Association between oral function and physical pre-frailty in community-dwelling older people: a cross-sectional study.
Few studies have examined the relationship between oral functions and the physical pre-frailty status, classified using physical function tests. This cross-sectional study aimed to clarify this association among community-dwelling older people from the Itoshima Frail Study in Itoshima Fukuoka Prefecture. Of the 1,555 individuals invited to join the study, 381 (188 males and 193 females) enrolled. Their physical pre-frailty was assessed with a classification system consisting of two physical indicators (fatigue and unintentional weight loss, determined with a questionnaire), two functional components (declined walking speed and muscle weakness, determined using a body function measuring instrument), and declined physical activity (examined using a triaxial accelerometer). Subsequently, the individuals were classified into three groups: robust, pre-frailty, and frailty. Along with the number of teeth remaining, oral functions, such as masticatory performance, tongue pressure strength, and oral diadochokinesis (ODK), were examined. Data regarding social activity and exercise habits were collected, and the individuals' body compositions were measured. Odds ratios (ORs) and 95% confidence intervals (CIs) for the physical pre-frailty were calculated using logistic regression models. In this study, 126 (33%) participants presented with physical pre-frailty. The participants in the robust group were younger, had stronger maximum handgrip strength, and walked faster than those in the physical pre-frailty group (p < 0.001). The robust group presented with better oral functions (masticatory performance, p = 0.015; oral ODK /ta/, p = 0.004). The physical pre-frailty status was significantly associated with age (OR, 1.111; 95% CI, 1.048-1.178; p < 0.001), masticatory performance (OR, 0.819; 95% CI, 0.680-0.986; p = 0.035), low ODK/ta/ (OR, 1.864; 95% CI, 1.069-3.250; p = 0.028), and low social activity (OR, 2.273; 95% CI, 1.308-3.951; p = 0.004). This study indicated that older people with higher age, lower anterior tongue movement, lower masticatory performance, and lower social activity are positively associated with physical pre-frailty.


Effect of Human Testicular Cells Conditioned Medium on In Vitro Maturation and Morphology of Mouse Oocytes.
Testicular cell conditioned medium (TCCM) has been shown to induce female germ cell development In Vitro from embryonic stem cells (ESCs). Testicular cells (TCs) secrete a variety of growth factors such as growth differentiation factor-9 (GDF-9), bone morphogenetic protein 4 (BMP-4), stem cell factor (SCF), leukemia inhibitory factor (LIF), and other, that could improve oocyte maturation. Here we have investigated the effect of human TCCM (hTCCM) on in vitro maturation (IVM) and morphology of mouse oocytes. In this experimental study, 360 germinal vesicle (GV) oocytes were obtained from NMRI mice, aged 4-6 weeks that had received 5 IU pregnant mare's serum gonadotropin (PMSG) 48 hours before. GV oocytes were subjected to IVM. 120 GV oocytes were cultured in each medium; hTCCM as the test group, DMEM + 20%FBS as the control group and Ham's F10 + HFF medium as the sham group. The rates of the IVM and perivitelline space (PVS) changes were recorded at 8, 16 and 24 hours after culture. The metaphase II (MII) oocytes were subjected for in vitro fertilization (IVF) and the fertilization rate was evaluated after 1, 2, and 3 days. There was a significant difference between the maturation rates in hTCCM (31.67% MII) and the control [0% MII, P<0.05, (7.5% MI, 52.5% deg. and 40%GV)] groups but there was not a significant difference between the maturation rates in hTCCM and the sham group (53.33% MII, P>0.05). IVF success rate for MII oocytes obtained from IVM in the hTCCM group was 28.94% (n=11). Our data showed that hTCCM is an effective medium for GV oocyte growth and maturation compared to the control medium. Our findings show that TCCM supports oocyte IVM in mice and affect oocyte morphology.


Development of phenotypic differences in sensillum populations on the antennae of a grasshopper, Schistocerca americana.
The development of diet-induced phenotypic differences in numbers of sensilla on the antennae of the grasshopper Schistocerca americana was studied using the exuviae produced at each molt. This made it possible to follow changes within an individual insect. In the first instar, insects had similar numbers of four sensillum types: uniporous trichoid sensilla, coeloconic sensilla, and large and small multiporous basiconic sensilla. Rearing on lettuce resulted in sixth instars with greater numbers of three sensillum types than siblings reared on an artificial diet. The first statistically significant differences between treatments in numbers of trichoid sensilla and large basiconic sensilla occurred in the third and fourth instars, respectively. No major reductions in sensillum numbers occurred at any time and the phenotypic differences resulted from differences in the numbers added at each molt.


Keeping support and clinical supervision on your agenda.
Support and clinical supervision can benefit staff and service users. Inquiries have highlighted lack of support and clinical supervision as potential contributory factors for adverse care events. For support and clinical supervision to be embedded effectively, leaders and managers must value and promote them in their organisations. This article describes practical steps to support implementation of clinical supervision. By examining the main stages of supervision and preparation, evaluation of process and outcomes, and practical considerations, the article supports healthcare managers to encourage staff engagement and to implement a clinical supervision process.


The IgE/IgG binding capacity and structural changes of Alaska Pollock parvalbumin glycated with different reducing sugars.
Parvalbumin (PV) is one of the major allergens in fish. The aim of our present work was to research the influence mechanism of glycation with different reducing sugars (glucose, fructose, ribose, lactose, and galactose) on the immunoglobulin E (IgE) and immunoglobulin G (IgG) binding capacity and structure changes of PV in Alaska Pollock. PV glycated with glucose or fructose (PV-Glu/ PV-Fru) exhibited the higher IgE/IgG binding capacities than that of ribose, galactose, or lactose. During glycation, the lysine (Lyr), tyrosine (Tyr), and phenylalanine (Phe) of PV were gradually embed into core area of three-dimensional structure of protein, which reflected in the ultraviolet (UV) spectrum and fluorescence spectra. Moreover, the increase of surface hydrophobicity had confirmed the conformation alteration of glycated PV. These results suggest that there is a specific association among the change of PV in glycation and in potential allergenicity. The types and conformation of reducing sugar greatly influenced the IgE/IgG binding capacity of PV, and glycation with ribose and galactose was a promising approach for reducing the IgE/IgG binding capacity of PV from Alaska Pollock. PRACTICAL APPLICATIONS: Parvalbumin (PV), the major allergen of fish, it can not only maintain the physiological activity of cells, but also cross react with human amyloid protein to alleviate Alzheimer's disease and Parkinson's syndrome. This study revealed that the IgE/IgG binding capacity and structural changes of PV from Alaska Pollock modified by glycation with different reducing sugars. This will help us to understand the sensitization and structural change of the glycated products after the reaction of PV with different reducing sugars. It provides an effective carbonyl source for the preparation of low antigenicity PV based on glycation and lays a foundation for glycation modification of other food allergens.


ECT-induced seizure durations.
Electroconvulsive therapy (ECT) efficacy is related to the stimulus intensity and clinically associated with the duration of the induced seizure. Convulsions lasting 30 to 60 seconds are conventionally considered to be of optimal length, and generally are achieved by applying routine ECT technique. An ictus slightly shorter or longer is usually also therapeutically satisfactory. In our study, seizures lasting between 30 and 60 seconds produced a favorable clinical outcome. A very similar effect was observed in all cases where the duration was within 16 to 120 seconds. However, subjects experiencing intal periods of less than 15 seconds and those over 120 seconds resulted in less favorable response. Detailed records as to medicinal and electrical stimulus doses, seizure timings, etc, were excellent guides for subsequent ECT to achieve appropriate convulsion durations and a safe, satisfactory outcome.


Blastocyst culture: facts and fiction.
The use of sequential media has made extended culture and transfer of blastocysts feasible for human IVF. Embryo transfer on day 5 has been claimed to result in higher implantation rates than transfer on day 3, on the basis of retrospective comparative studies. This is not supported convincingly, however, in randomized controlled trials published to date. Blastocyst culture imposes additional requirements in terms of personnel, equipment, education and cost and is associated with a greater incidence of monozygotic twinning and cycle cancellation rate than in the case of day 3 culture. In order for day 5 transfer to replace day 3 transfer, a convincing comparison between the two methods should therefore demonstrate the superiority of blastocyst transfer. There is still a need for properly designed randomized controlled trials to compare day 3 with day 5 transfer which will also address the effectiveness of a single blastocyst replacement in reducing the incidence of multiple pregnancies as well as the value of blastocyst cryopreservation.


Embryonic lethality in mice lacking mismatch-specific thymine DNA glycosylase is partially prevented by DOPS, a precursor of noradrenaline.
Thymine DNA glycosylase (TDG) is involved in the repair of G:T and G:U mismatches caused by hydrolytic deamination of 5-methylcytosine and cytosine, respectively. Recent studies have shown that TDG not only has G-T/U glycosylase activities but also acts in the maintaining proper epigenetic status. In order to investigate the function of TDG in vivo, mice lacking Tdg, Tdg (-/-), were generated. Tdg mutant mice died in utero by 11.5 days post coitum (dpc), although there were no significant differences in the spontaneous mutant frequencies between wild type and Tdg (-/-) embryos. On the other hand, the levels of noradrenaline in 10.5 dpc whole embryos, which is necessary for normal embryogenesis, were dramatically reduced in Tdg (-/-) embryos. Consequently, we tested the effect of D, L-threo-3, 4-dihydroxyphenylserine (DOPS), a synthetic precursor of noradrenaline, on the survival of the Tdg (-/-) embryos. DOPS was given to pregnant Tdg (+/-) mice from 6.5 dpc through drinking water. Most of the Tdg (-/-) embryos were alive at 11.5 dpc, and they were partially rescued up to 14.5 dpc by the administration of DOPS. In contrast, the administration of L-3, 4-dihydroxyphenylalanine (L-DOPA) had marginal effects on Tdg (-/-) embryonic lethality. No embryo was alive without DOPS beyond 11.5 dpc, suggesting that the lethality in (-/-) embryos is partially due to the reduction of noradrenaline. These results suggest that embryonic lethality in Tdg (-/-) embryos is due, in part, to the reduction of noradrenaline levels.


A novel, non-invasive, online-monitoring, versatile and easy plant-based probe for measuring leaf water status.
A high-precision pressure probe is described which allows non-invasive online-monitoring of the water relations of intact leaves. Real-time recording of the leaf water status occurred by data transfer to an Internet server. The leaf patch clamp pressure probe measures the attenuated pressure, P(p), of a leaf patch in response to a constant clamp pressure, P(clamp). P(p) is sensed by a miniaturized silicone pressure sensor integrated into the device. The magnitude of P(p) is dictated by the transfer function of the leaf, T(f), which is a function of leaf patch volume and ultimately of cell turgor pressure, P(c), as shown theoretically. The power function T(f)=f(P(c)) theoretically derived was experimentally confirmed by concomitant P(p) and P(c) measurements on intact leaflets of the liana Tetrastigma voinierianum under greenhouse conditions. Simultaneous P(p) recordings on leaflets up to 10 m height above ground demonstrated that changes in T(f) induced by P(c) changes due to changes of microclimate and/or of the irrigation regime were sensitively reflected in corresponding changes of P(p). Analysis of the data show that transpirational water loss during the morning hours was associated with a transient rise in turgor pressure gradients within the leaflets. Subsequent recovery of turgescence during the afternoon was much faster than the preceding transpiration-induced water loss if the plants were well irrigated. Our data show the enormous potential of the leaf patch clamp pressure probe for leaf water studies including unravelling of the hydraulic communication between neighbouring leaves and over long distances within tall plants (trees).


Magnetic resonance imaging of diabetic muscle infarction: report of two cases.
Diabetic muscle infarction (DMI) occurs as a rare complication of long standing or severe diabetes mellitus. The condition usually occurs spontaneously and patients usually present with acute pain and swelling of affected muscles which persists for weeks, and resolves spontaneously without intervention. Magnetic resonance (MR) imaging is the modality of choice in patients with suspected DMI based on appropriate clinical setting and plays a major role in the diagnosis, assessing the extent of involvement and differentiating DMI from other conditions. The DMI affected muscles are bulky and appear heterogeneous with hyperintense signals on T2-weighted and STIR sequences, hypo or isointense on T1-weighted images with loss of normal fatty intramuscular septae. Subcutaneous and perifascial edema can be present. On postgadolinium scans, there is diffuse heterogeneous enhancement with non-enhancing foci, which may represent areas of necrosis. Biopsy can be avoided as MR findings are highly sensitive and specific. Treatment is usually conservative. Surgical intervention is required only in patients who do not respond to conservative management. The common differential diagnosis includes cellulitis, abscess, necrotizing fasciitis and polymyositis. We present two cases below to highlight the clinical, MR imaging findings and differential diagnosis of DMI.


Hepatic neutrophil influx: eicosanoid and superoxide formation in endotoxemia.
We examined early changes, at 0.5, 1.5, and 3 hr of infusion of a nonlethal dose of Escherichia coli endotoxin (ET) in neutrophil (PMN) sequestration in the liver and accompanying alterations in [1-14C]arachidonic acid metabolism and superoxide anion release by Kupffer and endothelial cells and PMNs. One hundred fifty micrograms ET (268 micrograms/kg) was infused over 3 hr. Shorter infusions delivered proportionally less ET. By 30 min of ET infusion the number of PMNs in the 45 ml/min fraction was 2.41 x 10(7), eightfold higher than that in the NaCl-infused rats, representing 35.90 +/- 3.49% (n = 7) of the total cell yield vs 8.20 +/- 0.20% (n = 4) in NaCl controls. By 90 and 180 min of ET infusion the number of PMNs and their share of the total cell yield increased significantly further. Cells were separated by elutriation, followed by application of a Ficoll-Hypaque gradient, when appropriate. Kupffer cells and PMNs were recovered in the 45 ml/min fraction, endothelial cells in the 23 ml/min fraction. At 30 min of ET infusion the profile of arachidonic acid metabolites released from [1-14C]arachidonic acid-prelabeled nonparenchymal cells upon A23187 stimulation was not different from that of cells of NaCl-infused rats. Infusion of ET for 90 min accentuated PMN infiltration, and resulted in significant modulation of the eicosanoid profile, consisting of a major shift in PGD2/PGE2 to PGE2, and LTB4 and 12-HETE accounting for 34% of the total eicosanoids, compared to 12.9% in time-matched NaCL controls.(ABSTRACT TRUNCATED AT 250 WORDS)


The effect of masks on the emotion perception of a facial crowd.
The present study investigated the effect of facial masks on people's ability to perceive emotions in crowds. We presented faces with the bottom halves occluded by masks or full faces without occlusion. In two sequentially presented crowds, we varied the number of faces, emotional valence, and intensity of facial expressions, examining the impact of masks on the perception of crowd emotion. Participants reported which of the two crowds they would avoid based on the crowds' average emotions. The participants' ability to judge the average emotion of a crowd, especially a crowd expressing happiness, was impaired when the crowd wore masks. For faces covered by masks, crowd emotion judgments were more negatively biased than those without masks. However, participants could still distinguish the emotional intensities of a crowd wearing masks above chance. Additionally, participants responded more quickly to a crowd with more people without compromising accuracy, despite the perceptual challenges imposed by facial masks. Our results suggest that under ambiguous social situations in which individuals' emotions are partially hidden by masks, a large group may provide stronger social cues than a small group, thereby promoting communication and regulating social behaviors.


Surfactant proteins A and D in children with pulmonary disease due to gastroesophageal reflux.
Children with gastroesophageal reflux often suffer from chronic, severe lung damage and recurrent infections. The mechanisms may involve reflux induced lung injury with alterations of the surfactant proteins (SP) SP-A and SP-D, which bind specifically to various microbes and increase their elimination by granular leukocytes and macrophages. In 20 children with gastroesophageal reflux disease (GERD) the bronchoalveolar lavage content and macromolecular organization of SP-A and SP-D was determined by enzyme linked immunosorbent assay and gel chromatography. For comparison, lavages from 17 children without respiratory diseases were investigated. Both, SP-A and SP-D were significantly reduced in children with GERD-median (25, 75 percentiles) SP-A: 362 (169, 494) ng/ml versus 867 (656, 1,761) in control subjects and SP-D: 174 (73, 456) ng/ml versus 518 (295, 748) ng/ml in control subjects. The more active, higher molecular weight oligomers of SP-A and especially those of SP-D were diminished, whereas the smaller sized forms of SP-D were markedly increased. In children with GERD, significantly reduced amounts of SP-A and SP-D and an altered structural organization of the surfactant protein oligomers were demonstrated. Such impairments of central components of the innate host defense system may contribute to the pathogenesis of the chronic lung disease commonly observed in these children.


A systematic review investigating outcome measures and uptake barriers when children and youth with complex disabilities use eye gaze assistive technology.
Children with complex disabilities sometimes have difficulty communicating with their parents, caregivers, and teachers. For these children, eye gaze assistive technology can be used to facilitate communication. Eye gaze assistive technology outcomes for children and youth were analyzed in this systematic review. Database and hand-searches yielded 4412 unduplicated results, of which 11 articles were eligible for this review. Outcome measures, as well as environmental and personal factors, were mapped to the World Health Organization's International Classification of Functioning, Disability and Health framework. Communication outcomes were most prevalent and co-occurred with outcomes in all reported activities and participation domains. Environmental and personal factors were classified as either facilitators or as barriers in relation to device uptake and success. Although comprehensive professional and caregiver support was the primary facilitator for success, barriers could lead to rejection of the technology even when children were successful using the system.


Bisphosphonates affect migration ability and cell viability of HUVEC, fibroblasts and osteoblasts in vitro.
Bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) is a side effect in patients being treated with bisphosphonates. The bisphosphonates most often associated with BP-ONJ are the highly potent nitrogen-containing bisphosphonates, e.g. pamidronate or zoledronate. In terms of BP-ONJ aetiology, several theories are being discussed: inhibition of bone remodelling, effect on soft tissues, and antiangiogenic effect of bisphosphonates. The aim of this in vitro study was to investigate the effect of different potent bisphosphonates on osteoblasts, fibroblasts and human umbilicord vein endothelial cells (HUVEC). Three nitrogen-containing bisphosphonates (ibandronate, pamidronate and zoledronate) and one non-nitrogen-containing bisphosphonate (clodronate) were compared concerning their potency on apoptosis induction (tunel), cell viability (calcein assay) and migration potency (boyden chamber) on osteoblasts, fibroblasts and HUVEC. The nitrogen-containing bisphosphonates, particularly pamidronate and zoledronate, affect cell viability, cell migration and the induction of apoptosis of osteoblasts, fibroblasts and HUVEC. These results support the theory that BP-ONJ is a multifactorially caused disease because several cell lines of the oral cavity which are responsible for integrity and wound healing are negatively affected by nitrogen-containing bisphosphonates. Perioperative interruption of bisphosphonate application during dental surgical procedures--if possible--might be feasible to promote better wound healing.


Automated affinity capture-release of biotin-containing conjugates using a lab-on-valve apparatus coupled to UV/visible and electrospray ionization mass spectrometry.
We report a new method for automated affinity capture and release of biotin-containing conjugates on immobilized streptavidin using a lab-on-valve (LOV) bead injection apparatus. The apparatus is also coupled to UV/visible and electrospray ionization mass spectrometry (ESI-MS) for monitoring the captured and released biotin-containing conjugates. Dissociation rate constants for release from streptavidin of two chromophore-tagged biotin conjugates were measured by UV/visible spectrometry and the dissociation was simultaneously monitored by ESI-MS. The LOV-ESI-MS instrument was also used for repetitive assays of lysosomal beta-galactosidase in human cell homogenates. Fast analysis in 4.5 min/full cycle and robust operation in 60 repetitive analyses are demonstrated that are promising for transfer of the LOV-ESI-MS technology into clinical practice.


[Biochemical characteristics of operating bile composition in different types of cholecystolithiasis].
With a view to predicting the outcomes of surgical treatment of cholelithiasis, depending on the composition of concretions by high performance liquid chromatography was studied lipid composition and the spectrum of the operating bile acids in 10 patients with bile pigment cholelithiasis, 15--with cholesterol cholelithiasis, 15--with a combination of cholesterol cholelithiasis, and scab forms cholesterosis gallbladder, 6--to polypous-mesh form cholesterosis gallbladder. As a control, use the operating bile 6 patients with adenomatous and fibro-adenomatous polyps of the gallbladder. Based on the results of the study was proved the need for correction of biliary insufficiency in patients operated on for cholesterin associated pathology of the gallbladder. Spectrum of bile acids of operating bile helped justify holding litholytic therapy to prevent aggregation of bile.


Rapamycin inhibits mTORC1, but not completely.
Rapamycin is widely used as a complete inhibitor of the mTORC1 nutrient-sensitive signaling complex. Using a novel ATP-competitive inhibitor named Torin1, we have found that many mTORC1 functions that regulate cap-dependent translation and autophagy are resistant to inhibition by rapamycin.


Pair rule gene orthologs in spider segmentation.
The activation of pair rule genes is the first indication of the metameric organization of the Drosophila embryo and thus forms a key step in the segmentation process. There are two classes of pair rule genes in Drosophila: the primary pair rule genes that are directly activated by the maternal and gap genes and the secondary pair rule genes that rely on input from the primary pair rule genes. Here we analyze orthologs of Drosophila primary and secondary pair rule orthologs in the spider Cupiennius salei. The expression patterns of the spider pair rule gene orthologs can be subdivided in three groups: even-skipped and runt-1 expression is in stripes that start at the posterior end of the growth zone and their expression ends before the stripes reach the anterior end of the growth zone, while hairy and pairberry-3 stripes also start at the posterior end, but do not cease in the anterior growth zone. Stripes of odd-paired, odd-skipped-related-1, and sloppy paired are only found in the anterior portion of the growth zone. The various genes thus seem to be active during different phases of segment specification. It is notable that the spider orthologs of the Drosophila primary pair rule genes are active more posterior in the growth zone and thus during earlier phases of segment specification than most orthologs of Drosophila secondary pair rule genes, indicating that parts of the hierarchy might be conserved between flies and spiders. The spider ortholog of the Drosophila pair rule gene fushi tarazu is not expressed in the growth zone, but is expressed in a Hox-like fashion. The segmentation function of fushi tarazu thus appears to be a newly acquired role of the gene in the lineage of the mandibulate arthropods.


Role of AMPK/mTOR-independent autophagy in clear cell renal cell carcinoma.
We examined the status and role of autophagy, a process of lysosomal recycling of cellular material, in clear cell renal cell carcinoma (ccRCC). Paired samples of tumor and adjacent non-malignant tissue were collected from 20 patients with ccRCC after radical nephrectomy. The mRNA levels of apoptosis (BAD, BAX, BCL2, BCLXL, BIM) and autophagy (ATG4, BECN1, GABARAP, p62, UVRAG) regulators were measured by RT-qPCR. The protein levels of autophagosome-associated LC3-II, autophagy receptor p62, apoptotic marker PARP, as well as phosphorylation of autophagy initiator Unc 51-like kinase 1 (ULK1), its activator AMP-activated protein kinase (AMPK) and 4EBP1, the substrate of ULK1 inhibitor mechanistic target of rapamycin (mTOR), were analyzed by immunoblotting. The mRNA levels of pro-apoptotic BAX, anti-apoptotic BCLXL and pro-autophagic ATG4, p62 and UVRAG were higher in ccRCC tumors. Autophagy induction was confirmed by an increase in phospho-ULK1 and degradation of the autophagic target p62, while apoptotic PARP cleavage was unaltered. AMPK phosphorylation was reduced and 4EBP1 phosphorylation was increased in ccRCC tissue. The expression of apoptosis regulators did not correlate with clinicopathological features of ccRCC. Conversely, high mRNA levels of ATG4, GABARAP and p62 were associated with lower tumor stage, as well as with smaller tumor size and better disease-specific 5-year survival (ATG4 and p62). Accordingly, low p62 protein levels, corresponding to increased autophagic flux, were associated with lower tumor stage, reduced metastasis and improved 5-year survival. These data demonstrate that transcriptional induction of autophagy in ccRCC is accompanied by AMPK/mTOR-independent increase in ULK1 activation and autophagic flux, which might slow tumor progression and metastasis independently of apoptosis.


A Pilot Study on the Feasibility of Developing and Implementing a Mobile App for the Acquisition of Clinical Knowledge and Competencies by Medical Students Transitioning from Preclinical to Clinical Years.
Due to the COVID-19 pandemic and the consequent restrictions, universities have had to adapt their curricula substantially to new schemes in which remote learning is of the essence. In this study, we assess the feasibility of developing a mobile app supplementary to the distant teaching paradigm for the "Cardiology" module of the "General Pathology" subject in undergraduate Medical Education, and we evaluate its impact and acceptability. A cohort of volunteer second-year medical students (n = 44) had access to the app, and their opinions on its utility (1−10) were collected. Additionally, the students were invited to refer their expected satisfaction (1−10) with a blended learning methodology overlapping this new tool with the traditional resources. The average expected satisfaction had been compared to the average satisfaction obtained by just the traditional methodology in other modules from the same subject. Through a qualitative approach, we defined the strengths and weaknesses of the tool. Seventy-seven percent of the participants rated at 8/10 or more the potential learning value of the application and, if used as a supplement to traditional teaching, it would also statistically improve the satisfaction of students (6.52 vs. 8.70, p < 0.001). Similarly, the qualitative data corroborated the benefits of such innovation. Multidisciplinary collaborations are encouraged to develop teaching innovations, although further research should aim to better define the effectiveness of learning with these resources.


Mucosa-associated lymphoid tissue lymphoma.
A distinctive type of low-grade extranodal lymphoma recapitulates the cytomorphologic features of mucosa-associated lymphoid tissue (MALT). Typically, these MALT lymphomas arise from sites normally devoid of lymphoid tissue, but are preceded by chronic inflammatory, usually autoimmune, disorders that result in the accumulation of lymphoid tissue. The stomach is the most common site of MALT lymphoma, which arises from lymphoid tissue acquired as the result of Helicobacter pylori infection. The indolent clinical behavior of gastric MALT lymphoma coupled with certain histologic features suggests that its growth is subject to immunologic stimuli, and the role of H pylori in this respect has been examined in detail. In vitro experiments have shown that the growth of lymphoma cells is stimulated by contact with T cells, which, in turn, show strain specific responses to heat-killed H pylori. Clinically, approximately 70% of cases of stage IE gastric MALT lymphoma regress following eradication of H pylori with antibiotics. Large, deeply invasive tumors and those that have undergone high-grade transformation typically do not respond to antibiotic therapy. Other common sites of MALT lymphoma include the salivary glands, lung, and ocular adnexa. The clinicopathologic features of these lymphomas are remarkably similar to gastric MALT lymphoma, which suggests that they, too, may be antigen-driven.


Structural Characterization and Assessment of Anti-Inflammatory Activities of Polyphenols and Depsidone Derivatives from Melastoma malabathricum subsp. normale.
The roots of Melastoma malabathricum subsp. normale (D. Don) Karst. Mey have been used in traditional ethnic medicine systems in China to treat inflammation-triggered ailments, such as trauma, toothache, and fever. Therefore, the aim of this study is to screen for compounds with anti-inflammatory activity in the title plant. The extract of M. malabathricum subsp. normale roots was separated using various chromatographic methods, such as silica gel, ODS C18, MCI gel, and Sephadex LH-20 column chromatography, as well as semi-preparative HPLC. One new complex tannin, named whiskey tannin D (1), and an undescribed tetracyclic depsidone derivative, named guanxidone B (2), along with nine known polyphenols (2-10) and three known depsidone derivatives (12-14) were obtained from this plant. The structures of all compounds were elucidated by extensive NMR and CD experiments in conjunction with HR-ESI-MS data. All these compounds were isolated from this plant for the first time. Moreover, compounds 1-4, 8, and 10-14 were obtained for the first time from the genus Melastoma, and compounds 1, 2, and 11-14 have not been reported from the family Melastomataceae. This is the first report of complex tannin and depsidone derivatives from M. malabathricum subsp. normale, indicating their chemotaxonomic significance to this plant. Compounds 1-12 were investigated for their anti-inflammatory activities on the production of the nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and compounds 1, 11, and 12 showed anti-inflammatory activities with IC50 values of 6.46 ± 0.23 µM, 8.02 ± 0.35 µM, and 9.82 ± 0.43 µM, respectively. The structure-activity relationship showed that the catechin at glucose C-1 in ellagitannin was the key to its anti-inflammatory activity, while CH3O- at C-16 of aromatic ring A in depsidone derivatives had little effect on its anti-inflammatory activity. The study of structure-activity relationships is helpful to quickly discover new anti-inflammatory drugs. The successful isolation and structure identification of these compounds, especially complex tannin 1, not only provide materials for the screening of anti-inflammatory compounds, but also provide a basis for the study of chemical taxonomy of the genus Melastoma.


Construction of protein interaction network involved in lung adenocarcinomas using a novel algorithm.
Studies that only assess differentially-expressed (DE) genes do not contain the information required to investigate the mechanisms of diseases. A complete knowledge of all the direct and indirect interactions between proteins may act as a significant benchmark in the process of forming a comprehensive description of cellular mechanisms and functions. The results of protein interaction network studies are often inconsistent and are based on various methods. In the present study, a combined network was constructed using selected gene pairs, following the conversion and combination of the scores of gene pairs that were obtained across multiple approaches by a novel algorithm. Samples from patients with and without lung adenocarcinoma were compared, and the RankProd package was used to identify DE genes. The empirical Bayesian (EB) meta-analysis approach, the search tool for the retrieval of interacting genes/proteins database (STRING), the weighted gene coexpression network analysis (WGCNA) package and the differentially-coexpressed genes and links package (DCGL) were used for network construction. A combined network was also constructed with a novel rank-based algorithm using a combined score. The topological features of the 5 networks were analyzed and compared. A total of 941 DE genes were screened. The topological analysis indicated that the gene interaction network constructed using the WGCNA method was more likely to produce a small-world property, which has a small average shortest path length and a large clustering coefficient, whereas the combined network was confirmed to be a scale-free network. Gene pairs that were identified using the novel combined method were mostly enriched in the cell cycle and p53 signaling pathway. The present study provided a novel perspective to the network-based analysis. Each method has advantages and disadvantages. Compared with single methods, the combined algorithm used in the present study may provide a novel method to analyze gene interactions, with increased credibility.


Gefitinib: new preparation. Non small-cell lung cancer: stricter assessment needed.
(1) Platinum-based chemotherapy is generally used to treat advanced-stage non small-cell lung cancer (stages III and IV), but has only a modest impact on survival. There is no reference treatment. (2) Gefitinib inhibits the tyrosine kinase activity of the receptor for EGF (epidermal growth factor), which is thought to be involved in tumour growth. It has a temporary licence in France and is used on a named-patient basis, but full marketing authorisation has already been granted in Japan, the United States, and elsewhere. (3) Two double-blind dose-finding studies compared two doses of oral gefitinib monotherapy (250 mg/day and 500 mg/day) in patients in whom at least two lines of chemotherapy had failed. The results were favourable, with a median survival of 6 months and a symptomatic improvement in some patients, but they are undermined by the absence of a placebo group and by major protocol violations. (4) Two double-blind trials, each in more than 1000 patients, showed that gefitinib does not increase the efficacy of first-line platinum combinations. (5) About 15% of patients receiving gefitinib monotherapy in clinical trials stopped taking the treatment because of adverse events. The most frequent were gastrointestinal (diarrhea, nausea, vomiting) and cutaneous (rash, acne, dry skin, pruritus). (6) Interstitial pneumonitis occurred in about 1% of patients, and was fatal in about one-third of cases. (7) Gefitinib is metabolised by the cytochrome P450 isoenzyme CYP3A4, so carries a potentially high risk of interactions. (8) In practice, more thorough assessment of gefitinib is needed to determine whether this new drug is beneficial for patients with non small-cell lung cancer. Marketing authorisation is not currently justified.


[Treatment of a patient with obstructive sleep apnea syndrome superimposed on chronic obstructive pulmonary disease].
History of a middle aged obese male, presenting with severe obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) is described. Provisionally patient was started on CPAP and long-term domiciliary oxygen therapy (LTOT). OSA was successfully treated by surgical repair of nasal patency and partial uvulectomy. There was also remarkable improvement in ventilatory indices after steroid therapy. There was no further need for CPAP and LTOT.


A parallel circuit of LIF signalling pathways maintains pluripotency of mouse ES cells.
The cytokine leukaemia inhibitory factor (LIF) integrates signals into mouse embryonic stem (ES) cells to maintain pluripotency. Although the Jak-Stat3 pathway is essential and sufficient to mediate LIF signals, it is still unclear how these signals are linked to the core circuitry of pluripotency-associated transcription factors, consisting of Oct3/4 (also called Pou5f1), Sox2 and Nanog. Here we show that two LIF signalling pathways are each connected to the core circuitry via different transcription factors. In mouse ES cells, Klf4 is mainly activated by the Jak-Stat3 pathway and preferentially activates Sox2, whereas Tbx3 is preferentially regulated by the phosphatidylinositol-3-OH kinase-Akt and mitogen-activated protein kinase pathways and predominantly stimulates Nanog. In the absence of LIF, artificial expression of Klf4 or Tbx3 is sufficient to maintain pluripotency while maintaining the expression of Oct3/4. Notably, overexpression of Nanog supports LIF-independent self-renewal of mouse ES cells in the absence of Klf4 and Tbx3 activity. Therefore, Klf4 and Tbx3 are involved in mediating LIF signalling to the core circuitry but are not directly associated with the maintenance of pluripotency, because ES cells keep pluripotency without their expression in the particular context.


Effect of micronutrient supplementation on treatment outcomes in children with intrathoracic tuberculosis: a randomized controlled trial.
Micronutrients play an important role in immune function. To our knowledge, there have been no comprehensive studies on the role of micronutrient supplementation in children with tuberculosis. We assessed the effect of micronutrient supplementation in children treated with antituberculosis therapy (ATT). A randomized, double-blind, placebo-controlled trial that used a 2 × 2 factorial design was undertaken at 2 teaching hospitals in Delhi. Children with newly diagnosed intrathoracic tuberculosis were enrolled, and they received ATT together with daily supplementation for 6 mo with either zinc alone, micronutrients without zinc, micronutrients in combination with zinc, or a placebo. Main outcomes were weight gain and an improvement in a chest X-ray (CXR) lesion assessed at 6 mo of treatment. A total of 403 children were enrolled and randomly assigned. A microbiological diagnosis of tuberculosis was confirmed in 179 children (44.4%). The median (95% CI) increase in weight-for-age z score at 6 mo was not significantly different between subjects who received micronutrients [0.75 (0.66, 0.84)] and those who did not receive micronutrients [0.76 (0.67, 0.85)] and between subjects who received zinc [0.76 (0.68, 0.85)] and those who did not receive zinc [0.75 (0.66, 0.83)]. An improvement in CXR was observed in 285 children, but there was no difference between those receiving zinc and no zinc or between those receiving micronutrients and no micronutrients after 6 mo of ATT. However, children who received micronutrients had a faster gain in height over 6 mo than did those who did not receive micronutrients (height-for-age z score Δ = 0.08; P = 0.014). Micronutrient supplementation did not modify the weight gain or clearance of lesions on CXR in children with intrathoracic tuberculosis. However, micronutrient supplementation during treatment may improve height gain in children with intrathoracic tuberculosis. This trial was registered at clinicaltrials.gov as NCT00801606.


Optimisation of patient dose for the horizontal beam technique in lateral lumbar spine radiographic examinations.
In the emergency department, patients undergoing lateral lumbar spine radiography examinations are positioned either lying on their side on an X-ray table with the X-ray beam vertical or lying supine on a trolley with the X-ray beam horizontal. The measured dose-area product (DAP) values were found to differ significantly, typically 1.3 Gy cm(2) for those patients examined on the X-ray table and 2.7 Gy cm(2) for those on a trolley. This work investigates the reason for higher DAP values with the horizontal beam technique. The UK's current recommended national diagnostic reference level (NDRL) for the lateral lumbar spine is 2.5 Gy cm(2). The measurements of body diameter on volunteers showed that rotating the patients from their side to their back resulted in an increase in tissue thickness of between 2 cm and 9 cm for the lumbar region. X-ray absorption increases exponentially with increasing tissue thickness. An increase of 5 cm in body diameter for a lateral lumbar spine at 93 kV will increase the DAP by more than two-fold. Mathematical modelling and measurements with polymethyl methacrylate provided data to predict the tube potential increase necessary to reduce the DAP. For the horizontal beam technique, the tube potential was increased from 93 kV to 102 kV and the average DAP reduced to 2.3 Gy cm(2). Radiographic technique should be understood when auditing the dose. Tube potential must be increased to optimise the horizontal beam technique. The 2.5-Gy cm(2) NDRL relates predominantly to the more common vertical beam technique. Separate local diagnostic reference levels for horizontal and vertical beam techniques are recommended.


Thyroid gland in chronic obstructive pulmonary disease.
The risk of chronic obstructive pulmonary disease (COPD), as well as thyroid diseases increases with age. COPD is a common systemic disease associated with chronic inflammation. Many endocrinological disorders, including thyroid gland diseases are related to systemic inflammation. Epidemiological studies suggest that patients with COPD are at higher risk of thyroid disorders. These associations are not well-studied and thyroid gland diseases are not included on the broadly acknowledged list of COPD comorbidities. They may seriously handicap quality of life of COPD patients. Unfortunately, the diagnosis may be difficult, as many signs are masked by the symptoms of the index disease. The comprehension of the correlation between thyroid gland disorders and COPD may contribute to better care of patients. In this review, we attempt to revise available literature describing existing links between COPD and thyroid diseases.


Prevalence and potential determinants of chronic disease among elderly in India: Rural-urban perspectives.
Chronic diseases are the leading causes of disability and premature death among the elderly population in India. The study, using data from the 75th round of the NSSO survey (N = 44,631), examined the prevalence and determinants of chronic diseases among the population aged 60+ in India by applying bivariate and logistic regression analyses and used a non-linear decomposition technique to understand the urban-rural differences in the prevalence of chronic diseases. About 21% of the elderly in India reportedly have at least one chronic disease. Seventeen percent elderly in rural areas and 29% in urban areas suffer from a chronic disease. Hypertension and diabetes account for about 68% of all chronic diseases. The prevalence of chronic diseases is the highest in Kerala (54%), followed by Andhra Pradesh (43), West Bengal (36), and Goa (32). Those with higher levels of education, staying in urban areas, those who are economically dependent on others, staying alone or without spouse and children, and belonging to wealthy households have a higher likelihood of having a chronic disease. The probability of having a chronic disease is 1.15 times higher among urban residents as compared to their rural counterparts. Elderly rural women, compared to elderly rural men, and never-married, widowed, and divorced elderly urban women, compared to married elderly urban men, are significantly more likely to suffer from chronic ailments. Differences in education, wealth status, and caste are the three most significant contributors to the urban-rural gap in chronic diseases. The high risk of chronic diseases among certain subsets of the elderly population must be recognized as a key public health concern. The findings of our study will likely help promote healthy ageing in India.


Risk factors identification for ocular trauma in patients who presented in a suburban tertiary care hospital in Nigeria.
To determine the risk factors, and the pattern of ocular trauma in Irrua, a sub-urban community in Edo State, Nigeria. A prospective study of all cases of ocular trauma seen in the Irrua Specialist Teaching Hospital, Irrua, Nigeria from January to December 2005. The age, gender, occupation, activity at time of injury, use of protective eye wear, visual acuity, and findings on ocular examination were recorded. One hundred and eighty-two patients were seen during the period of study. There were 130 males (72.2%) and 52 females (28.8%), with a ratio of 2.5:1. Motorcycle-related road traffic accident was the most common cause of ocular injury occurring in 56 patients (30.8%), followed by assault in 40 patients (22%), and farming in 35 patients (19.2%). The conjunctiva, lids, and cornea were the ocular structures mostly affected. Fifty one patients (28%) were blind in the affected eye, at presentation. Only 22 patients (12.1%) presented within 24 hours of injury. Motorcycle-related accidents were the most significant cause of ocular injury. The use of protective helmets with plastic covering over the face should be enforced. Measures to reduce physical assault in schools, and in the civil society should also be enforced. Farmers should be encouraged to wear protective goggles.


Resonances and resonant fields in a fabry-perot resonator illuminated by a line source.
In the present paper, the field internal to an infinite-strip plane-parallel mirror resonator is evaluated in the case when the structure is illuminated by a cylindrical primary wave. The feeder where the primary wave originates constitutes a perturbation of the resonator and is assumed to scatter a cylindrical wave proportional to the field impinging on it. The quasi-stationary field pattern internal to the structure is evaluated for several values of the efficiency of the scatterer, that is, of the factor relating the wave scat- tered by the feeder to the wave impinging on the feeder. Resonant frequencies and fields are compared with the resonant frequencies and fields of a Fabry-Perot resonator not perturbed by the presence of the feeder. The effect of the persistent primary wave alone is analyzed by considering the case of a feeder with vanishing efficiency.


A debate: Can we recommend electronic cigarettes to our patients? Opinion 1.
A discussion about disadvantages of electronic cigarettes (e-cigarettes) has recently broken out. There are even opinions that they are as harmful as regular cigarettes. However, this has not been proved, and theoretical premises suggest that e-cigarettes should be definitely less harmful as while using them, tobacco is not burned and harmful substances, in particular carcinogens are not produced. Certain premises assume that e-cigarettes may be used as a new form of nicotine replacement therapy, but this has not been confirmed yet. Therefore, further research into harmfulness and safety of the use of e-cigarettes is required. This paper presents solely reasons for the possibility of recommending e-cigarettes to people addicted to nicotine.


Cross-reactivity of metocurine, atracurium, vecuronium and fazadinium with IgE antibodies from patients unexposed to these drugs but allergic to other myoneural blocking drugs.
An inhibition assay was used to determine quantitatively the allergenic cross-reactivity of some myoneural blocking drugs not yet released for use in Australia, in the sera of patients who had experienced anaphylactic reactions to neuromuscular blocking drugs. Two of the compounds, metocurine and atracurium were highly cross-reactive with the currently used myoneural blockers; fazadinium was weakly cross-reactive and vecuronium intermediate in potency between these two extremes. From these results, we predict that anaphylactic reactions to these compounds, and particularly to metocurine and atracurium, will occur in some patients allergic to the currently used neuromuscular blocking agents.


Stem Cell Therapy for Alzheimer's Disease.
Alzheimer's disease (AD) is the most common neurodegenerative disease caused by eventually aggregated amyloid β (Aβ) plaques in degenerating neurons of the aging brain. These aggregated protein plaques mainly consist of Aβ fibrils and neurofibrillary tangles (NFTs) of phosphorylated tau protein. Even though some cholinesterase inhibitors, NMDA receptor antagonist, and monoclonal antibodies were developed to inhibit neurodegeneration or activate neural regeneration or clear off the Aβ deposits, none of the treatment is effective in improving the cognitive and memory dysfunctions of the AD patients. Thus, stem cell therapy represents a powerful tool for the treatment of AD. In addition to discussing the advents in molecular pathogenesis and animal models of this disease and the treatment approaches using small molecules and immunoglobulins against AD, we will focus on the stem cell sources for AD using neural stem cells (NSCs); embryonic stem cells (ESCs); and mesenchymal stem cells (MSCs) from bone marrow, umbilical cord, and umbilical cord blood. In particular, patient-specific-induced pluripotent stem cells (iPS cells) are proposed as a future prospective and the challenges for the treatment of AD.


Prostate cancer in Brazil and Latin America: epidemiology and screening.
Prostate cancer is one of the tumors with higher incidence and mortality among men in the World. Epidemiological data are influenced by life expectancy of population, available diagnostic methods, correct collection of data and quality of health services. Screening of the disease is not standardized around the World. Up till now there is no consensus about the risks versus benefits of early detection. There are still missing data about this pathology in Latin America. to revise current epidemiologic situation and early diagnosis policies of prostate cancer in Brazil and Latin America. Medline, Cochrane Library and SciELO databases were reviewed on the subject of epidemiology and screening of prostate cancer. Screening research was performed in websites on national public health organizations and Latin America. Screening recommendations were obtained from those governmental organizations and from Latin American urological societies and compared to the most prominent regulatory agencies and societies of specialists and generalists from around the World. Brazil and Latin America have a special position in relation to incidence and mortality of prostate cancer. In Brazil, it occupies the first position regarding incidence of cancer in men and the second cause of mortality. Central America has the highest rate of mortality of the continent with lower incidence/mortality ratios. Screening recommendations are very distinct, mainly among regulatory organs and urological societies. prostate cancer epidemiology is an important health public topic. Data collection related to incidence and mortality is still precarious, especially in less developed countries. It is necessary to follow-up long term screening studies results in order to conclude its benefits.


Towards atomistic understanding of polymorphism in the solvothermal synthesis of ZrO2 nanoparticles.
Varying atomic short-range order is correlated with the ratio of the monoclinic (m) to tetragonal (t) phase in ZrO2 nanoparticle formation by solvothermal methods. Reactions from Zr oxynitrate in supercritical methanol and Zr acetate in water (hydrothermal route) were studied in situ by X-ray total scattering. Irrespective of the Zr source and solvent, the structure of the precursor in solution consists of edge-shared tetramer chains. Upon heating, the nearest-neighbor Zr-O and Zr-Zr distances shorten initially while the medium-range connectivity is broken. Depending on the reaction conditions, the disordered intermediate transforms either rapidly into m-ZrO2, or more gradually into mixed m- and t-ZrO2 with a concurrent increase of the shortest Zr-Zr distance. In the hydrothermal case, the structural similarity of the amorphous intermediate and m-ZrO2 favors the formation of almost phase-pure m-ZrO2 nanoparticles with a size of 5 nm, considerably smaller than the often-cited critical size below which the tetragonal is assumed to be favoured. Pair distribution function analysis thus unravels ZrO2 phase formation on the atomic scale and in this way provides a major step towards understanding polymorphism of ZrO2 beyond empirical approaches.


Line-defect patterns of unstable spiral waves in cardiac tissue.
Spiral wave propagation in period-2 excitable media is accompanied by line defects, the locus of points with period-1 oscillations. Here we investigate spiral line defects in cardiac tissue where period-2 behavior has a known arrhythmogenic role. We find that the number of line defects, which is constrained to be an odd integer, is 3 for a freely rotating spiral, with and without meander, but 1 for a spiral anchored around a fixed heterogeneity. We interpret this finding analytically using a simple theory where spiral wave unstable modes with different numbers of line defects correspond to quantized solutions of a Helmholtz equation. Furthermore, the slow inward rotation of spiral line defects is described in different regimes.


An unusual presentation of gastric mucosa-associated lymphoid tissue (MALT)-type lymphoma.
Mucosa-associated lymphoid tissue (MALT)-type lymphoma is a relatively rare disease; nevertheless, it is the third most common lymphoma type, accounting for 5-7% of all non-Hodgkin lymphomas. Case series and retrospective analysis published in the literature have suggested that extra gastrointestinal (GI) MALT-type lymphoma can occur simultaneously with MALT-type lymphoma involving the GI tract. We report the case of a healthy, 64-year-old Caucasian male who presented with progressive fatigue, non-productive cough, and worsening exertional shortness of breath for 3 months who was subsequently diagnosed with gastric extra-nodal marginal zone B-cell lymphoma or MALToma with simultaneous metastasis to the lung (bronchi) based on biopsy reports. A 64-year-old Caucasian male presented to the emergency room complaining of progressive fatigue for 3 months which had progressed to the point of hindering his usual activities of daily living (ADL). He had recently visited his primary care provider for evaluation of a non-productive cough and exertional shortness of breath. A chest radiography obtained at the time showed bilateral infiltrates. He was then treated for atypical pneumonia but his symptoms unfortunately did not improve. Initial investigations in the emergency room revealed severe anemia and a positive stool guaiac test. Imaging showed bilateral pulmonary infiltrates and an irregular gastric mass. Gastric and transbronchial biopsies were suggestive of extra-nodal marginal zone B-cell lymphoma with simultaneous metastasis to the bronchi. He was treated symptomatically with transfusion of packed red blood cells (PRBC) and intravenous iron followed by radiotherapy. Helicobacter pylori infection was ruled out eliminating the possibility of treating him with eradication therapy. Although the stomach is the most common and most extensively studied site of involvement of MALT lymphomas, they can also emerge in many other locations. MALT lymphomas have a high tendency to disseminate to other sites; therefore, extensive staging may be necessary to look for suspicious lesions.


The cost-effectiveness of using rapid diagnostic tests for the diagnosis of typhoid fever in patients with suspected typhoid fever: a systematic review.
Despite the availability of several commercial rapid diagnostic tests (RDTs) developed to detect typhoid fever, the cost-effectiveness in resource-limited settings is unclear. This review aimed to explore the literature on typhoid economic evaluations in order to assess the cost-effectiveness of using typhoid RDTs in resource-limited settings. A systematic review was conducted focusing on the identification of economic evaluations of typhoid RDTs to diagnose patients with suspected typhoid fever. Two studies were identified and included for narrative synthesis. Whilst highlighting a gap in the published literature, this review shows the use of typhoid RDTs to potentially be cost-effective in resource-limited settings. Factors that appeared as significant in determining cost-effectiveness related to test characteristics (such as sensitivity, specificity, and cost) and the prevalence of typhoid fever and should factor into any future evaluations. Concerted effort is needed in resource-limited settings with regard to medical device regulation to ensure that clinically effective and cost-effective typhoid RDTs are widely available and introduced into clinical practice. Typhoid modeling (with respect to typhoid testing and treatment strategies) represents an understudied area and further work is needed.


Beta-lactoglobulin B: a proposed standard for the study of reversible self-association reactions in the analytical ultracentrifuge?
Bovine beta-lactoglobulin B is proposed for use as a standard in the measurement of reversible self-association reactions in the analytical ultracentrifuge. The protein is well understood on a molecular level, is readily obtainable, and is stable under harsh conditions. Bovine beta-lactoglobulin B undergoes a simple monomer-dimer equilibrium which can be predictably controlled and consistently reproduced. In this investigation bovine beta-lactoglobulin B has been studied via sedimentation equilibrium experiments in the XL-A analytical ultracentrifuge at 5-30 degrees C in buffers of ionic strength 0.1-0.2 M and pH 2.0-3.0. Samples subjected to a number of different treatments and storage methods all yielded similar results. Molar equilibrium constants for the association reaction were determined by nonlinear regression fitting of a monomer-dimer model of association either to concentration versus radius data, using the programs NONLIN and ORIGIN, or to Omega versus concentration data using the program DUGOM. At 20 degrees C and pH 2.6, over the ionic strength range 0. 1-0.2 M, the equilibrium constant for the association reaction ranges between 1 x 10(4) and 5 x 10(4) M-1. The parameters of nonideal self-association behavior were found to be independent of the particular analysis strategy. Fitting to the concentration distribution, the apparent weight-average molecular weight, or the Omega function all returned identical parameters.


Hip strength and range of motion: Normal values from a professional football league.
To determine the normal profiles for hip strength and range of motion (ROM) in a professional football league in Qatar, and examine the effect of leg dominance, age, past history of injury, and ethnicity on these profiles. Cross-sectional cohort study. Participants included 394 asymptomatic, male professional football players, aged 18-40 years. Strength was measured using a hand held dynamometer with an eccentric test in side-lying for hip adduction and abduction, and the squeeze test in supine with 45° hip flexion. Range of motion measures included: hip internal and external rotation in 90° flexion, hip IR in prone, bent knee fall out and hip abduction in side-lying. Demographic information was collected and the effect on the profiles was analysed using linear mixed models with repeated measures. Strength values (mean±SD) were: adduction=3.0±0.6Nm/kg, abduction=2.6±0.4Nm/kg, adduction/abduction ratio=1.2±0.2, Squeeze test=3.6±0.8N/kg. Range of motion values: internal rotation in flexion=32±8°, external rotation=38±8°, internal rotation in prone=38±8°, bent knee fall out=13±4.4cm, abduction in side-lying=50±7.3°. Leg dominance had no clinically relevant effect on these profiles. Multivariate analysis demonstrated that age had a minor influence on squeeze strength (-0.03N/kg/year), external rotation (-0.30°/year) and abduction range (-0.19°/year) but past history of injury, and ethnicity did not. Normal values are documented for hip strength and range of motion that can be used as reference profiles in the clinical assessment, screening, and management of professional football players. Leg dominance, recent past injury history and ethnicity do not need to be accounted for when using these profiles for comparison purposes.


Reductive dehalogenase structure suggests a mechanism for B12-dependent dehalogenation.
Organohalide chemistry underpins many industrial and agricultural processes, and a large proportion of environmental pollutants are organohalides. Nevertheless, organohalide chemistry is not exclusively of anthropogenic origin, with natural abiotic and biological processes contributing to the global halide cycle. Reductive dehalogenases are responsible for biological dehalogenation in organohalide respiring bacteria, with substrates including polychlorinated biphenyls or dioxins. Reductive dehalogenases form a distinct subfamily of cobalamin (B12)-dependent enzymes that are usually membrane associated and oxygen sensitive, hindering detailed studies. Here we report the characterization of a soluble, oxygen-tolerant reductive dehalogenase and, by combining structure determination with EPR (electron paramagnetic resonance) spectroscopy and simulation, show that a direct interaction between the cobalamin cobalt and the substrate halogen underpins catalysis. In contrast to the carbon-cobalt bond chemistry catalysed by the other cobalamin-dependent subfamilies, we propose that reductive dehalogenases achieve reduction of the organohalide substrate via halogen-cobalt bond formation. This presents a new model in both organohalide and cobalamin (bio)chemistry that will guide future exploitation of these enzymes in bioremediation or biocatalysis.


Commentary: Applications of functional neuroimaging to civil litigation of mild traumatic brain injury.
The current definition of mild traumatic brain injury (MTBI) is in flux. Presently, there are at least three working definitions of this disorder in the United States, with no clear consensus. Functional neuroimaging, such as single photon emission computed tomography (SPECT) and positron emission tomography (PET), initially showed promise in their ability to improve the diagnostic credibility of MTBI. Over the past decade, that promise has not been fulfilled and there is a paucity of quality studies or standards for the application of functional neuroimaging to traumatic brain injury, particularly in litigation. The legal profession is ahead of the science in this matter. The emergence of neurolaw is driving a growing use of functional neuroimaging, as a sole imaging modality, used by lawyers in an attempt to prove MTBI at trial. The medical literature on functional neuroimaging and its applications to MTBI is weak scientifically, sparse in quality publications, lacking in well-designed controlled studies, and currently does not meet the complete standards of Daubert v. Merrell Dow Pharmaceuticals, Inc., for introduction of scientific evidence at trial. At the present time, there is a clear lack of clinical correlation between functional neuroimaging of MTBI and behavioral, neuropsychological, or structural neuroimaging deficits. The use of SPECT or PET, without concurrent clinical correlation with structural neuroimaging (CT or MRI), is not recommended to be offered as evidence of MTBI in litigation.


Calcium/calmodulin regulation of the rat prolactin gene is conferred by the proximal enhancer region.
The effects of the calcium/calmodulin signaling system on expression of the rat PRL gene were studied in rat pituitary GH3 cells using two specific naphthalene sulfonamide calmodulin (CaM) antagonist drugs, W7 and a more potent and more highly specific iodo-derivative, 5-iodo-1-C8. PRL (but not GH) mRNA accumulation was markedly inhibited by W7, which in coincubations abolished the stimulation normally seen with TRH. Transient transfection assays showed that expression of the reporter gene chloramphenicol acetyl transferase (CAT) linked to 5'-flanking sequences from the PRL gene was inhibited by the calcium-channel blocker verapamil and by the two CaM antagonists. The calcium effects showed partial promoter specificity, in that transcription of PRL-CAT constructs was markedly inhibited by verapamil, but the Rous sarcoma virus-CAT construct also showed significant inhibition, whereas the pBL-CAT2 construct was unaffected. Three hundred ninety five base pairs were sufficient to confer the full inhibitory effect of calcium channel blockade or CaM antagonist seen with longer constructs. The data indicate that CaM is important for PRL gene transcription, and that the effects of CaM are exerted on DNA sequences within the proximal 395bp of prolactin 5'-flanking DNA.


Secretion of transforming growth factor-alpha (TGF alpha) by postnatal rabbit alveolar macrophages.
Transforming growth factor-alpha (TGF alpha) is a cytokine secreted by stimulated alveolar macrophages (AM) in vitro and after in vivo particulate or hyperoxia exposure and has been implicated in the processes of postnatal lung development. It is unknown if AM TGF alpha secretion changes during normal postnatal lung development. After sacrifice of New Zealand white rabbits on postnatal d 0-2, 5-7, 9-10, 14, 21, and 28 and > 4 mo (adult), AM were isolated by discontinuous density centrifugation and placed in culture in the presence or absence of concanavalin A (ConA) for 24 h. Media were collected, and the concentration and isoforms of TGF alpha in AM media samples were determined by an epidermal growth factor/TGF alpha radioreceptor assay and Western immunodetection, respectively. TGF alpha was present in media of AM from the 1.06 and 1.08 g/dL Percoll densities, but not in the 1.10 g/dL density. Statistically significant differences in TGF alpha secretion by unstimulated and ConA-stimulated AM at the various ages were not detected until d 14 (p < 0.02). Western blot analysis of unstimulated AM media samples from d 0-7 rabbits demonstrated the presence of TGF alpha isoforms at 46, 30, and 14.3 kD. At later postnatal ages (> or = d 9), a single 14.3-kD isoform was present. In contrast, analysis of ConA-stimulated AM media samples showed TGF alpha isoforms at 46, 30, and 14.3 kD for all ages; however, the 6-kD mature isoform was present only in juvenile (d 28) and adult media.(ABSTRACT TRUNCATED AT 250 WORDS)


Reaction of gadolinium chelates with ozone and hydroxyl radicals.
Gadolinium chelates are used in increasing amounts as contrast agents in magnetic resonance imaging, and their fate in wastewater treatment has recently become the focus of research. Oxidative processes, in particular the application of ozone, are currently discussed or even implemented for advanced wastewater treatment. However, reactions of the gadolinium chelates with ozone are not yet characterized. In this study, therefore, rate constants with ozone were determined for the three commonly used chelates Gd-DTPA, Gd-DTPA-BMA, and Gd-BT-DO3A, which were found to be 4.8 ± 0.88, 46 ± 2.5, and 24 ± 1.5 M(-1) s(-1), respectively. These low rate constants indicate that a direct reaction with ozone in wastewater is negligible. However, application of ozone in wastewater leads to substantial yields of (•)OH. Different methods have been applied and compared for determination of k((•)OH+Gd chelate). From rate constants determined by pulse radiolysis experiments (k((•)OH+Gd-DTPA) = 2.6 ± 0.2 × 10(9) M(-1) s(-1), k((•)OH+Gd-DTPA-BMA) = 1.9 ± 0.7 × 10(9) M(-1) s(-1), k((•)OH+Gd-BT-DO3A) = 4.3 ± 0.2 × 10(9) M(-1) s(-1)), it is concluded that a reaction in wastewater via (•)OH radicals is feasible. Toxicity has been tested for educt and product mixtures of both reactions. Cytotoxicity (MTT test) and genotoxicity (micronuclei assay) were not detectable.


Smad4 deficiency in T cells leads to the Th17-associated development of premalignant gastroduodenal lesions in mice.
While there is evidence that specific T cell populations can promote the growth of established tumors, instances where T cell activity causes neoplasms to arise de novo are infrequent. Here, we employed two conditional mutagenesis systems to delete the TGF-β signaling pathway component Smad4 in T cells and observed the spontaneous development of massive polyps within the gastroduodenal regions of mice. The epithelial lesions contained increased levels of transcripts encoding IL-11, IL-6, TGF-β, IL-1β, and TNF-α, and lamina propria cells isolated from lesions contained abundant IL-17A+CD4+ T cells. Furthermore, we found that Smad4 deficiency attenuated TGF-β-mediated in vitro polarization of FoxP3+CD4+ T cells, but not IL-17A+CD4+ T cells, suggesting that the epithelial lesions may have arisen as a consequence of unchecked Th17 cell activity. Proinflammatory cytokine production likely accounted for the raised levels of IL-11, a cytokine known to promote gastric epithelial cell survival and hyperplasia. Consistent with IL-11 having a pathogenic role in this model, we found evidence of Stat3 activation in the gastric polyps. Thus, our data indicate that a chronic increase in gut Th17 cell activity can be associated with the development of premalignant lesions of the gastroduodenal region.


Structure of the monomeric outer-membrane porin OmpG in the open and closed conformation.
OmpG, a monomeric pore-forming protein from Escherichia coli outer membranes, was refolded from inclusion bodies and crystallized in two different conformations. The OmpG channel is a 14-stranded beta-barrel, with short periplasmic turns and seven extracellular loops. Crystals grown at neutral pH show the channel in the open state at 2.3 A resolution. In the 2.7 A structure of crystals grown at pH 5.6, the pore is blocked by loop 6, which folds across the channel. The rearrangement of loop 6 appears to be triggered by a pair of histidine residues, which repel one another at acidic pH, resulting in the breakage of neighbouring H-bonds and a lengthening of loop 6 from 10 to 17 residues. A total of 151 ordered LDAO detergent molecules were found in the 2.3 A structure, mostly on the hydrophobic outer surface of OmpG, mimicking the outer membrane lipid bilayer, with three LDAO molecules in the open pore. In the 2.7 A structure, OmpG binds one OG and one glucose molecule as sugar substrates in the closed pore.


Ab initio GB study of methylation reaction of adenine, cytosine, guanine, and thymine by methanediazonium ion.
Methylation reaction at ten nucleophilic sites in four DNA base molecules by methanediazonium ion (N(2)Me+) was examined by ab initio MO/GB calculation which includes the solvent effect with the continuum model using the generalized Born formula. The stabilization energy of the ion-dipole complex as well as the energy of the transition state are roughly consistent with the experimental fraction of methylation by N -methyl- N -nitrosourea. For the guanine N7 site, which is the principal site of methylation, the stabilization energy is the largest and the energy of the transition state is low. The reactions at the guanine O6 and N7 sites were analysed by drawing the potential energy surface with respect to two parameters, the O6-C(Me) distance and the N7-C(Me) distance. The methylation reactions of the guanine O6 and N7 sites begin from the common geometry, the global minimum in the two-dimensional potential energy surface.


Fertility after contraception or abortion.
There is a very small correlation, if any, between the prior use of OCs and congenital malformations, including Down's syndrome. There are few, if any, recent reports on masculinization of a female fetus born to a mother who took an OC containing 1 mg of a progestogen during early pregnancy. However, patients suspected of being pregnant and who are desirous of continuing that pregnancy should not continue to take OCs, nor should progestogen withdrawal pregnancy tests be used. Concern still exists regarding the occurrence of congenital abnormalities in babies born to such women. The incidence of postoperative infection after first trimester therapeutic abortion in this country is low. However, increasing numbers of women are undergoing repeated pregnancy terminations, and their risk for subsequent pelvic infections may be multiplied with each succeeding abortion. The incidence of prematurity due to cervical incompetence or surgical infertility after first trimester pregnancy terminations is not increased significantly. Asherman's syndrome may occur after septic therapeutic abortion. The pregnancy rate after treatment of this syndrome is low. The return of menses and the achievement of a pregnancy may be slightly delayed after OCs are discontinued, but the fertility rate is within the normal range by 1 year. The incidence of postpill amenorrhea of greater than 6 months' duration is probably less than 1%. The occurrence of the syndrome does not seem to be related to length of use or type of pill. Patients with prior normal menses as well as those with menstrual abnormalities before use of OCs may develop this syndrome. Patients with normal estrogen and gonadotropin levels usually respond with return of menses and ovulation when treated with clomiphene. The rate for achievement of pregnancy is much lower than that for patients with spontaneous return of menses. The criteria for defining PID or for categorizing its severity are diverse. The incidence of PID is higher among IUD users than among patients taking OCs or using a barrier method. The excess risk of PID among IUD users, with the exception of the first few months after insertion, is related to sexually transmitted diseases and not the IUD. Women with no risk factors for sexually transmitted diseases have little increased risk of PID or infertility associated with IUD use. There appears to be no increased risk of congenital anomalies, altered sex ratio, or early pregnancy loss among spermicide users. All present methods of contraception entail some risk to the patient. The risk of imparied future fertility with the use of any method appears to be low.(ABSTRACT TRUNCATED AT 400 WORDS)


The relationship between social network characteristics and breast cancer screening practices among employed women.
This study examined the relationship between social network characteristics and breast cancer screening practices among employed women. We hypothesized that larger social networks, higher levels of support from networks, and stronger social influences to undergo screening would be positively associated with regular utilization of mammograms and clinical breast examinations. Data were collected from women aged 52 and over who were employed in 27 worksites (N = 1,045). Social network characteristics, breast cancer screening practices, and sociodemographic factors were assessed in a self-administered survey. Bivariate analyses revealed that social influences were significantly associated with regular screening; social support was only marginally associated with regular screening; and social network size was not at all associated. In multivariate analyses, only the perception that screening is normative among one's peers was predictive of regular screening. Provider recommendation was the single most potent predictor of regular screening. These findings provide support for the importance of social norms in motivating women to adhere to screening guidelines. In addition, they underscore the potent impact of provider recommendations on women's screening practices.


The cephalosporins.
Structural modification of cephalosporin antibiotics has produced a broad array of new compounds, notable chiefly for greatly extended gram negative activity with minor toxicity. An understanding of basic principles will enable most clinicians to use these drugs appropriately and effectively.


Frozen-thawed cleavage stage versus blastocyst stage embryo transfer in high responder patients.
Clinical outcomes following frozen-thawed cleavage embryo transfer versus frozen-thawed blastocyst transfer in high responder patients undergoing in vitro fertilisation/intracytoplasmic sperm injection cycles are still debated. In a retrospective study, 106 high responder patients who were candidate for 'freeze-all embryos' were recruited. Frozen-thawed embryos were transferred at the cleavage stage (n = 53) or the blastocyst stage (n = 53). Clinical pregnancy was considered as the primary outcome and chemical pregnancy, ongoing pregnancy, implantation rate, and fertilization rate, as well as miscarriage rate, were measured as the secondary outcome. Clinical (47.2% vs. 24.5%), chemical (56.6% vs. 32.1%), and ongoing pregnancy rates (37.7% vs. 17%) as well as implantation rates (33.6% vs. 13.5%) were significantly higher in the blastocyst group compared with the cleavage group respectively (P < 0.05). Miscarriage rate was comparable between groups (P > 0.05). Transfer of frozen-thawed embryos at the blastocyst stage was preferable in the high responder patients to increase implantation, pregnancy and live birth rates compared with cleavage stage embryo transfer.


Components of NOTCH Signaling for Uterine Cancer Patients' Prognosis.
New molecular biomarkers that could have an independent prognostic value in endometrial cancer are currently under investigation. Recently, it was suggested that genetic changes in the Notch signaling pathway could be associated with the development of endometrial carcinoma. This study aimed to determine the expression of the Notch signaling pathway components in tumour and adjacent normal uterine tissue and to evaluate their importance for the survival of uterine cancer patients. The present study was performed on uterine body samples collected from 109 patients and paired adjacent noncancerous endometrial tissue samples. Kaplan-Meier curves and Cox regression were used for survival analyses. Expression alterations of NOTCH2, NOTCH3, NOTCH4, JAG2, and HES1 were evaluated as independent and significant prognostic factors for uterine cancer patients.


Clinical coverage of an archetype repository over SNOMED-CT.
Clinical archetypes provide a means for health professionals to design what should be communicated as part of an Electronic Health Record (EHR). An ever-growing number of archetype definitions follow this health information modelling approach, and this international archetype resource will eventually cover a large number of clinical concepts. On the other hand, clinical terminology systems that can be referenced by archetypes also have a wide coverage over many types of health-care information. No existing work measures the clinical content coverage of archetypes using terminology systems as a metric. Archetype authors require guidance to identify under-covered clinical areas that may need to be the focus of further modelling effort according to this paradigm. This paper develops a first map of SNOMED-CT concepts covered by archetypes in a repository by creating a so-called terminological Shadow. This is achieved by mapping appropriate SNOMED-CT concepts from all nodes that contain archetype terms, finding the top two category levels of the mapped concepts in the SNOMED-CT hierarchy, and calculating the coverage of each category. A quantitative study of the results compares the coverage of different categories to identify relatively under-covered as well as well-covered areas. The results show that the coverage of the well-known National Health Service (NHS) Connecting for Health (CfH) archetype repository on all categories of SNOMED-CT is not equally balanced. Categories worth investigating emerged at different points on the coverage spectrum, including well-covered categories such as Attributes, Qualifier value, under-covered categories such as Microorganism, Kingdom animalia, and categories that are not covered at all such as Cardiovascular drug (product).


[Research advances on the biomechanical micro- environment facilitated wound repair through the regulation of cell migration].
Biomechanical microenvironment refers to a variety of mechanical signals in the extracellular mechanical microenvironment, which will change correspondingly with time and space. It plays an important role in histological changes such as cell migration, proliferation, and differentiation, and can further affect wound healing. Wound healing is a complex pathophysiological process, and one of the important factors that affects wound healing is whether the cells can efficiently and quickly migrate to the wound center or not. Previous studies have shown that biomechanical microenvironment can not only induce the directional migration of cells, but also improve the migration rate of cells. In the complex natural environment, cells adopt various migration patterns and are dominated by special patterns such as local myosin contractility and extracellular microenvironment. In addition to overcoming the extracellular barrier, cells also need to interact with neighboring cells and tissue through local physical and mechanical forces and signals to complete migration and thus accelerate wound healing. Therefore, in recent years, scholars at home and abroad have been actively developing biological materials based on improving biomechanical microenvironment in order to further promote cell migration and thus accelerate wound healing. This paper reviews the recent research advances on the role of biomechanical environment in wound healing promotion via the regulating of cell migration and the development of related biomaterials.


Proximal canalicular imaging utilizing ultrasound biomicroscopy C Experimental balloon catheter dilatation.
If proximal canalicular obstruction is to be treated by balloon catheter dilatation, a technique must be available to measure the short-term and long-term effects of the dilatation. Ultrasound biomicroscopy can image the pre-dilated and post-dilated proximal canaliculus in vivo. Further in vivo studies will determine the potential of this technique in the clinical setting.


The application of new concepts of the assessment of the thyroid state to pregnant women.
Recently proposed concepts regarding the nature and assessment of the thyroid state have provided a model more consistent with empiric evidence. It now appears likely that there are no such entities as thyroid set points and individual euthyroidism. Rather than there being discrete thyroid states, peripheral organ parameters are associated with thyroid function in a continuous manner. Thyroid hormone levels and, in particular, levels of free thyroxine now appear to be superior to thyrotropin levels as indicators of the thyroid state. Complicating the assessment of the correlations of the thyroid state with pregnancy outcomes are the contribution of the placenta to maternal thyroid function, fetal thyroid development, the multiple potential pathways to any particular outcome, the likely presence of small critical periods of time, the differing genetics of fetal and maternal tissues, and the unreliability of thyroid hormone assays. Nevertheless, there is no apparent reason for there to be a change in pregnancy to the basic principles of thyroid hormone action. The relationships between mild abnormalities of the thyroid state and pregnancy outcomes and the value of treating such mild abnormalities remain uncertain and controversial. The evidence suggests that further investigation of these clinical questions might better be based on thyroid hormone, particularly free thyroxine, levels. In the investigation of borderline low thyroid states, the categories of subclinical hypothyroidism and isolated hypothyroxinemia might both be abandoned with attention being directed to low free thyroxine levels regardless of the thyroid-stimulating hormone (TSH) levels. For these changes to occur, there would ideally be improvements in the assays for free thyroxine in pregnancy. The evidence suggests that, just as in the non-pregnant situation, pregnancy guidelines based on thyrotropin levels may need revision.


Cloning by polymerase chain reaction of a new mouse TGF-beta, mTGF-beta 3.
Two TGF-beta s, TGF-beta 1 and 2, have previously been isolated from the mouse. Here we report the isolation of a murine TGF-beta 3 cDNA. RNAs extracted from 15-day-old mouse embryos and several mouse cell lines were reverse-transcribed. These cDNA mixtures were used as substrates for polymerase chain-reaction amplifications, using oligonucleotides designed on the basis of known human and chicken TGF-beta 3 sequences, including the initiation and stop codons. Several overlapping cDNAs containing either the amino-terminal domain or the carboxy-terminal domain, as well as the complete 1.2-kb coding region of the mouse TGF-beta 3 cDNA were obtained. The mouse TGF-beta 3 coding region is 1230 nucleotides long and codes for a 410 amino acid polypeptide very similar to its human counterpart. This cDNA hybridizes to a unique 3.5-kb RNA and is differentially expressed in various mouse tissues and at different embryonic stages.


Biomechanical study in vitro on the use of self-designed external fixator in diaphyseal III metacarpal fractures in horses.
Diaphyseal fractures of the III metacarpal bone represent 22% of all fractures of the long bones in horses. Treatment of such cases is difficult. The most popular solution used in these types of fractures is two plates applied directly to the bone surface, but they are not applicable on contaminated and infected fractures. External fixators are quite commonly used in human medicine, although in veterinary practice there is no typical stabilizer designed for the treatment of diaphyseal fractures of the III metacarpal bone so far. In this study, an external semicircular fixator of our own design was used and in vitro strength tests were conducted to determine the maximum force which would lead to the destruction of non-fractured bone and fractured bone treated with the stabilizer. On the basis of the strength tests, we can conclude that the stabilizer can be strong enough to allow the horse to stand up after surgery. It also has many favorable features which make it easy to assemble and to take care of a wound, while being safe enough for the animal at the same time.


The RAF proteins take centre stage.
Since their discovery over 20 years ago, the RAF proteins have been intensely studied. For most of that time, the focus of the field has been the C-RAF isoform and its role as an effector of the RAS proteins. However, a report that implicates B-RAF in human cancer has highlighted the importance of all members of this protein kinase family and recent studies have uncovered intriguing new data relating to their complex regulation and biological functions.


More than a sex crime: a feminist political economy of the 2014 iCloud hack.
This article examines the media framing of and relations to the 2014 iCloud hack, wherein hundreds of female celebrities' private photos were stolen and distributed online. In particular, I problematize the reading of this event as merely signalling the misogyny of 'toxic' online cultures and contextualize it as part of a larger political economy of female celebrity. I argue that, while the growth in feminist discourses emanating from both the mainstream media and celebrity women is encouraging, it perhaps occludes the broader power relations that extend across both new and traditional media, ensuring maintenance of the status quo. This event exemplifies problems with a popular form of feminism that seeks inclusion into these systems, rather than wider systemic change. Therefore, in addition to examining the celebrity and/or her audience as the site of political (feminist) work, I call for an excavation of the systems in which she is embedded and her relations to the means of media production and profit.


Fluoride, hydrogen ion and HEMA release from light-cured GIC restoratives.
To quantitatively measure the amount of fluoride, hydroxy ion and hydroxyethyl methacrylate (HEMA) released from various light-cured restorative materials. Three resin-modified glass-ionomer cements (RMGI): Photac-Fil Aplicap, Vitremer, and Fuji II LC and two polyacid-modified resin-based composites (compomer): Dyract and Variglass VLC were used in this study. Disc-shaped specimens were made as per manufacturer's recommendations and the surfaces were polished with a 600 grit abrasive paper. Immediately after setting, each disc was immersed into 10 ml of distilled water at 37 degrees C and the eluates were collected after 8- or 24-hour immersion. The concentration of HEMA in the eluate was determined by high performance liquid chromatography. In addition, the concentration of fluoride ion and pH were measured by the respective ion selective electrode. The RMGIs released the greater amount of fluoride and smaller amounts of HEMA compared to the compomers at both the 8- and 24-hour eluates. Although there were no significant differences in pH of the 8-hour eluates among the restoratives, the pHs of the RMGI were significantly higher than those of the compomers for the 24-hour eluates.


[Fall risk and fracture. Aging and fall/fracture].
Fall deteriorates QOL and ADL of elderly people, especially when they suffer from hip and vertebral fractures. It is not easy to identify the cause of falling, because falling usually result from multiple factors. Among various potential causes, osteoporosis, osteoarthritis, medication of hypnotic drugs, and environmental factors are important, because they are frequent and can be modifiable. When evaluating fall risks, grasping power, one-leg standing time, timed up&go test, are useful. On the other hand, fall risk index, 22-item self-assessment test, is easy and even better in predicting future falls. In the Cochrane systematic review article 2009, exercise such as Tai-Chi, withdrawal of hypnotic drugs, and vitamin D supplementation are shown to prevent falls in community-dwelling elderly.


A practical guide to the preparation and use of metal ion-buffered systems for physiological research.
Recent recognition that mobile pools of Zn2+ and Cu2+ are involved in the regulation of neuronal, endocrine and other cells has stimulated the development of tools to visualize and quantify the level of free trace metal ions. Most of the methods used to measure or control loosely bound metals require reference media that contain exactly defined free concentrations of the target ions. Despite the central importance of proper metal ion buffering, there is still a lack of international standards and beginners in the field may have difficulties finding a coherent description of how to prepare trace metal ion buffers, especially when experiments are to be performed in multimetal systems. To close this gap, we provide a guide for the design, preparation and use of metal ion-buffered systems that facilitate immediate application under physiologically relevant ionic conditions. Thermodynamic and kinetic concepts of chemical speciation as well as general protocols and specific examples are outlined for the accurate preparation of single- and dual-metal ion buffers. In addition, experiments have been performed with FluoZin-3 to illustrate that metal ion-buffered systems are required for reliable preparation of nanomolar Zn2+ solutions and that dual-metal ion buffers can be used to calibrate suitable fluorescent Zn2+ sensors in the presence of millimolar Ca2+ concentrations. Together, the information provided should sensitize readers to the many potential pitfalls and uncertainties that exist when working with physiologically relevant concentrations of trace metal ions and enable them to formulate their own metal ion buffers for most in vitro applications.


Susceptibility of newly established mouse strain MPS to Mycoplasma pneumoniae infection.
A newly established mouse strain, MPS, which is more sensitive to Mycoplasma pulmonis than ICR, ddY and other mouse strains was examined for its susceptibility to Mycoplasma pneumoniae. In experimental infections with M. pneumoniae, it was observed that M. pneumoniae attached to tracheas of MPS mice, and M. pneumoniae cells were isolated from tracheas and lungs of MPS mice even after four weeks of infection, while no mycoplasmas were isolated from ICR and ddY mice after one week of infection. Specific antibodies against M. pneumoniae were also observed by the Western blotting in the sera of MPS mice infected with M. pneumoniae. Although any lung lesion could not be observed in this work, this newly established mouse strain MPS may be useful for experiments of M. pneumoniae infection, especially for the analysis of strain differences in susceptibility to M. pneumoniae infection.


Neural correlates of contextual cueing are modulated by explicit learning.
Contextual cueing refers to the facilitated ability to locate a particular visual element in a scene due to prior exposure to the same scene. This facilitation is thought to reflect implicit learning, as it typically occurs without the observer's knowledge that scenes repeat. Unlike most other implicit learning effects, contextual cueing can be impaired following damage to the medial temporal lobe. Here we investigated neural correlates of contextual cueing and explicit scene memory in two participant groups. Only one group was explicitly instructed about scene repetition. Participants viewed a sequence of complex scenes that depicted a landscape with five abstract geometric objects. Superimposed on each object was a letter T or L rotated left or right by 90°. Participants responded according to the target letter (T) orientation. Responses were highly accurate for all scenes. Response speeds were faster for repeated versus novel scenes. The magnitude of this contextual cueing did not differ between the two groups. Also, in both groups repeated scenes yielded reduced hemodynamic activation compared with novel scenes in several regions involved in visual perception and attention, and reductions in some of these areas were correlated with response-time facilitation. In the group given instructions about scene repetition, recognition memory for scenes was superior and was accompanied by medial temporal and more anterior activation. Thus, strategic factors can promote explicit memorization of visual scene information, which appears to engage additional neural processing beyond what is required for implicit learning of object configurations and target locations in a scene.


Item response theory analyses of parent and teacher ratings of the ADHD symptoms for recoded dichotomous scores.
The two-parameter logistic model (2PLM) was used to evaluate the psychometric properties of the inattention (IA) and hyperactivity/impulsivity (HI) symptoms. To accomplish this, parents and teachers completed the Disruptive Behavior Rating Scale (DBRS) for a group of 934 primary school-aged children. The results for the discrimination parameters showed that all the IA and HI symptoms for both groups of respondents were generally good for discriminating those with and without IA and HI, respectively. For virtually all symptoms, their threshold values showed endorsement of the symptoms when the underlying trait levels were at least 1 to 1.5 SD above the mean. The item information function values for most symptoms indicated reasonable reliability from around the mean trait levels to moderately high trait levels. These findings indicate good discrimination and reliability for parent and teacher ratings of the DBRS for identifying children with relatively high levels of the ADHD symptoms.