments. To successfully train a nuclei segmentation network in a fully-supervised manner for a particular type of organ or cancer, we need the dataset with ground-truth annotations. However, such well-annotated nuclei segmentation datasets are highly rare, and manually labeling an unannotated dataset is an expensive, time-consuming, and tedious process. Consequently, we require to discover a way for training the nuclei segmentation network with unlabeled dataset. In this paper, we propose a model named NuSegUDA for nuclei segmentation on the unlabeled dataset (target domain). It is achieved by applying Unsupervised Domain Adaptation (UDA) technique with the help of another labeled dataset (source domain) that may come from different type of organ, cancer, or source. We apply UDA technique at both of feature space and output space. We additionally utilize a reconstruction network and incorporate adversarial learning into it so that the source-domain images can be accurately translated to the target-domain for further training of the segmentation network. We validate our proposed NuSegUDA on two public nuclei segmentation datasets, and obtain significant improvement as compared with the baseline methods. Extensive experiments also verify the contribution of newly proposed image reconstruction adversarial loss, and target-translated source supervised loss to the performance boost of NuSegUDA. Finally, considering the scenario when we have a small number of annotations available from the target domain, we extend our work and propose NuSegSSDA, a Semi-Supervised Domain Adaptation (SSDA) based approach.


Cardiac tumour in a patient with rheumatic heart disease.
A 45-year-old female known to suffer from rheumatic heart disease (RHD), presented with breathlessness of 1 year duration. Two-dimensional echocardiography revealed significant mitral and aortic valve disease mandating double valve replacement. In addition, an unusual finding in the form of a well-defined, densely calcified intramyocardial left ventricular mass was noted on echocardiography. The nature and extent of the mass was assessed by additional imaging modalities. Patient underwent excision of the mass followed by double valve replacement. Histopathology was consistent with cardiac calcific amorphous tumour (CAT). An unusual occurrence of CAT in a patient with RHD is presented herein. This rare tumour has not been previously described in patients with RHD.


Beyond a Differential Diagnosis: Cognitive and Morphometric Decoding of Information Processing Speed in Senior Adults with DSM-5 Mild Neurocognitive Disorders.
Processing speed has been highlighted as a diagnostic item for neurocognitive disorders (NCD) in DSM-5. The utility of information processing speed (IPS) enclosed with multiscale constructs in the diagnosis of NCD warrants exploration. We aimed to investigate the IPS with two types of measurements in the patients with NCD due to vascular disease (NCD-vascular) and NCD due to Alzheimer's disease (NCD-AD), and examine the associations between IPS measures and morphometric features. The IPS was evaluated using trail making test (TMT) and flanker test (n = 204). Direct scores, derived scores, and reaction time (RT) were used as IPS measures. Further, surface-based morphometry cortical volume was calculated in a subsample (n = 44) with structural MRI data. All IPS measures showed a significant value to differentiate NCD patients from healthy subjects. Only mean RT could distinguish NCD-AD from NCD-vascular groups. TMT-B score and difference score were correlated with gray matter volume (GMV) of inferior frontal gyrus, precuneus and superior temporal cortex. Mean RT was associated with the GMV of post-central gyrus (r = -0.327, p = 0.035), and executive speed was associated with inferior frontal cortex (r = -0.475, p = 0.001), cingulate gyrus (r = -0.497, p = 0.001), and superior temporal gyrus (r = -0.36, p = 0.019). The cognitive and morphometric correlates of IPS measures indicate that complex IPS might be decomposed into the domain-specific components with corresponding neural underpinnings. Our findings may also provide essential insights into the diagnostic item of NCD.


MR-guided ultrasound-stimulated microbubble therapy enhances radiation-induced tumor response.
High intensity focused ultrasound (HIFU) systems have been approved for therapeutic ultrasound delivery to cause tissue ablation or induced hyperthermia. Microbubble agents have also been used in combination with sonication exposures. These require temperature feedback and monitoring to prevent unstable cavitation and prevent excess tissue heating. Previous work has utilized lower power and pressure to oscillate microbubbles and transfer energy to endothelial cells in the absence of thermally induced damage that can radiosensitize tumors. This work investigated whether reduced acoustic power and pressure on a commercial available MR-integrated HIFU system could result in enhanced radiation-induced tumor response after exposure to ultrasound-stimulated microbubbles (USMB) therapy. A commercially available MR-integrated HIFU system was used with a hyperthermia system calibration provided by the manufacturer. The ultrasound transducer was calibrated to reach a peak negative pressure of - 750 kPa. Thirty male New Zealand white rabbits bearing human derived PC3 tumors were grouped to receive no treatment, 14 min of USMB, 8 Gy of radiation in a separate irradiation cabinet, or combined treatments. In vivo temperature changes were collected using MR thermometry at the tumor center and far-field muscle region. Tissues specimens were collected 24 h post radiation therapy. Tumor cell death was measured and compared to untreated controls through hematoxylin and eosin staining and immunohistochemical analysis. The desired peak negative pressure of - 750 kPa used for previous USMB occurred at approximately an input power of 5 W. Temperature changes were limited to under 4 °C in ten of twelve rabbits monitored. The median temperature in the far-field muscle region of the leg was 2.50 °C for groups receiving USMB alone or in combination with radiation. Finally, statistically significant tumor cell death was demonstrated using immunohistochemical analysis in the combined therapy group compared to untreated controls. A commercial MR-guided therapy HIFU system was able to effectively treat PC3 tumors in a rabbit model using USMB therapy in combination with radiation exposures. Future work could find the use of reduced power and pressure levels in a commercial MR-guided therapy system to mechanically stimulate microbubbles and damage endothelial cells without requiring high thermal doses to elicit an antitumor response.


Clinical learning environment at Shiraz Medical School.
Clinical learning occurs in the context of a dynamic environment. Learning environment found to be one of the most important factors in determining the success of an effective teaching program. To investigate, from the attending and resident's perspective, factors that may affect student leaning in the educational hospital setting at Shiraz University of Medical Sciences (SUMS). This study combined qualitative and quantitative methods to determine factors affecting effective learning in clinical setting. Residents evaluated the perceived effectiveness of the university hospital learning environment. Fifty two faculty members and 132 residents participated in this study. Key determinants that contribute to an effective clinical teaching were autonomy, supervision, social support, workload, role clarity, learning opportunity, work diversity and physical facilities. In a good clinical setting, residents should be appreciated and given appropriate opportunities to study in order to meet their objectives. They require a supportive environment to consolidate their knowledge, skills and judgment.


Differentiation of Bifidobacterium longum subspecies longum and infantis by quantitative PCR using functional gene targets.
Members of the genus Bifidobacterium are abundant in the feces of babies during the exclusively-milk-diet period of life. Bifidobacterium longum is reported to be a common member of the infant fecal microbiota. However, B. longum is composed of three subspecies, two of which are represented in the bowel microbiota (B. longum subsp. longum; B. longum subsp. infantis). B. longum subspecies are not differentiated in many studies, so that their prevalence and relative abundances are not accurately known. This may largely be due to difficulty in assigning subspecies identity using DNA sequences of 16S rRNA or tuf genes that are commonly used in bacterial taxonomy. We developed a qPCR method targeting the sialidase gene (subsp. infantis) and sugar kinase gene (subsp. longum) to differentiate the subspecies using specific primers and probes. Specificity of the primers/probes was tested by in silico, pangenomic search, and using DNA from standard cultures of bifidobacterial species. The utility of the method was further examined using DNA from feces that had been collected from infants inhabiting various geographical regions. A pangenomic search of the NCBI genomic database showed that the PCR primers/probes targeted only the respective genes of the two subspecies. The primers/probes showed total specificity when tested against DNA extracted from the gold standard strains (type cultures) of bifidobacterial species detected in infant feces. Use of the qPCR method with DNA extracted from the feces of infants of different ages, delivery method and nutrition, showed that subsp. infantis was detectable (0-32.4% prevalence) in the feces of Australian (n = 90), South-East Asian (n = 24), and Chinese babies (n = 91), but in all cases at low abundance (<0.01-4.6%) compared to subsp. longum (0.1-33.7% abundance; 21.4-100% prevalence). Our qPCR method differentiates B. longum subspecies longum and infantis using characteristic functional genes. It can be used as an identification aid for isolates of bifidobacteria, as well as in determining prevalence and abundance of the subspecies in feces. The method should thus be useful in ecological studies of the infant gut microbiota during early life where an understanding of the ecology of bifidobacterial species may be important in developing interventions to promote infant health.


Randomly stopped sums: models and psychological applications.
This paper describes an approach to modeling the sums of a continuous random variable over a number of measurement occasions when the number of occasions also is a random variable. A typical example is summing the amounts of time spent attending to pieces of information in an information search task leading to a decision to obtain the total time taken to decide. Although there is a large literature on randomly stopped sums in financial statistics, it is largely absent from psychology. The paper begins with the standard modeling approaches used in financial statistics, and then extends them in two ways. First, the randomly stopped sums are modeled as "life distributions" such as the gamma or log-normal distribution. A simulation study investigates Type I error rate accuracy and power for gamma and log-normal versions of this model. Second, a Bayesian hierarchical approach is used for constructing an appropriate general linear model of the sums. Model diagnostics are discussed, and three illustrations are presented from real datasets.


Implications of lifestyle changes on the incidence of childhood obesity - a systematic review and meta-analysis.
Childhood obesity, which is currently at epidemic levels, is the most prevalent chronic condition affecting young people's health worldwide. Along with the rise in juvenile obesity, illnesses like diabetes mellitus, hypertension, and fatty liver disease have become more prevalent in kids. Hence, through this systematic review and meta-analysis, we aimed to determine the lifestyle changes that would have the most impact on the incidence of childhood obesity. The databases of PubMed-MEDLINE, Web of Science, Cochrane, and Scopus were searched using keywords, such as "BMI", "childhood obesity", "lifestyle changes" and "nutritional intervention" and 482 documents were found overall after a thorough search of the online journals; 169 of them were first chosen. Only 58 original papers were left after 111 articles that were duplicates or exact copies of one another were eliminated. 12 studies were ultimately picked because they met the necessary inclusion and exclusion requirements. Reducing overall caloric intake and dietary factors specific to the child's parents were two of the most frequent impact factors on obesity levels, closely followed by physical activity levels and a sedentary lifestyle. The dietary intervention had the most positive results in modifying obesity-related dietary risk factors for obese children and adolescents in the majority of the studies. An overall balanced diet, parental awareness pertaining to BMI and physical activity in children were the three major factors influencing a child's obesity levels. However, more studies are needed in this regard so as to ascertain a complete, holistic treatment plan that can further validate the implementation of our findings.


Anticoagulant activity of a synthetic heparinoid in relation to molecular weight and N-sulfate content.
Addition of chlorosulfonyl isocyanate to C==C bonds in cis-1,4-polyisoprene and reaction of the adduct with NaOH resulted in the formation of a water-soluble polyelectrolyte with N-sulfate and carboxylate groups. The polyelectrolyte showed anticoagulant activity and it was found, just as with heparin, that the activity was related to molecular weight and N-sulfate content.


Functional overlap in mismatch repair by human MSH3 and MSH6.
Three human genes, hMSH2, hMSH3, and hMSH6, are homologues of the bacterial MutS gene whose products bind DNA mismatches to initiate strand-specific repair of DNA replication errors. Several studies suggest that a complex of hMSH2 x hMSH6 (hMutSalpha) functions primarily in repair of base x base mismatches or single extra bases, whereas a hMSH2 x hMSH3 complex (hMutSbeta) functions chiefly in repair of heteroduplexes containing two to four extra bases. In the present study, we compare results with a tumor cell line (HHUA) that is mutant in both hMSH3 and hMSH6 to results with derivative clones containing either wild-type hMSH3 or wild-type hMSH6, introduced by microcell-mediated transfer of chromosome 5 or 2, respectively. HHUA cells exhibit marked instability at 12 different microsatellite loci composed of repeat units of 1 to 4 base pairs. Compared to normal cells, HHUA cells have mutation rates at the HPRT locus that are elevated 500-fold for base substitutions and 2400-fold for single-base frameshifts. Extracts of HHUA cells are defective in strand-specific repair of substrates containing base x base mismatches or 1-4 extra bases. Transfer of either chromosome 5 (hMSH3) or 2 (hMSH6) into HHUA cells partially corrects instability at the microsatellite loci and also the substitution and frameshift mutator phenotypes at the HPRT locus. Extracts of these lines can repair some, but not all, heteroduplexes. The combined mutation rate and mismatch repair specificity data suggest that both hMSH3 and hMSH6 can independently participate in repair of replication errors containing base x base mismatches or 1-4 extra bases. Thus, these two gene products share redundant roles in controlling mutation rates in human cells.


Methotrexate for ankylosing spondylitis.
Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown cause, characterized by sacroiliitis and spondylitis. To date, treatment of AS has been limited to the alleviation of symptoms, mainly using non-steroidal anti-inflammatory drugs (NSAIDs). For patients refractory or intolerant to NSAIDs, the disease modifying antirheumatic drugs (DMARDs) have been used as a second line approach. Methotrexate (MTX) is currently one of the most widely used DMARDs and its efficacy in rheumatoid arthritis (RA) has been confirmed (Suarez-Almazor 2003). There is uncertainty whether MTX works in the treatment of AS. To evaluate the efficacy and toxicity of methotrexate in the treatment of ankylosing spondylitis. Relevant randomised and quasi-randomised trials in any language were sought using the following sources: CENTRAL (Cochrane Central Register of Controlled Trials, Issue 2, 2003), MEDLINE (1966 to June Week 4 2003), EMBASE (1980 to 2003 Week 26), CINAHL (1982 to June Week 3 2003) and the reference section of retrieved articles. We evaluated randomised and quasi-randomised trials examining the efficacy of methotrexate on AS. Unblinded trial reports were reviewed independently by two reviewers according to the selection criteria. Disagreements on the inclusion of the studies were resolved, where necessary, by recourse to a third reviewer. The methodological quality of included trials were independently assessed by the same reviewers on randomization, concealment, blindness (participants, care providers and outcome investigators), description of withdrawals and drop-outs and intention-to-treat analysis. The same reviewers independently entered the data extracted from the included trials, using RevMan's double entry facility. In the absence of significant heterogeneity, results were combined using weighted mean difference or standardised mean difference for continuous data, and relative risk for dichotomous data. Two trials met the inclusion criteria. Altan 2001compared naproxen plus MTX (7.5 mg/week orally) with naproxen alone and Roychowdhury 2002 compared MTX (10 mg/week orally) with placebo. The duration of the trials were 12 months and 24 weeks, respectively. They assessed different outcomes except for C-reactive protein (CRP). The included trials treated a total of 81 patients and assessed more than 10 outcomes relevant to the review, covering function, pain, peripheral arthritis/enthesitis, morning stiffness, patient and physician global assessment, CRP and erythrocyte sedimentation rate (ESR). No significant difference between intervention groups was found favouring MTX over no MTX. No serious side effect was reported in either trial. There was no statistically significant benefit of MTX in the examined outcomes for AS patients. High quality, larger sample and longer period of randomized controlled trials (possibly with higher dosage of MTX) are needed to verify the uncertainty about the efficacy and toxicity of MTX for the treatment of AS.


[Expression of Serotonin Receptor and Transporter Related Genes of CD4+ T Lymphocytes in Patients with Asthma and Depression].
To explore the comorbidity mechanism of asthma and depression. A self-developed questionnaire, which also contained Asthma Control Test (ACT), Asthma Quality of Life Questionnaire (AQLQ) and Hamilton Rating Scale for depression ( HRSD), was administered in 41 participants with asthma (AS), asthma and depression (AD), or none any of these conditions (health control, HC). Lung function and blood levels of eosnophils and IgE were also detected in those in the AS and AD groups. Blood CD4+ T cells were isolated in all of the participants to extract RNA for reverse transcription to cDNA. Real-time polymerase chain reaction (RT-PCR) was performed using cDNA as a template to detected the expression levels of HTR1A, HTR2A, HTR7, SLC6A4, and B2M genes. Participants with AS and AD had lower expression level of SLC6A4 than the healthy controls (P = 0.000). The expression level of HTR2A in participants with AS was lower than that in the healthy controls (P = 0.021) and marginally lower than that in participants with AD (P = 0.077). Participants with AD had lower AQLQ scores than participants with AS (P = 0.004). Asthma and depression is correlated at gene level. Decreased expression of SLC6A4 gene may be one of the possible comorbidity mechanisms of asthma and depression.


Infrequent mutations of the transforming growth factor beta-type II receptor gene at chromosome 3p22 in human lung cancers with chromosome 3p deletions.
Mutations in the transforming growth factor beta-type II receptor (TGFbeta RII) gene have been detected in several types of human cancers that represent the phenotype of genomic instability. The TGFbeta RII gene has been mapped to chromosome 3p, on which loss of heterozygosity (LOH) was frequently detected in both small cell lung carcinoma (SCLC) and non-small cell lung carcinoma (NSCLC). To investigate whether the TGFbeta RII gene on 3p22 is inactivated in lung cancers, we examined 35 sporadic lung cancers (15 SCLC and 20 NSCLC) with LOH on 3p for mutations of the TGFbeta RII gene. We previously produced eight intron based primer pairs for mutational analysis of the entire coding region of the TGFbeta RII gene. Using these primers, we screened for mutations of the TGFbeta RII gene by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) analysis. A mutation was detected in a case of SCLC: one base insertion in the polyadenine tract of exon 3. This tumor showed the replication error (RER) phenotype. There were no mutations in exons 1, 2, 4, 5, 6 and 7. These results indicate that the polyadenine tract is a mutational hot spot in the TGFbeta RII gene in RER positive tumors, and that TGFbeta RII mutations occur rarely in lung cancers with LOH on chromosome 3p.


COVID-19 cluster size and transmission rates in schools from crowdsourced case reports.
The role of schools in the spread of SARS-CoV-2 is controversial, with some claiming they are an important driver of the pandemic and others arguing that transmission in schools is negligible. School cluster reports that have been collected in various jurisdictions are a source of data about transmission in schools. These reports consist of the name of a school, a date, and the number of students known to be infected. We provide a simple model for the frequency and size of clusters in this data, based on random arrivals of index cases at schools who then infect their classmates with a highly variable rate, fitting the overdispersion evident in the data. We fit our model to reports from four Canadian provinces, providing estimates of mean and dispersion for cluster size, as well as the distribution of the instantaneous transmission parameter β, whilst factoring in imperfect ascertainment. According to our model with parameters estimated from the data, in all four provinces (i) more than 65% of non-index cases occur in the 20% largest clusters, and (ii) reducing instantaneous transmission rate and the number of contacts a student has at any given time are effective in reducing the total number of cases, whereas strict bubbling (keeping contacts consistent over time) does not contribute much to reduce cluster sizes. We predict strict bubbling to be more valuable in scenarios with substantially higher transmission rates.


Palliative care for patients with end-stage renal failure: reflections from Central Australia.
This paper explores palliative care issues for Australian Aboriginal patients with end-stage renal failure. Renal disease is epidemic amongst Aboriginal Australians. The Central Australian Palliative Care Service, based in the remote town of Alice Springs, sees a high proportion of renal patients, with different demographic characteristics to those seen in urban palliative care services. A case history illustrates distinctive concerns for local service provision, including communication issues, cultural requirements for maximizing quality of life, and the need to provide care in remote locations. Palliation for end-stage renal failure (ESRF) patients should be based on standard principles, but modified in accordance with local practical requirements and community needs.


Comparative evaluation of the marginal gingival epithelium in smokers and nonsmokers: a histomorphometric and immunohistochemical study.
Smoking is one of the strongest predictors of attachment and bone loss. Smokers demonstrate reduced inflammatory clinical signs, which could be due to local vasoconstriction and increased gingival epithelial thickness. The byproducts originating from tobacco oxidation modify the clinical characteristics and progression of periodontal disease. The aim of this study was to investigate the relationship between the thickness of marginal gingival oral epithelium, sulcular bleeding, and vascular caliber and density of the microvessels in smokers and nonsmokers with and without periodontitis and to better understand the role of smoking in relation to periodontal disease. One hundred twenty individuals were enrolled in this study and divided into four groups comprising 30 participants each. The clinical measurements carried out included probing depth, clinical attachment loss, and bleeding index, along with gingival biopsy specimens, which were subjected to immunohistochemical and histomorphometric analysis. Correlation of the clinical and histologic features revealed that smokers presented with fewer inflammatory signs, had fewer vascular elements in the subepithelial connective tissue layer, and showed a resultant increase in epithelial thickness irrespective of the presence of periodontitis. There was a mean increase of epithelial thickness of 181.3 μm (suprapapillary epithelial thickness [SET]) to 380.2 μm (maximal epithelial thickness [MET]) in smokers with periodontitis as compared to 157.4 μm (SET) to 325.3 μm (MET) in nonsmokers with periodontitis. The mean microvascular density in smokers with periodontitis was 325.4 per mm, which was found to be statistically significantly less than that of nonsmokers with periodontitis, who had a mean value of 412.13 per mm. The vessel caliber also was reduced in smokers, with a mean value ranging from 4.7 to 6.1 μm compared with a mean of 6.2 to 9.2 μm in nonsmokers, irrespective of the presence of periodontitis. Statistically significant differences were found in vascular density and thickness of gingival epithelium between smokers and nonsmokers with and without periodontitis. These differences may impact the progression of periodontal disease.


Evaluation of antioxidant and anti-melanogenic activities of different extracts from aerial parts of Nepeta binaludensis Jamzad in murine melanoma B16F10 cells.
Nepeta binaludensis Jamzad (Lamiaceae) has been used in folk medicine of Iran to cure various diseases. The plant is an endemic species to the country that has recently been identified in Razavi Khorasan province. To evaluate the antioxidant and anti-melanogenesis of N. binaludensis, in this study the inhibitory activity of different extracts of N. binaludensis in murine melanoma B16F10 cells is investigated. The effects of petroleum ether, dichloromethane, ethyl acetate, and methanol extracts isolated from the plant on melanogenesis in B16 melanoma cells were investigated. To assess the inhibitory effects of this plant on melanogenesis, various assays were used including cytotoxicity, inhibition of mushroom tyrosinase and cellular tyrosinase, determination of melanin content, the effect of extracts on reactive oxygen species and western blot analysis of proteins involved in melanogenesis process. The content of melanin and the activity of tyrosinase were significantly reduced with different extracts of N. binaludensis in cells. Reactive oxygen species was also significantly decreased following the treatment of cell with the mentioned extracts, while a resazurin assay showed no cytotoxicity. Furthermore, we have found that the plant decreased the amount of tyrosinase and microphthalmia-associated transcription factor proteins, which verify the role of suppression of microphthalmia-associated transcription factor protein in melanogenesis inhibition. Taken together the data indicate that N. binaludensis has inhibitory activity on melanin synthesis with no cytotoxic effects in B16 melanoma cells. Therefore, it merits future investigations to apply as whitening agent in hyperpigmentation.


Outcome prediction for renal cell carcinoma: evaluation of prognostic factors for tumours divided according to histological subtype.
A wide variety of parameters have been investigated for their prognostic significance in mixed series of renal cell carcinoma (RCC). The classification of RCC into separate types with differing morphology, genotype and probable clinical outcome has led to a re-evaluation of many prognostic parameters with studies confined to a single RCC morphotype. Tumour stage remains the most important predictor of RCC outcome and recent investigations have focused upon tumour diameter and the prognostic significance of stromal, vascular and lymphatic invasion within the renal sinus. In large tumour series, morphotype has been correlated with patient survival, with clear cell RCC being associated with a less favourable outcome than chromophobe RCC and to a lesser extent papillary RCC, for organ confined tumours. The prognostic significance of nuclear grading remains controversial. Fuhrman grading has been shown to have prognostic utility for clear cell RCC in some series. Recent studies have shown that for papillary RCC, grading should be based upon nucleolar size and that Fuhrman grading is inappropriate for chromophobe RCC. Proliferative indices based upon a variety of markers have been correlated with outcome for clear cell RCC (Ki-67, AgNORs, p21(waf1/cip1) and p27(Kip1)) and papillary RCC (Ki-67, AgNORs), although in some series prognostic significance was lost on multivariate analysis. The presence of tumour necrosis has been shown to predict survival for clear cell and chromophobe RCC, and in clear cell RCC quantification of tumour vascular density has been correlated with outcome. Several molecular markers have been investigated for prognostic significance, mostly in clear cell RCC. Although some of these markers have been shown to be significantly associated with survival, these findings remain to be confirmed in large scale follow-up studies.


Ross procedure in infants and toddlers followed into childhood.
The Ross procedure is commonly used to treat aortic valve disease in pediatric and adult patients. For infants, data are limited regarding survival, reintervention, autograft growth, and function. The Ross procedure was performed in 27 infants <18 months of age (median age 5.7 months). All patients had congenital aortic stenosis (AS); associated lesions included subAS (n=9), supravalvular AS (n=2), coarctation (n=5), and interrupted aortic arch (n=2). Median follow-up was 6.1 years (range 0.2 to 12.9). There were 3 early deaths and no late deaths. Freedom from reintervention for homograft dysfunction was 87% at 8 years; freedom from autograft reintervention was 100%. Follow-up echocardiograms were available in 17 patients. Estimated peak autograft gradient was 55 mm Hg in one patient and <10 mm Hg in 16. Mild autograft insufficiency was seen in 4 patients; 13 had none. Autograft diameter was measured early postoperatively and at latest follow-up. The mean z score increased from 0.63 to 3.2 (P<0.01) at the annulus and from 0.26 to 2.2 (P<0.01) at the sinus. In a subgroup, the mean autograft z score increased significantly from the postoperative period to 1 year for both the annulus (0.72 to 3.2, P<0.01) and the sinus (0.26 to 2.2, P<0.01), but remained unchanged thereafter. The Ross procedure effectively relieves AS in infants. Homograft reintervention occurred in 13% within 8 years. No patient developed significant autograft insufficiency or required autograft reintervention during the follow-up period. Dilatation of the autograft occurred during the first year after surgery and stabilized thereafter.


The biochemical mechanisms of the stimulating action of estradiol on the growth of mammary tumours.
The mechanisms of stimulating effect of estradiol on the growth of hormone-dependent mammary tumours in experimental animals were studied. Estradiol receptors were detected in plasmatic membranes of estradiol-dependent tumour cells. Estradiol-independence of tumours was found to be a result of the impairment of the estradiol receptors in the plasmatic membranes, intracellular receptors, or of their ability to interact with the chromatin of the target cells. It was shown that the interaction of receptors of plasmatic membranes of hormone-dependent tumour cells with estradiol results in activation of the membrane adenylate cyclase and in a short-term rise of a cAMP content. A treatment of the hormone-dependent tumours with ovarian hormones brings about an increase in the activity of the cAMP-dependent protein kinases in cell nuclei, which points to their translocation from cytosol. Under effect of estradiol the phosphorylation of nuclear proteins at the serine, threonine and tyrosine residues increases.


Structural, Physical, and Antifungal Characterization of Starch Edible Films Added with Nanocomposites and Mexican Oregano (Lippia berlandieri Schauer) Essential Oil.
The aim of this study was to evaluate the structural, physical, and antifungal characteristics of starch edible films added with nanocomposites and Mexican oregano (Lippia berlandieri Schauer) essential oil (EO). Starch edible films were formulated with Mexican oregano EO (0%, 1%, or 2% v/v) and bentonite or halloysite (2%). Physical properties such as L* (luminosity), hue, film thickness, and O2 and CO2 permeability were determined. Structural analysis was carried out via atomic force microscopy (AFM). Antifungal activity against Aspergillus niger, Fusarium spp., and Rhizopus spp. was evaluated. The addition of EO and nanocomposites reduced luminosity, providing color to the edible films. Film thickness increased through the addition of EO concentration. O2 and CO2 permeability was increased by bentonite/EO films, and for halloysite films, CO2 permeability decreased as EO concentration increased. The addition of EO with both nanocomposites shows an evident morphological change in film structure, decreasing pore density and increasing pore size. In general, Mexican oregano EO added to edible starch films has an adequate fungicidal effect. The most sensitive microorganism tested was A. niger. Edible films added with Mexican oregano EO and nanocomposites show better physical and antifungal properties due to an adequate structural change in the biopolymer matrix.


Night pain and morning stiffness in osteoarthritis: a crossover study of flurbiprofen and diclofenac sodium.
Forty patients took part in an observer-blind multiple dose crossover study to compare the efficacy and tolerability of 300 mg flurbiprofen (100 mg twice a day orally and 100 mg suppository at night) with 75 mg diclofenac sodium (25 mg twice daily orally and 25 mg suppository at night) in the relief of night pain and morning stiffness in patients with osteoarthritis. Equal numbers of patients were randomized to receive one of the treatments for the first 7-day treatment period and then the other treatment for the second 7-day treatment period. There were significant differences in favour of flurbiprofen for the reduction in night pain, improvement in quality of sleep and patients' assessment of overall improvement on treatment. Two patients withdrew from the study due to side-effects experienced whilst taking diclofenac sodium during the first treatment period. Eight patients in all reported a total of 18 side-effects during this study. Six patients reported 12 side-effects whilst taking diclofenac sodium compared with three patients who reported six side-effects whilst taking flurbiprofen. This study confirms the good efficacy and tolerability of flurbiprofen in the symptomatic relief of osteoarthritis.


Gender-modulated impact of apolipoprotein A5 gene (APOA5) -1131T>C and c.56C>G polymorphisms on lipids, dyslipidemia and metabolic syndrome in Turkish adults.
Apolipoprotein A5 (APOA5) gene polymorphisms are usually associated with plasma triglyceride levels. We evaluated the relationship of the APOA5 -1131T>C and c.56C>G polymorphisms [single nucleotide polymorphism (SNP)] with serum lipids, dyslipidemia [low high-density lipoprotein (HDL)/high triglyceride] and the risk for metabolic syndrome (MS) in the Turkish Adult Risk Factor study. We genotyped SNPs using the Taqman allelic discrimination assays in 1564 Turkish adults (51.4% female, mean age 54.1+/-11.6 years). MS and dyslipidemia were defined using the criteria of the National Cholesterol Education Program. For both SNPs, rare allele carriers had significantly higher fasting triglyceride levels in both genders, except the c.56G allele in men. The -1131C allele was associated with lower HDL cholesterol (HDL-C) levels in women. In relation to dyslipidemia, the c.56C>G and haplotype 1 had significant gender-genotype interactions (p<0.05). Otherwise, both SNPs were significantly associated with dyslipidemia after adjustment for risk factors in women. After similar adjustment, non-carriers of the haplotype 1 (odds ratio=4.1, p=0.003) increased the MS risk in women. However, no significant associations emerged between SNPs and HDL-C, dyslipidemia or MS in a similar analysis in men. Excess risk for low HDL-C, dyslipidemia and MS is associated with the rare alleles of the APOA5 SNPs and non-carriers of common haplotype in women.


Brain functional changes across the different phases of bipolar disorder.
Little is known about how functional imaging changes in bipolar disorder relate to different phases of the illness. To compare cognitive task activation in participants with bipolar disorder examined in different phases of illness. Participants with bipolar disorder in mania (n = 38), depression (n = 38) and euthymia (n = 38), as well as healthy controls (n = 38), underwent functional magnetic resonance imaging during performance of the n-back working memory task. Activations and de-activations were compared between the bipolar subgroups and the controls, and among the bipolar subgroups. All participants were also entered into a linear mixed-effects model. Compared with the controls, the mania and depression subgroups, but not the euthymia subgroup, showed reduced activation in the dorsolateral prefrontal cortex, the parietal cortex and other areas. Compared with the euthymia subgroup, the mania and depression subgroups showed hypoactivation in the parietal cortex. All three bipolar subgroups showed failure of de-activation in the ventromedial frontal cortex. Linear mixed-effects modelling revealed a further cluster of reduced activation in the left dorsolateral prefrontal cortex in the patients; this was significantly more marked in the mania than in the euthymia subgroup. Bipolar disorder is characterised by mood state-dependent hypoactivation in the parietal cortex. Reduced dorsolateral prefrontal activation is a further feature of mania and depression, which may improve partially in euthymia. Failure of de-activation in the medial frontal cortex shows trait-like characteristics.


Dual effects of growth hormone (GH)-releasing hormone infusion in normal men: somatotroph desensitization and increase in releasable GH.
Continuous infusion of human GH-releasing hormone (GHRH) stimulates GH secretion in normal subjects, but a single supramaximal iv dose of GHRH thereafter elicits a diminished serum GH response compared to that after a saline infusion; the response to the single dose challenge is inversely related to the dose of GHRH previously infused. To determine if this attenuated GH response is a result of depletion of available GH or desensitization of the somatotroph, a 6-h infusion of saline or GHRH (10 ng/kg . min) was administered to 10 normal men, and an iv bolus dose of either GHRH (3.3 micrograms/kg) or regular insulin (0.15 U/kg) was given after 5.5 h of infusion. On both days of GHRH infusion, there was significant stimulation of GH secretion compared to that after saline infusion. The GH response to the supramaximal dose of GHRH was greater after saline infusion than after GHRH infusion, and the GH response to insulin-induced hypoglycemia was significantly greater after GHRH infusion compared with the responses on the other 3 study days. The greatest GH secretion occurred during GHRH infusion followed by insulin administration; therefore, pituitary reserve was not decreased by prior exposure to GHRH. These studies suggest that somatotrophs become partially refractory to GHRH stimulation over time, but remain responsive to an alternate stimulus of GH secretion. We suggest that the hypoglycemia-induced GH response occurs via a reduction in hypothalamic somatostatin secretion, and the attenuated GH response to the supramaximal GHRH dose after GHRH infusion probably represents either partial desensitization or down-regulation of the GHRH receptor.


Focus on the Beauty of Body: The Mediation Role of Body Appreciation Between Perfectionism and Body-Related Shame and Body-Related Guilt.
Objectives: According to traditional views, perfectionists are prone to experience shame and guilt. As a relative part of negative body image, body appreciation reflects an appreciation attitude toward physical characteristics, functionality, and health, accepting and appreciating all parts and functions of the body, predicting body-related shame and guilt. Methods: Therefore, body appreciation was examined for its potential mediating role in the relationship between two dimensions of perfectionism (e.g., healthy perfectionism and unhealthy perfectionism) and body-related shame and body-related guilt among 514 females. Results: The results highlight that body appreciation partially mediated the relationship between perfectionism and body-related shame and body-related guilt. Implications for enhancing body appreciation among females between experiencing healthy or unhealthy perfectionism and body-related shame and body-related guilt feelings are discussed. Conclusions: These findings underscore the importance of considering body appreciation in addressing perfectionism dimensions and body-related shame and body-related guilt. Research and clinical implications are also addressed.


[Some new aspects of the Klinefelter syndrome].
Klinefelter syndrome (KS) is the most frequent form of male hypogonadism. Still, at least 50% ofcases are not diagnosed, partly because of the great variation in the clinical symptoms, partly because physicians are unfamiliar with KS. Timely treatment with testosterone can contribute to a more positive body image and, consequently, to a healthier psychosexual development in men with KS. Men with KS experience significantly more health problems and an increased risk ofa malignancy. New reproductive techniques no longer automatically mean that men with KS will remain infertile. Treatment with testosterone is in principle life-long to prevent osteoporosis and loss of muscle mass and strength.


The lethal response to Cdk1 inhibition depends on sister chromatid alignment errors generated by KIF4 and isoform 1 of PRC1.
Cyclin-dependent kinase 1 (Cdk1) is absolutely essential for cell division. Complete ablation of Cdk1 precludes the entry of G2 phase cells into mitosis, and is early embryonic lethal in mice. Dampening Cdk1 activation, by reducing gene expression or upon treatment with cell-permeable Cdk1 inhibitors, is also detrimental for proliferating cells, but has been associated with defects in mitotic progression, and the formation of aneuploid daughter cells. Here, we used a large-scale RNAi screen to identify the human genes that critically determine the cellular toxicity of Cdk1 inhibition. We show that Cdk1 inhibition leads to fatal sister chromatid alignment errors and mitotic arrest in the spindle checkpoint. These problems start early in mitosis and are alleviated by depletion of isoform 1 of PRC1 (PRC1-1), by gene ablation of its binding partner KIF4, or by abrogation of KIF4 motor activity. Our results show that, normally, Cdk1 activity must rise above the level required for mitotic entry. This prevents KIF4-dependent PRC1-1 translocation to astral microtubule tips and safeguards proper chromosome congression. We conclude that cell death in response to Cdk1 inhibitors directly relates to chromosome alignment defects generated by insufficient repression of PRC1-1 and KIF4 during prometaphase.


Does social exclusion motivate interpersonal reconnection? Resolving the "porcupine problem".
Evidence from 6 experiments supports the social reconnection hypothesis, which posits that the experience of social exclusion increases the motivation to forge social bonds with new sources of potential affiliation. Threat of social exclusion led participants to express greater interest in making new friends, to increase their desire to work with others, to form more positive impressions of novel social targets, and to assign greater rewards to new interaction partners. Findings also suggest potential boundary conditions to the social reconnection hypothesis. Excluded individuals did not seem to seek reconnection with the specific perpetrators of exclusion or with novel partners with whom no face-to-face interaction was anticipated. Furthermore, fear of negative evaluation moderated responses to exclusion such that participants low in fear of negative evaluation responded to new interaction partners in an affiliative fashion, whereas participants high in fear of negative evaluation did not.


Journey of an intruder through the fluidization and jamming transitions of a dense granular media.
We study experimentally the motion of an intruder dragged into an amorphous monolayer of horizontally vibrated grains at high packing fractions. This motion exhibits two transitions. The first transition separates a continuous motion regime at comparatively low packing fractions and large dragging force from an intermittent motion one at high packing fraction and low dragging force. Associated to these different motions, we observe a transition from a linear rheology to a stiffer response. We thereby call "fluidization" this first transition. A second transition is observed within the intermittent regime when the intruder's motion is made of intermittent bursts separated by long waiting times. We observe a peak in the relative fluctuations of the intruder's displacements and a critical scaling of the burst amplitudes' distributions. This transition occurs at the jamming point phi(J) defined as the point where the static pressure (i.e., the pressure measured in the absence of vibration) vanishes. Investigating the motion of the surrounding grains, we show that below the fluidization transition, there is a permanent wake of free volume behind the intruder. This transition is marked by the evolution of the reorganization patterns around the intruder, which evolve from compact aggregates in the flowing regime to long-range branched shapes in the intermittent regime, suggesting an increasing role of the stress fluctuations. Remarkably, the distributions of the kinetic energy of these reorganization patterns also exhibit a critical scaling at the jamming transition.


[Determination of 21 illegally added chemical drugs in health foods using ultra performance liquid chromatography-tandem mass spectrometry coupled with QuEChERS].
A method for the simultaneous determination of 21 illegally added chemical drugs in improving sleep and immunity health foods using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed. Oral liquid and health wine samples were shaken with acetonitrile and acetonitrile-water-formic acid (60:39:1, v/v/v), respectively, then purified by QuEChERS method. The extracts were separated on an Acquity UPLCTM BEH C18 column (50 mm×2.1 mm, 1.7 μm) with gradient elution of acetonitrile and 2 mmol/L ammonium acetate solution containing 0.1% (v/v) formic acid as mobile phases. The electrospray ionization in positive ion mode was used for analysis in multiple reaction monitoring (MRM) mode. The results showed that the target drugs had a good linear relationship in the range of 1-100 μg/L with the correlation coefficients (R2) ≥ 0.992. The limits of detection (LODs) and limits of quantification (LOQs) were 0.07-3.41 μg/kg and 0.22-11.36 μg/kg, respectively. The average recoveries of the 21 chemical drugs in oral liquid and health wine were in the range of 61.4%-116.5% and 67.4%-98.4% with the relative standard deviations (RSDs) of 0.2%-13.4% and 0.2%-11.8%, respectively. The developed method is sensitive and reliable. It has been successfully used for the detection of illegally added chemical drugs in real samples.


Historical factors that have shaped the evolution of tropical reef fishes: a review of phylogenies, biogeography, and remaining questions.
Biodiversity patterns across the marine tropics have intrigued evolutionary biologists and ecologists alike. Tropical coral reefs host 1/3 of all marine species of fish on 0.1% of the ocean's surface. Yet our understanding of how mechanistic processes have underpinned the generation of this diversity is limited. However, it has become clear that the biogeographic history of the marine tropics has played an important role in shaping the diversity of tropical reef fishes we see today. In the last decade, molecular phylogenies and age estimation techniques have provided a temporal framework in which the ancestral biogeographic origins of reef fish lineages have been inferred, but few have included fully sampled phylogenies or made inferences at a global scale. We are currently at a point where new sequencing technologies are accelerating the reconstruction and the resolution of the Fish Tree of Life. How will a complete phylogeny of fishes benefit the study of biodiversity in the tropics? Here, I review the literature concerning the evolutionary history of reef-associated fishes from a biogeographic perspective. I summarize the major biogeographic and climatic events over the last 65 million years that have regionalized the tropical marine belt and what effect they have had on the molecular record of fishes and global biodiversity patterns. By examining recent phylogenetic trees of major reef associated groups, I identify gaps to be filled in order to obtain a clearer picture of the origins of coral reef fish assemblages. Finally, I discuss questions that remain to be answered and new approaches to uncover the mechanistic processes that underpin the evolution of biodiversity on coral reefs.


Post-Traumatic Endophthalmitis Due to Acinetobacter radioresistens: Virulence Potential of Commensal Bacteria.
Acinetobacter species are widely distributed in soil, water and hospital environment. In addition to A. calcoaceticus-baumannii complex, the clinically most relevant species, there are other genomospecies which are less frequently identified, mostly due to lack of accurate methods for routine identification. We describe the first case of post-traumatic endophthalmitis caused by otherwise non-pathogenic A. radioresistens, in India. Gram-negative coccobacilli were observed on Gram stain and culture of vitreous fluid specimen, and identified biochemically as Acinetobacter spp. The species was identified by Matrix Assisted Laser Desorption Ionization- Time of Flight Mass Spectrometry (MALDI-TOF MS). The pathogenic potential of 'commensal' A. radioresistens and its role in dissemination of carbapenem resistance genes underlines the importance of species-level identification in Acinetobacter infections.


Structural and energetic basis of protein kinetic destabilization in human phosphoglycerate kinase 1 deficiency.
Protein kinetic destabilization is a common feature of many human genetic diseases. Human phosphoglycerate kinase 1 (PGK1) deficiency is a rare genetic disease caused by mutations in the PGK1 protein, which often shows reduced kinetic stability. In this work, we have performed an in-depth characterization of the thermal stability of the wild type and four disease-causing mutants (I47N, L89P, E252A, and T378P) of human PGK1. PGK1 thermal denaturation is a process under kinetic control, and it is described well by a two-state irreversible denaturation model. Kinetic analysis of differential scanning calorimetry profiles shows that the disease-causing mutations decrease PGK1 kinetic stability from ~5-fold (E252A) to ~100000-fold (L89P) compared to that of wild-type PGK1, and in some cases, mutant enzymes are denatured on a time scale of a few minutes at physiological temperature. We show that changes in protein kinetic stability are associated with large differences in enthalpic and entropic contributions to denaturation free energy barriers. It is also shown that the denaturation transition state becomes more nativelike in terms of solvent exposure as the protein is destabilized by mutations (Hammond effect). Unfolding experiments with urea further suggest a scenario in which the thermodynamic stability of PGK1 at least partly determines its kinetic stability. ATP and ADP kinetically stabilize PGK1 enzymes, and kinetic stabilization is nucleotide- and mutant-selective. Overall, our data provide insight into the structural and energetic basis underlying the low kinetic stability displayed by some mutants causing human PGK1 deficiency, which may have important implications for the development of native state kinetic stabilizers for the treatment of this disease.


Integrative surgical oncology: A model of acute integrative oncology.
Integrative oncology has emerged as a recognized medical subspecialty because of growing interest in the use of integrative medicine in modern cancer care on behalf of both patients and providers. Acutherapy and mind-body techniques, such as meditation and yoga, have been shown to aid in symptom control and improve quality of life in oncologic patient populations, and the Society of Integrative Oncology and American Society of Clinical Oncology have recently endorsed a set of guidelines for the implementation of these techniques specifically in patients with breast cancer. Although the current guidelines focus largely on the management of chronic symptoms, there exists evidence to support the use of these techniques in acute symptom management as well. With surgical resection representing the backbone of many cancer treatment regimens, symptoms that arise during the perioperative period are prime examples of the acute symptomatology common among patients with cancer. Here, the authors provide a detailed literature review of the current evidence supporting the use of integrative techniques during the perioperative period and demonstrate their applicability for acute symptom management within oncologic and surgical populations. In doing so, the authors introduce a new paradigm of surgical practice they call integrative surgical oncology and integrative surgery.


Cytochrome P450(cin) (CYP176A), isolation, expression, and characterization.
Cytochromes P450 are members of a superfamily of hemoproteins involved in the oxidative metabolism of various physiologic and xenobiotic compounds in eukaryotes and prokaryotes. Studies on bacterial P450s, particularly those involved in monoterpene oxidation, have provided an integral contribution to our understanding of these proteins, away from the problems encountered with eukaryotic forms. We report here a novel cytochrome P450 (P450(cin), CYP176A1) purified from a strain of Citrobacter braakii that is capable of using cineole 1 as its sole source of carbon and energy. This enzyme has been purified to homogeneity and the amino acid sequences of three tryptic peptides determined. By using this information, a PCR-based cloning strategy was developed that allowed the isolation of a 4-kb DNA fragment containing the cytochrome P450(cin) gene (cinA). Sequencing revealed three open reading frames that were identified on the basis of sequence homology as a cytochrome P450, an NADPH-dependent flavodoxin/ferrodoxin reductase, and a flavodoxin. This arrangement suggests that P450(cin) may be the first isolated P450 to use a flavodoxin as its natural redox partner. Sequencing also identified the unprecedented substitution of a highly conserved, catalytically important active site threonine with an asparagine residue. The P450 gene was subcloned and heterologously expressed in Escherichia coli at approximately 2000 nmol/liter of original culture, and purification was achieved by standard protocols. Postulating the native E. coli flavodoxin/flavodoxin reductase system might mimic the natural redox partners of P450(cin), it was expressed in E. coli in the presence of cineole 1. A product was formed in vivo that was tentatively identified by gas chromatography-mass spectrometry as 2-hydroxycineole 2. Examination of P450(cin) by UV-visible spectroscopy revealed typical spectra characteristic of P450s, a high affinity for cineole 1 (K(D) = 0.7 microm), and a large spin state change of the heme iron associated with binding of cineole 1. These facts support the hypothesis that cineole 1 is the natural substrate for this enzyme and that P450(cin) catalyzes the initial monooxygenation of cineole 1 biodegradation. This constitutes the first characterization of an enzyme involved in this pathway.


Cause of death in rheumatoid arthritis.
A series of 489 consecutive patients with definite or classical rheumatoid arthritis was followed for a mean of 11.2 years. Cohort-analysis of the series showed a three-fold increase in mortality overall in comparison with age- and sex-specific rates in the general population. In patients first seen in hospital early in the course of the disease (less than 5 years from onset), the excess of deaths from circulatory, respiratory and musculoskeletal disorders was highly significant. Malignant disease and digestive system disorders accounted for a small excess of borderline significance. Patients who were referred later (greater than 5 years from onset) experienced, in addition, a highly significant excess of deaths from infections and disorders of the digestive and genito-urinary system but not from malignant neoplasms.


Research Progress of N6-Methyladenosine in the Cardiovascular System.
According to the World Health Organization cardiovascular disease risk charts, the mortality rate of cardiovascular diseases in people is still high. The medical expenses caused by cardiovascular diseases are increasing daily, and the medical burden is becoming heavier; as such, it is imperative to prevent and cure cardiovascular diseases. A large number of scholars are analyzing the pathogenesis of cardiovascular diseases from various perspectives. Recent findings suggest that N6-methyladenosine (m6A) plays a multifaceted role in the cardiovascular system. m6A is a methylated modification product on RNA molecules and exists on various RNA molecules. It is one of the most common epigenetic modifications discovered to date. It regulates the expression of genes and subsequent responses. The amount of m6A is determined by methylases (writers) and demethylases (erasers). The third type of proteins, readers, selectively bind to m6A to regulate RNA stability and gene expression. In this paper, the relationship between m6A and related enzymes and cardiovascular structure and function was reviewed based on recent research results regarding the cardiovascular system.


[Intracellular gene delivery by polymer micelle vectors].
This review paper deals with the development of novel vector system for gene and antisense oligonucleotides. The system is based on the self-association of poly(ethylene glycol)-poly(L-lysine) block copolymer with DNA to form polyion complex micelles with unimodel size distribution in the range of 50-100 nm. DNA molecules are compactly assembled into the core of the micelle, surrounding with the dense corona of poly(ethylene glycol). High resistance to nuclease attack was demonstrated for micellized DNA in the serum-containing medium, indicating the potential of micelle vector system to stabilize DNA in physiological condition. Significant gene expression was confirmed by luciferase assay using 293 cell-line for these micelle vector systems with slightly cationic character.


[Epidemiological research on incidence of atopic disease in infants and children in relation to their nutrition in infancy].
Incidence and relative risk of atopic disease (atopic dermatitis; AD, bronchial asthma; BA, allergic rhinitis; AR) in Japanese infants and children in relation to their nutrition in infancy was analyzed from the data of the epidemiological survey which was conducted for 10,000 mothers of infants and children in 1993. A total of 4,610 replies were received: 2,714 from mothers of infants (12 months old) and 1,896 from mothers of children (2 years old). The subjects were allocated to following 3 groups based on their nutrition during first 3 months after birth; the breast-fed group (BF), the formula-fed group (EF), the mixed-fed group (MF). Incidence of atopic disease in BF, FF and MF was 23.5%, 22.2% and 21.8%, respectively and no statistical difference could be found among these 3 groups. AD was developed 17.0%, 14.4% and 13.9%; BA was 4.4%, 8.5% and 5.2%; AR was 4.9%, 6.5% and 5.8% in BF, FF and MF, respectively. Incidence of AD was significantly different between BF and MF (p < 0.01). Incidence of BA was also significantly different between BF and FF (p < 0.01). Risk of onset of BA and AR in FF was higher (adjusted odds ratio 2.2, 95% confidence interval 1.5-3.2 and adjusted odds ratio 1.5, 95% confidence interval 1.0-2.2, respectively) than that of BF controlled by age and family history with Cochran-Mantel-Haenzel test. With multiple logistic regression analysis, relative risk of the onset of BA in FF at the age of one year was 2.1, 95% confidence interval 1.2-3.5 and at the age of two years old was 2.5, 95% confidence interval 1.4-4.4. These results suggest that the breast-fed have certain suppression effects on incidence of bronchial asthma in infants and children.


Onion yellow phytoplasma P38 protein plays a role in adhesion to the hosts.
Adhesins are microbial surface proteins that mediate the adherence of microbial pathogens to host cell surfaces. In Mollicutes, several adhesins have been reported in mycoplasmas and spiroplasmas. Adhesins P40 of Mycoplasma agalactiae and P89 of Spiroplasma citri contain a conserved amino acid sequence known as the Mollicutes adhesin motif (MAM), whose function in the host cell adhesion remains unclear. Here, we show that phytoplasmas, which are plant-pathogenic mollicutes transmitted by insect vectors, possess an adhesion-containing MAM that was identified in a putative membrane protein, PAM289 (P38), of the 'Candidatus Phytoplasma asteris,' OY strain. P38 homologs and their MAMs were highly conserved in related phytoplasma strains. While P38 protein was expressed in OY-infected insect and plant hosts, binding assays showed that P38 interacts with insect extract, and weakly with plant extract. Interestingly, the interaction of P38 with the insect extract depended on MAM. These results suggest that P38 is a phytoplasma adhesin that interacts with the hosts. In addition, the MAM of adhesins is important for the interaction between P38 protein and hosts.


Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study: A Prospective Observational Cohort Study.
Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited. To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase-associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension). This is a 3-year observational prospective cohort study. The study includes 12 Canadian pediatric oncology centers. The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin. Exclusion criteria: Patients with an estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 or a pre-existing renal transplantation at baseline. Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected. Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR <90 mL/min/1.73m2 or albumin-to-creatinine ratio≥3mg/mmol. Hypertension is defined as per guidelines. Procedure: Patients are recruited before their first or second cisplatin cycle. Participants are evaluated during 2 cisplatin infusion episodes (AKI biomarker validation) and at 3, 12, and 36 months post-cisplatin treatment (late outcomes). The study has a relatively moderate sample size and short follow-up duration. There is potential for variability in data collection since multiple sites are involved. ABLE will provide a national platform to study biomarkers of late cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow-up needs.


Carcinoma of Maxillary Gingiva with Non-specific Cervical Lymph Node Swelling.
Swelling of the cervical lymph nodes may indicate lymphadenitis, malignant lymphoma, or metastasis. Lymph nodes larger than 10 mm on computed tomography (CT) are strongly indicative of postoperative metastasis from carcinoma. Here, we report a case of large, inflamed lymph nodes mimicking metastasis. The patient was a 76-year-old woman who experienced discomfort in the left-side maxillary gingiva commencing in August 2011. By September, the area had become painful, causing her to visit the Tokyo Dental College Chiba Hospital, at which time a 75×50-mm swollen ulcer was observed in the maxillary gingiva on the left side. A CT image revealed a neoplastic lesion between the alveolar bone on the left side of the maxilla and the base of the maxillary sinus, together with evidence of osteoclastic activity. The bilateral cervical lymph nodes were Level II and had a uniform interior of approximately 5 mm. The lesion was subsequently excised under general anesthesia. At 34 days postoperatively, CT imaging revealed bilateral 40-mm internal heterogeneous lymphadenopathy at Level II. No inflammation of the maxillary gingiva was observed, however, and blood tests revealed no inflammatory findings. Bilateral cervical lymph node metastasis was diagnosed based on CT and oral cavity observation. Radical neck dissection of left cervical region was performed under general anesthesia. Histopathological examination of the lymph nodes revealed no metastasis at Levels I-V, however. The reason for this increase in lymph node size is discussed.


An audit of cancer diagnosis in a Canadian children's hospital: Quality, timing and efficiency.
The diagnosis of paediatric cancer requires multidisciplinary cooperation to achieve both a timely diagnosis and efficient resource use. The authors undertook a 12-month audit of paediatric cancer cases to assess BC's Children's Hospital's (Vancouver, British Columbia) diagnostic process from the perspective of quality (timing and accuracy of diagnosis) and procedural efficiency, with an emphasis on the impact on resource use in the departments of radiology, pathology, anesthesia and surgery. Malignancies (excluding brain and cortical bone primary tumours, for which the preoperative diagnostic workup is often completed before admission) diagnosed between January 1 to December 31, 2003, were reviewed. Data collected included total outpatient versus inpatient procedures, number and timing of diagnostic procedures, general anesthesia (GA) requirements, and lag times from admission to biopsy to diagnosis during the initial hospitalization. Fifty-four patients were identified. Only 10 patients (19%) had an outpatient diagnostic procedure. One hundred seventeen inpatient diagnostic procedures were performed, with only 50% occurring within regular working hours. Thirty-one per cent of patients required two or more procedural GAs during their initial hospital admission. The mean lag time to biopsy was 2.6 days and to a pathological diagnosis was 1.2 days. Despite timeliness, the process of cancer diagnosis at BC Children's Hospital requires hospital admission and a significant consumption of resources outside of regular working hours. Opportunities for improvement include maximizing outpatient workup, allocating oncology operating room time to increase the percentage of weekday procedures and improving interdisciplinary procedural coordination to reduce the GA requirements per patient.


Flavobacterium hauense sp. nov., isolated from soil and emended descriptions of Flavobacterium subsaxonicum, Flavobacterium beibuense and Flavobacterium rivuli.
A strictly aerobic, Gram-staining-negative, rod-shaped, non-motile, yellow-pigmented bacterial strain, designated BX12(T), was isolated from soil collected from the peak area of Wudang Mountain in the city of Shiyan, Hubei province, China. Phylogenetic analysis of the 16S rRNA gene sequences showed that strain BX12(T) was most closely related to Flavobacterium subsaxonicum WB 4.1-42(T) (95.9% 16S rRNA gene sequence similarity), followed by Flavobacterium beibuense F44-8(T) (95.6%) and Flavobacterium rivuli WB 3.3-2(T) (94.1%). The major fatty acids (≥5%) of strain BX12(T) were summed feature 3 (comprising C(16:1)ω7c and/or C(16:1)ω6c), iso-C(15:0), C(16:0), iso-C(17:0) 3-OH, and C(16:0) 3-OH. The major polar lipid was phosphatidylethanolamine, and the major respiratory quinone was menaquinone-6. The genomic DNA G+C content was 43.9 mol%. On the basis of a high number of phenotypic differentiating properties and phylogenetic uniqueness, strain BX12(T) represents a novel species of the genus Flavobacterium for which the name Flavobacterium hauense sp. nov. is proposed. The type strain is BX12(T) ( =CCTCC AB 2012197(T) =KCTC 32147(T)). Emended descriptions of Flavobacterium subsaxonicum, Flavobacterium beibuense and Flavobacterium rivuli are also proposed.


[Unwanted wakefulness during general anesthesia].
Intraoperative wakefulness ("awareness") is still a relevant problem. Different stages of wakefulness exist: conscious awareness with explicit recall of pain in 0.03% and with nonpainful explicit recall in 0.1-0.2% of all anesthesias; amnesic awareness or implicit recall may occur with unknown, even higher incidences. Sufficient analgesia minimizes possible painful perceptions. Opioids, benzodiazepines, and N(2)O alone or combined lead to the highest incidences of nonpainful intraoperative wakefulness. Volatile anesthetics, etomidate, barbiturates, and propofol in sufficient doses effectively block any sensory processing and therefore abolish intraoperative wakefulness. Intraoperative awareness with recall may lead to sustained impairment of the patients, in severe cases even to a post-traumatic stress disorder (PTSD). The observation of clinical signs does not reliably detect intraoperative wakefulness in all cases; monitoring of end-tidal gas concentrations, EEG, or evoked potentials may help in prevention. Active information is recommended only for patients at higher risk. Complaints about recall of intraoperative events should be taken seriously; in cases of sustained symptoms psychological help may be necessary.


Prevalence and epidemiologic significance of antibody to hepatitis B core antigen in Greece.
The diagnostic and epidemiologic significance of antibody to hepatitis B core antigen (anti-HBc) detected by complement fixation was studied in a sample of 412 healthy persons, 0-70 years old of both sexes living in the Athens area. The prevalence of hepatitis B virus (HBV) infections was found to be very high (26.5%) and the hepatitis B surface antigen (HBsAg) carrier rate (4.1%) among the highest in Europe. Anti-HBc was detected in 63 (15.3%) of the examined infection. The prevalence of anti-HBc (without HBsAg or anti-HBs) increased with age, while the HBsAg carrier rate declined in older age groups. It was also found that the frequency of anti-HBc persists for a shorter period than the anti-HBs after HBV infection. These data stress the importance of anti-HBc testing in increasing the sensitivity of the detection of potentially infective HBV carriers as well as in studying various epidemiologic aspects of HBV infection.


Failure of dopexamine to protect the hypoxemic newborn rabbit kidney.
The renal effects of dopexamine, a new dopaminergic agonist devoid of any alpha-adrenergic effect, were studied in 11 anesthetized newborn rabbits undergoing an acute hypoxemic normocapnic stress. Acute hypoxemia (PaO2 = 41 mm Hg) was associated with a marked increase in renal vascular resistance and a consequent decrease in glomerular filtration rate and renal blood flow. These changes were not modified by the administration of dopexamine at 10 micrograms/kg/min. Failure of dopexamine to blunt the hypoxemia-induced vaso-constriction suggests vascular dopaminergic receptor immaturity.


POSTERIOR UVEAL EFFUSION POST TRABECULECTOMY IN UNILATERAL INFANTILE GLAUCOMA: A CASE REPORT AND MANAGEMENT CHALLENGES.
Choroidal effusion is an abnormal collection of fluid within the suprachoroidal potential space. It is a common complication following glaucoma filtering surgeries such as trabeculectomy. It is a clinical diagnosis that sometimes goes undetected or unreported, except when symptomatic. Reported incident rates is 7.9 - 18.8% for serous effusions and 0.7 - 3% for haemorrhagic effusions. This report aims to highlight a case of choroidal effusion after trabeculectomy and its management challenges. A seven year old boy presented to our facility with history of cloudy appearance of the right eye of five years duration. He was diagnosed with right infantile glaucoma. Intraocular pressures (IOP) were 44mmHg and 18mmHg right and left eyes respectively. Patient subsequently had right trabeculectomy. He developed hypotony at post-operative day two and a right choroidal effusion was noticed at post-operative day four. As a result of this, he initially had a right anterior chamber reformation with ocular viscoelastic on day seven. Later, a compression suture over the bleb and sclerostomy was performed 11 days post initial surgery. Choroidal effusion progressively regressed post-operatively and completely resolved at day five post-sclerostomy and effusion drainage. Choroidal effusion is a common complication after trabeculectomy in which conservative management results in resolution. However, when conservative management fails, surgical intervention should not be delayed to maximize good outcome.