Management of acquired cholesteatoma in children: a 15 year review in ENT service of CHNU de FANN Dakar.
To analyze the epidemiology, diagnosis, management and the prognosis of cholesteatoma of the middle ear in children. This was a retrospective study of 15 years (from 01 January 1995 to 31 December 2009) for patients aged 0-15 years admitted in ENT ward of FANN hospital for chronic otitis media complicated with cholesteatoma The parameters studied were epidemiology, clinical presentation, disease progression and management. Sixty-six participants were included. We noted a slight male predominance with a sex ratio of 1.44. The average mean age was 10 years. Most patients presented with signs of complications (69.7%) and mastoiditis was the most common complication (63.6%). The otorrhea was noted in almost all patients: n = 64 (97%) and deafness in 49 patients (74, 2%). There was a slight predominance of cholesteatoma on the right side (51.5%). Schuller's view of the mastoid cells was done in 21.2% of patients (n = 14) and showed sclerotic mastoid air cells for all them. Eighty-two percent (82%) of patients presented with conductive hearing loss. A radical mastoidectomy was performed in 66.7% and modified radical mastoidectomy in 33.3% of cases. Mean follow-up was 6 months. Recurrence of cholesteatoma was noted in 13% of cases. ENT ward of Hospital Fann is one of the two centers in Senegal where cholesteatoma of the middle ear are treated. This low number of cholesteatoma in children in a developing country is in relation to the fact that patients only present when complications develop: 70% of cases. The reason for this in our setting include insufficient human and manpower resources necessary for prompt management of the disease and also lack of awareness among the populace. In these settings we advocate canal wall down mastoidectomy (radical or modified radical) as the treatment of choice.


Modelling the mechanics of accommodation and presbyopia.
Finite element methods have been used to compute the expected relationship between changes in ciliary body diameter and the change in refractive power implied by the change in geometry of the human ocular lens, using values for the material properties and initial geometry taken from the literature (notably the slit lamp photography of Brown (1973) and the studies by Fisher (1969) of the lens material properties). The results show that if the non-linearity associated with the changing geometry is taken into account the lens does not respond to ciliary body stretch by an increase in power [as recently claimed by Schachar et al. (1993), but in the conventional way with a decrease in power. The models show a decrease in the amplitude of accommodation between the age of 29 and 45 years (using Brown's data, 1973), but using Brown's data for the 11-year-old eye leads to the paradoxical conclusion that accommodation amplitude in this eye would have been small. In the process of carrying out the modelling, we have examined the consistency of the published measurements and also the validity of the mathematical methods used in interpreting them, and this analysis suggests that further work is needed before one can be confident that the assumptions about geometry and material properties on which the modelling is based are sound.


Isomerization couples chemistry in the ATP sulfurylase-GTPase system.
ATP sulfurylase catalyzes and couples the free energies of two reactions: GTP hydrolysis and the synthesis of activated sulfate, or APS. The GTPase active site undergoes changes during its catalytic cycle that are driven by events that occur at the APS-forming active site, which is located in a separate subunit. GTP responds to its changing environment by moving along its reaction path. The response, which may change the affinity or reactivity of GTP, can, in turn, produce alterations at the APS active site that drive APS synthesis. The resulting stepwise progression of the two reactions couples their free energies. The mechanism of ATP sulfurylase involves an enzyme isomerization that precedes and rate limits cleavage of the beta,gamma-bond of GTP. These fluorescence studies demonstrate that the isomerization is controlled by the binding of activators that drive ATP sulfurylase into forms that mimic different stages of the APS reaction. Only certain activators elicit the isomerization, suggesting that the APS reaction must proceed to a specific point in the catalytic cycle before the conformational "switch" that controls GTP hydrolysis is thrown. The isomerization is shown to require occupancy of the gamma-phosphate subsite of the GTP binding pocket. This requirement establishes that the isomerization results in a change in the interaction between the enzyme and the gamma-phosphate of GTP that emerges in the catalytic cycle during the transition from the nonisomerized to the isomerized E.GTP complex. The newly formed contact(s) appears to carry into the bond-breaking transition state, and to be essential for the enhanced affinity and reactivity of the nucleotide.


Rapid enzyme system for the identification of pathogenic Neisseria spp.
Gonochek II is a combination of three enzyme substrates in one tube which will give a rapid identification (30 min) of those pathogenic Neisseria spp. which can be isolated on Thayer Martin or similar selective media. Eighty isolates were tested by Gonochek II and a carbohydrate utilization method; total agreement was achieved between the two methods.


Predictors of mortality and limb loss in necrotizing soft tissue infections.
Necrotizing soft tissue infections (NSTIs) require prompt diagnosis and treatment. Early identification of patients at greatest risk of limb amputation and death may help in targeting aggressive medical and surgical management. The aim of this study was to assess predictors of limb loss and mortality in patients with NSTI based on admission variables. We performed a retrospective review of two hospitals that care for a large volume of patients with NSTI. Univariate and multivariable analyses were used to determine the association of admission biochemical markers to limb loss and mortality. Of 174 patients with NSTI, there were 19 deaths (10.9%) and 42 required amputations (24.1%). Multivariable logistic regression analysis revealed that only arterial lactate was predictive for both mortality (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.1 to 2.0; P = 0.009) and limb loss (OR, 1.3; 95% CI, 1.0 to 1.7; P = 0.02). In patients with a suspected NSTI, an arterial lactate should be ordered early on to guide aggressive therapeutic interventions and to provide information with regard to long-term outcomes of amputation and death that is needed for early discussion with the patient and family.


Prenatal diagnosis of triploidy associated with holoprosencephaly: a case report and review of the literature.
We sought to identify risk factors of prenatal presentation of holoprosencephaly associated with triploidy. A case report is presented with review of the literature performed using the PubMed database. The latest search was done in June 2008. Literature review showed 11 reports with a total of 15 cases of holoprosencephaly associated with triploidy. The mean maternal age at diagnosis was 27 +/- 4.9 years, and the mean gestational age at diagnosis was 13.6 +/- 3.3 weeks. Triploidy was mainly associated with the alobar type of holoprosencephaly. Only 3 (20%) cases had associated placental abnormalities. In all cases, the pregnancy was terminated. The latest gestational age at which termination was performed was 23 weeks. Facial abnormalities were the most common associated feature (66.6%). The association of triploidy with holoprosencephaly is very rare. This association does not seem to be related to maternal age. It is mainly associated with alobar holoprosencephaly. Diagnosis is possible during the first trimester. Fetuses can survive up to the third trimester.


Refractory Syncope and Presyncope Associated with Atlantoaxial Instability: Preliminary Evidence of Improvement Following Surgical Stabilization.
The proclivity to atlantoaxial instability (AAI) has been widely reported for conditions such as rheumatoid arthritis and Down syndrome. Similarly, we have found a higher than expected incidence of AAI in hereditary connective tissue disorders. We demonstrate a strong association of AAI with manifestations of dysautonomia, in particular syncope and lightheadedness, and make preliminary observations as to the salutary effect of surgical stabilization of the atlantoaxial motion segment. In an institutional review board-approved retrospective study, 20 subjects (16 women, 4 men) with hereditary connective tissue disorders had AAI diagnosed by computed tomography. Subjects underwent realignment (reduction), stabilization, and fusion of the C1-C2 motion segment. All subjects completed preoperative and postoperative questionnaires in which they were asked about performance, function, and autonomic symptoms, including lightheadedness, presyncope, and syncope. All patients with AAI reported lightheadedness, and 15 had refractory syncope or presyncope despite maximal medical management and physical therapy. Postoperatively, subjects reported a statistically significant improvement in lightheadedness (P = 0.003), presyncope (P = 0.006), and syncope (P = 0.03), and in the frequency (P < 0.05) of other symptoms related to autonomic function, such as nausea, exercise intolerance, palpitations, tremors, heat intolerance, gastroesophageal reflux, and sleep apnea. This study draws attention to the potential for AAI to present with syncope or presyncope that is refractory to medical management, and for surgical stabilization of AAI to lead to improvement of these and other autonomic symptoms.


Comparative Study of Green and Synthetic Polymers for Enhanced Oil Recovery.
Several publications by authors in the field of petrochemical engineering have examined the use of chemically enhanced oil recovery (CEOR) technology, with a specific interest in polymer flooding. Most observations thus far in this field have been based on the application of certain chemicals and/or physical properties within this technique regarding the production of 50-60% trapped (residual) oil in a reservoir. However, there is limited information within the literature about the combined effects of this process on whole properties (physical and chemical). Accordingly, in this work, we present a clear distinction between the use of xanthan gum (XG) and hydrolyzed polyacrylamide (HPAM) as a polymer flood, serving as a background for future studies. XG and HPAM have been chosen for this study because of their wide acceptance in relation to EOR processes. To this degree, the combined effect of a polymer's rheological properties, retention, inaccessible pore volume (PV), permeability reduction, polymer mobility, the effects of salinity and temperature, and costs are all investigated in this study. Further, the generic screening and design criteria for a polymer flood with emphasis on XG and HPAM are explained. Finally, a comparative study on the conditions for laboratory (experimental), pilot-scale, and field-scale application is presented.


The orthodontic and surgical management of Zimmerman-Laband syndrome.
Zimmermann-Laband syndrome (ZLS) is a rare autosomal disorder characterized by gingival fibromatosis, abnormalities of the nose and/or ears, hypoplasia of the nails or terminal phalanges of the hands and feet, hyperextensibility of joints, hepatosplenomegaly, hirsutism, and intellectual disability. The characteristics of the syndrome are highly variable and complicated. This paper reports a case of ZLS and the clinical manifestations encountered in relation to the current available literature. The comprehensive management of the patient's dentition is described, focusing on the orthodontic and surgical considerations clinicians should be aware of when treating patients with the syndrome.


Comparative Study of Risk Factors and Cognitive Profile of Small- and Large-Vessel Vascular Dementia - A Clinic Based Study.
Vascular dementia (VaD) is a clinically heterogeneous entity. There is a dearth of studies for comparison of the cognitive profile of cerebral small-vessel disease (SVD) with large-vessel disease. We planned to evaluate and compare the cognitive profile of SVD and large-vessel VaD and evaluate various risk factors associated with them. Patients of VaD were recruited after excluding mixed and ambiguous cases. Patients were classified into SVD and large-vessel VaD and analyzed for their clinic-epidemiological and cognitive profiles. Among 76 patients, 48 (62.5%) have SVD and 28 (37.5%) have large-vessel disease. Hypertension (93.4%) was the commonest risk factor, followed by smoking (34.21%), hyperlipidemia (26.31%), and diabetes mellitus (DM, 22.36%). Hypertension (P < 0.05) and DM were common in SVD, whereas smoking, hyperlipidaemia, and cardiac diseases were common in large-vessel disease. Attention (77.1% vs 25%), executive function (68.8% vs 28.6%), and calculation (58.3% vs 32.1%) were significantly more impaired in SVD compared to large-vessel disease, whereas visuoperceptual (21.4% vs 6.3%), praxis (28.6% vs 4.2%), and gnosis (14.3% vs 2.1%) were significantly more impaired in large-vessel disease than in SVD. Disruption of frontal-subcortical connection was responsible for the cognitive profile in SVD, but in large-vessel disease, it resulted from the cumulative loss of function from different lesions. Despite having common vascular risk factors, few are more common in SVD than in large-vessel disease. The different clinical and cognitive profile is due to the diverse anatomical lesions in these two subclasses of VaD.


Spatial properties of koniocellular cells in the lateral geniculate nucleus of the marmoset Callithrix jacchus.
1. The receptive field dimensions, contrast sensitivity and linearity of spatial summation of koniocellular (KC), parvocellular (PC) and magnocellular (MC) cells in the lateral geniculate nucleus (LGN) of 11 adult marmosets were measured using achromatic sinusoidal gratings. 2. The receptive field centre diameter of cells in each (PC, KC and MC) class increases with distance from the fovea. There is substantial overlap in centre size between the three cell classes at any eccentricity, but the PC cells have, on average, the smallest centres and the KC cells have the largest. Some PC and KC cells did not respond at all to the grating stimulus. 3. The contrast sensitivity of the receptive field centre mechanism in KC cells decreases in proportion to the centre area. A similar trend was seen for the surround mechanism. These characteristics are common to PC and MC cells, suggesting that they originate at an early stage of visual processing in the retina. 4. The KC cells showed, in general, lower peak evoked discharge rates than PC or MC cells. The spontaneous discharge rate of KC cells was lower than that of PC cells and similar to that of MC cells. 5. The majority of cells in all divisions of the LGN show linear spatial summation. A few cells did show non-linear spatial summation; these cells were predominantly located in the MC and ventral KC layers. 6. The ventral KC layers below and between the MC layers contain cells with larger and more transiently responding receptive fields than cells in the more dorsal KC layers. 7. We conclude that many of the contrast-dependent spatial properties of cells in the marmoset LGN are common to PC, MC and KC cells. The main difference between KC cells and the other two classes is that there is more variability in their response properties, and they are less responsive to high spatial frequencies.


Causal analysis: theory and application.
Identified opportunities to make statistical analysis more closely approximate the conceptual issues that are apparent in current research in pediatric psychology. The paper proceeds by explicating the logic of multivariate analysis and its application to causal modeling. Causal modeling techniques are discussed and the ease of employing these techniques is evaluated. Several articles from earlier issues of this journal are reviewed in terms of the application of causal analysis.


Rep and PriA helicase activities prevent RecA from provoking unnecessary recombination during replication fork repair.
The rescue of replication forks stalled on the template DNA was investigated using an assay for synthetic lethality that provides a visual readout of cell viability and permits investigation of why certain mutations are lethal when combined. The results presented show that RecA and other recombination proteins are often engaged during replication because RecA is present and provokes recombination rather than because recombination is necessary. This occurs particularly frequently in cells lacking the helicase activities of Rep and PriA. We propose that these two proteins normally limit the loading of RecA on ssDNA regions exposed on the leading strand template of damaged forks, and do so by unwinding the nascent lagging strand, thus facilitating reannealing of the parental strands. Gap closure followed by loading of the DnaB replicative helicase enables synthesis of the leading strand to continue. Without either activity, RecA loads more frequently on the DNA and drives fork reversal, which creates a chickenfoot structure and a requirement for other recombination proteins to re-establish a viable fork. The assay also reveals that stalled transcription complexes are common impediments to fork progression, and that damaged forks often reverse independently of RecA.


Bacteriophage as models for virus removal from Pacific oysters (Crassostrea gigas) during re-laying.
A study was undertaken to examine the feasibility of using naturally-occurring bacteriophages to assess the impact of re-laying on levels of viral contamination in Crassostrea gigas, the Pacific oyster. Two phages were chosen. One, male-specific (F+), was enumerated using Salmonella typhimurium. The other, a somatic phage, was detected using an, as yet, uncharacterized Escherichia coli. Investigations, using a variety of re-laying sites, demonstrated that numbers of F+ phage in oyster tissue declined more rapidly than those of somatic phage. For example, in oysters placed in commercially-used sea water ponds, F+ phage reached undetectable levels within 2-3 weeks, whereas somatic phage could still be detected 5 weeks after re-laying. The studies suggest that F+ phage may not be a suitable indicator for virus removal and that somatic phage may be better suited to this role.


The ethical issues regarding consent to clinical trials with pre-term or sick neonates: a systematic review (framework synthesis) of the analytical (theoretical/philosophical) research.
Conducting clinical trials with pre-term or sick infants is important if care for this population is to be underpinned by sound evidence. Yet, approaching the parents of these infants at such a difficult time raises challenges to obtaining valid informed consent for such research. In this study, we asked, What light does the analytical literature cast on an ethically defensible approach to obtaining informed consent in perinatal clinical trials? In a systematic search, we identified 30 studies. We began our analysis by applying philosophical frameworks, which were then refined as concepts emerged from the analytical studies, to present a coherent picture of a broad literature. Between them, the studies addressed four themes. The first three were the ethical basis for parental informed consent for neonatal and/or perinatal research, the validity of parental consent in this context, and the range of possible options in methods for gaining consent. The last was the issue of risk and the possibility of a double-standard or asymmetry in the current approaches to the requirement for consent for research and consent for clinical treatment. In addressing these issues, the analysed studies showed that, whilst there are a variety of possible defences for seeking parental 'consent' to neonatal and/or perinatal clinical trials, these are all consistent with the strongly and widely held view that it is important that parents do give (or decline) consent for such research. So far as the method of obtaining consent is concerned, none of the existing consent processes reviewed by the research is satisfactory, and there are philosophical reasons for supposing that at least some parents will fail to give valid consent in a neonatal context. Furthermore, in giving parental 'consent' in a perinatal context, parents are authorising infant participation, not giving 'proxy consent'. Finally, there are reasons for giving weight to both parental 'consent' and the infant's best interests in both research and clinical treatment. However, there are also reasons to treat these factors differently in the two contexts, and this may be partly due to the differing relevance of risk in each case. A significant gap is the lack of any detailed discussion of a process of emergency and/or urgent 'assent', in which parents assent or refuse their baby's participation as best they can during the emergency and later give full consent to continuing participation and follow-up.


The "Deglutition Handicap Index" a self-adminitrated dysphagia-specific quality of life questionnaire: sensibility to change.
The aim of this study is to assess the efficacy of UES's dysfunction treatments with the DHI (Deglutition Handicap Index). 24 patients suffering of UES's dysfunction were included prospectively between 2008 and 2009 in 2 centers (France and Netherlands). Patients completed DHI before and after treatment. For statistics, Wilcoxon two-sample tests were used. The mean score was 57 +/- 17 in the preoperative and 26 +/- 19 in the post operative time. The statistical difference was significant p < 0.0001. The difference is also significant for the 3 subscales (symptoms, functional, emotional). The DHI has been validated in terms of content, concurrent, construct validity and temporal reliability. It can be used for assessing efficacy of treatments used for dysphagia.


Pharmacological treatment of portal hypertension.
The available pharmacological treatments for portal hypertension are reviewed. Vasoconstrictor treatments include vasopressin (VP), the synthetic VP analogue tGLVP, combined nitroglycerin (NTG)-VP, somatostatin (SRIF), SRIF analogues and non-selective beta-blockers. Vasodilator treatments include short- and long-acting organic nitrates. Infusions of VP > 1.0 U/min can cause severe side-effects. tGLVP can control variceal bleeding and improve survival and causes fewer complications than VP.SRIF is as effective as tGLVP in controlling bleeding and improving survival and has minimal side effects. Beta-blockers are effective in preventing the first variceal haemorrhage and are well tolerated.


Flight activity of two sympatric termite species, Macrotermes gilvus and Macrotermes carbonarius (Termitidae: Macrotermitinae).
Flight activities of two sympatric termite species, Macrotermes gilvus (Hagen) and Macrotermes carbonarius (Hagen), were studied in Penang Island, Malaysia. Herein, we present the first documentation of chronological reproductive isolation of M. gilvus and M. carbonarius. Flights of M. gilvus were recorded over a remarkably long 7-mo period from March to September, whereas swarming of M. carbonarius took place from November to January. Swarming events of M. gilvus and M. carbonarius occurred under atmospheric pressures of 1,005-1,011 and 1,006-1,010 hPa, respectively. Most flights of M. gilvus occurred on days with rain, whereas M. carbonarius avoided rain. Flight activity of M. gilvus was correlated significantly with atmospheric pressure and rainfall. The threshold temperature and relative humidity of M. gilvus flights were between 23 and 26 degrees C and 83 and 98% RH, respectively; M. carbonarius swarmed between 25 and 30 degrees C and 72 and 83% RH, respectively. The flight activity of M. gilvus concentrated in the warmer and humid months with a monthly total rainfall of 228 mm. Both species swarmed at distinct times of day during the limited field observations: Flights of M. gilvus began between 0300 and 0430 hours (light intensity <1 Lx), and flights of M. carbonarius lasted for only 4-10 min between 1900 and 1910 hours (at dusk; light intensity: 20-200 Lx). Windless conditions were preferred for the flights of both species.


Membrane transport of amino acid enantiomers in protoscoleces of Echinococcus granulosus (Cestoda).
Protoscoleces of Echinococcus granulosus absorb both L- and D-alanine. Concentration ratios exceed 1 with values for D-alanine exceeding those for the L-isomer, suggesting that both are absorbed by active mechanisms. Uptake of both isomers involves both diffusion and carrier-mediated components. Values for the diffusion component (Kd) for L- and D-alanine were 0.21 and 0.38 nmol mg-1 protein/1.5 min mM-1 respectively, and values for Kt, the transport constants, 0.17 mM and 0.21 mM respectively. Uptake of both isomers was inhibited competitively by a number of other amino acids.


Sequence-Based Prediction of Cysteine Reactivity Using Machine Learning.
As one of the most intrinsically reactive amino acids, cysteine carries a variety of important biochemical functions, including catalysis and redox regulation. Discovery and characterization of cysteines with heightened reactivity will help annotate protein functions. Chemical proteomic methods have been used to quantitatively profile cysteine reactivity in native proteomes, showing a strong correlation between the chemical reactivity of a cysteine and its functionality; however, the relationship between the cysteine reactivity and its local sequence has not yet been systematically explored. Herein, we report a machine learning method, sbPCR (sequence-based prediction of cysteine reactivity), which combines the basic local alignment search tool, truncated composition of k-spaced amino acid pair analysis, and support vector machine to predict cysteines with hyper-reactivity based on only local sequence features. Using a benchmark set compiled from hyper-reactive cysteines in human proteomes, our method can achieve a prediction accuracy of 98%, a precision of 95%, and a recall ratio of 89%. We utilized these governing features of local sequence motifs to expand the prediction to potential hyper-reactive cysteines in other proteomes deposited in the UniProt database. We validated our predictions in Escherichia coli by activity-based protein profiling and discovered a hyper-reactive cysteine from a functionally uncharacterized protein, YecH. Biochemical analysis suggests that the hyper-reactive cysteine might be involved in metal binding. Our computational method provides a large inventory of potential hyper-reactive cysteines in proteomes and is highly complementary to other experimental approaches to guide systematic annotation of protein functions in the postgenome era.


Clinical findings of intracranial vertebral artery disease using magnetic resonance angiography.
The vertebral artery lesion has a variety of clinical characteristics. We sought to clarify the clinical patterns and the location of the intracranial vertebral artery (ICVA) diseases according to analyses of images obtained using magnetic resonance angiography (MRA). We studied vascular lesions, risk factors, symptoms, signs, and outcomes in 35 patients with ICVA disease (3 had bilateral occlusion; 9, unilateral occlusion; 6, bilateral stenosis; and 17, unilateral stenosis). The most common site of unilateral and bilateral lesions was the distal ICVA after the origin of posterior inferior cerebellar artery (PICA). We found accompanying basilar artery disease in 28.6% of patients with unilateral and bilateral ICVA disease. The majority of the ICVA lesions were associated with internal carotid arteries disease (48.8%). The common vascular risk factors were hypertension (71%), diabetes mellitus (34%), hyperlipidemia (31%), smoking (29%), and coronary artery disease (23%). Eighteen patients (51.4%) had transient ischemic attacks (TIAs) only, 10 patients (28.6%) had TIAs before stroke, and 5 patients (14.3%) had strokes without TIAs. Most patients (80%) with TIAs, with or without stroke, had multiple episodes. Vertigo or dizziness, ataxia, limbs weakness and abnormal gait were the common symptoms and signs. At 6 months follow-up, 66.7% patients had no symptoms or only slight symptoms that caused no disability. Our data showed (1) the usual location of ICVA disease (occlusion or severe stenosis) was distal to PICA, especially near the vertebrobasilar junction; (2) the risk factors were hypertension, diabetes mellitus, hyperlipidemia, smoking, and coronary artery disease; (3) patients with ICVA disease had a high frequency of accompanying internal carotid, middle cerebral, or basilar artery disease; (4) vertigo or dizziness, and ataxia were the common symptoms and signs; (5) TIA was the most common clinical pattern; (6) the outcome was favorable, except in cases with bilateral ICVA occlusion.


Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate): Enhancement Strategies for Advanced Applications.
Poly(3-hydroxybutyrate-co-3-hydroxyvalerate), PHBV, is a microbial biopolymer with excellent biocompatible and biodegradable properties that make it a potential candidate for substituting petroleum-derived polymers. However, it lacks mechanical strength, water sorption and diffusion, electrical and/or thermal properties, antimicrobial activity, wettability, biological properties, and porosity, among others, limiting its application. For this reason, many researchers around the world are currently working on how to overcome the drawbacks of this promising material. This review summarises the main advances achieved in this field so far, addressing most of the chemical and physical strategies to modify PHBV and placing particular emphasis on the combination of PHBV with other materials from a variety of different structures and properties, such as other polymers, natural fibres, carbon nanomaterials, nanocellulose, nanoclays, and nanometals, producing a wide range of composite biomaterials with increased potential applications. Finally, the most important methods to fabricate porous PHBV scaffolds for tissue engineering applications are presented. Even though great advances have been achieved so far, much research needs to be conducted still, in order to find new alternative enhancement strategies able to produce advanced PHBV-based materials able to overcome many of these challenges.


Mechanism of hepatic megamitochondria formation by ammonia derivatives. Correlation between structure of chemicals and their ability to induce the formation of megamitochondria.
Correlation between the chemical structure and the ability to induce hepatic megamitochondria formation was studied by feeding mice and rats diets containing a wide spectrum of ammonia derivatives. Ammonia derivatives with electron-releasing groups, such as hydrazine, phenylhydrazine, hydroxylamine and aniline were effective in inducing megamitochondria. Ammonia derivatives with electron-withdrawing groups, such as formamide, sulfamic acid, acetamide were ineffective in inducing megamitochondria. Inducibility of ammonia derivatives with electron-releasing groups plus electron-withdrawing groups for the megamitochondria formation was dependent upon nucleophilicity of the chemical: 2,4-dinitrophenylhydrazine induced megamitochondria, while acetanilide did not induce megamitochondria. The megamitochondria formation induced by ammonia derivatives was a reversible process. Freeze-fracture studies on megamitochondria indicated that megamitochondria were formed by the fusion of adjacent mitochondria. Phosphorylating capacity of megamitochondria (hydrazine-induced megamitochondria, for example) were normal despite morphological changes. These data might suggest that the nucleophilicity of chemicals plays a key role in the induction of hepatic megamitochondria. These data might also suggest that the phenomenon is an adaptive process to changes of intracellular milieu.


Germs are germs, and why not take a risk? Patients' expectations for prescribing antibiotics in an inner-city emergency department.
. Extensive use of unnecessary antibiotics has driven the emergence of resistant bacterial strains, posing a threat to public health. Physicians are more likely to prescribe antibiotics when they believe that patients expect them. Current attempts to change these expectations highlight the distinction between viruses and bacteria ("germs are germs"). Fuzzy-trace theory further predicts that patients expect antibiotics because they make decisions based on categorical gist, producing strategies that encourage risk taking when the status quo is bad (i.e., "why not take a risk?"). We investigate both hypotheses. . We surveyed patients visiting the emergency department of a large urban hospital (72 [64%] were African American) using 17 Likert scale questions and 2 free-response questions regarding patient expectations for antibiotics. . After the clinical encounter, 113 patients completed the survey. Fifty-four (48%) patients agreed with items that assess the "germs are germs" hypothesis, whereas 86 (76%) agreed with items that assess the "why not take a risk?" hypothesis. "Why not take a risk?" captures significant unique variance in a factor analysis and is neither explained by "germs are germs" nor by patients' lack of knowledge regarding side effects. Of the 81 patients who rejected the "germs are germs" hypothesis, 61 (75%) still indicated agreement with the "why not take a risk?" hypothesis. Several other misconceptions were also investigated. . Our findings suggest that recent public health campaigns that have focused on educating patients about the differences between viruses and bacteria omit a key motivation for why patients expect antibiotics, supporting fuzzy-trace theory's predictions about categorical gist. The implications for public health and emergency medicine are discussed.


Prevalence of Congenital Ocular Anomalies among Children with Genetic Disorders: An Egyptian Study.
To assess the pattern and frequency of occurrence of ocular anomalies among other genetic disorders in Egypt. This is a cross-sectional study of 2500 cases presenting with genetic disorders. Cases were recruited from the clinical genetics department of the National Research Centre (NRC) over a four-year period between January 2011 and December 2014. Ophthalmological examination of the cases was performed in the pediatric ophthalmology department of Cairo University Hospitals. Out of 2500 cases with congenital disorders, 2.4% suffered one or more ocular anomalies with a male to female ratio of 1.7:1. Consanguinity was reported in 76.7% and family history was positive in 35% of ocular cases. The most common ocular anomalies were congenital cataract, retinal dystrophies, glaucoma, and retinoblastoma in order of frequency. Chromosomal aberrations were detected in two retinoblastoma cases and in one case of charge association with cataract and iris coloboma. A truncating mutation in exon 8 of OCRL1 was reported in a case of Lowe syndrome with cataract. A total of 51.7% of ocular cases were non-isolated (associated with other genetic disorders). In Egypt, ocular genetic disorders are not uncommon among other genetic disorders. Consanguinity is high, suggesting high incidence of autosomal recessive inheritance of genetic disorders with an ocular component. Proper systemic assessment of all cases with ocular anomalies is a necessity due to the high percentage of non-isolated ocular anomalies. Genetic counseling of parents would help in reducing recurrence rates through prenatal diagnosis whenever possible.


Efficacy of synbiotic supplementation in improving rheumatoid arthritis.
Today, improving rheumatoid arthritis (RA) as a chronic inflammatory disease is attributed to the proper status of the gut microbiota. Although some supplements containing beneficial live microorganisms (probiotics) can reduce inflammation by altering the bacterial composition of the gut, there is limited information on the effect of synbiotic (probiotics mixed with prebiotics) supplements on RA. Therefore, this study aimed to evaluate the anti-inflammatory effects of a synbiotic supplement as an adjuvant therapy in rheumatic patients. Moreover, for the first time, it was attempted to investigate whether addition of a synbiotic (1000 mg/day) to the combination of methotrexate and prednisolone increases the effectiveness of these antirheumatic drugs. Eligible patients (186 subjects) were randomly divided into two groups. Both groups received their standard routine antirheumatic drugs, methotrexate and prednisolone. Moreover, the first group received a daily oral synbiotic supplement (1000 mg) for 3 months while the second group received a placebo. Various parameters indicating RA status were evaluated at baseline (time 0) and 3 months after the treatment. The results showed the changes in the level of RA indicators, including tender joint count with a range of 0 to 28 joints, swollen joint count with a range of 0 to 28 joints, visual analog scale, erythrocyte sedimentation rate, CRP, and disease activity score based on 28 joints, after 3 months. Overall, no significant differences in the measured parameters were observed between synbiotic and placebo groups probably due to the short duration of the treatment period, and it is suggested to extend the treatment period to six months.


Evidence for transglutaminase activity in plant tissue.
An extract prepared from the apical meristematic region of etiolated pea seedlings was able to catalyze the incorporation of putrescine into trichloroacetic acid precipitable material. The enzyme was found to be soluble and followed a typical Michaelis-Menten kinetics when N-N-dimethyl casein was used as a substrate. Its activity was promoted by Ca(2+) and inhibited by Cu(2+) and dl-dithiothreitol. Other polyamines competed with putrescine as substrates and cadaverine was the most potent inhibitor of putrescine incorporation. Plant transglutaminase is capable of recognizing specific sites in substrates described for animal transglutaminase, like insulin, fibrinogen, pepsin, and thrombin. However, it can also use as substrates cellulase and creatine kinase which have not been described for transglutaminase from other sources.


[Pituitary adenomas: neurosurgical treatment].
Due to their diversity, pituitary adenomas represent an interdisciplinary therapeutic challenge in regard to endocrinology, radiology and neurosurgery. Advanced radiological methods such as magnetic resonance imaging (MRI) and the possibility of three-dimensional reconstruction have profoundly improved surgical planning and intraoperative neuronavigation. With the application of modern surgical techniques like endoscope-assisted microsurgery or pure endoscopic surgery further improvements in the treatment of pituitary adenomas at difficult locations can be expected. Major prognostic factors predicting surgical outcome are extension of the adenoma and invasivity into adjacent structures. Both may be perfectly visualized by high-resolution MRI. The proliferation marker MIB-1 as a parameter of growth-rate and invasivity of pituitary adenomas provides information for postoperative management in terms of additional treatment and follow-up imaging. The current management of pituitary adenomas is discussed according to the different therapeutic options available and new developments are presented.


On the line tension of curved boundary layers. I. boundary thermodynamics.
We present a formally exact thermodynamic treatment of curved boundary layers. Specifically, we extend the boundary layer analysis of Mandell and Reiss [ J. Stat. Phys. 1975 , 13 , 107 ] for a spherical cavity located within a uniform bulk fluid to the case of a cavity intersecting a hard, structureless wall. We derive various expressions for the line tension of an intersecting cavity, all of which can be evaluated for a hard-sphere fluid using existing versions of scaled particle theory. Since the analysis is similar to the standard approach for describing curved interfacial layers, several boundary analogues to conventional interfacial relations appear. In some instances, we obtain results that apparently have not yet been derived either for boundary layers or for their parallel relations in interfacial thermodynamics. Several results offer interesting insights into the behavior of the line tension of a cavity when the cavity approaches macroscopic sizes or in the specific limit where the cavity no longer intersects the wall.


MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines.
Mitogen-activated protein kinases (MAPK) are activated by phosphorylation on Thr and Tyr by MAPK kinases. Two MAPK kinases (MKK4 and MKK7) can activate the c-Jun NH(2)-terminal kinase (JNK) group of MAPK in vitro. JNK is phosphorylated preferentially on Tyr by MKK4 and on Thr by MKK7. Targeted gene-disruption studies in mice were performed to examine the role of MKK4 and MKK7 in vivo. Simultaneous disruption of the Mkk4 and Mkk7 genes was required to block JNK activation caused by exposure of cells to environmental stress. In contrast, disruption of the Mkk7 gene alone was sufficient to prevent JNK activation caused by proinflammatory cytokines. These data demonstrate that MKK4 and MKK7 serve different functions in the JNK signal transduction pathway.


An email alert system for internal medicine physicians.
This study evaluated the effectiveness of an email-based alerting system for internal medicine house staff and faculty in geographically dispersed locales. Responses to a test alert email message were used to quantify the rapidity by which physicians read the message, and to define subgroups in which this communication modality proved most successful. The results of this study are being used to improve our preparedness for emergencies.


Incorporation of C-Leucine into Apple Leaf Protein and Its Inhibition by Protein Synthesis Inhibitors during Growth and Senescence.
Of the total (14)C-leucine taken up by intact apple (Pyrus malus L., Golden Delicious) leaf discs, 44 to 62% is incorporated into protein from June to early October. Of this amount, an average of 35% is released by mild, room temperature acid hydrolysis. Prior to mid-August when leaf protein begins to decline, 15 to 20% of the (14)C-leucine incorporated into protein occurs in water-(buffer) soluble protein, of which only 3% is released by mild acid hydrolysis. After mid-August, 40% of the label in protein occurs in soluble protein. The specific radio-activity of the soluble protein increases by 4- to 5-fold after mid-August, while that of total protein increases by less than 2-fold. In presenescent leaves (before the decline of protein in August) 20 micrograms per milliliter cycloheximide inhibits the incorporation of (14)C-leucine into protein by 71%, and 20 micrograms per milliliter chloramphenicol inhibits it by 30%. In senescing leaves, cycloheximide inhibits (14)C-leucine by 85% or more, while chloramphenicol inhibits it by less than 15%. Coincident to the initial decline of leaf protein, chloramphenicol greatly loses its ability to inhibit the incorporation of (14)C-leucine into apple leaf protein. At all leaf ages, chloramphenicol increases the loss of chlorophyll from apple leaf discs. The effect of cycloheximide on leaf disc senescence changes with leaf age: in early season samples, it increases the loss of chlorophyll; in mid-season samples, it has no effect; and in late season samples, it retards the loss of chlorophyll.


[Options and limits in the treatment of overweight children and adolescents and their families in primary care].
The general practitioner or pediatrician mostly is the first point of contact for overweight children and may recognize adiposity early enough in order to start therapy of obesity or comorbidity or to initiate measures of prevention. Interventions against overweight are most efficient before age 7 in terms of short-and long-term results and should not be delayed. As obesity requires care of the entire family, close or recurring contact with the overweight child and its family is important as well as the treatment nearby their residence. In preschoolers, targeting parents exclusively for obesity therapy is highly effective. Changing cherished habits and style of education is the biggest challenge to parents. Therefore, various techniques of treatment of alcohol or tobacco addiction can be used and recommendations for improvement of self-worth as well as healthy eating behavior and exercise are presented. First feasible objectives include modest lifestyle changes and reduction of comorbidities; if an extreme obesity with a BMI above 99.5th percentile or mental disorders are present or if it becomes apparent within the first 6 months that the patient cannot achieve his own goals for changes in lifestyle and body weight, a referral to a specialized center is indicated. There, a multi-professional treatment of the child and his family is performed in common by specialists for nutrition, exercise and psychology. Childhood obesity is a chronic disease that requires a very long-term treatment and usually persists into adulthood.


Right sided colorectal cancer increases with age and screening should be tailored to reflect this: a national cancer database study.
In the United States, colorectal cancer (CRC) screening and surveillance is recommended until age 75. However, rates of surgery for CRC are greatest in the elderly, questioning current guidelines. Tumor sidedness is an emerging prognostic marker that may help guide screening and treatment decisions, with specific benefit evaluating CRC anatomic distribution in the elderly. Our objective was to investigate the anatomical distribution of CRC in the elderly and factors associated with right-sidedness. The National Cancer Database (2004-2016) was used to identify elderly patients with CRC. Cases were stratified by tumor sidedness and elderly subgroups: 65-74, 75-84, and ≥ 85 years of age, and further categorized by primary site. Multivariate analysis identified factors associated with CRC right-sidedness. The outcomes were CRC sidedness in the elderly, the anatomic distribution by age group, and factors associated with right-sidedness. There were 508,219 colorectal cancer patients aged over 65 years identified, 54% of whom had a right-sided cancer. The right-sided incidence rates by age group were 49% (65-74 years), 58.2% (75-84 years), and 65.9% (≥ 85 years) (p < 0.001). Variables associated with right-sidedness were age (OR 1.032; 95% CI 1.031-1.033; p < 0.001), female sex (OR 1.541; 95% CI 1.522-1.561; p < 0.001), Medicare (OR 1.023, 95% CI 1.003-1.043; p = 0.027), year of diagnosis ≥ 2010 (OR 1.133; 95% CI 1.119-1.147; p < 0.001), tumor size > 5 cm (OR 1.474; 95% CI 1.453-1.495; p < 0.001), pathologic stage IV (OR 1.036; 95% CI 1.012-1.060; p = 0.003). We found higher rates of right-sided colon cancer in the 75 and above age group. This is a population who would benefit greatly from a high-quality and complete colonoscopy for early diagnosis. As screening and surveillance for this age group are not currently recommended, our findings question the lack of universal recommendation of colonoscopy in patients over 75 years old. Guidelines for CRC screening and surveillance should consider the colon cancer right-shift in the elderly population. Based on these results, we recommend thorough assessment of the proximal colon in the elderly.


Effects of single parenteral indomethacin injection in rat fundic and antral epithelial proliferation.
To study the effects of a single parenteral dose of indomethacin on gastric epithelial proliferation, we performed the following study. Male Wistar rats weighing about 200 g were divided into two groups and given single intraperitoneal injections of indomethacin 5 mg/kg, either suspended in 0.5% carboxymethyl cellulose sodium salt or vehicle alone, after an overnight fast. After 6 h, all rats were injected by tail vein with tritiated thymidine, 1 microCi/g body weight, to label proliferating cells and were killed 1 h later. Sections from fundic and antral mucosae were processed for light autoradiography. Parenteral indomethacin resulted in spotty erosions in fundic mucosa. Histologically, there was congestion with or without epithelial disruption. These areas were excluded in the proliferation measurements. There was a significant decrease not only in the number of labeled cells but also in the thickness of the proliferative zone with the thinning of the entire mucosal thickness in the fundic mucosa. None of the measurements in antral mucosa showed significant difference. These results showed that a single parenteral injection of indomethacin inhibits epithelial proliferation and decreases mucosal thickness in fundic, but not antral mucosa of the rat.


Ligand stabilization of manganocene dianions - in defiance of the 18-electron rule.
Manganocene [Mn(C5H5)2], a 17-electron system, is expected to have a high electron affinity, as addition of an extra electron would make it a closed-shell 18-electron system. Surprisingly, it has a very low electron affinity of only 0.28 eV. Combined with its high ionization potential of around 7.0 eV, manganocene, therefore, should not be eager to either donate or accept an electron. We show that this property can be fundamentally altered with the proper choice of ligands, even though the total electron count remains the same. For example, the electron affinities of manganocene-derivatives Mn[C5(CN)5]2 and Mn[C5(BO)5]2, created by replacing H with CN or BO, are found to be 4.78 eV and 4.85 eV, respectively, making these species superhalogens. The power of the ligands is further demonstrated by studying the stability of their di-anions. Note that [Mn(C5X5)2]2- (X = H, CN, BO) di-anions, with 19-electrons, have one electron more than necessary to satisfy the 18-electron rule for stability. This factor, combined with the unavoidable repulsion between the two extra electrons, should destabilize [Mn(C5X5)2]2-. While that is the case for [Mn(C5H5)2]2-, we show that both Mn[C5(CN)5]22- and Mn[C5(BO)5]22- are stable against auto-detachment of the second electron by 0.7 eV and 0.38 eV, respectively. These results, based on first-principles calculations, demonstrate that ligand-manipulation can be used as an effective strategy to design and synthesize new materials with novel and tailored properties.


Renal artery occlusion in PAN.
A search of the literature has disclosed no other example of polyarteritis nodosa that involves the renal arteries without involvement of the smaller branches.


Design of a Collapse-Mode CMUT With an Embossed Membrane for Improving Output Pressure.
Capacitive micromachined ultrasonic transducers (CMUTs) have emerged as a competitive alternative to piezoelectric ultrasonic transducers, especially in medical ultrasound imaging and therapeutic ultrasound applications, which require high output pressure. However, as compared with piezoelectric ultrasonic transducers, the output pressure capability of CMUTs remains to be improved. In this paper, a novel structure is proposed by forming an embossed vibrating membrane on a CMUT cell operating in the collapse mode to increase the maximum output pressure. By using a beam model in undamped conditions and finite-element analysis simulations, the proposed embossed structure showed improvement on the maximum output pressure of the CMUT cell when the embossed pattern was placed on the estimated location of the peak deflection. As compared with a uniform membrane CMUT cell worked in the collapse mode, the proposed CMUT cell can yield the maximum output pressure by 51.1% and 88.1% enhancement with a single embossed pattern made of Si3N4 and nickel, respectively. The maximum output pressures were improved by 34.9% (a single Si3N4 embossed pattern) and 46.7% (a single nickel embossed pattern) with the uniform membrane when the center frequencies of both original and embossed CMUT designs were similar.


The effect of the plasticizer diethylhexyl phthalate on transport activity and expression of P-glycoprotein in parental and doxo-resistant human sarcoma cell lines.
Multidrug resistance (MDR) to cancer therapy is frequently associated with the over-expression of the multidrug transporter MDR1 gene product P-glycoprotein (Pgp) in several types of human tumours. Various chemosensitizers have been used to inhibit Pgp activity but toxicity limits their clinical application. Di(2-ethylhexyl)phthalate (DEHP) is a plasticizer that is released from polyvinyl chloride (PVC) medical devices. Therefore, cancer patients undertaking chemotherapy are exposed to a clinically important amount of DEHP through blood and blood component transfusions, apheresis products, intravenous chemotherapy, parenteral nutrition and other medical treatments. The present study was designed to investigate the effects of DEHP on transport activity and expression of Pgp in order to evaluate its potential use as a chemosensitizer in cancer therapy. Human doxorubicin (doxo) resistant sarcoma cells (MES-SA/Dx5) that over-express Pgp were treated with different doses of doxo (2, 4 and 8 μM) in the presence or absence of various concentrations of DEHP (3, 6 and 12 μM) that were clinically achievable in vivo. Our results show that co-treatment with 2, 4 and 8 μM doxo in the presence of the lowest concentration of DEHP (3 μM) enhanced significantly doxo accumulation in MES-SA/Dx5 cells and, consistently increased the sensitivity to doxo, when compared to controls receiving only doxo. In contrast, higher DEHP concentrations (6 and 12 μM) induced MES-SA/Dx5 to extrude doxo decreasing doxo cytotoxicity toward resistant cells below control values. These results are consistent with the increase in Pgp expression levels in parental MES-SA cells treated with 3, 6 and 12 μM DEHP for 24 h and compared to untreated controls. All in all, these findings suggest a potential clinical application of DEHP as a chemosensitizer to improve effectiveness of the antineoplastic drugs in MDR human tumours.


Construction of gene therapy vectors targeting adrenocortical cells: enhancement of activity and specificity with agents modulating the cyclic adenosine 3',5'-monophosphate pathway.
In preliminary studies we demonstrated that the CYP11B1 (11beta-hydroxylase) promoter could direct specific expression of a suicide gene in adrenocortical cancer cells, providing a potentially specific therapeutic option for adrenocortical cancer. In this present study we describe our attempts to enhance the activity of the CYP11B1 promoter while maintaining its specificity for adrenal cells. Using a putative enhancer element from the cholesterol side-chain cleavage (P450scc) gene, the activity of the CYP11B1 promoter in and its specificity for adrenocortical cells were enhanced. Treatment with 8-bromo-cAMP or forskolin resulted in further enhancement. In stably transfected Y-1 cells, in which the herpes simplex virus thymidine kinase (HSV-TK) gene was driven by the CYP11B1 promoter with the P450scc enhancer element, HSV-TK expression and ganciclovir sensitivity were augmented by treatment with 8-bromo-cAMP, forskolin, and ACTH. In summary, we report the construction of a suicide HSV-TK vector with preferential toxicity to adrenocortical cells. We propose that a similar strategy using differentiating agents may be useful in the gene therapy of tumors with unique differentiated properties, including those arising from other endocrine organs.


Association of prenatal maternal blood lead levels with birth outcomes in the Japan Environment and Children's Study (JECS): a nationwide birth cohort study.
Despite dramatic declines in prenatal maternal blood lead levels (BLLs) in most developed countries, little is known about the effects of extremely low-level (<1.0 µg/dL) lead exposure on fetal growth. We measured maternal BLL during the second or third trimester of pregnancy and assessed birth outcomes, including birthweight, preterm birth (<37 gestational weeks) risk, small for gestational age births (SGA; birthweight <10th percentile) and low birthweight (LBW; <2500 g). The association between birthweight and maternal BLL was estimated using linear and quadratic spline models. Multivariable logistic models were used to examine the risk of binary responses. From 103 099 pregnant women, 20 000 blood samples were randomly selected for analysis. The maternal BLL range was 0.16-7.4 µg/dL, and the median was 0.63 µg/dL. After adjusting for covariates, the linear model showed that each 0.1 μg/dL increase in maternal BLL was associated with a 5.4 g decrease in mean birthweight [95% confidence interval (CI), 3.4 to 7.5 g]. The risk of SGA [adjusted odds ratio (aOR), 1.03; 95% CI, 1.02 to 1.05) and LBW (aOR, 1.03; 95% CI, 1.02 to 1.05) increased, whereas the risk of preterm delivery did not (aOR, 0.99; 95% CI, 0.97 to 1.02). Even at a maternal BLL below 1.0 µg/dL, prenatal lead exposure was associated with decreased birthweight and increased risk of SGA and LBW, but not preterm delivery. The adverse effect estimates of prenatal lead exposure on birth outcomes were quantitatively small and clinically limited at this low level.


Detection of anticentromere antibodies using recombinant human CENP-A protein.
To evaluate CENP-A reactivity with anticentromere antibodies (ACA) using recombinant protein (rCENP-A). Human CENP-A antigen was overexpressed in insect cells using the baculovirus system. We tested for ACA activity against the full-length recombinant polypeptide by immunoblot and by enzyme-linked immunosorbent assay (ELISA). Of the ACA+ sera studied (n = 38), 95% were positive when tested against the rCENP-A in the ELISA system. Of the ACA- sera (n = 100), only 2% gave false-positive results in the assay. There was good correlation between the recombinant and bona fide antigens in assaying for ACA reactivity. CENP-A is a significant ACA target. The availability of the rCENP-A assay is a valuable adjunct to the previously described rCENP-B assay in analyses of the clinical significance of ACA.


Human insecurity and child deaths in conflict: evidence for improved response in Yemen.
Since the beginning of the ongoing conflict in Yemen, >23 000 air strikes and >100 000 fatalities have been recorded. Data from Yemen Data Project linked >1300 child fatalities and >900 child injuries to air raids. However, there is little literature on the effect of the protracted armed conflict on the pattern of child mortality using data from small-scale surveys. We aimed to identify the pattern of the death rate for children aged <5 years ('under-5') and its relationship with human insecurity in Yemen. We created a human insecurity index (i.e. severely insecure vs insecure) for the 22 governorates in Yemen from 2015 to 2019, using data from the Armed Conflict Location and Event Database. We matched this insecurity index with the corresponding under-5 mortality data from the Complex Emergency Database. We analysed the relationship between the under-5 death rate (U5DR) and the insecurity level using a Bayesian finite mixture model in order to account for unobserved heterogeneity in clustered finite subsets of a population. We extracted 72 surveys and 77.8% (n = 56) were included in this study. The mean of the recall period for mortality was 106 days with a standard deviation of 93 days. We identified two subpopulations: Subpopulation I-high average number of child deaths and Subpopulation II-low average number of child deaths. The log posterior mean of the U5DR is 1.10 (95% credible intervals: 0.36, 1.82) in the severely insecure group in Subpopulation I and 3-fold the estimate in Subpopulation II. However, in Subpopulation II, we found no association between the insecurity level and the U5DR. The pattern of child deaths is crucial in understanding the relationship between human insecurity and the U5DR.


The effect of female polyandry and sperm precedence on the evolution of sexual difference in dispersal timing.
Predispersal copulation and unpredictable environment facilitate the evolution of female-biased dispersal in species, where females are functionally monandrous. Females should migrate and reproduce over different habitats to spread their risks due to environmental fluctuation. On the other hand, males do not have to disperse because their risks are spread by their mating partners who produce their offspring in different habitats. However, when females are functionally polyandrous, it is expected that they will not contribute to spreading the male's risk extensively. Therefore, by simulation with the individual based model, the present study evaluated how female polyandry influences the sexual difference in dispersal timing. This model revealed that when females are polyandrous, the timing of female remating and sperm priority patterns have an important influence on the evolution of sex-biased dispersal. Particularly when female remating is not synchronized with dispersal or when last-male sperm precedence does not exist, female-biased dispersal is evolved.


Constructing bootstrap confidence intervals for principal component loadings in the presence of missing data: a multiple-imputation approach.
Earlier research has shown that bootstrap confidence intervals from principal component loadings give a good coverage of the population loadings. However, this only applies to complete data. When data are incomplete, missing data have to be handled before analysing the data. Multiple imputation may be used for this purpose. The question is how bootstrap confidence intervals for principal component loadings should be corrected for multiply imputed data. In this paper, several solutions are proposed. Simulations show that the proposed corrections for multiply imputed data give a good coverage of the population loadings in various situations.


Low frequency arterial wall movements for indirect blood pressure measurement in man. Validation of a method for non-invasive assessment of blood pressure under the influence of isoprenaline and angiotensin.
In order to measure blood pressure noninvasively, the second derivative of the low frequency wall movements of the brachial artery were registered with a piezo-electric pressure probe during deflation of a Riva-Rocci cuff along with the actual cuff pressure. Two characteristic phenomena of this signal have been suggested to reflect systolic and diastolic blood pressure. Appearance of a positive spike phenomenon (S) was suggested to indicate systolic blood pressure and disappearance of a negative preanacrotic notch (D) to indicate diastolic blood pressure. To prove the validity of these suggestions, these phenomena were assessed in 10 young healthy males during isoprenaline and angiotensin induced changes of blood pressure. Intraarterial (A. radialis) and auscultatory (A. brachialis) blood pressures were recorded simultaneously. Determination of systolic blood pressure with the S phenomenon agreed well with invasive and auscultatory results. Invasive diastolic values agreed well with the cuff pressure at the last signal before disappearance of the preanacrotic notch (D1). Data from auscultation agreed less well with the D1 phenomenon. With increasing doses of isoprenaline, the diastolic measurements (D1) tended to be lower than the invasive ones. However, this discrepancy was far discreeter than that seen with ordinary auscultatory blood pressure measurement. We therefore conclude that registrations of low frequency arterial wall movements yield distinct characteristic spike phenomena useful for measurement of blood pressure in good agreement with the invasive method. In addition, the method provides clearly documented records and should be useful in situations which rely on a valid indirect method.


Dual-Resonator-Based (DRB) and Multiple-Resonator-Based (MRB) MEMS Sensors: A Review.
Single-resonator-based (SRB) sensors have thrived in many sensing applications. However, they cannot meet the high-sensitivity requirement of future high-end markets such as ultra-small mass sensors and ultra-low accelerometers, and are vulnerable to environmental influences. It is fortunate that the integration of dual or multiple resonators into a sensor has become an effective way to solve such issues. Studies have shown that dual-resonator-based (DRB) and multiple-resonator-based (MRB) MEMS sensors have the ability to reject environmental influences, and their sensitivity is tens or hundreds of times that of SRB sensors. Hence, it is worth understanding the state-of-the-art technology behind DRB and MRB MEMS sensors to promote their application in future high-end markets.


Cyclooxygenase 2 Effector Genes as Potential Inflammation-Related Biomarkers for Colorectal Cancer Circulating Tumor Cells Detection by Liquid Biopsy.
Cyclooxygenase 2 (COX2) has been implicated in cancer development and metastasis. We have identified several COX2-regulated inflammation-related genes in human colorectal cancer cells and shown that some of them play important roles in tumor progression. In this work, we have studied the COX2-regulated genes in the mouse colorectal cancer cell line CT26, to find that many are also regulated by COX2 over-expression. On the other hand, we generated a CT26 cell line expressing Gfp and Luciferase, to study tumor growth and metastasis in immunocompetent Balb/c mice. We then collected solid tissue, and blood samples, from healthy and tumor-bearing mice. Using the Parsortix® cell separation system and taking advantage of the fact that the tumor cells expressed Gfp, we were able to identify circulating tumor cells (CTCs) in some of the mice. We compared the mRNA expression levels of Ptgs2 and effector genes in the samples obtained from tumor-bearing or healthy mice, namely, tumor or healthy colon, Ficoll purified buffy coat, and Parsortix-isolated cells to find different patterns between healthy, tumor-bearing mice with or without CTCs. Although for genes like Il15 we did not observe any difference between healthy and tumor-bearing mice in Ficoll or Parsortix samples; others, such as Egr1, Zc3h12a, Klf4, or Nfat5, allowed distinguishing for cancer or CTC presence. Gene expression analysis in Ficoll or Parsortix processed samples, after liquid biopsy, may offer valuable diagnostic and prognostic information and thus should be further studied.


Co3O4/Bi4O5I2/Bi5O7I C-Scheme Heterojunction for Degradation of Organic Pollutants by Light-Emitting Diode Irradiation.
Remediation of organic pollutant matrixes from wastewater by photodegradation using different heterojunctions is extensively studied to improve performance for potential application. Brilliant black (BB) and p-nitrophenol (PNP) have been detected in the environment and implicated as directly or indirectly carcinogenic to human health. This work analyzes their elimination from aqueous solutions under visible-light irradiation with composites of cobalt(II, III) oxide and bismuth oxyiodides (Co3O4/Bi4O5I2/Bi5O7I). The synthesized nanomaterial properties were investigated using various techniques such as BET, SEM/EDS, TEM, XRD, FTIR, PL, and UV-vis. All the nanocomposites absorbed in the visible range of the solar spectrum with band gaps between 1.68 and 2.79 eV, and the specific surface area of the CB2 composite increased by 35.8% from that of Bi4O5I2/Bi5O7I. There was an observed massive reduction in the rate of electron and hole recombination, and the band gaps of the composites decreased. The mineralization of PNP and BB was followed by determination of the total organic carbon with reductions of 93.6 and 83.7%, respectively. The main active species were the hydroxyl radicals, while the superoxide anion radical and generated holes were minor as confirmed by radical trapping experiments. The optimum pHs for degradation of PNP and BB were 9.6 and 5.3, respectively. The enhanced performance of the catalyst was due to C-scheme heterojunction formation that reduced the electron and hole recombination rate and was attributed to strong adsorption of the pollutants on the photocatalyst active surface. The nanocomposite is apposite for solar energy-driven remediation of organic pollutants from environmental aqueous samples.


Impact of Vocal Effort on Respiratory and Articulatory Kinematics.
The goal of this study was to examine the effects of increases in vocal effort, without changing speech intensity, on respiratory and articulatory kinematics in young adults with typical voices. A total of 10 participants completed a reading task under three speaking conditions: baseline, mild vocal effort, and maximum vocal effort. Respiratory inductance plethysmography bands around the chest and abdomen were used to estimate lung volumes during speech, and sensor coils for electromagnetic articulography were used to transduce articulatory movements, resulting in the following outcome measures: lung volume at speech initiation (LVSI) and at speech termination (LVST), articulatory kinematic vowel space (AKVS) of two points on the tongue dorsum (body and blade), and lip aperture. With increases in vocal effort, and no statistical changes in speech intensity, speakers showed: (a) no statistically significant differences in LVST, (b) statistically significant increases in LVSI, (c) no statistically significant differences in AKVS measures, and (d) statistically significant reductions in lip aperture. Speakers with typical voices exhibited larger lung volumes at speech initiation during increases in vocal effort, paired with reduced lip displacements. To our knowledge, this is the first study to demonstrate evidence that articulatory kinematics are impacted by modulations in vocal effort. However, the mechanisms underlying vocal effort may differ between speakers with and without voice disorders. Thus, future work should examine the relationship between articulatory kinematics, respiratory kinematics, and laryngeal-level changes during vocal effort in speakers with and without voice disorders. https://doi.org/10.23641/asha.17065457.


Deciphering the Host-Pathogen Interactome of the Wheat-Common Bunt System: A Step towards Enhanced Resilience in Next Generation Wheat.
Common bunt, caused by two fungal species, Tilletia caries and Tilletia laevis, is one of the most potentially destructive diseases of wheat. Despite the availability of synthetic chemicals against the disease, organic agriculture relies greatly on resistant cultivars. Using two computational approaches-interolog and domain-based methods-a total of approximately 58 M and 56 M probable PPIs were predicted in T. aestivum-T. caries and T. aestivum-T. laevis interactomes, respectively. We also identified 648 and 575 effectors in the interactions from T. caries and T. laevis, respectively. The major host hubs belonged to the serine/threonine protein kinase, hsp70, and mitogen-activated protein kinase families, which are actively involved in plant immune signaling during stress conditions. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the host proteins revealed significant GO terms (O-methyltransferase activity, regulation of response to stimulus, and plastid envelope) and pathways (NF-kappa B signaling and the MAPK signaling pathway) related to plant defense against pathogens. Subcellular localization suggested that most of the pathogen proteins target the host in the plastid. Furthermore, a comparison between unique T. caries and T. laevis proteins was carried out. We also identified novel host candidates that are resistant to disease. Additionally, the host proteins that serve as transcription factors were also predicted.


Evaluation of the development of lung hypoplasia in the premature lamb.
The death rate from human diaphragmatic hernia (CDH) ranges from 50 to 80%, mainly due to the associated lung hypoplasia. To prevent these irreversible pathological and physical defects, the question of intrauterine surgical intervention arises. The histological changes of the lung tissue after inducement of a diaphragmatic hernia were examined. Of special interest was the time elapsing until the development of lung hypoplasia. A model of intrauterine inducement of diaphragmatic hernia was established using five fetal lambs to study consecutive pulmonary hypoplasia. Inducement of a diaphragmatic hernia was undertaken between 105 and 108 days' gestation. Lung tissue was examined histologically on postoperative days 8, 17, 21, 22, and 25 after inducement of the defect. On postoperative days 8, 17, and 21, no signs of pulmonary hypoplasia were found on histological examination. A pulmonary hypoplasia was found in two fetuses (on the 22nd and 25th postoperative day). The pathological and anatomical examination of a unilateral pulmonary hypoplasia after a short period of time shows that the artificially created diaphragmatic defect is a good model for producing a congenital diaphragmatic hernia. The severity of the pulmonary hypoplasia is related to the duration of lung compression by the herniated organs. The time elapsing until the development of lung hypoplasia is shorter than expected. Tracheal occlusion seems to be an effective strategy for treatment of the defect CDH, but the best technique for achieving occlusion, and particularly the ideal point in time to carry out "Fetendo," are unknown. Further research into this congenital illness is required in order to treat it.


Triple aldose reductase/α-glucosidase/radical scavenging high-resolution profiling combined with high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy for identification of antidiabetic constituents in crude extract of Radix Scutellariae.
In this work, development of a new microplate-based high-resolution profiling assay using recombinant human aldose reductase is presented. Used together with high-resolution radical scavenging and high-resolution α-glucosidase assays, it provided the first report of a triple aldose reductase/α-glucosidase/radical scavenging high-resolution inhibition profile - allowing proof of concept with Radix Scutellariae crude extract as a polypharmacological herbal drug. The triple bioactivity high-resolution profiles were used to pinpoint bioactive compounds, and subsequent structure elucidation was performed with hyphenated high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy. The only α-glucosidase inhibitor was baicalein, whereas main aldose reductase inhibitors in the crude extract were baicalein and skullcapflavone II, and main radical scavengers were ganhuangemin, viscidulin III, baicalin, oroxylin A 7-O-glucuronide, wogonoside, baicalein, wogonin, and skullcapflavone II.


Brain and Blame.
This article addresses the law's concept of the person and its relation to responsibility and the excusing conditions. It demonstrates that causation of behavior in general, even pathological biological causation, is not itself and excuse and suggests that the incapacity for rationality is the genuline basis of moral and legal excuse. The paper concludes by applying its theses to the case of Spyder Cystkopf, a man with a confirmed subarachnoid cyst, who killed his wife during a heated argument with her.


The efficacy of protein supplementation during recovery from muscle-damaging concurrent exercise.
This study investigated the effect of protein supplementation on recovery following muscle-damaging exercise, which was induced with a concurrent exercise design. Twenty-four well-trained male cyclists were randomised to 3 independent groups receiving 20 g protein hydrolysate, iso-caloric carbohydrate, or low-calorific placebo supplementation, per serve. Supplement serves were provided twice daily, from the onset of the muscle-damaging exercise, for a total of 4 days and in addition to a controlled diet (6 g·kg-1·day-1 carbohydrate, 1.2 g·kg-1·day-1 protein, remainder from fat). Following the concurrent exercise session at time-point 0 h, comprising a simulated high-intensity road cycling trial and 100 drop-jumps, recovery of outcome measures was assessed at 24, 48, and 72 h. The concurrent exercise protocol was deemed to have caused exercise-induced muscle damage (EIMD), owing to time effects (p < 0.001), confirming decrements in maximal voluntary contraction (peaking at 15% ± 10%) and countermovement jump performance (peaking at 8% ± 7%), along with increased muscle soreness, creatine kinase, and C-reactive protein concentrations. No group or interaction effects (p > 0.05) were observed for any of the outcome measures. The present results indicate that protein supplementation does not attenuate any of the indirect indices of EIMD imposed by concurrent exercise, when employing great rigour around the provision of a quality habitual diet and the provision of appropriate supplemental controls.


Effects of a physical activity intervention on schoolchildren fitness.
The global prevalence of childhood obesity is high. Obesity main causes are linked to sedentary lifestyles. Increasing physical activity (PA) and reducing sedentary activities are recommended to prevent and treat obesity. This study aimed to evaluate the effectiveness of a 6-month school PA intervention on obesity prevention and healthy behaviors in school-aged children. Participating students (10-11 years of age) were randomly divided into an intervention group and a control group. Children in the intervention group (n = 80) participated in a multicomponent PA that included improvement in extracurricular physical activities (with an additional 40 min per day for 5/6 days per week). Children (n = 80) in the control group participated in usual practice. Participants had mean body mass index of 19.7 ± 2.9 kg/m2 , and 33.7% of them were overweight or with obesity at T0. The change in body mass index in intervention group (-2.4 ± 0.6 kg/m2 ) was significantly different from that in control group (3.01 ± 1.8 kg/m2 ). The effects on waist circumference, waist-to-height ratio, and physic fitness were also significant in intervention group compared with control group (all p < 0.05). Furthermore, there is a significant decrease in overweight or children with obesity in the experimental group (to 17.5%, p < 0.05). These findings suggest that a school-based intervention program represents an effective strategy for decreasing the number of overweight and children with obesity.


Effects of a lateral turn on mixed venous oxygen saturation and heart rate in critically ill adults.
The purpose of this study was to determine the effects of a lateral turn on mixed venous oxygen saturation (SvO2) and heart rate in 183 critically ill adults. Mean SvO2 decreased from a baseline of 67% to 61% saturation (p less than 0.0001) immediately after turning and gradually returned to 66% saturation (p less than 0.002) within 4 minutes. Mean heart rate increased slightly from a baseline of 99 beats/min to 102 beats/min (p less than 0.0001) immediately after turning and decreased slightly to 101 beats/min (p less than 0.0004) within 4 minutes. These statistically significant changes in SvO2 and heart rate were not clinically significant for most patients. However, physiologic responses to turning were highly variable. SvO2 reductions of 25% or more from baseline, heart rate increases and decreases of 10 beats/min or more, and signs of activity intolerance occurred in some patients. Nurses should expect critically ill patients to have a decrease in SvO2 of approximately 9% of baseline and small changes in heart rate after turning. These changes should be transient, with SvO2 and heart rate gradually returning toward baseline levels during the next 4 minutes. If turning triggers large or prolonged changes in SvO2 or heart rate, prompt repositioning and evaluation are needed to prevent adverse effects.


ED 'vending machine' sells patient meds 24/7.
A vending machine stocked with your most commonly used drugs can be a relatively inexpensive investment in patient and staff satisfaction. Rice Memorial Hospital in Willmar, MN, has installed such a machine, which includes several safeguards: * It has several internal cameras, serving as backup systems to ensure the proper drug is being dispensed to the proper patient. * The machine cannot be accessed by anyone unless they have received a magnetic swipe card from the prescribing physician. * The code is only given to a physician authorized to enter the web portal of the prescription vendor.


Intramolecular G-quartet motifs confer nuclease resistance to a potent anti-HIV oligonucleotide.
We have identified a potentially therapeutic anti-human immunodeficiency virus (HIV)-1 oligonucleotide composed entirely of deoxyguanosines and thymidines (T30177, also known as AR177: 5'-g.tggtgggtgggtggg.t-3', where asterisk indicates phosphorothioate linkage). In acute assay systems using human T-cells, T30177 and its total phosphodiester homologue T30175 inhibited HIV-1-induced syncytium production by 50% at 0.15 and 0.3 microM, respectively. Under physiological conditions, the sequence and composition of the 17-mer favors the formation of a compact, intramolecularly folded structure dominated by two stacked guanine quartet motifs that are connected by three loops of TGs. The molecule is stabilized by the coordination of a potassium ion between the two stacked quartets. We now show that these guanine quartet-containing oligonucleotides are highly resistant to serum nucleases, with t1/2 of 5 h and >4 days for T30175 and T30177, respectively. Both oligonucleotides were internalized efficiently by cells, with intracellular concentrations reaching 5-10-fold above the extracellular levels after 24 h of incubation. In contrast, single-base mutated variants or random sequence control oligonucleotides that could not form the compactly folded structure had markedly reduced half-lives (t1/2 from approximately 3 to 7 min), low cellular uptake, and no sequence-specific anti-HIV-1 activity. These data suggest that the tertiary structure of an oligonucleotide is a key determinant of its nuclease resistance, cellular uptake kinetics, and biological efficacy.


Magnetic iron oxide nanoparticles for drug delivery: applications and characteristics.
For many years, the controlled delivery of therapeutic compounds has been a matter of great interest in the field of nanomedicine. Among the wide amount of drug nanocarriers, magnetic iron oxide nanoparticles (IONs) stand out from the crowd and constitute robust nanoplatforms since they can achieve high drug loading as well as targeting abilities stemming from their remarkable properties (magnetic and biological properties). These applications require precise design of the nanoparticles regarding several parameters which must be considered together in order to attain highest therapeutic efficacy. This short review presents recent developments in the field of cancer targeted drug delivery using magnetic nanocarriers as drug delivery systems. The design of nanocarriers enabling efficient delivery of therapeutic compounds toward targeted locations is one of the major area of research in the targeted drug delivery field. By precisely shaping the structural properties of the iron oxide nanoparticles, drugs loaded onto the nanoparticles can be efficiently guided and selectively delivered toward targeted locations. With these goals in mind, special attention should be given to the pharmacokinetics and in vivo behavior of the developed nanocarriers.


Self-Powered Photodetector Using Two-Dimensional Ferroelectric Dion-Jacobson Hybrid Perovskites.
Dion-Jacobson (DJ) phase organic-inorganic hybrid perovskites (OIHPs) have emerged as promising alternatives to Ruddlesden-Poppers perovskites because of their chemical stability and ferroelectric phase. Here we fabricate a ferroelectricity-modulated photodetector based on the n = 2 homologue of the ferroelectric two-dimensional DJ-OIHP (AMP)(MA)Pb2I7 (DJPn=2, AMP = 4-(aminomethyl)piperidinium; MA = methylammonium), which shows an out-of-plane polarization and a saturated polarization (Ps) value of 3.7 μC/cm2. The coercive field of DJPn=2 (0.34 kV/cm) is lower than that for the n = 1 homologue (AMP)PbI4 (DJPn=1,0.4 kV/cm). DJPn=2 has a much longer carrier lifetime and absorption edge (580 nm, 2.13 eV) in comparison to DJPn=1 (523 nm, 2.37 eV); thus, DJPn=2 can be used for efficient photodetection in the visible range, in which a responsivity of 0.16 mA/W was achieved at 532 nm. The influence of remnant polarization on the direction and magnitude of the photocurrent was also demonstrated.


Occupational asthma due to piperazine citrate.
Piperazine is a secondary heterocyclic amine that may give rise to occupational asthma of uncertain mechanism. We report on a 42-year-old woman, a process operator in a chemical factory, who developed work-related symptoms of rhinitis and asthma upon exposure to piperazine citrate. She remained symptom free during holidays and days off work. Skin prick test with piperazine citrate was positive. Specific inhalation challenge with piperazine citrate at a concentration of 5 mg/m3 for 30 minutes elicited an isolated late asthmatic response. Airway hyperresponsiveness to methacholine significantly increased 3 hours after the piperazine challenge, preceding the late asthmatic response. This patient had developed occupational asthma caused by piperazine, as confirmed by the specific inhalation challenge test, possibly due to an immunological mechanism.


Afferent stimulation facilitates performance on a novel motor task.
Training on a motor task results in performance improvements that are accompanied by increases in motor cortex excitability. Moreover, periods of afferent stimulation result in increased motor cortex excitability. There is increasing evidence to suggest that raised motor cortical excitability may facilitate movement and learning. Here we examined whether a period of electrical stimulation of hand afferents ("associative stimulation"), known to increase motor cortex excitability, facilitated the performance of a complex sensorimotor task. Three groups of nine normal subjects participated in these studies. All subjects were trained on the grooved pegboard test (GPT). Training consisted of three blocks, each of five trials, of placing pegs as quickly as possible. The time to complete each block was recorded. One group of subjects had a 1-h period of associative stimulation prior to training on the GPT. A second group received non-associative stimulation (which does not change cortical excitability) of the same hand afferents while a third group received no stimulation prior to training. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous (FDI) and abductor digiti minimus (ADM) muscles both prior to and following stimulation and performance of the GPT. In contrast to non-associative stimulation, associative stimulation increased motor cortical excitability, as evidenced by an increase in the amplitude of MEPs evoked in the FDI, one of the stimulated muscles, but not the ADM. Training on the GPT resulted in significant improvements in the time taken to complete the task for all three groups. However, in subjects who had preconditioning associative stimulation, performance on the GPT improved more rapidly. Additionally, there was a strong trend for the improvement in the performance of the stimulated group to be greater than that of the control group. The results of the present study suggest that increased motor cortical excitability, induced by associative stimulation, may facilitate the performance of a novel complex sensorimotor task.


Making Bryostatin 1 through Smart Chemistry.
Scientists have come up with an efficient, scalable way to chemically synthesize bryostatin 1, a marine-derived natural PKC modulator that has been in scarce supply, impeding a thorough evaluation of its therapeutic potential.


[Evaluation of the blood flow in lung disease with color Doppler flow imaging].
Blood flow within the lesions was evaluated in 6 patients of lung cancer and in 4 patients with pulmonary tuberculosis with color Doppler flow imaging. Three different signal types were noted: pulsatile signal was detected in all patients with lung cancer and in 2 patients with pulmonary tuberculosis, continuous signal was only detected in 3 patients with lung cancer, triphasic signal was detected in 4 patients with pulmonary tuberculosis and in 2 patients with lung cancer. It was seemed to be that triphasic signal was blood flow signal in peripheral vessel of pulmonary vein and color Doppler flow imaging was useful for evaluation of blood flow patterns in lung disease.


[Development of a New Neuro-Endoscope Cylinder for Safer Neuro-Endoscopic Surgery].
Objective:Successful endoscopic surgery for intracerebral hemorrhage has previously been hampered by impaired visualization during the operation to remove the clot, leading to a relatively low removal efficiency for hematomas. However, in multiple case series, intracerebral hematomas have been reported to be removed using endoscopic visualization. Although using tubular retractors in cranial surgery is one technique to gain access to deep-seated lesions, it is difficult to confirm the depth of the retractor's sheath in the surgical field using only the outer sheath. We built various-sized cylinders, developed by the Japan Science and Technology Agency's(JST)program for revitalization promotion, with scales that are visible during both endoscopic and radiographic procedures. We report the use of these cylinders in clinical cases. Method and Results:The JST-developed cylinders benefit from new techniques for plating and tantalum film implantation used to form tubes made of fluorinated ethylene propylene. We successfully removed various hematomas using these cylinders, as we were able to clearly visualize the border of the brain parenchyma and the depth of the hematoma using the cylinder. Conclusion:Cylinders with visible scales for both endoscopic and radiographic uses developed by the JST programs may provide greater patient safety during endoscopic surgery. We next plan to improve the hardness, length, and smoothness of the groove on the cylinder.


Role of VEGF165b/VEGFTOTAL ratio in gestational diabetes mellitus.
Proper vascular function is important for well-being of mother and growing fetus. VEGFTOTAL, and VEGF165b levels and its vascular endothelial complications in gestational diabetes mellitus (GDM) together with the association of inflammation and advanced glycation end products (AGEs) are less studied. VEGF165b/VEGFTOTAL (VEGF RATIO) in GDM pregnant women was investigated in this study. Plasma VEGFTOTAL was lower in GDM (17.68 ± 1.30 pg/mL) compared to non-GDM (25.69 ± 1.40 pg/mL). VEGF165b, ICAM-1, and AGEs were higher in GDM (9.9 ± 1.4 pg/mL, 201.04 ± 7.85 µg/mL, and 10.40 ± 0.98 µg/mL, respectively) and lower in non-GDM (6.47 ± 0.70 pg/mL, 174.1 ± 7.11 µg/mL, and 4.71 ± 0.39 µg/mL, respectively). Compared to non GDM (0.25 ± 0.02), VEGF RATIO was higher in GDM (0.45 ± 0.04) and correlated with -ICAM-1 (r = 0.375, p < .001) and AGEs (r = 0.199, p < .05). Tertile stratification of VEGF RATIO implied that frequency of GDM increases with increasing tertiles of VEGF RATIO (p for trend <.001). Association of VEGF RATIO with GDM was significant even after adjusting for AGEs (OR = 1.279, CI = 1.118-1.462, p < .0010) but it lost its significance when adjusted for ICAM-1 (OR = 1.006, CI = 0.995-1.017, p = .308). VEGF RATIO plays an important role in GDM in association with vascular inflammation.


Some considerations in planning organizational change.
Three major types of organizational change are identified (alterations in behavior, technology, and structure), and the respective impact of each is explored. The difficulties in assessing the significance of a change idea are noted, and some criteria are suggested by which such an assessment can be made (e.g., the number of organizational elements affected by the change). The paper concludes by noting practice implications stemming from an understanding of the types of change and their significance for those participants who have limited formal power.


[1]Benzothieno[3,2-d]pyrimidine derivatives as ligands for the serotonergic 5-HT7 receptor.
The present paper describes the synthesis and the binding properties for the serotonergic 5-HT7 and 5-HT1A receptors of three new series (A-C) of (benzo)thienopyrimidinone derivatives. All series exhibit a basic moiety at the 2-position of the heterocyclic scaffold such as N,N-dialkylaminoalkylthio chain in series A and phenylpiperazine, benzylpiperazine, or benzylpiperidine alkyl chain in series B and C. Compounds endowed with the best binding properties at 5-HT7R belong to the B and C types. In particular, derivatives B2 and C1 (RSC4) exhibit notable affinity for 5-HT7R (Ki = 9.08 and 0.85 nM, respectively) and selectivity over the 5-HT1AR (254- and 48-fold, respectively). The structure-affinity relationships for these three new classes of 5-HT7R ligands are discussed and, in order to rationalize and deeply investigate the observed results, molecular modeling studies were performed. In particular, the binding poses of the synthesized compounds were studied by docking them in the two receptor proteins suitably built by homology modeling. The calculated binding energies resulted in an excellent agreement with the experimental measured Ki, further validating the quality of the models.


Progress of Exsolved Metal Nanoparticles on Oxides as High Performance (Electro)Catalysts for the Conversion of Small Molecules.
Utilizing electricity and heat from renewable energy to convert small molecules into value-added chemicals through electro/thermal catalytic processes has enormous socioeconomic and environmental benefits. However, the lack of catalysts with high activity, good long-term stability, and low cost strongly inhibits the practical implementation of these processes. Oxides with exsolved metal nanoparticles have recently been emerging as promising catalysts with outstanding activity and stability for the conversion of small molecules, which provides new possibilities for application of the processes. In this review, it starts with an introduction on the mechanism of exsolution, discussing representative exsolution materials, the impacts of intrinsic material properties and external environmental conditions on the exsolution behavior, and the driving forces for exsolution. The performances of exsolution materials in various reactions, such as alkane reforming reaction, carbon monoxide oxidation, carbon dioxide utilization, high temperature steam electrolysis, and low temperature electrocatalysis, are then summarized. Finally, the challenges and future perspectives for the development of exsolution materials as high-performance catalysts are discussed.


Copper-catalyzed formal [4 + 2] annulation between alkyne and fullerene bromide.
A copper-catalyzed reaction of arylacetylene or enyne with C(60)Ar(5)Br effects a formal [4 + 2] annulation reaction to form a dihydronaphthalene ring fused to the fullerene core. The reaction involves a formal C-H bond activation and takes place by a copper-mediated radical mechanism. This reaction takes place in 60-75% overall yield from [60]fullerene and creates axial chirality in the product because of restricted rotation of the top aryl groups.


Blockade of tumor necrosis factor reduces lipopolysaccharide lethality, but not the lethality of cecal ligation and puncture.
Inhibition of tumor necrosis factor (TNF) bioactivity has afforded protection in several animal models of sepsis. We examined whether inhibition of TNF could improve survival after lethal lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in CD-1 or BALB/c mice. Neutralizing rabbit anti-TNF antisera were evaluated in CD-1 mice by injecting the antisera 3 h before intravenous (i.v.) LPS (600 micrograms). Implantable radiotransmitters were used for continuous monitoring of temperature. No decrease in mortality was observed, and the anti-TNF failed to prevent the drop in temperature. In BALB/c mice injected with antisera before LPS (200 micrograms) mortality was reduced (dead/total: control sera, 14/14; anti-TNF, 4/12; p = .007 control sera vs. anti-TNF). CD-1 mice were pretreated with anti-TNF or control sera; CLP was performed followed by administration of antibiotics. Anti-TNF did not decrease pulmonary neutrophil sequestration, improve survival, or prevent the decrease in temperature observed as sepsis developed. CLP was performed in the BALB/c mice using antibiotics plus anti-TNF antisera, but no protection was observed. Our results demonstrate that anti-TNF treatment prevents LPS mortality only when using certain strains of mice and inhibition of TNF fails to reduce mortality in a more clinically relevant model of sepsis.


Clostridial neurotoxins and substrate proteolysis in intact neurons: botulinum neurotoxin C acts on synaptosomal-associated protein of 25 kDa.
Clostridial neurotoxins are zinc endopeptidases that block neurotransmission and have been shown to cleave, in vitro, specific proteins involved in synaptic vesicle docking and/or fusion. We have used immunohistochemistry and immunoblotting to demonstrate alterations in toxin substrates in intact neurons under conditions of toxin-induced blockade of neurotransmitter release. Vesicle-associated membrane protein, which colocalizes with synaptophysin, is not detectable in tetanus toxin-blocked cultures. Syntaxin, also concentrated in synaptic sites, is cleaved by botulinum neurotoxin C. Similarly, the carboxyl terminus of the synaptosomal-associated protein of 25 kDa (SNAP-25) is not detectable in botulinum neurotoxin A-treated cultures. Unexpectedly, tetanus toxin exposure causes an increase in SNAP-25 immunofluorescence, reflecting increased accessibility of antibodies to antigenic sites rather than increased expression of the protein. Furthermore, botulinum neurotoxin C causes a marked loss of the carboxyl terminus of SNAP-25 when the toxin is added to living cultures, whereas it has no action on SNAP-25 in vitro preparations. This study is the first to demonstrate in functioning neurons that the physiologic response to these toxins is correlated with the proteolysis of their respective substrates. Furthermore, the data demonstrate that botulinum neurotoxin C, in addition to cleaving syntaxin, exerts a secondary effect on SNAP-25.